Co-reporter:Mostafa Baghbanzadeh, Carleen M. Bowers, Dmitrij Rappoport, Tomasz Żaba, Li Yuan, Kyungtae Kang, Kung-Ching Liao, Mathieu Gonidec, Philipp Rothemund, Piotr Cyganik, Alan Aspuru-Guzik, and George M. Whitesides
Journal of the American Chemical Society June 7, 2017 Volume 139(Issue 22) pp:7624-7624
Publication Date(Web):May 11, 2017
DOI:10.1021/jacs.7b02770
This paper describes charge transport by tunneling across self-assembled monolayers (SAMs) of thiol-terminated derivatives of oligo(ethylene glycol) (HS(CH2CH2O)nCH3; HS(EG)nCH3); these SAMs are positioned between gold bottom electrodes and Ga2O3/EGaIn top electrodes. Comparison of the attenuation factor (β of the simplified Simmons equation) across these SAMs with the corresponding value obtained with length-matched SAMs of oligophenyls (HS(Ph)nH) and n-alkanethiols (HS(CH2)nH) demonstrates that SAMs of oligo(ethylene glycol) have values of β (β(EG)n = 0.29 ± 0.02 natom–1 and β = 0.24 ± 0.01 Å–1) indistinguishable from values for SAMs of oligophenyls (β(Ph)n = 0.28 ± 0.03 Å–1), and significantly lower than those of SAMs of n-alkanethiolates (β(CH2)n = 0.94 ± 0.02 natom–1 and 0.77 ± 0.03 Å–1). There are two possible origins for this low value of β. The more probable involves hole tunneling by superexchange, which rationalizes the weak dependence of the rate of charge transport on the length of the molecules of HS(EG)nCH3 using interactions among the high-energy, occupied orbitals associated with the lone-pair electrons on oxygen. Based on this mechanism, SAMs of oligo(ethylene glycol)s are good conductors (by hole tunneling) but good insulators (by electron and/or hole drift conduction). This observation suggests SAMs derived from these or electronically similar molecules are a new class of electronic materials. A second but less probable mechanism for this unexpectedly low value of β for SAMs of S(EG)nCH3 rests on the possibility of disorder in the SAM and a systematic discrepancy between different estimates of the thickness of these SAMs.
Co-reporter:Mathieu Gonidec, Mahiar M. Hamedi, Alex Nemiroski, Luis M. Rubio, Cesar Torres, and George M. Whitesides
Nano Letters 2016 Volume 16(Issue 7) pp:4125-4132
Publication Date(Web):May 31, 2016
DOI:10.1021/acs.nanolett.6b00952
This paper describes a strategy that uses template-directed self-assembly of micrometer-scale microspheres to fabricate arrays of microlenses for projection photolithography of periodic, quasiperiodic, and aperiodic infrared metasurfaces. This method of “template-encoded microlens projection lithography” (TEMPL) enables rapid prototyping of planar, multiscale patterns of similarly shaped structures with critical dimensions down to ∼400 nm. Each of these structures is defined by local projection lithography with a single microsphere acting as a lens. This paper explores the use of TEMPL for the fabrication of a broad range of two-dimensional lattices with varying types of nonperiodic spatial distribution. The matching optical spectra of the fabricated and simulated metasurfaces confirm that TEMPL can produce structures that conform to expected optical behavior.
Co-reporter:Alex Nemiroski; Siowling Soh; Sen Wai Kwok; Hai-Dong Yu
Journal of the American Chemical Society 2016 Volume 138(Issue 4) pp:1252-1257
Publication Date(Web):January 1, 2016
DOI:10.1021/jacs.5b10936
Magnetic levitation (MagLev) of diamagnetic or weakly paramagnetic materials suspended in a paramagnetic solution in a magnetic field gradient provides a simple method to measure the density of small samples of solids or liquids. One major limitation of this method, thus far, has been an inability to measure or manipulate materials outside of a narrow range of densities (0.8 g/cm3 < ρ < 2.3 g/cm3) that are close in density to the suspending, aqueous medium. This paper explores a simple method—“tilted MagLev”—to increase the range of densities that can be levitated magnetically. Tilting the MagLev device relative to the gravitational vector enables the magnetic force to be decreased (relative to the magnetic force) along the axis of measurement. This approach enables many practical measurements over the entire range of densities observed in matter at ambient conditions—from air bubbles (ρ ≈ 0) to osmium and iridium (ρ ≈ 23 g/cm3). The ability to levitate, simultaneously, objects with a broad range of different densities provides an operationally simple method that may find application to forensic science (e.g., for identifying the composition of miscellaneous objects or powders), industrial manufacturing (e.g., for quality control of parts), or resource-limited settings (e.g., for identifying and separating small particles of metals and alloys).
This paper describes the design and fabrication of electrically controlled paper actuators that operate based on the dimensional changes that occur in paper when the moisture absorbed on the surface of the cellulose fibers changes. These actuators are called “Hygroexpansive Electrothermal Paper Actuators” (HEPAs). The actuators are made from paper, conducting polymer, and adhesive tape. They are lightweight, inexpensive, and can be fabricated using simple printing techniques. The central element of the HEPAs is a porous conducting path (used to provide electrothermal heating) that changes the moisture content of the paper and causes actuation. This conducting path is made by embedding a conducting polymer (PEDOT:PSS) within the paper, and thus making a paper/polymer composite that retains the porosity and hydrophilicity of paper. Different types of HEPAs (straight, precurved, and creased) achieved different types of motions (e.g., bending motion, accordion type motion). A theoretical model for their behavior is proposed. These actuators have been used for the manipulation of liquids and for the fabrication of an optical shutter.
Co-reporter:Ana C. Glavan, Alar Ainla, Mahiar M. Hamedi, M. Teresa Fernández-Abedul and George M. Whitesides
Lab on a Chip 2016 vol. 16(Issue 1) pp:112-119
Publication Date(Web):27 Oct 2015
DOI:10.1039/C5LC00867K
This work describes the adaptive use of conventional stainless steel pins—used in unmodified form or coated with carbon paste—as working, counter, and quasi-reference electrodes in electrochemical devices fabricated using cotton thread or embossed omniphobic RF paper to contain the electrolyte and sample. For some applications, these pin electrodes may be easier to modify and use than printed electrodes, and their position and orientation can be changed as needed. Electroanalytical devices capable of multiplex analysis (thread-based arrays or 96-well plates) were easily fabricated using pins as electrodes in either thread or omniphobic RF paper.
This paper addresses a growing need in clinical diagnostics for parallel, multiplex analysis of biomarkers from small biological samples. It describes a new procedure for assembling arrays of ssDNA and proteins on paper. This method starts with the synthesis of DNA oligonucleotides covalently linked to paper and proceeds to assemble microzones of DNA-conjugated paper into arrays capable of simultaneously capturing DNA, DNA-conjugated protein antigens, and DNA-conjugated antibodies. The synthesis of ssDNA oligonucleotides on paper is convenient and effective with 32% of the oligonucleotides cleaved and eluted from the paper substrate being full-length by HPLC for a 32-mer. These ssDNA arrays can be used to detect fluorophore-linked DNA oligonucleotides in solution, and as the basis for DNA-directed assembly of arrays of DNA-conjugated capture antibodies on paper, detect protein antigens by sandwich ELISAs. Paper-anchored ssDNA arrays with different sequences can be used to assemble paper-based devices capable of detecting DNA and antibodies in the same device and enable simple microfluidic paper-based devices.
This paper presents methods that use Magnetic Levitation (MagLev) to measure very small differences in density of solid diamagnetic objects suspended in a paramagnetic medium. Previous work in this field has shown that, while it is a convenient method, standard MagLev (i.e., where the direction of magnetization and gravitational force are parallel) cannot resolve differences in density <10–4 g/cm3 for macroscopic objects (>mm) because (i) objects close in density prevent each other from reaching an equilibrium height due to hard contact and excluded volume, and (ii) using weaker magnets or reducing the magnetic susceptibility of the medium destabilizes the magnetic trap. The present work investigates the use of weak magnetic gradients parallel to the faces of the magnets as a means of increasing the sensitivity of MagLev without destabilization. Configuring the MagLev device in a rotated state (i.e., where the direction of magnetization and gravitational force are perpendicular) relative to the standard configuration enables simple measurements along the axes with the highest sensitivity to changes in density. Manipulating the distance of separation between the magnets or the lengths of the magnets (along the axis of measurement) enables the sensitivity to be tuned. These modifications enable an improvement in the resolution up to 100-fold over the standard configuration, and measurements with resolution down to 10–6 g/cm3. Three examples of characterizing the small differences in density among samples of materials having ostensibly indistinguishable densities—Nylon spheres, PMMA spheres, and drug spheres—demonstrate the applicability of rotated Maglev to measuring the density of small (0.1–1 mm) objects with high sensitivity. This capability will be useful in materials science, separations, and quality control of manufactured objects.
Co-reporter:Chien-Chung Wang, Jonathan W. Hennek, Alar Ainla, Ashok A. Kumar, Wen-Jie Lan, Judy Im, Barbara S. Smith, Mengxia Zhao, and George M. Whitesides
This paper describes the design and fabrication of a “pop-up” electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)—a biomarker for diabetic ketoacidosis—using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children’s books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer—a device that is more available than the combination BHB/glucometer. Strategies that use a “3D pop-up”—that is, large-scale changes in 3D structure and fluidic paths—by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.
Israel Journal of Chemistry 2016 Volume 56( Issue 1) pp:66-82
Publication Date(Web):
DOI:10.1002/ijch.201500061
Abstract
“Physical-organic chemistry” is the name given to a subfield of chemistry that applies physical-chemical techniques to problems in organic chemistry (especially problems involving reaction mechanisms). “Physical-organic” is, however, also a short-hand term that describes a strategy for exploratory experimental research in a wide range of fields (organic, organometallic, and biological chemistry; surface and materials science; catalysis; and others) in which the key element is the correlation of systematic changes in molecular structure with changes in properties and functions of interest (reactivity, mechanism, physical or biological characteristics). This perspective gives a personal view of the historical development, and of possible future applications, of the physical-organic strategy.
Co-reporter:Dian Yang, Lihua Jin, Ramses V. Martinez, Katia Bertoldi, George M. Whitesides, Zhigang Suo
Extreme Mechanics Letters 2016 Volume 6() pp:1-9
Publication Date(Web):March 2016
DOI:10.1016/j.eml.2015.11.004
This paper demonstrates a new soft structure that uses a meso- or macro-scale elastic instability to generate a shape-memory effect similar to that exhibited by a ferroelastic material. It demonstrates the phase transitions, state switching, and shape-memory effects in this system, both in experiment and in simulation. The new class of materials described in the paper is potentially useful, since it comprises what are effectively “shape-memory alloys” of arbitrarily low modulus and arbitrarily large remnant strain. The reproduction of properties of materials usually associated with atomic- or molecular-level changes in structure using meso-scale structural opens the door to development of new, soft materials with new properties and functions.
Current methods of monitoring breathing require cumbersome, inconvenient, and often expensive devices; this requirement sets practical limitations on the frequency and duration of measurements. This article describes a paper-based moisture sensor that uses the hygroscopic character of paper (i.e. the ability of paper to adsorb water reversibly from the surrounding environment) to measure patterns and rate of respiration by converting the changes in humidity caused by cycles of inhalation and exhalation to electrical signals. The changing level of humidity that occurs in a cycle causes a corresponding change in the ionic conductivity of the sensor, which can be measured electrically. By combining the paper sensor with conventional electronics, data concerning respiration can be transmitted to a nearby smartphone or tablet computer for post-processing, and subsequently to a cloud server. This means of sensing provides a new, practical method of recording and analyzing patterns of breathing.
Co-reporter:Dr. Firat Güder;Dr. Alar Ainla;Julia Redston; Bobak Mosadegh;Dr. Ana Glavan;T. J. Martin; George M. Whitesides
Angewandte Chemie International Edition 2016 Volume 55( Issue 19) pp:5727-5732
Publication Date(Web):
DOI:10.1002/anie.201511805
Abstract
Current methods of monitoring breathing require cumbersome, inconvenient, and often expensive devices; this requirement sets practical limitations on the frequency and duration of measurements. This article describes a paper-based moisture sensor that uses the hygroscopic character of paper (i.e. the ability of paper to adsorb water reversibly from the surrounding environment) to measure patterns and rate of respiration by converting the changes in humidity caused by cycles of inhalation and exhalation to electrical signals. The changing level of humidity that occurs in a cycle causes a corresponding change in the ionic conductivity of the sensor, which can be measured electrically. By combining the paper sensor with conventional electronics, data concerning respiration can be transmitted to a nearby smartphone or tablet computer for post-processing, and subsequently to a cloud server. This means of sensing provides a new, practical method of recording and analyzing patterns of breathing.
The Journal of Physical Chemistry C 2016 Volume 120(Issue 21) pp:11331-11337
Publication Date(Web):April 11, 2016
DOI:10.1021/acs.jpcc.6b01253
This paper reports rates of charge tunneling across self-assembled monolayers (SAMs) of compounds containing oligophenyl groups, supported on gold and silver, using Ga2O3/EGaIn as the top electrode. It compares the attenuation constant, β, and the pre-exponential parameter, J0, of the simplified Simmons equation across oligophenyl groups (R = Phn; n = 1, 2, 3) with three different anchoring groups (thiol, HSR; methanethiol, HSCH2R; and acetylene, HC≡CR) that attach R to the template-stripped gold or silver substrate. The results demonstrate that the structure of the molecular linker between the anchoring group (−S– or −C≡C−) and the oligophenyl moiety significantly influences the rate of charge transport. SAMs of SPhn and C≡CPhn on gold show similar values of β and log |J0| (β = 0.28 ± 0.03 Å–1 and log |J0| = 2.7 ± 0.1 for Au/SPhn; β = 0.30 ± 0.02 Å–1 and log |J0| = 3.0 ± 0.1 for Au/C≡CPhn). The introduction of a single intervening methylene (CH2) group between the anchoring sulfur atom and the aromatic units generates SAMs of SCH2Phn and increases β to ca. 0.66 ± 0.06 Å–1 on both gold and silver substrates. (For n-alkanethiolates on gold, the corresponding values are β = 0.76 ± 0.03 Å–1 and log |J0| = 4.2 ± 0.2). Density functional theory calculations indicate that the highest occupied molecular orbitals (HOMOs) of both SPhn and C≡CPhn extend beyond the anchoring group and onto the phenyl rings; SAMs composed of these two groups of molecules result in indistinguishable rates of charge transport. The introduction of the CH2 group, to generate SCH2Phn, disrupts the delocalization of the orbitals, localizes the HOMO on the anchoring sulfur atom, and results in the experimentally observed increase in β to a value closer to that of a SAM of n-alkylthiolate molecules.
Co-reporter:Kyungtae Kang, Jeong-Mo Choi, Jerome M. Fox, Phillip W. Snyder, Demetri T. Moustakas, and George M. Whitesides
The Journal of Physical Chemistry B 2016 Volume 120(Issue 27) pp:6461-6468
Publication Date(Web):June 12, 2016
DOI:10.1021/acs.jpcb.6b01105
This paper uses crystals of bovine carbonic anhydrase (CA) and its acetylated variant to examine (i) how a large negative formal charge can be accommodated in protein–protein interfaces, (ii) why lysine residues are often excluded from them, and (iii) how changes in the surface charge of a protein can alter the structure and organization of protein–protein interfaces. It demonstrates that acetylation of lysine residues on the surface of CA increases the participation of polar residues (particularly acetylated lysine) in protein–protein interfaces, and decreases the participation of nonpolar residues in those interfaces. Negatively charged residues are accommodated in protein–protein interfaces via (i) hydrogen bonds or van der Waals interactions with polar residues or (ii) salt bridges with other charged residues. The participation of acetylated lysine in protein–protein interfaces suggests that unacetylated lysine tends to be excluded from interfaces because of its positive charge, and not because of a loss in conformational entropy. Results also indicate that crystal contacts in acetylated CA become less constrained geometrically and, as a result, more closely packed (i.e., more tightly clustered spatially) than those of native CA. This study demonstrates a physical-organic approach—and a well-defined model system—for studying the role of charges in protein–protein interactions.
Co-reporter:Kung-Ching Liao; Liang-Yan Hsu; Carleen M. Bowers; Herschel Rabitz
Journal of the American Chemical Society 2015 Volume 137(Issue 18) pp:5948-5954
Publication Date(Web):April 14, 2015
DOI:10.1021/jacs.5b00448
Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure AgTS/O2C–R1–R2–H//Ga2O3/EGaIn, where AgTS is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units—(CH2)n and (C6H4)m—that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the AgTS/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(−β1d1 – β2d2), where J(V) is the current density (A/cm2) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.
Co-reporter:Jerome M. Fox; Kyungtae Kang; Woody Sherman; Annie Héroux; G. Madhavi Sastry; Mostafa Baghbanzadeh; Matthew R. Lockett
Journal of the American Chemical Society 2015 Volume 137(Issue 11) pp:3859-3866
Publication Date(Web):March 4, 2015
DOI:10.1021/jacs.5b00187
This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn2+ cofactor. In these ion pairs, the free energy of anion–Zn2+ association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the “law of matching water affinities”. Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn2+, trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to—and to alter the charge and hydration structure of—polar, nonpolar, and topographically complex concavities on the surfaces of proteins.
Co-reporter:Kung-Ching Liao; Carleen M. Bowers; Hyo Jae Yoon
Journal of the American Chemical Society 2015 Volume 137(Issue 11) pp:3852-3858
Publication Date(Web):March 9, 2015
DOI:10.1021/jacs.5b00137
This paper describes the influence of the substitution of fluorine for hydrogen on the rate of charge transport by hole tunneling through junctions of the form AgTSO2C(CH2)n(CF2)mT//Ga2O3/EGaIn, where T is methyl (CH3) or trifluoromethyl (CF3). Alkanoate-based self-assembled monolayers (SAMs) having perfluorinated groups (RF) show current densities that are lower (by factors of 20–30) than those of the homologous hydrocarbons (RH), while the attenuation factors of the simplified Simmons equation for methylene (β = (1.05 ± 0.02)nCH2–1) and difluoromethylene (β = (1.15 ± 0.02)nCF2–1) are similar (although the value for (CF2)n is statistically significantly larger). A comparative study focusing on the terminal fluorine substituents in SAMs of ω-tolyl- and -phenyl-alkanoates suggests that the C–F//Ga2O3 interface is responsible for the lower tunneling currents for CF3. The decrease in the rate of charge transport in SAMs with RF groups (relative to homologous RH groups) is plausibly due to an increase in the height of the tunneling barrier at the T//Ga2O3 interface, and/or to weak van der Waals interactions at that interface.
Soft devices can be bent, stretched, and compressed reversibly, but conventional wires are rigid. This work describes stretchable composites that are easily fabricated with simple tools and commodity materials, and that can provide a strategy for electrical wiring that meets certain needs of soft devices. These composites are made by combining metal wool and elastomeric polymers. Embedding fine (average fiber width ≈25 μm) steel wool (or other metal wools) in a silicone polymer creates an electrically conductive path through the nonconductive elastomer. This composite is flexible, stretchable, compressible, inexpensive, and simple to incorporate into the bodies of soft devices. It is also electrically anisotropic, and shows maximum conductivity along the majority axis of the fibers, but maximum extension perpendicular to this axis. The utility of this composite for creating an electrically conductive path through an elastomer was demonstrated in several devices, including: a soft, solderless breadboard, a soft touch sensor, and a soft strain gauge.
Combining aqueous multiphase systems (AMPS) and magnetic levitation (MagLev) provides a method to produce hybrid gradients in apparent density. AMPS—solutions of different polymers, salts, or surfactants that spontaneously separate into immiscible but predominantly aqueous phases—offer thermodynamically stable steps in density that can be tuned by the concentration of solutes. MagLev—the levitation of diamagnetic objects in a paramagnetic fluid within a magnetic field gradient—can be arranged to provide a near-linear gradient in effective density where the height of a levitating object above the surface of the magnet corresponds to its density; the strength of the gradient in effective density can be tuned by the choice of paramagnetic salt and its concentrations and by the strength and gradient in the magnetic field. Including paramagnetic salts (e.g., MnSO4 or MnCl2) in AMPS, and placing them in a magnetic field gradient, enables their use as media for MagLev. The potential to create large steps in density with AMPS allows separations of objects across a range of densities. The gradients produced by MagLev provide resolution over a continuous range of densities. By combining these approaches, mixtures of objects with large differences in density can be separated and analyzed simultaneously. Using MagLev to add an effective gradient in density also enables tuning the range of densities captured at an interface of an AMPS by simply changing the position of the container in the magnetic field. Further, by creating AMPS in which phases have different concentrations of paramagnetic ions, the phases can provide different resolutions in density. These results suggest that combining steps in density with gradients in density can enable new classes of separations based on density.
Co-reporter:Anand Bala Subramaniam, Mathieu Gonidec, Nathan D. Shapiro, Kayleigh M. Kresse and George M. Whitesides
Lab on a Chip 2015 vol. 15(Issue 4) pp:1009-1022
Publication Date(Web):04 Dec 2014
DOI:10.1039/C4LC01161A
This paper reports the development of Metal-amplified Density Assays, or MADAs – a method of conducting quantitative or multiplexed assays, including immunoassays, by using Magnetic Levitation (MagLev) to measure metal-amplified changes in the density of beads labeled with biomolecules. The binding of target analytes (i.e. proteins, antibodies, antigens) to complementary ligands immobilized on the surface of the beads, followed by a chemical amplification of the binding in a form that results in a change in the density of the beads (achieved by using gold nanoparticle-labeled biomolecules, and electroless deposition of gold or silver), translates analyte binding events into changes in density measureable using MagLev. A minimal model based on diffusion-limited growth of hemispherical nuclei on a surface reproduces the dynamics of the assay. A MADA – when performed with antigens and antibodies – is called a Density-Linked Immunosorbent Assay, or DeLISA. Two immunoassays provided a proof of principle: a competitive quantification of the concentration of neomycin in whole milk, and a multiplexed detection of antibodies against Hepatitis C virus NS3 protein and syphilis T. pallidum p47 protein in serum. MADAs, including DeLISAs, require, besides the requisite biomolecules and amplification reagents, minimal specialized equipment (two permanent magnets, a ruler or a capillary with calibrated length markings) and no electrical power to obtain a quantitative readout of analyte concentration. With further development, the method may be useful in resource-limited or point-of-care settings.
This paper describes a method of isolating small, highly accurate density-standard beads and characterizing their densities using accurate and experimentally traceable techniques. Density standards have a variety of applications, including the characterization of density gradients, which are used to separate objects in a variety of fields. Glass density-standard beads can be very accurate (±0.0001 g cm–3) but are too large (3–7 mm in diameter) for many applications. When smaller density standards are needed, commercial polymer microspheres are often used. These microspheres have standard deviations in density ranging from 0.006 to 0.021 g cm–3; these distributions in density make these microspheres impractical for applications demanding small steps in density. In this paper, commercial microspheres are fractionated using aqueous multiphase systems (AMPS), aqueous mixture of polymers and salts that spontaneously separate into phases having molecularly sharp steps in density, to isolate microspheres having much narrower distributions in density (standard deviations from 0.0003 to 0.0008 g cm–3) than the original microspheres. By reducing the heterogeneity in densities, this method reduces the uncertainty in the density of any specific bead and, therefore, improves the accuracy within the limits of the calibration standards used to characterize the distributions in density.
This paper demonstrates that, for applications in resource-limited environments, expensive microplate spectrophotometers that are used in many central laboratories for parallel measurement of absorbance of samples can be replaced by photometers based on inexpensive and ubiquitous, consumer electronic devices (e.g., scanners and cell-phone cameras). Two devices, (i) a flatbed scanner operating in transmittance mode and (ii) a camera-based photometer (constructed from a cell phone camera, a planar light source, and a cardboard box), demonstrate the concept. These devices illuminate samples in microtiter plates from one side and use the RGB-based imaging sensors of the scanner/camera to measure the light transmitted to the other side. The broadband absorbance of samples (RGB-resolved absorbance) can be calculated using the RGB color values of only three pixels per microwell. Rigorous theoretical analysis establishes a well-defined relationship between the absorbance spectrum of a sample and its corresponding RGB-resolved absorbance. The linearity and precision of measurements performed with these low-cost photometers on different dyes, which absorb across the range of the visible spectrum, and chromogenic products of assays (e.g., enzymatic, ELISA) demonstrate that these low-cost photometers can be used reliably in a broad range of chemical and biochemical analyses. The ability to perform accurate measurements of absorbance on liquid samples, in parallel and at low cost, would enable testing, typically reserved for well-equipped clinics and laboratories, to be performed in circumstances where resources and expertise are limited.
Co-reporter:Carleen M. Bowers, Kung-Ching Liao, Tomasz Zaba, Dmitrij Rappoport, Mostafa Baghbanzadeh, Benjamin Breiten, Anna Krzykawska, Piotr Cyganik, and George M. Whitesides
ACS Nano 2015 Volume 9(Issue 2) pp:1471
Publication Date(Web):January 9, 2015
DOI:10.1021/nn5059216
This paper investigates the influence of the interface between a gold or silver metal electrode and an n-alkyl SAM (supported on that electrode) on the rate of charge transport across junctions with structure Met(Au or Ag)TS/A(CH2)nH//Ga2O3/EGaIn by comparing measurements of current density, J(V), for Met/AR = Au/thiolate (Au/SR), Ag/thiolate (Ag/SR), Ag/carboxylate (Ag/O2CR), and Au/acetylene (Au/C≡CR), where R is an n-alkyl group. Values of J0 and β (from the Simmons equation) were indistinguishable for these four interfaces. Since the anchoring groups, A, have large differences in their physical and electronic properties, the observation that they are indistinguishable in their influence on the injection current, J0 (V = 0.5) indicates that these four Met/A interfaces do not contribute to the shape of the tunneling barrier in a way that influences J(V).Keywords: alkynes; charge transport; EGaIn; molecular electronics; self-assembled monolayer;
Spreading fires are noisy (and potentially chaotic) systems in which transitions in dynamics are notoriously difficult to
predict. As flames move through spatially heterogeneous environments, sudden shifts in temperature, wind, or topography can
generate combustion instabilities, or trigger self-stabilizing feedback loops, that dramatically amplify the intensities and
rates with which fires propagate. Such transitions are rarely captured by predictive models of fire behavior and, thus, complicate
efforts in fire suppression. This paper describes a simple, remarkably instructive physical model for examining the eruption
of small flames into intense, rapidly moving flames stabilized by feedback between wind and fire (i.e., “wind–fire coupling”—a
mechanism of feedback particularly relevant to forest fires), and it presents evidence that characteristic patterns in the
dynamics of spreading flames indicate when such transitions are likely to occur. In this model system, flames propagate along
strips of nitrocellulose with one of two possible modes of propagation: a slow, structured mode, and a fast, unstructured
mode sustained by wind–fire coupling. Experimental examination of patterns in dynamics that emerge near bifurcation points
suggests that symptoms of critical slowing down (i.e., the slowed recovery of the system from perturbations as it approaches
tipping points) warn of impending transitions to the unstructured mode. Findings suggest that slowing responses of spreading
flames to sudden changes in environment (e.g., wind, terrain, temperature) may anticipate the onset of intense, feedback-stabilized
modes of propagation (e.g., “blowup fires” in forests).
Co-reporter:Dr. Ashok A. Kumar;Dr. Jonathan W. Hennek;Dr. Barbara S. Smith;Dr. Shailendra Kumar;Patrick Beattie;Sidhartha Jain;Dr. Jason P. Roll;Dr. Thomas P. Stossel;Dr. Catherine Chunda-Liyoka; George M. Whitesides
Angewandte Chemie International Edition 2015 Volume 54( Issue 20) pp:5836-5853
Publication Date(Web):
DOI:10.1002/anie.201411741
Abstract
Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field—the processes intended to evaluate operation and performance under realistic conditions—are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments.
Co-reporter:Dr. Ashok A. Kumar;Dr. Jonathan W. Hennek;Dr. Barbara S. Smith;Dr. Shailendra Kumar;Patrick Beattie;Sidhartha Jain;Dr. Jason P. Roll;Dr. Thomas P. Stossel;Dr. Catherine Chunda-Liyoka; George M. Whitesides
Die universitäre Forschung an Point-of-Care-Diagnostik für die globale Gesundheit verzeichnet ein stetes Wachstum, allerdings verlassen viele Testsysteme niemals das Labor. Prozesse, die die diagnostische Technologie vom Labor ins Feld überführen – Prozesse, mit deren Hilfe Betrieb und Leistungsvermögen unter realistischen Bedingungen evaluiert werden sollen –, sind komplizierter, als sie scheinen mögen. Zwei Fallstudien illustrieren diesen Prozess: die Entwicklung eines papierbasierten Testsystems zur Messung der Leberfunktion sowie die eines Testsystems zur Identifikation von Sichelzellanämie, das auf wässrigen, mehrphasigen Systemen sowie Unterschieden in der Dichte normaler und sichelförmiger Zellen beruht. Aus den Details der Entwicklung dieser beiden Testsysteme lassen sich allgemeingültige Strategien zum Aufbau von Kooperationen, zum Herstellen von Prototypen, zur Validierung, zum Design von Studien und zur Evaluation von Point-of-Care-Diagnostik ableiten. Die aus diesen Erfahrungen gezogenen (verfahrens)technischen Lehren können Wissenschaftlern nutzen, die diagnostische Tests für Entwicklungsländer und – allgemeiner – Technologien für den Einsatz bei begrenzten Ressourcen entwerfen.
Co-reporter:Bobak Mosadegh, Matthew R. Lockett, Kyaw Thu Minn, Karen A. Simon, Karl Gilbert, Shawn Hillier, David Newsome, Howard Li, Amy B. Hall, Diane M. Boucher, Brenda K. Eustace, George M. Whitesides
Co-reporter:Douglas C. Watson, Ramses V. Martinez, Yannik Fontana, Eleonora Russo-Averchi, Martin Heiss, Anna Fontcuberta i Morral, George M. Whitesides, and Marko Lončar
Nano Letters 2014 Volume 14(Issue 2) pp:524-531
Publication Date(Web):January 20, 2014
DOI:10.1021/nl403552q
This paper describes the fabrication of functional optical devices by sectioning quantum-dot-in-nanowires systems with predefined lengths and orientations. This fabrication process requires only two steps, embedding the nanowires in epoxy and using an ultramicrotome to section them across their axis (“nanoskiving”). This work demonstrates the combination of the following four capabilities: (i) the control of the length of the nanowire sections at the nanometer scale; (ii) the ability to process the nanowires after cutting using wet etching; (iii) the possibility of modifying the geometry of the wire by varying the sectioning angle; and (iv) the generation of as many as 120 consecutive slabs bearing nanowires that have uniform size and approximately reproducible lateral patterns and that can subsequently be transferred to different substrates. The quantum dots inside the nanowires are functional and of a high optical quality after the sectioning process and exhibit photoluminescent emission with wavelengths in the range of 650–710 nm.
Co-reporter:Carleen M. Bowers, Kung-Ching Liao, Hyo Jae Yoon, Dmitrij Rappoport, Mostafa Baghbanzadeh, Felice C. Simeone, and George M. Whitesides
Nano Letters 2014 Volume 14(Issue 6) pp:3521-3526
Publication Date(Web):May 19, 2014
DOI:10.1021/nl501126e
Junctions with the structure AgTS/S(CH2)nT//Ga2O3/EGaIn (where S(CH2)nT is a self-assembled monolayer, SAM, of n-alkanethiolate bearing a terminal functional group T) make it possible to examine the response of rates of charge transport by tunneling to changes in the strength of the interaction between T and Ga2O3. Introducing a series of Lewis acidic/basic functional groups (T = −OH, −SH, −CO2H, −CONH2, and −PO3H) at the terminus of the SAM gave values for the tunneling current density, J(V) in A/cm2, that were indistinguishable (i.e., differed by less than a factor of 3) from the values observed with n-alkanethiolates of equivalent length. The insensitivity of the rate of tunneling to changes in the terminal functional group implies that replacing weak van der Waals contact interactions with stronger hydrogen- or ionic bonds at the T//Ga2O3 interface does not change the shape (i.e., the height or width) of the tunneling barrier enough to affect rates of charge transport. A comparison of the injection current, J0, for T = −CO2H, and T = −CH2CH3−two groups having similar extended lengths (in Å, or in numbers of non-hydrogen atoms)−suggests that both groups make indistinguishable contributions to the height of the tunneling barrier.
Co-reporter:Mostafa Baghbanzadeh ; Felice C. Simeone ; Carleen M. Bowers ; Kung-Ching Liao ; Martin Thuo ; Mahdi Baghbanzadeh ; Michael S. Miller ; Tricia Breen Carmichael
Journal of the American Chemical Society 2014 Volume 136(Issue 48) pp:16919-16925
Publication Date(Web):November 7, 2014
DOI:10.1021/ja509436k
This paper compares rates of charge transport across self-assembled monolayers (SAMs) of n-alkanethiolates having odd and even numbers of carbon atoms (nodd and neven) using junctions with the structure MTS/SAM//Ga2O3/EGaIn (M = Au or Ag). Measurements of current density, J(V), across SAMs of n-alkanethiolates on AuTS and AgTS demonstrated a statistically significant odd–even effect on AuTS, but not on AgTS, that could be detected using this technique. Statistical analysis showed the values of tunneling current density across SAMs of n-alkanethiolates on AuTS with nodd and neven belonging to two separate sets, and while there is a significant difference between the values of injection current density, J0, for these two series (log|J0Au,even| = 4.0 ± 0.3 and log|J0Au,odd| = 4.5 ± 0.3), the values of tunneling decay constant, β, for nodd and neven alkyl chains are indistinguishable (βAu,even = 0.73 ± 0.02 Å–1, and βAu,odd= 0.74 ± 0.02 Å–1). A comparison of electrical characteristics across junctions of n-alkanethiolate SAMs on gold and silver electrodes yields indistinguishable values of β and J0 and indicates that a change that substantially alters the tilt angle of the alkyl chain (and, therefore, the thickness of the SAM) has no influence on the injection current density across SAMs of n-alkanethiolates.
Co-reporter:Hyo Jae Yoon ; Kung-Ching Liao ; Matthew R. Lockett ; Sen Wai Kwok ; Mostafa Baghbanzadeh
Journal of the American Chemical Society 2014 Volume 136(Issue 49) pp:17155-17162
Publication Date(Web):November 12, 2014
DOI:10.1021/ja509110a
Molecular rectification is a particularly attractive phenomenon to examine in studying structure–property relationships in charge transport across molecular junctions, since the tunneling currents across the same molecular junction are measured, with only a change in the sign of the bias, with the same electrodes, molecule(s), and contacts. This type of experiment minimizes the complexities arising from measurements of current densities at one polarity using replicate junctions. This paper describes a new organic molecular rectifier: a junction having the structure AgTS/S(CH2)11-4-methyl-2,2′-bipyridyl//Ga2O3/EGaIn (AgTS: template-stripped silver substrate; EGaIn: eutectic gallium–indium alloy) which shows reproducible rectification with a mean r+ = |J(+1.0 V)|/|J(−1.0 V)| = 85 ± 2. This system is important because rectification occurs at a polarity opposite to that of the analogous but much more extensively studied systems based on ferrocene. It establishes (again) that rectification is due to the SAM, and not to redox reactions involving the Ga2O3 film, and confirms that rectification is not related to the polarity in the junction. Comparisons among SAM-based junctions incorporating the Ga2O3/EGaIn top electrode and a variety of heterocyclic terminal groups indicate that the metal-free bipyridyl group, not other features of the junction, is responsible for the rectification. The paper also describes a structural and mechanistic hypothesis that suggests a partial rationalization of values of rectification available in the literature.
Co-reporter:Siowling Soh ; Helena Liu ; Rebecca Cademartiri ; Hyo Jae Yoon
Journal of the American Chemical Society 2014 Volume 136(Issue 38) pp:13348-13354
Publication Date(Web):August 29, 2014
DOI:10.1021/ja506830p
Many processes involve the movement of a disordered collection of small particles (e.g., powders, grain, dust, and granular foods). These particles move chaotically, interact randomly among themselves, and gain electrical charge by contact electrification. Understanding the mechanisms of contact electrification of multiple interacting particles has been challenging, in part due to the complex movement and interactions of the particles. To examine the processes contributing to contact electrification at the level of single particles, a system was constructed in which an array of millimeter-sized polymeric beads of different materials were agitated on a dish. The dish was filled almost completely with beads, such that beads did not exchange positions. At the same time, during agitation, there was sufficient space for collisions with neighboring beads. The charge of the beads was measured individually after agitation. Results of systematic variations in the organization and composition of the interacting beads showed that three mechanisms determined the steady-state charge of the beads: (i) contact electrification (charging of beads of different materials), (ii) contact de-electrification (discharging of beads of the same charge polarity to the atmosphere), and (iii) a long-range influence across beads not in contact with one another (occurring, plausibly, by diffusion of charge from a bead with a higher charge to a bead with a lower charge of the same polarity).
Soft robots actuated by inflation of a pneumatic network (a “pneu-net”) of small channels in elastomeric materials are appealing for producing sophisticated motions with simple controls. Although current designs of pneu-nets achieve motion with large amplitudes, they do so relatively slowly (over seconds). This paper describes a new design for pneu-nets that reduces the amount of gas needed for inflation of the pneu-net, and thus increases its speed of actuation. A simple actuator can bend from a linear to a quasi-circular shape in 50 ms when pressurized at ΔP = 345 kPa. At high rates of pressurization, the path along which the actuator bends depends on this rate. When inflated fully, the chambers of this new design experience only one-tenth the change in volume of that required for the previous design. This small change in volume requires comparably low levels of strain in the material at maximum amplitudes of actuation, and commensurately low rates of fatigue and failure. This actuator can operate over a million cycles without significant degradation of performance. This design for soft robotic actuators combines high rates of actuation with high reliability of the actuator, and opens new areas of application for them.
This paper describes the modular magnetic assembly of reconfigurable, pneumatically actuated robots composed of soft and hard components and materials. The soft components of these hybrid robots are actuators fabricated from silicone elastomers using soft lithography, and the hard components are acrylonitrile–butadiene–styrene (ABS) structures made using 3D printing. Neodymium–iron–boron (NdFeB) ring magnets are embedded in these components to make and maintain the connections between components. The reversibility of these magnetic connections allows the rapid reconfiguration of these robots using components made of different materials (soft and hard) that also have different sizes, structures, and functions; in addition, it accelerates the testing of new designs, the exploration of new capabilities, and the repair or replacement of damaged parts. This method of assembling soft actuators to build soft machines addresses some limitations associated with using soft lithography for the direct molding of complex 3D pneumatic networks. Combining the self-aligning property of magnets with pneumatic control makes it possible for a teleoperator to modify the structures and capabilities of these robots readily in response to the requirements of different tasks.
This paper characterizes the ability of soft pneumatic actuators and robots to resist mechanical insults that would irreversibly damage or destroy hard robotic systems—systems fabricated in metals and structural polymers, and actuated mechanically—of comparable sizes. The pneumatic networks that actuate these soft machines are formed by bonding two layers of elastomeric or polymeric materials that have different moduli on application of strain by pneumatic inflation; this difference in strain between an extensible top layer and an inextensible, strain-limiting, bottom layer causes the pneumatic network to expand anisotropically. While all the soft machines described here are, to some extent, more resistant to damage by compressive forces, blunt impacts, and severe bending than most corresponding hard systems, the composition of the strain-limiting layers confers on them very different tensile and compressive strengths.
This paper describes adaptive composites that respond to mechanical stimuli by changing their Young's modulus. These composites are fabricated by combining a shorter layer of elastic material (e.g., latex) and a longer layer of stiffer material (e.g., polyethylene and Kevlar), and fixing them together at their ends. Tension along the layered composite increases its length, and as the strain increases, the composite changes the load-bearing layer from the elastic to the stiff material. The result is a step in the Young's modulus of the composite. The characteristics of the step (or steps) can be engineered by changing the constituent materials, the number of layers, and their geometries (e.g., sinusoidal, hierarchical, two-dimensional web-like, rod-coil, embedded, and ring structures). For composites with more than two steps in modulus, the materials within the composites can be layered in a hierarchical structure to fit within a smaller volume, without sacrificing performance. These composites can also be used to make structures with tunable, stepped compressive moduli. An adaptation of these principles can generate an electronic sensor that can monitor the applied compressive strain. Increasing or decreasing the strain closes or opens a circuit and reversibly activates a light-emitting diode.
The fabrication and properties of “fluoroalkylated paper” (“RF paper”) by vapor-phase silanization of paper with fluoroalkyl trichlorosilanes is reported. RF paper is both hydrophobic and oleophobic: it repels water (θappH2O>140°), organic liquids with surface tensions as low as 28 mN m-1, aqueous solutions containing ionic and non-ionic surfactants, and complex liquids such as blood (which contains salts, surfactants, and biological material such as cells, proteins, and lipids). The propensity of the paper to resist wetting by liquids with a wide range of surface tensions correlates with the length and degree of fluorination of the organosilane (with a few exceptions in the case of methyl trichlorosilane-treated paper), and with the roughness of the paper. RF paper maintains the high permeability to gases and mechanical flexibility of the untreated paper, and can be folded into functional shapes (e.g., microtiter plates and liquid-filled gas sensors). When impregnated with a perfluorinated oil, RF paper forms a “slippery” surface (paper slippery liquid-infused porous surface, or “paper SLIPS“) capable of repelling liquids with surface tensions as low as 15 mN m-1. The foldability of the paper SLIPS allows the fabrication of channels and flow switches to guide the transport of liquid droplets.
This paper describes the fabrication of 3D soft, inflatable structures from thin, 2D tiles fabricated from elastomeric polymers. The tiles are connected using soft joints that increase the surface area available for gluing them together, and mechanically reinforce the structures to withstand the tensile forces associated with pneumatic actuation. The ability of the elastomeric polymer to withstand large deformations without failure makes it possible to explore and implement new joint designs, for example “double-taper dovetail joints,” that cannot be used with hard materials. This approach simplifies the fabrication of soft structures comprising materials with different physical properties (e.g., stiffness, electrical conductivity, optical transparency), and provides the methods required to “program” the response of these structures to mechanical (e.g., pneumatic pressurization) and other physical (e.g., electrical) stimuli. The flexibility and modularity of this approach is demonstrated in a set of soft structures that expanded or buckled into distinct, predictable shapes when inflated or deflated. These structures combine easily to form extended systems with motions dependent on the configurations of the selected components, and, when fabricated with electrically conductive tiles, electronic circuits with pneumatically active elements. This approach to the fabrication of hollow, 3D structures provides routes to new soft actuators.
Co-reporter:Jabulani R. Barber, Hyo Jae Yoon, Carleen M. Bowers, Martin M. Thuo, Benjamin Breiten, Diana M. Gooding, and George M. Whitesides
Chemistry of Materials 2014 Volume 26(Issue 13) pp:3938
Publication Date(Web):June 4, 2014
DOI:10.1021/cm5014784
This paper investigates the influence of the atmosphere used in the fabrication of top electrodes from the liquid eutectic of gallium and indium (EGaIn) (the so-called “EGaIn” electrodes), and in measurements of current density, J(V) (A/cm2), across self-assembled monolayers (SAMs) incorporated into Ag/SR//Ga2O3/EGaIn junctions, on values of J(V) obtained using these electrodes. A gas-tight measurement chamber was used to control the atmosphere in which the electrodes were formed, and also to control the environment in which the electrodes were used to measure current densities across SAM-based junctions. Seven different atmospheres—air, oxygen, nitrogen, argon, and ammonia, as well as air containing vapors of acetic acid or water—were surveyed using both “rough” conical-tip electrodes, and “smooth” hanging-drop electrodes. (The manipulation of the oxide film during the creation of the conical-tip electrodes leads to substantial, micrometer-scale roughness on the surface of the electrode, the extrusion of the drop creates a significantly smoother surface.) Comparing junctions using both geometries for the electrodes, across a SAM of n-dodecanethiol, in air, gave log |J|mean = −2.4 ± 0.4 for the conical tip, and log |J|mean = −0.6 ± 0.3 for the drop electrode (and, thus, Δlog |J| ≈ 1.8); this increase in current density is attributed to a change in the effective electrical contact area of the junction. To establish the influence of the resistivity of the Ga2O3 film on values of J(V), junctions comprising a graphite electrode and a hanging-drop electrode were compared in an experiment where the electrodes did, and did not, have a surface oxide film; the presence of the oxide did not influence measurements of log |J(V)|, and therefore did not contribute to the electrical resistance of the electrode. However, the presence of an oxide film did improve the stability of junctions and increase the yield of working electrodes from ∼70% to ∼100%. Increasing the relative humidity (RH) in which J(V) was measured did not influence these values (across methyl (CH3)- or carboxyl (CO2H)-terminated SAMs) over the range typically encountered in the laboratory (20%–60% (RH)).
Co-reporter:Martin M. Thuo, Ramses V. Martinez, Wen-Jie Lan, Xinyu Liu, Jabulani Barber, Manza B. J. Atkinson, Dineth Bandarage, Jean-Francis Bloch, and George M. Whitesides
Chemistry of Materials 2014 Volume 26(Issue 14) pp:4230
Publication Date(Web):June 18, 2014
DOI:10.1021/cm501596s
This article describes the use of embossing and “cut-and-stack” methods of assembly, to generate microfluidic devices from omniphobic paper and demonstrates that fluid flowing through these devices behaves similarly to fluid in an open-channel microfluidic device. The porosity of the paper to gases allows processes not possible in devices made using PDMS or other nonporous materials. Droplet generators and phase separators, for example, could be made by embossing “T”-shaped channels on paper. Vertical stacking of embossed or cut layers of omniphobic paper generated three-dimensional systems of microchannels. The gas permeability of the paper allowed fluid in the microchannel to contact and exchange with environmental or directed gases. An aqueous stream of water containing a pH indicator, as one demonstration, changed color upon exposure to air containing HCl or NH3 gases.
Co-reporter:Xiaochuan Yang, Shin Yee Wong, David K. Bwambok, Manza B. J. Atkinson, Xi Zhang, George M. Whitesides and Allan S. Myerson
Chemical Communications 2014 vol. 50(Issue 56) pp:7548-7551
Publication Date(Web):21 May 2014
DOI:10.1039/C4CC02604G
Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.
Co-reporter:Ana C. Glavan, Dionysios C. Christodouleas, Bobak Mosadegh, Hai Dong Yu, Barbara S. Smith, Joshua Lessing, M. Teresa Fernández-Abedul, and George M. Whitesides
This work describes a device for electrochemical enzyme-linked immunosorbent assay (ELISA) designed for low-resource settings and diagnostics at the point of care. The device is fabricated entirely in hydrophobic paper, produced by silanization of paper with decyl trichlorosilane, and comprises two zones separated by a central crease: an embossed microwell, on the surface of which the antigen or antibody immobilization and recognition events occur, and a detection zone where the electrodes are printed. The two zones are brought in contact by folding the device along this central crease; the analytical signal is recorded from the folded configuration. Two proof-of-concept applications, an electrochemical direct ELISA for the detection of rabbit IgG as a model antigen in buffer and an electrochemical sandwich ELISA for the detection of malarial histidine-rich protein from Plasmodium falciparum (Pf HRP2) in spiked human serum, show the versatility of this device. The limit of detection of the electrochemical sandwich ELISA for the quantification of Pf HRP2 in spiked human serum was 4 ng mL–1 (102 pmol L–1), a value within the range of clinically relevant concentrations.
This paper describes the design and fabrication of ion-sensing electrochemical paper-based analytical devices (EPADs) in which a miniaturized paper reference electrode is integrated with a small ion-selective paper electrode (ISPE) for potentiometric measurements. Ion-sensing EPADs use printed wax barriers to define electrochemical sample and reference zones. Single-layer EPADs for sensing of chloride ions include wax-defined sample and reference zones that each incorporate a Ag/AgCl electrode. In EPADs developed for other electrolytes (potassium, sodium, and calcium ions), a PVC-based ion-selective membrane is added to separate the sample zone from a paper indicator electrode. After the addition of a small volume (less than 10 μL) of sample and reference solutions to different zones, ion-sensing EPADs exhibit a linear response, over 3 orders of magnitude, in ranges of electrolyte concentrations that are relevant to a variety of applications, with a slope close to the theoretical value (59.2/z mV). Ion-selective EPADs provide a portable, inexpensive, and disposable way of measuring concentrations of electrolyte ions in aqueous solutions.
Co-reporter:Bobak Mosadegh, Aaron D. Mazzeo, Robert F. Shepherd, Stephen A. Morin, Unmukt Gupta, Idin Zhalehdoust Sani, David Lai, Shuichi Takayama and George M. Whitesides
Lab on a Chip 2014 vol. 14(Issue 1) pp:189-199
Publication Date(Web):25 Oct 2013
DOI:10.1039/C3LC51083B
One strategy for actuating soft machines (e.g., tentacles, grippers, and simple walkers) uses pneumatic inflation of networks of small channels in an elastomeric material. Although the management of a few pneumatic inputs and valves to control pressurized gas is straightforward, the fabrication and operation of manifolds containing many (>50) independent valves is an unsolved problem. Complex pneumatic manifolds—often built for a single purpose—are not easily reconfigured to accommodate the specific inputs (i.e., multiplexing of many fluids, ranges of pressures, and changes in flow rates) required by pneumatic systems. This paper describes a pneumatic manifold comprising a computer-controlled Braille display and a micropneumatic device. The Braille display provides a compact array of 64 piezoelectric actuators that actively close and open elastomeric valves of a micropneumatic device to route pressurized gas within the manifold. The positioning and geometries of the valves and channels in the micropneumatic device dictate the functionality of the pneumatic manifold, and the use of multi-layer soft lithography permits the fabrication of networks in a wide range of configurations with many possible functions. Simply exchanging micropneumatic devices of different designs enables rapid reconfiguration of the pneumatic manifold. As a proof of principle, a pneumatic manifold controlled a soft machine containing 32 independent actuators to move a ball above a flat surface.
This paper demonstrates that the gas-filled compartments in the packing material commonly called “bubble wrap” can be repurposed in resource-limited regions as containers to store liquid samples, and to perform bioanalyses. The bubbles of bubble wrap are easily filled by injecting the samples into them using a syringe with a needle or a pipet tip, and then sealing the hole with nail hardener. The bubbles are transparent in the visible range of the spectrum, and can be used as “cuvettes” for absorbance and fluorescence measurements. The interiors of these bubbles are sterile and allow storage of samples without the need for expensive sterilization equipment. The bubbles are also permeable to gases, and can be used to culture and store micro-organisms. By incorporating carbon electrodes, these bubbles can be used as electrochemical cells. This paper demonstrates the capabilities of the bubbles by culturing E. coli, growing C. elegans, measuring glucose and hemoglobin spectrophotometrically, and measuring ferrocyanide electrochemically, all within the bubbles.
In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines which subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.
Co-reporter:Alex Nemiroski;Dionysios C. Christodouleas;Jonathan W. Hennek;Ashok A. Kumar;E. Jane Maxwell;Maria Teresa Fernández-Abedul
PNAS 2014 Volume 111 (Issue 33 ) pp:11984-11989
Publication Date(Web):2014-08-19
DOI:10.1073/pnas.1405679111
This paper describes an inexpensive, handheld device that couples the most common forms of electrochemical analysis directly
to “the cloud” using any mobile phone, for use in resource-limited settings. The device is designed to operate with a wide
range of electrode formats, performs on-board mixing of samples by vibration, and transmits data over voice using audio—an
approach that guarantees broad compatibility with any available mobile phone (from low-end phones to smartphones) or cellular
network (second, third, and fourth generation). The electrochemical methods that we demonstrate enable quantitative, broadly
applicable, and inexpensive sensing with flexibility based on a wide variety of important electroanalytical techniques (chronoamperometry,
cyclic voltammetry, differential pulse voltammetry, square wave voltammetry, and potentiometry), each with different uses.
Four applications demonstrate the analytical performance of the device: these involve the detection of (i) glucose in the blood for personal health, (ii) trace heavy metals (lead, cadmium, and zinc) in water for in-field environmental monitoring, (iii) sodium in urine for clinical analysis, and (iv) a malarial antigen (Plasmodium falciparum histidine-rich protein 2) for clinical research. The combination of these electrochemical capabilities in an affordable,
handheld format that is compatible with any mobile phone or network worldwide guarantees that sophisticated diagnostic testing
can be performed by users with a broad spectrum of needs, resources, and levels of technical expertise.
Co-reporter:Anand Bala Subramaniam;Dian Yang;Hai-Dong Yu;Alex Nemiroski;Audrey K. Ellerbee;Simon Tricard;Siowling Soh
PNAS 2014 Volume 111 (Issue 36 ) pp:12980-12985
Publication Date(Web):2014-09-09
DOI:10.1073/pnas.1408705111
This paper describes several noncontact methods of orienting objects in 3D space using Magnetic Levitation (MagLev). The methods
use two permanent magnets arranged coaxially with like poles facing and a container containing a paramagnetic liquid in which
the objects are suspended. Absent external forcing, objects levitating in the device adopt predictable static orientations;
the orientation depends on the shape and distribution of mass within the objects. The orientation of objects of uniform density
in the MagLev device shows a sharp geometry-dependent transition: an analytical theory rationalizes this transition and predicts
the orientation of objects in the MagLev device. Manipulation of the orientation of the levitating objects in space is achieved
in two ways: (i) by rotating and/or translating the MagLev device while the objects are suspended in the paramagnetic solution between the
magnets; (ii) by moving a small external magnet close to the levitating objects while keeping the device stationary. Unlike mechanical
agitation or robotic selection, orienting using MagLev is possible for objects having a range of different physical characteristics
(e.g., different shapes, sizes, and mechanical properties from hard polymers to gels and fluids). MagLev thus has the potential
to be useful for sorting and positioning components in 3D space, orienting objects for assembly, constructing noncontact devices,
and assembling objects composed of soft materials such as hydrogels, elastomers, and jammed granular media.
Co-reporter:Ashok A. Kumar;Jonathan W. Hennek;Si Yi Ryan Lee;Julie Kanter;Carlo Brugnara;Sergey S. Shevkoplyas;Gaetana D’Alesio-Spina;Matthew R. Patton;Xiaoxi Yang
PNAS 2014 Volume 111 (Issue 41 ) pp:14864-14869
Publication Date(Web):2014-10-14
DOI:10.1073/pnas.1414739111
Although effective low-cost interventions exist, child mortality attributable to sickle cell disease (SCD) remains high in
low-resource areas due, in large part, to the lack of accessible diagnostic methods. The presence of dense (ρ > 1.120 g/cm3) cells is characteristic of SCD. The fluid, self-assembling step-gradients in density created by aqueous multiphase systems
(AMPSs) identifies SCD by detecting dense cells. AMPSs separate different forms of red blood cells by density in a microhematocrit
centrifuge and provide a visual means to distinguish individuals with SCD from those with normal hemoglobin or with nondisease,
sickle-cell trait in under 12 min. Visual evaluation of a simple two-phase system identified the two main subclasses of SCD
[homozygous (Hb SS) and heterozygous (Hb SC)] with a sensitivity of 90% (73–98%) and a specificity of 97% (86–100%). A three-phase
system identified these two types of SCD with a sensitivity of 91% (78–98%) and a specificity of 88% (74–98%). This system
could also distinguish between Hb SS and Hb SC. To the authors’ knowledge, this test demonstrates the first separation of
cells by density with AMPSs, and the usefulness of AMPSs in point-of-care diagnostic hematology.
Co-reporter:Dr. Kung-Ching Liao;Dr. Hyo Jae Yoon;Dr. Carleen M. Bowers;Dr. Felice C. Simeone;Dr. George M. Whitesides
Angewandte Chemie International Edition 2014 Volume 53( Issue 15) pp:3889-3893
Publication Date(Web):
DOI:10.1002/anie.201308472
Abstract
This paper compares rates of charge transport by tunneling across junctions with the structures AgTSX(CH2)2nCH3 //Ga2O3 /EGaIn (n=1–8 and X= SCH2 and O2C); here AgTS is template-stripped silver, and EGaIn is the eutectic alloy of gallium and indium. Its objective was to compare the tunneling decay coefficient (β, Å−1) and the injection current (J0, A cm−2) of the junctions comprising SAMs of n-alkanethiolates and n-alkanoates. Replacing AgTSSCH2-R with AgTSO2C-R (R=alkyl chains) had no significant influence on J0 (ca. 3×103 A cm−2) or β (0.75–0.79 Å−1)—an indication that such changes (both structural and electronic) in the AgTSXR interface do not influence the rate of charge transport. A comparison of junctions comprising oligo(phenylene)carboxylates and n-alkanoates showed, as expected, that β for aliphatic (0.79 Å−1) and aromatic (0.60 Å−1) SAMs differed significantly.
Co-reporter:Alex Nemiroski, Mathieu Gonidec, Jerome M. Fox, Philip Jean-Remy, Evan Turnage, and George M. Whitesides
ACS Nano 2014 Volume 8(Issue 11) pp:11061
Publication Date(Web):September 11, 2014
DOI:10.1021/nn504214b
Optical metasurfaces—patterned arrays of plasmonic nanoantennas that enable the precise manipulation of light–matter interactions—are emerging as critical components in many nanophotonic materials, including planar metamaterials, chemical and biological sensors, and photovoltaics. The development of these materials has been slowed by the difficulty of efficiently fabricating patterns with the required combinations of intricate nanoscale structure, high areal density, and/or heterogeneous composition. One convenient strategy that enables parallel fabrication of periodic nanopatterns uses self-assembled colloidal monolayers as shadow masks; this method has, however, not been extended beyond a small set of simple patterns and, thus, has remained incompatible with the broad design requirements of metasurfaces. This paper demonstrates a technique—shadow-sphere lithography (SSL)—that uses sequential deposition from multiple angles through plasma-etched microspheres to expand the variety and complexity of structures accessible by colloidal masks. SSL harnesses the entire, relatively unexplored, space of shadow-derived shapes and—with custom software to guide multiangled deposition—contains sufficient degrees of freedom to (i) design and fabricate a wide variety of metasurfaces that incorporate complex structures with small feature sizes and multiple materials and (ii) generate, in parallel, thousands of variations of structures for high-throughput screening of new patterns that may yield unexpected optical spectra. This generalized approach to engineering shadows of spheres provides a new strategy for efficient prototyping and discovery of periodic metasurfaces.Keywords: colloidal lithography; metasurfaces; nanoantennas; nanofabrication; nanophotonics; nanosphere lithography; plasmonics; shadow-sphere lithography;
This paper compares rates of charge transport by tunneling across junctions with the structures AgTSX(CH2)2nCH3 //Ga2O3 /EGaIn (n=1–8 and X= SCH2 and O2C); here AgTS is template-stripped silver, and EGaIn is the eutectic alloy of gallium and indium. Its objective was to compare the tunneling decay coefficient (β, Å−1) and the injection current (J0, A cm−2) of the junctions comprising SAMs of n-alkanethiolates and n-alkanoates. Replacing AgTSSCH2-R with AgTSO2C-R (R=alkyl chains) had no significant influence on J0 (ca. 3×103 A cm−2) or β (0.75–0.79 Å−1)—an indication that such changes (both structural and electronic) in the AgTSXR interface do not influence the rate of charge transport. A comparison of junctions comprising oligo(phenylene)carboxylates and n-alkanoates showed, as expected, that β for aliphatic (0.79 Å−1) and aromatic (0.60 Å−1) SAMs differed significantly.
Co-reporter:Benjamin Breiten ; Matthew R. Lockett ; Woody Sherman ; Shuji Fujita ; Mohammad Al-Sayah ; Heiko Lange ; Carleen M. Bowers ; Annie Heroux ; Goran Krilov
Journal of the American Chemical Society 2013 Volume 135(Issue 41) pp:15579-15584
Publication Date(Web):September 17, 2013
DOI:10.1021/ja4075776
The mechanism (or mechanisms) of enthalpy–entropy (H/S) compensation in protein–ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands—human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination—that we use to define enthalpy/entropy (H/S) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.
Co-reporter:Felice C. Simeone ; Hyo Jae Yoon ; Martin M. Thuo ; Jabulani R. Barber ; Barbara Smith
Journal of the American Chemical Society 2013 Volume 135(Issue 48) pp:18131-18144
Publication Date(Web):November 4, 2013
DOI:10.1021/ja408652h
Analysis of rates of tunneling across self-assembled monolayers (SAMs) of n-alkanethiolates SCn (with n = number of carbon atoms) incorporated in junctions having structure AgTS-SAM//Ga2O3/EGaIn leads to a value for the injection tunnel current density J0 (i.e., the current flowing through an ideal junction with n = 0) of 103.6±0.3 A·cm–2 (V = +0.5 V). This estimation of J0 does not involve an extrapolation in length, because it was possible to measure current densities across SAMs over the range of lengths n = 1–18. This value of J0 is estimated under the assumption that values of the geometrical contact area equal the values of the effective electrical contact area. Detailed experimental analysis, however, indicates that the roughness of the Ga2O3 layer, and that of the AgTS-SAM, determine values of the effective electrical contact area that are ∼10–4 the corresponding values of the geometrical contact area. Conversion of the values of geometrical contact area into the corresponding values of effective electrical contact area results in J0(+0.5 V) = 107.6±0.8 A·cm–2, which is compatible with values reported for junctions using top-electrodes of evaporated Au, and graphene, and also comparable with values of J0 estimated from tunneling through single molecules. For these EGaIn-based junctions, the value of the tunneling decay factor β (β = 0.75 ± 0.02 Å–1; β = 0.92 ± 0.02 nC–1) falls within the consensus range across different types of junctions (β = 0.73–0.89 Å–1; β = 0.9–1.1 nC–1). A comparison of the characteristics of conical Ga2O3/EGaIn tips with the characteristics of other top-electrodes suggests that the EGaIn-based electrodes provide a particularly attractive technology for physical-organic studies of charge transport across SAMs.
Co-reporter:Hyo Jae Yoon ; Carleen M. Bowers ; Mostafa Baghbanzadeh
Journal of the American Chemical Society 2013 Volume 136(Issue 1) pp:16-19
Publication Date(Web):December 18, 2013
DOI:10.1021/ja409771u
This paper describes a physical-organic study of the effect of uncharged, polar, functional groups on the rate of charge transport by tunneling across self-assembled monolayer (SAM)-based large-area junctions of the form AgTSS(CH2)nM(CH2)mT//Ga2O3/EGaIn. Here AgTS is a template-stripped silver substrate, -M- and -T are “middle” and “terminal” functional groups, and EGaIn is eutectic gallium–indium alloy. Twelve uncharged polar groups (-T = CN, CO2CH3, CF3, OCH3, N(CH3)2, CON(CH3)2, SCH3, SO2CH3, Br, P(O)(OEt)2, NHCOCH3, OSi(OCH3)3), having permanent dipole moments in the range 0.5 < μ < 4.5, were incorporated into the SAM. A comparison of the electrical characteristics of these junctions with those of junctions formed from n-alkanethiolates led to the conclusion that the rates of charge tunneling are insensitive to the replacement of terminal alkyl groups with the terminal polar groups in this set. The current densities measured in this work suggest that the tunneling decay parameter and injection current for SAMs terminated in nonpolar n-alkyl groups, and polar groups selected from common polar organic groups, are statistically indistinguishable.
Co-reporter:Wen-Jie Lan, E. Jane Maxwell, Claudio Parolo, David K. Bwambok, Anand Bala Subramaniam and George M. Whitesides
Lab on a Chip 2013 vol. 13(Issue 20) pp:4103-4108
Publication Date(Web):08 Aug 2013
DOI:10.1039/C3LC50771H
This paper describes the development of a referenced Electrochemical Paper-based Analytical Device (rEPAD) comprising a sample zone, a reference zone, and a connecting microfluidic channel that includes a central contact zone. We demonstrated that the rEPADs provide a simple system for direct and accurate voltammetric measurements that are referenced by an electrode with a constant, well-defined potential. The performance of the rEPADs is comparable to commercial electrochemical cells, and the layout can be easily integrated into systems that permit multiplexed analysis and pipette-free sampling. The cost of this portable device is sufficiently low that it could be for single-use, disposable applications, and its method of fabrication is compatible with that used for other paper-based systems.
Co-reporter:Ana C. Glavan, Ramses V. Martinez, E. Jane Maxwell, Anand Bala Subramaniam, Rui M. D. Nunes, Siowling Soh and George M. Whitesides
Lab on a Chip 2013 vol. 13(Issue 15) pp:2922-2930
Publication Date(Web):10 May 2013
DOI:10.1039/C3LC50371B
This paper describes the fabrication of pressure-driven, open-channel microfluidic systems with lateral dimensions of 45–300 microns carved in omniphobic paper using a craft-cutting tool. Vapor phase silanization with a fluorinated alkyltrichlorosilane renders paper omniphobic, but preserves its high gas permeability and mechanical properties. When sealed with tape, the carved channels form conduits capable of guiding liquid transport in the low-Reynolds number regime (i.e. laminar flow). These devices are compatible with complex fluids such as droplets of water in oil. The combination of omniphobic paper and a craft cutter enables the development of new types of valves and switches, such as “fold valves” and “porous switches,” which provide new methods to control fluid flow.
Co-reporter:Ratmir Derda, Matthew R. Lockett, Sindy K. Y. Tang, Renee C. Fuller, E. Jane Maxwell, Benjamin Breiten, Christine A. Cuddemi, Aysegul Ozdogan, and George M. Whitesides
This paper describes a method to detect the presence of bacteria in aqueous samples, based on the capture of bacteria on a syringe filter, and the infection of targeted bacterial species with a bacteriophage (phage). The use of phage as a reagent provides two opportunities for signal amplification: (i) the replication of phage inside a live bacterial host and (ii) the delivery and expression of the complementing gene that turns on enzymatic activity and produces a colored or fluorescent product. Here we demonstrate a phage-based amplification scheme with an M13KE phage that delivers a small peptide motif to an F+, α-complementing strain of Escherichia coli K12, which expresses the ω-domain of β-galactosidase (β-gal). The result of this complementation—an active form of β-gal—was detected colorimetrically, and the high level of expression of the ω-domain of β-gal in the model K12 strains allowed us to detect, on average, five colony-forming units (CFUs) of this strain in 1 L of water with an overnight culture-based assay. We also detected 50 CFUs of the model K12 strain in 1 L of water (or 10 mL of orange juice, or 10 mL of skim milk) in less than 4 h with a solution-based assay with visual readout. The solution-based assay does not require specialized equipment or access to a laboratory, and is more rapid than existing tests that are suitable for use at the point of access. This method could potentially be extended to detect many different bacteria with bacteriophages that deliver genes encoding a full-length enzyme that is not natively expressed in the target bacteria.
Paramagnetic ionic liquids (PILs) provide new capabilities to measurements of density using magnetic levitation (MagLev). In a typical measurement, a diamagnetic object of unknown density is placed in a container containing a PIL. The container is placed between two magnets (typically NdFeB, oriented with like poles facing). The density of the diamagnetic object can be determined by measuring its position in the magnetic field along the vertical axis (levitation height, h), either as an absolute value or relative to internal standards of known density. For density measurements by MagLev, PILs have three advantages over solutions of paramagnetic salts in aqueous or organic solutions: (i) negligible vapor pressures; (ii) low melting points; (iii) high thermal stabilities. In addition, the densities, magnetic susceptibilities, glass transition temperatures, thermal decomposition temperatures, viscosities, and hydrophobicities of PILs can be tuned over broad ranges by choosing the cation–anion pair. The low melting points and high thermal stabilities of PILs provide large liquidus windows for density measurements. This paper demonstrates applications and advantages of PILs in density-based analyses using MagLev.
In vitro 3D culture could provide an important model of tissues in vivo, but assessing the effects of chemical compounds on cells in specific regions of 3D culture requires physical isolation of cells and thus currently relies mostly on delicate and low-throughput methods. This paper describes a technique (“cells-in-gels-in-paper”, CiGiP) that permits rapid assembly of arrays of 3D cell cultures and convenient isolation of cells from specific regions of these cultures. The 3D cultures were generated by stacking sheets of 200-μm-thick paper, each sheet supporting 96 individual “spots” (thin circular slabs) of hydrogels containing cells, separated by hydrophobic material (wax, PDMS) impermeable to aqueous solutions, and hydrophilic and most hydrophobic solutes. A custom-made 96-well holder isolated the cell-containing zones from each other. Each well contained media to which a different compound could be added. After culture and disassembly of the holder, peeling the layers apart “sectioned” the individual 3D cultures into 200-μm-thick sections which were easy to analyze using 2D imaging (e.g., with a commercial gel scanner). This 96-well holder brings new utilities to high-throughput, cell-based screening, by combining the simplicity of CiGiP with the convenience of a microtiter plate. This work demonstrated the potential of this type of assays by examining the cytotoxic effects of phenylarsine oxide (PAO) and cyclophosphamide (CPA) on human breast cancer cells positioned at different separations from culture media in 3D cultures.
Co-reporter:Siowling Soh, Xin Chen, Sarah J. Vella, Wonjae Choi, Jinlong Gong and George M. Whitesides
Soft Matter 2013 vol. 9(Issue 43) pp:10233-10238
Publication Date(Web):25 Sep 2013
DOI:10.1039/C3SM51983J
Charges generated by contact of solid surfaces (contact electrification) can be hazardous or useful depending on the circumstance. This paper describes a process to design a solid surface rationally to either induce or prevent charging during contact electrification; this process coats the surface with polyelectrolytes. It is observed experimentally that a surface coated with a layer of a polymer having multiple, covalently attached positive charges (a “polycation”) develops a positive charge after contacting another surface; a surface coated with a layer of polymer having negative charges (a “polyanion”) develops a negative charge. By coating the surface using layer-by-layer (LBL) deposition, the tendency of the surface to charge either positively or negatively can be switched: adding a layer of polyelectrolyte with charge opposite to the charge on the surface switches the polarity of the surface. Through microcontact printing (μCP), the surface can be stamped to create a mosaic pattern of polycation and polyanion — and importantly, the fraction of the surface area covered with polycation and polyanion can be tuned by using stamps of different patterns. Using poly(diallyldimethylammonium chloride) (PDDA) as the polycation and poly(sodium 4-styrenesulfonate) (PSS) as the polyanion, it is found that for a surface with >75% PSS, the surface charges negatively; with <75% PSS, the surface charges positively. At ∼75% PSS, the surface becomes non-charging. The patterns on the surface can, subsequently, be erased through coating the surface with a uniform layer of polyelectrolyte. After erasing, the surface is rewritable by depositing or patterning the surface with a desired polyelectrolyte.
Co-reporter:Simon Tricard, Claudiu A. Stan, Eugene I. Shakhnovich and George M. Whitesides
Soft Matter 2013 vol. 9(Issue 17) pp:4480-4488
Publication Date(Web):20 Mar 2013
DOI:10.1039/C3SM27385G
Equilibrium thermodynamic phenomena such as the Maxwell–Boltzmann distribution of molecular velocities are rare in systems of macroscopic particles interacting by mechanical collisions. This paper reports a system composed of millimeter-sized polymer objects that under mechanical agitation exhibits a “discretization” of the configurations of the system, and has a distribution of the probabilities of these configurations that is analogous to a Boltzmann distribution. The system is composed of spheres and a three-link chain on a bounded horizontal surface, shaken with an aperiodic but not completely random horizontal motion. Experiments were performed at different strengths of agitation (quantified by the frequency of agitation, f, at constant amplitude) and densities of spheres (quantified by the filling ratio, FR). The chain was typically found in one of three conformations – extended, single folded, and double folded – because, under collisions with the spheres, adjacent links were stable mechanically only when fully extended or fully folded. The probabilities of the different conformations of the chain could be described by a Boltzmann distribution in which the “temperature” depended on f and the “energies” of conformations on FR. The predictions of the Boltzmann formula using empirically determined “temperatures” and “energies” agreed with measurements within two experimental standard deviations in 47 out of 48 experiments.
Co-reporter:Dr. Robert F. Shepherd;Dr. Adam A. Stokes;Jacob Freake;Dr. Jabulani Barber;Dr. Phillip W. Snyder;Dr. Aaron D. Mazzeo;Dr. Ludovico Cademartiri;Dr. Stephen A. Morin; George M. Whitesides
Co-reporter:Dr. Matthew R. Lockett;Dr. Heiko Lange;Dr. Benjamin Breiten;Dr. Annie Heroux;Dr. Woody Sherman;Dr. Dmitrij Rappoport;Patricia O. Yau;Dr. Philip W. Snyder;Dr. George M. Whitesides
Co-reporter:Choon Chiang Foo;Jeong-Yun Sun;Philipp Rothemund;Christoph Keplinger;Zhigang Suo
Science 2013 Volume 341(Issue 6149) pp:984-987
Publication Date(Web):30 Aug 2013
DOI:10.1126/science.1240228
Hydrogel Stretch
A range of stretchable, conductive materials can be made either by making an electrical conductor more stretchable or by adding an electrical conductor to a stretchable material. Keplinger et al. (p. 984; see the Perspective by Rogers) have added to the possibilities of an alternative stretchable ionic conductor based on a hydrogel material used to make deformable devices that are fully transparent to light over the visible spectrum and that can withstand high voltages and high frequencies.
Co-reporter:Dr. Matthew R. Lockett;Dr. Heiko Lange;Dr. Benjamin Breiten;Dr. Annie Heroux;Dr. Woody Sherman;Dr. Dmitrij Rappoport;Patricia O. Yau;Dr. Philip W. Snyder;Dr. George M. Whitesides
Angewandte Chemie International Edition 2013 Volume 52( Issue 30) pp:7714-7717
Co-reporter:Dr. Manza B. J. Atkinson;Dr. David K. Bwambok;Dr. Jie Chen;Dr. Prashant D. Chopade;Dr. Martin M. Thuo;Dr. Charles R. Mace;Dr. Katherine A. Mirica;Ashok A. Kumar;Dr. Allan S. Myerson;Dr. George M. Whitesides
Angewandte Chemie International Edition 2013 Volume 52( Issue 39) pp:10208-10211
Co-reporter:Dr. Robert F. Shepherd;Dr. Adam A. Stokes;Jacob Freake;Dr. Jabulani Barber;Dr. Phillip W. Snyder;Dr. Aaron D. Mazzeo;Dr. Ludovico Cademartiri;Dr. Stephen A. Morin; George M. Whitesides
Angewandte Chemie International Edition 2013 Volume 52( Issue 10) pp:2892-2896
Co-reporter:Ozge Akbulut, Charles R. Mace, Ramses V. Martinez, Ashok A. Kumar, Zhihong Nie, Matthew R. Patton, and George M. Whitesides
Nano Letters 2012 Volume 12(Issue 8) pp:4060-4064
Publication Date(Web):June 5, 2012
DOI:10.1021/nl301452x
This paper demonstrates the use of aqueous multiphase systems (MuPSs) as media for rate-zonal centrifugation to separate nanoparticles of different shapes and sizes. The properties of MuPSs do not change with time or during centrifugation; this stability facilitates sample collection after separation. A three-phase system demonstrates the separation of the reaction products (nanorods, nanospheres, and large particles) of a synthesis of gold nanorods, and enriches the nanorods from 48 to 99% in less than ten minutes using a benchtop centrifuge.
Co-reporter:Martin M. Thuo ; William F. Reus ; Felice C. Simeone ; Choongik Kim ; Michael D. Schulz ; Hyo Jae Yoon
Journal of the American Chemical Society 2012 Volume 134(Issue 26) pp:10876-10884
Publication Date(Web):June 7, 2012
DOI:10.1021/ja301778s
This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a −CH2CH2– group with a −CONH– group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure AgTS-S(CH2)mX(CH2)nH//Ga2O3/EGaIn (TS = template stripped, X = −CH2CH2– or −CONH–, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS∼CONH∼R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.
Co-reporter:Siowling Soh ; Sen Wai Kwok ; Helena Liu
Journal of the American Chemical Society 2012 Volume 134(Issue 49) pp:20151-20159
Publication Date(Web):November 15, 2012
DOI:10.1021/ja309268n
The contact electrification of insulating organic polymers is still incompletely understood, in part because multiple fundamental mechanisms may contribute to the movement of charge. This study describes a mechanism previously unreported in the context of contact electrification: that is, “contact de-electrification”, a process in which polymers charged to the same polarity discharge on contact. Both positively charged polymeric beads, e.g., polyamide 6/6 (Nylon) and polyoxymethylene (Delrin), and negatively charged polymeric beads, e.g., polytetrafluoroethylene (Teflon) and polyamide-imide (Torlon), discharge when the like-charged beads are brought into contact. The beads (both with charges of ∼±20 μC/m2, or ∼100 charges/μm2) discharge on contact regardless of whether they are made of the same material, or of different materials. Discharge is rapid: discharge of flat slabs of like-charged Nylon and Teflon pieces is completed on a single contact (∼3 s). The charge lost from the polymers during contact de-electrification transfers onto molecules of gas in the atmosphere. When like-charged polymers are brought into contact, the increase in electric field at the point of contact exceeds the dielectric breakdown strength of the atmosphere and ionizes molecules of the gas; this ionization thus leads to discharge of the polymers. The detection (using a Faraday cup) of charges transferred to the cup by the ionized gas is compatible with the mechanism. Contact de-electrification occurs for different polymers and in atmospheres with different values of dielectric breakdown strength (helium, argon, oxygen, carbon dioxide, nitrogen, and sulfur hexafluoride): the mechanism thus appears to be general.
Co-reporter:Nathan D. Shapiro ; Katherine A. Mirica ; Siowling Soh ; Scott T. Phillips ; Olga Taran ; Charles R. Mace ; Sergey S. Shevkoplyas
Journal of the American Chemical Society 2012 Volume 134(Issue 12) pp:5637-5646
Publication Date(Web):February 24, 2012
DOI:10.1021/ja211788e
This paper describes the use of magnetic levitation (MagLev) to measure the association of proteins and ligands. The method starts with diamagnetic gel beads that are functionalized covalently with small molecules (putative ligands). Binding of protein to the ligands within the bead causes a change in the density of the bead. When these beads are suspended in a paramagnetic aqueous buffer and placed between the poles of two NbFeB magnets with like poles facing, the changes in the density of the bead on binding of protein result in changes in the levitation height of the bead that can be used to quantify the amount of protein bound. This paper uses a reaction–diffusion model to examine the physical principles that determine the values of rate and equilibrium constants measured by this system, using the well-defined model system of carbonic anhydrase and aryl sulfonamides. By tuning the experimental protocol, the method is capable of quantifying either the concentration of protein in a solution, or the binding affinities of a protein to several resin-bound small molecules simultaneously. Since this method requires no electricity and only a single piece of inexpensive equipment, it may find use in situations where portability and low cost are important, such as in bioanalysis in resource-limited settings, point-of-care diagnosis, veterinary medicine, and plant pathology. It still has several practical disadvantages. Most notably, the method requires relatively long assay times and cannot be applied to large proteins (>70 kDa), including antibodies. The design and synthesis of beads with improved characteristics (e.g., larger pore size) has the potential to resolve these problems.
Co-reporter:Charles R. Mace ; Ozge Akbulut ; Ashok A. Kumar ; Nathan D. Shapiro ; Ratmir Derda ; Matthew R. Patton
Journal of the American Chemical Society 2012 Volume 134(Issue 22) pp:9094-9097
Publication Date(Web):May 17, 2012
DOI:10.1021/ja303183z
This Communication demonstrates the generation of over 300 phase-separated systems—ranging from two to six phases—from mixtures of aqueous solutions of polymers and surfactants. These aqueous multiphase systems (MuPSs) form self-assembling, thermodynamically stable step-gradients in density using a common solvent, water. The steps in density between phases of a MuPS can be very small (Δρ ≈ 0.001 g/cm3), do not change over time, and can be tuned by the addition of co-solutes. We use two sets of similar objects, glass beads and pellets of different formulations of Nylon, to demonstrate the ability of MuPSs to separate mixtures of objects by differences in density. The stable interfaces between phases facilitate the convenient collection of species after separation. These results suggest that the stable, sharp step-gradients in density provided by MuPSs can enable new classes of fractionations and separations based on density.
Co-reporter:Bryan F. Shaw, Grégory F. Schneider, and George M. Whitesides
Journal of the American Chemical Society 2012 Volume 134(Issue 45) pp:18739-18745
Publication Date(Web):October 24, 2012
DOI:10.1021/ja3079863
This paper describes the interaction between ubiquitin (UBI) and three sodium n-alkyl sulfates (SCnS) that have the same charge (Z = −1) but different hydrophobicity (n = 10, 12, or 14). Increasing the hydrophobicity of the n-alkyl sulfate resulted in (i) an increase in the number of distinct intermediates (that is, complexes of UBI and surfactant) that form along the pathway of unfolding, (ii) a decrease in the minimum concentrations of surfactant at which intermediates begin to form (i.e., a more negative ΔGbinding of surfactant for UBI), and (iii) an increase in the number of surfactant molecules bound to UBI in each intermediate or complex. These results demonstrate that small changes in the hydrophobicity of a surfactant can significantly alter the binding interactions with a folded or unfolded cytosolic protein.
The development of soft pneumatic actuators based on composites consisting of elastomers with embedded sheet or fiber structures (e.g., paper or fabric) that are flexible but not extensible is described. On pneumatic inflation, these actuators move anisotropically, based on the motions accessible by their composite structures. They are inexpensive, simple to fabricate, light in weight, and easy to actuate. This class of structure is versatile: the same principles of design lead to actuators that respond to pressurization with a wide range of motions (bending, extension, contraction, twisting, and others). Paper, when used to introduce anisotropy into elastomers, can be readily folded into 3D structures following the principles of origami; these folded structures increase the stiffness and anisotropy of the elastomeric actuators, while being light in weight. These soft actuators can manipulate objects with moderate performance; for example, they can lift loads up to 120 times their weight. They can also be combined with other components, for example, electrical components, to increase their functionality.
Co-reporter:Sarah J. Vella, Patrick Beattie, Rebecca Cademartiri, Anna Laromaine, Andres W. Martinez, Scott T. Phillips, Katherine A. Mirica, and George M. Whitesides
This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase, ALP, and aspartate aminotransferase, AST) and total serum protein. A device consists of four components: (i) a top plastic sheet, (ii) a filter membrane, (iii) a patterned paper chip containing the reagents necessary for analysis, and (iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and “spiked” standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings.
This paper describes a method based on magnetic levitation (MagLev) that is capable of indirectly measuring the binding of unlabeled ligands to unlabeled protein. We demonstrate this method by measuring the affinity of unlabeled bovine carbonic anhydrase (BCA) for a variety of ligands (most of which are benzene sulfonamide derivatives). This method utilizes porous gel beads that are functionalized with a common aryl sulfonamide ligand. The beads are incubated with BCA and allowed to reach an equilibrium state in which the majority of the immobilized ligands are bound to BCA. Since the beads are less dense than the protein, protein binding to the bead increases the overall density of the bead. This change in density can be monitored using MagLev. Transferring the beads to a solution containing no protein creates a situation where net protein efflux from the bead is thermodynamically favorable. The rate at which protein leaves the bead for the solution can be calculated from the rate at which the levitation height of the bead changes. If another small molecule ligand of BCA is dissolved in the solution, the rate of protein efflux is accelerated significantly. This paper develops a reaction-diffusion (RD) model to explain both this observation, and the physical-organic chemistry that underlies it. Using this model, we calculate the dissociation constants of several unlabeled ligands from BCA, using plots of levitation height versus time. Notably, although this method requires no electricity, and only a single piece of inexpensive equipment, it can measure accurately the binding of unlabeled proteins to small molecules over a wide range of dissociation constants (Kd values within the range from ∼10 nM to 100 μM are measured easily). Assays performed using this method generally can be completed within a relatively short time period (20 min–2 h). A deficiency of this system is that it is not, in its present form, applicable to proteins with molecular weight greater than approximately 65 kDa.
This paper describes a method for the selective precipitation and purification of a monovalent protein (carbonic anhydrase is used as a demonstration) from cellular lysate using ammonium sulfate and oligovalent ligands. The oligovalent ligands induce the formation of protein–ligand aggregates, and at an appropriate concentration of dissolved ammonium sulfate, these complexes precipitate. The purification involves three steps: (i) the removal of high-molecular-weight impurities through the addition of ammonium sulfate to the crude cell lysate; (ii) the introduction of an oligovalent ligand and the selective precipitation of the target protein–ligand aggregates from solution; and (iii) the removal of the oligovalent ligand from the precipitate by dialysis to release the target protein. The increase of mass and volume of the proteins upon aggregate formation reduces their solubility, and results in the selective precipitation of these aggregates. We recovered human carbonic anhydrase, from crude cellular lysate, in 82% yield and 95% purity with a trivalent benzene sulfonamide ligand. This method provides a chromatography-free strategy of purifying monovalent proteins—for which appropriate oligovalent ligands can be synthesized—and combines the selectivity of affinity-based purification with the convenience of salt-induced precipitation.
Co-reporter:Rebecca Cademartiri, Claudiu A. Stan, Vivian M. Tran, Evan Wu, Liam Friar, Daryl Vulis, Logan W. Clark, Simon Tricard and George M. Whitesides
Soft Matter 2012 vol. 8(Issue 38) pp:9771-9791
Publication Date(Web):08 Aug 2012
DOI:10.1039/C2SM26192H
This paper surveys the variables controlling the lattice structure and charge in macroscopic Coulombic crystals made from electrically charged, millimeter-sized polymer objects (spheres, cubes, and cylinders). Mechanical agitation of these objects inside planar, bounded containers caused them to charge electrically through contact electrification, and to self-assemble. The processes of electrification and self-assembly, and the characteristics of the assemblies, depended on the type of motion used for agitation, on the type of materials used for the objects and the dish, on the size and shape of the objects and the dish, and on the number of objects. Each of the three different materials in the system (of the dish and of the two types of spheres) influenced the electrification. Three classes of structures formed by self-assembly, depending on the experimental conditions: two-dimensional lattices, one-dimensional chains, and zero-dimensional ‘rosettes’. The lattices were characterized by their structure (disordered, square, rhombic, or hexagonal) and by the electrical charges of individual objects; the whole lattices were approximately electrically neutral. The lattices observed in this study were qualitatively different from ionic crystals; the charge of objects had practically continuous values which changed during agitation and self-assembly, and depended on experimental conditions which included the lattice structure itself. The relationship between charge and structure led to the coexistence of regions with different lattice structures within the same assembly, and to transformations between different lattice structures during agitation.
Co-reporter:Simon Tricard, Efraim Feinstein, Robert F. Shepherd, Meital Reches, Phillip W. Snyder, Dileni C. Bandarage, Mara Prentiss and George M. Whitesides
Physical Chemistry Chemical Physics 2012 vol. 14(Issue 25) pp:9041-9046
Publication Date(Web):28 May 2012
DOI:10.1039/C2CP40593H
This paper describes an empirical model of polymer dynamics, based on the agitation of millimeter-sized polymeric beads. Although the interactions between the particles in the macroscopic model and those between the monomers of molecular-scale polymers are fundamentally different, both systems follow the Worm-Like Chain theory.
Co-reporter:William F. Reus, Christian A. Nijhuis, Jabulani R. Barber, Martin M. Thuo, Simon Tricard, and George M. Whitesides
The Journal of Physical Chemistry C 2012 Volume 116(Issue 11) pp:6714-6733
Publication Date(Web):February 22, 2012
DOI:10.1021/jp210445y
This paper applies statistical methods to analyze the large, noisy data sets produced in measurements of tunneling current density (J) through self-assembled monolayers (SAMs) in large-area junctions. It describes and compares the accuracy and precision of procedures for summarizing data for individual SAMs, for comparing two or more SAMs, and for determining the parameters of the Simmons model (β and J0). For data that contain significant numbers of outliers (i.e., most measurements of charge transport), commonly used statistical techniques—e.g., summarizing data with arithmetic mean and standard deviation and fitting data using a linear, least-squares algorithm—are prone to large errors. The paper recommends statistical methods that distinguish between real data and artifacts, subject to the assumption that real data (J) are independent and log-normally distributed. Selecting a precise and accurate (conditional on these assumptions) method yields updated values of β and J0 for charge transport across both odd and even n-alkanethiols (with 99% confidence intervals) and explains that the so-called odd–even effect (for n-alkanethiols on Ag) is largely due to a difference in J0 between odd and even n-alkanethiols. This conclusion is provisional, in that it depends to some extent on the statistical model assumed, and these assumptions must be tested by future experiments.
Co-reporter:Ludovico Cademartiri, Martin M. Thuo, Christian A. Nijhuis, William F. Reus, Simon Tricard, Jabulani R. Barber, Rana N. S. Sodhi, Peter Brodersen, Choongik Kim, Ryan C. Chiechi, and George M. Whitesides
The Journal of Physical Chemistry C 2012 Volume 116(Issue 20) pp:10848-10860
Publication Date(Web):February 27, 2012
DOI:10.1021/jp212501s
Tunneling junctions having the structure AgTS–S(CH2)n−1CH3//Ga2O3/EGaIn allow physical–organic studies of charge transport across self-assembled monolayers (SAMs). In ambient conditions, the surface of the liquid metal electrode (EGaIn, 75.5 wt % Ga, 24.5 wt % In, mp 15.7 °C) oxidizes and adsorbs―like other high-energy surfaces―adventitious contaminants. The interface between the EGaIn and the SAM thus includes a film of metal oxide, and probably also organic material adsorbed on this film; this interface will influence the properties and operation of the junctions. A combination of structural, chemical, and electrical characterizations leads to four conclusions about AgTS–S(CH2)n−1CH3//Ga2O3/EGaIn junctions. (i) The oxide is ∼0.7 nm thick on average, is composed mostly of Ga2O3, and appears to be self-limiting in its growth. (ii) The structure and composition (but not necessarily the contact area) of the junctions are conserved from junction to junction. (iii) The transport of charge through the junctions is dominated by the alkanethiolate SAM and not by the oxide or by the contaminants. (iv) The interface between the oxide and the eutectic alloy is rough at the micrometer scale.
Co-reporter:Christian A. Nijhuis, William F. Reus, Jabulani R. Barber, and George M. Whitesides
The Journal of Physical Chemistry C 2012 Volume 116(Issue 26) pp:14139-14150
Publication Date(Web):April 18, 2012
DOI:10.1021/jp303072a
This paper compares the J(V) characteristics obtained for self-assembled monolayer (SAM)-based tunneling junctions with top electrodes of the liquid eutectic of gallium and indium (EGaIn) fabricated using two different procedures: (i) stabilizing the EGaIn electrode in PDMS microchannels and (ii) suspending the EGaIn electrode from the tip of a syringe. These two geometries of the EGaIn electrode (with, at least when in contact with air, its solid Ga2O3 surface film) produce indistinguishable data. The junctions incorporated SAMs of SCn–1CH3 (with n = 12, 14, 16, or 18) supported on ultraflat, template-stripped silver electrodes. Both methods generated high yields of junctions (70–85%) that were stable enough to conduct measurements of J(V) with statistically large numbers of data (N = 400–1000). The devices with the top electrode stabilized in microchannels also made it possible to conduct measurements of J(V) as a function of temperature, almost down to liquid nitrogen temperatures (T = 110–293 K). The J(V) characteristics were independent of T, and linear in the low-bias regime (−0.10 to 0.10V); the current density decreased exponentially with increasing thickness of the SAM. These observations indicate that tunneling is the main mechanism of charge transport across these junctions. Both methods gave values of the tunneling decay coefficient, β, of ∼1.0 nC–1 (∼0.80 Å–1), and the pre-exponential factor, J0 (which is a constant that includes contact resistance), of ∼3.0 × 102 A/cm2. Comparison of the electrical characteristics of the junctions generated using EGaIn by both methods against the results of other systems for measuring charge transport indicated that the value of β generated using EGaIn electrodes is compatible with the consensus of values reported in the literature. Although there is no consensus for the value of J0, the value of J0 estimated using the Ga2O3/EGaIn electrode is compatible with other values reported in the literature. The agreement of experimental values of β across a number of experimental platforms provides strong evidence that the structures of the SAMs—including their molecular and supramolecular structure, and their interfaces with the electrodes—dominate charge transport in both types of EGaIn junctions. These results establish that studies of J(V) characteristics of AgTS-SAM//Ga2O3/EGaIn junctions are dominated by the structure of the organic component of the SAM, and not by artifacts due to the electrodes, the resistance of the Ga2O3 surface film, or to the work functions of the metals.
Co-reporter:William F. Reus, Martin M. Thuo, Nathan D. Shapiro, Christian A. Nijhuis, and George M. Whitesides
ACS Nano 2012 Volume 6(Issue 6) pp:4806
Publication Date(Web):May 2, 2012
DOI:10.1021/nn205089u
The liquid–metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film—consisting primarily of Ga2O3—that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in AgTS-SAM//Ga2O3/EGaIn (where AgTS = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga2O3 film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga2O3 film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through AgTS-SAM//Ga2O3/EGaIn junctions, and that the electrical characteristics of the Ga2O3 film have a negligible effect on these measurements.Keywords: charge transport; junctions; molecular electronics; molecular rectification; self-assembled monolayers
Co-reporter:Darren J. Lipomi, Ramses V. Martinez, Mikhail A. Kats, Sung H. Kang, Philseok Kim, Joanna Aizenberg, Federico Capasso, and George M. Whitesides
Nano Letters 2011 Volume 11(Issue 2) pp:632-636
Publication Date(Web):December 28, 2010
DOI:10.1021/nl103730g
Convenient and inexpensive methods to pattern the facets of optical fibers with metallic nanostructures would enable many applications. This communication reports a method to generate and transfer arrays of metallic nanostructures to the cleaved facets of optical fibers. The process relies on nanoskiving, in which an ultramicrotome, equipped with a diamond knife, sections epoxy nanostructures coated with thin metallic films and embedded in a block of epoxy. Sectioning produces arrays of nanostructures embedded in thin epoxy slabs, which can be transferred manually to the tips of optical fibers at a rate of approximately 2 min−1, with 88% yield. Etching the epoxy matrices leaves arrays of nanostructures supported directly by the facets of the optical fibers. Examples of structures transferred include gold crescents, rings, high-aspect-ratio concentric cylinders, and gratings of parallel nanowires.
Co-reporter:Jasmin Mecinović ; Phillip W. Snyder ; Katherine A. Mirica ; Serena Bai ; Eric T. Mack ; Richard L. Kwant ; Demetri T. Moustakas ; Annie Héroux
Journal of the American Chemical Society 2011 Volume 133(Issue 35) pp:14017-14026
Publication Date(Web):July 26, 2011
DOI:10.1021/ja2045293
The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H2NSO2C6H4-CONHCH2(CX2)nCX3, n = 0–4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein–ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks of hydrogen bonds among molecules of water) and entropy (from release of water from configurationally restricted positions).
Co-reporter:Christian A. Nijhuis ; William F. Reus ; Adam C. Siegel
Journal of the American Chemical Society 2011 Volume 133(Issue 39) pp:15397-15411
Publication Date(Web):August 15, 2011
DOI:10.1021/ja201223n
This paper describes the performance of junctions based on self-assembled monolayers (SAMs) as the functional element of a half-wave rectifier (a simple circuit that converts, or rectifies, an alternating current (AC) signal to a direct current (DC) signal). Junctions with SAMs of 11-(ferrocenyl)-1-undecanethiol or 11-(biferrocenyl)-1-undecanethiol on ultraflat, template-stripped Ag (AgTS) bottom electrodes, and contacted by top electrodes of eutectic indium–gallium (EGaIn), rectified AC signals, while similar junctions based on SAMs of 1-undecanethiol—SAMs lacking the ferrocenyl terminal group—did not. SAMs in these AC circuits (operating at 50 Hz) remain stable over a larger window of applied bias than in DC circuits. AC measurements, therefore, can investigate charge transport in SAM-based junctions at magnitudes of bias inaccessible to DC measurements. For junctions with SAMs of alkanethiols, combining the results from AC and DC measurements identifies two regimes of bias with different mechanisms of charge transport: (i) low bias (|V| < 1.3 V), at which direct tunneling dominates, and (ii) high bias (|V| > 1.3 V), at which Fowler–Nordheim (FN) tunneling dominates. For junctions with SAMs terminated by Fc moieties, the transition to FN tunneling occurs at |V| ≈ 2.0 V. Furthermore, at sufficient forward bias (V > 0.5 V), hopping makes a significant contribution to charge transport and occurs in series with direct tunneling (V ≲ 2.0 V) until FN tunneling activates (V ≳ 2.0 V). Thus, for Fc-terminated SAMs at forward bias, three regimes are apparent: (i) direct tunneling (V = 0–0.5 V), (ii) hopping plus direct tunneling (V ≈ 0.5–2.0 V), and (iii) FN tunneling (V ≳ 2.0 V). Since hopping does not occur at reverse bias, only two regimes are present over the measured range of reverse bias. This difference in the mechanisms of charge transport at forward and reverse bias for junctions with Fc moieties resulted in large rectification ratios (R > 100) and enabled half-wave rectification.
Co-reporter:Eric T. Mack ; Phillip W. Snyder ; Raquel Perez-Castillejos
Journal of the American Chemical Society 2011 Volume 133(Issue 30) pp:11701-11715
Publication Date(Web):June 14, 2011
DOI:10.1021/ja2038084
This paper describes the development of a new bivalent system comprising synthetic dimers of carbonic anhydrase linked chemically through thiol groups of cysteine residues introduced by site-directed mutagenesis. These compounds serve as models with which to study the interaction of bivalent proteins with ligands presented at the surface of mixed self-assembled monolayers (SAMs). Monovalent carbonic anhydrase (CA) binds to benzenesulfonamide ligands presented on the surface of the SAM with Kdsurf = 89 nM. The synthetic bivalent proteins—inspired by the structure of immunoglobulins—bind bivalently to the sulfonamide-functionalized SAMs with low nanomolar avidities (Kdavidity,surf = 1 – 3 nM); this difference represents a ∼50-fold enhancement of bivalent over monovalent association. The paper describes dimers of CA having (i) different lengths of the covalent linker that joined the two proteins and (ii) different points of attachment of the linker to the protein (either near the active site (C133) or distal to the active site (C185)). Comparison of the thermodynamics of their interactions with SAMs presenting arylsulfonamide groups demonstrated that varying the length of the linker between the molecules of CA had virtually no effect on the rate of association, or on the avidity of these dimers with ligand-presenting surfaces. Varying the point of attachment of the linker between monomeric CA’s also had almost no effect on the avidity of the dimers, although changing the point of attachment affected the rates of binding and unbinding. These observations indicate that the avidities of these bivalent proteins, and by inference the avidities of structurally similar bivalent proteins such as IgG, are unexpectedly insensitive to the structure of the linker connecting them.
Co-reporter:Bryan F. Shaw ; Grégory F. Schneider ; Haribabu Arthanari ; Max Narovlyansky ; Demetri Moustakas ; Armando Durazo ; Gerhard Wagner
Journal of the American Chemical Society 2011 Volume 133(Issue 44) pp:17681-17695
Publication Date(Web):September 22, 2011
DOI:10.1021/ja205735q
A previous study, using capillary electrophoresis (CE) [J. Am. Chem. Soc.2008, 130, 17384–17393], reported that six discrete complexes of ubiquitin (UBI) and sodium dodecyl sulfate (SDS) form at different concentrations of SDS along the pathway to unfolding of UBI in solutions of SDS. One complex (which formed between 0.8 and 1.8 mM SDS) consisted of native UBI associated with approximately 11 molecules of SDS. The current study used CE and 15N/13C–1H heteronuclear single quantum coherence (HSQC) NMR spectroscopy to identify residues in folded UBI that associate specifically with SDS at 0.8–1.8 mM SDS, and to correlate these associations with established biophysical and structural properties of this well-characterized protein. The ability of the surface charge and hydrophobicity of folded UBI to affect the association with SDS (at concentrations below the CMC) was studied, using CE, by converting lys-ε-NH3+ to lys-ε-NHCOCH3 groups. According to CE, the acetylation of lysine residues inhibited the binding of 11 SDS ([SDS] < 2 mM) and decreased the number of complexes of composition UBI-(NHAc)8·SDSn that formed on the pathway of unfolding of UBI-(NHAc)8 in SDS. A comparison of 15N–1H HSQC spectra at 0 mM and 1 mM SDS with calculated electrostatic surface potentials of folded UBI (e.g., solutions to the nonlinear Poisson–Boltzmann (PB) equation) suggested, however, that SDS binds preferentially to native UBI at hydrophobic residues that are formally neutral (i.e., Leu and Ile), but that have positive electrostatic surface potential (as predicted from solutions to nonlinear PB equations); SDS did not uniformly interact with residues that have formal positive charge (e.g., Lys or Arg). Cationic functional groups, therefore, promote the binding of SDS to folded UBI because these groups exert long-range effects on the positive electrostatic surface potential (which extend beyond their own van der Waals radii, as predicted from PB theory), and not because cationic groups are necessarily the site of ionic interactions with sulfate groups. Moreover, SDS associated with residues in native UBI without regard to their location in α-helix or β-sheet structure (although residues in hydrogen-bonded loops did not bind SDS). No correlation was observed between the association of an amino acid with SDS and the solvent accessibility of the residue or its rate of amide H/D exchange. This study establishes a few (of perhaps several) factors that control the simultaneous molecular recognition of multiple anionic amphiphiles by a folded cytosolic protein.
Co-reporter:Eric T. Mack ; Phillip W. Snyder ; Raquel Perez-Castillejos ; Başar Bilgiçer ; Demetri T. Moustakas ; Manish J. Butte
Journal of the American Chemical Society 2011 Volume 134(Issue 1) pp:333-345
Publication Date(Web):November 16, 2011
DOI:10.1021/ja2073033
This paper describes a synthetic dimer of carbonic anhydrase, and a series of bivalent sulfonamide ligands with different lengths (25 to 69 Å between the ends of the fully extended ligands), as a model system to use in examining the binding of bivalent antibodies to antigens. Assays based on analytical ultracentrifugation and fluorescence binding indicate that this system forms cyclic, noncovalent complexes with a stoichiometry of one bivalent ligand to one dimer. This dimer binds the series of bivalent ligands with low picomolar avidities (Kdavidity = 3–40 pM). A structurally analogous monovalent ligand binds to one active site of the dimer with Kdmono = 16 nM. The bivalent association is thus significantly stronger (Kdmono/Kdavidity ranging from ∼500 to 5000 unitless) than the monovalent association. We infer from these results, and by comparison of these results to previous studies, that bivalency in antibodies can lead to associations much tighter than monovalent associations (although the observed bivalent association is much weaker than predicted from the simplest level of theory: predicted Kdavidity of ∼0.002 pM and Kdmono/Kdavidity ∼ 8 × 106 unitless).
Co-reporter:Wonjae Choi, Michinao Hashimoto, Audrey K. Ellerbee, Xin Chen, Kyle J. M. Bishop, Piotr Garstecki, Howard A. Stone and George M. Whitesides
Lab on a Chip 2011 vol. 11(Issue 23) pp:3970-3978
Publication Date(Web):14 Oct 2011
DOI:10.1039/C1LC20444K
This paper describes the behavior of bubbles suspended in a carrier liquid and moving within microfluidic networks of different connectivities. A single-phase continuum fluid, when flowing in a network of channels, partitions itself among all possible paths connecting the inlet and outlet. The flow rates along different paths are determined by the interaction between the fluid and the global structure of the network. That is, the distribution of flows depends on the fluidic resistances of all channels of the network. The movement of bubbles of gas, or droplets of liquid, suspended in a liquid can be quite different from the movement of a single-phase liquid, especially when they have sizes slightly larger than the channels, so that the bubbles (or droplets) contribute to the fluidic resistance of a channel when they are transiting it. This paper examines bubbles in this size range; in the size range examined, the bubbles are discrete and do not divide at junctions. As a consequence, a single bubble traverses only one of the possible paths through the network, and makes a sequence of binary choices (“left” or “right”) at each branching intersection it encounters. We designed networks so that, at each junction, a bubble enters the channel into which the volumetric flow rate of the carrier liquid is highest. When there is only a single bubble inside a network at a time, the path taken by the bubble is, counter-intuitively, not necessarily the shortest or the fastest connecting the inlet and outlet. When a small number of bubbles move simultaneously through a network, they interact with one another by modifying fluidic resistances and flows in a time dependent manner; such groups of bubbles show very complex behaviors. When a large number of bubbles (sufficiently large that the volume of the bubbles occupies a significant fraction of the volume of the network) flow simultaneously through a network, however, the collective behavior of bubbles—the fluxes of bubbles through different paths of the network—can resemble the distribution of flows of a single-phase fluid.
Co-reporter:Xinyu Liu, Martin Mwangi, XiuJun Li, Michael O'Brien and George M. Whitesides
Lab on a Chip 2011 vol. 11(Issue 13) pp:2189-2196
Publication Date(Web):12 May 2011
DOI:10.1039/C1LC20161A
This paper describes the development of MEMS force sensors constructed using paper as the structural material. The working principle on which these paper-based sensors are based is the piezoresistive effect generated by conductive materials patterned on a paper substrate. The device is inexpensive (∼$0.04 per device for materials), simple to fabricate, lightweight, and disposable. Paper can be readily folded into three-dimensional structures to increase the stiffness of the sensor while keeping it light in weight. The entire fabrication process can be completed within one hour without expensive cleanroom facilities using simple tools (e.g., a paper cutter and a painting knife). We demonstrated that the paper-based sensor can measure forces with moderate performance (i.e., resolution: 120 μN, measurement range: ±16 mN, and sensitivity: 0.84 mV mN−1). We applied this sensor to characterizing the mechanical properties of a soft material. Leveraging the same sensing concept, we also developed a paper-based balance with a measurement range of 15 g, and a resolution of 0.39 g.
Co-reporter:Filip Ilievski, Katherine A. Mirica, Audrey K. Ellerbee and George M. Whitesides
Soft Matter 2011 vol. 7(Issue 19) pp:9113-9118
Publication Date(Web):12 Aug 2011
DOI:10.1039/C1SM05962A
Although self-assembly (SA) in two dimensions (2D) is highly developed (especially using surfaces as a templates), SA in three dimensions (3D) has been more difficult. This paper describes a strategy for SA in 3D of diamagnetic plastic objects (mm- to cm-sized in this work, but in principle in sizes from ∼10 μm to m) supported in a paramagnetic fluid by a non-uniform magnetic field. The magnetic field and its gradient levitate the objects, template their self-assembly, and influence the shape of the assembled cluster. The structure of the 3D assembling objects can be further directed using hard mechanical templates—either the walls of the container or co-levitating components—which coincide spatially with the soft template of the magnetic field gradient. Mechanical agitation anneals the levitating clusters; the addition of photocurable adhesive, followed by UV illumination, can permanently fuse components together.
Co-reporter:Dr. S. Elizabeth Hulme ; George M. Whitesides
Angewandte Chemie International Edition 2011 Volume 50( Issue 21) pp:4774-4807
Publication Date(Web):
DOI:10.1002/anie.201005461
Abstract
This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools—biological, chemical, and physical—that are available to researchers studying the worm.
Dieser Aufsatz diskutiert die Nützlichkeit des Wurms Caenorhabditis elegans als Modellorganismus für Chemiker, die an der Untersuchung lebender Systeme interessiert sind. C. elegans, ein 1 mm langer Rundwurm, ist ein beliebter Modellorganismus in nahezu allen Gebieten der modernen Biologie. Der Wurm hat zahlreiche Eigenschaften, die ihn für die Biologie attraktiv machen: Er ist klein (<1000 Zellen), transparent und genetisch leicht zu manipulieren. Trotz seiner Schlichtheit weist der Wurm komplexe Phänotypen auf, die mit seiner Mehrzelligkeit zusammenhängen: Er hat differenzierte Zelltypen und Organe, er altert und hat eine wohldefinierte Lebenserwartung, er kann lernen und besitzt ein Erinnerungsvermögen. Der Aufsatz will verdeutlichen, dass diese Mischung aus Einfachheit und Komplexität den Wurm zu einem besonders nützlichen Werkzeug macht, um die Beziehungen zwischen Phänomenen auf molekularer Ebene und der Ebene des Gesamtorganismus zu erforschen (Altern, Verhalten, Kognition, Anfälligkeit für Krankheiten). Es werden vornehmlich solche Forschungsarbeiten vorgestellt, die chemisch relevant sind. Außerdem werden Instrumente und Arbeitstechniken – biologischer, chemischer und physikalischer Natur – vorgestellt, die uns zur Erforschung des Wurms zur Verfügung stehen.
Dieser Aufsatz handelt von “Nanoskiving” (zu Deutsch etwa: Nano-Hartschälen oder Nano-Dünnschleifen) – einer einfachen und kostengünstigen Methode zur Nanofertigung, die die Notwendigkeit eines Zugangs zu Reinräumen und den dazugehörigen Einrichtungen minimiert, und die es zudem ermöglicht, Nanostrukturen aus Materialien und in Formen zu erstellen, für die herkömmlichere Methoden der Nanofertigung ungeeignet wären. Nanoskiving besteht aus drei Stufen: 1) Auftragung eines metallischen, halbleitenden, keramischen oder polymeren Dünnfilms auf eine Epoxidharz-Oberfläche; 2) Einbetten dieses Films in Epoxidharz, sodass ein Epoxidharzblock entsteht, in dem der Film eingeschlossen ist; und 3) Aufteilen des Epoxidharzblocks in dünne Scheiben mithilfe eines Ultramikrotoms. Die Scheiben, die zwischen 30 nm und 10 μm dick sind, enthalten Nanostrukturen, deren laterale Abmessungen den Stärken der eingebetteten Filme entsprechen. Elektronische Anwendungen der Strukturen, die über diesen Prozess erhalten werden, finden sich in der Fertigung von Nanoelektroden für die Elektrochemie, von chemoresistenten Nanodrähten und von Heterostrukturen organischer Halbleiter. Optische Anwendungen finden sich in den Bereichen der Resonatoren für Oberflächenplasmonen, der plasmonischen Hohlleiter und den frequenzselektiven Oberflächen.
Co-reporter:Andrew Lee, Katherine A. Mirica, and George M. Whitesides
The Journal of Physical Chemistry B 2011 Volume 115(Issue 5) pp:1199-1210
Publication Date(Web):December 23, 2010
DOI:10.1021/jp107765h
This paper examines the influence of acylation of the Lys-ε-NH3+ groups of bovine carbonic anhydrase (BCA, EC 4.2.1.1) to Lys-ε-NHCOR (R = −CH3, −CH2CH3, and −CH(CH3)2, −CF3) on the rate of denaturation of this protein in buffer containing sodium dodecyl sulfate (SDS). Analysis of the rates suggested separate effects due to electrostatic charge and hydrophobic interactions. Rates of denaturation (kAc,n) of each series of acylated derivatives depended on the number of acylations (n). Plots of log kAc,n vs n followed U-shaped curves. Within each series of derivatives, rates of denaturation decreased as n increased to ∼7; this decrease was compatible with increasingly unfavorable electrostatic interactions between SDS and protein. In this range of n, rates of denaturation also depended on the choice of the acyl group as n increased to ∼7, in a manner compatible with favorable hydrophobic interactions between SDS and the −NHCOR groups. As n increased in the range 7 < n < 14, however, rates of denaturation stayed approximately constant; analysis suggested that these rates were compatible with an increasingly important contribution to denaturation that depended both on the net negative charge of the protein and on the hydrophobicity of the R group. The mechanism of denaturation thus seems to change with the extent of acylation of the protein. For derivatives with the same net electrostatic charge, rates of denaturation increased with the acyl group (by a factor of ∼3 for n ∼ 14) in the order CH3CONH− < CH3CH2CONH− < (CH3)2CHCONH− < CF3CONH−. These results suggested that the hydrophobicity of CF3CONH− is slightly greater (by a factor of <2) than that of RHCONH− with similar surface area.
Co-reporter:Claudiu A. Stan, Sindy K. Y. Tang, Kyle J. M. Bishop, and George M. Whitesides
The Journal of Physical Chemistry B 2011 Volume 115(Issue 5) pp:1089-1097
Publication Date(Web):December 21, 2010
DOI:10.1021/jp110437x
The freezing of water can initiate at electrically conducting electrodes kept at a high electric potential or at charged electrically insulating surfaces. The microscopic mechanisms of these phenomena are unknown, but they must involve interactions between water molecules and electric fields. This paper investigates the effect of uniform electric fields on the homogeneous nucleation of ice in supercooled water. Electric fields were applied across drops of water immersed in a perfluorinated liquid using a parallel-plate capacitor; the drops traveled in a microchannel and were supercooled until they froze due to the homogeneous nucleation of ice. The distribution of freezing temperatures of drops depended on the rate of nucleation of ice, and the sensitivity of measurements allowed detection of changes by a factor of 1.5 in the rate of nucleation. Sinusoidal alternation of the electric field at frequencies from 3 to 100 kHz prevented free ions present in water from screening the electric field in the bulk of drops. Uniform electric fields in water with amplitudes up to (1.6 ± 0.4) × 105 V/m neither enhanced nor suppressed the homogeneous nucleation of ice. Estimations based on thermodynamic models suggest that fields in the range of 107−108 V/m might cause an observable increase in the rate of nucleation.
Co-reporter:Phillip W. Snyder;Jasmin Mecinović;Demetri T. Moustakas;Samuel W. Thomas III;Michael Harder;Matthew R. Lockett;Eric T. Mack;Woody Sherman;Annie Héroux
PNAS 2011 Volume 108 (Issue 44 ) pp:
Publication Date(Web):2011-11-01
DOI:10.1073/pnas.1114107108
The hydrophobic effect—a rationalization of the insolubility of nonpolar molecules in water—is centrally important to biomolecular
recognition. Despite extensive research devoted to the hydrophobic effect, its molecular mechanisms remain controversial,
and there are still no reliably predictive models for its role in protein–ligand binding. Here we describe a particularly
well-defined system of protein and ligands—carbonic anhydrase and a series of structurally homologous heterocyclic aromatic
sulfonamides—that we use to characterize hydrophobic interactions thermodynamically and structurally. In binding to this structurally
rigid protein, a set of ligands (also defined to be structurally rigid) shows the expected gain in binding free energy as
hydrophobic surface area is added. Isothermal titration calorimetry demonstrates that enthalpy determines these increases
in binding affinity, and that changes in the heat capacity of binding are negative. X-ray crystallography and molecular dynamics
simulations are compatible with the proposal that the differences in binding between the homologous ligands stem from changes
in the number and organization of water molecules localized in the active site in the bound complexes, rather than (or perhaps
in addition to) release of structured water from the apposed hydrophobic surfaces. These results support the hypothesis that
structured water molecules—including both the molecules of water displaced by the ligands and those reorganized upon ligand
binding—determine the thermodynamics of binding of these ligands at the active site of the protein. Hydrophobic effects in
various contexts have different structural and thermodynamic origins, although all may be manifestations of the differences
in characteristics of bulk water and water close to hydrophobic surfaces.
Origins of Life and Evolution of Biospheres 2011 Volume 41( Issue 5) pp:399-412
Publication Date(Web):2011 October
DOI:10.1007/s11084-011-9243-4
This article reports rate constants for thiol–thioester exchange (kex), and for acid-mediated (ka), base-mediated (kb), and pH-independent (kw) hydrolysis of S-methyl thioacetate and S-phenyl 5-dimethylamino-5-oxo-thiopentanoate—model alkyl and aryl thioalkanoates, respectively—in water. Reactions such as thiol–thioester exchange or aminolysis could have generated molecular complexity on early Earth, but for thioesters to have played important roles in the origin of life, constructive reactions would have needed to compete effectively with hydrolysis under prebiotic conditions. Knowledge of the kinetics of competition between exchange and hydrolysis is also useful in the optimization of systems where exchange is used in applications such as self-assembly or reversible binding. For the alkyl thioester S-methyl thioacetate, which has been synthesized in simulated prebiotic hydrothermal vents, ka = 1.5 × 10−5 M−1 s−1, kb = 1.6 × 10−1 M−1 s−1, and kw = 3.6 × 10−8 s−1. At pH 7 and 23°C, the half-life for hydrolysis is 155 days. The second-order rate constant for thiol–thioester exchange between S-methyl thioacetate and 2-sulfonatoethanethiolate is kex = 1.7 M−1 s−1. At pH 7 and 23°C, with [R″S(H)] = 1 mM, the half-life of the exchange reaction is 38 h. These results confirm that conditions (pH, temperature, pKa of the thiol) exist where prebiotically relevant thioesters can survive hydrolysis in water for long periods of time and rates of thiol–thioester exchange exceed those of hydrolysis by several orders of magnitude.
Co-reporter:Robert F. Shepherd;Filip Ilievski;Wonjae Choi;Stephen A. Morin;Adam A. Stokes;Aaron D. Mazzeo;Xin Chen;Michael Wang
PNAS 2011 108 (51 ) pp:
Publication Date(Web):2011-12-20
DOI:10.1073/pnas.1116564108
This manuscript describes a unique class of locomotive robot: A soft robot, composed exclusively of soft materials (elastomeric
polymers), which is inspired by animals (e.g., squid, starfish, worms) that do not have hard internal skeletons. Soft lithography
was used to fabricate a pneumatically actuated robot capable of sophisticated locomotion (e.g., fluid movement of limbs and
multiple gaits). This robot is quadrupedal; it uses no sensors, only five actuators, and a simple pneumatic valving system
that operates at low pressures (< 10 psi). A combination of crawling and undulation gaits allowed this robot to navigate a
difficult obstacle. This demonstration illustrates an advantage of soft robotics: They are systems in which simple types of
actuation produce complex motion.
Co-reporter:Adam C. Siegel, Sindy K. Y. Tang, Christian A. Nijhuis, Michinao Hashimoto, Scott T. Phillips, Michael D. Dickey and George M. Whitesides
Accounts of Chemical Research 2010 Volume 43(Issue 4) pp:518
Publication Date(Web):January 20, 2010
DOI:10.1021/ar900178k
This Account describes a strategy for fabricating multicomponent microsystems in which the structures of essentially all of the components are formed in a single step of micromolding. This strategy, which we call “cofabrication”, is an alternative to multilayer microfabrication, in which multiple layers of components are sequentially aligned (“registered”) and deposited on a substrate by photolithography. Cofabrication has several characteristics that make it an especially useful approach for building multicomponent microsystems. It rapidly and inexpensively generates correctly aligned components (for example, wires, heaters, magnetic field generators, optical waveguides, and microfluidic channels) over very large surface areas. By avoiding registration, the technique does not impose on substrates the size limitations of common registrations tools, such as steppers and contact aligners. We have demonstrated multicomponent microsystems with surface areas exceeding 100 cm2, but in principle, device size is only limited by the requirements of generating the original master. In addition, cofabrication can serve as a low-cost strategy for building microsystems. The technique is amenable to a variety of laboratory settings and uses fabrication tools that are less expensive than those used for multistep microfabrication. Moreover, the process requires only small amounts of solvent and photoresist, a costly chemical required for photolithography; in cofabrication, photoresist is applied and developed only once to produce a master, which is then used to produce multiple copies of molds containing the microfluidic channels. From a broad perspective, cofabrication represents a new processing paradigm in which the exterior (or shell) of the desired structures are produced before the interior (or core). This approach, generating the insulation or packaging structure first and injecting materials that provide function in channels in liquid phase, makes it possible to design and build microsystems with component materials that cannot be easily manipulated conventionally (such as solid materials with low melting points, liquid metals, liquid crystals, fused salts, foams, emulsions, gases, polymers, biomaterials, and fragile organics). Moreover, materials can be altered, removed, or replaced after the manufacturing stage. For example, cofabrication allows one to build devices in which a liquid flows through the device during use, or is replaced after use. Metal wires can be melted and reset by heating (in principle, repairing a break). This method leads to certain kinds of structures, such as integrated metallic wires with large cross-sectional areas or optical waveguides aligned in the same plane as microfluidic channels, that would be difficult or impossible to make with techniques such as sputter deposition or evaporation. This Account outlines the strategy of cofabrication and describes several applications. Specifically, we highlight cofabricated systems that combine microfluidics with (i) electrical wires for microheaters, electromagnets, and organic electrodes, (ii) fluidic optical components, such as optical waveguides, lenses, and light sources, (iii) gels for biological cell cultures, and (iv) droplets for compartmentalized chemical reactions, such as protein crystallization.
Replica molding with elastomeric polymers has been used routinely to replicate features less than 10 nm in size. Because the theoretical limit of this technique is set by polymer-surface interactions, atomic radii, and accessible volumes, replication at subnanometer length scales should be possible. Using polydimethylsiloxane to create a mold and polyurethane to form the replica, we demonstrate replication of elementary steps 3−5 Å in height that define the minimum separation between molecular layers in the lattices of the ionic crystals potassium dihydrogen phosphate and calcite. This work establishes the operation of replica molding at the molecular scale.
Co-reporter:Jinlong Gong, Darren J. Lipomi, Jiangdong Deng, Zhihong Nie, Xin Chen, Nicholas X. Randall, Rahul Nair and George M. Whitesides
Nano Letters 2010 Volume 10(Issue 7) pp:2702-2708
Publication Date(Web):June 17, 2010
DOI:10.1021/nl101675s
This paper describes the use of a nanoindenter, equipped with a diamond tip, to form patterns of indentations on planar substrates (epoxy, silicon, and SiO2). The process is called “Indentation Lithography” (IndL). The indentations have the form of pits and furrows, whose cross-sectional profiles are determined by the shapes of the diamond indenters, and whose dimensions are determined by the applied load and hardness of the substrate. IndL makes it possible to indent hard materials, to produce patterns with multiple levels of relief by changing the loading force, and to control the profiles of the indentations by using indenters with different shapes. This paper also demonstrates the transfer of indented patterns to elastomeric PDMS stamps for soft lithography, and to thin films of evaporated gold or silver. Stripping an evaporated film from an indented template produces patterns of gold or silver pyramids, whose tips concentrate electric fields. Patterns produced by IndL can thus be used as substrates for surface-enhanced Raman scattering (SERS) and for other plasmonic applications.
Co-reporter:Christian A. Nijhuis, William F. Reus, Jabulani R. Barber, Michael D. Dickey and George M. Whitesides
Nano Letters 2010 Volume 10(Issue 9) pp:3611-3619
Publication Date(Web):August 18, 2010
DOI:10.1021/nl101918m
This paper describes a method of fabrication that generates small arrays of tunneling junctions based on self-assembled monolayers (SAMs); these junctions have liquid-metal top-electrodes stabilized in microchannels and ultraflat (template-stripped) bottom-electrodes. The yield of junctions generated using this method is high (70−90%). The junctions examined incorporated SAMs of alkanethiolates having ferrocene termini (11-(ferrocenyl)-1-undecanethiol, SC11Fc); these junctions rectify currents with large rectification ratios (R), the majority of which fall within the range of 90−180. These values are larger than expected (theory predicts R ≤ 20) and are larger than previous experimental measurements. SAMs of n-alkanethiolates without the Fc groups (SCn−1CH3, with n = 12, 14, 16, or 18) do not rectify (R ranged from 1.0 to 5.0). These arrays enable the measurement of the electrical characteristics of the junctions as a function of chemical structure, voltage, and temperature over the range of 110−293 K, with statistically large numbers of data (N = 300−800). The mechanism of rectification with Fc-terminated SAMs seems to be charge transport processes that change with the polarity of bias: from tunneling (at one bias) to hopping combined with tunneling (at the opposite bias).
Co-reporter:Bryan F. Shaw ; Haribabu Arthanari ; Max Narovlyansky ; Armando Durazo ; Dominique P. Frueh ; Michael P. Pollastri ; Andrew Lee ; Basar Bilgicer ; Steven P. Gygi ; Gerhard Wagner
Journal of the American Chemical Society 2010 Volume 132(Issue 49) pp:17411-17425
Publication Date(Web):November 19, 2010
DOI:10.1021/ja9067035
This paper combines two techniques—mass spectrometry and protein charge ladders—to examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen−deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-ε-NH3+ groups—a type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structure—resulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15 °C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from H/D exchange during the 2 h exchange experiment at 15 °C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-ε-NHCOCH3) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observation—that faster rates of exchange are associated with slower rates of denaturation—is contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-ε-NHCO(CH2)2CH3]18) and peracetylated BCA II (e.g., [lys-ε-NHCOCH3]18) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).
Co-reporter:Christian A. Nijhuis, William F. Reus, and George M. Whitesides
Journal of the American Chemical Society 2010 Volume 132(Issue 51) pp:18386-18401
Publication Date(Web):December 2, 2010
DOI:10.1021/ja108311j
This paper proposes a mechanism for the rectification of current by self-assembled monolayers (SAMs) of alkanethiolates with Fc head groups (SC11Fc) in SAM-based tunneling junctions with ultra-flat Ag bottom electrodes and liquid metal (Ga2O3/EGaIn) top electrodes. A systematic physical-organic study based on statistically large numbers of data (N = 300−1000) reached the conclusion that only one energetically accessible molecular orbital (the HOMO of the Fc) is necessary to obtain large rectification ratios R ≈ 1.0 × 102 (R = |J(−V)|/|J(V)| at ±1 V). Values of R are log-normally distributed, with a log-standard deviation of 3.0. The HOMO level has to be positioned spatially asymmetrically inside the junctions (in these experiments, in contact with the Ga2O3/EGaIn top electrode, and separated from the Ag electrode by the SC11 moiety) and energetically below the Fermi levels of both electrodes to achieve rectification. The HOMO follows the potential of the Fermi level of the Ga2O3/EGaIn electrode; it overlaps energetically with both Fermi levels of the electrodes only in one direction of bias.
This paper describes several low-cost methods for fabricating flexible electronic circuits on paper. The circuits comprise i) metallic wires (e.g., tin or zinc) that are deposited on the substrate by evaporation, sputtering, or airbrushing, and ii) discrete surface-mountable electronic components that are fastened with conductive adhesive directly to the wires. These electronic circuits—like conventional printed circuit boards—can be produced with electronic components that connect on both sides of the substrate. Unlike printed circuit boards made from fiberglass, ceramics, or polyimides, however, paper can be folded and creased (repeatedly), shaped to form three-dimensional structures, trimmed using scissors, used to wick fluids (e.g., for microfluidic applications) and disposed of by incineration. Paper-based electronic circuits are thin and lightweight; they should be useful for applications in consumer electronics and packaging, for disposable systems for uses in the military and homeland security, for applications in medical sensing or low-cost portable diagnostics, for paper-based microelectromechanical systems, and for applications involving textiles.
Co-reporter:Paul J. Bracher, Malancha Gupta and George M. Whitesides
Journal of Materials Chemistry A 2010 vol. 20(Issue 24) pp:5117-5122
Publication Date(Web):14 May 2010
DOI:10.1039/C000358A
This article describes a method for patterning certain solids—insoluble salts and reduced metals—in sheets of paper. Chemical reactions that produce these solids as precipitates occur when a stamp of patterned paper inked with an aqueous solution of reagent comes into contact with a paper substrate containing a second reagent. The pattern is determined by a hydrophobic barrier on the stamp that restricts delivery of the ink in two dimensions. The technique is one of the few methods available to generate two-dimensional patterns of solids within the bulk of sheets of paper. It can reliably produce features with lateral dimensions only down to 1 mm, but is convenient, inexpensive, and amenable to use in large-area patterning. The method can be used to introduce function to paper-based systems: (i) paramagnetic salts precipitated within paper allow pieces of it to be manipulated or separated from mixtures with a bar magnet, (ii) the precipitation of transition metals or enzymes can be used to position and store catalysts on paper for subsequent use, (iii) catalysts patterned in two dimensions in paper can be used to generate dynamic 3-D structures when exposed to appropriate substrates: for example, a ring of Pd0 deposited on a sheet of paper will generate a cylindrical “cage” of rising oxygen bubbles when exposed to an aqueous solution of hydrogen peroxide, and (iv) patterns of catalysts or colored precipitates can serve as deterrents to counterfeiting.
This paper examines the factors that influence the quality of nanostructures fabricated by sectioning thin films with an ultramicrotome (“nanoskiving”). It surveys different materials (metals, ceramics, semiconductors, and conjugated polymers), deposition techniques (evaporation, sputter deposition, electroless deposition, chemical-vapor deposition, solution-phase synthesis, and spin-coating), and geometries (nanowires or two-dimensional arrays of rings and crescents). It then correlates the extent of fragmentation of the nanostructures with the composition of the thin films, the methods used to deposit them, and the parameters used for sectioning. There are four major conclusions. (i) Films of soft and compliant metals (those that have bulk values of hardness less than or equal to those of palladium, or ≤500 MPa) tend to remain intact upon sectioning, whereas hard and stiff metals (those that have values of hardness greater than or equal to those of platinum, or ≥500 MPa) tend to fragment. (ii) All conjugated polymers tested form intact nanostructures. (iii) The extent of fragmentation is lowest when the direction of cutting is perpendicular to the exposed edge of the embedded film. (iv) The speed of cutting−from 0.1 to 8 mm/s−has no effect on the frequency of defects. Defects generated during sectioning include scoring from defects in the knife, delamination of the film from the matrix, and compression of the matrix. The materials tested were: aluminum, titanium, nickel, copper, palladium, silver, platinum, gold, lead, bismuth, germanium, silicon dioxide (SiO2), alumina (Al2O3), tin-doped indium oxide (ITO), lead sulfide nanocrystals, the semiconducting polymers poly(2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH-PPV), poly(3-hexylthiophene) (P3HT), and poly(benzimidazobenzophenanthroline ladder) (BBL), and the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS).Keywords: microtome; nanofabrication; nanoskiving; nanowires; soft lithography; ultramicrotomy
This paper describes the use of thread as a matrix for the fabrication of diagnostic assay systems. The kinds of thread used for this study are inexpensive, broadly available, and lightweight; some of them are already familiar materials in healthcare. Fluids wick along these threads by capillary action; no external power source is necessary for pumping. This paper demonstrates three designs for diagnostic assays that use different characteristics of the thread. The first two designs—the “woven array” and the “branching design”—take advantage of the ease with which thread can be woven on a loom to generate fluidic pathways that enable multiple assays to be performed in parallel. The third design—the “sewn array”—takes advantage of the ease with which thread can be sewn through a hydrophobic polymer sheet to incorporate assays into bandages, diapers and similar systems. These designs lead to microfluidic devices that may be useful in performing simple colorimetric assays that require qualitative results. We demonstrate the function of thread-based microfluidic devices in the context of five different colorimetric assays: detection of ketones, nitrite, protein, and glucose in artificial urine, and detection of alkaline phosphatase in artificial plasma.Keywords: diagnosis; low-cost; microfluidic devices; paper; thread
This paper describes the development of a method that uses capillary gel electrophoresis (CGE) to analyze mixtures of inorganic polyphosphate ((Pi)n). Resolution of (Pi)n on the basis of n, the number of residues of dehydrated phosphate, is accomplished by CGE using capillaries filled with solutions of poly(N,N-dimethylacrylamide) (PDMA) and indirect detection by the UV absorbance of a chromophore, terephthalate, added to the running buffer. The method is capable of resolving peaks representing (Pi)n with n up to ∼70; preparation and use of authentic standards enables the identification of peaks for (Pi)n with n = 1−10. The main advantages of this method over previously reported methods for analyzing mixtures of (Pi)n (e.g., gel electrophoresis, CGE using polyacrylamide-filled capillaries) are its resolution, convenience, and reproducibility; gel-filled capillaries are easily regenerated by pumping in fresh, low-viscosity solutions of PDMA. The resolution is comparable to that of ion-exchange chromatography and detection of (Pi)n by suppressed conductivity. The method is useful for analyzing (Pi)n generated by the dehydration of Pi at low temperature (125−140 °C) with urea, in a reaction that may have been important in prebiotic chemistry. The method should also be useful for characterizing mixtures of other anionic, oligomeric, or polymeric species without an intrinsic chromophore (e.g., sulfated polysaccharides, oligomeric phospho-diesters).
Co-reporter:Chao-Min Cheng, Aaron D. Mazzeo, Jinlong Gong, Andres W. Martinez, Scott T. Phillips, Nina Jain and George M. Whitesides
Lab on a Chip 2010 vol. 10(Issue 23) pp:3201-3205
Publication Date(Web):15 Oct 2010
DOI:10.1039/C004903D
This communication describes a simple method for printing aqueous solutions with millimeter-scale patterns on a variety of substrates using an easily fabricated, paper-based microfluidic device (a paper-based “stamp”) as a contact printing device. The device is made from inexpensive materials, and it is easily assembled by hand; this method is thus accessible to a wide range of laboratories and budgets. A single device was used to print over 2500 spots in less than three minutes at a density of 16 spots per square centimetre. This method provides a new tool to pattern biochemicals—reagents, antigens, proteins, and DNA—on planar substrates. The accuracy of the volume of fluid delivered in simple paper-to-paper printing is low, and although the pattern transfer is rapid, it is better suited for qualitative than accurate, quantitative work. By patterning the paper to which the transfer occurs using wax printing or an equivalent technique, accuracy increases substantially.
Co-reporter:Zhihong Nie, Frédérique Deiss, Xinyu Liu, Ozge Akbulut and George M. Whitesides
Lab on a Chip 2010 vol. 10(Issue 22) pp:3163-3169
Publication Date(Web):07 Oct 2010
DOI:10.1039/C0LC00237B
The combination of simple Electrochemical Micro-Paper-based Analytical Devices (EµPADs) with commercially available glucometers allows rapid, quantitative electrochemical analysis of a number of compounds relevant to human health (e.g., glucose, cholesterol, lactate, and alcohol) in blood or urine.
Co-reporter:Zhihong Nie, Christian A. Nijhuis, Jinlong Gong, Xin Chen, Alexander Kumachev, Andres W. Martinez, Max Narovlyansky and George M. Whitesides
Lab on a Chip 2010 vol. 10(Issue 4) pp:477-483
Publication Date(Web):03 Dec 2009
DOI:10.1039/B917150A
This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, µPEDs). The µPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the µPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.
Co-reporter:Andres W. Martinez, Scott T. Phillips, Zhihong Nie, Chao-Min Cheng, Emanuel Carrilho, Benjamin J. Wiley and George M. Whitesides
Lab on a Chip 2010 vol. 10(Issue 19) pp:2499-2504
Publication Date(Web):30 Jul 2010
DOI:10.1039/C0LC00021C
This paper describes three-dimensional microfluidic paper-based analytical devices (3-D µPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them. These devices are programmed by pressing single-use ‘on’ buttons, using a stylus or a ballpoint pen. Pressing a button closes a small space (gap) between two vertically aligned microfluidic channels, and allows fluids to wick from one channel to the other. These devices are simple to fabricate, and are made entirely out of paper and double-sided adhesive tape. Programmable devices expand the capabilities of µPADs and provide a simple method for controlling the movement of fluids in paper-based channels. They are the conceptual equivalent of field-programmable gate arrays (FPGAs) widely used in electronics.
Co-reporter:S. Elizabeth Hulme, Sergey S. Shevkoplyas, Alison P. McGuigan, Javier Apfeld, Walter Fontana and George M. Whitesides
Lab on a Chip 2010 vol. 10(Issue 5) pp:589-597
Publication Date(Web):18 Dec 2009
DOI:10.1039/B919265D
This article describes the fabrication of a microfluidic device for the liquid culture of many individual nematode worms (Caenorhabditis elegans) in separate chambers. Each chamber houses a single worm from the fourth larval stage until death, and enables examination of a population of individual worms for their entire adult lifespans. Adjacent to the chambers, the device includes microfluidic worm clamps, which enable periodic, temporary immobilization of each worm. The device made it possible to track changes in body size and locomotion in individual worms throughout their lifespans. This ability to perform longitudinal measurements within the device enabled the identification of age-related phenotypic changes that correlate with lifespan in C. elegans.
Co-reporter:Paul J. Bracher, Malancha Gupta and George M. Whitesides
Soft Matter 2010 vol. 6(Issue 18) pp:4303-4309
Publication Date(Web):10 Jun 2010
DOI:10.1039/C0SM00031K
This account reviews the use of templates, fabricated by patterning paper, for the delivery of aqueous solutions of reactants (predominantly, ions) in the preparation of structured, thin materials (e.g., films of ionotropic hydrogels). In these methods, a patterned sheet of paper transfers an aqueous solution of reagent to a second phase—either solid or liquid—brought into contact with the template; this process can form solid structures with thicknesses that are typically ≤1.5 mm. The shape of the template and the pattern of a hydrophobic barrier on the paper control the shape of the product, in its plane, by restricting the delivery of the reagent in two dimensions. The concentration of the reagents, and the duration that the template remains in contact with the second phase, control growth in the third dimension (i.e., thickness). The method is especially useful in fabricating shaped films of ionotropic hydrogels (e.g., calcium alginate) by controlling the delivery of solutions of multivalent cations to solutions of anionic polymers. The templates can also be used to direct reactions that generate patterns of solid precipitates within sheets of paper. This review examines applications of the method for: (i) patterning bacteria in two dimensions within a hydrogel film, (ii) manipulating hydrogel films and sheets of paper magnetically, and (iii) generating dynamic 3-D structures (e.g., a cylinder of rising bubbles of O2) from sheets of paper with 2-D patterns of a catalyst (e.g., Pd0) immersed in appropriate reagents (e.g., 1% H2O2 in water).
Co-reporter:Katherine A. Mirica, Scott T. Phillips, Charles R. Mace and George M. Whitesides
Journal of Agricultural and Food Chemistry 2010 Volume 58(Issue 11) pp:6565-6569
Publication Date(Web):May 13, 2010
DOI:10.1021/jf100377n
This paper describes a method and a sensor that use magnetic levitation (MagLev) to characterize samples of food and water on the basis of measurements of density. The sensor comprises two permanent NdFeB magnets positioned on top of each other in a configuration with like poles facing and a container filled with a solution of paramagnetic ions. Measurements of density are obtained by suspending a diamagnetic object in the container filled with the paramagnetic fluid, placing the container between the magnets, and measuring the vertical position of the suspended object. MagLev was used to estimate the salinity of water, to compare a variety of vegetable oils on the basis of the ratio of polyunsaturated fat to monounsaturated fat, to compare the contents of fat in milk, cheese, and peanut butter, and to determine the density of grains.
Co-reporter:Darren J. Lipomi, Mikhail A. Kats, Philseok Kim, Sung H. Kang, Joanna Aizenberg, Federico Capasso and George M. Whitesides
ACS Nano 2010 Volume 4(Issue 7) pp:4017
Publication Date(Web):June 8, 2010
DOI:10.1021/nn100993t
This paper describes the fabrication of arrays of nanostructures (rings, crescents, counterfacing split rings, cylinders, coaxial cylinders, and other structures) by a four-step process: (i) molding an array of epoxy posts by soft lithography, (ii) depositing thin films on the posts, (iii) embedding the posts in epoxy, and (iv) sectioning in a plane parallel to the plane defined by the array of posts, into slabs, with an ultramicrotome (“nanoskiving”). This work demonstrates the combination of four capabilities: (i) formation of structures that are submicrometer in all dimensions; (ii) fabrication of 3D structures, and arrays of structures, with gradients of height; (iii) patterning of arrays containing two or more materials, including metals, semiconductors, oxides, and polymers; and (iv) generation of as many as 60 consecutive slabs bearing contiguous arrays of nanostructures. These arrays can be transferred to different substrates, and arrays of gold rings exhibit plasmonic resonances in the range of wavelengths spanning 2−5 μm.Keywords: metamaterials; nanofabrication; nanoskiving; plasmonics; soft lithography; ultramicrotomy
Co-reporter:Sarah J. Vella ; Xin Chen ; Samuel W. Thomas III ; Xuanhe Zhao ; Zhigang Suo
The Journal of Physical Chemistry C 2010 Volume 114(Issue 48) pp:20885-20895
Publication Date(Web):September 29, 2010
DOI:10.1021/jp107883u
This paper describes a method for determining the location of contact electrification-induced electrical discharges detected in a system comprising a steel sphere rolling in a circular path on an organic insulator. The electrode of the “rolling sphere tool” monitors, in real time, the separation of charge between the sphere and the organic insulator and the resultant electrostatic discharges. For every revolution of the sphere, the electrometer records a peak, the height of which represents the amount of charge on the sphere. As the charge on the sphere accumulates, the resulting electric field at the surface of the sphere eventually exceeds the breakdown limit of air and causes a discharge. The position of this discharge can be inferred from the relative amplitudes and positions of the peaks preceding and following the discharge event. We can localize each discharge event to one of several zones, each of which corresponds to a geometrically defined fraction of the circular path of the sphere. The fraction of charge on the sphere that could be detected by the electrode depended on the relative positions of the sphere and the electrode. The use of multiple electrodes improved the accuracy of the method in localizing discharge events and extended the range of angles over which they could be localized to cover the entire circular path followed by the sphere.
Co-reporter:Samuel W. Thomas III ; Sarah J. Vella ; Michael D. Dickey ; George K. Kaufman
Journal of the American Chemical Society 2009 Volume 131(Issue 25) pp:8746-8747
Publication Date(Web):June 5, 2009
DOI:10.1021/ja902862b
This communication describes a new approach for controlling static charging (contact electrification), and resulting electrical discharging, that occurs when two contacting materials separate. The prevention of contact electrification is an important problem; unwanted adhesion between oppositely charged materials, spark-initiated explosions, and damage to microelectronic circuitry are some of the deleterious effects of static charging. Current strategies for controlling contact electrification rely upon dissipating an accumulated charge by making contacting surfaces conductive and, therefore, can be difficult to implement with electrically insulating materials. Specifically, using our understanding of the ion-transfer mechanism of contact electrification, we patterned glass slides with negatively charging areas (clean glass) and positively charging areas (glass silanized with a cationic siloxane terminated with a quaternary ammonium group). The rate of charge separation due to a steel sphere rolling on the patterned glass surface correlated linearly with the percentage of the glass surface that was silanized; the rate of charge transfer was minimal when 50% of the glass surface area was silanized. Patterned surfaces also prevented electrical discharges between electrically conducting (bare steel) or insulating (acrylate-coated steel) spheres rolling on the glass, because the rate of charging was sufficiently slow to prevent electric fields greater than the dielectric strength of air to develop. This strategy for preventing static charging therefore does not require one of the two contacting surfaces to be electrically conductive. More generally, these results show that our enhanced understanding of the ion-transfer mechanism of contact electrification enables the rational design of chemically tailored surfaces for functional electrets.
Co-reporter:Başar Bilgiçer ; Samuel W. Thomas ; III; Bryan F. Shaw ; George K. Kaufman ; Vijay M. Krishnamurthy ; Lara A. Estroff ; Jerry Yang
Journal of the American Chemical Society 2009 Volume 131(Issue 26) pp:9361-9367
Publication Date(Web):June 17, 2009
DOI:10.1021/ja9023836
This paper describes a method for the purification of monoclonal antibodies (rat anti-2,4-dinitrophenyl IgG: IgGDNP; and mouse antidigoxin IgG: IgGDgn) from ascites fluid. This procedure (for IgGDNP) has three steps: (i) precipitation of proteins heavier than immunoglobulins with ammonium sulfate; (ii) formation of cyclic complexes of IgGDNP by causing it to bind to synthetic multivalent haptens containing multiple DNP groups; (iii) selective precipitation of these dimers, trimers, and higher oligomers of the target antibody, followed by regeneration of the free antibody. This procedure separates the targeted antibody from a mixture of antibodies, as well as from other proteins and globulins in a biological fluid. This method is applicable to antibodies with a wide range of monovalent binding constants (0.1 μM to 0.1 nM). The multivalent ligands we used (derivatives of DNP and digoxin) isolated IgGDNP and IgGDgn from ascites fluid in yields of >80% and with >95% purity. This technique has two advantages over conventional chromatographic methods for purifying antibodies: (i) it is selective for antibodies with two active Fab binding sites (both sites are required to form the cyclic complexes) over antibodies with one or zero active Fab binding sites; (ii) it does not require chromatographic separation. It has the disadvantage that the structure of the hapten must be compatible with the synthesis of bi- and/or trivalent analogues.
Co-reporter:Katherine A. Mirica ; Sergey S. Shevkoplyas ; Scott T. Phillips ; Malancha Gupta
Journal of the American Chemical Society 2009 Volume 131(Issue 29) pp:10049-10058
Publication Date(Web):July 2, 2009
DOI:10.1021/ja900920s
This paper describes an analytical system that uses magnetic levitation to measure densities of solids and water-immiscible organic liquids with accuracies ranging from ±0.0002 to ±0.02 g/cm3, depending on the type of experiment. The technique is compatible with densities of 0.8−3 g/cm3 and is applicable to samples with volumes of 1 pL to 1 mL; the samples can be either spherical or irregular in shape. The method employs two permanent NdFeB magnets positioned with like poles facing one another—with the axis between the poles aligned with the gravitational field—and a container filled with paramagnetic medium (e.g., MnCl2 dissolved in water) placed between these magnets. Density measurements are obtained by placing the sample into the container and measuring the position of the sample relative to the bottom magnet. The balance of magnetic and gravitational forces determines the vertical position of the sample within the device; knowing this position makes it possible to calculate the density of the sample.
Co-reporter:Michinao Hashimoto ; Ji Feng ; Roger L. York ; Audrey K. Ellerbee ; Greg Morrison ; Samuel W. Thomas III ; L. Mahadevan
Journal of the American Chemical Society 2009 Volume 131(Issue 34) pp:12420-12429
Publication Date(Web):August 5, 2009
DOI:10.1021/ja904788m
This article describes a new procedure for generating and transmitting a message—a sequence of optical pulses—by aligning a mask (an opaque sheet containing transparent “windows”) below a microfluidic channel in which flows an opaque continuous fluid containing transparent droplets. The optical mask encodes the message as a unique sequence of windows that can transmit or block light; the flow of transparent droplets in the channel converts this message into a sequence of optical pulses. The properties of the windows on the mask (e.g., their size, wavelength of transmittance, orientation of polarization) determine the information carried in these optical pulses (e.g., intensity, color, polarization). The structure of a transmitted signal depends on the number and spacing of droplets in the channel. Fourier transformation can deconvolve superimposed signals created by the flow of multiple droplets into the message that a single droplet would transmit. The research described in this contribution explores a new field at the intersection of chemistry, materials science, and information technology: infochemistry.
The use of delivery templates makes it possible to fabricate shaped, millimeter-thick heterogeneously patterned films of ionotropic hydrogels. These structures include two-dimensional (2-D) patterns of a polymer cross-linked by different ions (e.g., alginic acid cross-linked with Ca2+ and Fe3+) and patterns of step gradients in the concentration of a single cross-linking ion. The delivery templates consist of stacked sheets of chromatography paper patterned with hydrophobic barriers (waterproof tape, transparency film, or toner deposited by a color laser printer). Each layer of paper serves as a reservoir for a different solution of cross-linking ions, while the hydrophobic barriers prevent solutions on adjacent sheets from mixing. Holes cut through the sheets expose different solutions of cross-linking ions to the surface of the templates. Films with shaped regions of hydrogels cross-linked by paramagnetic ions can be oriented with a bar magnet. Variations in the concentrations of cations used to cross-link the gel can control the mechanical properties of the film: for single alginate films composed of areas cross-linked with different concentrations of Fe3+, the regions cross-linked with high concentrations of Fe3+ are more rigid than regions cross-linked with low concentrations of Fe3+. The heterogeneous hydrogel films can be used to culture bacteria in various 2-D designs. The pattern of toxic and nontoxic ions used to cross-link the polymer determines the pattern of viable colonies of Escherichia coli within the film.Keywords: alginate; biofilms; carrageenan; hydrogels; patterning bacteria
This paper describes a method to control the volume and the velocity of drops generated in a flow-focusing device dynamically and independently. This method involves simultaneous tuning of the temperature of the nozzle of the device and of the flow rate of the continuous phase; the method requires a continuous phase liquid that has a viscosity that varies steeply with temperature. Increasing the temperature of the flow-focusing nozzle from 0 to 80 °C increased the volume of the drops by almost 2 orders of magnitude. Tuning both the temperature and the flow rate controlled the drop volume and the drop velocity independently; this feature is not possible in a basic flow-focusing device. This paper also demonstrates a procedure for identifying the range of possible drop volumes and drop velocities for a given flow-focusing device and shows how to generate drops with a specified volume and velocity within this range. This method is easy to implement in on-chip applications where thermal management is already incorporated in the system, such as DNA amplification using the polymerase chain reaction and nanoparticle synthesis.
This paper describes 96- and 384-microzone plates fabricated in paper as alternatives to conventional multiwell plates fabricated in molded polymers. Paper-based plates are functionally related to plastic well plates, but they offer new capabilities. For example, paper-microzone plates are thin (∼180 μm), require small volumes of sample (5 μL per zone), and can be manufactured from inexpensive materials ($0.05 per plate). The paper-based plates are fabricated by patterning sheets of paper, using photolithography, into hydrophilic zones surrounded by hydrophobic polymeric barriers. This photolithography used an inexpensive formulation photoresist that allows rapid (∼15 min) prototyping of paper-based plates. These plates are compatible with conventional microplate readers for quantitative absorbance and fluorescence measurements. The limit of detection per zone loaded for fluorescence was 125 fmol for fluorescein isothiocyanate-labeled bovine serum albumin, and this level corresponds to 0.02 the quantity of analyte per well used to achieve comparable signal-to-noise in a 96-well plastic plate (using a solution of 25 nM labeled protein). The limits of detection for absorbance on paper was aproximately 50 pmol per zone for both Coomassie Brilliant Blue and Amaranth dyes; these values were 0.4 that required for the plastic plate. Demonstration of quantitative colorimetric correlations using a scanner or camera to image the zones and to measure the intensity of color, makes it possible to conduct assays without a microplate reader.
This technical note describes a detailed study on wax printing, a simple and inexpensive method for fabricating microfluidic devices in paper using a commercially available printer and hot plate. The printer prints patterns of solid wax on the surface of the paper, and the hot plate melts the wax so that it penetrates the full thickness of the paper. This process creates complete hydrophobic barriers in paper that define hydrophilic channels, fluid reservoirs, and reaction zones. The design of each device was based on a simple equation that accounts for the spreading of molten wax in paper.
Co-reporter:Adam C. Siegel, Scott T. Phillips, Benjamin J. Wiley and George M. Whitesides
Lab on a Chip 2009 vol. 9(Issue 19) pp:2775-2781
Publication Date(Web):23 Jun 2009
DOI:10.1039/B905832J
This article describes an electronic display that is fabricated by patterning electrically conductive wires (heaters) with micron-scale dimensions on one side of a sheet of paper, and thermochromic ink on the opposite side. Passing electrical current through the wires heats the paper and changes the thermochromic ink from colored (black, green, or other colors) to transparent; this change in property reveals the paper underneath the ink—exposing any messages printed on the paper—and serves as the basis for a two-state “shutter” display. This type of display is thin (100 µm), flat, lightweight (the display weighs <20 mg/cm2), can be folded, rolled, twisted, and creased while maintaining function, and ultimately can (if required) be disposed of by incineration. The display is appropriate for applications where information must be presented clearly (usually only once) for little cost (each display costs <$0.10/m2 in materials) and where limited electrical power is available.
Co-reporter:Sindy K. Y. Tang, Zhenyu Li, Adam R. Abate, Jeremy J. Agresti, David A. Weitz, Demetri Psaltis and George M. Whitesides
Lab on a Chip 2009 vol. 9(Issue 19) pp:2767-2771
Publication Date(Web):14 Aug 2009
DOI:10.1039/B914066B
We describe a multi-color microfluidic dye laser operating in whispering gallery mode based on a train of alternating droplets containing solutions of different dyes; this laser is capable of switching the wavelength of its emission between 580 nm and 680 nm at frequencies up to 3.6 kHz—the fastest among all dye lasers reported; it has potential applications in on-chip spectroscopy and flow cytometry.
Co-reporter:Claudiu A. Stan, Grégory F. Schneider, Sergey S. Shevkoplyas, Michinao Hashimoto, Mihai Ibanescu, Benjamin J. Wiley and George M. Whitesides
Lab on a Chip 2009 vol. 9(Issue 16) pp:2293-2305
Publication Date(Web):22 May 2009
DOI:10.1039/B906198C
This paper describes a microfluidic instrument that produces drops of supercooled water suspended in a moving stream of liquid fluorocarbon, and measures the temperatures at which ice nucleates in the drops. A microfluidic chip containing a monodisperse drop generator and a straight channel with 38 embedded resistance thermometers was placed in contact with a seven-zone temperature-control plate and imaged under a microscope with a high-speed camera. This instrument can record the freezing temperatures of tens of thousands of drops within minutes, with an accuracy of 0.4 °C. The ice-nucleation temperatures in ∼80-µm drops were reported for the freezing of 37061 drops of pure water, and of 8898 drops of water seeded with silver iodide. Nucleation of ice in pure water was homogenous and occurred at temperatures between −36 and −37.8 °C, while water containing silver iodide froze between −10 and −19 °C. The instrument recorded the largest sets of individual freezing temperatures (37061), had the fastest data acquisition rate (75 measurements/s), and the best optical (3 µm) and temporal (70 µs) resolutions among instruments designed to study nucleation of ice. The dendritic growth of ice in 150-µm drops of supercooled water at −35 °C was observed and imaged at a rate of 16000 frames/s.
Co-reporter:George K. Kaufman, Samuel W. Thomas III, Meital Reches, Bryan F. Shaw, Ji Feng and George M. Whitesides
Soft Matter 2009 vol. 5(Issue 6) pp:1188-1191
Publication Date(Web):16 Oct 2008
DOI:10.1039/B813590H
This paper describes the phase separation of millimetre-scale spheres based on electrostatic charge. Initially, polymeric (Teflon, T; Nylon-6,6, N) and metallic (gold-coated Nylon-6,6, AuN) spheres are uniformly mixed in a two-dimensional (2D) monolayer on a gold-coated plate. Oscillating the plate vertically caused the spheres to charge by contact electrification (tribocharging). Positively charged N and negatively charged T spheres attracted each other more strongly than they attracted the capacitively charged, AuN spheres. The T and N spheres formed 2D Coulombic crystals, and these crystals separated from the AuN spheres. The extent and rate of separation increased with increasing amplitude of agitation during tribocharging, and with decreasing density of spheres on the surface. At high surface density, the T and N spheres did not separate from the AuN spheres. This system models the 2D nucleation of an ionic crystal from a polarizable liquid.
Co-reporter:Ratmir Derda;Anna Laromaine;Akiko Mammoto;Sindy K. Y. Tang;Tadanori Mammoto;Donald E. Ingber
PNAS 2009 Volume 106 (Issue 44 ) pp:18457-18462
Publication Date(Web):2009-11-03
DOI:10.1073/pnas.0910666106
Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems
that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist
but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. Microfabrication
can create architecturally complex scaffolds for 3D cell cultures that circumvent some of these limitations; unfortunately,
these approaches require instrumentation not commonly available in biology laboratories. Here we report that stacking and
destacking layers of paper impregnated with suspensions of cells in extracellular matrix hydrogel makes it possible to control
oxygen and nutrient gradients in 3D and to analyze molecular and genetic responses. Stacking assembles the “tissue”, whereas
destacking disassembles it, and allows its analysis. Breast cancer cells cultured within stacks of layered paper recapitulate
behaviors observed both in 3D tumor spheroids in vitro and in tumors in vivo: Proliferating cells in the stacks localize in
an outer layer a few hundreds of microns thick, and growth-arrested, apoptotic, and necrotic cells concentrate in the hypoxic
core where hypoxia-sensitive genes are overexpressed. Altering gas permeability at the ends of stacks controlled the gradient
in the concentration of the O2 and was sufficient by itself to determine the distribution of viable cells in 3D. Cell cultures in stacked, paper-supported
gels offer a uniquely flexible approach to study cell responses to 3D molecular gradients and to mimic tissue- and organ-level
functions.
Co-reporter:Darren J. Lipomi, Filip Ilievski, Benjamin J. Wiley, Parag B. Deotare, Marko Lončar and George M. Whitesides
ACS Nano 2009 Volume 3(Issue 10) pp:3315
Publication Date(Web):September 16, 2009
DOI:10.1021/nn901002q
This paper describes a process for the fabrication and positioning of nanowires (of Au, Pd, and conjugated polymers) embedded in thin epoxy slabs. The procedure has four steps: (i) coembedding a thin film of metal or conducting polymer with a thin film of nickel metal (Ni) in epoxy; (ii) sectioning the embedded structures into nanowires with an ultramicrotome (“nanoskiving”); (iii) floating the epoxy sections on a pool of water; and (iv) positioning the sections with an external magnet to a desired location (“magnetic mooring”). As the water evaporates, capillary interactions cause the sections to adhere to the substrate. Both the Ni and epoxy can be etched to generate free-standing metallic nanowires. The average translational deviation in the positioning of two nanowires with respect to each other is 16 ± 13 μm, and the average angular deviation is 3 ± 2°. Successive depositions of nanowires yield the following structures of interest for electronic and photonic applications: electrically continuous junctions of two Au nanowires, two Au nanowires spanned by a poly(3-hexylthiophene) (P3HT) nanowire; single-crystalline Au nanowires that cross; crossbar arrays of Au nanowires; crossbar arrays of Au and Pd nanowires; and a 50 × 50 array of poly(benzimidazobenzophenanthroline ladder) (BBL) nanowires. Single-crystalline Au nanowires can be placed on glass wool fibers or on microfabricated polymeric waveguides, with which the nanowire can be addressed optically.Keywords: conjugated polymers; magnetic positioning; microtome; nanofabrication; nanophotonics; nanoskiving; nanowire positioning; nanowires
Co-reporter:Ryan C. Chiechi;Michael R. Webb;Samuel W. Thomas III;Andrew Lee;Benjamin J. Wiley;Mitchell R. Zakin;David R. Walt;Christopher N. LaFratta
PNAS 2009 Volume 106 (Issue 23 ) pp:9147-9150
Publication Date(Web):2009-06-09
DOI:10.1073/pnas.0902476106
This article describes a self-powered system that uses chemical reactions—the thermal excitation of alkali metals—to transmit
coded alphanumeric information. The transmitter (an “infofuse”) is a strip of the flammable polymer nitrocellulose patterned
with alkali metal ions; this pattern encodes the information. The wavelengths of 2 consecutive pulses of light represent each
alphanumeric character. While burning, infofuses transmit a sequence of pulses (at 5–20 Hz) of atomic emission that correspond
to the sequence of metallic salts (and therefore to the encoded information). This system combines information technology
and chemical reactions into a new area—“infochemistry”—that is the first step toward systems that combine sensing and transduction
of chemical signals with multicolor transmission of alphanumeric information.
The “beads-on-a-string” model for folding of polymers is a cornerstone of theoretical polymer science. This communication
describes a physical model of beads-on-a-string, based on the folding of flexible strings of electrostatically charged beads
in two dimensions. The system comprises millimeter-scale Teflon and Nylon-6,6 (spherical or cylindrical) beads (≈ 6 mm in
diameter) separated by smaller (≈3 mm) poly(methyl methacrylate) (PMMA) spherical beads, threaded on a flexible string. The
smaller, uncharged beads define the distances between the larger beads, and control the flexibility of the string. During
agitation of the sequence of beads on a planar, horizontal paper surface, tribocharging generates opposite electrostatic charges
on the larger Nylon and Teflon beads, but leaves the smaller PMMA beads essentially uncharged; the resulting electrostatic
interactions cause the string to fold. Examination and comparison of two models—one physical and one theoretical—may offer
a new approach to understanding folding, collapse, and molecular recognition at an abstract level, with particular opportunity
to explore the influence of the flexibility of the string and the shape of the beads on the pattern and rate of folding. The
physical system is, thus, an analog computer, simulating the theoretical beads-on-a-string model in two dimensions; this system
makes it possible to test hypotheses connecting “sequence” to “folding”, rapidly and conveniently, while exploring nonlinearities
and other complexities omitted from the theoretical model.
Co-reporter:Elizabeth J. Smythe, Michael D. Dickey, George M. Whitesides and Federico Capasso
ACS Nano 2009 Volume 3(Issue 1) pp:59
Publication Date(Web):December 30, 2008
DOI:10.1021/nn800720r
Conventional lithographic methods (e.g., electron-beam lithography, photolithography) are capable of producing high-resolution structures over large areas but are generally limited to large (>1 cm2) planar substrates. Incorporation of these features on unconventional substrates (i.e., small (<1 mm2) and/or non-planar substrates) would open possibilities for many applications, including remote fiber-based sensing, nanoscale optical lithography, three-dimensional fabrication, and integration of compact optical elements on fiber and semiconductor lasers. Here we introduce a simple method in which a thin thiol-ene film strips arbitrary nanoscale metallic features from one substrate and is then transferred, along with the attached features, to a substrate that would be difficult or impossible to pattern with conventional lithographic techniques. An oxygen plasma removes the sacrificial film, leaving behind the metallic features. The transfer of dense and sparse patterns of isolated and connected gold features ranging from 30 nm to 1 μm, to both an optical fiber facet and a silica microsphere, demonstrates the versatility of the method. A distinguishing feature of this technique is the use of a thin, sacrificial film to strip and transfer metallic nanopatterns and its ability to directly transfer metallic structures produced by conventional lithography.Keywords: metal nanoparticles; nanofabrication; nanopatterning; pattern transfer; soft lithography
Co-reporter:Qiaobing Xu, Robert M. Rioux, Michael D. Dickey and George M. Whitesides
Accounts of Chemical Research 2008 Volume 41(Issue 12) pp:1566
Publication Date(Web):July 23, 2008
DOI:10.1021/ar700194y
This Account reviews nanoskiving−a new technique that combines thin-film deposition of metal on a topographically contoured substrate with sectioning using an ultramicrotome−as a method of fabricating nanostructures that could replace conventional top-down techniques in selected applications. Photolithography and scanning beam lithography, conventional top-down techniques to generate nanoscale structures and nanostructured materials, are useful, versatile, and highly developed, but they also have limitations: high capital and operating costs, limited availability of the facilities required to use them, an inability to fabricate structures on nonplanar surfaces, and restrictions on certain classes of materials. Nanoscience and nanotechnology would benefit from new, low-cost techniques to fabricate electrically and optically functional structures with dimensions of tens of nanometers, even if (or perhaps especially if) these techniques have a different range of application than does photolithography or scanning beam lithography. Nanoskiving provides a simple and convenient procedure to produce arrays of structures with cross-sectional dimensions in the 30-nm regime. The dimensions of the structures are determined by (i) the thickness of the deposited thin film (tens of nanometers), (ii) the topography (submicrometer, using soft lithography) of the surface onto which the thin film is deposited, and (iii) the thickness of the section cut by the microtome (≥30 nm by ultramicrotomy). The ability to control the dimensions of nanostructures, combined with the ability to manipulate and position them, enables the fabrication of nanostructures with geometries that are difficult to prepare by other methods. The nanostructures produced by nanoskiving are embedded in a thin epoxy matrix. These epoxy slabs, although fragile, have sufficient mechanical strength to be manipulated and positioned; this mechanical integrity allows the nanostructures to be stacked in layers, draped over curved surfaces, and suspended across gaps, while retaining the in-plane geometry of the nanostructures embedded in the epoxy. After removal of the polymer matrix by plasma oxidation, these structures generate suspended and draped nanostructures and nanostructures on curved surfaces. Two classes of applications, in optics and in electronics, demonstrate the utility of nanostructures fabricated by nanoskiving. This technique will be of primary interest to researchers who wish to generate simple nanostructures, singly or in arrays, more simply and quickly than can be accomplished in the clean-room. It is easily accessible to those not trained in top-down procedures for fabrication and those with limited or no access to the equipment and facilities needed for photolithography or scanning-beam fabrication. This Account discusses a new fabrication method (nanoskiving) that produces arrays of metal nanostructures. The defining process in nanoskiving is cutting slabs from a polymeric matrix containing embedded, more extended metal structures.
Co-reporter:Benjamin J. Wiley, Darren J. Lipomi, Jiming Bao, Federico Capasso and George M. Whitesides
Nano Letters 2008 Volume 8(Issue 9) pp:3023-3028
Publication Date(Web):August 23, 2008
DOI:10.1021/nl802252r
This paper demonstrates the sectioning of chemically synthesized, single-crystalline microplates of gold with an ultramicrotome (nanoskiving) to produce single-crystalline nanowires; these nanowires act as low-loss surface plasmon resonators. This method produces collinearly aligned nanostructures with small, regular changes in dimension with each consecutive cross-section: a single microplate thus can produce a number of “quasi-copies” (delicately modulated variations) of a nanowire. The diamond knife cuts cleanly through microplates 35 μm in diameter and 100 nm thick without bending the resulting nanowire and cuts through the sharp edges of a crystal without deformation to generate nanoscale tips. This paper compares the influence of sharp tips and blunt tips on the resonator modes in these nanowires.
Co-reporter:Darren J. Lipomi, Ryan C. Chiechi, Michael D. Dickey and George M. Whitesides
Nano Letters 2008 Volume 8(Issue 7) pp:2100-2105
Publication Date(Web):June 3, 2008
DOI:10.1021/nl8009318
This paper describes the fabrication of conjugated polymer nanowires by a three stage process: (i) spin-coating a composite film comprising alternating layers of a conjugated polymer and a sacrificial material, (ii) embedding the film in an epoxy matrix and sectioning it with an ultramicrotome (nanoskiving), and (iii) etching the sacrificial material to reveal nanowires of the conjugated polymer. A free-standing, 100-layer film of two conjugated polymers was spin-coated from orthogonal solvents: poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) from chloroform and poly(benzimidazobenzophenanthroline ladder) (BBL) from methanesulfonic acid. After sectioning the multilayer film, dissolution of the BBL with methanesulfonic acid yielded uniaxially aligned MEH-PPV nanowires with rectangular cross sections, and etching MEH-PPV with an oxygen plasma yielded BBL nanowires. The conductivity of MEH-PPV nanowires changed rapidly and reversibly by >103 upon exposure to I2 vapor. The result suggests that this technique could be used to fabricate high-surface-area structures of conducting organic nanowires for possible applications in sensing and in other fields where a high surface area in a small volume is desirable.
This paper describes the fabrication of a nanostructured heterojunction of two conjugated polymers by a three-step process: i) spin-coating a multilayered film of the two polymers, ii) rolling the film into a cylinder (a “jelly roll”) and iii) sectioning the film perpendicular to the axis of the roll with an ultramicrotome (nanoskiving). The conjugated polymers are poly(benzimidazobenzophenanthroline ladder) (BBL, n-type) and poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV, p-type). The procedure produces sections with an interdigitated junction of the two polymers. The spacing between the phases is determined by spin-coating (∼15 nm to 100 nm) and the thickness of each section is determined by the ultramicrotome (100 to 1000 nm). The minimum width of the MEH-PPV layers accessible with this technique (∼15 nm) is close to reported exciton diffusion lengths for the polymer. When placed in a junction between two electrodes with asymmetric work functions (tin-doped indium oxide (ITO) coated with poly(3,4-ethylenedioxythiophene:poly(styrenesulfonate) (PEDOT:PSS), and eutectic gallium-indium, EGaIn) the heterostructures exhibit a photovoltaic response under white light, although the efficiency of conversion of optical to electrical energy is low. Selective excitation of BBL with red light confirms that the photovoltaic effect is the result of photoinduced charge transfer between BBL and MEH-PPV.
Co-reporter:Andres W. Martinez, Scott T. Phillips, Benjamin J. Wiley, Malancha Gupta and George M. Whitesides
Lab on a Chip 2008 vol. 8(Issue 12) pp:2146-2150
Publication Date(Web):22 Aug 2008
DOI:10.1039/B811135A
This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 µm in width and 70 µm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available.
Co-reporter:Amy P. Wong, Malancha Gupta, Sergey S. Shevkoplyas and George M. Whitesides
Lab on a Chip 2008 vol. 8(Issue 12) pp:2032-2037
Publication Date(Web):14 Oct 2008
DOI:10.1039/B809830C
This paper demonstrates that a hand-powered egg beater can be modified to serve as a centrifuge for separating plasma from human whole blood. Immunoassays used to diagnose infectious diseases often require plasma from whole blood, and obtaining plasma typically requires electrically-powered centrifuges, which are not widely available in resource-limited settings. Human whole blood was loaded into polyethylene (PE) tubing, and the tubing was attached to the paddle of an egg beater. Spinning the paddle pelleted the blood cells to the distal end of the PE tubing; the plasma remained as the supernatant. A cholesterol assay (run on patterned paper) demonstrated the suitability of this plasma for use in diagnostic assays. The physics of the system was also analyzed as a guide for the selection of other rotating systems for use in centrifugation. Egg beaters, polyethylene tubing, and paper are readily available devices and supplies that can facilitate the use of point-of-care diagnostics at sites far from centralized laboratory facilities.
Co-reporter:Derek A. Bruzewicz, Alison P. McGuigan and George M. Whitesides
Lab on a Chip 2008 vol. 8(Issue 5) pp:663-671
Publication Date(Web):20 Mar 2008
DOI:10.1039/B719806J
By combining microfluidics and soft-lithographic molding of gels containing mammalian cells, a device for three-dimensional (3D) culture of mammalian cells in microchannels was developed. Native components of the extracellular matrix, including collagen or Matrigel™, made up the matrix of each molded piece (module) of cell-containing gel. Each module had at least one dimension below ∼300 μm; in modules of these sizes, the flux of oxygen, nutrients, and metabolic products into and out of the modules was sufficient to allow cells in the modules to proliferate to densities comparable to those of native tissue (108–109cells cm−3). Packing modules loosely into microfluidic channels and chambers yielded structures permeated with a network of pores through which cell culture medium could flow to feed the encapsulated cells. The order in the packed assemblies increased as the width of the microchannels approached the width of the modules. Multiple cell types could be spatially organized in the small microfluidic channels. Recovery and analysis of modules after 24 h under constant flow of medium (200 μL h−1) showed that over 99% of encapsulated cells survived this interval in the microfluidic chamber.
Co-reporter:Sindy K. Y. Tang, Claudiu A. Stan and George M. Whitesides
Lab on a Chip 2008 vol. 8(Issue 3) pp:395-401
Publication Date(Web):14 Jan 2008
DOI:10.1039/B717037H
This paper describes the design and operation of a liquid-core liquid-cladding (L2) lens formed by the laminar flow of three streams of liquids in a microchannel whose width expands laterally in the region where the lens forms. Two streams of liquid with a lower refractive index (the cladding) sandwich a stream of liquid with a higher refractive index (the core). As the core stream enters the expansion chamber, it widens and becomes biconvex in shape, for some rates of flow. This biconvex fluidic element focuses light. Manipulating the relative rates of flow of the streams reconfigures the shape, and therefore the focal distance, of the L2 lens. This paper also describes a technique for beam tracing, and for characterization of a lens in an enclosed micro-scale optical system. The use of a cladding liquid with refractive index matched to that of the material used in the fabrication of the microfluidic system (here, poly(dimethylsiloxane)) improves the quality of the focused beam.
This paper analyzes the equilibria involved in the dimerization of monomeric receptors with homo-bifunctional ligands. We provide analytical expressions that can be used to estimate the concentration of each species present in a mixture of homo-bifunctional ligand and monomeric proteins, given initial conditions defining the total concentration of bivalent ligand [L2]0, the total concentration of protein [P]0, one dissociation constant Kd, and a parameter to account for cooperativity α. We demonstrate that the fraction of protein present in a complex of two proteins and one bivalent ligand (P·L2·P) is maximized at [L2]0 = Kd/2 + [P]0/2.
This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.
Co-reporter:Michinao Hashimoto, Piotr Garstecki, Howard A. Stone and George M. Whitesides
Soft Matter 2008 vol. 4(Issue 7) pp:1403-1413
Publication Date(Web):08 May 2008
DOI:10.1039/B715867J
This paper describes surfactant-sensitive, dynamic instabilities that occur to aqueous droplets translating in a continuous flow of hexadecane in a microfluidic Hele-Shaw cell (HSC). A very low interfacial tension (on the order of 0.01 mN m−1) between water and hexadecane allowed for deformation of the droplets along the fields of flow and tip-streaming from moving droplets. In the system of water and hexadecane that we investigated, the use of surfactants in both fluids was necessary to achieve interfacial tension sufficiently low for the instabilities to occur. The droplets entering the HSC stretched orthogonally to the main direction of flow into elongated shapes, with aspect ratios greater than ten to one (width to length). These droplets exhibited two types of instabilities. The first included elongation of droplets, and Rayleigh–Plateau instabilities in the stretched droplets. Arrays of these stretched droplets formed three characteristic patterns that depended on the rates of flow of water and hexadecane. The second was driven by the shear stress exerted on the interface between the two fluids by the top and bottom boundaries of the HSC; this instability is named a “shear-driven instability” (SDI). Our observations supported that the SDI—an effect similar to tip-streaming—resulted from a redistribution of surfactants at the interface between the two fluids.
Co-reporter:LoganS. McCarty Dr. ;GeorgeM. Whitesides
Angewandte Chemie International Edition 2008 Volume 47( Issue 12) pp:2188-2207
Publication Date(Web):
DOI:10.1002/anie.200701812
Abstract
This Review discusses ionic electrets: their preparation, their mechanisms of formation, tools for their characterization, and their applications. An electret is a material that has a permanent, macroscopic electric field at its surface; this field can arise from a net orientation of polar groups in the material, or from a net, macroscopic electrostatic charge on the material. An ionic electret is a material that has a net electrostatic charge due to a difference in the number of cationic and anionic charges in the material. Any material that has ions at its surface, or accessible in its interior, has the potential to become an ionic electret. When such a material is brought into contact with some other material, ions can transfer between them. If the anions and cations have different propensities to transfer, the unequal transfer of these ions can result in a net transfer of charge between the two materials. This Review focuses on the experimental evidence and theoretical models for the formation of ionic electrets through this ion-transfer mechanism, and proposes—as a still-unproved hypothesis—that this ion-transfer mechanism may also explain the ubiquitous contact electrification (“static electricity”) of materials, such as organic polymers, that do not explicitly have ions at their surface.
Gegenstand dieses Aufsatz sind ionische Elektrete: ihre Herstellung, ihr Bildungsmechanismus, Methoden zu ihrer Charakterisierung und ihre Anwendungen. Ein Elektret ist ein Material, das an seiner Oberfläche ein permanentes makroskopisches elektrisches Feld aufweist; dieses Feld kann aus einer Nettoausrichtung von polaren Gruppen im Material oder aus einer makroskopischen elektrostatischen Nettoladung auf dem Material resultieren. Ein ionisches Elektret ist ein Material, das aufgrund einer unterschiedlichen Zahl von kationischen und anionischen Ladungen eine elektrostatische Nettoladung aufbaut. Jedes Material, das Ionen auf seiner Oberfläche trägt oder verfügbare Ionen in der Volumenphase enthält, ist ein potenzielles ionisches Elektret. Wird ein derartiges Material mit einem anderen Material in Kontakt gebracht, können zwischen ihnen Ionen übertragen werden. Falls Anionen und Kationen unterschiedliche Transferneigungen haben, kann dies dazu führen, dass zwischen den beiden Materialien eine Nettoladung übertragen wird. Ionische Elektrete, deren Bildung auf diesem Ionentransfermechanismus basiert, sind das Thema dieses Aufsatzes, der sowohl experimentelle Nachweise als auch theoretische Modelle diskutiert; außerdem wird eine noch unbewiesene Hypothese vorgeschlagen, wonach dieser Ionentransfermechanismus auch die allgegenwärtige Kontaktelektrisierung (“statische Elektrizität”) von Materialien, z. B. organischen Polymeren, erklären könnte, die nicht explizit Ionen auf ihrer Oberfläche haben.
Co-reporter:Michael D. Dickey, Emily A. Weiss, Elizabeth J. Smythe, Ryan C. Chiechi, Federico Capasso and George M. Whitesides
ACS Nano 2008 Volume 2(Issue 4) pp:800
Publication Date(Web):March 22, 2008
DOI:10.1021/nn800036r
This paper describes a simple technique for fabricating uniform arrays of metal and metal oxide nanotubes with controlled heights and diameters. The technique involves depositing material onto an anodized aluminum oxide (AAO) membrane template using a collimated electron beam evaporation source. The evaporating material enters the porous openings of the AAO membrane and deposits onto the walls of the pores. The membrane is tilted with respect to the column of evaporating material, so the shadows cast by the openings of the pores onto the inside walls of the pores define the geometry of the tubes. Rotation of the membrane during evaporation ensures uniform deposition inside the pores. After evaporation, dissolution of the AAO in base easily removes the template to yield an array of nanotubes connected by a thin backing of the same metal or metal oxide. The diameter of the pores dictates the diameter of the tubes, and the incident angle of evaporation determines the height of the tubes. Tubes up to ∼1.5 μm in height and 20–200 nm in diameter were fabricated. This method is adaptable to any material that can be vapor-deposited, including indium−tin oxide (ITO), a conductive, transparent material that is useful for many opto-electronic applications. An array of gold nanotubes produced by this technique served as a substrate for surface-enhanced Raman spectroscopy: the Raman signal (per molecule) from a monolayer of benzenethiolate was a factor of ∼5 × 105 greater than that obtained using bulk liquid benzenethiol.Keywords: AAO (anodized aluminum oxide); ITO (indium−tin oxide); line-of-sight deposition; nanofabrication; nanotube arrays; SERS (surface-enhanced Raman spectroscopy); shadow evaporation; templated fabrication;
This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided
adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using
conventional open-channel microsystems made from glass or polymers. In particular, 3D paper-based devices wick fluids and
distribute microliter volumes of samples from single inlet points into arrays of detection zones (with numbers up to thousands).
This capability makes it possible to carry out a range of new analytical protocols simply and inexpensively (all on a piece
of paper) without external pumps. We demonstrate a prototype 3D device that tests 4 different samples for up to 4 different
analytes and displays the results of the assays in a side-by-side configuration for easy comparison. Three-dimensional paper-based
microfluidic devices are especially appropriate for use in distributed healthcare in the developing world and in environmental
monitoring and water analysis.
Co-reporter:Douglas B. Weibel,
Willow R. DiLuzio
and
George M. Whitesides
Nature Reviews Microbiology 2007 5(3) pp:209
Publication Date(Web):2007-03-01
DOI:10.1038/nrmicro1616
This Review summarizes methods for constructing systems and structures at micron or submicron scales that have applications in microbiology. These tools make it possible to manipulate individual cells and their immediate extracellular environments and have the capability to transform the study of microbial physiology and behaviour. Because of their simplicity, low cost and use in microfabrication, we focus on the application of soft lithographic techniques to the study of microorganisms, and describe several key areas in microbiology in which the development of new microfabricated materials and tools can have a crucial role.
The fabrication of complex metallic microstructures in 3D by injecting liquid solder into microfluidic channels and allowing the solder to cool and solidify is demonstrated; after fabrication, the metallic structures can be flexed, bent, or twisted (see figure and cover). With this method it is possible to build flexible electronic circuits, complex embedded or freestanding 3D metal microstructures, 3D electronic components, and hybrid electronic–microfluidic devices.
Co-reporter:A. C. Siegel;D. B. Weibel;G. M. Whitesides;D. A. Bruzewicz
Advanced Materials 2007 Volume 19(Issue 5) pp:
Publication Date(Web):27 FEB 2007
DOI:10.1002/adma.200790017
Flexible metallic wires embedded in poly(dimethylsiloxane) are produced with microscale dimensions by injecting heated, liquid solder into microfluidic channels and cooling, as reported by George Whitesides and co-workers on p. 727. This approach is used to fabricate complex, metallic microstructures that are twisted (as shown), rolled, or woven into fabrics. The structures can be rigid or flexible, depending on the type of solder used, and breaks in the metal can be “healed” by reheating the device. This method of fabrication may find applications in flexible electronic circuits, 3D metallic microstructures, and hybrid electronic–microfluidic devices.
Co-reporter:Douglas B. Weibel, Adam C. Siegel, Andrew Lee, Alexander H. George and George M. Whitesides
Lab on a Chip 2007 vol. 7(Issue 12) pp:1832-1836
Publication Date(Web):18 Oct 2007
DOI:10.1039/B714664G
This paper demonstrates a methodology for storing and pumping fluids that provide a useful capability for microfluidic devices. It uses microfluidic screw valves to isolate fluids in poly(dimethylsiloxane) (PDMS) microcompartments, in which the pressure of the liquid is stored in the elastic deformation of the walls and ceiling of the compartments. Fluids can be stored under pressure in these structures for months. When the valves are opened, the walls and ceiling push the fluid out of the compartments into microfluidic channels. The system has five useful characteristics: (i) it is made using soft lithographic techniques; (ii) it allows multiple reagents to be preloaded in devices and stored under pressure without any additional user intervention; (iii) it makes it possible to meter out fluids in devices, and to control rates of flow of fluids; (iv) it prevents the user from exposure to potentially toxic reagents; and (v) it is hand-operated and does not require additional equipment or resources.
Co-reporter:S. Elizabeth Hulme, Sergey S. Shevkoplyas, Javier Apfeld, Walter Fontana and George M. Whitesides
Lab on a Chip 2007 vol. 7(Issue 11) pp:1515-1523
Publication Date(Web):16 Aug 2007
DOI:10.1039/B707861G
This paper describes the fabrication of a microfluidic device for rapid immobilization of large numbers of live C. elegans for performing morphological analysis, microsurgery, and fluorescence imaging in a high-throughput manner. The device consists of two principal elements: (i) an array of 128 wedge-shaped microchannels, or clamps, which physically immobilize worms, and (ii) a branching network of distribution channels, which deliver worms to the array. The flow of liquid through the device (driven by a constant pressure difference between the inlet and the outlet) automatically distributes individual worms into each clamp. It was possible to immobilize more than 100 worms in less than 15 min. The immobilization process was not damaging to the worms: following removal from the array of clamps, worms lived typical lifespans and reproduced normally. The ability to monitor large numbers of immobilized worms easily and in parallel will enable researchers to investigate physiology and behavior in large populations of C. elegans.
Co-reporter:Michael J. Fuerstman, Ann Lai, Meghan E. Thurlow, Sergey S. Shevkoplyas, Howard A. Stone and George M. Whitesides
Lab on a Chip 2007 vol. 7(Issue 11) pp:1479-1489
Publication Date(Web):22 Aug 2007
DOI:10.1039/B706549C
This paper derives the difference in pressure between the beginning and the end of a rectangular microchannel through which a flowing liquid (water, with or without surfactant, and mixtures of water and glycerol) carries bubbles that contact all four walls of the channel. It uses an indirect method to derive the pressure in the channel. The pressure drop depends predominantly on the number of bubbles in the channel at both low and high concentrations of surfactant. At intermediate concentrations of surfactant, if the channel contains bubbles (of the same or different lengths), the total, aggregated length of the bubbles in the channel is the dominant contributor to the pressure drop. The difference between these two cases stems from increased flow of liquid through the “gutters”—the regions of the system bounded by the curved body of the bubble and the corners of the channel—in the presence of intermediate concentrations of surfactant. This paper presents a systematic and quantitative investigation of the influence of surfactants on the flow of fluids in microchannels containing bubbles. It derives the contributions to the overall pressure drop from three regions of the channel: (i) the slugs of liquid between the bubbles (and separated from the bubbles), in which liquid flows as though no bubbles were present; (ii) the gutters along the corners of the microchannels; and (iii) the curved caps at the ends of the bubble.
Co-reporter:Adam Winkleman, Raquel Perez-Castillejos, Michal Lahav, Max Narovlyansky, Leonard N. J. Rodriguez and George M. Whitesides
Soft Matter 2007 vol. 3(Issue 1) pp:108-116
Publication Date(Web):23 Nov 2006
DOI:10.1039/B611630B
This paper describes a photolithographic method to create sub-micron-scale patterns of cation-cross-linked poly(acrylic acid) (CCL-PAA). PAA can be cross-linked with a wide range of metal cations—including, but not limited to, Ag+, Ca2+, Pd2+, Al3+, La3+, and Ti4+. Upon patterning a positive photoresist (diazonaphthoquinone-novolac resin) on a film of CCL-PAA, the exposed regions of CCL-PAA were etched by either an aqueous NaOH or EDTA solution. The initial cross-linking cation could be exchanged for a second cation that could not be patterned photolithographically. We used these patterned films of CCL-PAA i) to host and template the reduction of metallic cations to metallic nanoparticles, and ii) to fabricate porous, low-k dielectric substrates.
Co-reporter:Andres W. Martinez;Scott T. Phillips Dr.;Manish J. Butte Dr.;George M. Whitesides
Angewandte Chemie 2007 Volume 119(Issue 8) pp:
Publication Date(Web):9 JAN 2007
DOI:10.1002/ange.200603817
Einfach überzeugend: Ein Verfahren zur Mustererzeugung auf Papier mit einem Fotolack liefert definierte, millimetergroße Kanäle aus hydrophilem Papier und hydrophobem Polymer. Diese Art von bedrucktem Papier ist ein Prototyp billiger, transportabler und technisch einfacher Plattformen für gebündelte Bioassays mit Mikrolitervolumina einer einzelnen biologischen Probe.
Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.
Co-reporter:Chu-Young Kim Dr.;Vijay M. Krishnamurthy Dr.;Demetri T. Moustakas Dr.;George M. Whitesides Dr.;David W. Christianson Dr.;Brooks R. Bohall
Chemistry – An Asian Journal 2007 Volume 2(Issue 1) pp:94-105
Publication Date(Web):14 DEC 2006
DOI:10.1002/asia.200600360
This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF5−nSO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure–activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the ZnII cofactor–sulfonamide bond (≈65 % of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10 %), and the contacts between the phenyl ring of the ligand and BCA (≈25 %). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by 19F NMR spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II).
Co-reporter:George M. Whitesides;George W. Crabtree
Science 2007 Volume 315(Issue 5813) pp:796-798
Publication Date(Web):
DOI:10.1126/science.1140362
Abstract
Achieving a fundamental understanding of the phenomena that will underpin both global stewardship and future technologies in energy calls for a thoughtful balance between large-scale immediate solutions using existing technology and the fundamental research needed to provide better solutions in the 50-year period.
Co-reporter:Adam W. Feinberg;Alex Feigel;Sergey S. Shevkoplyas;Sean Sheehy;Kevin Kit Parker
Science 2007 Volume 317(Issue 5843) pp:1366-1370
Publication Date(Web):07 Sep 2007
DOI:10.1126/science.1146885
Abstract
We demonstrate the assembly of biohybrid materials from engineered tissues and synthetic polymer thin films. The constructs were built by culturing neonatal rat ventricular cardiomyocytes on polydimethylsiloxane thin films micropatterned with extracellular matrix proteins to promote spatially ordered, two-dimensional myogenesis. The constructs, termed muscular thin films, adopted functional, three-dimensional conformations when released from a thermally sensitive polymer substrate and were designed to perform biomimetic tasks by varying tissue architecture, thin-film shape, and electrical-pacing protocol. These centimeter-scale constructs perform functions as diverse as gripping, pumping, walking, and swimming with fine spatial and temporal control and generating specific forces as high as 4 millinewtons per square millimeter.
Co-reporter:Logan S. McCarty;Adam Winkleman;George M. Whitesides
Angewandte Chemie International Edition 2007 Volume 46(Issue 1‐2) pp:
Publication Date(Web):30 NOV 2006
DOI:10.1002/anie.200602914
Stick with me: Electrostatic charges can be induced in functionalized polystyrene beads. Oppositely charged beads then aggregate to form superstructures. A coat of small beads can self-assemble around a large bead (see optical microscopy image). After annealing, another layer of beads can be added. The technique, based on contact electrification, avoids the use of expensive equipment and enables the use of large quantities of material.
Co-reporter:Qiaobing Xu, Robert M. Rioux and George M. Whitesides
ACS Nano 2007 Volume 1(Issue 3) pp:215
Publication Date(Web):October 31, 2007
DOI:10.1021/nn700172c
This paper describes the use of nanoskiving to fabricate complex metallic nanostructures by sectioning polymer slabs containing small, embedded metal structures. This method begins with the deposition of thin metallic films on an epoxy substrate by e-beam evaporation or sputtering. After embedding the thin metallic film in an epoxy matrix, sectioning (in a plane perpendicular or parallel to the metal film) with an ultramicrotome generates sections (which can be as thin as 50 nm) of epoxy containing metallic nanostructures. The cross-sectional dimensions of the metal wires embedded in the resulting thin epoxy sections are controlled by the thickness of the evaporated metal film (which can be as small as 20 nm) and the thickness of the sections cut by the ultramicrotome; this work uses a standard 45° diamond knife and routinely generates slabs 50 nm thick. The embedded nanostructures can be transferred to, and positioned on, planar or curved substrates by manipulating the thin polymer film. Removal of the epoxy matrix by etching with an oxygen plasma generates free-standing metallic nanostructures. Nanoskiving can fabricate complex nanostructures that are difficult or impossible to achieve by other methods of nanofabrication. These include multilayer structures, structures on curved surfaces, structures that span gaps, structures in less familiar materials, structures with high aspect ratios, and large-area structures comprising two-dimensional periodic arrays. This paper illustrates one class of application of these nanostructures: frequency-selective surfaces at mid-IR wavelengths. Keywords: manipulation; microtome sectioning; nanofabrication; nanophotonics; nanoskiving; nonplanar
Co-reporter:Andres W. Martinez;Scott T. Phillips Dr.;Manish J. Butte Dr.;George M. Whitesides
Angewandte Chemie International Edition 2007 Volume 46(Issue 8) pp:
Publication Date(Web):9 JAN 2007
DOI:10.1002/anie.200603817
By the book: A method for patterning paper with photoresist to create well-defined, millimeter-sized channels comprising hydrophilic paper bounded by hydrophobic polymer is described. This type of patterned paper is a prototype of a class of low-cost, portable, and technically simple platforms for running multiplexed bioassays with microliter volumes of a single biological sample.
Co-reporter:Logan S. McCarty;Adam Winkleman;George M. Whitesides
Angewandte Chemie 2007 Volume 119(Issue 1‐2) pp:
Publication Date(Web):30 NOV 2006
DOI:10.1002/ange.200602914
Bleib bei mir: Elektrostatisch unterschiedlich geladene funktionalisierte Polystyrolkügelchen aggregieren zu Überstrukturen. Eine Hülle aus kleinen Kügelchen kann sich um ein großes Kügelchen anlagern (siehe Mikroskopaufnahme). Nach dem Tempern kann eine weitere Schicht Kügelchen angefügt werden. Diese Technik, die auf einer Kontaktelektrifizierung beruht, benötigt keine teuren Geräte und ermöglicht das Arbeiten mit großen Mengen Material.
Two experimental approaches that enable control of current flow through metal–molecules–metal junctions are described. A number of studies using two-electrode metal–molecules–metal junctions have shown that the current between the electrodes depends on the structures of the incorporated molecules. When a tunneling mechanism dominates electron transport through organic molecules, the molecules behave similar to resistors with resistivities that can be controlled by changing the structure. Incorporation of molecules with increasing conjugation into Hg-based junctions increases the current flow dramatically. Alternatively, by using four-electrode electrochemical junctions that allow the potential of the electrodes to be controlled with respect to the energy levels of the incorporated molecules, it is possible to change the mechanism of electron transfer and produce abrupt increases in the current flow. These signals, analogous to solid-state diodes, are particularly significant for molecular electronics. Electrochemical junctions also permit prediction of the value of the applied potential at which the current will start taking off and to identify the mechanism of charge transport. New and recently published results obtained using junctions based on Hg electrodes in an “electrochemical” mode show that two junctions incorporating redox centers by different interactions behave as current switches, with the current flow dominated by different charge-transport mechanisms.
A thin film of crosslinked poly(acrylic acid) (PAA), patterned within microfluidic channels (see figure) and crosslinked with metal cations, serves as a platform for rapid “on-chip” growth of patterned metallic and semiconductor nanoparticles. The embedded particles serve as catalysts for electroless deposition of metal films.
Co-reporter:Piotr Garstecki, Michael J. Fuerstman, Howard A. Stone and George M. Whitesides
Lab on a Chip 2006 vol. 6(Issue 3) pp:437-446
Publication Date(Web):25 Jan 2006
DOI:10.1039/B510841A
This article describes the process of formation of droplets and bubbles in microfluidic T-junction geometries. At low capillary numbers break-up is not dominated by shear stresses: experimental results support the assertion that the dominant contribution to the dynamics of break-up arises from the pressure drop across the emerging droplet or bubble. This pressure drop results from the high resistance to flow of the continuous (carrier) fluid in the thin films that separate the droplet from the walls of the microchannel when the droplet fills almost the entire cross-section of the channel. A simple scaling relation, based on this assertion, predicts the size of droplets and bubbles produced in the T-junctions over a range of rates of flow of the two immiscible phases, the viscosity of the continuous phase, the interfacial tension, and the geometrical dimensions of the device.
Co-reporter:Irina Gitlin Dr.;Katherine L. Gudiksen Dr. Dr.
ChemBioChem 2006 Volume 7(Issue 8) pp:
Publication Date(Web):17 JUL 2006
DOI:10.1002/cbic.200600191
This work compares the denaturation of two proteins—bovine carbonic anhydrase II (BCA) and its derivative with all lysine groups acetylated (BCA-Ac18)—by urea, guanidinium chloride (GuHCl), heat, and sodium dodecyl sulfate (SDS). It demonstrates that increasing the net negative charge of the protein by acetylation of lysines reduces its stability to urea, GuHCl, and heat, but increases its kinetic stability (its thermodynamic stability cannot be measured) towards denaturation by SDS. Increasing the ionic strength of the buffer improves the stability of BCA-Ac18 to urea and heat, but still leaves it less stable than unacetylated BCA to those denaturants. In urea, the large change in electrostatic interactions not only modifies the free energy of denaturation, but also introduces a stable intermediate into the unfolding pathway. This work shows that modifications of charges on the surfaces of proteins can have a large effect—positive or negative, depending on the denaturant—on the stability of the proteins despite the exposure of these charges to high dielectric solvent and buffer ions.
Co-reporter:Adam C. Siegel;Sergey S. Shevkoplyas Dr.;Douglas B. Weibel Dr.;Derek A. Bruzewicz;Andres W. Martinez
Angewandte Chemie International Edition 2006 Volume 45(Issue 41) pp:
Publication Date(Web):26 SEP 2006
DOI:10.1002/anie.200602273
Metal in microfluidic channels: The fabrication of electromagnets (solder) with micron-scale dimensions in poly(dimethylsiloxane) in close proximity (ca. 10-μm separation) to microfluidic channels is described (see pictures, top view and cross section). The method only has four steps and can be completed in 10 min. By passing an electric current through the magnets, magnetic field gradients are generated inside the microfluidic channels, which can be used to capture and release superparamagnetic beads in the microfluidic channel.
Co-reporter:Qiaobing Xu;Jiming Bao Dr.;Federico Capasso
Angewandte Chemie 2006 Volume 118(Issue 22) pp:
Publication Date(Web):28 APR 2006
DOI:10.1002/ange.200600394
Auf Draht: Eine Top-down-Technik, die Photolithographie mit der Abscheidung und der Schnittpräparation dünner Metallfilme kombiniert, wurde zur Herstellung gemusterter Anordnungen von Goldnanodrähten gleicher, einstellbarer Länge, Breite und Höhe entwickelt. Die Abhängigkeit der Oberflächenplasmonenresonanz (siehe Bild) von der Geometrie dieser Drähte wurde untersucht.
Co-reporter:Qiaobing Xu;Jiming Bao Dr.;Federico Capasso
Angewandte Chemie International Edition 2006 Volume 45(Issue 22) pp:
Publication Date(Web):28 APR 2006
DOI:10.1002/anie.200600394
Down to the wire: A top-down technique that combines photolithography, thin-film metal deposition, and thin-film sectioning has been developed to fabricate patterned arrays of gold nanowires of uniform, controllable length, width, and height. A systematic study of the dependence of the surface plasmon resonance (see picture) on the geometry of these wires is presented.
Co-reporter:Vincent Semetey Dr.;Demetri Moustakas Dr.
Angewandte Chemie 2006 Volume 118(Issue 4) pp:
Publication Date(Web):12 DEC 2005
DOI:10.1002/ange.200502991
Ein oligomeres Rückgrat aus Piperidinringen kann sowohl in Lösung als auch durch Festphasensynthese erhalten werden. Diese Oligomere nehmen gut definierte, stäbchenförmige Strukturen an, in denen alle Piperidinreste in Lösung (D2O, CD3OD) wie im festen Zustand eine Sesselkonformation haben (siehe Bild).
Co-reporter:Irina Gitlin;Jeffrey D. Carbeck Dr. Dr.
Angewandte Chemie 2006 Volume 118(Issue 19) pp:
Publication Date(Web):18 APR 2006
DOI:10.1002/ange.200502530
Fast alle Proteine enthalten geladene Aminosäuren. Während für einzelne Ladungen im aktiven Zentrum die Funktion bei der Katalyse oder der Bindung häufig aufgeklärt werden kann, ist es weniger ersichtlich, welche Funktion den Ladungen außerhalb dieser Region zuzuordnen ist. Sind sie für die Löslichkeit notwendig? Oder haben sie andere Aufgaben? Lassen sich durch Verändern dieser Ladungen die Proteineigenschaften variieren? Eine Kombination aus Kapillarelektrophorese (CE) und “Proteinladungsleitern” ermöglicht es, die Funktionen geladener Reste auf der Proteinoberfläche außerhalb des aktiven Zentrums zu studieren. Dazu werden diese Reste durch Reaktionen modifiziert, die eine große Zahl unterschiedlich geladener Derivate des Proteins liefern. CE trennt diese Derivate in Fraktionen mit der gleichen Zahl modifizierter geladener Gruppen. Die Untersuchung des Ladungseinflusses auf die Proteineigenschaften unter Verwendung von Ladungsleitern ermöglicht es, die Nettoladung und den hydrodynamischen Radius der Proteine zu bestimmen und auf die Rolle geladener Reste bei Ligandbindung und Proteinfaltung zu schließen.
Co-reporter:Adam C. Siegel;Sergey S. Shevkoplyas Dr.;Douglas B. Weibel Dr.;Derek A. Bruzewicz;Andres W. Martinez
Angewandte Chemie 2006 Volume 118(Issue 41) pp:
Publication Date(Web):26 SEP 2006
DOI:10.1002/ange.200602273
Durch diese hohle Gasse …: Mikrometergroße Elektromagnete aus Lötmetall können in Poly(dimethylsiloxan) (PDMS) direkt neben Mikrofluidikkanälen (ca. 10 μm Abstand; siehe Aufsicht und Querschnitt) durch vier Schritte binnen 10 min erzeugt werden. Ein elektrischer Strom durch die Magnete führt zu Magnetfeldern, sodass Magnetfeldgradienten in den Mikrofluidikkanälen auftreten. Die Elektromagnete können superparamagnetische Kügelchen in den Mikrofluidikkanälen einfangen und wieder freisetzen.
This paper describes the application of a bifunctional polyacrylamide (pA–V–F) presenting both vancomycin and fluorescein groups, to modify the surfaces of multiple species of Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis) to control molecular recognition of these surfaces. The vancomycin groups allowed the specific recognition of a structural component of the bacterial cell wall: peptides terminated in d–Ala–d–Ala. The fluorescein groups allowed the imaging of binding of polymer to the surfaces of bacteria by fluorescence, and are representative, low molecular weight haptens; their recognition by anti-fluorescein antibodies provides proof-of-principle that bifunctional polymers can be used to introduce haptens onto the surface of the bacteria. Flow cytometry revealed that polymer-labeled S. aureus and S. pneumoniae were opsonized by anti-fluorescein antibodies ∼20-fold more than were untreated bacteria; nearly all (∼92%) polymer-labeled S. aureus, and a large (76%) fraction of polymer-labeled S. pneumoniae were opsonized. The bound antibodies then promoted phagocytosis of the bacteria by cultured J774 macrophage-like cells. Flow cytometry revealed that macrophages ingested S. aureus decorated with the polymer-antibody complexes ∼2-fold more efficiently than S. aureus in control groups, in spite of the high background (caused by efficient antibody-independent ingestion of S. aureus by macrophages). This paper, thus, demonstrates the ability of a bifunctional polymer to carry out three distinct functions based on polyvalent molecular recognition: (i) recognition of the surface of Gram-positive bacteria, (ii) modification of this surface to generate specific binding sites recognized by an antibody, and (iii) promotion of phagocytosis of the opsonized bacteria.
Co-reporter:S. Takeuchi;P. Garstecki;D. B. Weibel;G. M. Whitesides
Advanced Materials 2005 Volume 17(Issue 8) pp:
Publication Date(Web):7 APR 2005
DOI:10.1002/adma.200401738
An axisymmetric flow-focusing microfluidic device (AFFD) is described. The AFFD (see Figure, top) produces micrometer-sized (50–300 μm) polymer-coated droplets (see Figure, bottom) with narrow size distributions (< 5 %). The axisymmetric geometry confines droplets to the central axis of the channel and prevents them from being sheared or damaged at the channel walls. The device is used to prepare aqueous droplets encapsulated in nylon-6,6 membranes by carrying out interfacial polymerization reactions in situ.
Co-reporter:A. Winkleman;B. D. Gates;L. S. McCarty;G. M. Whitesides
Advanced Materials 2005 Volume 17(Issue 12) pp:
Publication Date(Web):7 JUN 2005
DOI:10.1002/adma.200401958
Self-assembly of 100 μm spheres on a patterned electrode under the influence of an applied electric field is demonstrated. This process occurs for ordered arrays and arbitrary patterns, over areas up to ∼0.7 cm2, with a defect rate (e.g., missing spheres or extra spheres, circled in Figure) of about 1 %. These arrays of microspheres can be transferred into polymeric matrices, such as poly(dimethylsiloxane), polyurethane, and epoxy.
A strategy for the formation of three-dimensional (3D) structures based on the spontaneous folding of elastomeric tapes is described. These tapes are fabricated in crimped, quasi-3D forms, and carry metal features supporting liquid solder. Self-assembly based on capillary interactions between drops of liquid solder results in folding of the tapes into structures that have quasi- and true 3D topology (see Figure).
Co-reporter:Douglas B. Weibel Dr.;Roman Boulatov Dr.;Andrew Lee;Rosaria Ferrigno Dr.
Angewandte Chemie 2005 Volume 117(Issue 35) pp:
Publication Date(Web):5 AUG 2005
DOI:10.1002/ange.200501192
Die partielle Oxidation von subbituminöser Kohle durch FeIII-Ionen in 5 M H2SO4 bei 100 °C wurde als Anodenreaktion in einer prototypischen Kohle-Brennstoffzelle mit einer Lösung von VO2+/VO2+ in 5 M H2SO4 als kathodischer Halbzelle kombiniert (siehe Schema). Die Zelle arbeitete 1000 h bei 100 °C ohne Leistungsabfall, die maximale Stromdichte betrug 5 A L−1 und die Leistungsdichte 0.6 W L−1.
Co-reporter:Matthieu Piel;Derek A. Bruzewicz;Amy P. Wong;Xingyu Jiang
PNAS 2005 Volume 102 (Issue 4 ) pp:975-978
Publication Date(Web):2005-01-25
DOI:10.1073/pnas.0408954102
This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move.
Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric
geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption
of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward
their blunt ends.
Co-reporter:Mila Boncheva;Stefan A. Andreev;L. Mahadevan;Adam Winkleman;Sue Whitesides;Mara G. Prentiss;David R. Reichman
PNAS 2005 Volume 102 (Issue 11 ) pp:3924-3929
Publication Date(Web):2005-03-15
DOI:10.1073/pnas.0500807102
This report describes the spontaneous folding of flat elastomeric sheets, patterned with magnetic dipoles, into free-standing,
3D objects that are the topological equivalents of spherical shells. The path of the self-assembly is determined by a competition
between mechanical and magnetic interactions. The potential of this strategy for the fabrication of 3D electronic devices
is demonstrated by generating a simple electrical circuit surrounding a spherical cavity.
Co-reporter:Willow R. DiLuzio;Linda Turner;Michael Mayer;Piotr Garstecki;Douglas B. Weibel;Howard C. Berg
Nature 2005 435(7046) pp:1271-1274
Publication Date(Web):2005-06-30
DOI:10.1038/nature03660
The motion of peritrichously flagellated bacteria close to surfaces is relevant to understanding the early stages of biofilm formation and of pathogenic infection1, 2, 3, 4. This motion differs from the random-walk trajectories5 of cells in free solution. Individual Escherichia coli cells swim in clockwise, circular trajectories near planar glass surfaces6, 7. On a semi-solid agar substrate, cells differentiate into an elongated, hyperflagellated phenotype and migrate cooperatively over the surface8, a phenomenon called swarming. We have developed a technique for observing isolated E. coli swarmer cells9 moving on an agar substrate and confined in shallow, oxidized poly(dimethylsiloxane) (PDMS) microchannels. Here we show that cells in these microchannels preferentially ‘drive on the right’, swimming preferentially along the right wall of the microchannel (viewed from behind the moving cell, with the agar on the bottom). We propose that when cells are confined between two interfaces—one an agar gel and the second PDMS—they swim closer to the agar surface than to the PDMS surface (and for much longer periods of time), leading to the preferential movement on the right of the microchannel. Thus, the choice of materials guides the motion of cells in microchannels.
Co-reporter:Nicolae Damean;Samuel K. Sia;Vincent Linder;Max Narovlyansky
PNAS 2005 102 (29 ) pp:10035-10039
Publication Date(Web):2005-07-19
DOI:10.1073/pnas.0504712102
This work describes a simple optical method for obtaining, in a single still-capture image, the continuous absorbance spectra
of samples at multiple locations of microsystems. This technique uses an unmodified bright-field microscope, an array of microlenses,
and a diffraction grating to disperse the light transmitted by samples of 10- to 500-μm dimensions. By analyzing in a single
image the first-order diffracted light, it is possible to collect the full and continuous absorbance spectra of samples at
multiple locations (to a spatial resolution of ≈8 μm) in microwells and microchannels to examine dynamic chemical events (to
a time resolution of <10 ms). This article also discusses the optical basis of this method. The simultaneous resolution of
wavelength, time, and space at a scale <10 μm provides additional capabilities for chemical and biological analysis.
Co-reporter:Piotr Garstecki;Douglas B. Weibel;Declan Ryan;Willow R. DiLuzio;Michael Mayer;Jennifer E. Seto
PNAS 2005 Volume 102 (Issue 34 ) pp:11963-11967
Publication Date(Web):2005-08-23
DOI:10.1073/pnas.0505481102
It is difficult to harness the power generated by biological motors to carry out mechanical work in systems outside the cell.
Efforts to capture the mechanical energy of nanomotors ex vivo require in vitro reconstitution of motor proteins and, often, protein engineering. This study presents a method for harnessing the power produced
by biological motors that uses intact cells. The unicellular, biflagellated algae Chlamydomonas reinhardtii serve as “microoxen.” This method uses surface chemistry to attach loads (1- to 6-μm-diameter polystyrene beads) to cells,
phototaxis to steer swimming cells, and photochemistry to release loads. These motile microorganisms can transport microscale
loads (3-μm-diameter beads) at velocities of ≈100–200 μm·sec–1 and over distances as large as 20 cm.
Co-reporter:Shengqing Xu Dr.;Zhihong Nie;Minseok Seo;Patrick Lewis;Eugenia Kumacheva Dr.;Howard A. Stone Dr.;Piotr Garstecki Dr.;Douglas B. Weibel Dr.;Irina Gitlin Dr.
Angewandte Chemie 2005 Volume 117(Issue 5) pp:
Publication Date(Web):20 DEC 2004
DOI:10.1002/ange.200462226
Miniaturisierte Technik: Eine neue Strategie für die größen-, form- und zusammensetzungsspezifische Herstellung monodisperser Kolloidpartikel wird vorgestellt. Hoch monodisperse Flüssigkeitstropfen werden mithilfe einer Mikrofluidikvorrichtung gebildet. Die Tropfen werden in einem Mikrokanal in Form gebracht (Kugeln, Scheiben und Stäbe; siehe Bilder) und in situ entweder durch Polymerisation oder durch Thermofixierung verfestigt.
Co-reporter:Shengqing Xu Dr.;Zhihong Nie;Minseok Seo;Patrick Lewis;Eugenia Kumacheva Dr.;Howard A. Stone Dr.;Piotr Garstecki Dr.;Douglas B. Weibel Dr.;Irina Gitlin Dr.
Co-reporter:Shengqing Xu Dr.;Zhihong Nie;Minseok Seo;Patrick Lewis;Eugenia Kumacheva Dr.;Howard A. Stone Dr.;Piotr Garstecki Dr.;Douglas B. Weibel Dr.;Irina Gitlin Dr.
Angewandte Chemie International Edition 2005 Volume 44(Issue 25) pp:
Co-reporter:Douglas B. Weibel Dr.;Roman Boulatov Dr.;Andrew Lee;Rosaria Ferrigno Dr.
Angewandte Chemie International Edition 2005 Volume 44(Issue 35) pp:
Publication Date(Web):5 AUG 2005
DOI:10.1002/anie.200501192
Mined over matter: The partial oxidation of sub-bituminous coal by FeIII ions in 5 M H2SO4 at 100 °C was used in the anodic compartment in a prototype coal fuel cell, with a solution of VO2+/VO2+ in 5 M H2SO4 in the cathodic compartment (see scheme). The cell operated without loss of performance for 1000 h at 100 °C, with a maximum current density of 5 A L−1 and a power density of 0.6 W L−1.
Co-reporter:Shengqing Xu Dr.;Zhihong Nie;Minseok Seo;Patrick Lewis;Eugenia Kumacheva Dr.;Howard A. Stone Dr.;Piotr Garstecki Dr.;Douglas B. Weibel Dr.;Irina Gitlin Dr.
Angewandte Chemie International Edition 2005 Volume 44(Issue 5) pp:
Publication Date(Web):21 DEC 2004
DOI:10.1002/anie.200462226
Small-scale engineering: A new strategy for the production of monodisperse colloid particles with precise control of their size, shape, and composition has been developed. Highly monodisperse liquid droplets are formed by using a microfluidic device. The droplets are shaped in a microchannel (spheres, disks, and rods; see images) and solidified in situ by either polymerization or thermal setting.
Co-reporter:Jerry Yang ;Michael Mayer Dr.;Jennah K. Kriebel;Piotr Garstecki Dr.
Angewandte Chemie 2004 Volume 116(Issue 12) pp:
Publication Date(Web):9 MAR 2004
DOI:10.1002/ange.200353161
Immunglobulin-G-Template: Cluster von Gold-Nanopartikeln (siehe Bild) wachsen um Template aus selbstorganisierten IgGs, die durch synthetische zweibindige Antigene verbunden sind. Kohlenhydrate, die Bestandteile der IgGs sind, wirken dabei als Keimstellen für die stromlose Goldabscheidung.
Zwei selbstorganisierte redoxaktive Monoschichten aus [Ru(NH3)5(NC5H4-4-CH2NHCO(CH2)10SH](PF6)2 sind die Grundlage eines Metall-Molekül-Metall-Kontakts, dessen Elektronentransporteigenschaften beschrieben werden (siehe Bild). Der Kontakt wird leitend, wenn die Elektrodenpotentiale an das formale Potential der Redoxzentren angepasst werden, und zeigt Dioden- und Transistor-artige Charakteristika ähnlich denen von Festkörpersystemen.
Angewandte Chemie International Edition 2004 Volume 43(Issue 29) pp:
Publication Date(Web):12 JUL 2004
DOI:10.1002/anie.200453945
Current affairs: The electron-transport properties of a metal–molecule–metal junction based on two contacting redox-active self-assembled monolayers of [Ru(NH3)5(NC5H4-4-CH2NHCO(CH2)10SH](PF6)2 (see picture) is described. The junction becomes conductive when the electrode potentials are adjusted to the formal potential of the redox centers and shows diode- and transistor-like characteristics analogous to those of solid-state devices.
Co-reporter:Samuel K. Sia Dr.;Vincent Linder Dr.;Babak Amir Parviz Dr.;Adam Siegel
Angewandte Chemie 2004 Volume 116(Issue 4) pp:
Publication Date(Web):14 JAN 2004
DOI:10.1002/ange.200353016
Alles im Kasten: Ein preisgünstiger, tragbarer Proteindetektor, der unter Feldbedingungen wie direktem Sonnenlicht arbeitet, wurde entwickelt. Der „POCKET-Immunoassay“ (siehe Bild) besteht aus kommerziellen Bauteilen und hat eine analytische Performance ähnlich der von herkömmlichen Laborgeräten. Er könnte z. B. für die Diagnose von HIV-Infektionen in Entwicklungsländern eingesetzt werden.
Co-reporter:Byron D. Gates Dr.;Qiaobing Xu;Venkat R. Thalladi Dr.;Tingbing Cao Dr.;Tanya Knickerbocker
Angewandte Chemie 2004 Volume 116(Issue 21) pp:
Publication Date(Web):2 APR 2004
DOI:10.1002/ange.200353009
Mit einfachen Mitteln werden komplexe, regelmäßig angeordnete 3D-Mikrostrukturen erzeugt, die mit anderen Methoden nur schwer oder überhaupt nicht zugänglich sind (siehe Bild). Das Besondere an der neuen Technik ist die Nutzung von Scherkräften. Als Anwendungsbeispiel ist die Erzeugung von nanoskaligen flachen Mustern beschrieben.
Co-reporter:Kateri E. Paul;Piotr Garstecki;Michael A. Fischbach;Brian T. Mayers;Daniel B. Wolfe;Richard S. Conroy;Mara Prentiss
PNAS 2004 Volume 101 (Issue 34 ) pp:12434-12438
Publication Date(Web):2004-08-24
DOI:10.1073/pnas.0404423101
This report describes the manipulation of light in waveguides that comprise a liquid core and a liquid cladding (liq/liq waveguide).
These waveguides are dynamic: Their structure and function depend on a continuous, laminar flow of the core and cladding liquids.
Because they are dynamic, they can be reconfigured and adapted continuously in ways that are not possible with solid-state
waveguides. The liquids are introduced into the channels of a microfluidic network designed to sandwich the flowing core liquid
between flowing slabs of the cladding fluid. At low and moderate Reynolds numbers, flow is laminar, and the liq/liq interfaces
are optically smooth. Small irregularities in the solid walls of the channels do not propagate into these interfaces, and
liq/liq waveguides therefore exhibit low optical loss because of scattering. Manipulating the rate of flow and the composition
of the liquids tunes the characteristics of these optical systems.
Co-reporter:Samuel K. Sia Dr.;Vincent Linder Dr.;Babak Amir Parviz Dr.;Adam Siegel
Angewandte Chemie International Edition 2004 Volume 43(Issue 4) pp:
Publication Date(Web):14 JAN 2004
DOI:10.1002/anie.200353016
An integrated approach for detecting proteins that is low-cost, portable, battery-operated, and works under field conditions such as direct sunlight has been developed. The “POCKET immunoassay” uses commercially available components, and exhibits an analytical performance approaching that of established bench-top techniques. It may be appropriate for the diagnosis of infectious diseases, such as HIV/AIDS, in developing countries (see picture).
Co-reporter:Byron D. Gates Dr.;Qiaobing Xu;Venkat R. Thalladi Dr.;Tingbing Cao Dr.;Tanya Knickerbocker
Angewandte Chemie International Edition 2004 Volume 43(Issue 21) pp:
Publication Date(Web):2 APR 2004
DOI:10.1002/anie.200353009
A simple technique for fabricating complex, repetitive 3D microstructures, and the application of this procedure to the generation of arrays of nanoscale (in-plane) features is described. This technique, which involves the use of shearing forces, is capable of fabricating regular, 3D arrays of microstructures that are difficult or impossible to obtain by other methods (see picture).
Co-reporter:Jerry Yang ;Michael Mayer Dr.;Jennah K. Kriebel;Piotr Garstecki Dr.
Angewandte Chemie International Edition 2004 Volume 43(Issue 12) pp:
Publication Date(Web):9 MAR 2004
DOI:10.1002/anie.200353161
Immunoglobulin G templates: Clusters of gold nanoparticles are grown (see picture) from templates formed from the self-assembly of immunoglobulin Gs (IgGs) by using a synthetic divalent antigen. Carbohydrates inherent to IgGs create local nucleation centers for the electroless deposition of gold.
Two soft lithographic techniques—topographically directed photolithography (TOP) and near-field contact-mode photolithography—have been used to pattern spherical surfaces with features as small as 175 nm. Each technique has the ability to pattern more than a 60° arc of a spherical surface, albeit with distortions at the edge. Use as an optical polarizer demonstrates an application of these types of patterned surface.
Künstliche Wirbelsäule: Selbstheilende mechanische Strukturen aus millimetergroßen Perlen wurden nach dem Vorbild des Wirbeltier-Rückgrates aufgebaut. Die Einheiten sind auf Elastomerfäden aufgereiht und über Lötstellen miteinander verbunden. Nach Bruch oder Ausrenken heilen die Aggregate spontan unter Wiederherstellung der ursprünglichen linearen Anordnung (siehe Bild).
Co-reporter:Mila Boncheva Dr.;Rosaria Ferrigno Dr.;Derek A. Bruzewicz Dr.
Angewandte Chemie 2003 Volume 115(Issue 29) pp:
Publication Date(Web):24 JUL 2003
DOI:10.1002/ange.200351533
Millimetergroße Bauelemente bilden durch Selbstorganisation dreidimensionale Aggregate, deren Aufbau elektrischen Anschlüssen entspricht und durch die geometrischen Randbedingungen bei der Selbstorganisation vorgegeben ist. Im Prinzip lassen sich damit durch Steuerung einer makroskopischen Variablen vielfältige Funktionseinheiten ausgehend vom gleichen Satz an Bauelementen ableiten (siehe Bild).
Angewandte Chemie International Edition 2003 Volume 42(Issue 23) pp:
Publication Date(Web):12 JUN 2003
DOI:10.1002/anie.200351010
The organization of the vertebrate spine was the source of the concepts used to design self-healing structures. These structures comprise mm-sized beads self-assembled on elastomeric threads and connected by solder joints. The structures spontaneously realign and heal (top) after breaking and dislocation (bottom).
Co-reporter:Mila Boncheva Dr.;Rosaria Ferrigno Dr.;Derek A. Bruzewicz Dr.
Angewandte Chemie International Edition 2003 Volume 42(Issue 29) pp:
Publication Date(Web):24 JUL 2003
DOI:10.1002/anie.200351533
The structures and patterns of electrical connections within 3D self-assembled aggregates can be templated by the geometry of the space in which the self-assembly proceeds. This finding demonstrates that, in principle, multiple functions can be derived from the same set of components by controlling a macroscopic variable (see picture).
This paper describes an experimentally simple method for assembling junctions with nanometer-scale, structured organic films positioned between two metal electrodes. These junctions comprise two metal electrodes that sandwich two self-assembled monolayers (SAMs) – that is, metal (mercury)–SAM//SAM–metal (mercury, gold or silver) junctions. The junctions are easy to assemble (because the mercury electrode is compliant) and they are compatible with SAMs incorporating organic groups having a range of structures. This paper describes three different variations on this type of Hg-based junction. The first junction, formed by two contacting mercury drops covered by the same type of SAM, is a prototype system that provided useful information on the structure and electrical properties of the Hg-based junctions. The second junction consists of a Hg drop covered by one SAM (Hg–SAM(1)) in contact with a second SAM supported on a silver film (Ag–SAM(2)) – that is, a Hg–SAM(1)//SAM(2)–Ag junction. This junction allowed systematic measurements of the current that flowed across SAM(2), as a function of structure (for example, using aliphatic or aromatic thiols of different length), and a common SAM(1) of hexadecane thiol. The current density follows the relation I=I0e−βdAg,Hg, where dAg,Hg is the distance between the electrodes, and β is the structure-dependent attenuation factor for the molecules making up SAM(2): β was for alkanethiols, for oligophenylene thiols, and for benzylic derivatives of oligophenylene thiols, in general agreement with the values calculated by other approaches. The same type of junction, but using SAM(1) and SAM(2) carrying suitable chemical groups, X and Y, was used to measure the rate of electron transfer across different types of functional groups and bonds: van der Waal interactions, H bonds, and covalent bonds. The third type of junction, Hg–SAM//R//SAM–Hg, is an electrochemical junction that can (i) trap redox-active molecules (R) in the interfacial region between the SAMs, and (ii) control the potential of the electrodes with respect to the redox potential of R using an external reference electrode. This system shows I–V curves with steps that can be interpreted in terms of redox cycling mechanism.
Co-reporter:Xingyu Jiang;Zhiying Li;Venkatesh N. Murthy;Stephan K. W. Dertinger
PNAS 2002 Volume 99 (Issue 20 ) pp:12542-12547
Publication Date(Web):2002-10-01
DOI:10.1073/pnas.192457199
Little is known about the influence of substrate-bound gradients on neuronal development, since it has been difficult to fabricate
gradients over the distances typically required for biological studies (a few hundred micrometers). This article demonstrates
a generally applicable technique for the fabrication of substrate-bound gradients of proteins with complex shapes, using laminar
flows in microchannels. Gradients that range from pure laminin to pure BSA were formed in solution by using a network of microchannels,
and these proteins were allowed to adsorb onto a homogeneous layer of poly-l-lysine. Rat hippocampal neurons were cultivated on these substrate-bound gradients. Analysis of optical images of these neurons
showed that axon specification is oriented in the direction of increasing surface density of laminin. Linear gradients in
laminin adsorbed from a gradient in solution having a slope of ∇[laminin] > about 0.06 μg (ml⋅μm)−1 (defined by dividing the change of concentration of laminin in solution over the distance of the gradient) orient axon specification,
whereas those with ∇[laminin] < about 0.06 μg (ml⋅μm)−1 have no effect.
Co-reporter:Mila Boncheva;David H. Gracias;Heiko O. Jacobs
PNAS 2002 Volume 99 (Issue 8 ) pp:4937-4940
Publication Date(Web):2002-04-16
DOI:10.1073/pnas.032667599
This paper introduces a biomimetic strategy for the fabrication of asymmetrical, three-dimensional electronic devices modeled
on the folding of a chain of polypeptide structural motifs into a globular protein. Millimeter-size polyhedra—patterned with
logic devices, wires, and solder dots—were connected in a linear string by using flexible wire. On self-assembly, the string
folded spontaneously into two domains: one functioned as a ring oscillator, and the other one as a shift register. This example
demonstrates that biomimetic principles of design and self-organization can be applied to generate multifunctional electronic
systems of complex, three-dimensional architecture.
Self-assembly is a process in which components, either separate or linked, spontaneously form ordered aggregates. Self-assembly
can occur with components having sizes from the molecular to the macroscopic, provided that appropriate conditions are met.
Although much of the work in self-assembly has focused on molecular components, many of the most interesting applications
of self-assembling processes can be found at larger sizes (nanometers to micrometers). These larger systems also offer a level
of control over the characteristics of the components and over the interactions among them that makes fundamental investigations
especially tractable.
Künstliche millimetergroße „autonom bewegte“ Objekte gleiten ohne Einwirkung einer äußeren Kraft auf der Oberfläche einer Flüssigkeit. Das System basiert auf der Kombination zweier Prozesse: der durch katalytische Zersetzung von Wasserstoffperoxid angetriebenen Bewegung von Einzelobjekten und deren durch Kapillarwechselwirkungen an der Flüssigkeits/Luft-Schnittstelle verursachten Relativbewegung (Selbstanordnung). Das Bild zeigt die Rotations/Translations-Bewegung eines Einzelobjekts; die Art der Bewegung eines Paares dieser Objekte hängt von ihrer Chiralität ab.
The artificial millimeter-scale “autonomous movers” glide across the surface of a liquid without an external power source. This system is based on a combination of two processes: Motion of individual objects powered by the catalytic decomposition of hydrogen peroxide, and relative motion (self-assembly) caused by capillary interactions at the fluid/air interface. The picture shows the rotational/translational motion of a single object; the motion of a pair of these object depends on their chirality.
This paper is a theoretical study of dynamic self assembly in a system of millimeter-sized magnetized disks floating at a
liquid–air interface and spinning under the influence of a rotating magnetic field. Equations of motions are derived that
account for the hydrodynamic and magnetic forces acting in the system. Numerical integration of these equations predicts formation
of ordered structures of spinning disks; the simulated structures reproduce the patterns observed experimentally.
Das Titelbild zeigt eine Hg-SAM1//SAM2-Ag-Nanoschnittstelle, mit der eine Vielzahl an selbstorganisierten Monoschichten (SAMs) auf ihre elektronischen Eigenschaften untersucht werden kann. Der Aufbau dieser molekularen Schnittstelle, die aus einer Quecksilberelektrode mit der SAM1 (oben) und einem silberbeschichteten Siliciumwafer mit der SAM2 (unten) besteht, ist einfach und erlaubt das schnelle Screening unterschiedlich funktionalisierter Monoschichten. Im Bild erkennt man eine Grenzflächenreflexion (ein Spiegelbild) des Quecksilbertropfens an der unteren Silberschicht. In dieser Messanordnung wurden die elektronischen Eigenschaften einer Reihe von aromatischen und terminal funktionalisierten SAMs gemessen; diese wurden dann mit der molekularen Struktur der jeweiligen SAM korreliert. Einzelheiten über diese Nanoschnittstelle finden sich im Beitrag von M. A. Rampi, G. M. Whitesides et al. auf S. 2378 ff.
Basteln mit Büroklammern? Nein, eine allgemeine Methode zur Herstellung komplexer 3D-Mikrostrukturen wird vorgestellt. Die 3D-Struktur wird in Untereinheiten zerlegt, deren Mikromuster auf getrennte Substrate aufgebracht werden, aus denen die Gesamtstruktur durch geeignetes Anordnen zusammengesetzt werden kann. Die Abbildung zeigt eine lichtmikroskopische Aufnahme eines Mikrokettengewebes aus Nickel.
Co-reporter:Daniel T. Chiu;Elena Pezzoli;Hongkai Wu;Abraham D. Stroock
PNAS 2001 Volume 98 (Issue 6 ) pp:2961-2966
Publication Date(Web):2001-03-13
DOI:10.1073/pnas.061014198
This paper describes the design of a parallel algorithm that uses
moving fluids in a three-dimensional microfluidic system to solve a
nondeterministically polynomial complete problem (the maximal clique
problem) in polynomial time. This algorithm relies on
(i) parallel fabrication of the microfluidic system,
(ii) parallel searching of all potential solutions by
using fluid flow, and (iii) parallel optical readout of
all solutions. This algorithm was implemented to solve the maximal
clique problem for a simple graph with six vertices. The successful
implementation of this algorithm to compute solutions for small-size
graphs with fluids in microchannels is not useful, per
se, but does suggest broader application for microfluidics
in computation and control.
Co-reporter:Daniel T. Chiu;Noo Li Jeon;Sui Huang;Ravi S. Kane;Christopher J. Wargo;Insung S. Choi;Donald E. Ingber
PNAS 2000 Volume 97 (Issue 6 ) pp:2408-2413
Publication Date(Web):2000-03-14
DOI:10.1073/pnas.040562297
Three-dimensional microfluidic systems were fabricated and used to
pattern proteins and mammalian cells on a planar substrate. The
three-dimensional topology of the microfluidic network in the stamp
makes this technique a versatile one with which to pattern multiple
types of proteins and cells in complex, discontinuous structures on a
surface. The channel structure, formed by the stamp when it is in
contact with the surface of the substrate, limits migration and growth
of cells in the channels. With the channel structure in contact with
the surface, the cells stop dividing once they form a confluent layer.
Removal of the stamp permits the cells to spread and divide.
Co-reporter:Insung S. Choi;Stephen P. Smith;Mara Prentiss;Michael N. Liang;Steven J. Metallo
PNAS 2000 Volume 97 (Issue 24 ) pp:13092-13096
Publication Date(Web):2000-11-21
DOI:10.1073/pnas.230451697
Mechanisms of bacterial pathogenesis have become an increasingly
important subject as pathogens have become increasingly resistant to
current antibiotics. The adhesion of microorganisms to the surface of
host tissue is often a first step in pathogenesis and is a plausible
target for new antiinfective agents. Examination of bacterial adhesion
has been difficult both because it is polyvalent and because bacterial
adhesins often recognize more than one type of cell-surface molecule.
This paper describes an experimental procedure that measures the forces
of adhesion resulting from the interaction of uropathogenic
Escherichia coli to molecularly well defined models of
cellular surfaces. This procedure uses self-assembled monolayers (SAMs)
to model the surface of epithelial cells and optical tweezers to
manipulate the bacteria. Optical tweezers orient the bacteria relative
to the surface and, thus, limit the number of points of attachment
(that is, the valency of attachment). Using this combination, it was
possible to quantify the force required to break a single interaction
between pilus and mannose groups linked to the SAM. These results
demonstrate the deconvolution and characterization of complicated
events in microbial adhesion in terms of specific molecular
interactions. They also suggest that the combination of optical
tweezers and appropriately functionalized SAMs is a uniquely
synergistic system with which to study polyvalent adhesion of bacteria
to biologically relevant surfaces and with which to screen for
inhibitors of this adhesion.
Co-reporter:Andrew J Black, Paul F Nealey, Joseph H Thywissen, Mandar Deshpande, Nada El-Zein, George N Maracas, Mara Prentiss, George M Whitesides
Sensors and Actuators A: Physical 2000 Volume 86(1–2) pp:96-102
Publication Date(Web):30 October 2000
DOI:10.1016/S0924-4247(00)00422-2
The fabrication of two layer structures of electrically isolated wire — crossed wire structures and a surface coil inductor — is described. The fabrication process utilizes the tools of soft lithography and incorporates two levels of self-assembly. The use of microcontact printing and patterned self-assembly of liquid polymers removes the need for registration of the insulating layer with the underlying layer as required in conventional lithography techniques. The performance characteristics of the surface coil inductor are measured and closely resemble those predicted by theory.
Co-reporter:Junmin Hu, Tao Deng, Rex G Beck, Robert M Westervelt, Kevin D Maranowski, Arthur C Gossard, George M Whitesides
Sensors and Actuators A: Physical 2000 Volume 86(1–2) pp:122-126
Publication Date(Web):30 October 2000
DOI:10.1016/S0924-4247(00)00435-0
This paper establishes the feasibility of soft lithography for fabrication of submicron-scale electronic devices. Near-field conformal phase shift lithography — a representative soft lithographic technique — was used on a broadband exposure tool to fabricate the gate fingers of a high electron mobility transistor (HEMT). The gates of this proof-of-concept device had lengths of 250 nm and widths of 40 μm. The device had a transconductance of 4 mS and a current–voltage response similar to that of a conventional HEMT.
Spontaneous pattern formation by self-assembly is of long-standing1, 2, 3 and continuing interest4, 5 not only for its
aesthetic appeal6, 7, but also for its fundamental8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18
and technological relevance19. So far, the study of self-organization
processes has mainly focused on static structures, but dynamic systems20, 21, 22—those that develop order only when dissipating energy—are
of particular interest for studying complex behaviour23, 24.
Here we describe the formation of dynamic patterns of millimetre-sized magnetic
disks at a liquid–air interface, subject to a magnetic field produced
by a rotating permanent magnet. The disks spin around their axes with angular
frequency equal to that of the magnet, and are attracted towards its axis
of rotation while repelling each other. This repulsive hydrodynamic interaction
is due to fluid motion associated with spinning; the interplay between attractive
and repulsive interactions leads to the formation of patterns exhibiting various
types of ordering, some of which are entirely new. This versatile system should
lead to a better understanding of dynamic self-assembly, while providing a
test-bed for stability theories of interacting point vortices25, 26, 27, 28
and vortex patches29.
Co-reporter:Joanna Aizenberg,
Andrew J. Black
and
George M. Whitesides
Nature 1999 398(6727) pp:495
Publication Date(Web):
DOI:10.1038/19047
An important requirement in the fabrication of advanced inorganic materials, such as ceramics and semiconductors, is control over crystallization1, 2, 3, 4. In principle, the synthetic growth of crystals can be guided by molecular recognition at interfaces5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. But it remains a practical challenge to control simultaneously the density and pattern of nucleation events, and the sizes and orientations of the growing crystals. Here we report a route to crystal formation, using micropatterned self-assembled monolayers17,18, which affords control over all these parameters. We begin with a metal substrate patterned with a self-assembled monolayer having areas of different nucleating activity—in this case, an array of acid-terminated regions separated by methyl-terminated regions. By immersing the patterned substrates in a calcium chloride solution and exposing them to carbon dioxide, we achieve ordered crystallization of calcite in the polar regions, where the rate of nucleation is fastest; crystallization can be completely suppressed elsewhere by a suitable choice of array spacing, which ensures that the solution is undersaturated in the methyl-terminated regions. The nucleation density (the number of crystals formed per active site) may be controlled by varying the area and distribution of the polar regions, and we can manipulate the crystallographic orientation by using different functional groups and substrates.
Durch die Feinabstimmung der Kapillarkräfte an einer Flüssig/Flüssig-Grenzfläche gelang eine hierarchische, zweidimensionale Selbstorganisation millimetergroßer, sechseckiger Poly(dimethylsiloxan)-Platten (siehe Bild). Die Kontrolle der Stärke und Richtungsabhängigkeit der Kapillarkräfte zwischen den Platten war dadurch möglich, daß man die Seitenflächen der Platten hydrophob oder hydrophil gestalten konnte. Dicke Linien stellen hydrophobe Seiten dar, die sich gegenseitig aufgrund von Kapillarkräften anziehen.
By tailoring capillary interactions at a fluid–fluid interface, a hierarchical two-dimensional self-assembly of hexagonal millimeter-sized poly(dimethylsiloxane) plates has been demonstrated (see picture). The strength and direction of capillary forces between plates was controlled by patterning of the surfaces of the plates to be hydophobic or hydrophilic. The thick lines indicate hydrophobic faces whose mutual attraction forms the basis of capillarity.
Elastomeric stamps and molds provide a great opportunity to eliminate some of the disadvantages of photolithograpy, which is currently the leading technology for fabricating small structures. In the case of “soft lithography” there is no need for complex laboratory facilities and high-energy radiation. Therefore, this process is simple, inexpensive, and accessible even to molecular chemists. The current state of development in this promising area of research is presented here.
Found throughout biology, polyvalent interactions are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another (top part of the illustration) and have a number of characteristics that monovalent interactions do not (bottom). In particular, polyvalent interactions can be collectively much stronger than corresponding monovalent interactions, and they can provide the basis for mechanisms of both agonizing and antagonizing biological interactions that are fundamentally different from those available in monovalent systems.
Elastomere Stempel und Gußformen bieten die große Chance, die Nachteile der derzeit in der Erzeugung kleiner Strukturen führenden Photolithographie zu eliminieren. Bei den „Softlithographie” genannten Verfahren werden keine aufwendigen Laborausrüstungen und hochenergetischen Strahlungen benötigt. Damit sind diese Techniken einfach, billig und auch für Molekülchemiker leicht zugänglich. Der derzeitige Entwicklungsstand auf diesem zukunftsweisenden Forschungsgebiet wird hier vorgestellt.
Co-reporter:Ned Bowden,
Scott Brittain,
Anthony G. Evans,
John W. Hutchinson
and
George M. Whitesides
Nature 1998 393(6681) pp:146
Publication Date(Web):
DOI:10.1038/30193
Spontaneous generation of complex order in apparently simple systems is both arresting and potentially useful1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. Here we describe the appearance of complex, ordered structures induced by the buckling of thin metal films owing to thermal contraction of an underlying substrate. We deposit the films from the vapour phase on a thermally expanded polymer (polydimethylsiloxane, PDMS). Subsequent cooling of the polymer creates compressive stress in the metal film that is relieved by buckling with a uniform wavelength of 20–50 micrometres. The waves can be controlled and orientated by relief structures in the surface of the polymer, which can set up intricate, ordered patterns over large areas. We can account qualitatively for the size and form of the patterned features in terms of the non-uniform stresses developed in the film near steps on the polymer substrate. This patterning process may find applications in optical devices such as diffraction gratings and optical sensors, and as the basis for methods of strain analysis in materials.
Co-reporter:Joanna Aizenberg,
Andrew J. Black
and
George M. Whitesides
Nature 1998 394(6696) pp:868
Publication Date(Web):
DOI:10.1038/29730
Micropatterning is a powerful method for controlling surface properties, with applications from cell biology to electronics1, 2, 3, 4, 5, 6, 7, 8. Self-assembled monolayers (SAMs) of alkanethiolates on gold and silver9, 10, 11—the structures most widely used for preparing organic films with specific surface properties—are usually patterned by partitioning the surface into regions formed from different thiols12, 13, 14, 15. Here we describe a way to pattern SAMs using a single alkanethiol on substrates consisting of regions of different topography: planar islands of one metal on the surface of a second (which may be different from or the same as the first). These topographically patterned SAMs consist of three regions: two planar surfaces and a transition region between the two. The characters of the SAMs on these three regions were inferred from images of three structures that form on them: condensation figures, patterns of crystals of CaCO3 and regions of selective etching. The transition region is more active in the processes generating these structures than either of the two planar regions, and we propose that this activity is due to the relatively high disorder in the organic film there. We believe that this ability to control the local disorder in a SAM with high resolution will be important in controlling processes such as nucleation, wetting, adhesion and etching on scales of below 50 nm to 5 m.
Überall in der Biologie kommen polyvalente Wechselwirkungen vor. Sie zeichnen sich durch die gleichzeitige Bindung mehrerer Liganden einer biologischen Einheit an mehrere Rezeptoren einer anderen biologischen Einheit aus (oberer Teil der Graphik) und haben eine Reihe von Charakteristika, die monovalenten Wechselwirkungen fehlen (unten). Besonders im Verbund können polyvalente Wechselwirkungen viel stärker sein als entsprechende monovalente Wechselwirkungen, und sie können die Basis für das Verständnis fördernder und hemmender biologischer Wechselwirkungen liefern, die sich grundsätzlich von denen in monovalenten Systemen unterscheiden.
Electrostatic interactions between charges on ligands and charges on proteins that are remote from the binding interface can influence the free energy of binding (ΔGb). The binding affinities between charged ligands and the members of a charge ladder of bovine carbonic anhydrase (CAII) constructed by random acetylation of the amino groups on its surface were measured by affinity capillary electrophoresis (ACE). The values of ΔGb derived from this analysis correlated approximately linearly with the charge. Opposite charges on the ligand and the members of the charge ladder of CAII were stabilizing; like charges were destabilizing. The combination of ACE and protein charge ladders provides a tool for quantitatively examining the contributions of electrostatics to free energies of molecular recognition in biology.
Co-reporter:Karen A. Simon, Bobak Mosadegh, Kyaw Thu Minn, Matthew R. Lockett, Marym R. Mohammady, Diane M. Boucher, Amy B. Hall, Shawn M. Hillier, Taturo Udagawa, Brenda K. Eustace, George M. Whitesides
Co-reporter:Karen A. Simon, Bobak Mosadegh, Kyaw Thu Minn, Matthew R. Lockett, Marym R. Mohammady, Diane M. Boucher, Amy B. Hall, Shawn M. Hillier, Taturo Udagawa, Brenda K. Eustace, George M. Whitesides
Biomaterials (July 2016) Volume 95() pp:47-59
Publication Date(Web):July 2016
DOI:10.1016/j.biomaterials.2016.03.002
This work demonstrates the application of a 3D culture system—Cells-in-Gels-in-Paper (CiGiP)—in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct—prepared by stacking multiple sheets of paper containing cell-embedded hydrogels—generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation.
Co-reporter:Michael D. Dickey ; Darren J. Lipomi ; Paul J. Bracher
Nano Letter () pp:
Publication Date(Web):November 4, 2008
DOI:10.1021/nl8028174
This paper describes the fabrication of arrays of parallel, electrically addressable metallic nanowires by depositing alternating layers of thin films of metal and polymer—both planar and topographically patterned—and sectioning the laminated structures with an ultramicrotome (nanoskiving). The structures that resulted from this process had two distinct regions: one in which parallel Au nanowires were separated by a minimum distance of 30 nm, and one in which the nanowires diverged such that the distal ends were individually addressable by low-resolution (≥10 μm) photolithography. Conductive polyaniline (PANI) was electrochemically deposited across the nanowire electrodes to demonstrate their electrical addressability, continuity, and physical separation. Before deposition, the wires were electrically isolated; with the PANI, they were electrically connected. After dry etching to remove the polymer, the gap between the nanowire electrodes returned to an insulating state. This procedure provides a method for making wires with dimensions and separations of <50 nm without the use of e-beam or focused-ion-beam “writing” and opens applications in organic and molecular electronics, chemical and biological sensing, and other fields where nanoscale distances between parallel conductive electrodes are desirable.
Co-reporter:Martin M. Thuo ; William F. Reus ; Christian A. Nijhuis ; Jabulani R. Barber ; Choongik Kim ; Michael D. Schulz
Journal of the American Chemical Society () pp:
Publication Date(Web):February 16, 2011
DOI:10.1021/ja1090436
This paper compares charge transport across self-assembled monolayers (SAMs) of n-alkanethiols containing odd and even numbers of methylenes. Ultraflat template-stripped silver (AgTS) surfaces support the SAMs, while top electrodes of eutectic gallium−indium (EGaIn) contact the SAMs to form metal/SAM//oxide/EGaIn junctions. The EGaIn spontaneously reacts with ambient oxygen to form a thin (∼1 nm) oxide layer. This oxide layer enables EGaIn to maintain a stable, conical shape (convenient for forming microcontacts to SAMs) while retaining the ability to deform and flow upon contacting a hard surface. Conical electrodes of EGaIn conform (at least partially) to SAMs and generate high yields of working junctions. Ga2O3/EGaIn top electrodes enable the collection of statistically significant numbers of data in convenient periods of time. The observed difference in charge transport between n-alkanethiols with odd and even numbers of methylenes — the “odd−even effect” — is statistically discernible using these junctions and demonstrates that this technique is sensitive to small differences in the structure and properties of the SAM. Alkanethiols with an even number of methylenes exhibit the expected exponential decrease in current density, J, with increasing chain length, as do alkanethiols with an odd number of methylenes. This trend disappears, however, when the two data sets are analyzed together: alkanethiols with an even number of methylenes typically show higher J than homologous alkanethiols with an odd number of methylenes. The precision of the present measurements and the statistical power of the present analysis are only sufficient to identify, with statistical confidence, the difference between an odd and even number of methylenes with respect to J, but not with respect to the tunneling decay constant, β, or the pre-exponential factor, J0. This paper includes a discussion of the possible origins of the odd−even effect but does not endorse a single explanation.
Co-reporter:Xiaochuan Yang, Shin Yee Wong, David K. Bwambok, Manza B. J. Atkinson, Xi Zhang, George M. Whitesides and Allan S. Myerson
Chemical Communications 2014 - vol. 50(Issue 56) pp:NaN7551-7551
Publication Date(Web):2014/05/21
DOI:10.1039/C4CC02604G
Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.
Co-reporter:Paul J. Bracher, Malancha Gupta and George M. Whitesides
Journal of Materials Chemistry A 2010 - vol. 20(Issue 24) pp:NaN5122-5122
Publication Date(Web):2010/05/14
DOI:10.1039/C000358A
This article describes a method for patterning certain solids—insoluble salts and reduced metals—in sheets of paper. Chemical reactions that produce these solids as precipitates occur when a stamp of patterned paper inked with an aqueous solution of reagent comes into contact with a paper substrate containing a second reagent. The pattern is determined by a hydrophobic barrier on the stamp that restricts delivery of the ink in two dimensions. The technique is one of the few methods available to generate two-dimensional patterns of solids within the bulk of sheets of paper. It can reliably produce features with lateral dimensions only down to 1 mm, but is convenient, inexpensive, and amenable to use in large-area patterning. The method can be used to introduce function to paper-based systems: (i) paramagnetic salts precipitated within paper allow pieces of it to be manipulated or separated from mixtures with a bar magnet, (ii) the precipitation of transition metals or enzymes can be used to position and store catalysts on paper for subsequent use, (iii) catalysts patterned in two dimensions in paper can be used to generate dynamic 3-D structures when exposed to appropriate substrates: for example, a ring of Pd0 deposited on a sheet of paper will generate a cylindrical “cage” of rising oxygen bubbles when exposed to an aqueous solution of hydrogen peroxide, and (iv) patterns of catalysts or colored precipitates can serve as deterrents to counterfeiting.
Co-reporter:Simon Tricard, Efraim Feinstein, Robert F. Shepherd, Meital Reches, Phillip W. Snyder, Dileni C. Bandarage, Mara Prentiss and George M. Whitesides
Physical Chemistry Chemical Physics 2012 - vol. 14(Issue 25) pp:NaN9046-9046
Publication Date(Web):2012/05/28
DOI:10.1039/C2CP40593H
This paper describes an empirical model of polymer dynamics, based on the agitation of millimeter-sized polymeric beads. Although the interactions between the particles in the macroscopic model and those between the monomers of molecular-scale polymers are fundamentally different, both systems follow the Worm-Like Chain theory.
![[1,1':4',1''-Terphenyl]-4-methanethiol](http://img.cochemist.com/ccimg/78600/78540-82-6.png)
![[1,1':4',1''-Terphenyl]-4-methanethiol](http://img.cochemist.com/ccimg/78600/78540-82-6_b.png)
![[1,1'-BIPHENYL]-4-METHANETHIOL](http://img.cochemist.com/ccimg/6300/6258-69-1.png)
![[1,1'-BIPHENYL]-4-METHANETHIOL](http://img.cochemist.com/ccimg/6300/6258-69-1_b.png)
![Glycine,N,N-bis[2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethyl]-,2,5-dioxo-1-pyrrolidinyl ester](http://img.cochemist.com/ccimg/401600/401514-72-5.png)
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![Benzenesulfonamide, 4-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-](http://img.cochemist.com/ccimg/154800/154715-61-4_b.png)
![Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]](http://img.cochemist.com/ccimg/138200/138184-36-8.png)
![Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]](http://img.cochemist.com/ccimg/138200/138184-36-8_b.png)
![1H-Pyrrole-2,5-dione,1,1'-[1,2-ethanediylbis(oxy-2,1-ethanediyl)]bis-](http://img.cochemist.com/ccimg/115600/115597-84-7.png)
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![2-tricyclo[3.3.1.1~3,7~]dec-1-ylethanaminium](http://img.cochemist.com/ccimg/26500/26482-53-1.png)
![2-tricyclo[3.3.1.1~3,7~]dec-1-ylethanaminium](http://img.cochemist.com/ccimg/26500/26482-53-1_b.png)
![Benzoic acid, 4-[(1E)-2-phenylethenyl]-](http://img.cochemist.com/ccimg/13100/13041-75-3.png)
![Benzoic acid, 4-[(1E)-2-phenylethenyl]-](http://img.cochemist.com/ccimg/13100/13041-75-3_b.png)
![1H-Benzo[d]imidazole-2-sulfonamide](http://img.cochemist.com/ccimg/5500/5435-31-4.png)
![1H-Benzo[d]imidazole-2-sulfonamide](http://img.cochemist.com/ccimg/5500/5435-31-4_b.png)
![1,2,3,4-Tetrahydrobenzo[h]quinolin-3-ol](http://img.cochemist.com/ccimg/5500/5423-67-6.png)
![1,2,3,4-Tetrahydrobenzo[h]quinolin-3-ol](http://img.cochemist.com/ccimg/5500/5423-67-6_b.png)
![3',6'-Dihydroxy-3H-spiro[isobenzofuran-1,9'-xanthen]-3-one](http://img.cochemist.com/ccimg/2400/2321-07-5.png)
![3',6'-Dihydroxy-3H-spiro[isobenzofuran-1,9'-xanthen]-3-one](http://img.cochemist.com/ccimg/2400/2321-07-5_b.png)
![Benzo[b]thiophene-2-sulfonamide](http://img.cochemist.com/ccimg/123200/123126-59-0.png)
![Benzo[b]thiophene-2-sulfonamide](http://img.cochemist.com/ccimg/123200/123126-59-0_b.png)
![Benzo[d]thiazole-2-sulfonamide](http://img.cochemist.com/ccimg/500/433-17-0.png)
![Benzo[d]thiazole-2-sulfonamide](http://img.cochemist.com/ccimg/500/433-17-0_b.png)
