Wearable pressure sensors have attracted increasing attention for biomechanical monitoring due to their portability and flexibility. Although great advances have been made, there are no facile methods to produce sensors with good performance. Here, we present a simple method for manufacturing flexible and self-powered piezoelectric sensors based on LiNbO3 (LN) particles. The LN particles are dispersed in polypropylene (PP) doped with multiwalled carbon nanotubes (MWCNTs) by hot pressing (200 °C) to form a flexible LN/MWCNT/PP piezoelectric composite film (PCF) sensor. This cost-effective sensor has high sensitivity (8 Pa), fast response time (ca. 40 ms), and long-term stability (>3000 cycles). Measurements of pressure changes from peripheral arteries demonstrate the applicability of the LN/MWCNT/PP PCF sensor to biomechanical monitoring as well as its potential for biomechanics-related clinical diagnosis and forecasting.Keywords: epilepsy seizure forecasting; heart rate monitoring; LiNbO3; piezoelectric composite; pressure sensor;

The discovery of endogenous sulfide in mammalian brain opens up a door to understanding of the physiological function of hydrogen sulfide (H2S). The transformation of different forms of sulfide (i.e., S2–, HS–, H2S, bound sulfane sulfur, et al.) in various physiological conditions hurdles the direct detection of hydrogen sulfide in vivo. Here, we find that ammineruthenium(III) (Ru(NH3)63+) can catalyze the electrochemical oxidation of free sulfide including HS– and H2S in a neutral solution (pH 7.4). This property is used to constitute an electrochemical mechanism for selective detection of hydrogen sulfide. By coupling in vivo microdialysis with selective electrochemical detection, we successfully developed an integrated microchip-based online electrochemical system (OECS) for continuous monitoring of free endogenous hydrogen sulfide in the central nervous system (CNS). The microchip-based OECS is well responsive toward hydrogen sulfide with high stability, sensitivity and selectivity. Compared with the existing methods, the OECS does not require offline treatment of brain tissue or adjustment of the detection solutions into acidic or strong basic atmosphere. These priorities essentially enable the system to accurately and reliably track dynamics of hydrogen sulfide in the CNS.

AbstractResisting biomolecule adsorption onto the surface of brain-implanted microelectrodes is a key issue for in vivo monitoring of neurochemicals. Herein, we demonstrate that an ultrathin cell-membrane-mimic film of ethylenedioxythiophene tailored with zwitterionic phosphorylcholine (EDOT-PC) electropolymerized onto the surface of a carbon fiber microelectrode (CFE) not only resists protein adsorption but also maintains the sensitivity and time response for in vivo monitoring of dopamine (DA). As a consequence, the as-prepared PEDOT-PC/CFEs could be used as a new reliable platform for tracking DA in vivo and would help understand the physiological and pathological functions of DA.

AbstractResisting biomolecule adsorption onto the surface of brain-implanted microelectrodes is a key issue for in vivo monitoring of neurochemicals. Herein, we demonstrate that an ultrathin cell-membrane-mimic film of ethylenedioxythiophene tailored with zwitterionic phosphorylcholine (EDOT-PC) electropolymerized onto the surface of a carbon fiber microelectrode (CFE) not only resists protein adsorption but also maintains the sensitivity and time response for in vivo monitoring of dopamine (DA). As a consequence, the as-prepared PEDOT-PC/CFEs could be used as a new reliable platform for tracking DA in vivo and would help understand the physiological and pathological functions of DA.

In vivo monitoring of hydrogen peroxide (H2O2) in the brain is of importance for understanding the function of both reactive oxygen species (ROS) and signal transmission. Producing a robust microelectrode for in vivo measurement of H2O2 is challenging due to the complex brain environment and the instability of electrocatalysts employed for the reduction of H2O2. Here, we develop a new kind of microelectrode for in vivo monitoring of H2O2, which is prepared by, first, electrodeposition of Prussian blue (PB) onto carbon nanotube (CNT) assembled carbon fiber microelectrodes (CFEs) and then overcoating of the CFEs with a thin membrane of polydopamine (PDA) through self-polymerization. Scanning electron microscopic and X-ray proton spectroscopic results confirm the formation of PDA/PB/CNT/CFEs. The PDA membrane enables PB-based electrodes to show high stability in both in vitro and in vivo studies and to stably catalyze the electrochemical reduction of H2O2. The microelectrode is selective for in vivo measurements of H2O2, interference-free from O2 and other electroactive species coexisting in the brain. These properties, along with good linearity, high biocompatibility, and stability toward H2O2, substantially enable the microelectrode to track H2O2 changes in vivo during electrical stimulation and microinfusion of H2O2 and drug, which demonstrates that the microelectrode could be well suited for in vivo monitoring of dynamic changes of H2O2 in rat brain.

In vivo electrochemistry is one powerful strategy for probing brain chemistry. However, the decreases in sensitivity mainly caused by the adsorption of proteins onto electrode surface in short-term in vivo measurements unfortunately render great challenges in both electrode calibration and selectivity against the alternation of proteins. In this study, we observe that the pretreatment of carbon fiber microelectrodes (CFEs) with bovine serum albumin (BSA) would offer a simple but effective strategy to the challenges mentioned above. We verify our strategy for dopamine (DA) with conventionally used CFEs and for ascorbate with our previously developed carbon nanotube-modified CFEs. We find that, in artificial cerebral spinal fluid (aCSF) solution containing BSA, the current responses of the microelectrodes equilibrate shortly and the results for precalibration carried out in this solution are found to be almost the same as those for the postcalibration in pure aCSF. This observation offers a new solution to electrode calibration for in vivo measurements with a technical simplicity. Furthermore, we find that the use of BSA pretreated CFEs to replace bare CFEs would minimize the interference from the alternation of proteins in the brain. This study offers a new general and effective approach to in vivo electrochemistry with a high reliability and a simplified procedure.

Nanoscaled electrode has been attracting increasing attention because of striking fundamentals and practical applications. Usually, the nanoscaled electrode is fabricated by manual or photo or electron-beam lithography, which is not easy to reproducibly fabricate with simple equipment. In this paper, a cost-effective method, nanoskiving, is developed to fabricate an ultralong nanowire electrode (ULNE). The ULNE is reproducibly obtained by simply sectioning a sandwich epoxy block with a Au film. The width of ULNE could be down to nanometer dependence on the thickness of the Au film, while the length could reach to the millimeter. Thus, the created Au ULNE shows steady-state microamperometric current, characteristic of the nanoelectrode array attributed to its macroscopic length and nanoscaled width without considering the overlap of the diffusion layer of the neighboring nanoelectrode. The electrodeposited Pt/Au ULNE displays unusual electrocatalytic performance toward both the oxidation and reduction of hydrogen peroxide and, as a nanosensor, gives rise to high sensitivity and selectivity of monitoring hydrogen peroxide released from cells stimulated by ascorbic acid.

Hydrogen sulfide (H2S) has been drawing increasing attention because it plays an important role in the nervous system and has been deemed as a third endogenous gas signal molecule besides nitric oxide (NO) and carbon monoxide (CO). In this study, using a ruthenium complex, [Ru(bpy)2(bpy-DPA)Cu]4+ (where bpy = 2,2′-bipyridine and bpy-DPA = 4-methyl-4′-[N,N-bis(2-picolyl)aminomethylene]-2,2′-bipyridine) as recognition unit, we report a new reaction-based turn-on electrochemiluminescent (ECL) sensor to selectively detect extracellular H2S in rat brain, coupled with in vivo microdialysis for dialysate sampling. To prepare the sensor for sensing endogenous H2S, [Ru(bpy)2(bpy-DPA)]2+ is first designed and synthesized, showing high ECL efficiency with tri-n-propylamine (TPA) as a coreactant and quenching after reaction with Cu2+ (forming [Ru(bpy)2(bpy-DPA)Cu]4+). Then a Nafion membrane is coated on the surface of glassy carbon (GC) electrode and [Ru(bpy)2(bpy-DPA)Cu]4+ is confined onto the Nafion membrane through ion exchange. The resulting [Ru(bpy)2(bpy-DPA)Cu]4+/Nafion/GC sensor exhibits a low ECL signal. The [Ru(bpy)2(bpy-DPA)Cu]4+/Nafion/GC sensor demonstrates enhanced ECL signal after reacting with volatile H2S due to the high-affinity binding between sulfur and Cu2+, returning to [Ru(bpy)2(bpy-DPA)]2+/Nafion/GC. The changes of ECL signal at the sensor depend linearly on the concentration of Na2S in the range from 0.5 to 10 μM, with a detection limit of 0.25 μM. Moreover, the sensor demonstrates high selectivity, free from interference especially by other nonvolatile thiol-containing species, such as cysteine and glutathione. The basal dialysate level of H2S in the microdialysate from the cortex of adult male Sprague-Dawley rats is determined to be 2.3 ± 0.9 μM (n = 4). This method is reliable and is envisaged to help understand the regulation of H2S in physiological and pathological events.

This study demonstrates a new electrochemical microbiosensor for selective in vivo monitoring of glucose in rat brains. The microbiosensor is prepared by using Prussian blue (PB)/polyaniline (PANI)/multi-walled carbon nanotubes (MWNTs) as the electrocatalyst for the reduction and determination of H2O2 generated from the glucose oxidase (GOx)-based enzymatic catalytic reaction. PANI and MWNTs are used to stabilize PB nanoparticles in physiological solutions. As a result, the as-formed three-dimensional (3D) PB/PANI/MWNT nanostructure exhibits a stable and large electrochemical response compared to the PB-modified electrode. The use of PB/PANI/MWNTs in this work to replace “natural peroxidase” (i.e., horseradish peroxidase) used in the existing microbiosensors enables the method developed here to be facile but selective for in vivo measurements of glucose virtually interference-free from ascorbic acid and other electroactive species coexisting in the brain. This property, along with the good linearity and stability toward glucose, makes this microbiosensor competent for continuous in vivo monitoring of the changes of glucose in rat brains during intraperitoneal injection of insulin. The method demonstrated here can be applied to develop other oxidase-based microbiosensors for other neurochemicals, which would be helpful for understanding the chemical process involved in some physiological and pathological events.

The abnormal level of O2 could disturb various neurochemical processes and even induce neural injury and brain dysfunction. In order to assess critical roles of O2 in the neurochemical processes, it is essential to perform in vivo monitoring of the dynamic changes of O2. In this study, we develop a new electrochemical method for selectively monitoring O2 in vivo, using platinized vertically aligned carbon nanotube (VACNT)-sheathed carbon fibers (Pt/VACNT-CFs) as the electrodes. The VACNT-sheathed CFs (VACNT-CFs) are produced via the pyrolysis of iron phthalocyanine (FePc) on the surface of CFs, followed by electrochemical deposition of platinum nanoparticles to form Pt/VACNT-CFs. The resulting Pt/VACNT-CF microelectrodes exhibit fast overall kinetics for the O2 reduction via a four-electron reduction process without the formation of toxic H2O2 intermediate. Consequently, effective and selective electrochemical methods are developed for the measurements of O2 in rat brain with the Pt/VACNT-CF microelectrodes, even in the presence of some species at their physiological levels, such as ascorbic acid, dopamine, uric acid, 5-hydroxytryptamine, and of the O2 fluctuation in rat brain in the early stage of global cerebral ischemia/reperfusion, mild hyperoxia, and hypoxia induced by exposing the animal, for a short time, to O2 and N2, respectively, and hindfeet pinch. The use of VACNT-CF as the support for Pt effectively improves the stability of Pt, as compared with the bare CF support, while the FePc pyrolysis ensures the VACNT-CFs to be reproducibly produced. Thus, this study offers a novel and reliable strategy for preparing new microelectrodes for in vivo monitoring of O2 in various physiological processes with a high sensitivity and selectivity.

Using as-synthesized vertically aligned carbon nanotube-sheathed carbon fibers (VACNT-CFs) as microelectrodes without any postsynthesis functionalization, we have developed in this study a new method for in vivo monitoring of ascorbate with high selectivity and reproducibility. The VACNT-CFs are formed via pyrolysis of iron phthalocyanine (FePc) on the carbon fiber support. After electrochemical pretreatment in 1.0 M NaOH solution, the pristine VACNT-CF microelectrodes exhibit typical microelectrode behavior with fast electron transfer kinetics for electrochemical oxidation of ascorbate and are useful for selective ascorbate monitoring even with other electroactive species (e.g., dopamine, uric acid, and 5-hydroxytryptamine) coexisting in rat brain. Pristine VACNT-CFs are further demonstrated to be a reliable and stable microelectrode for in vivo recording of the dynamic increase of ascorbate evoked by intracerebral infusion of glutamate. Use of a pristine VACNT-CF microelectrode can effectively avoid any manual electrode modification and is free from person-to-person and/or electrode-to-electrode deviations intrinsically associated with conventional CF electrode fabrication, which often involves electrode surface modification with randomly distributed CNTs or other pretreatments, and hence allows easy fabrication of highly selective, reproducible, and stable microelectrodes even by nonelectrochemists. Thus, this study offers a new and reliable platform for in vivo monitoring of neurochemicals (e.g., ascorbate) to largely facilitate future studies on the neurochemical processes involved in various physiological events.

In this study, we describe the quenching of electrochemiluminescence (ECL) of tris(2,2′-bipyridine)-ruthenium(II)(Ru(bpy)32+)/tri-n-propylamine(TPA) at pristine multiwall carbon nanotube (MWNT) modified glassy carbon (GC) electrode. Even though the faradic current of the Ru(bpy)32+/TPA system and the oxidation of TPA obtained at pristine MWNT-modified GC electrode is enhanced compared with those at the bare GC electrode, the intensity of ECL produced at MWNT electrode is smaller than that at GC electrode. For testing the possible reason of quenching, a comparison of ECL behavior of Ru(bpy)32+/TPA at pristine MWNT and acid-treated, heat-treated, and polyethylene glycol (PEG)-wrapped MWNT-modified GC electrode is studied. The results demonstrate that the oxygen-containing groups at the surface of MWNT and the intrinsic electron properties of MWNT are considered to be the major reason for the suppression of ECL. The comparison also demonstrates that this quenching is related to the distance between MWNT and Ru(bpy)32+/TPA. Utilizing this essential quenching mechanism, a new signal-on DNA hybridization assay is proposed on the basis of the MWNT modified electrode, where single-stranded DNA (ssDNA) labeled with Ru(bpy)32+ derivatives probe (Ru-ssDNA) at the distal end is covalently attached onto the MWNT electrode. ECL signal is quenched where Ru-ssDNA is self-organized on the surface of MWNT electrode; however, the quenched ECL signal returns in case of the presence of complementary ssDNA. The developed approach for sequence-specific DNA detection has good selectivity, sensitivity, and signal-to-background ratio. Therefore, the quenching of the ECL of Ru(bpy)32+/TPA system by the pristine MWNT can be an excellent platform for nucleic acid studies and molecular sensing.

Strong Au–S chemistry to self-assemble thiolated oligonucleotides at gold electrode is an efficient strategy to construct electrochemiluminescent (ECL) aptasensor. However, it remains challenging to precisely control the orientation and conformation of surface-tethered oligonucleotides and to reuse ECL aptasensor because of the narrow electrochemical window of thiolated DNA film on Au surface (below ∼0.80 V versus Ag/AgCl). Here, we demonstrate adenine/thymine diblock oligonucleotides (d(Am-Tn)) to substitute DNA-SH in DNA immobilization for constructing ECL aptasensor. As a proof-of-principle, thrombin was used to present the properties of the proposed sensor. The as-formed ECL aptasensor had a wide electrochemical window and good stability (decreased 5.38% after 200 cyclic potential cycles, 0–1.2 V versus Ag/AgCl). Moreover, the aptasensor exhibited an extremely low detection limit (0.017 pM) and offered good selectivity toward thrombin. This detection limit was at least one order of magnitude lower than those of previous methods for thrombin. Additionally, the ECL aptasensor was reusable (n = 3) and showed good reproducibility (relative standard derivation, 4.7% (n = 6)). We believe that the strategy demonstrated here provides a good platform for DNA immobilization in constructing ECL even electrochemical aptasensor for the detection of targets in clinical analysis conveniently.

A facile method, cool microcontact printing (cool μCP), of fabricating microgel patterns under ambient conditions is developed. By using spontaneously condensed water on the surface of cold items and the phase transition of polymer microgels below the lower critical solution temperature (LCST), a cool poly(dimethylsiloxane) (PDMS) stamp can be easily decorated with a thin layer of water ink and its pattern can substantially transfer to a substrate that is assembled with microgels. As a proof of concept, one kind of thermosensitive microgel (i.e., poly(N-isopropylacrylamide) (pNIPAM)) is selected to demonstrate our method. A series of pNIPAM microgel patterns with various geometries can be easily generated by featured PDMS stamps through a cool μCP method. The results of control experiment using room-temperature PDMS stamps or patterning the pNIPAM microgel-incorporated fluorescent probe reveal that condensed cold water on a cool PDMS stamp plays an important role when microgel particles are lifted off. In addition, it is also observed that both humidity and contact pressure have effects on the shapes of the pattern fabricated by cool μCP, and more precise or sophisticate patterns can be obtained by adjusting the conditions. It is envisioned that this practically available method, as a good extension to μCP, can facilitate the design of complex patterns, affording great convenience for many inherent applications ranging from photonics to chemical sensing to biotechnology.

In this study, we develop a new technique to fabricate a reduced graphene oxide (rGO)-based microelectrode array (MEA) with low-cost soft lithography. To prepare patterned rGO, a polydimethylsiloxane (PDMS) mold with an array of microwells on its surface is fabricated using soft lithography, and GO is assembled on an indium tin oxide (ITO) electrode with a layer-by-layer method. The rGO pattern is formed by closely contacting the assembled GO film onto the ITO electrode with the PDMS mold filled with hydrazine solution in the microwells to selectively reduce the localized GO into the rGO. The MEA with patterned rGO as the microelectrode is characterized with Kelvin probe force microscopy (KFM), atomic force microscopy (AFM), and cyclic voltammetry (CV) with ferricyanide in aqueous solution as the redox probe. The KFM and AFM results demonstrate that each rGO pattern prepared under the present conditions is 3 μm in diameter, which is close to that of the PDMS mold we use. The CV results show that the rGO patterned onto the ITO exhibits a sigmoid-shaped voltammogram up to 200 mVs–1 with a microampere level current response, suggesting that the rGO-based electrode fabricated with soft lithography behalves like a MEA. To demonstrate the potential electroanalytical application of the rGO-based MEA, prussian blue (PB) is electrodeposited onto the rGO-based MEA to form the PB/rGO-based MEA. Electrochemical studies on the formed PB/rGO-based MEA reveal that MEA shows a lower detection limit and a larger current density for the detection of H2O2, as compared with the macroscopic rGO electrode. The method demonstrated here provides a simple and low-cost strategy for the fabrication of graphene-based MEA that are useful for electroanalytical applications.

To explore graphene applications in various fields, the processability of graphene becomes one of the important key issues, particularly with the increasing availability of synthetic graphene approaches, because the direct dispersion of hydrophobic graphene in water is prone to forming agglomerates irreversibly. Here, a facile method is proposed to increase the dispersity of graphene through noncovalent functionalization graphene with a water-soluble aromatic electroactive dye, methylene green (MG), during chemical reduction of graphene oxide (GO) with hydrazine. Atomic force microscopic and UV−vis spectrophotometric results demonstrate that chemically reduced graphene (CRG) functionalized with MG (CRG-MG) is well-dispersed into water through the coulomb repulsion between MG-adsorbed CRG sheets. The electrochemical properties of the formed CRG-MG are investigated, and the results demonstrate that CRG-MG confined onto a glassy carbon (GC) electrode has lower charge-transfer resistance and better electrocatalytic activity toward the oxidation of NADH, in relation to pristine CRG (i.e., without MG functionalization). This method not only offers a facile approach to dispersing graphene in water but also is envisaged to be useful for investigations on graphene-based electrochemistry.