A core–shell structured nanocatalyst (Fe3O4@SiO2-NH2-RhNPs@mSiO2) that is encapsulated with porous silica has been designed and prepared for catalyzing the transfer hydrogenation of nitro compounds into corresponding amines. Rh nanoparticles serve as the activity center, and the porous silica shell plays an important role in the “slow-release” of the hydrogen source hydrazine. This reaction can be carried out smoothly in the green solvent water, and the atom economy can be improved by decreasing the amount of hydrazine hydrate used to a stoichiometric 1.5 equivalent of the substrate. Significantly, high catalytic efficiency is obtained and the turnover frequency (TOF) can be up to 4373 h−1 in the reduction of p-nitrophenol (4-NP). A kinetics study shows that the order of reaction is ∼0.5 towards 4-NP, and the apparent active energy Ea is 58.18 kJ mol−1, which also gives evidence of the high catalytic efficiency. Additionally, the excellent stability of the catalyst has been verified after 15 cycles without any loss of catalytic activity, and it is easily recovered by a magnet after reaction due to the Fe3O4 nucleus.

A novel oCNT-Chitosan-xFe2O3⋅yBi2O3 nanocomposite has been synthesized as a catalyst for the reduction of nitroarenes to afford corresponding anilines. This catalyst exhibits excellent efficiency and high chemoselectivity towards varieties of nitro-compounds by using hydrazine hydrate as the reductant, and this magnetically separable nanocatalyst can be used for more than ten cycles. The synergy between iron and bismuth gives the catalyst competitive activity towards precious metallic catalyst, and the active sites are immobilized on the chitosan noncovalently functionalized oxidized carbon nanotubes gives the catalyst long life time. Furthermore, this heterogeneous catalyst was used in a continuous-flow processing by filling up it into a packed bed reactor. It was used for more than 1000 min without any loss of catalytic activity in a scaled-up reduction of p-nitrophenol with a productivity of 0.5mmol min−1.Download high-res image (204KB)Download full-size image

Materials with microchannels have attracted increasing attention due to their promising perfusability and biomimetic geometry. However, the fabrication of microfibers with more geometrically complex channels in the micro- or nanoscale remains a big challenge. Here, a novel method for generating scalable microfibers with consecutive embedded helical channels is presented using an easily made coaxial microfluidic device. The characteristics of the helical channel can be accurately controlled by simply adjusting the flow rate ratio of the fluids. The mechanism of the helix formation process is theorized with newly proposed heterogenerated rope-coil effect, which enhances the tunability of helical patterns and promotes the comprehension of this abnormal phenomenon. Based on this effect, microfibers with embedded Janus channels and even double helical channels are generated in situ by changing the design of the device. The uniqueness and potential applications of these tubular microfibers are also demonstrated by biomimetic supercoiling structures as well as the perfusable and permeable spiral vessel.

Given their easy structural modification and good biocompatibility advantages, near-infrared (NIR) organic dyes with a large molar extinction coefficient, while a superlow fluorescence quantum yield shows considerable potential application in photothermal therapy (PTT). Herein, a new NIR-absorbing asymmetric cyanine dye, namely, RC, is designed and synthesized via the hybrid of rhodamine and hemicyanine derivatives. RC-BSA nanoparticles (NPs) are fabricated by using the bovine serum albumin (BSA) matrix. The NPs exhibit a strong NIR absorption peak at ∼868 nm and 28.7% photothermal conversion efficiency. Based on these features, RC-BSA NPs exhibit excellent performance in ablating tumor under a 915 nm laser radiation through a PTT mechanism. These NPs show no obvious toxicity to the treated mice. Thus, RC-BSA NPs can used as a new NIR laser-triggered PTT agent in cancer treatment.Keywords: cancer; nanoparticle; near-infrared; organic dye; photothermal therapy

Development of approach or device to allow continuous multiple measurements, such as integrating cytotoxic and genotoxic analysis, is quite appealing for study of the drug’s activity and mechanism of action or resistance. In this study, a single-cell-arrayed agarose chip system was developed to combine cell cultivation with subsequent in situ analysis of cytotoxicity and genotoxicity of the chemotherapeutic agent. The modified alkaline comet assay coupled with the Live/Dead assay was used to monitor the interstrand cross-links (ICLs) formation and the cytotoxic effects in different glioma cell lines. In addition, the ICL-induced double strand breaks (DSBs) was measured on the chip to reflect the level of ICLs indirectly. Compared with the traditional methods, the microarray agarose device offers higher throughput, reproducibility, and robustness, exhibiting good potential for high-content drug screening.

Oxygen participates in numbers of cellular activities and behaviors in both normal and pathological tissues. In physiological microenvironment, oxygen tension is generally below 21 % and varies in different species, states and regions of organs. However, present studies of cellular behavior in vitro are performed in an ambient level, which is not conformity to the reality in vivo. In this study, a microfluidic device was developed to generate controllable oxygen tensions on a multiple-channel array chip for high-throughput drug screening. Controlling various concentrations of chemical reagents with confined flow rate, specific oxygen tensions can be established from 1.6 to 21 %, where the oxygen tension of each channel can be modulated in demand. When the concentrations of pyrogallol change from 100 to 700 μg/mL with the flow rate of 5 μL/min, oxygen tensions in cell chambers range from 12.5 to 3.87 %. Pyrogallol with the concentration of 0 μg/mL is used as the control group to obtain 20.9 % oxygen condition. The developed microfluidic chip was used to investigate the cytotoxicity of TPZ and cisplatin, and the results demonstrate different manners of two oxygen-sensitive anti-tumor drugs in oxygen-dependent cytotoxic responses. Due to its character, the microfluidic device is believed to establish any desired and measurable oxygen tension distribution for pharmacology development, which is promising to improve efficiency and reduce tedious operation for pharmaceutical studies.

Fluidic patterning is a convenient and versatile tool for the patterning of materials, cells and microstructures on surface and in microchannels. However, its performance is usually limited by transverse diffusion between fluid streams. It would blur the boundary and deteriorate the precision of patterns. In this paper, we adopted geometric confinement to generate biphasic parallel flow that is constituted of oil and water. Since there is minimum transverse diffusion in biphasic parallel flow, the performance of fluid patterning is expected to be improved. The results show that the metal (Silver and Chromium) patterns have distinct boundary and well-controlled geometry in comparison with that by conventional laminar flow patterning. Furthermore, the high biocompatibility of oil phase (perfluorodecalin, PFD) enables the precise patterning of viable bacteria inside microchannels. Our work demonstrated a new route of using biphasic parallel flow to patterning, which would serve wide applications in prototyping and research settings.

Chlamydomonas reinhardtii is widely used for studying cilia/flagella, organelles important for human health and disease. In situ monitoring of flagellar assembly/disassembly kinetics in single living cells has been difficult with conventional methods because of time-consuming media exchange and the requirement of whole cell fixation. Here, we develop a PDMS/glass hybrid microfluidic device for real-time tracking of flagellar length in single living cells of Chlamydomonas. Media exchange is precisely controlled by sequential gas–liquid plugs and complete medium replacement occurs within seconds. Rapid medium exchange allows the capture of transient flagellar dynamics. We show that Chlamydomonas cells respond to acidic medium exchange and deflagellate. However, the two flagella may shed asynchronously. After subsequent medium exchange, cells regenerate full-length flagella. Cells are also induced to shorten their flagella after being exposed to extracellular stimuli. The long-term kinetics of flagellar regeneration and disassembly for the whole cell population on the chip are comparable to those from conventional methods; however, individual cells display non-uniform response kinetics. We also find that flagellar growth rate is dependent on flagellar length. This device provides a potential platform to continuously monitor molecular activities associated with changes in flagellar length and to capture transient molecular changes upon flagellar loss, and initiation of flagellar assembly/disassembly.

The purpose of this study is to evaluate the steaming-induced chemical transformation of red ginseng manufactured from fresh ginseng by means of simultaneous quantitative and qualitative analyses with a combinative high-performance liquid chromatography–electrospray tandem mass spectrometry (HPLC-ESI-MS/MSn) technique. Thirty-six ginsenosides were identified in red ginseng and white ginseng by comparing the mass spectrum and/or matching the empirical molecular formula with that of known published compounds, and 11 of them were determined to be newly generated during the red ginseng preparatory process. The mechanisms involved were further deduced to be hydrolysis, dehydration, isomerization, and decarboxylation at C-20, and hydrolysis also occurs at C-3 or C-6 of the original ginsenosides through the mimic process of steaming and heating in laboratory. The multicomponent quantification fingerprint of ginseng was also established by HPLC-UV method, and the contents of 12 ginsenosides in red and white ginsengs from different sources were determined simultaneously. The ratio of the total content of determined malonyl ginsenosides to the corresponding neutral ginsenosides (Tm-PPD/TPPD) in white ginseng ranged from 0.46 to 0.62 and from 0 to 0.19 in red ginseng. The validated method is expected to provide an effective approach to standardize the processing procedures of ginseng products and regulate the usage of ginseng in Traditional Chinese Medical prescription.

A droplet-based microfluidic device for long-term culture and longitudinal observation of Caenorhabditis elegans was presented. The worms were encapsulated in W/O droplets and controllably introduced into separate chambers, where the medium/oil or medium/air interface can be manipulated by a gravity-actuated technique, for lifelong culture. This device also contained clamp structures for reversibly immobilization of each worm separately, and thus we were able to track more details about each worm. Several phenotypes of worms were monitored from their fourth larva stage to death. The relationship between worm body length, stroke frequency and lifespan with this device was then studied. This device had a potential in various longitudinal researches on C. elegans including aging, drug screening, toxicity evaluation and etc.

An on-line comprehensive two-dimensional liquid chromatography (HPLC×UPLC-TOF MS) was set up just using the injection valve of the ultra performance liquid chromatography (UPLC) as the interface through which the effluent of high performance liquid chromatography (HPLC) was injected automatically to UPLC coupled to time-of-flight mass spectrometry (TOF MS). As a demonstrative application, a complex sample of Traditional Chinese Medicine, Qingkailing was analyzed. As a result, a four-dimensional (4D) data containing 2D retention times, peak intensity and m/z ratios was plotted, where 398 peaks were counted and low concentration components were distinguished from the high concentration ones with a total peak capacity of 1090. Comparing with traditional 3D data acquired by HPLC×HPLC, the 4D data generated by HPLC×UPLC-TOF MS can increase the number of recognized components by three times, reduce the analysis time by 75%. Such a configuration of HPLC×UPLC-TOF MS can realize easily upon commercial chromatographs while exhibited enhanced separation efficiency, high sensitivity, huge peak capacity and great potential in complex sample analysis.Highlights► Set up HPLC×UPLC-TOF MS based on commercial chromatographs. ► 4D data containing 2D retention times, intensity and m/z ratios. ► As many as 398 peaks detected from a complex sample, TCM Qingkailing. ► Compared with HPLC×HPLC, reduce the analysis time by 75%. ► Increase the number of recognized components by three times.

Multiple essential microdroplet operation units, including splitting, dispensing, oil-phase exchange, trapping, release and demulsification, were successfully implemented by combining hydrophobic ferrofluid with microfluidic chips.

A two-step counter-current chromatography (CCC) method was developed for the preparation of ginsenoside-Re, Rb1, Rc and Rb2 from ginseng with two solvent systems, methylene chloride–methanol–water–isopropanol (6:2:4:3, v/v) and n-hexane–n-butanol–0.1% formic acid (0.7:3:4, v/v). The classical CCC mode was applied in the first separation step while the elution-extrusion counter-current chromatography (EECCC) in the second separation step. The preparation yielded 76.1 mg, 137.0 mg, 58.8 mg and 85.1 mg of ginsenoside-Re, Rb1, Rc and Rb2 with the purity of 97.5%, 94.4%, 91.6% and 92.2%, respectively, from 1440.0 mg of crude sample. The recoveries of these ginsenosides after the two-step separation were 68.7%, 65.6%, 40.1% and 46.6%, respectively. The process throughput of crude sample was 5.14 mg/min while the process efficiencies of ginsenoside-Re, Rb1, Rc and Rb2 were 0.54 mg/mL, 0.49 mg/min, 0.21 mg/min and 0.30 mg/min, respectively. The structures of the targets were characterized by liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) and confirmed with the standards.Graphical abstractResearch highlights▶ Large-scale and efficient preparation of ginsenoside-Re, Rb1, Rc and Rb2. ▶ EECCC was applied in the second step separation. ▶ Ginsenoside-Rc and Rb2 were prepared by CCC for the first time.

In this article, we present a simple PDMS surface modification method based on poly(vinyl alcohol)/glycerol (PVA/Gly) solution immersion, self-assembled absorption, and heat treatment. The results of contact angle and ATR-FTIR demonstrate the superhydrophilic surface in modified PDMS. It can allow for the stable production of monodisperse droplet in a highly reproducible manner. In addition, we demonstrate the fabrication of monodisperse paclitaxel (PTX) loaded poly(l-lactic acid) (PLLA) microspheres on this kind of modification chip with solvent evaporation. The PLLA microspheres can be adjusted to a range of different sizes depending on the system flow rate. Determination of microsphere size is carried out by optical microscopy and image analysis to reveal less than 4% variation in microsphere size. Compared with the results of published papers, the presented data demonstrate that PTX-loaded PLLA microspheres show good physical properties (spherical and discrete), high-drug loading, encapsulation efficiency, a small initial burst, and sustained-release behavior due to outstanding monodispersity. With the characteristic to prepare high-quality, monodisperse, biodegradable microspheres, the versatile and simple microfluidic method facilitates the development of more reliable and reproducible drug delivery systems, which have great potential to benefit pharmaceutical and biological applications.

Ginsenoside-Ro which belongs to the oleanane-type saponins has anti-inflammatory, anti-platelet, anticomplementary and immunomodulatory activities. The present paper described the preparation of ginsenoside-Ro from panax ginseng with high recovery and efficiency by combination of normal-phase medium-pressure liquid chromatography (NP-MPLC) and high-performance counter-current chromatography (HPCCC). The crude sample was preliminarily chromatographed by NP-MPLC to enrich ginsenoside-Ro to the purity of 70.2% with 95.0% recovery. Then, the enriched sample was further purified by HPCCC with a solvent system composed of ethyl acetate–isopropanol–0.1% formic acid (3:1:5, v/v), where 61 mg ginsenoside-Ro was obtained from 100 mg enriched sample with 96.0% purity and 83.4% recovery. The overall recovery of ginsenoside-Ro was 79.2%, whose structure was identified by liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) finally.

Radix Salvia Miltiorrhiza, a famous herb medicine is widely used in China and limitedly used in USA, Japan, and other countries for the treatment of cardiovascular and cerebrovascular diseases. This herb medicine has two groups (non-polar and polar) of active ingredients with distinct clinical effects, and thus theses ingredients should be separately used to enhance therapeutic efficacy and reduce side effect. In this article, as an alternative of conventional mechanical shaking and separatory funnel, laminar flow extraction in microfluidic chip is proposed to separate the two kinds of herb ingredients. Compared with conventional methods, microfluidic chip provides continuous extraction, less labor intensity, and better performance. Furthermore, we employ three-phase laminar flow to provide double liquid–liquid interface area, circumventing the low efficiency of two-phase laminar flow. Therefore, the extraction ratio is dramatically improved to 92% (tanshinone IIA). To predict the extraction ratio, a straightforward theoretical model is also established and agrees well with the experimental results. This microfluidic chip would be a powerful technical platform for handling complicated natural products.

A microfluidic device for generating monodisperse superparamagnetic droplets and rapidly manipulating desired droplets into designated sub-microchannels by an external magnetic force is described. Superparamagnetic magnetite (Fe3O4) nanoparticles are synthesized by a chemical co-precipitation method. They are well dispersed in the water-phase to form a superparamagnetic fluid that is sheared into picoliter-volume monodisperse superparamagnetic droplets by the oil-phase in a T-junction PDMS microchannel. Superparamagnetic droplets always flow into sub-microchannel 1 due only to laminar flow without a magnetic field. But they are deflected from the direction of laminar flow by a perpendicular magnetic field. The results show that the deflection is proportional to the magnetic field gradient and magnetic nanoparticle concentration, and it is closely related to the magnet position. The observed experimental results make a good match with theoretical analysis. Single or bulk superparamagnetic droplets are successfully manipulated into the designated sub-microchannels 2 and 3 respectively, only by changing the positions of the magnet. Relatively high efficiency is obtained with more than 10 superparamagnetic droplets precisely manipulated per second. This simple and robust apparatus has wide applications in high throughput drug delivery/screening, immunoassay, cell research and synthesis of magnetic microparticles due to good biological compatibility and monodispersity of superparamagnetic droplets.

A new method of anisotropic etching an amorphous bulk material is proposed in this paper. Laminar flow is employed in this method to mask the flow of an etchant and is termed as “liquid etch mask”. Since this mask has the physical properties of a liquid, it brings several advantages that could not be achieved by any kind of other etch mask in the solid phase. As a consequence, the aspect ratio of the glass channel could be improved to ∼1 while in an inexpensive and convenient manner.

Adrenal was believed to affect the prostate tumor tissue growth by its secretion of adrenal androgens. However, the mechanisms regulating these effects were not fully understood. In this work, a sensitive and specific method for the determination of 15 steroids in blood via gas chromatography–mass spectrometry in selective ion storage detection mode was established to evaluate the impact of emasculation on adrenal steroids metabolism. Steroids were isolated by solid-phase extraction using Oasis HLB cartridge, and then derivated with heptafluorobutyric anhydride before analysis. The limits of detection were between 0.15 and 1.0 ng/mL and limits of quantification were between 0.62 and 2.6 ng/mL. The recoveries of steroids were above 83%, and both the intra-day and inter-day precisions (RSD%) were lower than 8%. Pregnenolone, progesterone, 17α-hydroxyprogesterone (17αP), 17α-hydroxypregnenolone (17αH), dehydroepiandrosterone (DHEA), estrone, 17β-estradiol, dihydrotestosterone (DHT), testosterone (T), 4-androstenedione (4-A), 1,4-androstadiene-3,17-dione, 11-deoxycortisol, 11-deoxycorticosterone, cortisol and aldosterone were quantified in 156 major male SD rats at 0, 1, 2, 4, 7 days, 2, 4, 6, 8, 10, 12, 14, and 16 weeks following emasculation. T and DHT decreased by 86.2% and 73.4%, respectively in the first 7 days following emasculation, but adrenal androgens (DHEA, 4-A) stabled at the normal level accordingly. Adrenal androgens and their precursors (17αH, 17αP) increased from the 2nd week along with the increase of androgens and the decrease of mineralocorticoids. These facts revealed that adrenal possibly enhanced its function of producing adrenal androgens from the 2nd week responding to the low androgens level induced by emasculation.

A two-step counter-current chromatography (CCC) method was developed for the preparation of ginsenoside-Re, Rb1, Rc and Rb2 from ginseng with two solvent systems, methylene chloride–methanol–water–isopropanol (6:2:4:3, v/v) and n-hexane–n-butanol–0.1% formic acid (0.7:3:4, v/v). The classical CCC mode was applied in the first separation step while the elution-extrusion counter-current chromatography (EECCC) in the second separation step. The preparation yielded 76.1 mg, 137.0 mg, 58.8 mg and 85.1 mg of ginsenoside-Re, Rb1, Rc and Rb2 with the purity of 97.5%, 94.4%, 91.6% and 92.2%, respectively, from 1440.0 mg of crude sample. The recoveries of these ginsenosides after the two-step separation were 68.7%, 65.6%, 40.1% and 46.6%, respectively. The process throughput of crude sample was 5.14 mg/min while the process efficiencies of ginsenoside-Re, Rb1, Rc and Rb2 were 0.54 mg/mL, 0.49 mg/min, 0.21 mg/min and 0.30 mg/min, respectively. The structures of the targets were characterized by liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) and confirmed with the standards.Graphical abstractDownload full-size imageResearch highlights▶ Large-scale and efficient preparation of ginsenoside-Re, Rb1, Rc and Rb2. ▶ EECCC was applied in the second step separation. ▶ Ginsenoside-Rc and Rb2 were prepared by CCC for the first time.