Microfluidic chip accomplishing self-fluid replacement using only capillary force and its bioanalytical application

A polymer microfluidic chip accomplishing automated sample flow and replacement without external controls and an application of the chip for bioanalytical reaction were described. All the fluidic operations in the chip were achieved by only natural capillary flow in a time-planned sequence. For the control of the capillary flow, the geometry of the channels and chambers in the chip was designed based on theoretical considerations and numerical simulations. The microfluidic chip was made by using polymer replication techniques, which were suitable for fast and cheap fabrication. The test for a biochemical analysis, employing an enzyme (HRP)-catalyzed precipitation reaction, exhibited a good performance using the developed chip. The presented microfluidic method would be applicable to biochemical lab-on-a-chips with integrated fluid replacement steps, such as affinity elution and solution exchange during biosensor signaling.     

基于单螺旋微流控芯片的细菌气溶胶的高效富集

设计了一种单螺旋通道的聚二甲基硅氧烷(Poly(dimethylsiloxane),PDMS)微流控芯片,用于副溶血性弧菌气溶胶的快速有效富集。该芯片的特征在于其通道呈螺旋分布,且通道内部含有均匀分布的鱼骨形结构。结果表明,在不同富集时间段内,采用该芯片方法捕获的细菌总数均远高于传统落板法。对于传统落板法无法有效捕获的低浓度样本(10~4CFU/mL)的缺陷,该方法的优势在于:芯片内部的螺旋通道可增大对气溶胶中微生物的离心力;鱼骨形结构的设计增加了待测样品与芯片内壁间的接触几率。此外,以无鱼骨形的螺旋芯片作为对照,验证了鱼骨形结构对于高效富集的意义。此芯片设计巧妙、易于制备、高效便携、富集效果较好,在气溶胶污染严重的水产加工等场所具有较大的应用前景。     

Electrochromatographic separation on a poly(dimethylsiloxane)/glass chip by integration of a capillary containing an acrylate monolithic stationary phase

In this paper, we present an approach to perform electrochromatographic separations on poly(dimethylsiloxane) chips: a fused-silica capillary containing a stationary phase was introduced directly into the chip. This approach would offer great flexibility since capillary modification methods are well known, and thus, with this kind of chip, different microfluidic devices having various functions could be prepared. Electrophoretic separations were first achieved by integrating an empty capillary into the chip to evaluate the analytical performances of this system. They were compared to those obtained with a classical chip. Finally, an electrochromatographic separation involving a capillary containing a hexyl acrylate-based monolith was performed. These preliminary results show this approach to be promising.     

单细胞分析的研究

单细胞分析是分析化学、生物学和医学之间渗透发展形成的跨学科前沿领域。近年来,毛细管电泳及微流控芯片用于单细胞分析已取得显著进展,特别表现在微流控芯片用于细胞的培养、分选、操纵、定位、分离及检测细胞的组分,实时监测细胞释放,及高通量阵列检测等方面。芯片的单元操作可根据需要灵活组合,显示出其独特的优点。本文重点介绍作者研究组的工作,并对近三年来国内外在毛细管电泳及芯片毛细管电泳用于单细胞分析的新进展进行评论。最后从毛细管电泳与微流控芯片、微流控芯片与细胞界面以及量子点用于探测活细胞等方面,展望了单细胞分析的发展前景。     

Microfluidic chip electrophoresis for biochemical analysis

Microfluidic chip electrophoresis has been widely employed for separation of various biochemical species owing to its advantages of low sample consumption, low cost, fast analysis, high throughput, and integration capability. In this article, we reviewed the development of four different modes of microfluidics‐based electrophoresis technologies including capillary electrophoresis, gel electrophoresis, dielectrophoresis, and field (electric) flow fractionation. Coupling detection schemes on microfluidic electrophoresis platform were also reviewed such as optical, electrochemical, and mass spectrometry method. We further discussed the innovative applications of microfluidic electrophoresis for biomacromolecules (nucleic acids and proteins), biochemical small molecules (amino acids, metabolites, ions, etc.), and bioparticles (cells and pathogens) analysis. The future direction of microfluidic chip electrophoresis was predicted.     

Electrochemical Immunosensing Chip Using Selective Surface Modification,Capillary‐Driven Microfluidic Control,and Signal Amplification by Redox Cycling

A sensitive electrochemical immunosensing chip is presented by employing (i) selective modification of protein‐resistant surfaces; (ii) fabrication of a stable Ag/AgCl reference electrode; (iii) capillary‐driven microfluidic control; (iv) signal amplification by redox cycling along with enzymatic reaction. Purely capillary‐driven microfluidic control is combined with electrochemical sandwich‐type immunosensing procedure. Selective modification of the surfaces is achieved by chemical reactivity‐controlled patterning and electrochemical deposition. Fluidic control of the immunosensing chip is achieved by spontaneous capillary‐driven flows and passive washing. The detection limit for mouse IgG in the immunosensing chip is 10 pg/mL.     

Fluorescence affinity sensing by using a self-contained fluid manoeuvring microfluidic chip

An application of a novel polymer microfluidic chip for sample exchange via natural capillary forces for immuno-analysis is described. The microfluidic device was designed to achieve sample replacement by capillary force only, which would therefore be suitable for point-of-care-testing. Complete and automatic replacement of the sample in the reaction chamber with another one makes the chip able to mimic affinity chromatography and immunoassay processes. The microfluidic chip was made using polymer replication techniques, which were suitable for fast and cheap fabrication. Micrometre-sized polystyrene beads were used for the functionalization of biomolecules. Dinitrophenyl (DNP) and anti-DNP antibody coordination was employed on the chip for fluorescence analysis. DNP was immobilized on the polymer beads via a pre-adsorbed dendrimer layer and the beads were placed in the reaction chamber. Fluorescein tagged anti-DNP was successfully observed by a fluorescence microscope after the completion of the entire flow sequence. A calibration curve was registered based on the anti-DNP concentration. A multiplex sensing was accomplished by adding biotin/streptavidin coordination to the system. DNP and biotin conjugated beads were placed in the reaction chamber in an ordered fashion and biospecific bindings of anti-DNP antibody and streptavidin were observed at their expected sites. A ratiometric analysis was carried out with different concentration ratios of anti-DNP/streptavidin. The microfluidic chip described in this work could be applied to various biological and chemical analyses using integrated washing steps or fluid replacement steps with minimum sample handling.     

Recent advances in microfluidic production of Janus droplets and particles

Microfluidic production of multicompartmental emulsion droplets and particles has received considerable attention of late. In particular, droplets having two physically and chemically distinct segments (so-called Janus droplets) and the anisotropic particles synthesized from these droplets, are becoming increasingly popular because of their novel and promising properties, which make them suitable for use in numerous applications, including for controlled drug release, display devices, and self-assembly. So far, a range of interesting anisotropies have been accorded to Janus droplets and particles via microfluidics; these span from chromatic, magnetic, and hydrophobic–hydrophilic characteristics to selective degradation properties. Here, we summarize and discuss the recent trends related to Janus droplets and particles produced through microfluidic processing. We also review the parallelization technologies being developed for scaling up microfluidic emulsification in the industry.     

Microfluidic chip of concentration gradient and fluid shear stress on a single cell level

Concentration gradient and fluid shear stress(FSS) for cell microenvironment were investigated through microfluidic technology. The Darcy–Weisbach equation combined with computational fluid dynamics modeling was exploited to design the microfluidic chip, and the FSS distribution on the cell model with varying micro-channels(triangular, conical, and elliptical). The diffusion with the incompressible laminar flow model by solving the time-dependent diffusion–convection equation was applied to simu...     

微流控芯片二维电泳研究进展

综述了微流控芯片二维电泳技术及其在生命科学中的应用,包括胶束电动力学毛细管色谱(MEKC)与毛细管区带电泳(CZE)、等电聚焦(IEF)与CZE、开管电色谱(OCEC)与CZE耦联等模式的二维微流控芯片。展望了二维微流控芯片的应用前景。     

Rapid Analysis of Oligonucleotides on a Planar Microfluidic Chip

State-of-the-art microfluidic analytical systems are briefly surveyed. Attention is focused on the use of microchip capillary electrophoresis. The main results obtained in the development of a prototype analytical system with a laser-induced fluorescence detector for electrophoresis on a glass microfluidic chip are presented. Experimental data on electroosmotic flow and the distribution of sample fluorescence intensity over the cross section of a microchannel are analyzed. A procedure for the rapid analysis of oligonucleotides on a microfluidic chip is described.     

On-chip fluorescence-activated particle counting and sorting system

A fluorescence-activated particle counting and sorting system is developed for lab-on-a-chip applications. This system integrates the microfluidic chip, fluorescence excitation and detection, electronic power switch control, and optical visualization. The automatic sorting function is achieved by electrokinetic flow switching, which is triggered by a pre-set fluorescent threshold. A direct current electric pulse is generated to dispense the fluorescent particles to the collection reservoir. A user-friendly software interface is developed for automatic real-time counting, sorting and visualization. The design of the disposable microfluidic chip is simple and easy for integration. This system represents a promising prototype for development of affordable and portable flow cytometric instruments.     

水凝胶微流控芯片的快速加工及在细胞培养检测中的应用

采用具有紫外光聚合性能的聚乙二醇(PEG)基水凝胶材料, 通过紫外光聚合作用快速加工双层水凝胶微流控芯片, 并验证了其对肿瘤细胞代谢液进行检测的可行性. 与传统微流控芯片材料相比, 该水凝胶芯片材料具有更好的生物相容性及可操控性, 可直接加工成形, 在生物学领域特别是细胞培养过程控制方面具有良好的应用前景. 实验结果表明, 该水凝胶微流控芯片可在微尺度空间有效模拟细胞生长环境, 并实现对细胞连续捕获后的原位培养. 将该芯片与卟啉可视阵列传感器系统结合, 经代谢特征分析可有效区分不同种类肿瘤细胞, 实现芯片细胞培养平台上的细胞代谢指纹快速可视化传感检测.     

在微流控芯片上合成对甲氧基苯甲醛肟

本文用负压进样的方法, 在自制的玻璃微流控芯片中进行了对甲氧基苯甲醛和盐酸羟胺合成对甲氧基苯甲醛肟的相转移反应. 测定了不同反应时间的产率, 并与常规方法进行了比较. 讨论了相接触面积和塞流对产率的影响.     

An approach to optimize the design of microfluidic chips for electrophoretic separations

The precise design and operational control of the separation process of liquid matrices is key to the performance of on-chip liquid analysis. Present research attempts from the engineering point of view to investigate of the process occurring in the microfluidic channels for chip design with the best separation efficiency. An one-dimensional model of electrokinetic sample motion was developed to simulate the separation process of sample containing amino acids (tryptophan, tyrosine, proline, methionine) that migrate in a buffer solution through a straight separation channel made of poly(methyl methacrylate) within a microfluidic chip under different conditions. On the basis of the simulations by the finite-difference method the effects of the channel size, the chip material, the applied voltage difference and the test solution pH on separation rate are discussed. It was found that for the channel length of 2 cm the resolution of peaks is optimal and the fastest time of amino acids separation is 4 s.     

A smart and portable micropump for stable liquid delivery

Precise and reliable liquid delivery is vital for microfluidic applications. Here, we illustrate the design, fabrication, characterization, and application of a portable, low cost, and robust micropump, which brings solution to stable liquid delivery in microfluidic environment. The pump is designed with three optional speeds of different pumping flow rates, and it can be simply actuated by spring‐driven mechanism. The different flow rates of the pump are realized via passive microvalves in a compact microfluidic chip, which is installed in the pump. Importantly, the membrane structures of the microvalves allow accurate liquid control, and stable flow rates can be achieved via a spring setup. The proposed pump is applied to continuously and stably infuse microbead suspension into an inertial microfluidic chip, and good particle focusing is realized in the spiral channel of the inertial microfluidic chip. The proposed portable, self‐powered, and cost‐efficient pump is crucial for microfluidic lab‐on‐a‐chip system integration, which may facilitate microfluidic application for precise liquid delivery, control, measurement, and analysis.     

Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.     

Low-cost multi-core inertial microfluidic centrifuge for high-throughput cell concentration

We developed a low-cost multi-core inertial microfluidic centrifuge (IM-centrifuge) to achieve a continuous-flow cell/particle concentration at a throughput of up to 20 mL/min. To lower the cost of our IM-centrifuge, we clamped a disposable multilayer film-based inertial microfluidic (MFIM) chip with two reusable plastic housings. The key MFIM chip was fabricated in low-cost materials by stacking different polymer-film channel layers and double-sided tape. To increase processing throughput, multiplexing spiral inertial microfluidic channels were integrated within an all-in-one MFIM chip, and a novel sample distribution strategy was employed to equally distribute the sample into each channel layer. Then, we characterized the focusing performance in the MFIM chip over a wide flow-rate range. The experimental results showed that our IM-centrifuge was able to focus various-sized particles/cells to achieve volume reduction. The sample distribution strategy also effectively ensured identical focusing and concentration performances in different cores. Finally, our IM-centrifuge was successfully applied to concentrate microalgae cells with irregular shapes and highly polydisperse sizes. Thus, our IM-centrifuge holds the potential to be employed as a low-cost, high-throughput centrifuge for disposable use in low-resource settings.     

Highly monodisperse conjugated polymer particles synthesized with drop-based microfluidics

A facile method for preparing highly monodisperse, sub-micrometre conjugated polymer particles is reported. The particles are prepared through emulsification of a conjugated polymer solution on a microfluidic chip followed by solvent evaporation. The particle size is tuned between 150 nm to 2 μm, by controlling the polymer concentration.