微流控芯片系统在单细胞研究中的应用

微流控芯片具有网络式通道结构,扩展了在细胞和亚细胞水平进行生命科学研究的能力,为单细胞研究提供了一个新的平台.在微流控芯片通道中,人们利用气压、液压和电压,或利用介电电泳、光学陷阱、行波介电电泳以及磁场等技术,可以操纵细胞通过或驻留在通道内的任意位置,从而使单细胞计数、筛选以及胞内组分分析等操作大大简化.本文对微流控芯片系统在血液流变学、单细胞操纵与计数以及单细胞胞内组分分析中的应用进行了综述,介绍了用于单细胞研究的多种微芯片系统,讨论了芯片上进行单细胞操纵的各种方法     

A multi-functional electrochemical sensing system using microfluidic technology for the detection of urea and creatinine

This study presents a new microfluidic system capable of precise measurements of two important biomarkers, urea and creatinine, automatically. In clinical applications, high levels of these two biomarkers are early indicators of nephropathy or renal failure and should be monitored on a regular basis. The microfluidic system is composed of a microfluidic chip, a control circuit system, a compressed air source and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using micro-electromechanical systems and microfluidic techniques comprising electrochemical sensor arrays and polydimethylsiloxane-based microfluidic structures such as micropumps/micromixers, normally closed valves and microchannels. The microfluidic system performs a variety of critical processes including sample pretreatment, mixing, transportation and detection on a single chip. The experimental results show that the entire procedure takes approximately 40 min, which is much faster than the traditional method (more than 6 h). Furthermore, the total sample volume consumed in each operation is only 0.1 mL, which is significantly less than that required in a large system (5 mL). The developed automatic microfluidic system may provide a powerful platform for further clinical applications.     

微流控芯片分析化学实验室

以作者课题组近10年所开展的系统研究工作为基础, 介绍微流控芯片分析化学实验室操作单元构建及系统整体集成, 并特别关注芯片分析化学实验室在分子水平、细胞水平和模式生物水平的应用, 在科学研究层面上证明了这种置于芯片上的分析化学实验室的可行性, 显示了其在生物医学领域广阔的应用前景.     

微流控芯片技术在蛋白质分析中的应用进展

近年来,微流控芯片技术取得了显著的发展。随着微电子及微机械等制作技术的不断进步,高通量、高效、快速、低成本的微流控分析芯片在蛋白质和多肽分析方面获得了令人瞩目的成果。本文主要介绍了微流控芯片在蛋白质组学分析研究的应用和发展。引用文献52篇。     

Mixing characteristics of a bubble mixing microfluidic chip for genomic DNA extraction based on magnetophoresis: CFD simulation and experiment

Mixing a small amount of magnetic beads and regents with large volume samples evenly in microcavities of a microfluidic chip is always the key step for the application of microfluidic technology in the field of magnetophoresis analysis. This article proposes a microfluidic chip for DNA extraction by magnetophoresis, which relies on bubble rising to generate turbulence and microvortices of various sizes to mix magnetic beads with samples uniformly. The construction and working principle of the microfluidic chip are introduced. CFD simulations are conducted when magnetic beads and samples are irritated by the generation of gas bubbles with the variation of supply pressures. The whole mixing process in the microfluidic chip is observed through a high-speed camera and a microfluidic system when the gas bubbles are generated continuously. The influence of supply pressure on the mixing characteristics of the microfluidic chip is investigated and discussed with both simulation and experiments. Compared with magnetic mixing, bubble mixing can avoid the magnetic beads gather phenomenon caused by magnetic forces and provide a rapid and high efficient solution to realize mixing small amount of regents in large volume samples in a certain order without complex moving structures and operations in a chip. Two applications of mixing with the proposed microfluidic chip are also carried out and discussed.     

Microfluidics technology for manipulation and analysis of biological cells

Analysis of the profiles and dynamics of molecular components and sub-cellular structures in living cells using microfluidic devices has become a major branch of bioanalytical chemistry during the past decades. Microfluidic systems have shown unique advantages in performing analytical functions such as controlled transportation, immobilization, and manipulation of biological molecules and cells, as well as separation, mixing, and dilution of chemical reagents, which enables the analysis of intracellular parameters and detection of cell metabolites, even on a single-cell level. This article provides an in-depth review on the applications of microfluidic devices for cell-based assays in recent years (2002–2005). Various cell manipulation methods for microfluidic applications, based on magnetic, optical, mechanical, and electrical principles, are described with selected examples of microfluidic devices for cell-based analysis. Microfluidic devices for cell treatment, including cell lysis, cell culture, and cell electroporation, are surveyed and their unique features are introduced. Special attention is devoted to a number of microfluidic devices for cell-based assays, including micro cytometer, microfluidic chemical cytometry, biochemical sensing chip, and whole cell sensing chip.     

Portable Microfluidic Chip Based Surface-Enhanced Raman Spectroscopy Sensor for Crystal Violet

This paper describes the development of a portable microfluidic chip based on a surface-enhanced Raman spectroscopy (SERS) sensor for crystal violet analysis. A Y-shape microfluidic chip with a staggered herringbone structure was designed to efficiently mix the analyte and SERS active silver colloid. The subsequent detection of the analyte was performed on the microfluidic chip by a portable Raman system. Compared with other methods, this sensor is easy to operate and is expected to have applications for rapid and sensitive on-site analysis. A good linear correlation over the concentration range of 10 to 750 nM of crystal violet with a correlation coefficient of 0.992 was obtained. The recovery was between 98.6% and 102.9% for crystal violet in river water with relative standard deviations between 2.43% and 4.26%.     

化学发光检测在微流控芯片中的应用综述

综述了近年来化学发光检测在微流控芯片中的应用.指出微流控芯片(又称为"芯片实验室"或者"微型全分析系统")因具有小型化、集成化和自动化等特点而在近20年来日益受到关注,而化学发光检测具有仪器结构简单、背景噪音低、操作和维护成本低等优点,非常适合用作微流控芯片的检测手段.     

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.     

微流控芯片技术在生命科学研究中的应用

微流控芯片最初起源于分析化学领域,是一种采用精细加工技术,在数平方厘米的基片,制作出微通道网络结构及其它功能单元,以实现集微量样品制备、进样、反应、分离及检测于一体的快速、高效、低耗的微型分析实验装置.随着微电子及微机械制作技术的不断进步,近年来微流控芯片技术发展迅猛,并开始在化学、生命科学及医学器件等领域发挥重要作用.本文首先简单介绍了微流控芯片制作材料和工艺,然后主要阐述了其在蛋白质分离、免疫分析、DNA分析和测序、细胞培养及检测等方面的应用进展.     

微流控芯片实验室

以作者所在课题组近年来的研究工作为基础,就芯片实验室平台建设及相应的以系统生物学为最终目标的功能化研究作一说明,对在分子和细胞层面,甚至是单分子、单细胞水平上实现以规模集成为特征的临床诊断和药物筛选的努力予以特别的关注。     

Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics

Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.     

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.     

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.     

化学发光联用技术在兽药残留分析中的应用进展

本文对近年来化学发光联用技术在兽药残留分析中的应用进展进行了评述,主要包括化学发光免疫分析、分子印迹-化学发光分析、微流控芯片-化学发光检测等,引用文献31篇.     

A plug and play microfluidic device

Chip-to-world interface is a major issue in the field of microfluidics and its applications. We developed a plug and play microfluidic device composed of a fluid driving unit and a polymer chip containing microfluidic channels and reservoirs. The one and only connection of the device to the external world is a set of electric control lines for the driving unit. Just putting the reagents and samples onto the reservoirs, the chip can be operated for chemical or biochemical reaction and analysis. We demonstrate here that silicon-based micropumps embedded in the present device allow us to achieve flexible fluidic manipulations with minimum time delay and dead volume.     

Analytical and numerical study of Joule heating effects on electrokinetically pumped continuous flow PCR chips

Joule heating is an inevitable phenomenon for microfluidic chips involving electrokinetic pumping, and it becomes a more important issue when chips are made of polymeric materials because of their low thermal conductivities. Therefore, it is very important to develop methods for evaluating Joule heating effects in microfluidic chips in a relatively easy manner. To this end, two analytical models have been established and solved using the Green's function for evaluating Joule heating effects on the temperature distribution in a microfluidic-based PCR chip. The first simplified model focuses on the understanding of Joule heating effects by ignoring the influences of the boundary conditions. The second model aims to consider practical experimental conditions. The analytical solutions to the two models are particularly useful in providing guidance for microfluidic chip design and operation prior to expensive chip fabrication and characterization. To validate the analytical solutions, a 3-D numerical model has also been developed and the simultaneous solution to this model allows the temperature distribution in a microfluidic PCR chip to be obtained, which is used to compare with the analytical results. The developed numerical model has been applied for parametric studies of Joule heating effects on the temperature control of microfluidic chips.     

Controllable Synthesis of Multicompartmental Particles Using 3D Microfluidics

A microfluidic assembly method based on a microfluidic chip and capillary device was developed to create multicompartmental particles. The microfluidic chip design endows the particles with regulable internal structure. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components, and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely varied. As a proof of concept, we have produced some complicated particles that even contain 20 compartments. Furthermore, the potential applications of the anisotropic particles are explored by encapsulating magnetic beads, fluorescent nanoparticles, and the cells into different compartments of the microparticles. We believe that this method will open new avenues for the design and application of multicompartmental particles.     

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。     

Biofunctionalization of electrowetting-on-dielectric digital microfluidic chips for miniaturized cell-based applications

In this paper we report on the controlled biofunctionalization of the hydrophobic layer of electrowetting-on-dielectric (EWOD) based microfluidic chips with the aim to execute (adherent) cell-based assays. The biofunctionalization technique involves a dry lift-off method with an easy to remove Parylene-C mask and allows the creation of spatially controlled micropatches of biomolecules in the Teflon-AF(?) layer of the chip. Compared to conventional methods, this method (i) is fully biocompatible; and (ii) leaves the hydrophobicity of the chip surface unaffected by the fabrication process, which is a crucial feature for digital microfluidic chips. In addition, full control of the geometry and the dimensions of the micropatches is achieved, allowing cells to be arrayed as cell clusters or as single cells on the digital microfluidic chip surface. The dry Parylene-C lift-off technique proves to have great potential for precise biofunctionalization of digital microfluidic chips, and can enhance their use for heterogeneous bio-assays that are of interest in various biomedical applications.