精准入微——将微流控技术引入分析化学教学的探讨

微流控技术凭借其优异的微尺度操控能力,在分析化学和其他诸多领域得到了广泛而快速的发展。在本科阶段的分析化学课程引入微流控技术有助于提高分析化学教学的前沿性和趣味性,促进创新型人才的培养。本文回顾了微流控技术的发展史并挖掘了其中蕴含的课程思政元素,简要介绍了微流控技术的重要理论和微流控芯片的基本制作方法,讨论了微流控技术与分析化学的联系。在此基础上介绍了近年来微流控技术在分析化学领域,尤其是生命分析科学领域的研究进展,以期为分析化学教学引入微流控技术提供参考。     

微流控芯片上细胞相互作用及质谱联用分析方法研究

细胞分析在生命科学领域中占有重要地位,为了解决常规细胞分析中遇到的难于操纵、成分复杂且含量微小、无法提供复杂微尺度生长环境等问题。微流控芯片技术的出现,从很大程度上克服了这些难点。微流控芯片由于自身微尺寸的特点,具有试剂消耗量小、分析速度快、便于集成化,微型化和自动化程度高等优势,已被广泛应用于分析化学、生命科学等领域。近年来,微流控芯片技术在细胞分析中的研究受到了越来越广泛的关注。清华大学化学系林金明教授     

生命分析微流控芯片的多尺度应用:从分子水平到个体水平

微流控芯片技术是多学科、多领域交叉的新兴分析技术,具有微型化、集成化、高通量、低消耗、高灵敏、分析速度快等特点。如今,微流控芯片技术已发展成为自然科学研究中不可或缺的技术平台,展现出巨大的优势,尤其在生命科学研究中得到了广泛应用。该文概述了近年来微流控芯片技术在分子水平、细胞水平、组织器官水平和生物个体水平等多个尺度上的应用,并对其发展前景进行了展望。     

微流控芯片测定单细胞内化学组分的进展

细胞是生命的基本单元。由于细胞的个体差异,传统分析群体细胞的方法难以得到单细胞的重要信息。准确可靠地测定单细胞内化学组分的含量能大大提高从正常细胞中辨别不正常细胞的能力,为进一步研究和发展生物化学、医学和临床检验等领域奠定基础。近年来,用微流控芯片进行单细胞分析已引起广泛的兴趣。微流控芯片可以集成单细胞进样、溶膜、电泳分离胞内化学组分和高灵敏度测定等一系列操作步骤,为分析单细胞内的化学组分提供了新的技术平台。本文主要综述了近年来微流控芯片测定单细胞内化学组分的进展。重点在于利用电渗流、压力结合电渗流和激光镊子等技术操控单细胞在微流控芯片上完成单细胞进样、溶膜、细胞内化学组分的电泳分离和高灵敏度测定等一系列操作步骤。对在微流控芯片上的衍生技术也做了较为详细的阐述。     

微流控细胞芯片生命分析应用多元化

微流控芯片是现代生命科学研究领域的重要分析工具.结合研究者近年来开展的研究工作和取得的相关进展,本文主要介绍了微流控细胞芯片的功能特征,同时从动物细胞、植物细胞以及微生物细胞三方面系统阐述了微流控芯片生命分析多元化的发展现状,并对其应用前景进行了展望.     

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-质谱联用细胞分析方法研究进展

细胞分析和代谢物分析在生物系统中起着重要的作用。微流控技术已成为细胞生物学研究的一个重要工具。该文总结了最近微流控芯片在细胞和代谢物的分析,尤其是微流控芯片与质谱联用技术的应用。同时对微流控芯片上细胞的生物学研究提出了见解和看法,希望能对感兴趣者提供一些启发。     

数字微流控技术及其在生物分析中的应用

数字微流控技术是一种基于微电极阵列来实现离散液滴精确控制的新型液滴操纵技术。这种基于介电润湿现象实现的液滴电操纵体系,相比于传统微流控芯片具有自动化、可寻址、可动态配置、易集成等特点。该文介绍了数字微流控技术液滴驱动原理,总结了芯片的结构和常用的制作方法,举例阐述了现阶段该技术在生物分析化学领域的应用,并对其应用前景做了展望。     

微流控技术应用于细胞分析的研究进展

微流控技术由于其固有的优势已发展成为细胞分析中一个强有力的工具.本文从微流控芯片上的细胞培养、细胞微环境的模拟和控制、单细胞分析、芯片器官以及微流控芯片与质谱联用技术等方面对微流控技术在细胞分析研究中的应用进展进行了介绍,并对这一技术的发展前景进行了总结和展望,希望能为相关研究的开展提供启发.     

微流控芯片-质谱联用技术在细胞代谢与药物代谢中的研究进展

细胞代谢与药物代谢是新药筛选和研发的关键环节,在推动人类大健康发展进程中具有重要意义。通常情况下,细胞代谢和药物筛选以传统细胞培养测定研究为主,多为静态培养条件,无法很好地模拟体内细胞动态微环境。微流控芯片-质谱联用是近年发展起来的一种新型高通量分析技术。微流控芯片模块可高度模拟细胞体内动态微环境,与质谱联用可实时在线检测样品物质,具有高效、快速、简便、样品和试剂消耗低等特点,广泛应用于细胞代谢和药物代谢分析,有利于加速药物筛选研发进程。该文重点综述了微流控芯片-质谱联用技术及其在细胞代谢和药物代谢方面的应用概况,并对目前存在的局限性进行了讨论和展望,以期为微流控芯片-质谱联用技术在新药研发与细胞分析领域的发展提供参考。     

Acoustofluidics 13: Analysis of acoustic streaming by perturbation methods

In this Part 13 of the tutorial series "Acoustofluidics--exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation," the streaming phenomenon is presented from an analytical standpoint, and perturbation methods are developed for analyzing such flows. Acoustic streaming is the phenomenon that takes place when a steady flow field is generated by the absorption of an oscillatory field. This can happen either by attenuation (quartz wind) or by interaction with a boundary. The latter type of streaming can also be generated by an oscillating solid in an otherwise still fluid medium or vibrating enclosure of a fluid body. While we address the first kind of streaming, our focus is largely on the second kind from a practical standpoint for application to microfluidic systems. In this Focus article, we limit the analysis to one- and two-dimensional problems in order to understand the analytical techniques with examples that most-easily illustrate the streaming phenomenon.     

Analytical detection techniques for droplet microfluidics—A review

In the last decade, droplet-based microfluidics has undergone rapid progress in the fields of single-cell analysis, digital PCR, protein crystallization and high throughput screening. It has been proved to be a promising platform for performing chemical and biological experiments with ultra-small volumes (picoliter to nanoliter) and ultra-high throughput. The ability to analyze the content in droplet qualitatively and quantitatively is playing an increasing role in the development and application of droplet-based microfluidic systems. In this review, we summarized the analytical detection techniques used in droplet systems and discussed the advantage and disadvantage of each technique through its application. The analytical techniques mentioned in this paper include bright-field microscopy, fluorescence microscopy, laser induced fluorescence, Raman spectroscopy, electrochemistry, capillary electrophoresis, mass spectrometry, nuclear magnetic resonance spectroscopy, absorption detection, chemiluminescence, and sample pretreatment techniques. The importance of analytical detection techniques in enabling new applications is highlighted. We also discuss the future development direction of analytical detection techniques for droplet-based microfluidic systems.     

Recent advances in the development of single cell analysis—A review

Development of techniques for the analysis of the content of individual cells represents an important direction in modern bioanalytical chemistry. While the analysis of chromosomes, organelles, or location of selected proteins has been traditionally the domain of microscopic techniques, the advances in miniaturized analytical systems bring new possibilities for separations and detections of molecules inside the individual cells including smaller molecules such as hormones or metabolites. It should be stressed that the field of single cell analysis is very broad, covering advanced optical, electrochemical and mass spectrometry instrumentation, sensor technology and separation techniques. The number of papers published on single cell analysis has reached several hundred in recent years. Thus a complete literature coverage is beyond the limits of a journal article. The following text provides a critical overview of some of the latest developments with the main focus on mass spectrometry, microseparation methods, electrophoresis in capillaries and microfluidic devices and respective detection techniques for performing single cell analyses.     

Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device.     

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.     

Microfabricated analytical systems for integrated cancer cytomics

Tracking and understanding cell-to-cell variability is fundamental for systems biology, cytomics and computational modelling that aids e.g. anti-cancer drug discovery. Limitations of conventional cell-based techniques, such as flow cytometry and single cell imaging, however, make the high-throughput dynamic analysis on cellular and subcellular processes tedious and exceedingly expensive. The development of microfluidic lab-on-a-chip technologies is one of the most innovative and cost-effective approaches towards integrated cytomics. Lab-on-a-chip devices promise greatly reduced costs, increased sensitivity and ultrahigh throughput by implementing parallel sample processing. The application of laminar fluid flow under low Reynolds numbers provides an attractive analytical avenue for the rapid delivery and exchange of reagents with exceptional accuracy. Under these conditions, the fluid flow has no inertia, enabling the precise dosing of drugs, both spatially and temporally. In addition, by confining the dimensions of the microfluidic structure, it is possible to facilitate the precise sequential delivery of drugs and/or functional probes into the cellular systems. As only low cell numbers and operational reagent volumes are required, high-throughput integrated cytomics on a single cell level finally appears within the reach of clinical diagnostics and drug screening routines. Lab-on-a-chip microfluidic technologies therefore provide new opportunities for the development of content-rich personalized clinical diagnostics and cost-effective drug discovery. It is largely anticipated that advances in microfluidic technologies should aid in tailoring of investigational therapies and support the current computational efforts in systems biology.     

Microfluidics for cell-based high throughput screening platforms—A review

In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery.     

Recent progress of microfluidic sample preparation techniques

Sample preparation turns out to be one of the important procedures in complex sample analysis by affecting the accuracy, selectivity, and sensitivity of analytical results. However, the majority of the conventional sample preparation techniques still suffer from time-consuming and labor-intensive operations. These shortcomings can be addressed by reforming the sample preparation process in a microfluidic manner. Inheriting the advantages of rapid, high efficiency, low consumption, and easy integration, microfluidic sample preparation techniques receive increasing attention, including microfluidic phases separation, microfluidic field-assisted extraction, microfluidic membrane separation, and microfluidic chemical conversion. This review overviews the progress of microfluidic sample preparation techniques in the last 3 years based on more than 100 references, we highlight the implementation of typical sample preparation methods in the formats of microfluidics. Furthermore, the challenges and outlooks of the application of microfluidic sample preparation techniques are discussed.     

Analytical methods for separating and isolating magnetic nanoparticles

Despite the large body of literature describing the synthesis of magnetic nanoparticles, few analytical tools are commonly used for their purification and analysis. Due to their unique physical and chemical properties, magnetic nanoparticles are appealing candidates for biomedical applications and analytical separations. Yet in the absence of methods for assessing and assuring their purity, the ultimate use of magnetic particles and heterostructures is likely to be limited. In this review, we summarize the separation techniques that have been initially used for this purpose. For magnetic nanoparticles, it is the use of an applied magnetic flux or field gradient that enables separations. Flow based techniques are combined with applied magnetic fields to give methods such as magnetic field flow fractionation and high gradient magnetic separation. Additional techniques have been explored for manipulating particles in microfluidic channels and in mesoporous membranes. Further development of these and new analytical tools for separation and analysis of colloidal particles is critically important to enable the practical use of these, particularly for medicinal purposes.     

微流控芯片上大肠杆菌的电化学阻抗检测方法研究

基于细菌悬浮液的阻抗特性和微流控芯片电化学阻抗检测技术,采用所构建的微流控芯片电化学阻抗分析系统,以大肠杆菌为样本,优化了扰动振幅、缓冲溶液电导率、扫描频率和新制大肠杆菌标本静置时间等参数,对大肠杆菌标本、大肠杆菌标准合成样本进行电化学阻抗检测,建立了一种大肠杆菌快速定量检测方法.在扰动振幅500 mV、缓冲溶液电导率...