第9章 微流控分析芯片-制作
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Research into miniaturization is primarily driven by the need to reduce costs by reducing the consumption of expensive reagents and by increasing throughput and automation. For example, most are aware of the increasing cost of health care, driven in part by the cost of implementing the latest diagnostic assays. These assays, which are usually performed in microtiter plates that consume hundreds of microliters of reagents, would benefit from the use of microfabricated arrays of nanoliter volume vials. By reducing reagent consumption by a factor of 103–104, these devices could provide dramatic savings for the repetitive assays often performed in diagnostic laboratories.
Growing to Critical Mass: 1994-1997 • In 1994, the number of published papers related to TAS increased abruptly since more research groups joined the efforts to develop the area.
Manz, A.; et al. Sensors and Actuators, B: Chemical (1990), B1(1-6), 249
• A novel concept of high pressure liquid chromatog. • a silicon chip with an open-tubular column and a conductometric detector. • A 5×5mm chip containing an open-tubular column of 6 m×2m×15cm was fabricated, which has theor. separation efficiencies of 8000 and 25,000 plates in 1 and 5 min, resp. • The total column volume is 1.5 nL and the detection cell volume 1.2 pL.
9-1 发展历史
The Early Days: 1975-1989 • The first analytical miniaturized device A gas chromatographic air analyzer fabricated on a silicon wafer
Terry, S. C. Ph.D. Thesis, Stanford, Stanford, CA, 1975 Terry, Stephen C.; et al. IEEE Transactions on Electron Devices, 1979, ED-26(12), 1880
Anal. Chem. 2000, 72, 330A-335A
尺寸效应（cm→100m）
• 尺寸 • 分子扩散时间 • 体积 试剂用量 • 传热速度 1500oC/s 1/100 1/10,000 (1h→0.36s) 1/1,000,000 1t→1g, ml→nl
由此将带来：
– 方法上的变革 – 理论上的突破 – 还有巨大的经济和社会效益
Micrograph of Liquid Chromatograph chip manufactured by Manz and co-workers at Hitachi Ltd.
• The concept of "miniaturized total chemical analysis system" or TAS was proposed by Manz et al. • the main reason for miniaturization was therefore to enhance the analytical performance of the device rather than to reduce its size. • it was also recognized that a small size presented the advantage of a smaller consumption of carrier, reagent, and mobile phase.
The Renaissance: 1990-1993
• the reemergence of silicon-based analyzers
Design of an open-tubular column liquid chromatograph using silicon chip technology
目 录
9-1 发展历史 9-2 相关理论 9-2-1 基本概念 9-2-2 理论描述和模拟 9-3 基础技术 9-3-1 微制造 9-3-2 界面和连接 9-3-3 流体控制 9-4 单元操作 9-4-1 样品制备 9-4-2 注射 9-4-3 流体和颗粒操作 9-4-4 反应器和混合器 9-4-5 分离 9-4-6 检测 9-5 应用 9-5-1 细胞培养和操作 9-5-2 免疫分析和临床检验 9-5-3 蛋白质分析 9-5-4 核酸分析
阵列芯片
微流控芯片
微流控分析芯片
• 微流控分析芯片目的是通过化学分析设备的微型 化与集成化，最大限度地把分析实验室的功能转 移到便携的芯片中。 • 微流控分析芯片通过微机电加工技术把整个实验 室的功能，包括采样、稀释、加试剂、反应、分 离、检测等集成在几平方厘米的微流控芯片上， 且可多次使用，因而极大地减少了样品和分析试 剂的用量，降低了分析的成本，加快了分析的速 度，具有广泛的适用性 。
参考文献
• D. Figeys, D. Pinto, Lab-on-a-Chip: A Revolution in Biological and Medical Sciences, Analytical Chemistry, 2000, 72, 330A • D.R. Reyes, D. Iossifidis, P.A. Auroux, A. Manz, Micro Total Analysis Systems. 1. Introduction, Theory, and Technology, Analytical Chemistry, 2002, 74, 2623 • P.A. Auroux, D. Iossifidis, D.R. Reyes, A. Manz, Micro Total Analysis Systems. 2. Analytical Standard Operations and Applications, Analytical Chemistry, 2002, 74, 2637 • T. Vilkner, D. Janasek, A. Manz, Micro Total Analysis Systems. Recent Developments, Analytical Chemistry, 2004, 76, 3373 • 马立人，蒋中华，生物芯片，化学工业出版社，北京，2002 • 方肇伦，微流控分析芯片，科学出版社，北京，2003
第九章 微流控分析芯片
Do you know?
• Biochip 生物芯片 • Lab-on-a-Chip 芯片实验室 Labchip • Microfluidic Chip 微流控芯片 • Micro Total Analysis System (MicroTAS, TAS) 微全分析系统
Why miniaturization？
• A miniature gas anal. system based on the principles of gas chromatog. • The major components are fabricated in Si using photolithog. and chem. etching techniques, which allows size redns. of nearly 3 orders of magnitude compared to conventional laboratory instruments. • consists of a sample injection valve, a 1.5-m-long capillary column. A thermal conductivity detector fabricated on a separate silicon wafer . • sepns. of gaseous hydrocarbon mixts. are performed in <10 s.
目 录
9-1 发展历史 9-2 相关理论 9-2-1 基本概念 9-2-2 理论描述和模拟 9-3 基础技术 9-3-1 微制造 9-3-2 界面和连接 9-3-3 流体控制 9-4 单元操作 9-4-1 样品制备 9-4-2 注射 9-4-3 流体和颗粒操作 9-4-4 反应器和混合器 9-4-5 分离 9-4-6 检测 9-5 应用 9-5-1 细胞培养和操作 9-5-2 免疫分析和临床检验 9-5-3 蛋白质分析 9-5-4 核酸分析
Байду номын сангаас
Photograph of a gas chromatograph integrated on a planar silicon wafer fabricated by Terry and co-workers at Stanford University.
• Ho wever , the response of the scientific community to this first silicon chip device was virtually none, presumably because of the lack of technological experience (of the separation scientists) to deal with this kind of device. • the research work related to miniaturization on silicon focused on the fabrication of components such as micropumps, microvalves, and chemical sensors.
Anal. Chem. 2000, 72, 330A-335A
In the same way that integrated circuits allowed for the miniaturization of computers from the size of a room to the size of a notebook, miniaturization has the potential to shrink a room full of instruments into a compact lab-on-a-chip.
Growing to Critical Mass: 1994-1997 • In 1994, the number of published papers related to TAS increased abruptly since more research groups joined the efforts to develop the area.
Manz, A.; et al. Sensors and Actuators, B: Chemical (1990), B1(1-6), 249
• A novel concept of high pressure liquid chromatog. • a silicon chip with an open-tubular column and a conductometric detector. • A 5×5mm chip containing an open-tubular column of 6 m×2m×15cm was fabricated, which has theor. separation efficiencies of 8000 and 25,000 plates in 1 and 5 min, resp. • The total column volume is 1.5 nL and the detection cell volume 1.2 pL.
9-1 发展历史
The Early Days: 1975-1989 • The first analytical miniaturized device A gas chromatographic air analyzer fabricated on a silicon wafer
Terry, S. C. Ph.D. Thesis, Stanford, Stanford, CA, 1975 Terry, Stephen C.; et al. IEEE Transactions on Electron Devices, 1979, ED-26(12), 1880
Anal. Chem. 2000, 72, 330A-335A
尺寸效应（cm→100m）
• 尺寸 • 分子扩散时间 • 体积 试剂用量 • 传热速度 1500oC/s 1/100 1/10,000 (1h→0.36s) 1/1,000,000 1t→1g, ml→nl
由此将带来：
– 方法上的变革 – 理论上的突破 – 还有巨大的经济和社会效益
Micrograph of Liquid Chromatograph chip manufactured by Manz and co-workers at Hitachi Ltd.
• The concept of "miniaturized total chemical analysis system" or TAS was proposed by Manz et al. • the main reason for miniaturization was therefore to enhance the analytical performance of the device rather than to reduce its size. • it was also recognized that a small size presented the advantage of a smaller consumption of carrier, reagent, and mobile phase.
The Renaissance: 1990-1993
• the reemergence of silicon-based analyzers
Design of an open-tubular column liquid chromatograph using silicon chip technology
目 录
9-1 发展历史 9-2 相关理论 9-2-1 基本概念 9-2-2 理论描述和模拟 9-3 基础技术 9-3-1 微制造 9-3-2 界面和连接 9-3-3 流体控制 9-4 单元操作 9-4-1 样品制备 9-4-2 注射 9-4-3 流体和颗粒操作 9-4-4 反应器和混合器 9-4-5 分离 9-4-6 检测 9-5 应用 9-5-1 细胞培养和操作 9-5-2 免疫分析和临床检验 9-5-3 蛋白质分析 9-5-4 核酸分析
阵列芯片
微流控芯片
微流控分析芯片
• 微流控分析芯片目的是通过化学分析设备的微型 化与集成化，最大限度地把分析实验室的功能转 移到便携的芯片中。 • 微流控分析芯片通过微机电加工技术把整个实验 室的功能，包括采样、稀释、加试剂、反应、分 离、检测等集成在几平方厘米的微流控芯片上， 且可多次使用，因而极大地减少了样品和分析试 剂的用量，降低了分析的成本，加快了分析的速 度，具有广泛的适用性 。
参考文献
• D. Figeys, D. Pinto, Lab-on-a-Chip: A Revolution in Biological and Medical Sciences, Analytical Chemistry, 2000, 72, 330A • D.R. Reyes, D. Iossifidis, P.A. Auroux, A. Manz, Micro Total Analysis Systems. 1. Introduction, Theory, and Technology, Analytical Chemistry, 2002, 74, 2623 • P.A. Auroux, D. Iossifidis, D.R. Reyes, A. Manz, Micro Total Analysis Systems. 2. Analytical Standard Operations and Applications, Analytical Chemistry, 2002, 74, 2637 • T. Vilkner, D. Janasek, A. Manz, Micro Total Analysis Systems. Recent Developments, Analytical Chemistry, 2004, 76, 3373 • 马立人，蒋中华，生物芯片，化学工业出版社，北京，2002 • 方肇伦，微流控分析芯片，科学出版社，北京，2003
第九章 微流控分析芯片
Do you know?
• Biochip 生物芯片 • Lab-on-a-Chip 芯片实验室 Labchip • Microfluidic Chip 微流控芯片 • Micro Total Analysis System (MicroTAS, TAS) 微全分析系统
Why miniaturization？
• A miniature gas anal. system based on the principles of gas chromatog. • The major components are fabricated in Si using photolithog. and chem. etching techniques, which allows size redns. of nearly 3 orders of magnitude compared to conventional laboratory instruments. • consists of a sample injection valve, a 1.5-m-long capillary column. A thermal conductivity detector fabricated on a separate silicon wafer . • sepns. of gaseous hydrocarbon mixts. are performed in <10 s.
目 录
9-1 发展历史 9-2 相关理论 9-2-1 基本概念 9-2-2 理论描述和模拟 9-3 基础技术 9-3-1 微制造 9-3-2 界面和连接 9-3-3 流体控制 9-4 单元操作 9-4-1 样品制备 9-4-2 注射 9-4-3 流体和颗粒操作 9-4-4 反应器和混合器 9-4-5 分离 9-4-6 检测 9-5 应用 9-5-1 细胞培养和操作 9-5-2 免疫分析和临床检验 9-5-3 蛋白质分析 9-5-4 核酸分析
Байду номын сангаас
Photograph of a gas chromatograph integrated on a planar silicon wafer fabricated by Terry and co-workers at Stanford University.
• Ho wever , the response of the scientific community to this first silicon chip device was virtually none, presumably because of the lack of technological experience (of the separation scientists) to deal with this kind of device. • the research work related to miniaturization on silicon focused on the fabrication of components such as micropumps, microvalves, and chemical sensors.
Anal. Chem. 2000, 72, 330A-335A
In the same way that integrated circuits allowed for the miniaturization of computers from the size of a room to the size of a notebook, miniaturization has the potential to shrink a room full of instruments into a compact lab-on-a-chip.