Marchand Gilles, Broyer Patrick, Lanet Véronique, Delattre Cyril, Foucault Frédéric, Menou Lionel, Calvas Bernard, Roller Denis, Ginot Frédéric, Campagnolo Raymond, Mallard Frédéric
Equipe commune bioMérieux/Leti, CEA/Leti/DTBS, 17 avenue des Martyrs, 38054 Grenoble Cedex 09, France.
Biomed Microdevices. 2008 Feb;10(1):35-45. doi: 10.1007/s10544-007-9107-x.
Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip or lab-on-card systems. DNA chips, which provide multiparametric data, are privileged tools for genomic analysis. However, automation of molecular biology protocol and use of these DNA chips in fully integrated systems remains a great challenge. Simplicity of chip and/or card/instrument interfaces is amongst the most critical issues to be addressed. Indeed, current detection systems for DNA chip reading are often complex, expensive, bulky and even limited in terms of sensitivity or accuracy. Furthermore, for liquid handling in the lab-on-cards, many devices use complex and bulky systems, either to directly manipulate fluids, or to ensure pneumatic or mechanical control of integrated valves. All these drawbacks prevent or limit the use of DNA-chip-based integrated systems, for point-of-care testing or as a routine diagnostics tool. We present here a DNA-chip-based protocol integration on a plastic card for clinical diagnostics applications including: (1) an opto-electronic DNA-chip, (2) fluid handling using electrically activated embedded pyrotechnic microvalves with closing/opening functions. We demonstrate both fluidic and electric packaging of the optoelectronic DNA chip without major alteration of its electronical and biological functionalities, and fluid control using novel electrically activable pyrotechnic microvalves. Finally, we suggest a complete design of a card dedicated to automation of a complex biological protocol with a fully electrical fluid handling and DNA chip reading.
临床诊断是微流控芯片实验室或卡片实验室系统最具前景的应用之一。能提供多参数数据的DNA芯片是基因组分析的重要工具。然而,分子生物学实验流程的自动化以及这些DNA芯片在完全集成系统中的应用仍然是巨大的挑战。芯片和/或卡片/仪器接口的简易性是需要解决的最关键问题之一。事实上,当前用于读取DNA芯片的检测系统通常复杂、昂贵、体积庞大,甚至在灵敏度或准确性方面存在局限。此外,对于卡片实验室中的液体处理,许多设备使用复杂且庞大的系统,要么直接操控流体,要么确保对集成阀进行气动或机械控制。所有这些缺点都阻碍或限制了基于DNA芯片的集成系统用于即时检测或作为常规诊断工具。我们在此展示了一种基于DNA芯片的实验流程集成在塑料卡片上,用于临床诊断应用,包括:(1)一个光电DNA芯片,(2)使用具有关闭/开启功能的电激活嵌入式烟火微阀进行流体处理。我们展示了光电DNA芯片的流体和电气封装,且其电子和生物学功能未发生重大改变,以及使用新型电激活烟火微阀进行流体控制。最后,我们提出了一种卡片的完整设计,该卡片致力于通过全电动流体处理和DNA芯片读取实现复杂生物学实验流程的自动化。