基于流动的微流体生物芯片的测试

Kai Hu, Tsung-Yi Ho, K. Chakrabarty
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引用次数: 24

摘要

基于流动的微流体技术的最新进展导致了生物化学芯片的出现,成为临床诊断和生物分子识别的新范式。然而,微流控生物芯片部署的一个潜在障碍是缺乏在用于生化分析之前筛选缺陷设备的测试技术。有缺陷的芯片导致重复实验,这是不希望的,因为高试剂成本和有限的样品可用性。先前在生物芯片故障检测方面的工作仅限于数字(“液滴”)微流体和其他基于电极的技术平台。我们提出了第一种自动测试基于流动的微流控生物芯片的方法,这种芯片是用基于膜的阀门设计的,用于流量控制。所提出的测试技术是基于对微通道和阀门物理缺陷的行为抽象。微流控装置中的流动路径和流动控制被建模为由布尔门组成的逻辑电路,这使我们能够使用标准的ATPG工具进行测试生成。使用逻辑电路模型导出的测试然后映射到生物芯片中涉及泵和压力表的流体操作。压力表的反馈可以与基于逻辑电路模型的预期响应进行比较,从而识别缺陷的类型和位置。我们展示了如何使用所提出的方法测试制造的生物芯片,并且我们实现了100%覆盖通道和阀门中模型缺陷的故障。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Testing of flow-based microfluidic biochips
Recent advances in flow-based microfluidics have led to the emergence of biochemistry-on-a-chip as a new paradigm in clinical diagnostics and biomolecular recognition. However, a potential roadblock in the deployment of microfluidic biochips is the lack of test techniques to screen defective devices before they are used for biochemical analysis. Defective chips lead to repetition of experiments, which is undesirable due to high reagent cost and limited availability of samples. Prior work on fault detection in biochips has been limited to digital (“droplet”) microfluidics and other electrode-based technology platforms. We propose the first approach for automated testing of flow-based microfluidic biochips that are designed using membrane-based valves for flow control. The proposed test technique is based on a behavioral abstraction of physical defects in microchannels and valves. The flow paths and flow control in the microfluidic device are modeled as a logic circuit composed of Boolean gates, which allows us to carry out test generation using standard ATPG tools. The tests derived using the logic circuit model are then mapped to fluidic operations involving pumps and pressure meters in the biochip. Feedback from pressure meters can be compared to expected responses based on the logic circuit model, whereby the types and positions of defects are identified. We show how a fabricated biochip can be tested using the proposed method, and we achieve 100% coverage of faults that model defects in channels and valves.
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