A Novel All-Purpose Programmable and Scalable Biochip for Biomedical Applications

描述（由申请人提供）：本项目的目标是开发一种新型的通用可编程和可扩展的数字生物芯片仪器，具有前所未有的功能和灵活性的微阵列和实验室上的芯片应用。主要的方法是将有源矩阵驱动电路集成到基于液滴的微流控平台中。首次将有源矩阵电路集成到微流控系统中，在生物芯片的功能和可用性方面带来了多项突破。首先，生物芯片是一个真正通用的生物分析和生物合成平台。生物芯片的功能可以根据液滴内的内容物而改变。通过选择性地寻址阵列中的电极的子集，生物芯片可以根据预先设计的应用协议由计算机动态地重新配置以适合特定任务。其次，生物芯片能够同时处理大量并行反应。通过有源矩阵电路的液滴致动的自由度允许同时并行操纵多个液滴。有源矩阵电路可以很容易地扩展到包含数千行和列，因此可以直接同时处理一百多万个液滴。这将为解决传统上被认为是禁止的大型和复杂的生物分析任务提供前所未有的能力。第三，与目前的微阵列和针对特定应用定制的芯片实验室设备不同，数字生物芯片是完全可重复使用的，从而降低了拥有成本，并使其广泛使用。数字化生物芯片仪器的研制主要包括四个方面的工作：1）设计并制作一个具有有源矩阵电极阵列的微滴操纵数字化生物芯片原型; 2）设计并研制一个用于计算机-生物芯片接口的控制电路板; 3）研制并实现微滴操纵的有源矩阵电路驱动算法; 4）演示原型仪器在蛋白质结晶筛选中的操作。生物芯片原型仪器的成功开发和构建可以被认为是微阵列技术和芯片实验室发展的重大进步。它将为将来将原型仪器扩展为一种完全成熟的数字生物芯片仪器铺平道路，该仪器可以同时处理数百万个液滴。 公共卫生相关性（由申请人提供）：完成后，该项目将提出一种新型的通用可编程和可扩展的数字生物芯片仪器。该仪器有可能成为生物医学和临床研究人员的革命性工具，以显着减少的时间，劳动力和成本进行基于阵列的生物分析和生物合成任务。原型仪器的成功开发将证明这一概念的可行性，并为将来将原型仪器扩展为可同时处理数百万个液滴的成熟数字生物芯片仪器铺平道路。具有数百万像素的数字生物芯片将为生物医学或临床研究人员提供前所未有的能力，灵活性，简单性和可重复使用性，以执行生物医学应用的各种生物分析和生物合成任务。潜在的应用包括但不限于基因组和蛋白质组学测定、单细胞研究、即时临床诊断、毒素和病原体检测和鉴定、环境监测、新药筛选和精细化学合成。

DESCRIPTION (provided by applicant): The goal of this project is to develop a novel all-purpose programmable and scalable digital biochip instrument that has unprecedented power and flexibility for microarray and lab-on-a-chip applications. The main approach is to integrate active-matrix driving circuitry into droplet-based microfluidic platform. The first-ever integration of an active-matrix circuitry into microfluidic system brings forth multiple breakthroughs in biochip functionality and usability. Firstly, the biochip is a truly all-purpose bioanalytical and biosynthetic platform. The functionality of the biochip can be changed based on the content inside the droplets. By selectively addressing a subset of electrodes in the array, the biochip can be dynamically reconfigured to suit a specific task by a computer according to pre-designed application protocols. Secondly, the biochip is capable of handling massive parallel reactions at one time. The freedom in droplet actuation through active-matrix circuitry allows parallel manipulation of multiple droplets simultaneously. Active-matrix circuitry can be easily scaled up to contain thousands of rows and columns, thus it is straightforward to process more than a million droplets concurrently. This would provide unprecedented power for addressing large and complex bioanalysis tasks that conventionally deemed prohibitive. Thirdly, unlike current microarray and custom-built lab-on-a-chip device for a specific application, the digital biochip is completely reusable, thus lowering its cost-of- ownership and making it broadly accessible. The development of the prototype digital biochip instrument will be accomplished through four tasks: 1) Design and fabricate a prototype digital biochip with an active-matrix electrode array for droplet manipulation; 2) Design and develop a control circuit board for computer-biochip interfacing; 3) Develop and implement active-matrix circuitry driving algorithm for droplet manipulation; 4) Demonstrate prototype instrument operation in screening for protein crystallization. The successful development and construction of the prototype biochip instrument can be considered as a major advancement in microarray technology and lab-on-a-chip development. It will pave the way for future extension of the prototype instrument into a full- fledged digital biochip instrument that can handle millions of droplets simultaneously. PUBLIC HEALTH RELEVANCE (provided by the applicant): Upon completion, this project will present a novel all-purpose programmable and scalable digital biochip instrument. The instrument has the potential to become a revolutionary tool for biomedical and clinical researchers to carry out array-based bioanalytical and biosynthetic tasks with significantly reduced time, labor and cost. The successful development of the prototype instrument will prove the feasibility of the concept and pave the way for future extension of the prototype instrument into a full-fledged digital biochip instrument that can handle millions of droplets simultaneously. Digital biochips with millions of pixels will provide unprecedented capability, flexibility, simplicity and reusability to biomedical or clinical researchers to carry out a wide-variety of bioanalytical and biosynthetic tasks for biomedical applications. Potential applications include, but are not limited to, genomic and proteomic assays, single cell study, point-of-care clinical diagnostics, toxin and pathogen detection and identification, environmental monitoring, screening for new drugs and fine-chemical synthesis.