Portable Lab-on-a-chip Flow Cytometer: Prototype and Application Development

描述（由申请人提供）：流式细胞术是一种生物分析技术，可以根据细胞和颗粒的物理和生化特性进行计数和分选。流式细胞仪广泛应用于各种研究和临床环境，例如白血病、HIV和干细胞生物学的诊断和/或研究。由于所采用的技术，目前的流式细胞仪无法移动，体积庞大，购买和操作非常昂贵（5万至60万美元），这意味着这些仪器通常只能在集中的核心设施中找到。小型实验室、医疗点或偏远地区（如农村地区或前沿战区）的研究人员和临床医生使用此类设施的机会有限或无法获得。该项目将尖端的芯片实验室技术（微流体、光学、微声学）与癌症和其他领域的研究应用相结合，开发出一种突破性的流式细胞仪，其尺寸和成本仅为传统仪器的1/100，同时达到或超过其性能标准。NanoSort设备采用廉价的、可批量生产的芯片，在一次使用后可以丢弃，这在需要无菌条件或涉及生物有害样品的情况下是一个有价值的特征。项目目标包括三个具体目标，即(1)展示当前alpha原型在癌症研究中的应用；(2)利用新材料开发beta原型芯片，改善其机械特性（如细胞流速）和可量产性；(3)通过改进现有的专有信号处理算法，显著提高了细胞检测和分选率。这项新技术将把流式细胞术引入小型实验室、医疗点诊所、偏远地区和其他市场，传统仪器体积庞大、移动不便、价格昂贵，无法为这些市场提供服务，从而加快了包括癌症研究、干细胞生物学、基因组学等多个领域的科学发现步伐。此外，开发这种价格合理、便携、易于维护和高性能的流式细胞仪系统将履行人道主义使命（例如，在发展中国家进行疾病诊断和监测）。这项工作通过为不同临床和研究背景下的新用户提供复杂和广泛适用的技术资源来服务公众，并通过为试剂制造商和分析开发商开辟新市场创造商业增长机会。

DESCRIPTION (provided by applicant): Flow cytometry is a bioanalysis technique that enables counting and sorting of cells and particles based on their physical and biochemical properties. Flow cytometer instruments are widely used in diverse research and clinical settings, for example the diagnosis and/or study of leukemia, HIV, and stem cell biology. Due to the technology employed, current flow cytometers are immobile, bulky, and very expensive to purchase ($50k-$600k) and operate, meaning that these instruments are typically found only in centralized core facilities. Access to such facilities is limited or unavailable to researchers and clinicians in small labs, at the point-of-care, or in remote locations such as rural areas or far-forward combat zones. This proposed project combines cutting edge lab-on-a-chip technology (microfluidics, optics, microacoustics) with expertise in research applications in cancer and other fields to develop a breakthrough flow cytometer that is 1/100 the size and cost of conventional instruments while meeting or surpassing their performance standards. The NanoSort device employs inexpensive, mass-manufacturable chips that can be discarded after a single use, a valuable feature in circumstances requiring sterile conditions or involving biohazardous samples. The project objectives entail three specific aims, namely (1) demonstration of current alpha prototype utility in cancer research application; (2) development of beta prototype chip using new materials with improved mechanical features (such as cell flow rate) and mass-manufacturability; and (3) significantly increased cell detection and sorting rates via improvements to existing proprietary signal processing algorithms. This new technology will bring flow cytometry to small labs, point-of-care clinics, remote locations, and additional markets not served by conventional instrumentation that is bulky, immobile, and prohibitively expensive, thereby accelerating the pace of scientific discovery in diverse fields including cancer research, stem cell biology, genomics, and more. Further, the development of this affordable, portable, easy-to-maintain, and high performance flow cytometry system will fulfill humanitarian missions (for example, disease diagnosis and monitoring in developing countries). This work serves the public by offering a sophisticated and broadly applicable technology resource to new users in diverse clinical and research contexts, and creates business growth opportunities by opening new markets for reagent manufacturers and assay developers. PUBLIC HEALTH RELEVANCE: The proposed project aims to build a prototype cytometer that integrates various patented technologies (integrated photonic, acoustic, and microfluidic lab-on-a-chip technology and software). This prototype will be mass-manufacturable and will have capabilities for cell detection and sorting at rates comparable to leading industry machines that are large (non-portable and centralized) and prohibitively expensive to most researchers and clinicians. This new fully developed cytometer will serve demands for decentralized, inexpensive tools for cutting edge research applications in diverse fields including cancer, stem cell biology, immunology, pathology, and epigenetics.