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

描述(申请人提供)：流式细胞术是一种生物分析技术，能够根据细胞和颗粒的物理和生化特性对其进行计数和分类。流式细胞仪广泛应用于各种研究和临床环境中，例如白血病、艾滋病毒和干细胞生物学的诊断和/或研究。由于所采用的技术，目前的流式细胞仪不能移动，体积庞大，购买(5万-60万美元)和操作非常昂贵，这意味着这些仪器通常只能在集中的核心设施中找到。在小型实验室、护理地点或偏远地区，如农村地区或遥远的战区，研究人员和临床医生使用此类设施的机会有限或不可用。这个拟议的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专业知识相结合，开发出一种突破性的流式细胞仪，其尺寸和成本是传统仪器的1/100，同时达到或超过它们的性能标准。NanoSort设备使用廉价的、可批量制造的芯片，这些芯片可以在一次使用后丢弃，这在需要无菌条件或涉及生物危险样本的环境中是一个宝贵的功能。项目目标包括三个具体目标，即(1)展示当前阿尔法原型在癌症研究应用中的实用性；(2)使用新材料开发具有改进的机械特性(如细胞流速)和大规模制造能力的贝塔原型芯片；以及(3)通过改进现有的专有信号处理算法，显著提高细胞检测和分选率。这项新技术将把流式细胞仪带到小型实验室、医疗诊所、偏远地区，以及传统仪器无法服务的更多市场，这些仪器笨重、固定且昂贵得令人望而却步，从而加快了包括癌症研究、干细胞生物学、基因组学等不同领域的科学发现的步伐。此外，这种负担得起、便携、易于维护和高性能的流式细胞仪系统的开发将完成人道主义任务(例如，发展中国家的疾病诊断和监测)。这项工作通过在不同的临床和研究环境中向新用户提供复杂和广泛适用的技术资源来服务于公众，并通过为试剂制造商和分析开发商打开新的市场来创造商业增长机会。 与公共健康相关：拟议的项目旨在建立一个集成了各种专利技术(集成的光子、声学和微流控芯片实验室技术和软件)的细胞仪原型。这种原型将可大规模生产，并将具有与领先的行业机器相当的细胞检测和分选能力，这些机器体积大(非便携式和集中式)，对大多数研究人员和临床医生来说昂贵得令人望而却步。这种新的完全开发的细胞仪将满足分散的、廉价的工具的需求，用于包括癌症、干细胞生物学、免疫学、病理学和表观遗传学在内的不同领域的尖端研究应用。

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.