Integrated flow cytometer system on a chip platform

描述（由申请人提供）：流式细胞仪是一种不可或缺的生物医学工具，可测量细胞/样本的光角散射和/或细胞/样本发出的荧光，为常规血细胞计数、癌症筛查以及各种其他诊断和测定奠定基础。流式细胞仪采用高质量的光学系统和复杂的电或机械细胞分选装置，以实现细胞的灵敏、可再现的检测和分选，但这些相同的系统使得仪器的制造和维护昂贵。该项目的目的是创建一个低成本，紧凑的流式细胞仪，可以广泛提供给临床医生和研究人员。该系统还将具有当今系统所没有的独特功能。塑料光子电路将与微流体和微声致动细胞分选器集成在微芯片平台上。这种设计很容易允许创建用于有序去除少量感兴趣细胞的分选方案，允许研究人员去除他们感兴趣的特定细胞用于额外的个体研究，例如个体癌细胞的基因分型。器件设计将根据对聚合物结构进行的光学和流体模拟的综合结果进行。在三年的过程中，几个设备测试和重新设计周期将成为可能的快速原型允许聚合物复制模塑和使用现成的压电致动器，LED/二极管激光源，和硅光电探测器。该装置可行性的成功证明将通过以下方式进行测量：（1）实现能够同时检测来自标准细胞计数校准聚合物珠的前向散射、侧向散射和荧光的细胞检测模块，其具有足够的灵敏度，以产生由商业台式细胞计数器测量的11%的变异系数。(2)开发具有足以从高通量流动通道中去除单个细胞的能力的系统原型（即，每个通道高达100，000个细胞/分钟，乘以通道的数量）。(3)选择和移除流动中的单个细胞至空间索引分选通道以用于进一步研究（例如单个癌细胞的基因分型）的能力。 廉价的一次性芯片流式细胞仪的开发将使该设备从财务角度更广泛地提供给临床医生和研究人员，有助于降低净测试成本，包含生物危害材料，并提供更快的周转结果从目前在流式细胞仪上运行的各种测试，如常规临床血液检查，艾滋病毒和癌症进展监测，或基于研究的细胞研究。此外，我们提出的单细胞分选能力的发展将自动分离感兴趣的单个细胞，使其成为促进我们对癌症的理解等领域的生物医学突破的宝贵工具，其中进行单细胞基因分型的能力对于癌症演变的研究至关重要。

DESCRIPTION (provided by applicant): Flow cytometers are an indispensable biomedical tool that measures the angular scattering of light from a cell/sample and/or the fluorescence the cell/sample emits, creating the basis for routine blood counts, cancer screenings, and a wide range of other diagnostics and assays. Flow cytometers employ high-quality optical systems and complex electrical or mechanical cell sorting devices to enable sensitive, reproducible detection and sorting of cells, but these same systems make the instrument expensive to fabricate and maintain. The aim of the project is to create a low-cost, compact flow cytometer that can be widely available to clinicians and researchers. The system will also possess unique functionality unavailable by today's system. Plastic photonic circuits will be integrated with microfluidics and microacoustically actuated cell sorters on a microchip platform. This design readily allows the creation of a sorting scheme for the ordered removal of a small number of cells of interest, allowing researchers to remove the specific cells they are interested in for additional individual studies, such as the genotyping of individual cancer cells. Device design will be carried out based on combined results from optical and fluidic simulations performed for polymer-based structures. Over the course of three years, several device test and redesign cycles will be made possible by the rapid prototyping allowed by polymer replica molding and the use of off-the-shelf piezoelectric actuators, LED/diode laser sources, and Si photodetectors. Successful demonstration of the feasibility of this device will be measured by (1) the realization of a cell detection module capable of simultaneously detecting forward scatter, side scatter, and fluorescence from standard cytometry calibration polymer beads with sufficient sensitivity to yield a coefficient of variation with 11% of that measured by a commercial benchtop cytometer. (2) the development of a system prototype with capabilities sufficient for removal of a single cell from a high-throughput flow channel (i.e. up to 100,000 cells/min per channel, multiplied by the number of channels). (3) the ability to choose and remove individual cells in flow to a spatially-indexed sorting channel for further study (e.g. genotyping of single cancer cells). The development of an inexpensive, disposable chip-based flow cytometer would make the device more widely available from a financial standpoint to both clinicians and researchers alike, helping to lower net testing costs, contain biohazard materials, and provide a more rapid turnaround on results from the wide range of tests currently run on flow cytometers, such as routine clinical bloodwork, HIV and cancer progression monitoring, or research-based cell studies. In addition, the development of our proposed single-cell sorting capabilities would automate the isolation of individual cells of interest, making it an invaluable tool for facilitating biomedical breakthroughs in areas such as our understanding of cancer, where the ability to perform single-cell genotyping for studies of the evolution of cancers will be critical.