Lab-on-a-chip Flow Cytometer Using COlor-Space-Time (COST) Coding Method

描述(申请人提供)：荧光激活细胞分选(FACS)或流式细胞术使临床医生和研究人员能够定量表征细胞的物理(细胞大小、形状、粒度)和生化(DNA含量、细胞周期分布、细胞表面标记和活性)属性。通过高通量分选来激发生物标本和提取稀有细胞类型，最先进的流式细胞仪使进行罕见事件研究成为可能，例如鉴定或分离细菌细胞、干细胞和肿瘤细胞。然而，目前用于检测多种颜色并对细胞进行分类的流式细胞仪价格昂贵(约50万美元)、复杂、危险、体积大且笨重。由于这些原因，流式细胞仪经常在实验室之间共享，导致样本处理和调度方面的冲突。随着不断增长的市场预计到2015年将达到30亿美元以上，流式细胞仪可以应对一系列多样化的生物医学挑战。然而，目前还没有任何实验室都能负担得起的具有细胞分选能力的高性能流式细胞仪。尽管对负担得起的细胞分选机的需求不断增加，但流式细胞仪行业在当前技术及其发展道路上面临着根本限制。当前的系统架构在适应和充分利用不断增加的可用荧光颜色、灵敏度、易用性和分类能力方面效率极低。我们提出了一种可访问的、负担得起的、高性能的流式细胞仪技术，它将允许任何科学家在自己的实验室进行细胞分析和分类。在这个实验室到市场的第二阶段计划中，我们建议大幅改进我们的流式细胞仪细胞分选平台Wolf Cell Sorter，包括扩大荧光检测的动态范围，实施实时细胞分选验证，扩大芯片批量制造，并与早期采用者(如对我们系统的独特功能感到兴奋的诱导多能干细胞研究人员)验证系统。这些技术和商业目标将对人类健康和疾病的基础研究和临床应用产生直接影响。

DESCRIPTION (provided by applicant): Fluorescence-activated-cell-sorting (FACS) or flow cytometry enables clinicians and researchers to quantitatively characterize the physical (cell size, shape, granularity) and biochemical (DNA content, cell cycle distribution, cell surface markers, and viability) properties of cells. With the capability of high-throughput sorting to enrih biospecimens and extract rare cell types, a state-of-the-art flow cytometer makes it possible to conduct rare-event studies such as the identification or isolation of bacterial cells, stem cells, r tumor cells. However, current flow cytometers that detect multiple colors and sort cells are expensive (~$500K), complicated, hazardous, large and bulky. For these reasons, flow cytometers are often shared amongst labs, leading to conflicts in sample handling and scheduling. With a growing market expected to reach over $3 billion by 2015, flow cytometry can address a diverse array of biomedical challenges. However, there are no high performance flow cytometers with cell sorting capabilities that are affordable for any lab. Despite the increasing demand for affordable cell sorters, the flow cytometry industry faces fundamental limits in the current technology and its evolutionary path. The current system architectures are highly inefficient in accommodating and fully utilizing the increasing number of available fluorescent colors, sensitivity, ease of use, and sorting capabilities. We propose an accessible, affordable, and high performance flow cytometry technology that will allow any scientist to perform cell analysis and sorting in their own laboratory. In this Lab-to-Market Phase II program, we propose to dramatically improve our flow cytometric cell sorting platform, the WOLF Cell Sorter, including extending the dynamic range of the fluorescent detection, implementing real time cell sorting verification, expanding chip volume manufacturing, and validating the system with early adopters such as induced pluripotent stem cell researchers excited by the unique features of our system. These technology and business goals will have a direct impact on basic research and clinical applications in human health and disease.