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

使用颜色时空 (COST) 编码方法的芯片实验室流式细胞仪

• 批准号: 8290279
• 负责人: Yu-Hwa Lo
• 金额: $ 34.93万
• 依托单位: NANOCELLECT BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8290279
• 关键词: AIDS/HIV problem; Acute Myelocytic Leukemia; Address; Architecture; Basic Science; Benchmarking; Biochemical; Biomedical Research; Businesses; Cell Count; Cell Cycle; Cell Separation; Cell Size; Cell Survival; Cell surface; Cells; Cellular biology; Clinic; Clinical; Code; Color; Core Facility; Detection; Devices; Disease Progression; Doctor of Philosophy; Engineering; Epigenetic Process; Event; Face; Failure; Flow Cytometry; Fluorescence; Fluorescence-Activated Cell Sorting; Goals; Health; Immunology; Incidence; Intellectual Property; Laboratories; Laboratory Research; Legal patent; Maintenance; Marketing; Methods; Metric; Microfluidics; Mission; Molecular Biology; Monitor; Optics; Performance; Phase; Photons; Ploidies; Population; Price; Property; Research; Research Personnel; Risk; Shapes; Side; Signal Transduction; Sorting - Cell Movement; Specialist; Stem cells; System; Techniques; Technology; Time; Training; Tube; Universities; base; cell type; clinical application; clinical practice; commercialization; cost; cost effective; design; detector; fluorescence activated cell sorter device; innovation; instrument; meetings; micro-total analysis system; neoplastic cell; operation; photomultiplier; point of care; professor; prototype; research study; shear stress; simulation; system architecture; tumor

DESCRIPTION (provided by applicant): "Lab-on-a-chip flow cytometer using color-space-time (CoST) coding method" NanoSort, LLC RESEARCH & RELATED Other Project Information 7. PROJECT SUMMARY 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 cels. Besides its applications in basic research (e.g. immunology, cell and molecular biology), the instrument has allowed clinicians to detect and monitor the progression of diseases such as acute myeloid leukemia (AML) and HIV/AIDS. With the capability of high- throughput sorting to enrich 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, or tumor cells. However, today's flow cytometers face two chalenges that limit the ability to drastically reduce their cost and extend their day-to-day utilization to clinical settings. The first limit is that the system's architecture is highly inefficient in utilizing the increasing number of available fluorescent colors. In today's flow cytometer design, each fluorescent color requires a dedicated PMT and optics; and the cost, complexity, and risk of failure grow with the number of detection parameters. Secondly, there exists a huge price gap (2-3X price difference) between flow cytometers (that count cells) and FACS (that count and assort cells). FACS are mostly located in shared core facilities and operated by well-trained, PhD level specialists. There is a large demand for FACS that would increase if cell sorting were to become more accessible and affordable than it is now. Based on nearly 10 years of research of Professor Lo's group at UCSD, we will develop the lab-on-a-chip technology into products that can address the above two challenges. To facilitate the transformation, we will apply our patented game-changing technologies: 1) COlor-Space-Time (COST) coding method to detect multiple parameters using a single PMT. The COST technique fundamentaly changes the relationship between the system performance and the system complexity in all existing flow cytometers. We also propose a highly efficient and cost effective on-chip piezoelectric cell sorting technique with low shearing and high cell viability. Our proposed research includes the systematic study of post-sorting cell viability for lab-on-a-chip FACS system, a limiting problem for successful commercialization that is overloked by most research laboratories. The proposed Phase I research uses innovative approaches to transform a laboratory technology into commercial products that have a market of over $1B and the potential for an expanded market following the proposed cost reductions and functionality improvements. These technology and business goals will have a direct impact on basic research and clinical applications to enhance the health and wellbeing of the entire population.

描述（由申请人提供）：“使用颜色时空 (CoST) 编码方法的芯片实验室流式细胞仪” NanoSort, LLC 研究及相关其他项目信息 7. 项目摘要 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） 标记和活力）细胞的特性。除了在基础研究（例如免疫学、细胞和分子生物学）中的应用外，该仪器还使临床医生能够检测和监测急性髓性白血病（AML）和艾滋病毒/艾滋病等疾病的进展。最先进的流式细胞仪具有高通量分选功能来丰富生物样本并提取稀有细胞类型，使得进行稀有事件研究成为可能，例如细菌细胞、干细胞或肿瘤细胞的识别或分离。然而，当今的流式细胞仪面临两个挑战，限制了其大幅降低成本和将其日常使用扩展到临床环境的能力。第一个限制是系统架构在利用越来越多的可用荧光颜色方面效率极低。在当今的流式细胞仪设计中，每种荧光颜色都需要专用的 PMT 和光学器件；成本、复杂性和失败风险随着检测参数的数量而增加。其次，流式细胞仪（计数细胞）和FACS（计数和分类细胞）之间存在巨大的价格差距（2-3倍的价格差异）。 FACS 大多位于共享核心设施中，并由训练有素的博士级专家操作。如果细胞分选变得比现在更容易获得和负担得起，对 FACS 的巨大需求将会增加。基于加州大学圣地亚哥分校罗教授团队近10年的研究，我们将把芯片实验室技术开发成能够解决上述两个挑战的产品。为了促进这一转变，我们将应用我们的专利技术：1) 色彩时空 (COST) 编码方法，使用单个 PMT 检测多个参数。 COST技术从根本上改变了所有现有流式细胞仪的系统性能和系统复杂性之间的关系。我们还提出了一种高效且具有成本效益的片上压电细胞分选技术，具有低剪切和高细胞活力。我们提出的研究包括对芯片实验室 ​​FACS 系统分选后细胞活力的系统研究，这是大多数研究实验室忽视的成功商业化的限制问题。拟议的第一阶段研究使用创新方法将实验室技术转化为商业产品，这些产品的市场价值超过 10 亿美元，并且在拟议的成本降低和功能改进后有扩大市场的潜力。这些技术和商业目标将对基础研究和临床应用产生直接影响，以增强全体人民的健康和福祉。