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: 8123538
• 负责人: Yu-Hwa Lo
• 金额: $ 34.8万
• 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/8123538
• 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. PUBLIC HEALTH RELEVANCE: "Lab-on-a-chip flow cytometer using color-space-time (CoST) coding method" NanoSort, LLC RESEARCH & RELATED Other Project Information 8. PROJECT NARRATIVE The proposed project aims to develop lab-on-a-chip flow cytometers that are high performance, easy to operate and maintain, and significantly lower cost than any flow cytometers or fluorescence-activated-cell- sorters (FACS) available today, thus providing this broadly applicable technique to new settings in research and clinical practice. The research will transform the lab-on-a-chip technologies developed in Professor Lo's laboratory into products that meet the market needs in advanced biomedical research and point-of-care clinics. The proposed system substantially extends the original university technology with the invention of the COlor- Space-Time (COST) coding technique which allows multi-parameter detection using a single photo multiplier tube (PMT) detector.

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标记和生存能力）CELS的性质。除了其在基础研究中的应用（例如免疫学，细胞和分子生物学）外，该仪器还允许临床医生检测和监测诸如急性髓样白血病（AML）和HIV/AIDS等疾病的进展。最先进的流式细胞仪，具有高吞吐量分类富集生物测量并提取稀有细胞类型的能力，可以进行稀有事实研究，例如鉴定或隔离细菌细胞，干细胞或肿瘤细胞。但是，当今的流式细胞仪面临两个chalenges，限制了大幅度降低成本并将日常利用扩展到临床环境的能力。第一个限制是系统的体系结构在利用可用荧光颜色数量的增加方面效率很低。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和光学元件。随着检测参数的数量，成本，复杂性和失败风险会增加。其次，流式细胞仪（计数细胞）和FAC（计数和分类单元）之间存在巨大的价格差距（2-3倍的价格差）。 FACS主要位于共享核心设施中，并由训练有素的博士级专家运营。对于FACS的需求很大，如果细胞分类变得比现在更容易获得和负担得起，则会增加。根据UCSD的LO教授小组的近10年的研究，我们将开发实验室芯片技术，以应对以上两个挑战的产品。为了促进转换，我们将应用我们的专利游戏改变技术：1）使用单个PMT检测多个参数的颜色空间时间（成本）编码方法。成本技术基本上改变了所有现有流式细胞仪中系统性能与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实验室芯片FACS系统的分类细胞活力的系统研究，这是大多数研究实验室对成功商业化的限制问题。拟议中的I阶段研究使用创新的方法将实验室技术转变为具有超过1B市场的商业产品，并且在提议降低成本和功能改善之后，可能会扩大市场。这些技术和业务目标将直接影响基础研究和临床应用，以增强整个人群的健康和福祉。 公共卫生相关性：“使用颜色空间时间（成本）编码方法实验室流式细胞仪” NanoSort，LLC研究及相关其他项目信息8。项目叙述旨在拟议项目旨在开发具有高性能的实验室流式细胞仪，其性能是高性能的，易于操作，因此与任何流式化的成本相比，较低的流式化侵蚀剂（均可提供流式化的细胞），或者提供流式化的cor（coversive corpersiv），或者提供流式化的毛刺侵蚀剂（广泛适用于研究和临床实践的新环境。这项研究将改变LO教授实验室的实验室芯片技术，转变为满足高级生物医学研究和护理诊所市场需求的产品。拟议的系统通过发明颜色时空（成本）编码技术实质上扩展了原始的大学技术，该技术允许使用单个照片乘数管（PMT）检测器进行多参数检测。