PFI:AIR - TT: Integrated Microfluidic System for Cell Separation and Enrichment

PFI:AIR - TT：用于细胞分离和富集的集成微流体系统

• 批准号: 1604014
• 负责人: Abraham Lee
• 金额: $ 20万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1604014&HistoricalAwards=false
• 关键词: PFI; AIR; TT; Integrated; Microfluidic

This PFI: AIR Technology Translation project focuses on translating an integrated microfluidic device capable of processing milliliters of whole blood by rapidly isolating and enriching rare cells (such as circulating tumor cells, CTCs), resulting in faster sample preparation for high fidelity diagnostic and prognostic measurements that are critically needed in many therapeutic applications. This integrated microfluidic platform is important due to the direct impact on cancer patients and supporting infrastructure resulting from bringing this game-changing microfluidic device to market. Patient diagnosis and monitoring would become simpler, cheaper, faster, and more convenient. Moreover, the usage of this microfluidic platform is not limited to cancer diagnosis, but extends to any disease or condition measured via changes in cellular physical properties in a sample of biological fluid. The project will result in an optimized, integrated cell separator and enrichment prototype microfluidic device. The team will demonstrate its utility with clinically relevant levels of CTCs in whole blood to determine its feasibility for improved cancer diagnosis and monitoring. This integrated microfluidic device has the following unique features: (a) label-free cell separation, enrichment, and release, (b) clinical scale sample volumes and single pass through device to achieve complete cell isolation and enrichment (100% target capture) in approximately 20 minutes, and (c) device is amenable to mass production. When compared to the leading competing methods for CTC isolation and purification from whole blood in this market space, these features provide the following advantages: (a) simpler operation, (b) quicker, more reliable test results, and (c) lower cost per test and small form factor towards a potentially portable system for use in various point-of-care applications or resource limited settings. The main technology gaps to be addressed during the project are associated with optimizing the microfluidic device to achieve the rigorous performance levels required for CTC analysis (isolate and enrich 5 CTCs/7.5mL whole blood for downstream detection). These gaps will be bridged by having multiple integrated microfluidic devices working simultaneously in parallel and improving the sensitivity of the device to sufficiently separate and capture cells of similar size. In addition, personnel involved in this project, especially undergraduate students, graduate students, and post-docs, will gain innovation and technology translation experiences. They will become well versed in microfluidic cell sorting, enrichment, chip design, manufacturing, and the needs of primary end-users in multiple business spaces around the world. They will also gain firsthand experience in working in a multidisciplinary academic-industrial environment.

该PFI：空气技术翻译项目专注于翻译一种集成的微流控设备，该设备能够通过快速分离和浓缩稀有细胞(如循环中的肿瘤细胞，CTCs)来处理毫升全血，从而实现更快的样品制备，用于许多治疗应用中至关重要的高保真诊断和预后测量。这个集成的微流控平台非常重要，因为将这种改变游戏规则的微流控设备推向市场会对癌症患者和支持基础设施产生直接影响。患者的诊断和监测将变得更简单、更便宜、更快、更方便。此外，这种微流控平台的使用不仅限于癌症诊断，还扩展到通过生物液体样本中细胞物理性质的变化来测量的任何疾病或状况。该项目将产生一个优化的、集成的细胞分离器和浓缩原型微流控装置。该团队将通过全血中临床相关水平的CTCs来证明其实用性，以确定其用于改进癌症诊断和监测的可行性。这种集成的微流控设备具有以下独特功能：(A)无标记细胞分离、浓缩和释放，(B)临床规模的样品体积和单次通过设备，在大约20分钟内实现完全的细胞分离和浓缩(100%靶标捕获)，以及(C)设备适合大规模生产。与市场上领先的从全血中分离和提纯CTC的竞争方法相比，这些特点提供了以下优势：(A)操作更简单，(B)更快、更可靠的测试结果，以及(C)每次测试成本更低，外形尺寸小，可用于各种医疗保健应用或资源有限的环境中。项目期间需要解决的主要技术差距涉及优化微流控装置，以达到CTC分析所需的严格性能水平(分离和浓缩5个CTCs/7.5ml全血，用于下游检测)。这些差距将通过让多个集成的微流控设备同时并行工作并提高设备的灵敏度来弥合，以充分分离和捕获类似大小的细胞。此外，参与该项目的人员，特别是本科生、研究生和博士后，将获得创新和技术翻译经验。他们将精通微流控细胞的分类、浓缩、芯片设计、制造，以及世界各地多个业务领域的主要终端用户的需求。他们还将获得在多学科学术-工业环境中工作的第一手经验。