Low-cost microfluidic system for detection of CTCs

为了充分发挥CTC的诊断潜力，在护理点（PoC）环境中开发用于CTC选择和分析的新型仪器和技术至关重要。该二期项目的重点是开发一种集成的便携式系统（即一次性流体盒、仪器和分析），用于直接从全血中快速全自动处理ctc。具体目标集中于：(i)解决与药筒和仪器构造和操作有关的第一阶段研究所产生的技术挑战；（ii）通过增加成像功能来扩展仪器的功能和易用性；（iii）通过胰腺导管腺瘤癌（PDAC， fda批准的系统尚未很好地服务的疾病）的研究，验证该仪器的性能，以提供临床应用。该仪器将能够直接处理全血，选择回收率为90%的CTC亚群和纯度为80%的CTC亚群，电子枚举CTC，用一组核和免疫染色剂对其进行荧光标记，并对所选的CTC进行成像。该仪器的操作将实现自动化，从样品到答案的整体处理时间约为1.5小时。该二期工作的最终产品将满足fda批准和CLIA中等复杂性的一组目标监管要求。

Development of novel instrumentation and techniques for CTC selection and analysis in point-of-care (PoC) settings is essential in order to fully realize the diagnostic potential of CTCs. This Phase II project is focused on the development of an integrated, portable, system (i.e., disposable fluidic cartridge, instrument, and assay) for the rapid and fully automated processing of CTCs directly from whole blood. The specific aims are focused on: (i) Addressing the technical challenges emanating from the Phase I research related to the cartridge and instrument construction and operation; (ii) expansion of the instrument capabilities and ease of use by the addition of imaging functionality; and (iii) performance verification of the instrument for providing clinical utility via studies of pancreatic ductal adenoma carcinoma, PDAC, a disease that has not been serviced well by the FDA-approved system. The instrument will be able to directly process whole blood, select CTC sub-populations at >90% recovery and >80% purities, electronically enumerate CTCs, fluorescently label them with a set of nuclear and immunological stains, and image the selected CTCs. Operation of the instrument will be automated with overall sample-to-answer processing time of ~1.5 h. The final product of this Phase II effort will meet a set of targeted regulatory requirements for FDA-approval and CLIA moderate complexity.