Microarray System for Phenotypic and Functional Cytometry

描述（由申请人提供）：拟议努力的长期目标是开发一种自主临床诊断系统，用于监测在感染、炎症、哮喘、自身免疫性疾病和肿瘤形成背景下发生的正常和患病免疫功能。该系统将是一个基于微阵列的生物测定平台，可以从患者的血液样本中特异性地捕获不同的细胞类型和可溶性大分子，并将其定位在生物传感器芯片上的空间分离区域。可以量化大分子和细胞的初始捕获，以评估白细胞、细胞因子、抗体和其他免疫相关分子的特定亚群的存在。随后在不同条件下培养捕获的细胞可用于在真实的时间内测量特定细胞产物的产生，以评估免疫细胞功能能力。该技术允许高度平行的测量，从而能够同时进行数百个单独的功能性细胞测定，而无需使用分子标记。该系统将能够使用用微创程序容易地收获的微升规模的血液样本（例如，手指针刺毛细血管血液取样）。这种实时测量对于持续监测疾病进展以及评估维持和支持免疫机制的预防性治疗和治疗操作至关重要。该项目将开发工具，以改进对自身免疫性疾病和传染病的诊断。

DESCRIPTION (provided by applicant): The long-term objective of the proposed effort is to develop an autonomous clinical diagnostics system for monitoring normal and diseased immune function that occurs in the context of infection, inflammation, asthma, autoimmune disease, and neoplasia. This system will be a microarray-based bioassay platform that specifically captures distinct cell types and soluble macromolecules from a patient's blood sample onto spatially separate regions on a biosensor chip. Initial capture of macromolecules and cells can be quantified to assess the presence of specific subpopulations of leukocytes, cytokines, antibodies and other immunologically relevant molecules. Subsequent culture of the captured cells under different conditions can be used to measure the production of specific cell products in real time to assess immune cell functional capacities. The technology allows for highly parallel measurements that result in the capability to perform hundreds of individual functional cellular assays simultaneously without the use of molecular labels. The system will enable assessment of patients' immune capacity in near-real time using microliter-scaled samples of blood readily harvested with minimally invasive procedures (e.g., fingerstick capillary blood sampling). Such real-time measurements will be crucial for the ongoing monitoring of disease progression as well as the evaluation of prophylactic treatments and therapeutic manipulations that sustain and support immune mechanisms. This project will develop tools that will enable improved diagnostics for autoimmune diseases and for infectious diseases.