Microarray System for Phenotypic and Functional Cytometry

描述(由申请人提供)：拟议工作的长期目标是开发一个自主的临床诊断系统，用于监测在感染、炎症、哮喘、自身免疫性疾病和肿瘤的情况下发生的正常和疾病的免疫功能。该系统将是一个基于微阵列的生物分析平台，专门将患者血液样本中不同的细胞类型和可溶大分子捕获到生物传感器芯片上空间分离的区域。最初捕获的大分子和细胞可以量化，以评估特定的白细胞亚群、细胞因子、抗体和其他免疫相关分子的存在。在不同条件下对捕获的细胞进行后续培养可用于实时测量特定细胞产物的产量，以评估免疫细胞的功能能力。该技术允许高度并行的测量，从而能够在不使用分子标记的情况下同时执行数百种单独的功能细胞分析。该系统将能够使用微升规模的血液样本，几乎实时地评估患者的免疫能力，这些样本随时可以通过微创程序(例如，手指毛细采血)采集。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.