Use of microfluidics in determining hemostatic phenotypes

描述（由申请方提供）：出血和血栓性疾病的特征在于显著的表型变异性。在过去的十年中，在理解这些疾病的分子基础方面取得了重要进展;然而，所观察到的变异性的很大一部分仍然未知。由于过度出血是一个重大的医学问题，具有令人印象深刻的发病率和死亡率，因此发现新的出血生物标志物可能会对公共卫生产生非常重大的影响。目前用于诊断出血性疾病的测定具有局限性，特别是对于鉴别轻度至中度出血和区分止血系统中的常见变异。此外，临床出血的量化也非常困难。因此，高度期望显示高灵敏度和特异性的方法。我们建议开发一种高通量的微流控流动分析，以量化血小板粘附，聚集和纤维蛋白沉积在健康个体和已建立的出血性疾病的个人的血液样本。这项研究将代表迄今为止临床环境中微流体测定的最大分析。我们将把这些检测结果与目前临床和实验室测量的出血表型相关联。我们的长期目标是开发一种高度敏感和特异性的方法来确定出血性疾病患者的止血潜力。 公共卫生相关性：了解为什么有些人比其他人出血更多很重要。目前，还没有方法可以准确预测这个问题。我们正试图开发一个系统，我们可以诊断出血性疾病，并最终预测出血的风险，例如在手术中。

DESCRIPTION (provided by applicant): Bleeding and thrombotic disorders are characterized by significant phenotypic variability. Over the last decade important advances have been made in the understanding of the molecular basis of these disorders; however a large portion of the observed variability remains unknown. Since excessive bleeding represents a significant medical issue with impressive morbidity and mortality, discovering new biomarkers of bleeding could have a very significant public health impact. Current assays for the diagnosis of bleeding disorders have limitations, particularly for the identification of mild to moderate bleeding and the discrimination of common variations in the hemostatic system. Also, quantifying clinical bleeding is extremely difficult. Therefore, a method that shows high sensitivity and specificity is highly desirable. We propose to develop a high-throughput microfluidic flow assay to quantify platelet adhesion, aggregation and fibrin deposition in blood samples of healthy individuals and individuals with established bleeding disorders. This study will represent the largest analysis to date of microfluidic assays in the clinical setting. We will correlate the results of these assays with current clinical and laboratory measures of bleeding phenotypes. It is our long term goal to develop a highly sensitive and specific method to determine the hemostatic potential of individuals with bleeding disorders. PUBLIC HEALTH RELEVANCE: It important to understand why some people bleed more than others. Currently, there are no methods that can accurately predict this problem. We are trying to develop a system where we can diagnose bleeding disorders and eventually predict risk for bleeding for example during surgery.