Drop-of-blood technology for diagnosis and therapeutic drug monitoring in patients with infectious disease

项目摘要 2019冠状病毒病大流行在全球夺去了250多万人的生命，其中包括50多万人。 美国在一年内许多死亡发生在健康状况迅速恶化之后，在疾病症状出现后不久， 显现出来从严重疾病患者中收集的临床证据表明，这种恶化的发生是因为 的细胞因子风暴和凝血系统的激活，导致不受控制的血栓事件， 肺微血管和整个身体。与COVID-19类似，其他感染性疾病的严重并发症 已知疾病与引起弥散性血管内凝血、静脉内凝血和血管内凝血的凝血异常有关， 血栓栓塞、动脉血栓形成或缺血性中风。高水平的D-二聚体，高活性凝血的测试 系统，被发现与包括COVID-19在内的传染病患者的高死亡率相关。许多 这些病人如能根据传染病风险评估而得到适当和及时的治疗，是可以挽救生命的。然而，在这方面， 目前还没有有效预测传染病严重程度的测试方法。 该提案的目的是开发一种用于传染病快速护理点评估的滴血测试 严重程度，基于集成准静态声学镊子血栓弹性测定法（i-QATT）。在这种独特的方法中， 在不引起血液样品与人造表面接触的情况下， 一滴血液，其体积（4-6微升）几乎是目前所需的最小样本体积的100倍 进行凝血试验为了快速评估医院内或门诊环境下的传染病风险，我们建议 将该方法用于静脉血样品或手指针刺毛细血管血样品。我们假设1）i-QATT 毛细血管血液分析可以检测凝血异常，2）由于感染性疾病的严重并发症， 细胞因子风暴诱导的凝血系统激活，以及3）感染性疾病的严重程度可以从 凝血分析传染病严重程度评估和检测技术的发展 本论文的研究目标是：1）建立和规范声镊技术 对于毛细血管血液的凝血测量，2）评估由细胞因子风暴诱导的凝血系统的变化 3）测试滴血声镊技术用于感染性疾病的可行性， 疾病严重程度评估。

PROJECT SUMMARY The COVID-19 pandemic took lives of more than 2.5 million people globally including more than 500 thousand in the United States in one year. Many deaths occurred after rapid health deterioration, shortly after symptoms of the disease were manifested. Clinical evidence collected from patients with severe disease indicates that this deterioration occurred because of the cytokine storm and resulting activation of the coagulation system, leading to uncontrolled thrombotic events in pulmonary microvasculature and throughout the body. Similar to COVID-19, severe complications of other infectious diseases are known to be associated with coagulation abnormalities causing disseminated intravascular coagulation, venous thromboembolism, arterial thrombosis, or ischemic stroke. High levels of D-dimer, the test for hyperactive coagulation system, were found to be correlated with high mortality in patients with infectious disease including COVID-19. Many of these patients could be saved if they were properly and timely treated based on infectious disease risk assessment. However, tests that effectively predict the severity of infectious diseases are not available yet. The objective of this proposal is to develop a drop-of-blood test for rapid point-of-care assessment of infectious disease severity, based on integrated quasi-static acoustic tweezing thromboelastometry (i-QATT). In this unique approach, comprehensive coagulation analysis is done without inducing blood sample contact with artificial surfaces and by using a single drop of blood, which volume (4-6 microliters) is nearly 100 times less the minimal sample volume currently required for coagulation tests. For rapid assessment of infectious disease risk inside a hospital or under outpatient settings, we propose to use this method on venous blood samples or finger prick capillary blood samples. We hypothesize that 1) i-QATT capillary blood analysis can detect coagulation abnormalities, 2) severe complications from infectious diseases develop due to cytokine storm-induced activation of the coagulation system, and 3) severity of infectious diseases can be assessed from blood coagulation analysis. The technology development for infectious disease severity assessment and testing the above hypotheses will be achieved via the following specific aims: 1) establish and standardize the acoustic tweezing technology for coagulation measurements of capillary blood, 2) assess changes in the coagulation system induced by cytokine storm via drop-of-blood measurements, and 3) test the feasibility of drop-of-blood acoustic tweezing technology for infectious disease severity assessment.