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

项目总结 新冠肺炎大流行在全球夺走了250多万人的生命，其中包括 美国在一年内。许多人在健康状况迅速恶化后死亡，在疾病症状出现后不久 显示出来。从重症患者收集的临床证据表明，这种恶化是因为 细胞因子风暴和由此激活的凝血系统，导致无法控制的血栓形成事件 肺微血管和全身。与新冠肺炎类似，其他感染性疾病的严重并发症 已知的疾病与凝血异常导致弥漫性血管内凝血、静脉 血栓栓塞症、动脉血栓形成或缺血性中风。D-二聚体水平高，是凝血过度活跃的测试 在包括新冠肺炎在内的传染病患者中，被发现与高死亡率有关。许多. 这些患者如果在传染病风险评估的基础上得到适当和及时的治疗，是可以挽救的。然而， 目前还没有有效预测传染病严重程度的测试方法。 这项建议的目标是开发一种快速护理点传染病评估的血滴试验。 严重程度，基于积分准静态声钳血栓弹性测定法(I-QATT)。在这种独特的方法中， 全面的凝血分析是在不引起血液样本与人造表面接触的情况下进行的，通过使用 一滴血，其体积(4-6微升)几乎是目前所需最小样本量的100倍 用于凝血测试。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 对静脉血样或指刺毛细血管血样使用该方法。我们假设1)i-QATT 毛细血管血液分析可以检测凝血功能异常，2)感染性疾病的严重并发症 细胞因子诱导的凝血系统的激活，以及3)传染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 通过以下具体目标来实现假设：1)建立和规范声镊子技术 对于毛细血管血液的凝血测量，2)评估细胞因子风暴引起的凝血系统的变化 通过血滴测量，以及3)检验血滴声学钳技术治疗传染性疾病的可行性 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.