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

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.