(B-64) Development of a multiplexed microfluidic device to assess blood coagulation status

Introduction:: COVID-19 remains a global health challenge, and many patients develop cardiovascular abnormalities including thrombosis. Consequently, the International Society of Thrombosis and Haemostasis recommends frequent monitoring of coagulation status in patients diagnosed with COVID-19. Although the precise etiology of such coagulopathies in COVID-19 is not clear, damage to lung tissue, increased cytokine levels and alteration of blood chemistry due to inflammation and sepsis all likely contribute. The resulting inappropriate hemostasis is a major challenge in the care of these patients. Importantly, the coagulation profile of a COVID-19 patient – and consequently the appropriate medical treatment – might change from hour to hour. Because asymptomatic patients can develop life-threatening coagulopathy-related thrombotic events, robust, frequent and inexpensive tests for blood coagulation aberrations would help identify at-risk patients. Current methods for clinical assessment of coagulation status are cumbersome, expensive and limited in scope. As such there is an urgent need to better characterize COVID-19-specific thrombophilia and understand its role over time. Point of care tests are needed to accurately analyze the coagulation state of a blood sample, thereby assessing a patient’s clinical hemostasis condition and allowing clinicians to rapidly diagnose and treat specific elements of coagulopathy.

Materials and Methods:: We developed a new device for diagnosing coagulopathies that can be used for COVID-19 and other clinical applications where robust and repeated measurements of blood coagulation status are needed. The device is multiplexed, combining many of the existing tests into one assay, and is biomimetic – i.e. the flow of blood through channels recapitulates the blood flow in vivo. The assay is self-contained and disposable, so minimizes the risk of exposure to infected blood or aerosols. The blood is allowed to enter multiple parallel channels driven by a vacuum-induced pressure drop across the device. Coagulation will increase viscosity and flow resistance in the channels. The distance traveled in each channel is measured and compared with existing assays. We coat the PDMS channels with substances that activate or inhibit various coagulation pathways (Fig.1). The design of the coagulation microfluidic device, fabrication, loading of the device, and experimental set-up are shown in Fig. 1.

Results, Conclusions, and Discussions:: < ![if !supportLists] >o < ![endif] >Results

We tested two configurations of the device. The first has serpentine channels in parallel and the second has six "pie-shaped" compartments, and the flow moves from the center inlet port radially outward. The second design proved to be more reproducible and robust.

< ![if !supportLists] >o < ![endif] >Conclusions and Discussion

< ![if !supportLists] >· < ![endif] >Optimization of device to perform the experiments with whole blood and exhibit varying levels of coagulability.

< ![if !supportLists] >· < ![endif] >Robust method for analyzing coagulation status in COVID-19 patients with the potential to complement or supplant existing assays.

The technology will be invaluable in a wide spectrum of clinical applications such as trauma surgery, emergency procedures and other applications where patients can experience shock or require transfusion

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