Project Summary/Abstract Work under this proposal supports development of a broad-spectrum point-of-care (POC) coagulometer by Perosphere Technologies (The Perosphere Technologies POC Coagulometer) with the intent to create and offer an automated, microfluidic version of the manual Lee/White clotting time method. The device is based on novel technology and utilizes reagent-less, single-use microfluidic cuvettes made of silicon and glass for measurement of blood samples. Clot activation occurs at the beginning of the intrinsic clotting pathway through contact of a blood sample with the inner glass and silicon surfaces of the cuvette. The device detects clot formation by monitoring the intensity of near-infrared light, transmitted through cuvette and blood sample, and sensing of fibrin assembly at the end of the common clotting pathway. The clot detection scheme affords development of two main assays, a Clotting Time Assay, that measures the time to onset of clot formation and is currently implemented on the coagulometer platform, and a Clot Lysis Time assay, that measures the time to onset of subsequent clot breakdown and is in development. Research indicates that the device is broadly sensitive to the effects of anticoagulants across drug class, their reversal agents and thrombolytic drugs. Initial marketing efforts will focus on use of the device with implemented Clotting Time assay for monitoring of the direct oral anticoagulants (DOACs) and low molecular weight heparins (LMWHs). Research under this proposal targets establishment of clotting time reference ranges for healthy volunteers and patients on the DOACs rivaroxaban, apixaban, dabigatran and edoxaban, in direct support of initial marketing goals. In support of future device applications, the research also targets assessment of the device’s ability to detect inherited or acquired coagulopathies, based on abnormal clotting times, as well as assessment of the device’s sensitivity to abelacimab, a novel anticoagulant and direct factor XI/XIa inhibitor, currently in clinical development. Perosphere Technologies intends to commercialize the device through a marketing, sales and distribution partnership with a global medical device company. The device is similarly suited for use in emergency situations (e.g. emergency room, emergency vehicle) and for routine care in the inpatient and outpatient settings (hospitals, clinics, surgical suites, doctor’s offices, pharmacies) by healthcare professionals who can perform or order fresh venous whole blood draws. The device promises to address several unmet medical needs, including point-of- care monitoring of DOACs, and has the potential to define new standards of care. The device is expected to improve patient care, clinical outcome and to reduce healthcare costs, by providing physicians with the means to make faster and better-informed treatment decisions. The developed Clotting Time and Clot Lysis Time assays will present a new way to describe a patient’s coagulation state and enable opportunities for fundamental research of disease mechanisms and therapeutic approaches.

Project Narrative Work under this proposal supports development and commercialization of a broad-spectrum coagulometer based on novel technology that promises to enable rapid and precise measurements of the effects of anticoagulants, their reversal agents and thrombolytic drugs on blood clotting and clot lysis processes, respectively, directly at the point-of-care. Initial marketing efforts will focus on use of the coagulometer for monitoring of the direct oral anticoagulants (DOACs) and low molecular weight heparins (LMWHs) with a Clotting Time assay. The proposed research will yield clinical clotting time reference ranges for the DOACs, in direct support of initial, future marketing goals, and assessment of the device’s ability to detect and measure inherited or acquired coagulopathies as well as to monitor effects of the novel factor XI/XIa inhibitor abelacimab, in support of future device applications.