ABSTRACT Our goal is to advance a novel, hand-sized hemostasis profiler, iCoagLAB as a companion diagnostic during mechanical circulatory support (MCS) to predict potentially lethal bleeding in patients. MCS involves a broad group of technologies that provide hemodynamic support to manage a range of complex cardiac conditions, including advanced heart failure, cardiogenic shock, high-risk coronary interventions, severe cardiac or lung dysfunction, or to facilitate cardiac surgery. Although MCS technologies have expanded treatment options for high-risk patients, between 15-40% of patients experience life-threatening bleeding. Multiple factors including underlying coagulopathies, clotting factor consumption, shear stresses created by mechanical pumping, platelet impairments and fibrinolytic activation increase bleeding risk, exacerbated by heparin administered to prevent clotting in the MCS circuit. Therefore, to assess bleeding risk, frequent coagulation testing is essential. Unfortunately, conventional laboratory tests take too long, are ineffective in the context of rapidly changing coagulation in critical patients, and are poorly correlated with bleeding events, resulting in hemostasis management that is often imprecise with devastating consequences. The ability to treat rapidly evolving coagulation impairments in those at risk is therefore restricted by the absence of tools to assess coagulation comprehensively and swiftly at the point-of-care. As a consequence, major bleeding resulting from impaired coagulation, remains the leading cause of death during MCS. Coalesenz Inc., a Boston-based start-up, is developing a novel hemostasis profiler (iCoagLAB) to rapidly quantify several relevant coagulation and platelet parameters concurrently during MCS and provide a decisive risk score to identify the likelihood of major bleeding. In iCoagLAB, a laser source illuminates the blood sample and a camera images laser speckle patterns reflected from the sample over time. By analyzing laser speckle intensity fluctuations during coagulation, we can quantify multiple coagulation metrics including prothrombin time, activated clotting time, fibrin polymerization, fibrinolysis, platelet function, and hemoglobin and hematocrit. With 1/10th the weight and footprint of competing technologies, Coalesenz’s new hand-sized iCoagLAB instrument lends itself for comprehensive coagulation and platelet profiling at the poc. Although iCoagLAB opens the opportunity to assess bleeding at the poc, the existing technology currently is not tailored for use in patients during MCS. A key limitation is that current reagents are not suitable for testing the wide range of heparin doses typical in MCS patients. Moreover, our existing single-channel disposables permit only one assay at a time using blood that is pre-mixed with liquid reagents, increasing the test duration and complexity of workflow. Therefore, in this Phase 1 proposal our objectives are to develop and test novel mill...