Triple Analysis of Blood Clotting using Driven and Diffusing Microbeads

DESCRIPTION (provided by applicant): Population studies and drug research require a high-throughput measurement of clot stiffness, permeability. The single largest cause of death in the US over the latter half of the 20 century was and still is a thrombotic event: a clot in the heart, brain, or lungs. Assessing clot quality is essential for studying, diagnosing, and treating disease Conventional blood coagulation tests can be grouped into three areas: clotting time, mechanical stability, and permeability.Clot stiffness and permeability are correlated with a broad range of diseases, but because they are not available in high throughput screening (HTS) format, the tests are under-applied. An HTS system for these tests would illuminate the relationship of disease etiology and abnormalities of blood clots, enable large- population screens, and speed development of new pharmaceuticals. We anticipate that these measurements will one day provide superior clinical monitoring for patients receiving treatment thatmodifies thrombotic activity. With this Phase 1 SHIFT SBIR Rheomics will develop a triple-analysis of clotting that uses small beads. Clotting time is measured by seeing microbeads (1-5 5m) become trapped in a forming clot. Mechanical Stability is measured by tugging on microbeads using our patented magnetic force technology. Permeability is measured using a novel technique invented by the PI/PD, in which hindered diffusion of nanoparticles is used to derive the clot's permeability by applying the effective medium theory. This Phase 1 SBIR will test the feasibility of an HTS triple-analysis that will simultaneously and automatically measure clot kinetics, strength, and permeability. This Phase 1 SBIR comprises two specific aims: assembling an imaging/magnetics platform to perform the tests, and validating the tests against standard coagulometers. We are aware of no existing system (commercial or otherwise) that can perform all three measurements, let alone perform them simultaneously, automatically, orin high throughput. In success, the Rheomics triple-analysis will deliver a stiffness assay that, unlike existing techniques, can be scaled to high throughput (eg, 96-well tray) format, and a permeability assay that is up to 60x faster, fully automated, and uses small sample volumes. Rheomics is uniquely positioned to deliver on these aims. Our team features an intersection of expertise in optical and magnetic systems development, soft-matter physics, and technology commercialization, including key personnel who patented, developed, and transferred for commercialization the technology behind the widely adopted CoaguChek(R) System, and who founded Cardiovascular Diagnostics, a successful IPO. PUBLIC HEALTH RELEVANCE: Rheomics is developing a coagulometer that will simultaneously measure clotting time, clot stiffness, and clot permeability in a high throughput, small volume format that is up to 60x faster than existing techniques. This system will advance scientific research into blood clot structureand function, enable large-population clinical research studies, and speed development of new pharmaceuticals.