Digital Microfluidics ? Minimizing Blood Volume for Pediatric Coagulation Screening (SBIR Phase IIB) Newborns and young children undergoing cardiac surgery are at significantly increased risk for a major thrombosis event, and comprehensive hypercoagulability screening is indicated in children who have suffered a major thrombotic or thromboembolic event, or who have a family history of thrombosis. Currently available coagulation screening tests are expensive, time-consuming, and must be ordered individually, which increases the cumulative volume of blood sample required. These issues make screening and monitoring for a full hypercoagulability panel clinically impractical, especially in newborns and high-risk pediatric patients undergoing cardiac surgery. Hence, there is a compelling need for an inexpensive hypercoagulability test panel that requires very small volumes of blood, has a rapid turn-around time, and has the potential to be applied to a larger number of at-risk patients at multiple time points during their surgical management. Throughout Phase I and II of this SBIR project (HL125484), we developed a panel of five critical coagulation assays on our near patient digital microfluidic instrument. The assays include antigen assays for von Willebrand factor (VWF) and Protein S, plus activity assays for Antithrombin III (ATIII), Protein C, and Factor VIII. All 5 assays are collectively run from one drop of whole blood sample (< 50 ?L). Additional Phase IIB funding will allow us to develop complementary molecular assays for Factor V Leiden and Prothrombin (Factor II) genetic mutations, which would be automated on the same assay platform. The addition of these molecular assays will provide a more comprehensive evaluation of coagulation risk and will improve the commercial potential of our final product. We will also perform CLSI guided analytical and clinical validations of the complete panel of coagulation tests and prepare regulatory applications for 510(k) FDA clearance. There is currently no single, small volume testing platform on the market that can support rapid testing of antigen, activity, and molecular analytes to provide a comprehensive assessment of hypercoagulability risk. Our testing platform and assays have been purposefully designed to meet the technical requirements for rapid, low complexity testing from small sample volumes and address a critical unmet need in pediatric coagulation management. Our approach is strengthened by collaborations with our clinical partner at Boston Children?s Hospital, the high potential clinical impact of the tests, the novel application of digital microfluidic technology for whole blood testing near the patient, and by thorough market analysis and other strategic marketing that has been initiated for the product through other sources of funding. The digital microfluidic assays will be suitable for use near the patient with minimal training requirements. Lead intended users of our tests will be nurses or laboratory technicians in pediatric care settings, but we anticipate that the system can be readily expanded to other markets, such as adult cardiac patients and rural or limited resource hospital settings that are not currently capable of performing the full coagulation assay panel.
Abnormalities of blood coagulation increase the risk of clot formation inside a blood vessel (thrombosis) and excessive bleeding. Thrombosis is a common but under-diagnosed medical condition, especially in pediatric patients with congenital heart disease or complex medical conditions. If not diagnosed and treated in a timely and effective manner, blood clotting results in life-threatening complications. Many of these complications can be avoided if comprehensive and timely risk assessments are utilized. Our Phase IIB SBIR project builds upon our success developing a novel near-patient screening platform to support rapid, low-blood volume, and highly comprehensive testing of thrombosis risk factors. The validation and commercialization of this product will allow for critical and comprehensive assessment of risk for thrombophilia in pediatric populations and will potentially lead to improved health outcomes, especially during pediatric cardiac surgery.
