Phase II year
2016
(last award dollars: 2022)
Phase II Amount
$4,397,908
Digital Microfluidics Minimizing blood volume for pediatric coagulation screening (HL125484) It is reported that up to 20% of neonates undergoing cardiac surgery suffer a major thrombosis event. Mortality related to pediatric stroke, pulmonary embolism, or thrombosis in patients undergoing cardiac surgery may be as high as 10%. In addition to mortality, the morbidity of pediatric thrombosis is significant, and includes prolonged hospitalization and permanent disability. Pediatric patients who are at increased risk for thrombosis due to either congenital or acquired hypercoagulability require individualized anticoagulation management. A hypercoagulability panel allows both risk stratification for guiding therapeutic management, as well as a panel to monitor anticoagulation therapy during and post cardiac surgical procedures. Screening for hypercoagulability is indicated in pediatric patients with a family history of thrombosis, or in those who have suffered a major thrombotic or thromboembolic event. Widespread screening of low risk pediatric patients is controversial, and therefore not an optimal target population for this proposal. Unfortunately, there are no large randomized trials in pediatrics due to the large volume of blood necessary to perform the testing; this is a major deterrent to collecting the data necessary to resolve this controversy. Currently available screening tests are expensive, time-consuming and ordered individually, requiring large volumes of blood sample. These issues make screening and monitoring for a full hypercoagulability panel clinically impractical, especially in high-risk pediatric patients undergoing cardiac surgery. Hence, there is a compelling need for an inexpensive hypercoagulability laboratory 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 potentially at-risk patients at multiple time points during their surgical management. Such a diagnostic panel is possible by employing a digital microfluidic system. Hypercoagulability tests on a digital microfluidic cartridge will enable portable automation, rapid turn-around time, and multiplexing several assays, including different types of assays (immunoassays and functional) utilizing about 350 nL sample per test. A disposable single-use cartridge for hypercoagulability panel testing using digital microfluidic manipulation of droplets will be used on a small form factor instrument. In Phase I, we successfully translated immunoassays (Anti-thrombin III, Protein C and Plasminogen Activator Inhibitor-1) and functional assays (Anti- thrombin III, Protein C, Plasminogen, Factor VIII and Thrombin generation) onto a digital microfluidic cartridge. In Phase II, we will multiplex the assays for a complete thrombophilia panel on a single disposable cartridge, perform comprehensive analytical validations, and conduct a pilot study at Boston Children's Hospital. The ultimate goal is the development of a single platform that can perform multiplexed immunoassays and functional assays using less than 50 µL whole blood sample to determine hypercoagulability risk and guide anticoagulation management, with initial emphasis on high-risk pediatric patients undergoing cardiac surgery.
Public Health Relevance Statement: PROJECT NARRATIVE Digital Microfluidics Minimizing blood volume for pediatric coagulation screening (HL125484) Abnormalities of blood coagulation increase the risk of clot formation inside a blood vessel (thrombosis) and 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 deaths can be avoided if appropriate risk assessments and preventive measures are applied. In this project, a cost-effective microfluidic platform that uses just a drop of blood from pediatric patients will be developed to screen for risk factors for thrombosis (a hypercoagulability panel).
NIH Spending Category: Bioengineering; Biotechnology; Cardiovascular; Clinical Research; Heart Disease; Hematology; Pediatric; Prevention
Project Terms: Antibodies; Anticoagulation; Automation; Biochemistry; Biological Assay; Blood; Blood coagulation; Blood Coagulation Disorders; Blood specimen; Blood Vessels; Blood Volume; Boston; Cardiac; Cardiac Surgery procedures; Cessation of life; Child; Childhood; Childhood stroke; Chronic; Clinical; Coagulation Process; commercialization; Complex; congenital heart disorder; cost effective; cross reactivity; Data; design; Detection; Development; Device Approval; Devices; Diagnosis; diagnostic panel; digital; disability; Drops; Event; experience; Factor VIII; Family history of; Fluorescence; Generations; Goals; Hematologist; Hematology; Hemorrhage; high risk; Hospitalization; Hour; Immunoassay; Incidence; innovation; instrument; Laboratories; Life; Measurement; Medical; meetings; Microfluidics; Modality; Monitor; Morbidity - disease rate; mortality; neonate; Pathologist; Patient risk; Patients; Pediatric Hospitals; pediatric patients; Pediatrics; Phase; Pilot Projects; Plasminogen; Plasminogen Activator Inhibitor 1; Population; pre-clinical; Preventive measure; Protein C; Protocols documentation; Pulmonary Embolism; randomized trial; rapid detection; Reporting; Risk; Risk Assessment; Risk Factors; Running; Sampling; screening; Stratification; Surgeon; Surgical Management; System; Target Populations; Technology; Testing; Therapeutic; Thrombin; Thrombophilia; Thrombosis; Time; Translating; Validation; Whole Blood
