Improving Anticoagulation Monitoring in Pediatric Patients: Use of a Microfluidic Platform to Test Low Volume Blood Samples Obtained by Heel-Stick Collection

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ABSTRACT Improving Anticoagulation Monitoring in Pediatric Patients: Use of a Microfluidic Platform to Test Low Volume Blood Samples Obtained by Heel-Stick Collection (HL140662 Phase IIB SBIR) Anticoagulation therapy is indicated for children who suffer from congenital heart defects, thrombosis, or who are at risk of developing thrombosis. Over the past decade, there has been a dramatic increase in the use of anticoagulation therapies in pediatric patients, with up to 15% of hospitalized children receiving heparin or heparinoids. The use of these therapies necessitates frequent laboratory testing (every 4 hours) of multiple analytes -- anti-thrombin function (ATIII), Factor Xa activity (Xa), and activated partial thromboplastin time (aPTT) -- to avoid underdosing (thrombotic events) or overdosing (bleeding). Existing diagnostics for heparin therapy are problematic in newborns and children as they are generally standardized for adult samples and require as much as 2 mL of whole blood per analyte or a cumulative blood volume of up to 12 mL per day for the full panel. There is a critical unmet need to develop a low-volume, minimally invasive, and rapid turn-around diagnostic test panel for monitoring heparin therapy in children that features multiple analyte testing on a single platform. Work completed through Phase I and II of this project (R44HL140662) has established feasibility to perform a panel of three critical assays (ATIII, Xa, and aPTT) for laboratory quality monitoring of anticoagulants (heparin, heparinoids) on our near patient digital microfluidic platform (FINDER). This platform was recently CE marked for glucose-6-phosphate dehydrogenase (G6PD) testing and is pending 510(k) clearance from the FDA. The proposed Phase IIB project will support full analytical validation per CLSI guidelines and a rigorous clinical validation necessary to obtain FDA clearance for our heparin assay panel. We are preparing to engage in a pre- submission with the FDA regarding our validation protocols and design of the validation studies to meet 510(k) requirements based on single test predicate devices for each analyte. We are working closely with our clinical partners at Boston Children’s Hospital to optimize the heparin testing platform workflow for seamless integration into a hospital laboratory setting upon commercialization. Funding through this Phase IIB mechanism will complete the developmental path for our FINDER heparin monitoring platform, from concept to market through anticipated FDA clearance. There is currently no single point-of-care testing platform available that supports rapid testing of ATIII, Xa, and aPTT. The small volume format inherent to our digital microfluidic technology enables all three assays to be performed with less than 50 L of whole blood or plasma, collected via heel-stick or venipuncture, and is perfectly suited for use in pediatric settings where frequent blood draws significantly increase the risk of iatrogenic anemia. By combining three technically complex assays into a single, automated platform, we can improve both technical performance of heparin monitoring assays (reduced sample-to-answer time, three analyte test results from a single blood sample) and improve clinical outcomes through reduced blood volume needed for recurrent testing of heparin and other anticoagulants.