Development of POC system for patient condition and treatment monitoring in Sickle Cell Disease through hypoxia-induced sickling

PROJECT SUMMARY Functional Fluidics (FF) is developing a rapid integrated test for assessing RBC sickling based on hypoxia- induced changes in cell morphology as a potential indicator of efficacy of Sickle Cell Disease (SCD) treatment efficacy and overall patient condition. The medical care for persons with SCD has been recognized as a significant burden to healthcare with an annual cost exceeding $1.1 billion in the US alone with up to 80% of the costs associated with inpatient care. There is a pressing need for assays to both assess patient condition and to monitor the progress of new SCD therapies, especially when such are expected to affect Hb polymerization kinetics and outcomes. It could be beneficial for such an assay to allow assessment of oxygen dissociation under both equilibrium (mimicking a longer-term effects) and non-equilibrium (simulating in-vivo process) conditions. Also desirable is the CLIA-waived system suitable for use at Point of Care (POC) for monitoring in a doctor’s office or a clinic. Measurements using such systems could improve personalized treatment for patients using different drugs and in clinical trials for new therapeutics targeting RBC. For SCD, many clinical trials are presently performed in developing countries, further highlighting the need for a simple and inexpensive system to track treatment progress. The goal of this Phase I Project is to develop and initially validate a SS-RBC hypoxia-induced sickling assay (the Dynamic Sickling Assay, DSA) as a simple to use, stand-alone, and potentially CLIA-waived POC device with single use disposable cartridges to be used in a) a research tool assist in drug development in SCD space, and b) a clinical system to assess SCD patient condition and to assist in monitoring and optimization of SCD treatment, especially with drugs affecting Hb-oxygen affinity. The system proposes the use of an enzymatic oxygen scrubbing system for both quasi-equilibrium measurements and for fast kinetic sickling assessment. The goal of this work will be 1) the proposed assay can show sufficient relevance to Hb profile of blood samples from SCD patients and 2) the test results can provide sufficient sensitivity and specificity to monitor therapeutic response of RBC modifying agents. The goal of future Phase 2 work would be to further optimize and clinically validate where future work would support an FDA submission (likely a Class 2 diagnostic device through De NOVO pathway) for use in clinical management of SCD patients. Success with these goals would improve therapeutic outcomes in patients with dramatically different SCD clinical presentations.