A point of care-device for the determination of creatinine phosphokinase (CPK), the CPK Now

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Abstract This application is in regard to the National Center for Advancing Translational Sciences SBIR/STTR Omnibus Solicitation. In Vitro Diagnostic Solutions, LLC (IVDS) proposes to develop a point-of-care test (POCT) to rapidly determine blood creatine phosphokinase (CPK) activity for the improved management of long-chain fatty acid oxidation disorders (LCFAODs). FAODs are inborn errors of metabolism inherited in an autosomal recessive pattern that result in deficient energy production within the mitochondria and severe downstream effects. Infantile or adolescent-onset FAODs are associated with hepatic dysfunction, hypoketotic hypoglycemia, encephalopathy, and intercurrent illness, with severe cases resulting in sudden death. Later or adult-onset FAODs are typically associated with muscle weakness, myalgias, and rhabdomyolysis. The prevalence of FAODs is about 1 in 10,000 births globally, and it is estimated that FAOD patients require 17.55 hospital days per year comprising a significant time, cost, and effort burden on the patients, caregivers, and the healthcare system. CPK is an important biomarker for rhabdomyolysis and metabolic decompensation and is the most frequently monitored biomarker for patients with long-term manifestations of LCFAODs. There is an urgent, unmet need for simple-to-use and accurate home monitoring for CPK determination to help patients manage their hydration, diet, activity levels, and medication (Ultragenyx). IVDS has pioneered a universal POCT platform based on a cost-effective, portable, and simple-to-use device for determining accurate concentrations of analytes in whole blood from a finger-stick, heel-stick, or microtainer draw. The platform is based on colorimetric detection via a reflectometer embedded with a panel of LEDs chosen to cover over 85% of colorimetric indicators currently on the market. Test strips provide in situ separation of blood components from plasma and utilize a chemical indicator with absorbance maximum outside the range of common interferents, e.g., hemoglobin and bilirubin, to provide precise detection of CPK activity. The CPK Now is a single step, accurate, and rapid POCT requiring only 20 µL of blood. A mobile app displays and stores results of blood CPK levels which can be remotely disseminated to the care provider to make essential decisions on whether the patient should go to the emergency room or manage from home. Successful execution of this proposal will have a lasting, positive impact on those suffering from LCFAODs and shift the clinical paradigms surrounding recurrent rhabdomyolysis. The specific aims of this proposal are: 1) Finalize CPK Detection Formulation, 2) Analytical Validation of Membrane Formulations, 3) Eliminate Hematocrit Bias in the Range of 30% to 52%, 4) Establish Concordance of CPK Now to the Reference Using Patient Samples, and 5) Prepare Final Report.