Development of a minimally invasive optical biosensor to improve hyperphosphatemia management

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PROJECT SUMMARY Calcium and phosphate homeostasis is significantly disrupted in advanced chronic kidney disease (CKD) and end-stage kidney disease. Elevated serum phosphate concentration – a condition known as hyperphosphatemia – is a significant cause of cardiovascular morbidity and mortality in this population. Thus, physicians treat these patients with dietary restriction of phosphorus intake and medications that inhibit the absorption of ingested phosphorus. The standard of care is to titrate these interventions to a patient’s serum phosphate concentration, but this level is checked only at monthly intervals, which provides only an infrequent snapshot of a patient’s dynamic condition. Thus, new technology for phosphate monitoring is needed to empower physicians and patients to better manage hyperphosphatemia. The objective of this project is to address this need through the development of an optical biosensor that can be used to non-invasively measure serum phosphate concentration. Aim 1 is focused on biosensor development, which will be approached by designing hydrogel composites encapsulating metalloporphyrin-containing biosensor particles that will transduce phosphate concentration to an optical signal that can be detected through the skin. In vitro testing under simulated physiologic conditions will be performed to optimize the range and sensitivity of the biosensor. Aim 2 encompasses in vivo testing of the biosensor. Testing will be performed in the Col4a3 knockout mouse model of CKD, which exhibits dysregulated calcium and phosphate metabolism and hyperphosphatemia. Biosensor performance will be evaluated by comparison to blood and interstitial fluid measurements of phosphate. If successful, this project will provide a foundation for subsequent testing in a large animal model of CKD and efforts toward clinical translation.