Sustained-release synthetic biomarkers for monitoring thrombosis and inflammation using point-of-care compatible readouts.

Abstract

Postoperative infection and thromboembolism represent significant sources of morbidity and mortality but cannot be easily tracked after hospital discharge. Therefore, a molecular test that could be performed at home would significantly impact disease management. Our lab has previously developed intravenously delivered 'synthetic biomarkers' that respond to dysregulated proteases to produce a urinary signal. These assays, however, have been limited to chronic diseases or acute diseases initiated at the time of diagnostic administration. Here, we formulate a subcutaneously administered sustained release system by using small PEG scaffolds (<10 nm) to promote diffusion into the bloodstream over a day. We demonstrate the utility of a thrombin sensor to identify thrombosis and an MMP sensor to measure inflammation. Finally, we developed a companion paper ELISA using printed wax barriers with nanomolar sensitivity for urinary reporters for point-of-care detection. Our approach for subcutaneous delivery of nanosensors combined with urinary paper analysis may enable facile monitoring of at-risk patients.