Sustained-Release Synthetic Biomarkers for Monitoring Thrombosis and Inflammation Using Point-of-Care Compatible Readouts

PUBLICATION TYPE:

Journal Article

AUTHORS:

Dudani, Jaideep S.; Buss, Colin G.; Akana, Reid T. K.; Kwong, Gabriel A.; Bhatia, Sangeeta N.

SOURCE:

Advanced Functional Materials, Volume 26, Issue 17, p.2919-2928 (2016)

URL:

http://onlinelibrary.wiley.com/doi/10.1002/adfm.201505142/abstract

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. The laboratory 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, a subcutaneously administered sustained-release system, using small poly(ethylene glycol) scaffolds (<10 nm) to promote diffusion into the bloodstream over a day, is formulated. The utility of a thrombin sensor to identify thrombosis and an Matrix metalloproteinase (MMP) sensor to measure inflammation is demonstrated. Finally, a companion paper ELISA (Enzyme-linked immunosorbent assay), using printed wax barriers, with nanomolar sensitivity for urinary reporters for point-of-care detection is developed. The approach for subcutaneous delivery of nanosensors combined with urinary paper analysis may enable facile monitoring of at-risk patients.

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