Sustained‐Release Synthetic Biomarkers for Monitoring Thrombosis and Inflammation Using Point‐of‐Care Compatible Readouts |
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| Authors: | Jaideep S Dudani Colin G Buss Reid T K Akana Sangeeta N Bhatia |
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| Affiliation: | 1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA;2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;3. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA;4. Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA;5. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA;6. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;7. Howard Hughes Medical Institute, Cambridge, MA, USA |
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| 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 sssay), 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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| Keywords: | bionanotechnology protease sensors subcutaneous delivery urinary diagnostics |
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