New Interfaces To Advance Point-Of-Care Biosensor Diagnostics

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ZHANG-DISSERTATION-2022.pdf (5.07 MB)
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Zhang, Yan
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School of Chemical and Biomolecular Engineering
School established in 1901 as the School of Chemical Engineering; in 2003, renamed School of Chemical and Biomolecular Engineering
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https://hdl.handle.net/1853/72597
Abstract
Inexpensive and field-deployable diagnostics that can detect and characterize different analyte concentrations at the point of care have the potential to enable efficient disease diagnosis and monitoring, leading to better patient outcomes. Cell-free biosensors, which harness living cells’ sense and response capabilities to accomplish the same reactions outside of cells, have emerged as an enabling technology to implement point-of-care diagnostics due to their simplicity, portability, and affordability. To date, numerous cell-free biosensors have been developed and demonstrated in the field to detect pathogens, environmental contaminants, and clinically relevant micronutrients. However, critical gaps in areas of simultaneous detection of multiple analytes (multiplexed detection), point-of-care analyte quantification, and protein biomarker identification still exist and have limited the reach of cell-free diagnostics for point-of-care use. This thesis describes my work in exploring new interfaces to augment current cell-free biosensor designs and endow them with new sets of analyte detection and quantification capabilities. Specifically, I developed the first-of-its-kind protocell arrays system interfacing cell-free biosensors with polymer aqueous two-phase system, enabling multiplexed detection of analytes spanning multiple molecular classes from a single sample. I also linked cell-free biosensor outputs with ubiquitous personal glucose monitors for point-of-care analyte quantification without the need for bulky analytical instruments. Lastly, I demonstrated that immunoassays detecting protein biomarkers could be coupled to cell-free biosensors, with emerging applications to enable affordable and accessible virus subtyping using protein biomarkers. Taken together, this work presents several approaches aiming to address the current limitations in point-of-care cell-free diagnostics and provides highly generalizable design frameworks for rapid test reconfiguration toward other analytes.
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2022-06-23
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