Date of Award
Summer 8-15-2022
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Point-of-care (POC) biosensors, although rapid and easy-to-use, are orders magnitude less sensitive than laboratory-based tests. Further they are plagued by poor stability of recognition element thus limiting its widespread applicability in resource-limited settings. Therefore, there is a critical need for realizing stable POC biosensors with sensitivity comparable to gold-standard laboratory-based tests. This challenge constitutes the fundamental basis of this dissertation work– to expand access to quality and accurate biodiagnostic tools. At the heart of these solutions lies plasmonic nanoparticles which exhibit unique optical properties which are attractive for label-free and labelled biosensors.Firstly, we improve the stability and applicability of label-free plasmonic biosensors for implementing biodiagnostics in POC and resource-limited settings. We demonstrate a cost-effective plasmonic paper-based biosensor for non-invasive detection of renal cancer. We also demonstrate a facile integration of plasmonic paper and microneedle patch to realize a POC biosensor which enables detection of target biomarkers present in interstitial fluid in an easy-to-use two-step process. We introduce a polymer encapsulation strategy to realize a stable and refreshable biosensor for long-term monitoring of protein biomarkers under harsh conditions. Next, we demonstrate dramatic improvement in bioanalytical parameters of POC biosensors by designing and realizing an ultrabright fluorescent nanolabel, plasmonic fluor. We discuss a novel approach for detection and quantification of inflammatory disease burden via plasmonically-active tissue analog which can undergo in vivo or ex vivo degradation in the presence of biological fluid associated with the tissue. We demonstrate a partition-free digital fluoroimmunoassay for ultrasensitive, multiplexed, and quantitative detection of protein biomarkers present in human biospecimens. Significantly, utilizing plasmonic-fluor, we overcome long-standing limitations associated with lateral flow immunoassays (LFA)– limited sensitivity, low accuracy and smaller analytical range compared to laboratory tests, and limited quantitation ability. Taken together, these advances are expected to overcome fundamental challenges associated with POC biosensors, and to bridge the gap between laboratory-based and at-home or point-of-care (POC) diagnosis. Through this dissertation work we demonstrate a complete workflow of a POC diagnostic platform that outperforms gold-standard laboratory tests in sensitivity, speed, dynamic range, ease of use, and cost.
Language
English (en)
Chair
Srikanth Singamaneni
Committee Members
Shantanu Chakrabartty, Jianjun Guan, Jeremiah J. Morrissey, Erica L. Scheller,
Included in
Biomedical Engineering and Bioengineering Commons, Elementary Particles and Fields and String Theory Commons, Materials Science and Engineering Commons, Mechanics of Materials Commons