Date of Award
Doctor of Philosophy (PhD)
Detection and quantification of biomolecules within biological fluids and tissues is of fundamental importance to biomedical research and clinical diagnostics. It is impossible to fully characterize complex, non-linear, biochemical systems without being able to accurately and quantitatively determine the component molecules. This problem is ubiquitous across all domains of biomedical research, and it is a major barrier to fully understanding health, ageing, and disease. Such bottlenecks are extremely challenging to be solved, especially for proteins and peptides, which do not have amplification schemes such as polymerase chain reaction for nucleic acids, because relevant concentrations of molecules related to diseases such as cancer, heart disease, and neurodegeneration can range in concentration many orders of magnitude from fg/mL to μg/mL. Simple and effective approaches enabling sensitive and accurate measurement of biomarkers in point-of-care and resource-limited settings will significantly benefit the timely diagnosis and effective therapeutic intervention of various pathological conditions. However, there is an unmet need for ultrasensitive biosensors, applicable for point-of-care diagnostics to provide accessibility in patient’s home, rural or underserved areas, including those in developing countries. In this thesis, we introduce novel biodetection technologies based on plasmon-enhanced fluorescence for minimally-invasive and POC biodiagnostics. In the first part, we demonstrate the ultrasensitive serological assay for SARS-CoV-2 diagnosis using a plasmonically-enhanced sandwich immunoassay. We also demonstrate the detection of clinically-relevant small molecules using a competitive immunoassay. In the second part, we focus on the design and demonstration of plasmonically-enhanced microneedle patch for minimally-invasive detection of protein biomarkers in interstitial fluid. Overall, we establish the proof-of-concept of various plasmon-enhanced ultrasensitive biodetection methods, which can be potentially deployed in point-of-care and resource-limited settings.
Jianjun Guan, Erica Scheller, Mark Meacham, Bryce Sadtler,