UC Riverside

Biosensing technology represents a core and often underappreciated pillar upon which most of the major discoveries in the life sciences rest. The development of new biosensing materials and methodologies has continually enabled life-saving advancements in medical diagnostics, drug discovery, and environmental monitoring, to name only a few major areas. Surface-based biosensing techniques mark a major subclass of biosensors, ranging from the simple colorimetric lateral flow assays found in COVID-19 tests to powerful techniques used for characterizing the binding behavior of a broad range of biological interactions. Among these is surface plasmon resonance (SPR), a highly sensitive real-time biosensing modality that has been used extensively in the fields of drug discovery, vaccine research, toxicology, and fundamental explorations of other biophysical interactions. The aim of the work presented in this dissertation is the advancement of all major aspects of the SPR sensing workflow, including the underlying plasmonic materials, the sensing biointerface, and experimental design. These developments enable, and are utilized in combination with, numerous other analytical techniques for the exploration of previously unanswered biophysical questions. Chapter 2 presents the development and application of the rarely explored metal of indium for use in thin film plasmonic sensing, thereby expanding the range of available materials to researchers in the field. Chapter 3 focuses on the methodological considerations for achieving optimal characterization of the binding kinetics of therapeutics based on their valency, providing an experimental and analytical framework for SPR analysis of drugs with non-standard binding behaviors. In Chapters 4 and 5, new SPR biointerfaces are designed to quantify and correlate the effects of membrane composition on lateral diffusion and transmembrane protein function. All of these developments contribute to the overall aim of this dissertation, which is to provide tools that inform our understanding of biological systems and enable both identification and treatment of human disease.