| Whispering gallery mode (WGM) optical resonator sensors have emerged as promising tools for label-free detection of biomolecules in solution. These devices have even demonstrated single-molecule limits of detection in complex biological uids. This extraordinary sensitivity makes them ideal for low-concentration analytical and diagnostic measurements, but a great deal of work must be done toward understanding and optimizing their performance before they are capable of reliable quantitative measurents. The present work explores the physical processes behind this extreme sensitivity and how to best take advantage of them for practical applications of this technology. I begin by examining the nature of the interaction between the intense electromagnetic elds that build up in the optical biosensor and the biomolecules that bind to its surface. This work addresses the need for a coherent and thorough physical model that can be used to predict sensor behavior for a range of experimental parameters. While this knowledge will prove critical for the development of this technology, it has also shone a light on nonlinear thermo-optical and optical phenomena that these devices are uniquely suited to probing. The surprisingly rapid transient response of toroidal WGM biosensors despite sub-femtomolar analyte concentrations is also addressed. The development of asymmetric boundary layers around these devices under ow is revealed to enhance the capture rate of proteins from solution compared to the spherical sensors used previously. These lessons will guide the design of ow systems to minimize measurement time and consumption of precious sample, a key factor in any medically relevant assay. Finally, experimental results suggesting that WGM biosensors could be used to improve the quantitative detection of small-molecule biomarkers in exhaled breath condensate demonstrate how their exceptional sensitivity and transient response can enable the use of this noninvasive method to probe respiratory distress. WGM bioensors are unlike any other analytical tool, and the work presented here focuses on answering engineering questions surrounding their performance and potential. |
