Analytical Development and Application of Optical Microcavities

Abstract

Optical microcavities are desirable label-free sensors due to their sensitive detection capabilities. In particular, microsphere resonators achieve high sensitives by confining and recirculating light within their spherical cavity. Recirculation of light within these small, compact resonators amplifies sample-light interactions, contributing to improved sensing performance. By taking advantage of their desirable performance metrics, we have developed a variety of innovative label-free analytical platforms. For label-free biosensing, we have integrated whispering gallery mode (WGM) resonators with fluorescence imaging for the simultaneous analysis of multiple microspheres. Using this approach, we have demonstrated multiplexed detection of protein biomarkers. Current clinical tools used to diagnose ovarian cancer lack specificity and sensitivity required to achieve an accurate early diagnosis. Label-free platforms provide an opportunity to detect identified protein and non-protein disease biomarkers in order to improve diagnostic capabilities. Whispering gallery mode resonators offer a sensitive, multiplexed detection scheme to accomplish this. Specifically, our developed imaging approach allows multiple targets to be analyzed in a single assay by simultaneously monitoring WGM resonances of numerous microspheres. Microsphere resonators of particular sizes are functionalized for the detection of specific biomarkers. Putative ovarian cancer biomarkers CA-125, osteopontin, and prolactin were simultaneously quantified using WGM imaging. Additionally, the label-free platform was utilized for the detection of non-protein ovarian cancer target microRNA miR-142-3p. For biosensing applications, the small, compact size of microsphere resonators is also advantageous for integration with small volume systems. We demonstrate the incorporation of hundreds of WGM resonators in a 10 L droplet. By incorporating WGM resonators in small volume systems, such as microfluidic platforms, on-chip detection capabilities can be improved. In particular, digital microfluidic systems provide an analytical tool for precise control of discrete volume droplets, improving assay fluidics. In order to integrate WGM resonators with these small volume droplet systems, initial studies demonstrate real-time WGM detection in 10 L droplets. After determining evaporation was not an interferent, picomolar protein concentrations were measured by WGM resonators. Ultimately, these measurements can be extended to improve on-chip multiplexed immunoassay capabilities. To further explore WGM sensing applications, we developed a new analytical technique for label-free analysis of surfaces. Scanning resonator microscopy (SRM) utilizes a modified probe tip to analyze optical and topographic surface features. This novel scanning probe technique provides a label-free, non-invasive approach to investigate a variety of sample types. For material science applications, we demonstrate analysis of thin polymer films patterned by UV light using SRM. Additionally, we are interested in extending SRM measurements for the investigation of biological samples. Scanning resonator microscopy provides a label-free technique to measure protein coated surfaces, such as protein microarrays. Furthermore, for cell-based assays, label-free approaches allow for real time analysis of native biological systems. Initial investigations indicate SRM is a promising analytical tool for improving pre-clinical analysis methods for drug development and for applications in clinical diagnostics. Overall, WGM resonators are demonstrated as sensitive label-free detectors for the development of a variety of analytical tools.