Progress in Developing a Clinically Viable Diagnostics Using Whispering Gallery Mode Resonators

Abstract

Whispering gallery mode (WGM) resonators enable the label-free detection of analytes based on refractive index sensing. These WGM microsphere resonators achieve high sensitivities by confining light within their cavity. This enhances the pathlength amplifying sample-light interactions leading to improved sensing metrics. By taking advantage of their small footprint, high sensitivity and flexible design, we have developed a variety of unique label-free analytical platforms. We recently demonstrated a large scale multiplexed imaging platform where hundreds of resonators are simultaneously characterized by coupling a fluorescent dye to the resonator surface. This scheme was used to quantify several biomarkers of ovarian cancer with detection limits comparable to ELISA. Recently, we extended this technique by developing an evanescent scattering approach for characterizing the WGM resonances. Since signal levels scale with excitation power, measurements can be done with high temporal resolution using less expensive imaging equipment. This approach, therefore, offers promise for developing fast, inexpensive, sensitive detection for the multiplexed detection of disease biomarkers. Making improvements to clinical tools used for diagnosing cancer have been of considerable interest as it can drastically improve the prognosis of patients. One such example is the introduction of prostate specific antigen as an early screening tool using ELISA. Since its introduction prostate cancer mortality rates have dramatically decreased due to the detection of the disease in early stages where the cancer is more treatable. The early detection approach can be adopted for all diseases such as ovarian cancer and multiple myeloma. However, challenges in identifying a single biomarker that exists in lower, undetectable concentrations have limited the development of early screening tools for many types of cancers. Additionally, immunoassay platforms amenable to routine screening must be quick, cost-effective and easily-integrated into the clinic. WGM platforms provide an opportunity to detect and identify protein and non-protein disease biomarkers as a sensitive and multiplex approach. Additionally, WGM can be integrated with numerous fluidic platforms that improve the practical aspects of the development of a device which is critical for the translation of the tool into a clinical setting. Here, the integration of WGM detectors into platforms such as capillary electrophoresis (CE) and droplet analysis will be presented. Separation of serum using CE presents the advantage of separation non-diagnostically relevant proteins which can reduce non-specific binding. The progress of developing a WGM resonators platform for the diagnostics of multiple myeloma using CE-WGM separations will be discussed.