This NSF award by the Biosensing/CBET program supports work by Professor Dunn at the University of Kansas to develop innovative biosensing platforms that enable large scale multiplexing capabilities. These projects revolve around integrating sensitive fluorescence imaging with small whispering gallery mode (WGM) resonators to develop new, inexpensive bioassays. WGM resonators can sense analyte binding through changes in their surrounding refractive index which offers a sensitive label-free approach for biosensing. By coupling these resonators with fluorescence imaging, we overcome many of the difficulties associated with integrating them into useful biosensing platforms for multiplexed detection of analytes. Moreover, this approach provides a unique window into WGM structure and can track how this structure evolves with changes in external conditions. The fundamental studies proposed here comparing results from state-of-the-art high resolution microscopy measurements with detailed numerical simulations, therefore, will add insights into the fundamental properties of these interesting structures and lead to new approaches for biosensor development.
The multiplexed biosensing capabilities of these new platforms will be exploited to develop new bioassays for the early detection of ovarian cancer. Ovarian cancer remains a leading cause of cancer related deaths among the female population despite the development of aggressive surgical and chemotherapeutic treatments that have been extraordinarily successful at treating the cancer in early stages. New screening approaches capable of early stage diagnosis, therefore, can potentially have a significant impact in the health and quality of life for many. These projects, therefore, combine fundamental aspects of chemistry, physics, and biology to create new biosensing platforms with an applied overall goal of developing early screens for ovarian cancer.
The development of inexpensive and sensitive bioassays for the early detection of disease will always occupy a central position of importance in quality managed health care. For almost every disease state, early diagnosis is associated with more favorable outcomes, reduced cost, and enhanced quality of life. Moreover, the implementation of effective treatment strategies often relies on the ability to reliably monitor metrics of disease progression. The goal of our program is to develop inexpensive platforms for the multiplexed detection of cancer biomarkers using whispering gallery mode (WGM) resonators. These resonators are small, inexpensive glass spheres that detect biomarker binding through changes in refractive index. The approach does not require labels for detection, thus simplifying the chemistry, and is easily multiplexed for the simultaneous detection of several biomarkers in one assay. Moreover, because of their small footprint (tens of microns), they are ideally suited for integration with many of the developments taking place in the microfluidics and lab-on-a-chip fields. We have developed new fluorescence approaches for using resonators in the multiplexed detection of ovarian cancer biomarkers (see figure) and developed methods for integrating them with the fluidics necessary for bioassays. Recently we have begun using evanescently scattered light to characterize their resonances, which offers a robust readout capable of extended measurements (see figure). This has led to the development of a new scanning probe technique that uses a small WGM resonator attached to the end of an atomic force microscopy tip (see figure). By integrating the WGM resonator, high-resolution refractive index and topography signals are simultaneously measured on surfaces with micron level spatial resolution (see figure). For assay development, this enables binding at immobilized arrays to be characterized using the same resonator, which offers advantages in quantification. This approach, however, should also have wide appeal in materials characterization and polymer sciences where refractive index gradients are often used in device fabrication. Integration of WGM sensing with atomic force microscopy, therefore, provides a new tool for a wide range of applications.
