Photonics-based Fluorescence Imaging for Research, Diagnostics, and Pathology

Abstract - Photonics-based Fluorescence Imaging for Research, Diagnostics and Pathology During the past several decades fluorescence detection has become a central technology throughout the biosciences. The basic applications include studies of biomolecule function, properties of cell membranes and localization of target molecules in cells. The more clinical applications include immunoassays, flow cytometry, point-of-care diagnostics, genetic testing, and cell imaging by fluorescence microscopy. Fluorescence is expanding to include in-vivo measurements on brain tissues using multi-photon excitation. While fluorescence technology has advanced, it has not kept pace with the advances in electronics and array detectors (cameras). The sizes of optical components such as lenses and filters are much larger than electronic components as can be seen from a cell phone with millions of transistors, but only one or two lenses in a cell phone. This mismatch in size cannot be circumvented by making smaller lenses, filters or fiber optics. These optical components require dimensions of many wavelengths to manipulate freely propagating light. We propose to overcome this limitation by using fluorophores positioned within sub-wavelength near-field distances from the plasmonic, photonic or plasmonic multi-layer structures (MLS). We are NOT proposing to use the fluorophores as electronic components, but rather to directly couple their emission into CMOS imaging detectors with MLSs without free-space propagation of light. The MLS controls the propagation of optical energy, can separate wavelengths and can direct the energy (coupled photons) towards nearby detectors. This concept will provide the basis for new devices for research and medicine. To demonstrate the usefulness of these devices we have established collaborations with senior faculty in the School of Medicine. These collaborations include detection of weak binding in drug discovery or high throughput screening (HTS) because much of the HTS is used with drug fragments which bind weakly to target molicules. Most of the MLS retain spatial information in the x-y plane which allows either ensemble or virus particle counting assays for HIV and the Covid-19 virus SARS-CoV-2. The wide field of view will allow whole slide imaging of pathology specimens. Our goal is to develop this new area of near-field effects in fluorescence, with easy to fabricate strruvtures, to enable a new generation of instruments and devices for fluorescence detection in research, sensing and imaging.