I-Corps: Translation Potential of a Hong-Ou-Mandel Quantum Imaging System Combined with a Microscope for Live-Cell Analysis

This I-Corps project is based on the development of a quantum imaging microscope for the field of life sciences. Current microscopes using high power light laser sources that excite light-emitting contrast markers (fluorescence microscopy) are powerful but can kill live cells and shift their biological pathways due to stress created by the fluorescence markers. This affects large-scale cell cultures used for drug discovery, three dimensional (3D) organoids and tissues, and sensitive biospecimens such as neuronal cultures. This technology uses no markers (label-free) and employs quantum imaging that is sensitive to subtle optical changes that are difficult or impossible to measure using current imaging techniques. These capabilities may accelerate fundamental biological research, improve drug discovery and pharmaceutical screening, advance regenerative medicine, and enhance disease diagnostics by providing new insights into cellular structure and dynamics. Future applications may expand the use of quantum photonics, creating new opportunities for life science and biotechnology industries. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of integrating a Hong-Ou-Mandel (HOM) interferometric quantum imaging system into an optical microscope for live-cell analysis. Current optical microscopy relies on local intensity variations imaging (brightfield or fluorescence). This technology introduces a fundamentally new imaging contrast mechanism based on the preservation of quantum correlations between photon pairs. This technology uses heralded photon pairs generated by spontaneous parametric down-conversion to measure changes in quantum interference after one photon interacts with a biological specimen. Previous research demonstrated stable photon pair generation, high-visibility HOM interference, and the feasibility of integrating these components into a microscope platform. This microscope may enable longer term, high throughput, and high-sensitivity studies of cellular morphology and dynamic biological processes. Translating advances in quantum photonics into practical biomedical instrumentation may accelerate quantum-enabled life science technologies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.