NSF Award
2326758
This project is jointly funded by the Quantum Sensing Challenges (QuSeC) Program, and the Established Program to Stimulate Competitive Research (EPSCoR). Two-photon imaging uses intense laser pulses to excite fluorescent proteins within living tissues and is widespread in the biological sciences for functional imaging of time-varying processes. The two-photon absorption process has increased spatial resolution compared to one-photon absorption but is less efficient and thus requires high light intensity to increase the likelihood that two photons will arrive at a fluorophore simultaneously. This research project will produce excitation light sources with quantum entanglement between photons, which will increase the likelihood of two photons arriving simultaneously, thus making two-photon absorption and imaging more efficient. Improved efficiency will enable lower laser intensities, reducing damage to tissue, enabling longer and more frequent measurements. Similar entanglement effects will also improve the efficiency of three-photon absorption, which operates at a wavelength that penetrates more deeply into tissue. Existing two-photon imaging facilities at West Virginia University will be upgraded with quantum-entangled light sources. Postdoctoral, graduate and undergraduate researchers will be trained in an interdisciplinary laboratory setting combining physics, biology, and neuroscience. Teaching modules will be devised to raise quantum awareness in a Quantum Summer School for undergraduates. <br/><br/>Fluorescence imaging using 2-photon excitation represents the state-of-the-art for functional imaging of neurons within the nervous system. Neural dynamics can be captured by recording fluorescence images as a function of time. Yet there remain limitations to 2-photon fluorescence imaging stemming from the inefficiency of the excitation process, which relies on simultaneous absorption of two independent photons from a laser pulse. Simultaneous absorption is unlikely with classical photon distributions; thus 2-photon excitation requires intense excitation that can damage tissue and reduces the experimental duration in live animals. This project leverages quantum correlations between time-energy-entangled photons to enhance the efficiency of multi-photon imaging in the brains of living animals (fruit flies and mice). Multi-photon imaging will report neuron activity through the excitation of the GCaMP family of fluorescent calcium indicators. Improved efficiency will enable imaging deeper into the tissue, better imaging earlier in development, and imaging of otherwise weakly expressed fluorophores, all while reducing damage due to phototoxicity. This will allow longer measurement times and require fewer live animals to be prepared, increasing the efficiency of time and money allotted to research. Extension to 3-photon absorption with even longer wavelengths will allow penetration through more opaque materials such as insect cuticle or rodent skull.<br/><br/>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.
