QuSeC-TAQS: Entanglement- Enhanced Multiphoton Fluorescence Imaging of in Vivo Neural Function

该项目由量子传感挑战（QuSeC）计划和刺激竞争研究的既定计划（EPSCoR）共同资助。双光子成像使用强激光脉冲来激发活组织内的荧光蛋白，并且在生物科学中广泛用于时变过程的功能成像。与单光子吸收相比，双光子吸收过程具有增加的空间分辨率，但效率较低，因此需要高的光强度来增加两个光子同时到达荧光团的可能性。该研究项目将产生光子之间具有量子纠缠的激发光源，这将增加两个光子同时到达的可能性，从而使双光子吸收和成像更有效。效率的提高将使激光强度降低，减少对组织的损伤，实现更长时间和更频繁的测量。类似的纠缠效应也将提高三光子吸收的效率，三光子吸收的波长可以更深地穿透到组织中。西弗吉尼亚大学现有的双光子成像设备将升级为量子纠缠光源。博士后，研究生和本科生研究人员将在一个结合物理学，生物学和神经科学的跨学科实验室环境中接受培训。将设计教学模块，以提高本科生量子暑期学校的量子意识。使用双光子激发的荧光成像代表了神经系统内神经元功能成像的最新技术水平。神经动力学可以通过记录荧光图像作为时间的函数来捕获。然而，由于激发过程的低效率，仍然存在对双光子荧光成像的限制，这依赖于同时吸收来自激光脉冲的两个独立光子。同时吸收是不可能与经典的光子分布;因此，2-光子激发需要强烈的激发，可以损伤组织，并减少在活体动物的实验持续时间。该项目利用时间-能量纠缠光子之间的量子相关性来提高活体动物（果蝇和小鼠）大脑中多光子成像的效率。多光子成像将通过荧光钙指示剂的GCaMP家族的激发来报告神经元活动。提高效率将使成像更深入组织，在发育早期更好地成像，以及对其他弱表达的荧光团成像，同时减少由于光毒性造成的损害。这将允许更长的测量时间，并需要更少的活动物准备，提高时间和资金分配给研究的效率。扩展到3光子吸收，甚至更长的波长将允许穿透更不透明的材料，如昆虫角质层或啮齿动物头骨。该奖项反映了NSF的法定使命，并已被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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. 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.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.