Capital call for ST/T000651/1, "Harnessing Photonic Technologies for Deep-Tissue Imaging"

多光子成像是生命科学研究中普遍存在的工具，其中需要脉冲可调谐激光器用于精密显微镜。大多数多光子成像研究采用双光子荧光技术，然而三光子荧光正在成为深层组织（> 1 mm）成像的强大工具，因为它提供了减少的组织散射，并能够获得各种荧光染料和蛋白质。通过周围组织和骨骼对细胞进行非破坏性和非侵入性的高分辨率成像，对于再生医学和白血病等领域的研究将是开创性的。理想的三光子激发源是低重复频率、高能量的飞秒激光器，可在近红外范围内以低平均功率调谐，以避免组织加热。激光行业专注于双光子成像市场，由经过验证的~ 100 MHz固定波长和可调谐光源提供服务。基于光学参量放大器（OPA）的三光子激发系统可从选择的制造商获得，然而这些是非常低效的，并且对于大多数研究设施来说过于昂贵。该项目是一家工业激光器制造商（英国Chromacity）与STFC资助的光子学学术研究（赫瑞瓦特大学McCracken）之间的合作，将展示用于三光子显微镜的原型成本效益激光器，通过探索两种新型激光器架构来满足客户驱动的需求，以实现几MHz的光学参量振荡器（OPO），由Chromacity强大的光纤激光器技术泵浦。我们将联合收割机专利HWU IP在几MHz高能量OPO脉冲的产生与色散控制紧凑型腔体的构建技术相结合，以开发一种商业替代主导市场的产品。我们将直接与早期采用者（Packer，牛津; Lo Celso，帝国;威廉姆斯，爱丁堡）和工业受益者（Scientific）合作，评估我们的OPO并将其发展到可以在压缩时间内推向市场的水平。

Multi-photon imaging is a ubiquitous tool in life sciences research, where pulsed tuneable lasers are required for precision microscopy. The majority of multi-photon imaging research employs two-photon fluorescent techniques, however three-photon fluorescence is emerging as a powerful instrument for deep-tissue (> 1mm) imaging as it offers reduced tissue scattering and enables access to a wide variety of fluorescent dyes and proteins. Non-destructive and non-invasive high-resolution imaging of cells through surrounding tissue and bone would be groundbreaking for research into areas including regenerative medicine and leukemia. The ideal three-photon excitation source is a low repetition frequency, high-energy femtosecond laser tuneable in the near-infrared with low average power to avoid tissue heating. The laser industry is focused on the two-photon imaging market, serviced by well-proven ~100MHz fixed wavelength and tunable sources. Three-photon excitation systems based on optical parametric amplifiers (OPAs) are available from select manufacturers, however these are highly inefficient and are prohibitively expensive for the majority of research facilities. A collaboration between an industrial laser manufacturer (Chromacity, UK) and STFC-funded academic research in photonics (McCracken, Heriot-Watt University), this project will demonstrate prototype cost-efficient lasers for three-photon microscopy, addressing this customer-driven demand by exploring two novel laser architectures to realize few-MHz optical parametric oscillators (OPOs), pumped by Chromacity's robust fiber laser technology. We will combine patented HWU IP in the generation of few-MHz high-energy OPO pulses with know-how in the construction of dispersion- controlled compact cavities to develop a commercial alternative to the dominant market offering. Working directly with early-adopters (Packer, Oxford; Lo Celso, Imperial; Williams, Edinburgh) and industrial beneficiaries (Scientifica), we will evaluate our OPO and develop it to a level where it can be brought to market in a compressed timeframe.