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

多光子成像在生命科学研究中是一种无处不在的工具，其中脉冲可调谐激光器需要精密显微镜。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（bbb1mm）成像的强大工具，因为它可以减少组织散射，并且可以使用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，将对再生医学和白血病等领域的研究具有开创性意义。理想的三光子激发源是低重复频率、高能量的飞秒激光，可在近红外波段调谐，平均功率低，可避免组织加热。激光产业的重点是双光子成像市场，由成熟的~100MHz固定波长和可调谐光源提供服务。基于光学参量放大器（OPAs）的三光子激发系统可以从特定的制造商那里获得，但是这些系统效率非常低，并且对于大多数研究机构来说过于昂贵。该项目是一家工业激光制造商（Chromacity，英国）和stfc资助的光子学学术研究（herot - watt大学McCracken）之间的合作，该项目将展示三光子显微镜的成本效益原型激光器，通过探索两种新型激光架构来实现低mhz光学参量振荡器（opo），解决客户驱动的需求，由Chromacity公司强大的光纤激光技术泵浦。我们将把专利的HWU知识产权与色散控制紧凑腔的构建技术相结合，以开发占主导地位的市场产品的商业替代品。我们将直接与早期采用者（Packer, Oxford; Lo Celso, Imperial; Williams, Edinburgh）和工业受益者（scientiica）合作，评估我们的OPO，并将其发展到可以在短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.