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一种工具，精密显微镜需要脉冲可调谐激光器。大多数多光子成像研究使用双光子荧光技术，然而，三光子荧光正在成为一种强大的深层组织成像工具，因为它减少了组织散射，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将是再生医学和白血病等领域研究的突破性进展。理想的三光子激发源是低重复频率、高能量的飞秒激光，可在低平均功率下近红外调谐，以避免组织加热。激光行业专注于双光子成像市场，由久经考验的~100 MHz固定波长和可调谐光源提供服务。基于光学参数放大器(OPA)的三光子激发系统可以从特定的制造商获得，但是这些系统效率很低，而且对于大多数研究机构来说，价格昂贵得令人望而却步。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(Heriot-Watt University，McCracken)之间的合作项目，将展示用于三光子显微镜的低成本激光原型，通过探索两种新的激光架构来实现低MHz光学参数振荡器(OPO)，并利用Chromacity强大的光纤激光技术来满足客户驱动的需求。我们将结合获得专利的HWU IP在产生低MHz高能OPO脉冲方面与在构建色散控制紧凑型腔方面的专有技术相结合，开发一种替代占主导地位的市场产品的商业替代方案。我们将直接与早期采用者(牛津的帕克、帝国的Lo Celso、爱丁堡的威廉姆斯)和工业受益者(Science Fica)合作，评估我们的OPO，并将其开发到可以在压缩的时间框架内推向市场的水平。

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.