Fibre-integrated Picosecond mid-Infrared Laser (fPIRL) for biomolecular analysis

电磁波谱的中红外波段在医疗保健技术中具有巨大的潜力。许多生物分子在该区域表现出非常强的辐射（光）吸收。这种吸收很大程度上取决于光的波长（颜色）与每个分子特有的分子键拉伸的匹配。例如，水吸收2.94 μ m的中红外波长的辐射比1 μ m的近红外波长的辐射强近100，000倍。激光是一种强烈的、高度定向的单色辐射束。由于生物组织的高含水量（>70%），2.94 μ m的中红外激光作为医疗工具的潜力很早就被认识到。将2.94 μ m激光聚焦在组织上，可在非常局部的区域内高效吸收辐射。随后在该区域中的快速加热导致组织蒸发成气体（消融），从而产生去除组织的超精确方法，例如用作激光手术刀或活检替代品。然而，缺乏脉冲持续时间短于1纳秒（十亿分之一秒）的超快中红外激光器，适用于组织消融。现有的超快中红外商业激光器没有足够的能量来启动烧蚀，通常太大和太复杂而不能部署在专业激光实验室之外，或者光束质量差，导致样品上的光束尺寸大（空间分辨率差）。因此，2.94 μ m组织消融的标准方法是使用更广泛使用的具有更长脉冲的激光器（Er：YAG/Nd：YAG OPO）。然而，这些较长的脉冲对组织的影响可能是非常有问题的，会导致周围细胞的组织碳化（燃烧）和坏死（细胞死亡），这在使用皮秒（超快）脉冲时可以避免。在这个项目中，我将创建一个紧凑，坚固，光纤集成的皮秒中红外激光（fPIRL）平台。该平台将基于一种新型级联非线性波长转换方案，采用先进的光纤技术和新型中红外材料相结合，创建一个完全光纤集成的光源，适合在非专业实验室和诊所广泛部署。fPIRL平台将用作超精密激光手术刀，去除微小体积的组织，用于随后的质谱分析。该工具将比现有技术具有更小的破坏性和更精确的精度。该团队汇集了工业界和学术界，包括材料科学家，激光物理学家，分析化学家和系统医学专家。我们将共同推动各种生物分子分析技术的重大进展。拟议的单细胞分辨率分子映射设置将有助于推动癌症肿瘤切除手术的改进。我们的纤维输送源将支持未来在难以到达的手术部位进行机器人手术干预。与现有的消融技术相比，我们的长波长光源（6 um）旨在揭示不同的生物指纹，改善对某些疾病的诊断。该项目将创建一个新的基于光子学的医疗技术工具。该工具将通过适用于研究和体内应用的生物分子分析技术的进步，在疾病诊断和干预方面取得重大进展。这些进步将最终改善英国NHS的患者结局，从而建立一个更健康，更快乐，更富有成效的社会。除此之外，fPIRL还可用于任何精密手术干预、古代艺术中的文化保护以及生物植入物的聚合物处理。

The mid-infrared band of the electromagnetic spectrum has huge potential in healthcare technologies. Many biological molecules exhibit very strong absorption of radiation (light) in this region. This absorption depends strongly on matching the wavelength (colour) of the light to the stretching of the molecular bonds, unique to each molecule. For example, water absorbs radiation at a mid-infrared wavelength of 2.94 um nearly 100,000 times more strongly than a near-infrared wavelength of 1 um. A laser is an intense, highly directional, and monochromatic beam of radiation. The potential of mid-infrared lasers at 2.94 um as medical tools was recognised early on, due to the high-water content of biological tissue (>70%). Focussing a 2.94 um laser on tissue results in highly efficient absorption of the radiation in a very localised area. The subsequent rapid heating in this area causes the tissue to vaporise into a gas (ablation), resulting in an ultra-precise method of removing tissue, e.g. for use as laser scalpels or biopsy replacements. There are, however, a lack of ultrafast mid-infrared lasers with pulse durations shorter than 1 nanosecond (a billionth of a second) suitable for tissue ablation. Existing ultrafast mid-infrared commercial lasers do not have enough energy to initiate ablation, are often too large and complex to be deployed outside of specialist laser laboratories, or have poor beam qualities leading to large beam sizes on the sample (poor spatial resolution). As a result, the standard approach to 2.94 um tissue ablation is to use more widely available lasers (Er:YAG/Nd:YAG OPO) with longer pulses. However, the effect of these longer pulses on tissue can be highly problematic, causing tissue carbonisation (burning) and necrosis (cell-death) in surrounding cells, which can be avoided when using picosecond (ultrafast) pulses.In this project, I will create a compact, robust, fibre-integrated picosecond mid-infrared laser (fPIRL) platform. The platform will be based on a novel cascaded nonlinear wavelength conversion scheme, employing a combination of advanced fibre optic technology and new mid-infrared materials to create a completely fibre-integrated source suitable for wide deployment in non-specialist laboratories and clinics. The fPIRL platform will be employed as an ultra-precise laser scalpel, removing minute volumes of tissue for subsequent analysis with mass spectrometry. The tool will be much less destructive and much more precise than existing techniques. The team assembled crosses industry and academia, including materials scientists, laser physicists, analytical chemists, and systems medicine specialists. Together, we will enable significant advances in various biomolecular analysis techniques. The proposed single-cell resolution molecular mapping setup will help drive improvements in cancer tumour removal surgeries. Our fibre-delivered source will underpin future robotic surgical interventions in hard-to-reach surgical sites. With our long-wavelength source (6 um) we aim to reveal different biological fingerprints, improving diagnoses for certain diseases, than with existing ablation techniques.This project will create a new photonics-based healthcare technologies tool. The tool will enable significant advances in disease diagnosis and intervention, through advances in biomolecular analysis techniques suitable for both research and in-vivo applications. These advances will ultimately improve patient outcomes in the UK for the NHS, leading to a healthier, happier, and more productive society. Beyond this project, the fPIRL could be used for any precision surgical intervention, cultural preservation in ancient art, and polymer processing for biological implants.