Laser manufacturing distal-end-optical-systems for endoscopic optical-biopsy diagnostics

食道癌是发达国家所有癌症中增长速度最快的，预后差，五年后存活率低。早期识别食道组织的变化有助于改善预后，但目前的技术依赖于传统的内窥镜和活检，这些技术具有侵入性，采样较差，只能识别已经通过细胞结构变化表现出来的问题。基于光子技术的最新发展意味着，现在可以开发一种医学诊断方法，通过分析从组织中非弹性散射的激光的光谱特性(拉曼光谱)来识别癌前病变(巴雷特综合征)、癌症和非癌症组织。通过在细长而灵活的光纤末端进行拉曼光谱，这种光纤被用来精确地引导光线进入和离开感兴趣的区域，这将有可能在体内测试食道组织是恶性的还是正常的。这项技术还可能发现在组织病理学过程中不会发现的异常情况，这些关键信息可以使早期诊断成为可能，并意味着可以避免不必要的侵入性手术。这种技术还将应用于Barrett‘s食道和食道癌的内窥镜治疗，使临床医生能够在切除前和切除过程中评估相关组织区域的边缘。然而，有一个重大的制造问题阻碍了这些新的和令人兴奋的基于光子的临床工具的开发；为了控制离开和进入光纤远端(体内)端的光的性质，有必要使用某种形式的远端光学系统(DOS)。这种DOS可以像单个透镜一样简单，也可以是更复杂的结构，需要反射镜、滤光片和透镜，就像基于拉曼的光学活检仪一样。目前，制造这种DOS器件需要将离散的微光学元件对准并粘合在一起。这些技术是劳动密集型、耗时和昂贵的。总之，当前的DOS制造技术不是最优的，不适合商业制造，需要一种新的、更灵活的制造技术。在这个STFC-CLAP项目中，我们将开发基于超快激光技术的新的DOS制造工艺。这些过程使用聚焦的超短激光脉冲，每个脉冲只有几百飞秒长，以局部和精确地改变三维衬底材料的结构。激光诱导的改性以各种方式表现出来，例如改变了改性材料的化学蚀刻速率和/或折射率。利用这些表现形式，可以直接在衬底材料中写入光学元件，例如衍射栅，并且通过使用辐照后的化学蚀刻步骤，我们可以雕刻精密的微型光学元件。“超快激光刻字”使透镜、反射镜和光波导等微光学元件能够使用单一的制造工艺组合到单一基板上，这一事实使其成为商业化制造精密DOS技术的理想途径。

Oesophageal cancer has the fastest rate of increase of any cancer in the developed world and a poor prognosis with low survival after five years. Early identification of changes in oesophageal tissue leads to improved prognosis, but current techniques rely on traditional endoscopy and biopsy, which are invasive and exhibit poor sampling, and are only capable of identify issues that have already manifested through changes in the cellular structure. Recent developments in photonic-based technologies mean that it is now feasible to develop a medical diagnostic that is capable of identifying pre-cancerous (Barrett's syndrome), cancerous and non-cancerous tissues, by analysing the spectral properties of laser light inelastically scattered from tissue (Raman spectroscopy). By performing Raman spectroscopy at the end of a thin and flexible fibre-optic, that is used to precisely guide light into and out from the region of interest, it will be possible to test in-vivo whether oesophageal tissue is malignant or normal. This technique may also be able to pick up abnormalities that would not be picked up during histopathology, crucial information that could enable early diagnosis and mean that unnecessary invasive surgical procedures could be avoided. Such a technology would also find applications in the endoscopic treatment of Barrett's oesophagus and oesophageal cancer, enabling the clinician to assess the margins of the relevant tissue regions before and during resection.There is, however, a significant manufacturing issue that stands in the way of fully developing these new and exciting photonic-based clinical tools; in order to control the properties of the light leaving and entering the distal (in-vivo) end of the fibre-optic, it is necessary to use a distal-end-optical-system (DOS) of some form. This DOS can be as simple as a single lens, or a more complicated construction, requiring mirrors, spectral filters and lenses, as is the case in the optical-biopsy Raman-based instrument. Currently, manufacturing such DOS devices requires discrete micro-optic components to be aligned and bonded together. These techniques are labour intensive, time-consuming and expensive. In short, current DOS fabrication techniques are non-optimal and are not suitable to commercial manufacturing; a new and more flexible manufacturing technique is required.During this STFC-CLASP project, we will develop new DOS manufacturing processes using ultrafast laser based techniques. These processes use focused ultrashort laser pulses, each only a few hundred femtoseconds long, to locally and precisely modify the structure of a substrate material in three-dimensions. The laser-induced modification manifests itself in a variety of ways, examples of which include changes to the chemical etch-rate and/or refractive index of the modified material. Using these manifestations, it is possible to directly write optical components, such as diffraction gratings, into the substrate material, and by using a post-irradiation chemical-etch step we can sculpt precision micro-optics. The fact that "ultrafast laser inscription" enables micro-optic components, such as lenses, mirrors and optical waveguides to be combined onto a single substrate, using a single manufacturing process, makes it the ideal route to commercially manufacture precision DOS technologies.