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

在发达国家，食管癌的发病率增长速度是所有癌症中最快的，而且预后很差，5年后生存率很低。早期识别食管组织的变化可以改善预后，但目前的技术依赖于传统的内窥镜检查和活检，这是侵入性的，采样效果差，并且只能通过细胞结构的变化来识别已经表现出来的问题。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），开发一种能够识别癌前病变（巴雷特综合征）、癌性和非癌性组织的医学诊断方法。通过在薄而柔韧的光纤末端执行拉曼光谱，用于精确引导光线进出感兴趣的区域，将有可能在体内测试食道组织是恶性还是正常。这项技术还可以发现组织病理学无法发现的异常，这是早期诊断的关键信息，也意味着可以避免不必要的侵入性手术。该技术也可应用于巴雷特食管和食管癌的内镜治疗，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、令人兴奋的基于光子的临床工具的全面开发；为了控制离开和进入远端（体内）光纤的光的特性，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，也可以是一个更复杂的结构，需要反射镜、光谱滤光片和透镜，就像光学活检拉曼仪器一样。目前，制造这样的DOS设备需要将离散的微光学元件对齐并粘合在一起。这些技术是劳动密集型的，耗时且昂贵的。简而言之，目前的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-CLASP项目中，我们将使用基于超快激光的技术开发新的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，在三维空间中局部精确地修改衬底材料的结构。激光诱导的改性以多种方式表现出来，其中的例子包括改变化学蚀刻速率和/或改性材料的折射率。利用这些表现形式，可以直接将光学元件，如衍射光栅，写入衬底材料，并通过使用辐照后化学蚀刻步骤，我们可以雕刻精密的微光学。事实上，“超快激光铭刻”使微光学元件，如透镜、反射镜和光波导，可以使用单一的制造工艺组合到单个基板上，使其成为商业制造精密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.