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

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.

This project will achieve impact in a number of important areas:

Patients: Through this project, we will develop ultrafast laser based processes to manufacture a key component for an important fibre-optical medical diagnostic instrument. This instrument will find clinical applications in the diagnosis and treatment of Barratt's oesophagus and oesophageal-cancer, diseases of particular and growing importance in the UK - as highlighted in CRUK's recently published research strategy. The route to clinical trial and market for these instruments is reliant on the development of manufacturable distal-end-optical-system (DOS) devices, and this is the goal of this project. Thus, this project will have a significant impact on patients, by improving patient prognosis.


NHS: As a first target, we will develop technologies that improve, and reduce the costs of, the diagnosis and treatment of a Barrett's oesophagus and oesophageal cancer. Thus, this project will result in a proportionate economic benefit to the NHS. In the future, however, we will also explore other applications for the optical-biopsy instrument e.g. brain and colon cancer - areas where substantial potential benefits to the NHS would also be expected.

UK Industry: We have partnered with Renishaw, who will benefit directly from the results of this project:

Renishaw is a world-leader in the commercial supply of metrology equipment, and in recent years they have been working to develop a Raman-based optical-fibre-fed optical-biopsy instrument. As detailed in their Letter-of-Support, the route to market for this instrument has been hampered by the lack of a manufacturable distal-end-optical-system technology - despite encouraging preliminary in-vitro results using a prototype instrument. Through this project, we will directly address this issue, and open the way to clinical trials of the optical-biopsy instrument. This project will, therefore, clearly benefit Renishaw by opening up new commercial opportunities in healthcare.

UK PLC: This project aims to maintain and develop the UK's lead in an emerging manufacturing technology (ultrafast laser inscription) and emerging healthcare technologies (optical-biopsy instruments). Thus, the project will impact UK PLC by enhancing its standing and position in these important areas. The project will also train young multi-skilled, cross-discipline scientists and engineers, the key to a high-tech / value economy.

Academia: This project will benefit academics working to develop fibre-optic based medical instrumentation by demonstrating the power of ultrafast laser inscription for the development of compact precision distal optics. To maximise the widest possible academic impact of the project, we will disseminate our project results (following suitable IP protection steps) at dedicated international biophotonic and biomedical instrumentation conferences and sessions (e.g. BiOS - Biophotonics at Photonics West). The project will also impact academics working in the specific fields of ultrafast laser inscription and advanced laser manufacturing, by pushing ultrafast laser inscription into a manufacturing arena. We will engage this specific community by attending laser manufacturing conferences such as The International Congress on Applications of Lasers & Electro-Optics (ICALEO).

General: As part of our impact strategy, we will seek out opportunities for public-engagement. We will, for example, build a user-friendly and interactive resource that can be used to demonstrate the developed project technologies. We will take this exhibition to schools, and events such as the IOP Physics in Field events, and aim to exhibit at events such as the Royal Society Summer Science Exhibition.