Abstract

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Highlights

  • Delayed diagnosis, often due to the late onset of recognisable symptoms, is a major contributor to the high mortality rates of many cancers

  • Addressing the manufacturing limitations, we propose that a direct-laser-writing technique called ultrafast laser-assisted etching (ULAE) is ideally suited towards the fabrication of distal-end optical system (DOS)’s for Raman probe instruments, overcoming many of the shortfalls of traditional techniques

  • We have developed a miniaturised confocal Raman probe with a novel distal-end optical system and demonstrated that ultrafast laser-assisted etching is the ideal manufacturing tool for such a system, with potential for large-scale manufacture

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Summary

Introduction

Often due to the late onset of recognisable symptoms, is a major contributor to the high mortality rates of many cancers. Cancers that develop deep within the body such as oesophageal, bowel, and lung cancer may not present noticeable symptoms until the cancer is already at an aggressive stage. Oesophageal cancer (OC) has a poor prognosis, with a five-year survival rate of between 12% and 18% [1]. OC is commonly diagnosed by a surgical endoscopic biopsy followed by histopathology; clinicians must rely on very subtle guidance from white-light endomicroscopy and, biopsy sampling can be poor. Histopathology is complex and time-consuming, and staging the cancer can be subjective. To improve the overall prognosis of OC and other cancers, a diagnostic tool that is minimally invasive and provides real-time tissue classification at an early stage of cancer development is needed

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