A Miniature Fibre-Optic Raman Probe Fabricated by Ultrafast Laser-Assisted Etching

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.

Keywords: Raman spectroscopy; micro-optics; optical biopsy; ultrafast laser-assisted etching.

Figure 1

A partial cut-away rendering of the proposed distal-end optical system (DOS) for the laser-written Raman probe. The optical system consists of two components, L1 and L2, which interface with one light delivery and six light return optical fibres. Excitation light (represented in blue) is delivered by a central fibre and focused beyond the tip of the probe. Raman-scattered light (one sixth shown only—represented in red) is collected by the DOS and coupled back into the six return fibres for analysis.

Figure 2

Ray diagrams for each of the three lens surfaces in the DOS: (a) L1_C, (b) L1_O, (c) L2. Each lens takes the form of a prolate asphere, which efficiently collimates or focuses the rays over the desired spectral range.

Figure 3

Micrographs of the two distal-end probe components L1 (a,b) and L2 (c,d) after ultrafast laser inscription (a,c) and after etching (b,d). The outer diameter of each component was 960 μm.

Figure 4

Example lens profiles measured before and after flame polishing using an atomic force microscope (AFM). (a–c) Shows a 3D colour plot, 2D surface profile, and micrograph, respectively before flame polishing. (d–f) Shows the same plots made after flame polishing for 0.25 s. The colour maps in (a,d) were measured over 50 μm × 50 μm areas. The arithmetic roughness, R_a, was reduced from 48.7 to 2.26 nm.

Figure 5

(a) The single delivery fibre and six return fibres were manually inserted into the passive alignment slots using precision translation stages and fixed in place with a UV-cured optical adhesive. (b) Similarly, the two distal-end probe components were joined and UV cured, with optical alignment achieved passively.

Figure 6

(a) At the proximal end, the return fibres (shown here with 50 μm diameter cores), were re-arranged into a linear array using an ultrafast laser-assisted etching (ULAE)-fabricated precision slot for efficient interfacing with traditional spectrometers. (b) A micrograph of the assembled distal end with heat-shrink tubing added for protection.

Figure 7

A scatter plot mapping the lateral positions of an optical fibre randomly inserted into an alignment slot 100 times. The alignment slot confined the fibre to within ±0.83 and ±0.52 μm of the optical axis in the horizontal and vertical axes respectively to two standard deviations.

Figure 8

The Raman spectra of common Raman active reference materials obtained with the Raman probe. The spectra shown were measured over 5 s with 25 mW of laser power delivered onto the samples. The spectra are shown without any data processing applied with the exception of the silicon sample (red) which has had the fibre background (FB) (black) removed for clarity.

Figure 9

(a) A mouse intestine sample prepared on a fused silica substrate during spectral analysis with the Raman probe, embedded within the bore of a blunt needle, in light contact. (b) The average Raman spectra of eight tissue samples (red) and the FB (black) measured with the probe during 5 s acquisitions. (c) A portion of the spectrum between 1300 and 1800 cm⁻¹ highlighting relevant tissue Raman peaks measured with the Raman probe (red) and compared with the same measurement performed with a commercial inVia Raman microscope (blue).