Raman spectroscopy for medical diagnostics — From in-vitro biofluid assays to in-vivo cancer detection

Abstract

Raman spectroscopy is an optical technique based on inelastic scattering of light by vibrating molecules and can provide chemical fingerprints of cells, tissues or biofluids. The high chemical specificity, minimal or lack of sample preparation and the ability to use advanced optical technologies in the visible or near-infrared spectral range (lasers, microscopes, fibre-optics) have recently led to an increase in medical diagnostic applications of Raman spectroscopy. The key hypothesis underpinning this field is that molecular changes in cells, tissues or biofluids, that are either the cause or the effect of diseases, can be detected and quantified by Raman spectroscopy. Furthermore, multivariate calibration and classification models based on Raman spectra can be developed on large "training" datasets and used subsequently on samples from new patients to obtain quantitative and objective diagnosis. Historically, spontaneous Raman spectroscopy has been known as a low signal technique requiring relatively long acquisition times. Nevertheless, new strategies have been developed recently to overcome these issues: non-linear optical effects and metallic nanoparticles can be used to enhance the Raman signals, optimised fibre-optic Raman probes can be used for real-time in-vivo single-point measurements, while multimodal integration with other optical techniques can guide the Raman measurements to increase the acquisition speed and spatial accuracy of diagnosis. These recent efforts have advanced Raman spectroscopy to the point where the diagnostic accuracy and speed are compatible with clinical use. This paper reviews the main Raman spectroscopy techniques used in medical diagnostics and provides an overview of various applications.

High sensitivity non‐invasive detection of calcifications deep inside biological tissue using Transmission Raman Spectroscopy

“…Raman spectroscopy has been proposed as a non-invasive and label free analytical method with a very consistent and prolific track record of in-vitro biomedical applications [22][23][24] for histopathological screening [25][26][27][28][29] as well as probing of lymph node pathology using fibre probes [30][31][32].…”

Cellular discrimination using in vitro Raman micro spectroscopy: the role of the nucleolus

“…4,5 Raman micro spectroscopy can detect chemical, biological and physical changes of biomolecules, and the specific information contained in the cellular Raman spectrum provides a molecular fingerprint of the sample of interest, which allows Raman micro spectroscopy to differentiate between normal and abnormal cells and tissues, indicating possible applications for example in cancer research. 5,6 Indeed, Raman micro spectroscopy has been shown to provide high specificity and sensitivity, even for pre-cancer detection, [7][8][9][10] and is noninvasive and potentially automatable, thus avoiding the disadvantages of many biomedical techniques used to identify and sort cancerous cells from normal ones, which exhibit low specificity and are destructive or perturb the cellular biology. [11][12][13] As an optical microscopic technique, Raman micro spectroscopy also has the potential to probe the molecular structure on a cellular and subcellular level.…”

Application of nanoparticles in cancer detection by Raman scattering based techniques

“…by selection of longer wavelength excitations for less fluorescence background productions or using noble metals in SERS to resolve weak signal problems. In addition, SERS optimization has been considered in the detection of biological materials [8,9,11–22]. …”

“…Similar to wave-dependent imaging techniques, RS can provide real-time (or near real-time) molecular information and high resolution imaging at relatively low cost compared to other well-established medical imaging techniques (e.g. ultrasound and magnetic resonance imaging (MRI)) [8]. RS yields a spectrum containing several peaks, each of which is characteristic of a specific molecular bond.…”