Spatially offset Raman spectroscopy for biomedical applications.

Fay Nicolson,Nick Stone,Pavel Matousek,Moritz F Kircher

doi:10.1039/d0cs00855a

Abstract

In recent years, Raman spectroscopy has undergone major advancements in its ability to probe deeply through turbid media such as biological tissues. This progress has been facilitated by the advent of a range of specialist techniques based around spatially offset Raman spectroscopy (SORS) to enable non-invasive probing of living tissue through depths of up to 5 cm. This represents an improvement in depth penetration of up to two orders of magnitude compared to what can be achieved with conventional Raman methods. In combination with the inherently high molecular specificity of Raman spectroscopy, this has therefore opened up entirely new prospects for a range of new analytical applications across multiple fields including medical diagnosis and disease monitoring. This article discusses SORS and related variants of deep Raman spectroscopy such as transmission Raman spectroscopy (TRS), micro-SORS and surface enhanced spatially offset Raman spectroscopy (SESORS), and reviews the progress made in this field during the past 5 years including advances in non-invasive cancer diagnosis, monitoring of neurotransmitters, and assessment of bone disease.

Highlights

A number of medical conditions such as cancer and bone disorders are accompanied by significant chemical alterations in the composition of associated cells and tissues
The results demonstrated that fractured femora were 5–10% more mineralized than nonfractured controls.[82]
In this review we have discussed the use of spatially offset Raman spectroscopy (SORS) for the detection of bone disease, neurotransmitters and cancer, in the future, we envisage that the application of SORS and SESO(R)RS imaging will not remain exclusive to these three areas

Summary

Introduction

A number of medical conditions such as cancer and bone disorders are accompanied by significant chemical alterations in the composition of associated cells and tissues. The ability to precisely determine the specific depth at which SERRS NPs are located without any prior knowledge remains a significant challenge and the means to do so is especially important for in vivo applications where SERRS NPs will be distributed at different and unknown depths, e.g. within a cancerous lesion.[108] Using SORS and transmission Raman, Mosca et al, recently reported a viable and robust method capable of predicting the depth of both a single buried object and SERRS NPs through turbid phantoms by monitoring the relative intensity of two Raman bands exhibiting differential absorption by the matrix (Fig. 8).[67,68] A proof-of-concept study demonstrated possibility of achieving better than B10% accuracy of determining the depth of a buried target relative to the overall sample thickness in SORS and TRS measurements.[67] The results demonstrate a potential effective means of calculating the depth at which SERRS NPs are localized in vivo as well as determining the optimum distribution of laser radiation around a sample in PTT applications.[68]. Consideration of the above, as well as a number of other factors, will help to reduce off-target accumulation and potential long-term toxicity in vivo.[111]

Conclusion and outlook

Findings

Conflicts of interest