Raman in the Clinic
Ananya Barui discusses the potential – and pitfalls – of Raman spectroscopy in the clinic
Jonathan James | | Interview
What’s the focus of your work?
The goal of my group at the Indian Institute of Engineering Science and Technology in Shibpur is to develop effective diagnostic tools for early cancer detection. Despite histopathological methods being the clinical gold standard, their invasive nature prevents real-time disease monitoring – a clear objective for pathologists worldwide.
We’ve started collecting exfoliated cells from susceptible regions of oral and cervical tissues, and are analyzing these using different modes of quantitative microscopy. The evaluation of collected samples using Fourier-transform infrared (FTIR) spectroscopy provides useful information about alterations in cellular functional groups, strengthening our screening processes; capitalizing on the complementary nature of Raman and FTIR spectroscopy then allows us to give our measurements higher sensitivity and specificity.
We’re now trying to incorporate advanced chemometric techniques into our workflows to aid in data analysis. The aim: development of a label-free cancer prediction system. We want to explore the application of surface-enhanced Raman scattering in label-free genomic and transcriptomic biomarker detection for stratifying epithelial cancers by stage.
Why should we be excited by Raman spectroscopy in the clinic?
Raman spectroscopy has the potential to become an important clinical tool for the real-time analysis of early disease. The inelastic interaction of light with biological tissues can highlight abnormal characteristics, by monitoring molecular level changes with high sensitivity and specificity. By reducing the chance of false negative results, we have the opportunity to develop “optical biopsies.”
Each Raman subspecialty has something to offer. For example, Wei and colleagues developed a Raman-based volumetric chemical imaging method capable of elucidating the complex 3D architecture, chemical composition, and metabolic dynamics of a variety of different tissues (2). Elsewhere, Raman scattering microscopy has been used to image chemical bonds with high sensitivity, resolution, speed, and specificity (3). Other groups have used Raman to characterize the microheterogeneity of oral cancer tissues, which would otherwise have remained undetected (4). All in all, there’s clearly enormous scope for Raman spectroscopy to transform a number of research fields.
Despite great promise, translation has proven difficult. Why?
The clinical acceptability and utility of any new technology is dependent on performance, cost, and sustainability. Compared with clinical biopsies, so called “optical biopsies” may not conduct measurement in the same location; moreover, the small sampling volume of Raman-based approaches may not necessarily reflect tissue heterogeneity. As a result, a more detailed histopathological assessment is required to compensate.
The nature of biological tissue, which auto-fluoresces when studied, also enhances the undesired noise in Raman spectra; thus, appropriate signal processing is required to obtain a useful signal. One must also select an appropriate laser source and power setup. The repeatability, cost, and duration of analysis – particularly to withstand competition from other technologies – are also important considerations.
How will the field move forwards?
The development of clinical technologies is influenced either by “technology push” or “clinical pull.” In the early years of development, these technologies were developed for non-clinical purposes, but found a clinical utility. Now, the technology is being developed specifically to address clinical needs. In the next few decades, we can expect a proliferation of biomedical optics – providing information for screening, diagnosis, interventional guidance, treatment response, monitoring, and, ultimately, disease treatment.
- A Ghosh et al., “Chemometric analysis of integrated FTIR and Raman spectra obtained by non-invasive exfoliative cytology for the screening of oral cancer”, Analyst, 4, 1309 (2019). DOI: 10.1039/c8an02092b
- M Wei et al., “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy”, Proc Natl Acad Sci USA, 14, 6608 (2019). DOI: 10.1073/pnas.1813044116
- F Hu et al., “Biological imaging of chemical bonds by stimulated Raman scattering microscopy”, Nat Methods, 9, 830 (2019). DOI: 10.1038/s41592-019-0538-0
- P Kumar et al., “Raman spectroscopy of experimental oral carcinogenesis: Study on sequential cancer progression in hamster buccal pouch model”, Tech Cancer Res & Treat, 5, NP60 (2015). DOI: 10.1177/1533034615598622