Raman spectroscopy is a widely developing approach for noninvasive analysis that can provide information on chemical composition and molecular structure. High chemical specificity calls for developing different medical diagnostic applications based on Raman spectroscopy. This review focuses on the Raman-based techniques used in medical diagnostics and provides an overview of such techniques, possible areas of their application, and current limitations. We have reviewed recent studies proposing conventional Raman spectroscopy and surface-enhanced Raman spectroscopy for rapid measuring of specific biomarkers of such diseases as cardiovascular disease, cancer, neurogenerative disease, and coronavirus disease (COVID-19). As a result, we have discovered several most promising Raman-based applications to identify affected persons by detecting some significant spectral features. We have analyzed these approaches in terms of their potentially diagnostic power and highlighted the remaining challenges and limitations preventing their translation into clinical settings.

The differentiation of skin melanomas and basal cell carcinomas (BCCs) was demonstrated based on combined analysis of Raman and autofluorescence spectra stimulated by visible and NIR lasers. It was ex vivo tested on 39 melanomas and 40 BCCs. Six spectroscopic criteria utilizing information about alteration of melanin, porphyrins, flavins, lipids, and collagen content in tumor with a comparison to healthy skin were proposed. The measured correlation between the proposed criteria makes it possible to define weakly correlated criteria groups for discriminant analysis and principal components analysis application. It was shown that the accuracy of cancerous tissues classification reaches 97.3% for a combined 6-criteria multimodal algorithm, while the accuracy determined separately for each modality does not exceed 79%. The combined 6-D method is a rapid and reliable tool for malignant skin detection and classification.

Malignant skin tumors of different types were studied in vivo using optical coherence tomography (OCT), backscattering (BS), and Raman spectroscopy (RS). A multimodal method is proposed for early cancer detection based on complex analysis of OCT images by their relative alteration of scattered-radiation spectral intensities between malignant and healthy tissues. An increase in average accuracy of diagnosis was observed for a variety of cancer types (9% sensitivity, 8% specificity) by a multimodal RS-BS-OCT system in comparison with any of the three methods used separately. The proposed approach equalizes the processing rates for all methods and allows for simultaneous imaging and classification of tumors.