Emerging Raman spectroscopy and saliva-based diagnostics: from challenges to applications

The study of salivary manifestation of various health disorders via Raman spectroscopy, as a noninvasive molecular sensing technique to analyze molecular signatures in the saliva projections of health, is an emerging field of investigation of combined spectroscopy-biofluidics for early-diagnostics and monitoring, enabling structural and chemical biomarkers to be monitored overtime to predict prognosis for translation to real-world sensing applications. Here, we review the potential uses in healthcare, illicit drug detection, forensics and dental/orthodontic uses, and expound the specific challenges related to the detection of certain classes of biomolecules or smaller compounds. We highlight the potential of extracellular vesicles, a salivary constituent and its potential as an emerging vehicle for medical applications. Furthermore, portable devices for Raman-saliva based detection are discussed with a specific attention on the associated microfluidic advances for miniaturization and integration of such technologies and multimodal systems are examined. Given the low concentrations of target analytes and thus, the high analytical sensitivity required, surface-enhanced Raman spectroscopy (SERS) methods are noted across the different application areas and for development of portable devices.