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Spectroscopic studies increasingly employ Raman tags exhibiting a signal in the cell – silent region of the Raman spectrum (1800–2800 cm ⁻¹ ), where bands arising from biological molecules are inherently absent. Raman tags bearing functional groups which contain a triple bond, such as alkyne and nitrile or a carbon–deuterium bond, have a distinct vibrational frequency in this region. Due to the lack of spectral background and cell-associated bands in the specific area, the implementation of those tags can help overcome the inherently poor signal-to-noise ratio and presence of overlapping Raman bands in measurements of biological samples. The cell – silent Raman tags allow for bioorthogonal imaging of biomolecules with improved chemical contrast and they have found application in analyte detection and monitoring, biomarker profiling and live cell imaging. This review focuses on the potential of the cell – silent Raman region, reporting on the tags employed for biomedical applications using variants of Raman spectroscopy.

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