Quantitative detection of C-deuterated drugs by CARS microscopy and Raman microspectroscopy

The introduction of carbon-deuterium (C-D) bonds into drug compounds by organic synthesis is a non-invasive labelling approach, which does not alter the chemical and physiological properties of the drug itself. C-deuterated drugs exhibit characteristic vibrational signatures in the C-D stretching region around 2100-2300 cm-1, which avoids spectral interference with contributions from a complex biological environment. In this contribution, the quantitative detection of C-deuterated drugs by Raman microspectroscopy and single-band CARS microscopy is examined. Concentration-dependent studies on drugs with aliphatic and aromatic C-D moieties were performed in a two-channel microfluidic chip, using the corresponding non-deuterated (C-H) isotopomers as an internal reference. Under the experimental conditions employed, conventional Raman microspectroscopy is at least one order of magnitude more sensitive than single-band CARS microscopy with picosecond laser pulses (FWHM ~30 cm-1).