Label-free multimodal coherent anti-Stokes Raman scattering analysis of microparticles in unconstrained microfluidics

Fast, label-free optical identification and quantification of biomolecules and other relevant biological materials in microfluidic devices and the vascular system will play a major role in liquid biopsy and related diagnoses. An optical microscope probing simultaneously non-linear coherent anti-Stokes Raman scattering (CARS) and linear scattering (LS) was used to probe microparticles in aqueous solutions flowed unconstrained in microfluidic channels. Despite the optical complexity of these systems, where out-of-focus microparticles randomly impede CARS and LS, and where water CARS generates a substantial background, we demonstrate that in-focus microparticles can be individually and unambiguously detected when CARS and LS are co-analyzed. The ability to chemically discriminate microscale features in optically realistic flows supports the relevance of multimodal CARS platforms for liquid biopsy.