Increased SERS detection efficiency for characterizing rare events in flow.

Improved surface-enhanced Raman scattering (SERS) measurements of a flowing aqueous sample are accomplished by combining line focus optics with sheath-flow SERS detection. The straightforward introduction of a cylindrical lens into the optical path of the Raman excitation laser increases the efficiency of SERS detection and the reproducibility of SERS signals at low concentrations. The width of the line focus is matched to the width of the sample capillary from which the analyte elutes under hydrodynamic focusing conditions, allowing for increased collection across the SERS substrate while maintaining the power density below the damage threshold at any specific point. We show that a 4× increase in power spread across the line increases the signal-to-noise ratio by a factor of 2 for a variety of analytes, such as rhodamine 6G, amino acids, and lipid vesicles, without any detectable photodamage. COMSOL simulations and Raman maps elucidate the hydrodynamic focusing properties of the flow cell, providing a clearer picture of the confinement effects at the surface where the sample exits the capillary. The lipid vesicle results suggest that the combination of hydrodynamic focusing and increased optical collection enables the reproducible detection of rare events, in this case individual lipid vesicles.