A Reproducible Surface-Enhanced Raman Spectroscopy Approach. Online SERS Measurements in a Segmented Microfluidic System

Abstract
The application of a liquid/liquid microsegmented flow for serial high-throughput microanalytical systems shows promising prospects for applications in clinical chemistry, pharmaceutical research, process diagnostics, and analytical chemistry. Microscopy and microspectral analytics offer powerful approaches for the analytical readout of droplet based assays. Within the generated segments, individuality and integrity are retained during the complete diagnostic process making the approach favored for analysis of individual microscaled objects like cells and microorganisms embedded in droplets. Here we report on the online application of surface-enhanced micro-Raman spectroscopy for the detection and quantization of analytes in a liquid/liquid segmented microfluidic system. Data acquisition was performed in microsegments down to a volume of 180 nl. With this approach, we overcome the well-known problem of adhesion of colloid/analyte conjugates to the optical windows of detection cuvettes, which causes the so-called “memory effect”. The combination of the segmented microfluidic system with the highly sensitive SERS technique reaches in a reproducible quantification of analytes with the SERS technique.