Analytical optimization of nanocomposite surface‐enhanced Raman spectroscopy/scattering detection in microfluidic separation devices

Adding vibrational spectroscopies to the arsenal of detection modes for microfluidics (μfluidics) offers benefits afforded by structurally descriptive identification of separated electrophoretic bands. We have previously applied surface‐enhanced Raman spectroscopy (SERS) detection with nanocomposite metal–elastomer substrates as a detection mode in μfluidic channels. To create these μfluidic‐SERS devices, silver‐PDMS substrate regions are integrated into the architecture of a separation chip fabricated from PDMS or glass. Herein, we investigate analytical figures of merit for integrated μfluidic‐SERS devices by implementing improvements in fluidic and SERS substrate fabrication as well as data collection strategies. Improvements are achieved by chemical modification of the PDMS channel, increasing effective detection efficiency by minimizing analyte partitioning into nonsensing walls rendering more analyte available to the metallized cover slide of channels and also by uniquely fabricating deep channels that have larger volume to SERS surface area ratios than conventional channels. A method is developed to exploit the inherent concentration profile of analyte material within an electrophoretic band in order to extend the linear dynamic range of detection on the SERS nanostructured surface. This is accomplished by spatially interrogating the Gaussian concentration profile of said bands. The subtleties of this technique give insight into the analytical utility of SERS detection in general. Finally, SERS substrates uniquely created via electron beam lithography with controllable morphologies are integrated into μfluidic‐SERS devices to prove feasibility of such a coupling for future work. A separation of endocrine disrupting chemicals in a hybrid SERS nanocomposite‐glass device is the capstone of this work.