Ultrasensitive Surface-Enhanced Raman Scattering Flow Detector Using Hydrodynamic Focusing

Abstract

Label-free, chemical specific detection in flow is important for high throughput characterization of analytes in applications such as flow injection analysis, electrophoresis, and chromatography. We have developed a surface-enhanced Raman scattering (SERS) flow detector capable of ultrasensitive optical detection on the millisecond time scale. The device employs hydrodynamic focusing to improve SERS detection in a flow channel where a sheath flow confines analyte molecules eluted from a fused silica capillary over a planar SERS-active substrate. Increased analyte interactions with the SERS substrate significantly improve detection sensitivity. The performance of this flow detector was investigated using a combination of finite element simulations, fluorescence imaging, and Raman experiments. Computational fluid dynamics based on finite element analysis was used to optimize the flow conditions. The modeling indicates that a number of factors, such as the capillary dimensions and the ratio of the sheath flow to analyte flow rates, are critical for obtaining optimal results. Sample confinement resulting from the flow dynamics was confirmed using wide-field fluorescence imaging of rhodamine 6G (R6G). Raman experiments at different sheath flow rates showed increased sensitivity compared with the modeling predictions, suggesting increased adsorption. Using a 50-millisecond acquisitions, a sheath flow rate of 180 μL/min, and a sample flow rate of 5 μL/min, a linear dynamic range from nanomolar to micromolar concentrations of R6G with a LOD of 1 nM is observed. At low analyte concentrations, rapid analyte desorption is observed, enabling repeated and high-throughput SERS detection. The flow detector offers substantial advantages over conventional SERS-based assays such as minimal sample volumes and high detection efficiency.

SERS and DFT investigation of the adsorption behavior of 4-mercaptobenzoic acid on silver colloids

“…Applications using SERS as the research tool can be found in the fields of analytical chemistry, surface science, and biomedical studies [4][5][6][7][8][9]. Most of the SERS studies have been carried out with molecules adsorbed on the surfaces of transition metals [10][11][12][13], particularly Ag and Au.…”

Online SERS detection of the 20 proteinogenic l-amino acids separated by capillary zone electrophoresis

“…SERS-active substrates were incorporated into a custom-built flow cell by affixing individual substrates onto a standard microscope glass slide, as described before, 31 and shown in Figure S-1 (ESI). One end of a 72 μm i.d., 143 μm o.d.…”

“…22 Our recent work demonstrated that sheath-flow SERS detection lowers the limit of detection of rhodamine to concentrations of 10 −9 –10 −10 M and enables high throughput online detection in CZE. 31, 32 This suggests that sheath-flow SERS may enable high sensitivity characterization of more common analytes.…”

A new SERS substrate based on silver nanoparticle functionalized polymethacrylate monoliths in a capillary, and it application to the trace determination of pesticides

“…The fabrication of periodic nanostructures by nanometer-scale lithography techniques can achieve moderate sensitivity and high reproducibility, but it is currently limited to research laboratories due to its high cost and complications associated with the fabrication of SERS-active substrates. In order to make SERS more applicable, the synergistic integration of SERS with micro-fluidics has been carried out [13][14][15]. However, micro-fluidic SERS also introduces additional complexity to the fabrication of these devices and time-consuming, so far, this technique is impractical to meet the needs for sensitive, ultra-low-cost disposable analytical devices.…”