Digital surface enhanced Raman spectroscopy for quantifiable single molecule detection in flow
Hannah C. Schorr, Zachary D. Schultz
Abstract
Surface enhanced Raman scattering (SERS) provides a label free method of analyzing molecules from diverse and complex signals, potentially with single molecule sensitivity. The chemical specificity inherent in the SERS spectrum can identify molecules; however signal variability arising from the diversity of plasmonic environments can limit quantification, particularly at low concentrations. Here we show that digitizing, or counting SERS events, can decrease the limit of detection in flowing solutions enabling quantification of single molecules. By using multivariate curve resolution and establishing a score threshold, each individual spectrum can be classified as containing an event or not. This binary "yes/no" can then be quantified, and a linear region can be established. This method was shown to lower the limit of detection to the lowest physical limit, and lowered the limit of detection by an order of magnitude from the traditional, intensity based LOD calculations.