Fast Digital Colloid-Enhanced Raman Spectroscopy with Fixed Voxel Acquisition for On-Site Detection

Digital colloid-enhanced Raman spectroscopy (dCERS) based on single-molecule counting was recently developed for ultrasensitive and reproducible quantification of extremely low concentrations of substances even in a complex background. To enable the application of this novel technology in demanding situations, such as forensic on-site analysis, bioterror agent detection, or even toxicity monitoring in domestic homes, we have developed a compact and portable dCERS system based on fixed voxel acquisitions of single-molecule events. We demonstrate that the fixed voxel acquisition is also dominated by Poisson distribution, with comparable sensitivity and reproducibility, in comparison to that of the original scanning-based dCERS system. The measurement time required for the same accumulated single-molecule count has also been further reduced by 26% due to the elimination of spatial scanning. The incorporation of built-in stirring further improved the detection efficiency by about 4 folds, resulting in a 2-fold improvement in the relative standard deviation (34.4 vs 17.8%) for the same detection time. The above results have thus provided a solid basis for the construction of portable, compact, and robust dCERS devices that can meet the challenge of most demanding on-site applications.