A Statistical\nRoute to Robust SERS Quantitation Beyond\nthe Single-Molecule Level

Single-molecule surface-enhanced\nRaman spectroscopy (SM-SERS)\nholds\ngreat potential to revolutionize ultratrace quantitative analysis.\nHowever, achieving quantitative SM-SERS is challenging because of\nstrong intensity fluctuation and blinking characteristics. In this\nstudy, we reveal the relation <i>P</i> = 1 – e<sup>–α</sup> between the statistical SERS probability <i>P</i> and the microscopic average molecule number α in\nSERS spectra, which lays the physical foundation for a statistical\nroute to implement SM-SERS quantitation. Utilizing SERS probability\ncalibration, we achieve quantitative SERS analysis with batch-to-batch\nrobustness, extremely wide detection range of concentration covering\n9 orders of magnitude, and ultralow detection limit far below the\nsingle-molecule level. These results indicate the physical feasibility\nof robust SERS quantitation through statistical route and certainly\nopen a new avenue for implementing SERS as a practical analysis tool\nin various application scenarios.