Functionalized, Complementary Live-Charge Quantum Surface-Enhanced Raman Scattering Probes for Biomolecular Detection

The detection of molecules that cannot access the hot spots of plasmonic nanostructures with surface-enhanced Raman scattering (SERS) is challenging. This can result in weak SERS as well as low repeatability and reproducibility. To overcome this, here, semiconductor-based quantum probes were functionalized with positive and negative live charge. The extremely small size of the probes approaching quantum scale in combination with multilayered assemblies resulted in an ∼120-fold increase in SERS even with zero-charge quantum probes. This was attributed to the increased surface area for analyte adsorption. Upon functionalization with live charge, we achieved ∼700-fold improvement in SERS. This was attributed to improved binding of the analytes due to the presence of a complementary live charge. The synthesis of functionalized, live-charge probes up to the quantum scale was achieved using a multiphoton ionization mechanism. The detection limit was up to nanomolar (10–9 M) concentration. Substantially improved repeatability as well as reproducibility was achieved by the introduction of complementary, live-charge quantum probes. Applicability was demonstrated by the detection of Raman labels as well as cancer biomarkers up to nanomolar concentration. This mechanism has the potential to create avenues for SERS-based detection in many fields of life sciences.