Controlled nano-agglomerates as stabile SERS reporters for unequivocal labelling

Biosensors, especially those with a SERS readout, are required for an early and precise healthcare diagnosis. Unreproducible SERS platforms hamper clinical SERS. Here we report a synthetic procedure to obtain stabile, reproducible and robust highly-SERS performing nanocomposites for labelling. We controlled the NPs agglomeration and codification which resulted in an increased number of hot spots, thus exhibiting reproducible and superior Raman enhancement. We studied fundamental aspects affecting the plasmonic thiol bond resulting in pH exhibiting a determining role. We validated their biosensing performance by designing a SERS-based detection assay model for SARS-CoV-2. The limit of detection of our assay detecting the spike RBD was below 10 ng/mL.