Matrix-Insensitive Sensor Arrays via Peptide-Coated Nanoparticles: Rapid Saliva Screening for Pathogens in Oral and Respiratory Diseases

Plasmonic nanoparticle-based biosensors often report a colorimetric signal through the aggregation or clustering of the nanoparticles (NPs), but these mechanisms typically struggle to function in complex biofluids. Here, we report a matrix-insensitive sensor array approach to detect bacteria, fungi, and viruses whose signal is based on the dissociation of the peptide-aggregated NPs by thiolated polyethylene glycol (HS-PEG) polymers. We show that the HS-PEGs of differing sizes have varying capabilities to dissociate citrate-capped gold nanoparticle (AuNP) and silver nanoparticle (AgNP) assemblies. The dissociative abilities of the HS-PEGs were used in this sensor array to discriminate at the 90% confidence level the microorganisms <i>Porphyromonas gingivalis</i>, <i>Fusobacterium nucleatum</i>, and <i>Candida albicans</i> in water and saliva using linear discriminant analysis (LDA). We further demonstrate the versatility of the sensor array by detecting various subtypes of the viruses SARS-CoV-2 (beta, delta, and omicron) and influenza (H3N2) spiked in saliva samples using LDA. In the final demonstration, the sensor array design stratified healthy saliva samples from patient samples diagnosed with periodontitis as well as COVID-19.