Matrix-Insensitive\nSensor Arrays via Peptide-Coated\nNanoparticles: Rapid Saliva Screening for Pathogens in Oral and Respiratory\nDiseases

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