Kinetically arrested SERS-Active aggregates for biosensing

Abstract

There is a demand for biosensors capable of long-term, non-invasive monitoring of low analyte concentrations in various biofluids for diagnostics, personalized healthcare, and disease monitoring. Biofluids present challenges to biosensor sensing and stability on account of their complex composition and dynamic nature. Surface Enhanced Raman Spectroscopy (SERS) offers ultra-high sensitivity, non-destructive, real-time monitoring and non-invasive detection, ideal for sensing in complex media. Plasmonic gold nanoparticle (AuNP) SERS-active assemblies have been widely explored owning to their biocompatibility and tuneable sensitivity based on AuNP morphology. Controlled aggregation of AuNPs has been achieved by incorporating a 'molecular-glue', cucurbit[7]uril (CB[7]), to produce AuNP:CB[7] aggregates containing robust nanogaps (ca. 1 nm) and displaying strong, reproducible SERS signals at low concentrations, but eventually leads to irreversible precipitation. Here we employ thiolated poly(ethylene glycol) (PEG-SH) to produce kinetically trapped metastable AuNP:CB[7]:PEG aggregates. The aggregates maintain SERS-activity, are highly tuneable through facile modification of the PEG chain length and grafting density, and possess improved stability. Moreover, the AuNP:CB[7]:PEG aggregates demonstrate low concentration detection of a common Raman reporter alongside a bioanalyte in a range of biofluids highlighting the potential application of these aggregates for non-invasive in vivo long-term monitoring alongside future customized SERS biosensing applications.