Tuning the Aggregation of Plasmonic Probes to Shed Light on Diagnostic Strategies

Gold nanoparticle (GNP)-based aggregation assays were tuned by systematically varying the length and concentration of the plasmonic probes, which are two critical factors that influence the detection range and sensitivity. Plasmonic probes were engineered by conjugating antibodies to fixed-size GNPs via poly(ethylene glycol) (PEG) linkers of varying molecular weights. The performance of these probes was evaluated in the detection of hemagglutinin (HA) protein, a marker of the influenza A virus, with a focus on the corresponding shifts in localized surface plasmon resonance. The results demonstrated that shorter plasmonic probes exhibited enhanced sensitivity and produced more pronounced colorimetric signals, thereby achieving a broader detection range. Additionally, the probe concentration was critical for modulating the measurable concentration range of the HA protein. Quantitative analysis using the plasmon ruler equation confirmed that the interparticle distance, governed by the probe length and concentration, is a key determinant of assay performance. Our study provides insights into the design of GNP-based diagnostic tools that allow customizable detection ranges tailored to specific applications. These findings suggest that by fine-tuning the plasmonic probe parameters, the balance between sensitivity and detection range can be optimized, offering a versatile approach to the design of point-of-care diagnostic assays.