Nanoplasmonic swarm biosensing using single nanoparticle colorimetry.

We demonstrate a swarm biosensing platform that detects analyte based on the change in plasmonic signal from thousands of single nanoparticles sensors, leading to increased quantitative accuracy. Following dark field microscopy, we perform computational image registration and analyses to compile the hue change from thousands of single gold nanoparticles acting as individual quantitative biosensors. This platform demonstrated a limit of detection of 10 pM with a dynamic range of at least 4 orders of magnitude in buffer solution, and the successful detection of c-reactive protein (CRP) in serum compatible with 3-tier clinical cutoffs within a 10-fold difference without the need for a blocking step. By analyzing the before-and-after status of each plasmonic sensor, our sensing scheme provides informative sensing capabilities with the flexibility to select a subset of nanoparticles with optimal performance based on their initial states. Hue comparisons within and among devices also render the platform tolerant to particle and device variation. In addition, the simplicity of the readout instrumentation based on optical imaging and the implementation of microfluidics make it promising for future adaptation into point-of-care systems.