A rapid readout for many single plasmonic nanoparticles using dark-field microscopy and digital color analysis

The integration of plasmonic nanoparticles into biosensors has the potential to increase the sensitivity and dynamic range of detection, through the use of single nanoparticle assays. The analysis of the localized surface plasmon resonance (LSPR) of plasmonic nanoparticles has allowed the limit of detection of biosensors to move towards single molecules. However, due to complex equipment or slow analysis times, these technologies have not been implemented for point-of-care detection. Herein, we demonstrate an advancement in LSPR analysis by presenting a technique, which utilizes an inexpensive CMOS-equipped digital camera and a dark-field microscope, that can analyse the 2k.ma, of over several thousand gold nanospheres in less than a second, without the use of a spectrometer. This improves the throughput of single particle spectral analysis by enabling more nano particles to be probed and in a much shorter time. This technique has been demonstrated through the detection of interleukin-6 through a core-satellite binding assay. We anticipate that this technique will aid in the development of high-throughput, multiplexed and point-of-care single nanoparticle biosensors.