Photonic resonator interferometric scattering microscopy

Interferometric scattering microscopy is a newly emerging alternative to fluorescence microscopy in biomedical research and diagnostic testing due to its ability to detect nano-objects such as individual proteins, extracellular vesicles, and virions individually through their intrinsic elastic light scattering. To improve the signal-to-noise ratio, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a photonic crystal (PC) resonator is used as the sample substrate. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create intensity contrast. Importantly, the scattered photons assume the wavevectors defined by PC's photonic band structure, resulting in the ability to utilize a non-immersion objective without significant loss at illumination density as low as 25 W/cm2. We demonstrate virus and protein detection, including highly selective capture and counting of intact pseudotype SARS-CoV-2 from saliva with sensitivity equivalent to conventional nucleic acid tests. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies, and as a single step, room temperature, and rapid viral detection technology.