In essence, the detected signal is generated by the interference between the object-scattered light and the background reference light, which scales linearly with the object size instead of the square dependence for pure scattering. Demonstrations of biomolecular and nanomaterial mass determination 1, 2, sample heterogeneity analysis 3, and dynamic molecular binding characterization 4 have been achieved recently by interferometric imaging. The detection and characterization of individual (bio)nano-objects directly in solution, across length scales that range from tens to hundreds of nanometers, with the high spatiotemporal resolution, and without the need for extrinsic labels or elaborate procedural steps, is the central utility of interferometric scattering microscopy. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies. An analytical model of the scattering process is discussed, followed by demonstration of virus and protein detection. Importantly, the scattered photons assume the wavevectors delineated 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 cm −2. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create a large intensity contrast.

To significantly improve the signal-to-noise ratio without increasing illumination intensity, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a dielectric photonic crystal (PC) resonator is utilized as the sample substrate. Interferometric scattering microscopy is increasingly employed in biomedical research owing to its extraordinary capability of detecting nano-objects individually through their intrinsic elastic scattering.

Crystal disk mark 6 sample results