Photonic resonator interferometric scattering microscopy

Abstract

Interferometric scattering microscopy is increasingly employed in biomedical research owing to its extraordinary capability of detecting nano-objects individually through their intrinsic elastic scattering. 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. 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. 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. An analytical model of the scattering process is discussed, followed by demonstration of virus and protein detection. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies.

Microscopies Enabled by Photonic Metamaterials

“…where is the resonant wavelength, is the energy confinement of the PC mode in the NP layer, is the refractive index of water and is the effective length of the evanescent field. This enhancement effect prediction exhibits good agreement with finite element method simulations [71]. Besides magnifying the scattered light, the benefits of incorporating a PC and small scatterer include improving the collection efficiency and attenuating the reference light.…”

“…At resonance, the PC only allows 1% of the incident light to transmit, eliminating the need for additional measures to attenuate the reference light. Compared to the traditional iSCAT, PRISM has shown approximately 5 times greater signal contrast for detection of gold nanoparticles in the 5-30 nm diameter range [71].…”

“…In this case, one should expect a higher signal intensity compared to solely measuring the scattered light on small particles. Combining the ideas behind SPRM and iSCAT, researchers have developed photonic resonator interferometric scattering microscopy (PRISM) [71], shown schematically in Figure 5. PRISM utilizes a metasurface to enhance scattering signals while mitigating the intensity penalty of small objects by measuring the interfered light.…”

Overcoming the limitations of COVID-19 diagnostics with nanostructures, nucleic acid engineering, and additive manufacturing

“…The above DDN-based approach can be applied to create SARS-CoV-2 virus particle capture probes by generating the requisite “binder” patterns with customized DNA architectures that afford maximum SARS-CoV-2 binding avidity via polyvalent, pattern-matching interactions. Importantly, instead of using a fluorophore, which is subject to photobleaching and delivers low signal-to-noise ratio, to report detection, we will utilize a newly invented form of biosensor microscopy called Photonic Resonator Interference Scattering Microscopy (PRISM) in which the photonic crystal surface amplifies laser light scattering from captured intact virions, enabling each one to be counted with high signal-to-noise ratio [44] . Such “digital” counting of intact virions offered by PRISM ensures high sensitivity, which is critical for the early detection of any virus.…”

Real-Time analysis of exosome secretion of single cells with single molecule imaging

“…This indicates that single molecule imaging is capable for single exosome detection. Recently, label free single molecule imaging approaches, such as interferometric scattering ( Young et al ., 2018 ), photonic crystal resonant scattering ( Li et al ., 2021 ) and plasmonic scattering imaging ( Zhang et al ., 2020 ; Zhang et al ., 2021 ), are developed for single molecule detection by measuring the natural Rayleigh scattering instead of the fluorescence emission. The label free single molecule imaging provides the quantitative measurement of the intrinsic molecular properties, such as molecular size and mass, allows the long-term precise monitoring of molecular interaction for kinetic analysis without the influence of photobleaching, photoblinking or limited excited-state lifetimes, and avoids the tracking error caused by nonuniform distribution of fluorescent labels.…”