Abstract Label-free optical detection of nanometer-scale bioparticles is highly desirable for noninvasive biological studies but challenging due to the weak scattering signals that are difficult to distinguish from the illumination background. Interferometric scattering microscopy (iSCAT) has enabled high-sensitivity imaging by detecting the interference between the particle’s scattered light and a reference beam. However, enhancing the detection sensitivity and the image contrast for small particles continues to be a challenge in iSCAT. Here, we introduce meta-amplified dark-field interferometric scattering microscopy (MAD-iSCAT), which leverages a plasmonic metasurface to drastically enhance nanoparticle detection sensitivity in iSCAT. By employing a metasurface comprising sub-diffraction plasmonic meta-atom arrays, MAD-iSCAT generates bright radiation modes that intensely scatter light toward the far field in the presence of a detection nanoparticle, substantially amplifying the sensitivity. In the absence of a nanoparticle, the metasurface produces minimal background due to the dark collective mode, resulting in improved image contrast. We present a theoretical analysis of amplified interferometric imaging using designed metasurfaces and experimentally demonstrate enhancements in contrast and signal-to-noise ratio for detecting dielectric nanoparticles, exosomes, and proteins. Our approach offers broad applications in label-free biosensing and optical mass spectrometry, enabling significantly improved throughput and sensitivity.
Lee et al. (Fri,) studied this question.