Label-free chip-based evanescent light scattering super-resolution and superior-contrast optical microscopy (cELS)

Chip-based Evanescent Light Scattering (cELS) utilizes the multiple modes of a high-index contrast optical waveguide for near-field illumination of unlabeled samples, thereby repositioning the highest spatial frequencies of the sample into the far-field. The multiple modes scattering off the sample with different phase differences is engineered to have random spatial distributions within the integration time of the camera, mitigating the coherent speckle noise. This enables label-free superior-contrast imaging of weakly scattering nanosized specimens such as extra-cellular vesicles (EVs) and liposomes, dynamics of living HeLa cells etc. The article explains and validates experimentally the physics behind cELS by demonstrating a multi-moded straight waveguide as a partially coherent light source. For isotropic super-resolution, spatially incoherent light engineered via multiple-arms waveguide chip and intensity-fluctuation based algorithms are used. The proof-of-concept results are demonstrated on 100 nm polystyrene beads and resolution improvement of close to 2X is shown. cELS also realizes (2-10)X more contrast as opposed to conventional imaging techniques. In addition, cELS platform is miniaturized and enables large field-of-view imaging compared to state of the art label-free techniques. cELS holds a potential for label-free super-resolution imaging of nanosized biological specimens at high-throughput.