Abstract: A method of increasing the interference contrast in interferometric scattering optical microscopy. The method comprises providing a particle detection region comprising a chamber or channel having a boundary defined by one or more interfaces, illuminating a particle in the particle detection region with coherent light using an objective lens such that the light is reflected from the interface and scattered by the particle, capturing the reflected light and the scattered light using the objective lens, and providing the captured reflected and scattered light to an imaging device to image interference between the reflected light and the scattered light. The particle is illuminated by coherent light at an oblique angle to the interface.