Prism-based TIRFM uses single reflection of the excitation beam, which goes in and out through opposite facets of the dovetail prism. The prism is in optical contact with 1-mm TIRF slide. TIRF surface of the slide is imaged through thin layer of solution and optical window in the fluidics block, which creates closed flow cell at the surface of TIRF slide. Prism-based TIRFM is designed for use with dry objectives.