Hamamatsu Corp.’s ORCA-Flash2.8, a high-sensitivity digital camera based on the FL-280 scientific CMOS image sensor, is designed for low-light imaging at high frame rates. The FL-280 features 2.8 megapixels and a pixel size of 3.63 x 3.63 μm. Its wavelength sensitivity ranges from the UV to the visible, with peak sensitivity at ~450 to 500 nm and with >60% quantum efficiency. Typical readout noise is 3 e— rms, even at fast readout speeds. Producing low dark current, it requires cooling to only 5 °C. The camera’s readout speed ranges from 45 fps at full resolution to 1273 fps with subarray readout. Applications include ratio imaging; Förster resonance energy transfer, fluorescence in situ hybridization and total internal reflection fluorescence microscopy; real-time confocal microscopy; semiconductor inspection; and industrial imaging.