CMOS image sensors optimized for charged particle imaging applications, such as electron microscopy and particle physics, have been designed and characterized. These directly image charged particles without reliance on performance-degrading hybrid technologies such as the use of scintillating materials. Based on standard CMOS active pixel sensor (APS) technology, the sensor arrays uses an 8–20μm epitaxial layer that acts as a thicker sensitive region for the generation and collection of ionization electrons resulting from impinging high-energy particles. This results in a 100% fill factor and a far larger signal per incident electron than a standard CMOS photodiode could provide. A 512×550 pixels prototype has been fabricated and used extensively in an electron microscope, including having been used to take sample images. Temporal noise was measured to be 0.9mV RMS, and the dynamic range was 60dB. Power consumption at 70frames/s is 20mW. The full-width half-maximum of the collected ionization electron distribution was found to be 5.5μm, yielding a spatial resolution of approximately 2.3μm for individual incident electrons, and the modulation transfer function of the sensor at the Nyquist limit is to be 32%.