A Complementary Metal–Oxide–Semiconductor Image Sensor for On-Chip in Vitro and in Vivo Imaging of the Mouse Hippocampus

This paper describes the development of a complementary metal–oxide–semiconductor (CMOS) image sensor for in vitro and in vivo imaging of the hippocampus. The 176×144 pixel array image sensor is designed based on a modified three-transistor active pixel sensor circuit. Flexibility in readout for real-time imaging and wide dynamic range measurement is implemented using analog and digital output. A minimum light intensity detection level of 50 nW/cm² has been measured using the image sensor. A novel packaging method is developed to enable both in vitro and in vivo imaging. In this method, a color filter is applied onto the image sensor that selectively blocks excitation light transmittance to below -44 dB. The packaged device thickness measuring 350 µm, limits tissue damage during invasive imaging. Using the device, static images of the mouse brain slice and real time imaging of the hippocampus of a mouse are successfully demonstrated for the first time.