A CMOS In-Pixel CTIA High-Sensitivity Fluorescence Imager

Traditionally, charge-coupled device (CCD)-based image sensors have held sway over the field of biomedical imaging. Complementary metal-oxide semiconductor (CMOS)-based imagers so far lack sensitivity leading to poor low-light imaging. Certain applications including our work on animal-mountable systems for imaging in awake and unrestrained rodents require the high sensitivity and image quality of CCDs and the low power consumption, flexibility, and compactness of CMOS imagers. We present a 132 x 124 high sensitivity imager array with a 20.1-mu m pixel pitch fabricated in a standard 0.5-mu m CMOS process. The chip incorporates n-well/p-sub photodiodes, capacitive transimpedance amplifier (CTIA)-based in-pixel amplification, pixel scanners, and delta differencing circuits. The 5-transistor all-nMOS pixel interfaces with peripheral pMOS transistors for column-parallel CTIA. At 70 frames/s, the array has a minimum detectable signal of 4 nW/cm(2) at a wavelength of 450 nm while consuming 718 mu A from a 3.3-V supply. The peak signal-to-noise ratio (SNR) was 44 dB at an incident intensity of 1 mu W/cm(2). Implementing 4 x 4 binning allowed the frame rate to be increased to 675 frames/s. Alternately, sensitivity could be increased to detect about 0.8 nW/cm(2) while maintaining 70 frames/s. The chip was used to image single-cell fluorescence at 28 frames/s with an average SNR of 32 dB. For comparison, a cooled CCD camera imaged the same cell at 20 frames/s with an average SNR of 33.2 dB under the same illumination while consuming more than a watt.