Chip-Scale Angle-Selective Imager for In Vivo Microscopic Cancer Detection.

We present an image sensor incorporating angle-selective gratings for resolution enhancement in contact imaging applications. Optical structures designed in the CMOS metal layers above each photodiode form the angle-selective gratings that limit the sensor angle of view to ±18 °, rejecting background light and deblurring the image. The imager is based on a high-gain capacitive transimpedance amplifier pixel using a custom 11fF MOM capacitor, achieving [Formula: see text] sensitivity. The pixel includes a leakage current minimization circuit to remove signal-dependent reset switch leakage and the corresponding dark current is [Formula: see text]. The resulting 4.7 mm by 2.25 mm sensor (80 by 36 pixels) is designed specifically for intraoperative cancer imaging in order to solve the pervasive challenge of identifying microscopic residual cancer foci in vivo, where they can be removed. We demonstrate imaging and detection of foci containing less than 200 cancer cells labeled with fluorescent biomarkers in 50 ms with signal-to-noise ratios greater than 15 dB and the detection of microscopic residual tumor in mice models. The absence of large optical elements enables extreme miniaturization, allowing manipulation within a small, morphologically complex, tumor cavity.