Chip-scale fluorescence imager for in vivo microscopic cancer detection

Abstract

Modern cancer treatment faces the pervasive challenge of identifying microscopic cancer foci in vivo, but no imaging device exists with the ability to identify these cells intraoperatively, where they can be removed. We introduce a novel CMOS sensor that identifies foci of less than 200 cancer cells labeled with fluorescent biomarkers in 50ms. The sensor's miniature size enables manipulation within a small, morphologically complex, tumor cavity. Recognizing that focusing optics traditionally used in fluorescence imagers present a barrier to miniaturization, we integrate stacked CMOS metal layers above each photodiode to form angle-selective gratings, rejecting background light and deblurring the image. A high-gain capacitive transimpedance amplifier based pixel with 8.2V/s per pW sensitivity and a dark current minimization circuit enables rapid detection of microscopic clusters of 100s of tumor cells with minimal error.