Abstract
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 36pixels) 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.
Highlights
M INIATURIZED optical imaging systems are critical for both consumer and medical applications
These imagers generally fall into two categories: those that are capable of performing in vivo imaging ([8], [9]) and those that have been designed for lab-on-a-chip applications ([4], [10], [11])
The former sensors are only capable of imaging single points or large areas of tumor tissue and do not have sufficient resolution to image microscopic residual cancer consisting of foci containing only hundreds of cancer cells
Summary
M INIATURIZED optical imaging systems are critical for both consumer and medical applications. One of the high impact applications for chip-scale angle-selective contact imagers is the successful treatment of early stage cancers. This treatment requires the surgical removal of microscopic cancer foci from a background of 108 to 109 physically similar healthy cells. Other chip-scale sensors requiring microfluidics or tissue samples need handling that is incompatible with the constraints of surgical procedures [4], [10], [11] Some works, such as [10], have used fiber optic faceplates to reduce the angle of incident.
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