Optics-Free Chip-Scale Intraoperative Imaging Using NIR-Excited Upconverting Nanoparticles

Abstract

Here we present an optics-free CMOS image sensor that incorporates a novel time-gated dual-photodiode pixel design to allow filter- and lens-less image acquisition of near-infrared-excited (NIR-excited) upconverting nanoparticles. Recent biomedical advances have highlighted the benefits of NIR excitation, but NIR interaction with silicon has remained a challenge, even with high-performance optical blocking filters. Using a secondary diode and a dual-photodiode design, this sensor is able to remove the 100s of mV of NIR background on pixels and bring it down to single-digit mV level, nearing its noise floor of 2.2 mV rms, not achievable with any optical filter. Non-linear effects of background cancellation using the diode pair has been mitigated using an initial one-time pixel-level curve fitting and calibration in a post-processing setting. This imager comprises a highly linear 11 fF metal-oxide-metal (MOM) capacitor and includes integrated angle-selective gratings to reject oblique light and enhance sharpness. Each pixel also includes two distinct correlated double sampling schemes, to remove low frequency flicker noise and systematic offset in the datapath. We demonstrate the performance of this imager using pulsed NIR-excited upconverting nanoparticles on standard United-States-Air-Force (USAF) resolution targets and achieve an SNR of 15 dB, while keeping NIR background below 6 mV. This 36-by-80-pixel array measures only 2.3 mm by 4.8 mm and can be thinned down to 25 µm, allowing it to become surgically compatible with intraoperative instruments and equipment, while remaining optics-free.