Pixel-wise programmability enables dynamic high-SNR cameras for high-speed microscopy

High-speed widefield fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio (SNR) at high frame rates, limiting their ability to detect faint fluorescent events. Here we introduce an image sensor where each pixel has individually programmable sampling speed and phase, so that pixels can be arranged to simultaneously sample at high speed with a high SNR. In high-speed voltage imaging experiments, our image sensor significantly increases the output SNR compared to a low-noise scientific CMOS camera (~2–3 folds). This SNR gain enables the detection of weak neuronal action potentials and subthreshold activities missed by the standard scientific CMOS cameras. Our proposed camera with flexible pixel exposure configurations offers versatile sampling strategies to improve signal quality in various experimental conditions.