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

Jie Zhang (), Jonathan Newman, Zeguan Wang, Yong Qian, Pedro Feliciano-Ramos, Wei Guo, Takato Honda, Zhe Sage Chen, Changyang Linghu, Ralph Etienne-Cummings, Eric Fossum, Edward Boyden and Matthew Wilson
Additional contact information
Jie Zhang: MIT
Jonathan Newman: MIT
Zeguan Wang: MIT
Yong Qian: MIT
Pedro Feliciano-Ramos: MIT
Wei Guo: MIT
Takato Honda: MIT
Zhe Sage Chen: NYU Grossman School of Medicine
Changyang Linghu: University of Michigan
Ralph Etienne-Cummings: Johns Hopkins University
Eric Fossum: Dartmouth College
Edward Boyden: MIT
Matthew Wilson: MIT

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract High-speed wide-field fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio 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 signal-to-noise ratio. In high-speed voltage imaging experiments, our image sensor significantly increases the output signal-to-noise ratio compared to a low-noise scientific CMOS camera (~2–3 folds). This signal-to-noise ratio gain enables the detection of weak neuronal action potentials and subthreshold activities missed by the standard scientific CMOS cameras. Our camera with flexible pixel exposure configurations offers versatile sampling strategies to improve signal quality in various experimental conditions.

Date: 2024
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DOI: 10.1038/s41467-024-48765-5

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