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  4. A review of recent developments on CMOS single-photon avalanche diode-based cameras for biomedical time-resolved applications
 
conference paper

A review of recent developments on CMOS single-photon avalanche diode-based cameras for biomedical time-resolved applications

Bruschini, Claudio  
•
Charbon, Edoardo  
Berezin, Mikhail Y.
•
Raghavachari, Ramesh
2024
Progress in Biomedical Optics and Imaging - Proceedings of SPIE
15 Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications

All-solid-state time-resolved cameras based on CMOS single-photon avalanche diode (SPAD) arrays have made very significant advances since the fabrication of the first CMOS SPADs back in 2003. These natively digital sensors are now available in large formats and with timing resolutions of a few tens of picoseconds, when operated in time-correlated single-photon counting (TCPSC) mode, or nanoseconds in gated implementations. They are capable of virtually noiseless read-out at very high speed, up to a hundred kfps. Designers have explored a host of architectures over the years, ranging from reconfigurable linear arrays relying entirely on FPGA-based processing to kpx TCSPC systems with in-built timestamping and histogramming and reduced histogramming, all the way to Mpx cameras featuring built-in gates. State-of-the-art 3D-stacked sensors are also emerging, based both on fully-silicon and hybrid-technology solutions, with very high potential at the cost of demanding design and fabrication cycles. We will discuss the related challenges in terms of sensing and timing performance, data read-out and processing, before addressing several time-resolved applications of interest to the biomedical community, including shot-noise limited fluorescence lifetime imaging of endogenous and exogenous fluorophores, compressive Raman spectroscopy, and diffuse correlation spectroscopy. Thanks to unprecedented sensitivity, noise, and speed performance at sensor and system level, these applications have a considerable potential towards diagnostic and clinical uses, operating in real time. An outlook on chip-level hyperspectral and/or polarization enhancements will complete the review.

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