Single-photon avalanche diode (SPAD) arrays are solid-state detectors that offer imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at a very fast pace in the past 15 years, since its inception in standard CMOS technology in 2003. A host of architectures have been investigated, ranging from simpler implementations, based solely on off-chip data processing, to progressively “smarter” sensors including on-chip, or even pixel level, time-stamping and processing capabilities. As the technology has matured, a range of biophotonics applications have been explored, including (endoscopic) FLIM, (multibeam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman spectroscopy, NIROT and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.
Substantial improvements have been made in the past 15 years to imagers based on a device that acts like a 3-in-1 light particle detector, counter and stopwatch, furthering their potential use in biological imaging technologies. Claudio Bruschini of Switzerland’s École polytechnique fédérale de Lausanne and colleagues reviewed the developments in the use of single-photon avalanche diode (SPAD) arrays for biophotonics applications. They found that, while most SPAD imagers are still used in specialised research settings, significant improvements have been made to their sensitivity, reliability and reproducibility, and a host of sensor architectures have been explored. When a photon, the unit of light, hits a SPAD, it triggers an almost immediate electric current. Compact SPAD arrays implemented in standard CMOS electronic circuits can thus be used, for example, to measure in parallel the fluorescence lifetime of molecules tagged onto living cells and tissues, improving our ability to observe them. The review was completed by an outlook of this fascinating technology and an analysis of the most relevant challenges still lying ahead.