Single-photon avalanche diode imagers in biophotonics: review and outlook

Abstract

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.

Quantum correlation measurement with single photon avalanche diode arrays

“…The number of pixels in this work was chosen to best fit ISM [14]. However, the compatibility of the manufacturing process of on-chip SPAD arrays with CMOS technology offers an affordable path to scale-up the number of pixels to hundreds, with small changes to the design and performance [10]. The combination of scalability with low DCR can offer a higher PNR dynamic range than any of the current methods.…”

Wide-field time-gated SPAD imager for phasor-based FLIM applications

“…Theoretically, with a very bright calibration sample (or a calibration sample measured using a long integration time), the F-value would scale as described by Eq. (13) and thus decrease as the measured lifetime increases.…”

Time-Gated Single-Photon Detection in Time-Domain Diffuse Optics: A Review

“…TG modality can be applied to FLIM: a moving gate and a simple counter allow to measure the lifetime. This simple scheme enables the use of large area detectors [163]. Furthermore, the TG capability can be used in order to reject the excitation signal without using a spectral filter by exploiting the different timing between excitation and fluorescence signals.…”

“…Furthermore, the TG capability can be used in order to reject the excitation signal without using a spectral filter by exploiting the different timing between excitation and fluorescence signals. Similar detection architectures used for FLIM can be applied also in Raman spectroscopies [163].…”