Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution, and ease of integration into modern microscopy architectures. Recent advances in single-photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays composed of 25 fully independent and asynchronously operated pixels, both having fill factor of about 50% and specifically designed for being integrated into existing laser scanning microscopes. We used two different microelectronics technologies to fabricate our detectors: the first technology exhibiting very low noise (roughly 200 dark counts per second at room temperature) and the second one showing enhanced detection efficiency (more than 60% at a wavelength of 500 nm). Starting from the silicon-level device structures and moving towards the in-pixel and readout electronics description, we present performance assessments and comparisons between the two detectors. Images of a biological sample acquired after their integration into our custom image-scanning microscope finally demonstrate their exquisite on-field performance in terms of spatial resolution and contrast enhancement. We envisage that this work can trigger the development of a new class of SPAD-based detector arrays able to substitute the typical single-element sensor used in fluorescence laser scanning microscopy.

We present the design and the experimental characterization of a new InGaAs/InP single-photon avalanche diode (SPAD), with two different diameters: i) a 10 μm device, suitable for optical fiber-based quantum applications; ii) a 25 μm one, more appropriate for free-space applications. Compared to a previous generation, we improved the design of the double zinc diffusion and optimized the layer structure. We achieved low dark count rate, around 1 kcps and 4 kcps at 225 K and 5 V excess bias for 10 μm and 25 μm devices, respectively, and down to few tens of counts per seconds at 175 K for the 10 μm detector. At 5 V excess bias and 225 K temperature, both devices also show a high photon detection efficiency (33% at 1064 nm, 31% at 1310 nm and 25% at 1550 nm for the 10 μm SPAD). Afterpulsing has been measured with a custom readout integrated circuit, achieving very low probability values. Timing jitter is comparable to previous-generation devices.

We present the design and characterization of a large-area, fast-gated, all-digital single-photon detector with programmable active area, internal gate generator, and time-to-digital converter (TDC) with a built-in histogram builder circuit, suitable for performing high-sensitivity time-domain near-infrared spectroscopy (TD-NIRS) measurements when coupled with pulsed laser sources. We used a novel low-power differential sensing technique that optimizes area occupation. The photodetector is a time-gated digital silicon photomultiplier (dSiPM) with an 8.6-mm² photosensitive area, 37% fill-factor, and ~300 ps (20%-80%) gate rising edge, based on low-noise single-photon avalanche diodes (SPADs) and fabricated in 0.35-μm CMOS technology. The built-in TDC with a histogram builder has a least-significant-bit (LSB) of 78 ps and 128 time-bins, and the integrated circuit can be interfaced directly with a low-cost microcontroller with a serial interface for programming and readout. Experimental characterization demonstrated a temporal response as good as 300-ps full-width at half-maximum (FWHM) and a dynamic range >100 dB (thanks to the programmable active area size). This microelectronic detector paves the way for a miniaturized, stand-alone, multi-wavelength TD-NIRS system with an unprecedented level of integration and responsivity, suitable for portable and wearable systems.

Traditional paradigms for imaging rely on the use of a spatial structure, either in the detector (pixels arrays) or in the illumination (patterned light). Removal of the spatial structure in the detector or illumination, i.e., imaging with just a single-point sensor, would require solving a very strongly ill-posed inverse retrieval problem that to date has not been solved. Here, we demonstrate a data-driven approach in which full 3D information is obtained with just a single-point, single-photon avalanche diode that records the arrival time of photons reflected from a scene that is illuminated with short pulses of light. Imaging with single-point time-of-flight (temporal) data opens new routes in terms of speed, size, and functionality. As an example, we show how the training based on an optical time-of-flight camera enables a compact radio-frequency impulse radio detection and ranging transceiver to provide 3D images.

The single-photon timing and sensitivity performance and the imaging ability of asynchronous-readout single-photon avalanche diode (SPAD) array detectors have opened up enormous perspectives in fluorescence (lifetime) laser scanning microscopy (FLSM), such as super-resolution image scanning microscopy and high-information content fluorescence fluctuation spectroscopy. However, the strengths of these FLSM techniques depend on the many different characteristics of the detector, such as dark noise, photon-detection efficiency, after-pulsing probability, and optical cross talk, whose overall optimization is typically a trade-off between these characteristics. To mitigate this trade-off, we present, to our knowledge, a novel SPAD array detector with an active cooling system that substantially reduces the dark noise without significantly deteriorating any other detector characteristics. In particular, we show that lowering the temperature of the sensor to −15°C significantly improves the signal/noise ratio due to a 10-fold decrease in the dark count rate compared with room temperature. As a result, for imaging, the laser power can be decreased by more than a factor of three, which is particularly beneficial for live-cell super-resolution imaging, as demonstrated in fixed and living cells expressing green-fluorescent-protein-tagged proteins. For fluorescence fluctuation spectroscopy, together with the benefit of the reduced laser power, we show that cooling the detector is necessary to remove artifacts in the correlation function, such as spurious negative correlations observed in the hot elements of the detector, i.e., elements for which dark noise is substantially higher than the median value. Overall, this detector represents a further step toward the integration of SPAD array detectors in any FLSM system.

We present the design and characterization of a fully-integrated array of 16 × 16 Single-Photon Avalanche Diodes (SPADs) with fast-gating capabilities and 16 on-chip 6 ps time-to-digital converters, which has been embedded in a compact imaging module. Such sensor has been developed for Non-Line-Of-Sight imaging applications, which require: i) a narrow instrument response function, for a centimeter-accurate single-shot precision; ii) fast-gated SPADs, for time-filtering of directly reflected photons; iii) high photon detection probability, for acquiring faint signals undergoing multiple scattering events. Thanks to a novel multiple differential SPAD-SPAD sensing approach, SPAD detectors can be swiftly activated in less than 500 ps and the full-width at half maximum of the instrument response function is always less than 75 ps (60 ps on average). Temporal responses are consistently uniform throughout the gate window, showing just few picoseconds of time dispersion when 30 ns gate pulses are applied, while the differential non-linearity is as low as 250 fs. With a photon detection probability peak of 70% at 490 nm, a fill-factor of 9.6% and up to 1.6 ∙ 10⁸ photon time-tagging measurements per second, such sensor fulfills the demand for fully-integrated imaging solutions optimized for non-line-of-sight imaging applications, enabling to cut exposure times while also optimizing size, weight, power and cost, thus paving the way for further scaled architectures.