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In this letter we present a compact photon detection module, based on an 8×8 array of single-photon avalanche diodes (SPADs). The use of a dedicated silicon technology for the fabrication of the sensors allows us to combine large active areas (50-μm diameter), high photon detection efficiency (49% at 550-nm wavelength) and low dark count rate. Thanks to a fully parallel architecture, the module provides voltage pulses synchronous to each photon detection for a maximum global count rate exceeding 1 Gcps. These properties makes the system suitable for operation in two different free-running modes. The first, suitable to acquire faint signals, allows multi-spot acquisitions and can be used to considerably reduce the measurement time in applications like single-molecule analysis. With the second it is possible to use all the pixels in a combined mode, to extend and move the dynamic range of the module to very high count rates and to attain number resolving capabilities.

In order to fulfill the requirements of many applications, we recently developed a new technology aimed at combining the advantages of traditional thin and thick silicon Single Photon Avalanche Diodes (SPAD). In particular we demonstrated single-pixel detectors with a remarkable improvement in the Photon Detection Efficiency in the red/near-infrared spectrum (e.g. 40% at 800nm) while maintaining a timing jitter better than 100ps. In this paper we discuss the limitations of such Red-Enhanced (RE) technology from the point of view of the fabrication of small arrays of SPAD and we propose modifications to the structure aimed at overcoming these issues. We also report the first preliminary experimental results attained on devices fabricated adopting the improved structure., Competing Interests: M. Ghioni discloses equity in Micro Photon Devices S.r.l. (MPD).

Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements.

Fluorescence correlation spectroscopy (FCS) is a well-established technique to study binding interactions or the diffusion of fluorescently labeled biomolecules in vitro and in vivo. Fast FCS experiments require parallel data acquisition and analysis which can be achieved by exploiting a multi-channel Single Photon Avalanche Diode (SPAD) array and a corresponding multi-input correlator. This paper reports a 32-channel FPGA based correlator able to perform 32 auto/cross-correlations simultaneously over a lag-time ranging from 10 ns up to 150 ms. The correlator is included in a 32 × 1 SPAD array module, providing a compact and flexible instrument for high throughput FCS experiments. However, some inherent features of SPAD arrays, namely afterpulsing and optical crosstalk effects, may introduce distortions in the measurement of auto- and cross-correlation functions. We investigated these limitations to assess their impact on the module and evaluate possible workarounds.

We propose a novel circuit for single photon avalanche diode (SPAD) current read-out, for photon timing applications. The circuit consists of a single transistor trans-impedance amplifier with a GHz bandwidth: the feedback loop fixes the SPAD anode voltage and allows us to obtain a high time resolution with a very high equivalent current threshold (almost 700 μA). The trans-impedance stage is followed by a low pass filter that reduces the crosstalk of other on-chip detectors and makes the designed structure suitable for multi-detector systems. The discrete components prototype presented in this letter achieves a state-of-art resolution of 34.4 ps FWHM, presents negligible crosstalk between the different pixels and opens the way for the development of an integrated structure with a large number of channels.

Nowadays, an increasing number of applications require high-performance analytical instruments capable to detect the temporal trend of weak and fast light signals with picosecond time resolution. The Time-Correlated Single-Photon Counting (TCSPC) technique is currently one of the preferable solutions when such critical optical signals have to be analyzed and it is fully exploited in biomedical and chemical research fields, as well as in security and space applications. Recent progress in the field of single-photon detector arrays is pushing research towards the development of high performance multichannel TCSPC systems, opening the way to modern time-resolved multi-dimensional optical analysis. In this paper we describe a new 8-channel high-performance TCSPC acquisition system, designed to be compact and versatile, to be used in modern TCSPC measurement setups. We designed a novel integrated circuit including a multichannel Time-to-Amplitude Converter with variable full-scale range, a D∕A converter, and a parallel adder stage. The latter is used to adapt each converter output to the input dynamic range of a commercial 8-channel Analog-to-Digital Converter, while the integrated DAC implements the dithering technique with as small as possible area occupation. The use of this monolithic circuit made the design of a scalable system of very small dimensions (95 × 40 mm) and low power consumption (6 W) possible. Data acquired from the TCSPC measurement are digitally processed and stored inside an FPGA (Field-Programmable Gate Array), while a USB transceiver allows real-time transmission of up to eight TCSPC histograms to a remote PC. Eventually, the experimental results demonstrate that the acquisition system performs TCSPC measurements with high conversion rate (up to 5 MHz/channel), extremely low differential nonlinearity (<0.04 peak-to-peak of the time bin width), high time resolution (down to 20 ps Full-Width Half-Maximum), and very low crosstalk between channels.

In order to fulfill the requirements of many applications, we recently developed a new technology aimed at combining the advantages of traditional thin and thick silicon Single Photon Avalanche Diodes (SPAD). In particular we demonstrated single-pixel detectors with a remarkable improvement in the Photon Detection Efficiency at the longer wavelengths (e.g. 40% at 800nm) while maintaining a timing jitter better than 100ps. In this paper we will analyze the factors the currently prevent the fabrication of arrays of SPADs by adopting such a Red-Enhanced (RE) technology and we will propose further modifications to the device structure that will enable the fabrication of high performance RE-SPAD arrays for photon timing applications.

Single-molecule Förster resonance energy transfer (smFRET) techniques are now widely used to address outstanding problems in biology and biophysics. In order to study freely diffusing molecules, current approaches consist in exciting a low concentration (<100 pM) sample with a single confocal spot using one or more lasers and detecting the induced single-molecule fluorescence in one or more spectrally- and/or polarization-distinct channels using single-pixel Single-Photon Avalanche Diodes (SPADs). A large enough number of single-molecule bursts must be accumulated in order to compute FRET efficiencies with sufficient statistics. As a result, the minimum timescale of observable phenomena is set by the minimum acquisition time needed for accurate measurements, typically a few minutes or more, limiting this approach mostly to equilibrium studies. Increasing smFRET analysis throughput would allow studying dynamics with shorter timescales. We recently demonstrated a new multi-spot excitation approach, employing a novel multi-pixel SPAD array, using a simplified dual-view setup in which a single 8-pixel SPAD array was used to collect FRET data from 4 independent spots. In this work we extend our results to 8 spots and use two 8-SPAD arrays to collect donor and acceptor photons and demonstrate the capabilities of this system by studying a series of doubly labeled dsDNA samples with different donor-acceptor distances ranging from low to high FRET efficiencies. Our results show that it is possible to enhance the throughput of smFRET measurements in solution by almost one order of magnitude, opening the way for studies of single-molecule dynamics with fast timescale once larger SPAD arrays become available.

In this paper we present an array of 48 Single Photon Avalanche Diodes (SPADs) specifically designed for multispot Single Molecule Analysis. The detectors have been arranged in a 12×4 square geometry with a pitch-to-diameter ratio of ten in order to minimize the collection of the light from non-conjugated excitation spots. In order to explore the trade-offs between the detectors' performance and the optical coupling with the experimental setup, SPADs with an active diameter of 25 and of 50µm have been manufactured. The use of a custom technology, specifically designed for the fabrication of the detectors, allowed us to combine a high photon detection efficiency (peak close to 50% at a wavelength of 550nm) with a low dark count rate compatible with true single molecule detection. In order to allow easy integration into the optical setup for parallel single-molecule analysis, the SPAD array has been incorporated in a compact module containing all the electronics needed for a proper operation of the detectors.

Single-molecule fluorescence spectroscopy of freely diffusing molecules in solution is a powerful tool used to investigate the properties of individual molecules. Single-Photon Avalanche Diodes (SPADs) are the detectors of choice for these applications. Recently a new type of SPAD detector was introduced, dubbed red-enhanced SPAD (RE-SPAD), with good sensitivity throughout the visible spectrum and with excellent timing performance. We report a characterization of this new detector for single-molecule fluorescence resonant energy transfer (smFRET) studies on freely diffusing molecules in a confocal geometry and alternating laser excitation (ALEX) scheme. We use a series of doubly-labeled DNA molecules with donor-to-acceptor distances covering the whole range of useful FRET values. Both intensity-based (μs-ALEX) and lifetime-based (ns-ALEX) measurements are presented and compared to identical measurements performed with standard thick SPADs. Our results demonstrate the great potential of this new detector for smFRET measurements and beyond.

Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level.

Emerged as a solid state alternative to photo multiplier tubes (PMTs), single-photon avalanche diodes (SPADs) are nowadays widely used in the field of single-photon timing applications. Custom technology SPADs assure remarkable performance, in particular a 10 counts/s dark count rate (DCR) at low temperature, a high photon detection efficiency (PDE) with a 50% peak at 550 nm and a 30 ps (full width at half maximum, FWHM) temporal resolution, even with large area devices, have been obtained. Over the past few years, the birth of novel techniques of analysis has led to the parallelization of the measurement systems and to a consequent increasing demand for the development of monolithic arrays of detectors. Unfortunately, the implementation of a multidimensional system is a challenging task from the electrical point of view; in particular, the avalanche current pick-up circuit, used to obtain the previously reported performance, has to be modified in order to enable high parallel temporal resolution, while minimizing the electrical crosstalk probability between channels. In the past, the problem has been solved by integrating the front-end electronics next to the photodetector, in order to reduce the parasitic capacitances and consequently the filtering action on the current signal of the SPAD, leading to an improvement of the timing jitter at higher threshold. This solution has been implemented by using standard complementary metal-oxide-semiconductor (CMOS) technologies, which, however, do not allow a complete control on the SPAD structure; for this reason the intrinsic performance of CMOS SPADs, such as DCR, PDE, and afterpulsing probability, are worse than those attainable with custom detectors. In this paper, we propose a pixel architecture, which enables the development of custom SPAD arrays in which every channel maintains the performance of the best single photodetector. The system relies on the integration of the timing signal pick-up circuit next to the photodiode, achieved by modifying the technological process flow used for the fabrication of the custom SPAD. The pixel is completed by an external standard CMOS active quenching circuit, which assures stable timing performance at quite high count rate (>1 MHz).

Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for extracting distance information between two fluorophores (a donor and acceptor dye) on a nanometer scale. This method is commonly used to monitor binding interactions or intra- and intermolecular conformations in biomolecules freely diffusing through a focal volume or immobilized on a surface. The diffusing geometry has the advantage to not interfere with the molecules and to give access to fast time scales. However, separating photon bursts from individual molecules requires low sample concentrations. This results in long acquisition time (several minutes to an hour) to obtain sufficient statistics. It also prevents studying dynamic phenomena happening on time scales larger than the burst duration and smaller than the acquisition time. Parallelization of acquisition overcomes this limit by increasing the acquisition rate using the same low concentrations required for individual molecule burst identification. In this work we present a new two-color smFRET approach using multispot excitation and detection. The donor excitation pattern is composed of 4 spots arranged in a linear pattern. The fluorescent emission of donor and acceptor dyes is then collected and refocused on two separate areas of a custom 8-pixel SPAD array. We report smFRET measurements performed on various DNA samples synthesized with various distances between the donor and acceptor fluorophores. We demonstrate that our approach provides identical FRET efficiency values to a conventional single-spot acquisition approach, but with a reduced acquisition time. Our work thus opens the way to high-throughput smFRET analysis on freely diffusing molecules.

Light is strictly connected with life, and its presence is fundamental for any living environment. Thus, many biological mechanisms are related to light interaction or can be evaluated through processes involving energy exchange with photons. Optics has always been a precious tool to evaluate molecular and cellular mechanisms, but the discovery of lasers opened new pathways of interactions of light with biological matter, pushing an impressive development for both therapeutic and diagnostic applications in biomedicine. The use of light in different fields has become so widespread that the word photonics has been utilized to identify all the applications related to processes where the light is involved. The photonics area covers a wide range of wavelengths spanning from soft X-rays to mid-infrared and includes all devices related to photons as light sources, optical fibers and light guides, detectors, and all the related electronic equipment. The recent use of photons in the field of telecommunications has pushed the technology toward low-cost, compact, and efficient devices, making them available for many other applications, including those related to biology and medicine where these requirements are of particular relevance. Moreover, basic sciences such as physics, chemistry, mathematics, and electronics have recognized the interdisciplinary need of biomedical science and are translating the most advanced researches into these fields. The Politecnico school has pioneered many of them,and this article reviews the state of the art of biomedical research at the Politecnico in the field internationally known as biophotonics.

Background: cancer-testis (CT) antigens, frequently expressed in human germline cells but not in somatic tissues, may become aberrantly reexpressed in different cancer types. The aim of this study was to investigate the expression of CT antigens in breast cancer., Patients and Methods: a total of 100 selected invasive breast cancers, including 50 estrogen receptor (ER) positive/HER2 negative and 50 triple negative (TN), were examined for NY-ESO-1 and MAGE-A expression by immunohistochemistry., Results: a significantly higher expression of MAGE-A and NY-ESO-1 was detected in TN breast cancers compared with ER-positive tumors (P = 0.04). MAGE-A expression was detected in 13 (26%) TN cancers compared with 5 (10%) ER-positive tumors (P = 0.07). NY-ESO-1 expression was confirmed in nine (18%) TN tumor samples compared with two (4%) ER-positive tumors., Conclusions: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

We present a novel approach to high-throughput Fluorescence Correlation Spectroscopy (FCS) which enables us to obtain one order of magnitude improvement in acquisition time. Our approach utilizes a liquid crystal on silicon spatial light modulator to generate dynamically adjustable focal spots, and uses an eight-pixel monolithic single-photon avalanche photodiode array. We demonstrate the capabilities of this system by showing FCS of Rhodamine 6G under various viscosities, and by showing that, with proper calibration of each detection channel, one order of magnitude improvement in acquisition speed is obtained. More generally, our approach will allow higher throughput single-molecule studies to be performed.

Over the past years an always growing interest has arisen about the measurement technique of time-correlated single photon counting TCSPC), since it allows the analysis of extremely fast and weak light waveforms with a picoseconds resolution. Consequently, many applications exploiting TCSPC have been developed in several fields such as medicine and chemistry. Moreover, the development of multianode PMT and of single photon avalanche diode arrays led to the realization of acquisition systems with several parallel channels to employ the TCSPC technique in even more applications. Since TCSPC basically consists of the measurement of the arrival time of a photon, the most important part of an acquisition chain is the time measurement block, which must have high resolution and low differential nonlinearity, and in order to realize multidimensional systems, it has to be integrated to reduce both cost and area. In this paper we present a fully integrated time-to-amplitude converter, built in 0.35 μm Si-Ge technology, characterized by a good time resolution (60 ps), low differential nonlinearity (better than 3% peak to peak), high counting rate (16 MHz), low and constant power dissipation (40 mW), and low area occupation (1.38×1.28 mm(2)).

Solution-based single-molecule fluorescence spectroscopy is a powerful new experimental approach with applications in all fields of natural sciences. The basic concept of this technique is to excite and collect light from a very small volume (typically femtoliter) and work in a concentration regime resulting in rare burst-like events corresponding to the transit of a single-molecule. Those events are accumulated over time to achieve proper statistical accuracy. Therefore the advantage of extreme sensitivity is somewhat counterbalanced by a very long acquisition time. One way to speed up data acquisition is parallelization. Here we will discuss a general approach to address this issue, using a multispot excitation and detection geometry that can accommodate different types of novel highly-parallel detector arrays. We will illustrate the potential of this approach with fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence measurements obtained with different novel multipixel single-photon counting detectors.

Solution-based single-molecule spectroscopy and fluorescence correlation spectroscopy (FCS) are powerful techniques to access a variety of molecular properties such as size, brightness, conformation, and binding constants. However, this is limited to low concentrations, which results in long acquisition times in order to achieve good statistical accuracy. Data can be acquired more quickly by using parallelization. We present a new approach using a multispot excitation and detection geometry made possible by the combination of three powerful new technologies: (i) a liquid crystal spatial light modulator to produce multiple diffraction-limited excitation spots; (ii) a multipixel detector array matching the excitation pattern and (iii) a low-cost reconfigurable multichannel counting board. We demonstrate the capabilities of this technique by reporting FCS measurements of various calibrated samples as well as single-molecule burst measurements.

Time correlated single photon counting techniques allow in depth examinations of very important chemical and biological processes involving complex interactions of biomolecules. Understanding of these processes is of the utmost importance to address vital medical issues such as the origin and growth of tumors. Modern developments of fluorescence analysis techniques require compact, low cost, and high performance instrumentation, and a major path to these goals is the successful integration of the electronics. In this paper we present a fully monolithic time to amplitude converter, built in standard 0.35 microm CMOS technology, characterized by good time resolution (60 ps), low differential nonlinearity (better than 0.5% rms), short dead time (80 ns), low power dissipation (60 mW), and low area occupation (1.8x1.4 mm(2)).

A novel microchip electrophoresis instrument based on single-photon avalanche diodes was used for the molecular characterization of mutations in disease genes. The identification of the main mutation causing cystic fibrosis, named DeltaF508, by the Amplification Refractory Mutation System was used to validate the technology. In our implemented protocol the wild-type and mutant allele-specific primers are labeled with Cy5 and Cy5.5, respectively. The protocol enables the amplification of the DNA sample in a single PCR. The genotype was deduced from the fluorescence of the amplicons run in the CE microchip. Validation on 15 DNA samples from either homozygous wild-type or heterozygous and homozygous mutated control subjects proved the complete reliability of the system, thus confirming its high diagnostic potential.

One of the main issues of Single Photon Avalanche Diode arrays is optical crosstalk. Since its intensity increases with reducing the distance between devices, this phenomenon limits the density of integration within arrays. In the past optical crosstalk was ascribed essentially to the light propagating from one detector to another through direct optical paths. Accordingly, reflecting trenches between devices were proposed to prevent it, but they proved to be not completely effective. In this paper we will present experimental evidence that a significant contribution to optical crosstalk comes from light reflected internally off the bottom of the chip, thus being impossible to eliminate it completely by means of trenches. We will also propose an optical model to predict the dependence of crosstalk on the distance between devices.

We present a new photon timing circuit that achieves a time resolution of 35 ps full width at half maximum with single photon avalanche diodes having active area diameters up to 200 microm. The timing circuit is based on a double avalanche current sensing network that makes it particularly suited to operation at high photon counting rates. Thanks to its self-adjusting capabilities, no trimming is needed even when changing the photodetector operating conditions over a wide range.

This article reports a complete characterization of single photon avalanche diodes (SPADs) at temperatures down to 120 K. We show that deep cooling of the device by means of a compact liquid-nitrogen Dewar brings several advantages, such as extremely low dark counting rates (down to 1 counts/s), better time resolution, and higher quantum efficiency in the visible range. By using a special current pick-off circuit, we achieved a time resolution of 20 ps full width at half maximum at 120 K for a 50 mum diameter SPAD. Afterpulsing effects are avoided by using a sufficiently long hold-off time (microseconds).

Modern techniques for DNA and protein analysis and separation rely on measurements of LIF and face a trend toward employing progressively smaller samples. The currently employed detectors that provide the required ultrahigh sensitivity, e.g. photomultiplier tubes (PMTs), are bulky and/or costly and delicate, whereas a key issue for the development of compact and economical instruments is the availability of miniaturized, inexpensive, and ultrasensitive photodetectors. The planar epitaxial silicon single-photon avalanche diodes (SPADs) combine the typical advantages of microelectronics (miniaturization, ruggedness, low voltage, low power, low cost, etc.) with high sensitivity, even better than that of PMTs. The suitability of such SPADs to microchip CE has been here ascertained by developing a new apparatus with dual-wavelength LIF detection. The apparatus has been experimented in studies on the EOF suppression and on the coating stability and tested in rapid sizing of DNA fragments. The experimental results obtained in the separation of Cy5-labeled oligonucleotide demonstrate sensitivity better than 3 pM, which corresponds to less than 100 fluorescent molecules in the 50 pL illuminated volume.

Caveolin-1 (Cav-1) is the main protein in caveolae, and serves as a scaffolding protein onto which many classes of signalling molecules are assembled. Through interaction with proto-oncogene products, Cav-1 may suppress cell proliferation; or when phosphorylated, may also stimulate cell growth. The aim of this study was to determine Cav-1 expression in human fetal tissues, tissues composed of cells undergoing growth and differentiation processes which require a nurturing environment provided by transmembrane vesicular transport. By using immunohistochemistry, Cav-1 was detected in several fetal tissues during mid- and late gestation (from 14 to 39 weeks). The protein was present in adipocytes, endothelial cells, smooth muscle fibers and in a number of sites with a pattern of distribution similar to that of the adult. Intriguingly, a positive immunoreaction for Cav-1 was also noticed in tissues, such as the urothelium, which normally do not express this protein in adulthood. This unexpected pattern of Cav-1 in human fetus may predict novel roles for Cav-1 during fetal development.

A new integrated active quenching circuit (i-AQC) designed in a standard CMOS process is presented, capable of operating with any available single photon avalanche diode (SPAD) over wide temperature range. The circuit is suitable for attaining high photon timing resolution also with wide-area SPADs. The new i-AQC integrates the basic active-quenching loop, a patented low-side timing circuit comprising a fast pulse pick-up scheme that substantially improves time-jitter performance, and a novel active-load passive quenching mechanism (consisting of a current mirror rather than a traditional high-value resistor) greatly improves the maximum counting rate. The circuit is also suitable for portable instruments, miniaturized detector modules and SPAD-array detectors. The overall features of the circuit may open the way to new developments in diversified applications of time-correlated photon counting in life sciences and material sciences.

Avalanche photodiodes, which operate above the breakdown voltage in Geiger mode connected with avalanche-quenching circuits, can be used to detect single photons and are therefore called singlephoton avalanche diodes SPAD's. Circuit configurations suitable for this operation mode are critically analyzed and their relative merits in photon counting and timing applications are assessed. Simple passive-quenching circuits (PQC's), which are useful for SPAD device testing and selection, have fairly limited application. Suitably designed active-quenching circuits (AQC's) make it possible to exploit the best performance of SPAD's. Thick silicon SPAD's that operate at high voltages (250-450 V) have photon detection efficiency higher than 50% from 540- to 850-nm wavelength and still ~3% at 1064 nm. Thin silicon SPAD's that operate at low voltages (10-50 V) have 45% efficiency at 500 nm, declining to 10% at 830 nm and to as little as 0.1% at 1064 nm. The time resolution achieved in photon timing is 20 ps FWHM with thin SPAD's; it ranges from 350 to 150 ps FWHM with thick SPAD's. The achieved minimum counting dead time and maximum counting rate are 40 ns and 10 Mcps with thick silicon SPAD's, 10 ns and 40 Mcps with thin SPAD's. Germanium and III-V compound semiconductor SPAD's extend the range of photon-counting techniques in the near-infrared region to at least 1600-nm wavelength.