Fast fully-integrated front-end circuit to overcome pile-up limits in time-correlated single photon counting with single photon avalanche diodes

Time-Correlated Single Photon Counting (TCSPC) is an essential tool in many scientific applications, where the recording of optical pulses with picosecond precision is required. Unfortunately, a key issue has to be faced: distortion phenomena can affect TCSPC experiments at high count rates. In order to avoid this problem, TCSPC experiments have been commonly carried out by limiting the maximum operating frequency of a measurement channel below 5% of the excitation frequency, leading to a long acquisition time. Recently, it has been demonstrated that matching the detector dead time to the excitation period allows to keep distortion around zero regardless of the rate of impinging photons. This solution paves the way to unprecedented measurement speed in TCSPC experiments. In this scenario, the front-end circuits that drive the detector play a crucial role in determining the performance of the system, both in terms of measurement speed and timing performance. Here we present two fully integrated front-end circuits for Single Photon Avalanche Diodes (SPADs): a fast Active Quenching Circuit (AQC) and a fully-differential current pick-up circuit. The AQC can apply very fast voltage variations, as short as 1.6ns, to reset external custom-technology SPAD detectors. A fast reset, indeed, is a key parameter to maximize the measurement speed. The current pick-up circuit is based on a fully differential structure which allows unprecedented rejection of disturbances that typically affect SPAD-based systems at the end of the dead time. The circuit permits to sense the current edge resulting from a photon detection with picosecond accuracy and precision even a few picoseconds after the end of the dead time imposed by the AQC. This is a crucial requirement when the system is operated at high rates. Both circuits have been deeply characterized, especially in terms of achievable measurement speed and timing performance

High-efficiency integrated readout circuit for single photon avalanche diode arrays in fluorescence lifetime imaging

In recent years, lifetime measurements by means of the Time Correlated Single Photon Counting (TCSPC) technique have led to a significant breakthrough in medical and biological fields. Unfortunately, the many advantages of TCSPC-based approaches come along with the major drawback of a relatively long acquisition time. The exploitation of multiple channels in parallel could in principle mitigate this issue, and at the same time it opens the way to a multi-parameter analysis of the optical signals, e.g., as a function of wavelength or spatial coordinates. The TCSPC multichannel solutions proposed so far, though, suffer from a tradeoff between number of channels and performance, and the overall measurement speed has not been increased according to the number of channels, thus reducing the advantages of having a multichannel system. In this paper, we present a novel readout architecture for bi-dimensional, high-density Single Photon Avalanche Diode (SPAD) arrays, specifically designed to maximize the throughput of the whole system and able to guarantee an efficient use of resources. The core of the system is a routing logic that can provide a dynamic connection between a large number of SPAD detectors and a much lower number of high-performance acquisition channels. A key feature of our smart router is its ability to guarantee high efficiency under any operating condition

High-voltage integrated active quenching circuit for single photon count rate up to 80 Mcounts/s

Single photon avalanche diodes (SPADs) have been subject to a fast improvement in recent years. In particular, custom technologies specifically developed to fabricate SPAD devices give the designer the freedom to pursue the best detector performance required by applications. A significant breakthrough in this field is represented by the recent introduction of a red enhanced SPAD (RE-SPAD) technology, capable of attaining a good photon detection efficiency in the near infrared range (e.g. 40% at a wavelength of 800 nm) while maintaining a remarkable timing resolution of about 100ps full width at half maximum. Being planar, the RE-SPAD custom technology opened the way to the development of SPAD arrays particularly suited for demanding applications in the field of life sciences. However, to achieve such excellent performance custom SPAD detectors must be operated with an external active quenching circuit (AQC) designed on purpose. Next steps toward the development of compact and practical multichannel systems will require a new generation of monolithically integrated AQC arrays. In this paper we present a new, fully integrated AQC fabricated in a high-voltage 0.18 µm CMOS technology able to provide quenching pulses up to 50 Volts with fast leading and trailing edges. Although specifically designed for optimal operation of RE-SPAD devices, the new AQC is quite versatile: it can be used with any SPAD detector, regardless its fabrication technology, reaching remarkable count rates up to 80 Mcounts/s and generating a photon detection pulse with a timing jitter as low as 119 ps full width at half maximum. The compact design of our circuit has been specifically laid out to make this IC a suitable building block for monolithically integrated AQC arrays

Improving the counting efficiency in time-correlated single photon counting experiments by dead-time optimization

Time-Correlated Single Photon Counting (TCSPC) has been long recognized as the most sensitive method for fluorescence lifetime measurements, but often requiring “long” data acquisition times. This drawback is related to the limited counting capability of the TCSPC technique, due to pile-up and counting loss effects. In recent years, multi-module TCSPC systems have been introduced to overcome this issue. Splitting the light into several detectors connected to independent TCSPC modules proportionally increases the counting capability. Of course, multi-module operation also increases the system cost and can cause space and power supply problems. In this paper, we propose an alternative approach based on a new detector and processing electronics designed to reduce the overall system dead time, thus enabling efficient photon collection at high excitation rate. We present a fast active quenching circuit for single-photon avalanche diodes which features a minimum dead time of 12.4 ns. We also introduce a new Time-to-Amplitude Converter (TAC) able to attain extra-short dead time thanks to the combination of a scalable array of monolithically integrated TACs and a sequential router. The fast TAC (F-TAC) makes it possible to operate the system towards the upper limit of detector count rate capability (∼80 Mcps) with reduced pile-up losses, addressing one of the historic criticisms of TCSPC. Preliminary measurements on the F-TAC are presented and discussed

A physically based model for evaluating the Photon DetectionEfficiency and the Temporal Response of SPAD detectors

We present a physically-based model aimed at calculating the Photon Detection Efficiency (PDE) and the temporal response of a Single-Photon Avalanche Diode (SPAD) with a given structure. A comparison between simulation and experimental results is also reported in order to confirm the model accuracy

High-speed and low-distortion solution for time-correlated single photon counting measurements: A theoretical analysis

In this paper, we describe a novel solution to increase the speed of Time-Correlated Single Photon Counting (TCSPC) measurements by almost an order of magnitude while providing, in principle, zero distortion regardless of the experimental conditions. Typically, the relatively long dead time associated with the conversion electronics requires a proper tune of the excitation power in order to avoid distortions of the reconstructed waveform due to pileup and counting loss. As a result, the maximum operating rate of a TCSPC channel is now limited between 1% and 5% of the excitation frequency, thus leading to relatively long acquisition times. We show that negligible distortion (below 1%) is guaranteed if the dead time associated with the converter is kept below the dead time of the detector, and at the same time the detector dead time is matched to the duration of the excitation period. In this way, unprecedented high-speed operation is possible. In this paper, we provide a theoretical analysis of the technique, including the main non-idealities which are introduced by a generic physical implementation. The results are supported by both numerical simulations and analytical calculations

Note: Fully integrated active quenching circuit achieving 100 MHz count rate with custom technology single photon avalanche diodes

The minimization of Single Photon Avalanche Diodes (SPADs) dead time is a key factor to speed up photon counting and timing measurements. We present a fully integrated Active Quenching Circuit (AQC) able to provide a count rate as high as 100 MHz with custom technology SPAD detectors. The AQC can also operate the new red enhanced SPAD and provide the timing information with a timing jitter Full Width at Half Maximum (FWHM) as low as 160 ps

SPAD array detectors for parallel photon timing applications

Over the past few years there has been a growing interest in monolithic arrays of single photon avalanche diodes (SPAD) for spatially resolved detection of faint ultrafast optical signals. SPADs implemented in CMOS-compatible planar technologies offer the typical advantages of microelectronic devices (small size, ruggedness, low voltage, low power, etc.). Furthermore, they have inherently higher photon detection efficiency than PMTs and are able to provide, beside sensitivities down to single-photons, very high acquisition speeds. In order to make SPAD array more and more competitive in time-resolved application it is necessary to face problems like electrical crosstalk between adjacent pixels

48-spot single-molecule FRET setup with periodic acceptor excitation

Single-molecule Förster resonance energy transfer (smFRET) allows measuring distances between donor and acceptor fluorophores on the 3–10 nm range. Solution-based smFRET allows measurement of binding-unbinding events or conformational changes of dye-labeled biomolecules without ensemble averaging and free from surface perturbations. When employing dual (or multi) laser excitation, smFRET allows resolving the number of fluorescent labels on each molecule, greatly enhancing the ability to study heterogeneous samples. A major drawback to solution-based smFRET is the low throughput, which renders repetitive measurements expensive and hinders the ability to study kinetic phenomena in real-time. Here we demonstrate a high-throughput smFRET system that multiplexes acquisition by using 48 excitation spots and two 48-pixel single-photon avalanche diode array detectors. The system employs two excitation lasers allowing separation of species with one or two active fluorophores. The performance of the system is demonstrated on a set of doubly labeled double-stranded DNA oligonucleotides with different distances between donor and acceptor dyes along the DNA duplex. We show that the acquisition time for accurate subpopulation identification is reduced from several minutes to seconds, opening the way to high-throughput screening applications and real-time kinetics studies of enzymatic reactions such as DNA transcription by bacterial RNA polymerase

32-channel time-correlated-single-photon-counting system for high-throughput lifetime imaging

Time-Correlated Single Photon Counting (TCSPC) is a very efficient technique for measuring weak and fast optical signals, but it is mainly limited by the relatively “long” measurement time. Multichannel systems have been developed in recent years aiming to overcome this limitation by managing several detectors or TCSPC devices in parallel. Nevertheless, if we look at state-of-the-art systems, there is still a strong trade-off between the parallelism level and performance: the higher the number of channels, the poorer the performance. In 2013, we presented a complete and compact 32 × 1 TCSPC system, composed of an array of 32 single-photon avalanche diodes connected to 32 time-to-amplitude converters, which showed that it was possible to overcome the existing trade-off. In this paper, we present an evolution of the previous work that is conceived for high-throughput fluorescence lifetime imaging microscopy. This application can be addressed by the new system thanks to a centralized logic, fast data management and an interface to a microscope. The new conceived hardware structure is presented, as well as the firmware developed to manage the operation of the module. Finally, preliminary results, obtained from the practical application of the technology, are shown to validate the developed system