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

Abstract

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.

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

“…Linear arrays can also be used as single point detectors, for example by means of optical 1D to 2D transformations, to reduce the effect of single SPAD dead time and increase the throughput in FLIM measurements [59]; an example of the corresponding results is shown in Figure 3(f, g). This and other approaches could open the way to high-throughput biotechnological applications, such as high-throughput screening or cell sorting [60,68], based on nanosecond-lived fluorophores.…”

“…The FluoCam system has been used in several in vivo studies to demonstrate the capabilities of such an approach, employing indocyanine green (ICG)-modified derivates, such as ICG-RGD, (d, e) Label-free FLIM of an unstained liver tissue excised from a tumorogenic murine model [58], imaged with a 64×4 SPAD array [17]. (f, g) A Convallaria FLIM measurement done with a linear 32×1 SPAD array [59]. Images reprinted from [25,[56][57][58][59].…”

“…(f, g) A Convallaria FLIM measurement done with a linear 32×1 SPAD array [59]. Images reprinted from [25,[56][57][58][59].…”

Fast Timing Techniques in FLIM Applications

“…For this reason TDCs have found widespread use in SPAD arrays, and the development of this technology is expected to continue. Recently a 32-channel TCSPC system has been developed employing the hybrid integration of a custom 32 SPAD array with 32-channel active quench and time to analog converter array [87, 133,134]. Although the fill-factor and SPAD performance are compromised by having such a large number of detectors and timing electronics on a single substrate, this detector has a TDC in each pixel with 55 ps resolution, allowing independent TCSPC in each pixel of a 32×32 pixel array simultaneously.…”

Custom-Technology Single-Photon Avalanche Diode Linear Detector Array for Underwater Depth Imaging

“…The hardware consists of two main parts: a detection head and a TCSPC module. The detection module is based on the architecture reported in [ 39 , 40 ], with a new firmware specifically developed to meet the requirements of underwater depth imaging. The TCSPC module asynchronously time-tagged the events detected by the detection head, providing the timing information needed to build the depth profile.…”