A 192×128 Time Correlated SPAD Image Sensor in 40-nm CMOS Technology

A 192 X 128 pixel single photon avalanche diode (SPAD) time-resolved single photon counting (TCSPC) image sensor is implemented in STMicroelectronics 40-nm CMOS technology. The 13% fill factor, 18.4\,\,\mu \text {m} \times 9.2\,\,\mu \text{m} pixel contains a 33-ps resolution, 135-ns full scale, 12-bit time-to-digital converter (TDC) with 0.9-LSB differential and 5.64-LSB integral nonlinearity (DNL/INL). The sensor achieves a mean 219-ps full-width half-maximum (FWHM) impulse response function (IRF) and is operable at up to 18.6 kframes/s through 64 parallelized serial outputs. Cylindrical microlenses with a concentration factor of 3.25 increase the fill factor to 42%. The median dark count rate (DCR) is 25 Hz at 1.5-V excess bias. A digital calibration scheme integrated into a column of the imager allows off-chip digital process, voltage, and temperature (PVT) compensation of every frame on the fly. Fluorescence lifetime imaging microscopy (FLIM) results are presented

High-Speed Wide-Field Time-Correlated Single-Photon Counting Fluorescence Lifetime Imaging Microscopy

Fluorescence microscopy is a powerful imaging technique used in the biological sciences to identify labeled components of a sample with specificity. This is usually accomplished through labeling with fluorescent dyes, isolating these dyes by their spectral signatures with optical filters, and recording the intensity of the fluorescent response. Although these techniques are widely used, fluorescence intensity images can be negatively affected by a variety of factors that impact the fluorescence intensity. Fluorescence lifetime imaging microscopy (FLIM) is an imaging technique that is relatively immune to intensity fluctuations and also provides the unique ability to directly monitor the microenvironment surrounding a fluorophore. Despite the benefits associated with FLIM, the applications to which it is applied are fairly limited due to long image acquisition times and high cost of traditional hardware. Recent advances in complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diodes (SPADs) have enabled the design of low-cost imaging arrays that are capable of recording lifetime images with acquisition times greater than one order of magnitude faster than existing systems. However, these SPAD arrays have yet to realize the full potential of the technology due to limitations in their ability to handle the vast amount of data generated during the commonly used time-correlated single-photon counting (TCSPC) lifetime imaging technique. This thesis presents the design, implementation, characterization, and demonstration of a high speed FLIM imaging system. The components of this design include a CMOS imager chip in a standard 0.13 μm technology containing a custom CMOS SPAD, a 64-by-64 array of these SPADs, pixel control circuitry, independent time-to-digital converters (TDCs), a FLIM specific datapath, and high bandwidth output buffers. In addition to the CMOS imaging array, a complete system was designed and implemented using a printed circuit board (PCB) for capturing data from the imager, creating histograms for the photon arrival data using field-programmable gate arrays, and transferring the data to a computer using a cabled PCIe interface. Finally, software is used to communicate between the imaging system and a computer.The dark count rate of the SPAD was measured to be only 231 Hz at room temperature while maintaining a photon detection probability of up to 30\%. TDCs included on the array have a 62.5 ps resolution and a 64 ns range, which is suitable for measuring the lifetime of most biological fluorophores. Additionally, the on-chip datapath was designed to handle continuous data transfers at rates capable of supporting TCSPC-based lifetime imaging at 100 frames per second. The system level implementation also provides sufficient data throughput for transferring up to 750 frames per second from the imaging system to a computer. The lifetime imaging system was characterized using standard techniques for evaluating SPAD performance and an electrical delay signal for measuring the TDC performance. This thesis concludes with a demonstration of TCSPC-FLIM imaging at 100 frames per second -- the fastest 64-by-64 TCSPC FLIM that has been demonstrated. This system overcomes some of the limitations of existing FLIM systems and has the potential to enable new application domains in dynamic FLIM imaging

SPAD Figures of Merit for Photon-Counting, Photon-Timing, and Imaging Applications: A Review

Single-photon avalanche diodes (SPADs) emerged as the most suitable photodetectors for both single-photon counting and photon-timing applications. Different complementary metal-oxide-semiconductor (CMOS) devices have been reported in the literature, with quite different performance and some excelling in just few of them, but often at different operating conditions. In order to provide proper criteria for performance assessment, we present some figures of merit (FoMs) able to summarize the typical SPAD performance (i.e., photon detection efficiency, dark counting rate, afterpulsing probability, hold-off time, and timing jitter) and to identify a proper metric for SPAD comparisons, when used either as single-pixel detectors or in imaging arrays. The ultimate goal is not to define a ranking list of best-in-class detectors, but to quantitatively help the end-user to state the overall performance of different SPADs in either photon-counting, timing, or imaging applications. We review many CMOS SPADs from different research groups and companies, we compute the proposed FoMs for all them and, eventually, we provide an insight on present CMOS SPAD technologies and future trends

A 72 × 60 Angle-Sensitive SPAD Imaging Array for Lens-less FLIM

We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing

Single-Photon Avalanche Diodes in a 0.16 μm BCD Technology With Sharp Timing Response and Red-Enhanced Sensitivity

CMOS single-photon avalanche diodes (SPADs) have recently become an emerging imaging technology for applications requiring high sensitivity and high frame-rate in the visible and near-infrared range. However, a higher photon detection efficiency (PDE), particularly in the 700-950 nm range, is highly desirable for many growing markets, such as eye-safe three-dimensional imaging (LIDAR). In this paper, we report the design and characterization of SPADs fabricated in a 0.16 mu m BCD (Bipolar-CMOS-DMOS) technology. The overall detection performance is among the best reported in the literature: 1) PDE of 60% at 500 nm wavelength and still 12% at 800 nm; 2) very low dark count rate of < 0.2 cps/mu m(2) (in counts per second per unit area); 3) < 1% afterpulsing probability with 50 ns dead-time; and 4) temporal response with 30 ps full width at half-maximum and less than 50 ps diffusion tail time constant

Enhanced single-photon time-of-flight 3D ranging

We developed a system for acquiring 3D depth-resolved maps by measuring the Time-of-Flight (TOF) of single photons. It is based on a CMOS 32 × 32 array of Single-Photon Avalanche Diodes (SPADs) and 350 ps resolution Time-to-Digital Converters (TDCs) into each pixel, able to provide photon-counting or photon-timing frames every 10 μs. We show how such a system can be used to scan large scenes in just hundreds of milliseconds. Moreover, we show how to exploit TDC unwarping and refolding for improving signal-to-noise ratio and extending the full-scale depth range. Additionally, we merged 2D and 3D information in a single image, for easing object recognition and tracking

Fluorescence lifetime biosensing with DNA microarrays and a CMOS-SPAD imager

Fluorescence lifetime of dye molecules is a sensitive reporter on local microenvironment which is generally independent of fluorophores concentration and can be used as a means of discrimination between molecules with spectrally overlapping emission. It is therefore a potentially powerful multiplexed detection modality in biosensing but requires extremely low light level operation typical of biological analyte concentrations, long data acquisition periods and on-chip processing capability to realize these advantages. We report here fluorescence lifetime data obtained using a CMOS-SPAD imager in conjunction with DNA microarrays and TIRF excitation geometry. This enables acquisition of single photon arrival time histograms for a 320 pixel FLIM map within less than 26 seconds exposure time. From this, we resolve distinct lifetime signatures corresponding to dye-labelled HCV and quantum-dot-labelled HCMV nucleic acid targets at concentrations as low as 10 nM

GPU acceleration of time-domain fluorescence lifetime imaging

Fluorescence lifetime imaging microscopy (FLIM) plays a significant role in biological sciences, chemistry, and medical research. We propose a Graphic Processing Units (GPUs) based FLIM analysis tool suitable for high-speed and flexible time-domain FLIM applications. With a large number of parallel processors, GPUs can significantly speed up lifetime calculations compared to CPU-OpenMP (parallel computing with multiple CPU cores) based analysis. We demonstrate how to implement and optimize FLIM algorithms on GPUs for both iterative and non-iterative FLIM analysis algorithms. The implemented algorithms have been tested on both synthesized and experimental FLIM data. The results show that at the same precision the GPU analysis can be up to 24-fold faster than its CPU-OpenMP counterpart. This means that even for high precision but time-consuming iterative FLIM algorithms, GPUs enable fast or even real-time analysis