Studies increasingly support the idea that fluorescence lifetime imaging (FLI) offers superior tumor detection contrast, but conventional methods are limited by low frame rates and high computational load. We present a compact, real-time FLI system based on a QVGA SPAD sensor with in-pixel switched-capacitor circuits that compute the average photon time-of-arrival in the analog domain. This single-shot, center-of-mass approach avoids photon binning and gated integration, enabling high frame rate FLI up to 30 FPS. Experimental validation with visible (fluorescein and acridine orange) and near-infrared fluorophores (ICG and IRDye800CW), confirms accurate performance. Future work will evaluate the system in preclinical in vivo settings for fluorescence-guided surgical applications.

A video-rate fluorescence lifetime (FLT) imaging system is presented featuring in-pixel lifetime calculation based on the center of mass of the times of arrival (ToAs) of photons received by the single-photon avalanche diode of the pixel. The ToAs of photons received during a gating window placed in the decay of the returned fluorescent emission are averaged by a switched-capacitor circuit, implementing the center-of-mass method (CMM) in a compact pixel circuit. Binning of ToAs or complex time-to-digital circuits are avoided, and instead, optimal use of all received photons is achieved on a small pixel area with low communication and computational overhead. The system is validated through analytical modeling, Monte Carlo simulations, and real-world experiments using fluorophores with known lifetimes, demonstrating agreement with the analytical model and achieving accurate FLT estimations across a large range of photon counts. A dedicated quarter video graphics array (QVGA) (320 x 240 pixel) image sensor that includes all necessary circuitry for the CMM currently reaches 10 frames per second and demonstrates the real-time FLT imaging capability of the system.

Fluorescence imaging has been widely used in fields like (pre)clinical imaging and other domains. With advancements in imaging technology and new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the tauCAMTM, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700–900 nm) region. Incorporating fluorescence lifetime into endoscopy could further improve the differentiation of malignant and benign cells based on their distinct lifetimes. In this work, the capabilities of an endoscopic lifetime imaging system are demonstrated using a rigid endoscope involving various phantoms and an IRF-free deep learning-based method with only 6-time points. The results show that this application’s fluorescence lifetime image has better lifetime uniformity and precision with 6-time points than the conventional methods.

A 128 x 128-pixel current-assisted photonic sampler (CAPS) image sensor is designed for macroscale fluorescence lifetime imaging (MFLI). Current assistance is used for swift detection and time gating of the photogenerated carriers within the whole substrate. The sensor is fabricated in a commercial 350-nm CMOS process on a 15-mu m epilayer, with 19-mu m pixels and a 62% FF. The pixel features gating widths below 1 ns subject to a 42-ps standard deviation on the gate width uniformity and a 27-ps standard deviation on its temporal position. The pixel has a quantum efficiency (QE) above 40% for near-infrared (NIR) wavelengths, whereas the peak QE is 60% at 675 nm. The gate's intrinsic decay is observed to be 280 ps, which allows for the MFLI of subnanosecond lifetime dyes. A multiexposure method has been implemented, where the pixel is nondestructively read-out multiple times-with different exposure times-after each reset. This allows for imaging with an extended dynamic range (DR) and is validated on commercial fluorescence phantoms. The MFLI capabilities are further demonstrated in a preclinical experiment.

Correlation-Assisted Direct Time-of-Flight (CA-dToF) is demonstrated for the first time on a large 320 × 240-pixel SPAD array sensor that includes on-chip high-speed timing support circuitry. SPAD events are processed in-pixel, avoiding data communication over the array and/or storage bottlenecks. This is accomplished by sampling two orthogonal triangle waves that are synchronized with short light pulses illuminating the scene. Using small switched-capacitor circuits, exponential moving averaging (EMA) is applied to the sampled voltages, delivering two analog voltages (VQ2, VI2). These contain the phase delay, or the time of flight between the light pulse and photon’s time of arrival (ToA). Uncorrelated ambient photons and dark counts are averaged out, leaving only their associated shot noise impacting the phase precision. The QVGA camera allows for capturing depth-sense images with sub-cm precision over a 6 m range of detection, even with a small PDE of 0.7% at an 850 nm wavelength.

In vivo fluorescence lifetime (FLT) imaging is an emerging and promising modality with the potential to provide additional biological information compared to fluorescence intensity (FI) imaging. Until now, nearly all studies evaluating the benefits of FLT imaging in vivo have been conducted using cyanine dyes. While these fluorophores are highly successful for conventional in vivo fluorescence imaging due to their unmatched brightness in the NIR-I region (700-900 nm), they might be suboptimal for FLT imaging. Indeed, NIR-I cyanines are characterized by short singlet excited-state lifetime (generally below 1 ns) making it challenging to differentiate them from tissue autofluorescence. Therefore, there is a pressing need for biocompatible fluorophores with longer FLTs. Herein, we report a novel bioconjugatable water-soluble NIR-emissive aza-BODIPY dye with extended FLT values in physiological conditions, compared to cyanine dyes (increase of 100% compared to IRDye® 800CW). The suitability of aza-BODIPY for FLT imaging when conjugated to an antibody was assessed to enhance this technology. Beyond rational design and synthesis of a long-wavelength fluorophore with attractive features for in vivo FLT imaging, this study also highlights for the first time the impact of the conjugation method on the FLT characteristics of the resulting fluorescent antibody conjugates.

This letter proposes a novel single photon avalanche diode (SPAD)-based pixel, designed for direct Time-of-Flight (ToF) imaging with in-pixel averaging, which provides a promising advancement in low-power and potentially high image resolution for outdoor applications. By utilizing a laser pulse and two orthogonal sinusoidal signals, the pixel averages out the detected ambient light while accumulating the laser pulse round-trip time. A prototype pixel array was fabricated using a 180 nm CMOS process, featuring a commercial SPAD cell. By characterizing one pixel and employing a 100 klux solar emulator as an ambient light source with a fixed 40 ambient-to-signal ratio over a 360(degrees) phase shift, equivalent to 6 m detection range, the maximum detected accuracy error was 3.3%, with a 5 cm precision.

Recent studies demonstrated the added-value of fluorescence lifetime (FLT) imaging in tumor identification to intensity-based imaging. The tauCAM is a novel macroscale FLT imaging system that detects the FLT of a fluorophore by measuring fluorescence in the time-domain. FLT images are made simultaneously to fluorescence intensity- and grayscale reflectance images, under ambient illumination. In vivo imaging in subcutaneous tumor bearing-mice revealed that FLT imaging with the tauCAM provides additional information on environmental parameters between tumor and healthy tissue, for tracers sensitive to their physiological environment. This research emphasizes the importance of fluorophore selection for future (pre-) clinical FLT imaging trials.

Fluorescence imaging has been widely used in fields like (pre)clinical imaging, as well as in other domains. With advancements in imaging technology and the development of new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the CAPS camera, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700-900nm) region. Incorporating fluorescence lifetime into endoscopy would further differentiate malignant and benign cells based on their distinct lifetimes. Therefore, the capabilities of the system are demonstrated using a rigid endoscope involving various phantoms and various lifetime processing approaches to get the uniform lifetime image because of the independence of fluorescence lifetime to the intensity when the intensity image is not.

Macroscale fluorescence lifetime (FLT) imaging is emerging as a promising tool to improve tumor margin delineation and enhance contrast between tumor and healthy tissue during fluorescence-guided surgery. We have been developing the tauCAM, a custom-built time-gated CMOS camera with a high quantum efficiency (QE) in NIR (46%) and a resolution of 128x128 pixels, specifically for this application. The images obtained from the tauCAM are overlaid on high-resolution color images acquired with a dedicated color camera. We demonstrate the capabilities of our camera by performing in vivo studies on subcutaneous mice tumor models administered with nanobody- and antibody-based NIR tumor-targeted fluorescent contrast agents. The results indicate that FLT imaging enhances the contrast between tumor and healthy tissue.

A 64 x 64 pixel current-assisted photonic sampler (CAPS) image sensor is designed for real-time fluorescence lifetime (FLT) imaging. Current assistance is used for swift detection and time-gating of the photogenerated carriers within the whole substrate. An additional bias node is used to decrease the dynamic power consumption, and a photogate is applied to the sensor to reduce the carrier transfer time. The sensor is fabricated in a commercial 350-nm CMOS process on a 15- mu m epi-layer, with 30- mu m pixels and a 61% fill factor. The pixel features gating widths below 1 ns subject to a 17-ps standard deviation on the gate width uniformity and a 31-ps standard deviation on its temporal position. The pixel has a quantum efficiency (QE) above 40% for near-infrared (NIR) wavelengths, whereas the peak QE is 61% at 675 nm. The gate's intrinsic decay is observed to be 320 ps, which allows for the FLT imaging of sub-nanosecond lifetime dyes. The real-time FLT imaging capabilities are demonstrated on commercial fluorescence phantoms and in a preclinical experiment.

Fluorescence imaging is widely used in many different domains, one of which is fluorescence-guided surgery. The temporal behavior called fluorescence lifetime gives deeper insights, making it an additional tool. Current fluorescence-guided surgery imaging typically utilizes two different cameras for natural color and NIR fluorescence imaging, making the system complex and expensive. We propose an alternative approach of sequential RGB+NIR fluorescence lifetime imaging and overlaying the images on each other. Sequential RGB+NIR fluorescence imaging is achieved with a high-speed time-gated camera combined with an RGB LED ring illumination for natural color imaging and a picosecond NIR pulsed laser source for fluorescence lifetime imaging.

Time-gated image sensors with (sub-) nanosecond gating times enable applications in multiple domains. Commercial Intensified CCD cameras or the more recent time-gated SPAD image sensors suffer from low Quantum Efficiency. We present an imaging system based on the tauCAM, a compact time-gated camera with our new 128x128-pixel CAPS sensor. The higher resolution is achieved with a new pixel architecture, yielding an improved fill factor. The capabilities of the new imaging system are demonstrated in a pre-clinical experimental setup. In vivo imaging in subcutaneous mice tumor models reveal that FLT imaging with the tauCAM provides additional contrast between tumor and healthy tissue, in particular for tracers sensitive to their physiological environment.

Novel hybrid binder concrete mixes with alkali-activated non-ferrous slag (NFS), either alone or in combination with blast furnace slag (BFS), as partial replacement of Portland cement, and containing 50% recycled aggregates, were successfully manufactured. The compressive strength, carbonation resistance, chloride resistance, frost scaling, sorptivity coefficient, and water penetration resistance were thoroughly assessed. The presence of recycled aggregates had an adverse effect on early-age strength, but after 91 days there was no difference between concrete with and without recycled aggregates. The chloride-binding capacity was enhanced in the BFS/NFS system with recycled aggregates (reduction in chloride ingress coefficients of ~28–35% compared to recycled concrete with NFS only). This is most likely caused by the binding of Cl ions in calcium alumina silicate hydrates (C-A-S-H) and ettringite phases. However, when compared to the system with virgin aggregates, BFS/NFS concrete with recycled aggregates showed increased carbonation rate (+30%) and frost scaling (+15%). Durability properties, such as sorptivity and water penetration resistance, were positively affected by the curing time for the BFS/NFS system (~35–45% further improvement from 28 to 90 days with respect to the NFS system). Specimens that were wet cured for 91 days showed improved results compared to the 28-day cured samples due to the slow pozzolanic reaction of the NFS.

Materials subjected to irradiation damage often undergo local microstructural changes that can affect their expected performance. To investigate such changes, this work proposes a novel approach to detect strain localisation caused by irradiation-induced damage in nuclear materials on the microstructural level, considering a statistically relevant number of grains. This approach determines local strains using highresolution digital image correlation (HRDIC) and compares them with the underlying material microstructure. Sets of images captured before and after irradiation are compared to generate full-field displacement maps that can then be differentiated to yield high-resolution strain maps. These strain maps can subsequently be used to understand the effects of irradiation-induced dimensional change and cracking on the microscale. Here, the methodology and challenges involved in combining scanning electron microscopy (SEM) with HRDIC to generate strain maps associated with radiation-induced damage are presented. Furthermore, this work demonstrates the capabilities of this methodology by analysing three different materials subjected to proton irradiation: a zircaloy-4 (Zry-4) metal irradiated to 1 & 2 dpa, and two ceramics based on MAX phase compounds, i.e., the Nb4AlC3 ternary compound and a novel (Ta,Ti)(3) AlC2 solid solution, both irradiated to -0.1 dpa. These results demonstrated that all materials show measurable expansion, and the very high strains seen in the MAX phase ceramics can be easily attributed to their microstructure. Grain-to-grain variability was observed in Zry-4 with a macroscopic expansion along the rolling direction that increased with irradiation damage dose, the Nb4AlC3 ceramic showed significant expansion within individual grains, leading to intergranular cracking, while the less phase-pure (Ta,Ti)(3) AlC2 ceramic exhibited very high strains at phase boundaries, with limited expansion in the binary carbide phases. This ability to measure irradiation-induced dimensional changes at the microstructural scale is important for designing microstructures that are structurally resilient during irradiation. (c) 2023TheAuthors. Publishedby Elsevier B.V.

There was an error in the original publication, in Equation (5) [...].

Time-resolved fluorescence spectroscopy is a promising and versatile spectroscopy technique. While conventional fluorescence spectroscopy is concerned with the spectral features of fluorescence emission, time-resolved fluorescence spectroscopy (TRFS) also captures the temporal behavior of the excited molecules. In addition to applications in rapid medical diagnoses, several applications were reported in forensics, chemical analysis and biology. The existing TRFS systems are based on complex optical setups which results in bulky and large systems. Therefore, using them in practice is still not feasible. In this work, we present a miniaturized system that combines a compact Czerny-Turner based spectrometer layout with our high-speed time-gated image sensor of 32×32 pixels based on the Current-Assisted Photonic Sampler (CAPS) sensor. The system operates in the visible wavelength range with a high spectral resolution. The novel image sensor is capable of measuring down to sub-nanosecond lifetimes. The proof-of-concept module was assembled and characterized for three fluorophores.

In this paper, we present the tauCAM, a compact sub-nanosecond time-gated video framerate imaging camera, with our new 64×64-pixel Current-Assisted Photonic Sampler (CAPS) sensor. It features gating widths of less than 1 ns with a jitter of less than 60 ps rms on the gating width and less than 50 ps rms on the position. It has a quantum efficiency (QE) of more than 40% for near-infrared wavelengths. It's peak QE is 61% at 675 nm. The sensor is fabricated in a conventional 350 nm CMOS process. We give an overview of the design of the new camera hardware, with characterization of the timing circuitry and gating signals. Furthermore, the new sensor is discussed in detail. The revised pixel design yields improvements in QE, with high QE even for very short gating windows. Additionally, the Instrument Response Function of the pixel is characterized. The capabilities of the tauCAM are demonstrated in an experimental setup where we image a scene that is sequentially illuminated with red, green and blue light, on a nanosecond time scale. Due to its fast-gating mechanism, our CAPS sensor can distinguish and image these colors separately, while the human eye merely sees white illumination.

Fluorescence imaging has been used for quite some time in microscopy, preclinical and medical imaging, as well as in other domains. There has been interest in using the time-behaviour of fluorophores to gain additional information. This time-behaviour, called the fluorescence lifetime, is a property of the fluorophore and can also reveal information about its environment through modulation of this lifetime. Fluorescence-lifetime imaging could improve imaging of existing fluorescent contrast agents or could enable novel applications. The tauCAM, based on the Current-assisted photonic sampler (CAPS), is being developed at our research department with the purpose of achieving real-time fluorescence lifetime imaging. Previous versions have already shown some results in doing lifetime imaging through experiments and demonstrations. Elaborate characterisation of its imaging capabilities in this domain has yet to be performed due to the lack of standardisation and phantoms available for lifetime imaging. In this publication we will discuss the (real-time) lifetime and intensity imaging capabilities of the tauCAM, the latest iteration of our CAPS camera, housing a new 64×64-pixel sensor. The groundwork will be laid for the development of phantoms for lifetime imaging based on phantoms made for fluorescence intensity imaging. These will in turn be measured using reference equipment and used to characterize the accuracy and precision of the results from the tauCAM.