256 × 2 SPAD line sensor for time resolved fluorescence spectroscopy

Krstajić, Nikola; Levitt, James A.; Poland, Simon P.; Ameer-Beg, Simon; Henderson, Robert K.

doi:10.1364/oe.23.005653

Cited by 60 publications

(60 citation statements)

References 53 publications

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“…The linear 256×2 array by Krstajić et al [23], which was already mentioned in the FLIM section, has also been used for surface-enhanced Raman spectroscopy (SERS), again within the PROTEUS project. Significant hardware and software improvements of the same sensor are reported in [66], whereas removal of fluorescent background signals (in addition to DCR) is illustrated in [65].…”

Section: Raman Spectroscopymentioning

confidence: 99%

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

et al. 2019

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Single-photon avalanche diode (SPAD) arrays are solid-state detectors that offer imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at a very fast pace in the past 15 years, since its inception in standard CMOS technology in 2003. A host of architectures have been investigated, ranging from simpler implementations, based solely on off-chip data processing, to progressively “smarter” sensors including on-chip, or even pixel level, time-stamping and processing capabilities. As the technology has matured, a range of biophotonics applications have been explored, including (endoscopic) FLIM, (multibeam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman spectroscopy, NIROT and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.

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Section: Raman Spectroscopymentioning

confidence: 99%

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

et al. 2019

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“…Therefore, seFRET is commonly used as a fast, simpler and more cost-effective alternative. Breakthroughs in FLIM-enabling technologies [42][43][44][45][46][47][48] and data analysis [49][50][51] are reducing the barrier to adoption for FLIM; therefore, as the choice between the two techniques might be slowly drift away from technical requirements, we aimed to develop a comparative analysis of the limits of both techniques from an information theory perspectives to provide guidance on the selection and also optimization of these methodologies.…”

Section: Discussionmentioning

confidence: 99%

Photon-statistics in sensitized emission FRET and FLIM: a comparative theoretical analysis

Esposito

2019

Preprint

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Förster resonance energy transfer (FRET) imaging is an essential analytical method in biomedical research. Sensitized emission FRET (seFRET) and fluorescence lifetime imaging microscopy (FLIM) are the most common techniques used for the quantification of FRET. The limited photon-budget available in a typical experiment, however, imposes compromises between spatiotemporal and biochemical resolutions, photodamage and phototoxicity. The study of photon-statistics in biochemical imaging is thus important in guiding the efficient design of instrumentation and assays. Here, we show a comparative theoretical analysis of photon-statistics and provide computational tools to investigate the performance of FRET imaging by FLIM and seFRET. We show how the performance of FRET imaging can vary vastly with imaging parameters that should be thus always optimized. Therefore, we provide analytical tools, an open source computational framework and suggestions on assay optimization. FLIM is a very robust technique and provides excellent photon-efficiencies, but we show that also seFRET utilizes the available photon-budgets rather efficiently by utilizing information from both donor and acceptor fluorescence. We, also because of the utilization of the entire photon

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“…The sensor has been applied to fluorescence lifetime imaging applications and as a true random number generator. In [11], authors characterize a linear 256×2-pixel sensor fabricated in standard 130nm CMOS process in a testbed for application in time-resolved fluorescence spectroscopy. Each pixel contains four time-gated SPADs and a Time-to-Digital Converter (TDC) that records the SPAD triggering time with 40ps resolution.…”

Section: State Of the Art In Cmos Spad Arraysmentioning

confidence: 99%

“…Binary images are acquired at a rate of 16kfps, while timing performance is not reported. These SPAD-based sensors are good potential candidates for coincidence detection of spatially correlated photon pairs, however, they suffer from very low fill factors [1,4], time-coincidence detection capability longer than 0.6ns [1,11,4], acquisition frame rates below 160kHz [1,11,4,5], limited spatial resolution of the 2D pixel array arrangement [1,11].…”

Section: State Of the Art In Cmos Spad Arraysmentioning

confidence: 99%

SUPERTWIN: towards 100kpixel CMOS quantum image sensors for quantum optics applications

et al. 2017

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Quantum imaging uses entangled photons to overcome the limits of a classical-light apparatus in terms of image quality, beating the standard shot-noise limit, and exceeding the Abbe diffraction limit for resolution. In today experiments, the spatial properties of entangled photons are recorded by means of complex and slow setups that include either the motorized scanning of single-pixel single-photon detectors, such as Photo-Multiplier Tubes (PMT) or Silicon PhotoMultipliers (SiPM), or the use of low frame rate intensified CCD cameras. CMOS arrays of Single Photon Avalanche Diodes (SPAD) represent a relatively recent technology that may lead to simpler setups and faster acquisition. They are spatially-and time-resolved single-photon detectors, i.e. they can provide the position within the array and the time of arrival of every detected photon with <100 ps resolution. SUPERTWIN is a European H2020 project aiming at developing the technological building blocks (emitter, detector and system) for a new, all solid-state quantum microscope system exploiting entangled photons to overcome the Rayleigh limit, targeting a resolution of 40nm. This work provides the measurement results of the 2 nd order cross-correlation function relative to a flux of entangled photon pairs acquired with a fully digital 8×16 pixel SPAD array in CMOS technology. The limitations for application in quantum optics of the employed architecture and of other solutions in the literature will be analyzed, with emphasis on crosstalk. Then, the specifications for a dedicated detector will be given, paving the way for future implementations of 100kpixel Quantum Image Sensors.

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256 × 2 SPAD line sensor for time resolved fluorescence spectroscopy

Cited by 60 publications

References 53 publications

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

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

Photon-statistics in sensitized emission FRET and FLIM: a comparative theoretical analysis

SUPERTWIN: towards 100kpixel CMOS quantum image sensors for quantum optics applications

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