52
views
0
recommends
+1 Recommend
0 collections
    8
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Monitoring progress of single light particle detectors for biophotonics applications

          Substantial improvements have been made in the past 15 years to imagers based on a device that acts like a 3-in-1 light particle detector, counter and stopwatch, furthering their potential use in biological imaging technologies. Claudio Bruschini of Switzerland’s École polytechnique fédérale de Lausanne and colleagues reviewed the developments in the use of single-photon avalanche diode (SPAD) arrays for biophotonics applications. They found that, while most SPAD imagers are still used in specialised research settings, significant improvements have been made to their sensitivity, reliability and reproducibility, and a host of sensor architectures have been explored. When a photon, the unit of light, hits a SPAD, it triggers an almost immediate electric current. Compact SPAD arrays implemented in standard CMOS electronic circuits can thus be used, for example, to measure in parallel the fluorescence lifetime of molecules tagged onto living cells and tissues, improving our ability to observe them. The review was completed by an outlook of this fascinating technology and an analysis of the most relevant challenges still lying ahead.

          Related collections

          Most cited references153

          • Record: found
          • Abstract: not found
          • Article: not found

          Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung

          E. Abbe (1873)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Microscopy and its focal switch.

            Until not very long ago, it was widely accepted that lens-based (far-field) optical microscopes cannot visualize details much finer than about half the wavelength of light. The advent of viable physical concepts for overcoming the limiting role of diffraction in the early 1990s set off a quest that has led to readily applicable and widely accessible fluorescence microscopes with nanoscale spatial resolution. Here I discuss the principles of these methods together with their differences in implementation and operation. Finally, I outline potential developments.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Fluorescence lifetime imaging--techniques and applications.

              W. Becker (2012)
              Fluorescence lifetime imaging (FLIM) uses the fact that the fluorescence lifetime of a fluorophore depends on its molecular environment but not on its concentration. Molecular effects in a sample can therefore be investigated independently of the variable, and usually unknown concentration of the fluorophore. There is a variety of technical solutions of lifetime imaging in microscopy. The technical part of this paper focuses on time-domain FLIM by multidimensional time-correlated single photon counting, time-domain FLIM by gated image intensifiers, frequency-domain FLIM by gain-modulated image intensifiers, and frequency-domain FLIM by gain-modulated photomultipliers. The application part describes the most frequent FLIM applications: Measurement of molecular environment parameters, protein-interaction measurements by Förster resonance energy transfer (FRET), and measurements of the metabolic state of cells and tissue via their autofluorescence. Measurements of local environment parameters are based on lifetime changes induced by fluorescence quenching or conformation changes of the fluorophores. The advantage over intensity-based measurements is that no special ratiometric fluorophores are needed. Therefore, a much wider selection of fluorescence markers can be used, and a wider range of cell parameters is accessible. FLIM-FRET measures the change in the decay function of the FRET donor on interaction with an acceptor. FLIM-based FRET measurement does not have to cope with problems like donor bleedthrough or directly excited acceptor fluorescence. This relaxes the requirements to the absorption and emission spectra of the donors and acceptors used. Moreover, FLIM-FRET measurements are able to distinguish interacting and noninteracting fractions of the donor, and thus obtain independent information about distances and interacting and noninteracting protein fractions. This is information not accessible by steady-state FRET techniques. Autofluorescence FLIM exploits changes in the decay parameters of endogenous fluorophores with the metabolic state of the cells or the tissue. By resolving changes in the binding, conformation, and composition of biologically relevant compounds FLIM delivers information not accessible by steady-state fluorescence techniques. © 2012 The Author Journal of Microscopy © 2012 Royal Microscopical Society.
                Bookmark

                Author and article information

                Contributors
                claudio.bruschini@epfl.ch
                Journal
                Light Sci Appl
                Light Sci Appl
                Light, Science & Applications
                Nature Publishing Group UK (London )
                2095-5545
                2047-7538
                18 September 2019
                18 September 2019
                2019
                : 8
                : 87
                Affiliations
                [1 ]ISNI 0000000121839049, GRID grid.5333.6, AQUA, , EPFL, ; Neuchâtel, Switzerland
                [2 ]ISNI 0000 0001 2097 4740, GRID grid.5292.c, AQUA, , TU Delft, ; Delft, The Netherlands
                Article
                191
                10.1038/s41377-019-0191-5
                6804596
                31645931
                e1476476-55f9-41a7-bc90-dbd4c18aeaab
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 November 2018
                : 30 July 2019
                : 7 August 2019
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2019

                biophotonics,imaging and sensing
                biophotonics, imaging and sensing

                Comments

                Comment on this article