0.5 billion events per second time correlated single photon counting using CMOS SPAD arrays.

We present a digital architecture for fast acquisition of time correlated single photon counting (TCSPC) events from a 32×32 complementary metal oxide semiconductor (CMOS) single photon avalanche detector (SPAD) array (Megaframe) to the computer memory. Custom firmware was written to transmit event codes from 1024-TCSPC-enabled pixels for fast transfer of TCSPC events. Our 1024-channel TCSPC system is capable of acquiring up to 0.5×10(9) TCSPC events per second with 16 histogram bins spanning a 14 ns width. Other options include 320×10(6) TCSPC events per second with 256 histogram bins spanning either a 14 or 56 ns time window. We present a wide-field fluorescence microscopy setup demonstrating fast fluorescence lifetime data acquisition. To the best of our knowledge, this is the fastest direct TCSPC transfer from a single photon counting device to the computer to date.

[1]  G. E. Thomas,et al.  Measurement of the Time Dependence of Scintillation Intensity by a Delayed‐Coincidence Method , 1961 .

[2]  P. French,et al.  Fluorescence lifetime spectroscopy and imaging: Principles and applications in biomedical diagnostics , 2014 .

[3]  I. Young,et al.  Photon budget analysis for fluorescence lifetime imaging microscopy. , 2011, Journal of biomedical optics.

[4]  Nikola Krstajić,et al.  Development of a doubly weighted Gerchberg-Saxton algorithm for use in multibeam imaging applications. , 2014, Optics letters.

[5]  Michael Wahl,et al.  Time-Correlated Single Photon Counting , 2009 .

[6]  Jürgen Wolfrum,et al.  How many photons are necessary for fluorescence-lifetime measurements? , 1992 .

[7]  B. Vojnovic Advanced Time‐Correlated Single Photon Counting Techniques , 2006 .

[8]  J A Richardson,et al.  Scaleable Single-Photon Avalanche Diode Structures in Nanometer CMOS Technology , 2011, IEEE Transactions on Electron Devices.

[9]  B. Albinsson,et al.  FRETmatrix: a general methodology for the simulation and analysis of FRET in nucleic acids , 2012, Nucleic acids research.

[10]  Simao Coelho,et al.  Improving TCSPC data acquisition from CMOS SPAD arrays , 2013, European Conference on Biomedical Optics.

[11]  Frauke Zipp,et al.  Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation , 2013, PloS one.

[12]  H. Gerritsen,et al.  Multiple Time-Gate Module for Fluorescence Lifetime Imaging , 2001 .

[13]  Klaus Suhling,et al.  Time-resolved multifocal multiphoton microscope for high speed FRET imaging in vivo. , 2014, Optics letters.

[14]  N. Krstajić,et al.  A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging. , 2015, Biomedical optics express.

[15]  Alix Le Marois,et al.  Fluorescence lifetime imaging (Flim): Basic concepts and recent applications , 2015 .

[16]  E. Charbon Single-photon imaging in complementary metal oxide semiconductor processes , 2014, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[17]  Edoardo Charbon,et al.  A 32×32 50ps resolution 10 bit time to digital converter array in 130nm CMOS for time correlated imaging , 2009, 2009 IEEE Custom Integrated Circuits Conference.