Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier

Mattioli Della Rocca, Francescopaolo and Nedbal, Jakub and Tyndall, David and Krstajic, Nikola and Li, David Day-Uei and Ameer-Beg, Simon M. and Henderson, Robert K. (2016) Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier. Optics Letters, 41 (4). pp. 673-676. ISSN 1539-4794

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    Abstract

    Time-correlated single photon counting (TCSPC) is a fundamental fluorescence lifetime measurement technique offering high signal to noise ratio (SNR). However, its requirement for complex software algorithms for histogram processing restricts throughput in flow cytometers and prevents on-the-fly sorting of cells. We present a single-point digital Silicon Photomultiplier (SiPM) detector accomplishing real-time fluorescence lifetime-activated actuation targeting cell sorting applications in flow cytometry. The sensor also achieves burst-integrated fluorescence lifetime (BIFL) detection by TCSPC. The SiPM is a single-chip complementary metal oxide semiconductor (CMOS) sensor employing a 3232 single-photon avalanche diode (SPAD) array and 8 pairs of time-interleaved time to digital converters (TI-TDCs) with a 50 ps minimum timing resolution. The sensor’s pile-up resistant embedded centre of mass method (CMM) processor accomplishes lowlatency measurement and thresholding of fluorescence lifetime. A digital control signal is generated with a 16.6 s latency for cell sorter actuation allowing a maximum cell throughput of 60,000 cells per second and an error rate of 0.6%.