Real-Time Fluorescence Lifetime Actuation for Cell Sorting using a CMOS SPAD Silicon Photomultiplier

Francescopaolo Mattioli della Rocca, Jakub Nedbal, David Tyndall, Nikola Krstajic, David Day-Uei Li, Simon Ameer-Beg, Robert Henderson

Research output: Contribution to journalArticlepeer-review

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 32×32 single-photon avalanche diode (SPAD) array and eight pairs of time-interleaved time to digital converters (TI-TDCs) with a 50 ps minimum timing resolution. The sensor’s pile-up resistant embedded center of mass method (CMM) processor accomplishes low-latency measurement and thresholding of fluorescence lifetime. A digital control signal is generated with a 16.6 μs latency for cell sorter actuation allowing a maximum cell throughput of 60,000 cells per second and an error rate of 0.6%.
Original languageEnglish
Pages (from-to)673-676
Number of pages4
JournalOptics Letters
Volume41
Issue number4
DOIs
Publication statusPublished - 15 Feb 2016

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