title: Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier.
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%.
authors.forename: Francescopaolo Mattioli Della
authors.initials: FM
authors.lastname: Rocca
authors.forename: Jakub
authors.initials: J
authors.lastname: Nedbal
authors.forename: David
authors.initials: D
authors.lastname: Tyndall
authors.forename: Nikola
authors.initials: N
authors.lastname: Krstajić
authors.forename: David Day-Uei
authors.initials: DD
authors.lastname: Li
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ameer-Beg
authors.forename: Robert K
authors.initials: RK
authors.lastname: Henderson
mesh_terms: D005434:Flow Cytometry / Q000295:instrumentation*; D061848:Optical Imaging; D010087:Oxides / Q000737:chemistry*; D017785:Photons; D012666:Semiconductors; D059629:Signal-To-Noise Ratio; D012825:Silicon / Q000737:chemistry*
chemical_list: D010087:Oxides; D012825:Silicon