Low-Latency Time-Resolved Fluorescence Lifetime Flow Cytometry and Cell Sorting using a CMOS Silicon Photomultiplier

Accurate and fast measurement of fluorescence lifetime in flow cytometry would prompt
application to studies of protein-protein interactions by Forster resonance energy transfer (FRET), which
are otherwise difficult or impossible to analyse [1]. Time-correlated single photon counting (TCSPC) has
the best signal to noise ratio of any fluorescence lifetime technique [2] but cannot readily be implemented
within a cytometer due to the requirement of complex software algorithms, severely restricting the
throughput and preventing real-time sorting of cells [3].
The SiPM is a single-chip silicon photomultiplier detector employing a CMOS single-photon avalanche
diode (SPAD) array light detector and time to digital converters (TDCs) [4]. The sensor's pile-up resistant
embedded centre of mass (CMM) processor accomplishes low-latency measurement and thresholding of
fluorescence lifetime. A digital control signal is generated with a maximum 16.6μs latency for cell sorter
actuation.