Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier
Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier
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DOI：
10.1364/ol.41.000673
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发表时间：
2016-02-15
期刊：
影响因子：
3.6
通讯作者：
Henderson, Robert K.
中科院分区：
文献类型：
--
作者：
Della Rocca, Francescopaolo Mattioli;Nedbal, Jakub;Henderson, Robert K.
时间相关单光子计数 (TCSPC) 是一种基本的荧光寿命测量技术，可提供高信噪比 (SNR)。然而，它对直方图处理的复杂软件算法的要求限制了流式细胞仪的吞吐量并阻碍了细胞的即时分选。我们提出了一种单点数字硅光电倍增管 (SiPM) 检测器，可实现流式细胞术中实时荧光寿命激活的靶向细胞分选应用。该传感器还实现了 TCSPC 的突发积分荧光寿命 (BIFL) 检测。 SiPM 是一款单芯片互补金属氧化物半导体 (CMOS) 传感器，采用 32 x 32 单光子雪崩二极管 (SPAD) 阵列和八对时间交错时间数字转换器 (TI-TDC)，最小定时分辨率为 50 ps。该传感器的抗堆积嵌入式质心法 (CMM) 处理器可实现低延迟测量和荧光寿命阈值设置。数字控制信号的生成延迟为 16.6 μs，用于细胞分选机的启动，允许最大细胞吞吐量为每秒 60,000 个细胞，错误率为 0.6%。 (C) 2016年美国光学学会
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 x 32 single-photon avalanche diode (SPAD) array and eight pairs of time-interleaved time to digital converters (TI-TDCs) with a 50 psminimum 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 mu s latency for cell sorter actuation allowing a maximum cell throughput of 60,000 cells per second and an error rate of 0.6%. (C) 2016 Optical Society of America