Time-Resolved Four-Tap Lock-In Pixel CMOS Image Sensor for Real-Time Fluorescence Lifetime Imaging Microscopy
Time-Resolved Four-Tap Lock-In Pixel CMOS Image Sensor for Real-Time Fluorescence Lifetime Imaging Microscopy
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DOI：
10.1109/jssc.2018.2827918
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发表时间：
2018-08-01
影响因子：
5.4
通讯作者：
Kawahito, Shoji
中科院分区：
文献类型：
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作者：
Seo, Min-Woong;Shirakawa, Yuya;Kawahito, Shoji
开发了一种可编程亚纳秒时间选通四抽头CMOS锁定像素（LIP）图像传感器，其使用像素内脉冲发生器（PG），用于时间分辨（TR）生物医学成像应用，例如荧光寿命成像显微镜（FLIM）。我们证明了系统的有效性与模拟和测量。使用像素级PG电路，小于0.8 ns的非常窄的时间窗口（TW）可用于电荷调制。这种快速门控允许以高信噪比（SNR）捕获来自活细胞的非常弱的信号。原型CMOS成像系统在472 nm处显示出170 ps的快速本征响应，并且在使用两级电荷转移的真正相关双采样操作下，在45帧/秒处显示出0.85 e-rms的非常低的时间随机噪声。来自LIP的四个输出允许实时荧光寿命（FLT）测量，即使是来自具有多个FLT组分的样品。
A programmable sub-nanosecond time-gated four-tap CMOS lock-in pixel (LIP) image sensor that uses an in pixel pulse generator (PG) is developed for time-resolved (TR) biomedical imaging applications, such as a fluorescence lifetime imaging microscopy (FLIM). We demonstrate the system's effectiveness with simulations and measurements. Using pixel-level PG circuits, very narrow time windows (TWs) that are less than 0.8 ns can be used for charge modulation. This rapid gating allows very weak signals from living cells to be captured with a high signal-to-noise ratio (SNR). The prototype CMOS imaging system displays a fast intrinsic response of 170 ps at 472 nm and a very low temporal random noise of 0.85 e-rms at 45 frames/s under truly correlated-double-sampling operation using two-stage charge transfer. Four outputs from the LIPs allow real-time fluorescence lifetimes (FLTs) measurement, even from samples with multiple FLT components.