Combined with confocal imaging, Fluorescence lifetime imaging microscopy (FLIM) can achieve 3-dimensional optical sectional capability with sub-nanosecond lifetime information. As confocal FLIM acquires multi-dimensional data 4D (3D space + time), it is inherently slow. Recent developments in lock-in pixel imagers with time gated pixels show such detectors are capable of collecting as many as 8-time gates in a single pixel cycle. We present a multiplexed confocal FLIM microscope, equipped with a 4-taps time-gated lock-in pixel imager. The multiplexing setup allows the use of the sparse array with sub-nanosecond time-gating to achieve high throughput FLIM acquisition.
We have developed and evaluated the large full well capacity (FWC) for wide signal detection range and low temporal noise for high sensitivity lock-in pixel CMOS image sensor (CIS) embedded with two storage-diodes (SDs). In addition, for fast charge transfer from photodiode (PD) to SDs, a lateral electric field charge modulator (LEFM) is used for the developed lock-in pixel. As a result, the time-resolved CIS achieves a very large FWC of approximately 7000e-, low temporal random noise of 1.17e-rms at 45fps with true correlated double sampling (CDS) operation, and fast intrinsic response less than 500ps at 635nm. The proposed imager has an effective pixel array of 128(H)×256(V) and a pixel size of 11.2×11.2μm2. The sensor chip is fabricated by a Dongbu HiTek 1P4M 0.11μm CIS process.
Recently, CMOS time-resolved imaging devices are being widely used for scientific and medical applications. A fluorescence lifetime imaging microscopy (FLIM), which is a powerful analysis tool in fundamental physics as well as in the life science, is a typical application for the time-resolved imaging devices. For better time-resolution in the lock-in pixel design, a multi-tap pixel architecture is very effective and useful. In this paper, we have proposed an 8-tap CMOS lock-in pixel with lateral electric field charge modulator (LEFM) and demonstrated the effectiveness of designed pixel by CAD simulation. The proposed pixel makes possible to measure the highly time-resolved images with a high signal to noise ratio (SNR) and to observe various images of cells even if a sample has a multi-lifetime component. An 8-tap time-resolved CMOS image sensor chip is developed by 0.11μm 1P4M CIS process technology.