Abstract
We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing.
Highlights
Fluorescence imaging has become one of major enabling techniques of modern biology, allowing sub-micron resolution of multiple markers within a single sample in three dimensions, to monitor dynamic cellular behaviors
The integrated circuit (IC) was interfaced with a field-programmable gate array (FPGA)
(Cyclone II, Altera, San Jose, CA, USA) for serial peripheral interface (SPI) control, and 20 low-voltage differential signaling (LVDS) (2 × 10 bit) output channels were connected to a high speed digital data acquisition module (NI PXIe-6555, National Instruments, Austin, TX, USA)
Summary
Fluorescence imaging has become one of major enabling techniques of modern biology, allowing sub-micron resolution of multiple markers (fluorophores) within a single sample in three dimensions, to monitor dynamic cellular behaviors. Such a system lowers manufacturing cost by orders of magnitude and miniaturizes the system while still maintaining core functionality (albeit with reduced resolution and signal-to-noise ratio (SNR)). This approach is amenable to a wide range of applications poorly suited to conventional FLIM systems, including: implantable applications where small size and weight are critical, surgical and endoscopic instruments, cost-sensitive field deployments, and massively parallel assays. The largest and most expensive components in the aforementioned conventional fluorescent imaging setup are the stimulus light, optical filters, and lens. Stimulus light cannot be eliminated because it is the source of excitation energy; many efficient solutions have been proposed to reduce its cost and size, such as the use of a μLED [7] or an on-chip optical waveguides that couples solid-state excitation through the chip from a shared off-chip source [8]
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