A CMOS In-Pixel CTIA High Sensitivity Fluorescence Imager.

Area of Science:

• Biomedical Imaging
• Image Sensor Technology
• Low-Light Imaging

Background:

• Charge-Coupled Device (CCD) sensors dominate biomedical imaging due to high sensitivity.
• Complementary Metal-Oxide-Semiconductor (CMOS) imagers traditionally lack sensitivity, hindering low-light performance.
• A need exists for imagers combining CCD sensitivity with CMOS advantages like low power and compactness, especially for animal-mountable systems.

Purpose of the Study:

• To develop a high-sensitivity CMOS imager array suitable for demanding biomedical applications.
• To achieve performance metrics comparable to CCDs while retaining CMOS benefits.
• To demonstrate the imager's capability in real-world biological imaging scenarios.

Main Methods:

• Fabrication of a 132×124 imager array using a standard 0.5 μ CMOS process with 20.1 μm pixel pitch.
• Integration of n-well/p-sub photodiodes, capacitive transimpedance amplifier (CTIA) for in-pixel amplification, pixel scanners, and delta differencing circuits.
• Utilized a 5-transistor all-nMOS pixel design with peripheral pMOS transistors for column-parallel CTIA.

Main Results:

• Achieved a minimum detectable signal of 4 nW/cm² at 450 nm and 70 frames per second (fps), consuming only 718 μA at 3.3 V.
• Demonstrated a peak signal-to-noise ratio (SNR) of 44 dB at 1 μW/cm² incident intensity.
• Enabled high frame rates (675 fps) via 4×4 binning or enhanced sensitivity (0.8 nW/cm² detection) at 70 fps. Single-cell fluorescence imaging achieved 28 fps with 32 dB SNR, outperforming a cooled CCD camera in power consumption.

Conclusions:

• The developed CMOS imager offers a compelling alternative to CCDs in biomedical imaging, particularly for low-light and power-constrained applications.
• The imager provides high sensitivity, excellent image quality, and flexibility for various scientific investigations, including in vivo imaging.
• This technology advances the development of compact, low-power, high-performance imaging systems for biological research.