CMOS imaging arrays for high-speed fluorescence lifetime imaging

This technology is a CMOS-based imaging array with single-photon avalanche diodes (SPADs) and on-chip timing circuitry for high-speed fluorescence lifetime imaging microscopy (FLIM) using time-correlated single photon counting (TCSPC).

Unmet Need: Faster and scalable fluorescence lifetime imaging microscopy (FLIM) for live imaging

Current fluorescence lifetime imaging microscopy (FLIM) systems using time-correlated single photon counting (TCSPC) are limited to capture rates of at most 7 frames per second in conventional applications or require several seconds per image for high-resolution scanned imaging. These slow acquisition speeds prevent observation of dynamic biological processes and limit throughput for screening applications. Additionally, existing FLIM systems consist of large, expensive modular units that lack portability and require complex external readers for data acquisition and processing.

The Technology: Integrated CMOS-SPAD FLIM array with on-chip timing

This technology is a CMOS-based imaging array consisting of a 64 x 64 pixel array of single-photon avalanche diodes (SPADs) integrated with independent time measurement circuitry on a single CMOS chip, fabricated in 130-nm technology. Each pixel achieves photon arrival time measurements using delay-locked loop (DLL) based time-to-digital converters with sub-70 picosecond timing resolution and a 64-nanosecond range. The system utilizes a custom high-speed data path specifically designed for the sparse photon detection characteristic of FLIM measurements, allowing for data transmission rates of up to 42 Gbps via parallel low-voltage differential signaling drivers. The integrated design enables wide-field FLIM imaging at 200 frames per second or high-resolution (256×256) scanned imaging at up to 20 frames per second.

Applications:

• High-speed in vivo imaging of cellular structures and auto-fluorescent samples
• DNA and antibody-based assays through FRET (Förster Resonance Energy Transfer) interactions
• High-throughput screening assays for drug discovery
• Single molecule detection and identification
• DNA sequencing applications
• Optical tomography

Advantages:

• Enables fluorescence lifetime imaging microscopy (FLIM) video at up to 200 fps (vs. ~7 fps currently)
• Integrated SPAD detectors and timing circuitry on a CMOS chip
• Compact and potentially lower cost compared to modular systems
• Enables portable FLIM applications not possible with conventional modular systems
• Provides 20 fps high-resolution imaging versus several seconds per frame for existing scanning systems

Lead Inventor:

Kenneth L. Shepard, Ph.D.

Patent Information:

Patent Issued (US 9,831,283)

Tech Ventures Reference:

• IR CU12003

• Licensing Contact: Greg Maskel