A miniaturized 1.4mm × 1.4mm, 128 × 120 single photon avalanche diode (SPAD) image sensor with a 5-wire interface is designed for time-resolved fluorescence microendoscopy. This is the first endoscopic chip-on-tip sensor capable of fluorescence lifetime imaging microscopy (FLIM). The sensor provides a novel, compact means to extend the photon counting dynamic range (DR) by partitioning the required bitdepth between in-pixel counters and off-pixel noiseless frame summation. The sensor is implemented in STMicroelectronics 40nm/90nm 3D-stacked backside-illuminated (BSI) CMOS process with 8 µm pixels and 45% fill factor. The sensor capabilities are demonstrated through FLIM examples, including ex-vivo human lung tissue, obtained at video rate.
In this work a handheld Fluorescent Lifetime IMaging (FLIM) system based on a distally mounted < 2 mm2 128 × 120 single photon avalanche diode (SPAD) array operating over a > 1 m long wired interface is demonstrated. The head of the system is ∼4.5 cm x 4.5 cm x 4.5 cm making it suitable for hand-held ex vivo applications. This is, to the best of the authors’ knowledge, the first example of a SPAD array mounted on the distal end of a handheld FLIM system in this manner. All existing systems to date use a fibre to collect and relay fluorescent light to detectors at the proximal end of the system. This has clear potential biological and biomedical applications. To demonstrate this, the system is used to provide contrast between regions of differing tissue composition in ovine kidney samples, and between healthy and stressed or damaged plant leaves. Additionally, FLIM videos are provided showing that frame rates of > 1 Hz are achievable. It is thus an important step in realising an in vivo miniaturized chip-on-tip FLIM endoscopy system.
Fluorescence lifetime imaging (FLIM) is a valuable technique which can be used to provide label free contrast between different tissue types and provide information about their molecular makeup and local environment. FLIM systems based on single photon avalanche diode (SPAD) arrays are increasingly being used in applications such as medical imaging due to their high sensitivity and excellent temporal resolution [1]. Additionally, SPAD arrays are also commonly employed for time of flight (ToF) imaging techniques such as light detection and ranging (LiDAR) [2]. Here we demonstrate a system which employs both of these modalities into a single instrument, allowing us to acquire both depth and widefield FLIM images simultaneously using a single 32 x 32 pixel SPAD array operating in time correlated single-photon counting (TCSPC) mode with 50 ps temporal resolution. Initial results show that we can correctly measure depths and distances of sample objects with < 1 cm resolution while maintaining excellent and consistent fluorescence contrast. Lifetime is consistent over a distance of 10 cm with a standard deviation of < 0.5 ns, showing that it is possible to decouple depth and lifetime data. We believe this work is the first demonstration of a widefield FLIM system capable of 3D imaging. The next step will be the addition of a miniaturized system [1] and future applications for this technology include fields such as surgical guidance, endoscopy and diagnostic imaging.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.