Fluorescence lifetime imaging with distance and ranging using a miniaturised SPAD system.

In this work we demonstrate a miniaturised imaging system based around a time-gated SPAD array operating in a "chip-on-tip" manner. Two versions of the system are demonstrated, each measuring 23 mm × 23 mm × 28 mm with differing fields of view and working distances. Initial tests demonstrate contrast between materials in widefield fluorescence imaging (WFLIm) mode, with frame rates of > 2 Hz achievable. Following this, WFLIm images of autofluorescence in ovine lung tissue are obtained at frame rates of ~ 1 Hz. Finally, the ability of the second system to perform simultaneous WFLIm and time of flight (aka Flourescence Lifetime Imaging Distance and Ranging, FLImDAR) is also tested. This shows that the system is capable of 4 mm resolution of object separation when tested on 3D printed samples. It is further demonstrated as being able to perform scene reconstruction on autofluorescent lung tissue. This system is, to date, the smallest chip on tip WFLIm system published, and is the first demonstration of the FLImDAR technique in a compact, portable system.

Combined fluorescence lifetime and surface topographical imaging of biological tissue.

In this work a combined fluorescence lifetime and surface topographical imaging system is demonstrated. Based around a 126 × 192 time resolved single photon avalanche diode (SPAD) array operating in time correlated single-photon counting (TCSPC) mode, both the fluorescence lifetime and time of flight (ToF) can be calculated on a pixel by pixel basis. Initial tests on fluorescent samples show it is able to provide 4 mm resolution in distance and 0.4 ns resolution in lifetime. This combined modality has potential biomedical applications such as surgical guidance, endoscopy, and diagnostic imaging. The system is demonstrated on both ovine and human pulmonary tissue samples, where it offers excellent fluorescence lifetime contrast whilst also giving a measure of the distance to the sample surface.

Handheld wide-field fluorescence lifetime imaging system based on a distally mounted SPAD array.

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.