Novel tools for in vivo fluorescence lifetime imaging using miniaturised SPAD arrays
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Date
2026-03-31
Authors
Angelone, Dario
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Publisher
University College Cork
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Abstract
This thesis presents the development, validation, and application of novel tools for in vivo fluorescence lifetime imaging (FLIm) using miniaturised single-photon avalanche diode (SPAD) arrays. FLIm can enhance biochemical specificity by enabling discrimination between fluorophores with overlapping emission spectra but distinct fluorescence lifetimes (FLT). It is also sensitive to the local molecular environment, making it valuable for label-free diagnostics. The core technology applied in the thesis is the EndoCam, a compact 128 × 120 SPAD array with time-gated photon counting capability and a footprint of 2.0 mm × 1.4 mm, designed for integration into chip-on-tip endoscopic systems.
The thesis demonstrates the integration of the EndoCam into three distinct FLIm platforms: (i) a bench-top wide-field system for metabolic imaging of ex vivo tumour tissue using planar pH sensors (Paper I); (ii) a miniaturised imager for portable diagnostics, validated through measure ment of polymer beads and imaging of stained porcine tissue (Paper II); and (iii) a chip-on-tip FLIm micro-camera with a 4 mm outer diameter – the first of its kind at a scale compatible with endoscopic deployment – capable of resolving features below 30 μm and benchmarked against a time-correlated single-photon counting (TCSPC) system (Paper III).
To support system benchmarking and clinical translation, a set of solid-state fluorescence lifetime standards using dyed epoxy resins was developed (Paper IV). These standards span lifetimes from sub-nanosecond to over 3.5 ns, and were evaluated for photostability, fabrication repeatability, and microstructural uniformity using a confocal microscope.
Together, these contributions establish a foundation for compact, disposable chip-on-tip FLIm systems suitable for clinical applications such as endoscopy and image-guided surgery; this helps advance the translation of FLIm from research to real-world diagnostics, paving the way for future clinical deployment.
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Keywords
Fluorescence lifetime imaging , Single-photon avalanche diode , Chip-on-tip imaging , Time-gated photon counting , Wide-field FLIm , Biophotonics , Miniaturised imaging systems , Endoscopy , Tissue diagnostics
Citation
Angelone, D. 2026. Novel tools for in vivo fluorescence lifetime imaging using miniaturised SPAD arrays. PhD Thesis, University College Cork.