Novel tools for in vivo fluorescence lifetime imaging using miniaturised SPAD arrays

dc.contributor.advisorAndersson-Engels, Stefan
dc.contributor.advisorKonugolu, Sanathana
dc.contributor.advisorBurke, Ray
dc.contributor.authorAngelone, Darioen
dc.contributor.funderHorizon 2020en
dc.contributor.funderResearch Irelanden
dc.contributor.funderEngineering and Physical Sciences Research Councilen
dc.date.accessioned2026-05-20T14:20:32Z
dc.date.available2026-05-20T14:20:32Z
dc.date.issued2026-03-31
dc.date.submitted2026-03-31
dc.description.abstractThis 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.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAngelone, D. 2026. Novel tools for in vivo fluorescence lifetime imaging using miniaturised SPAD arrays. PhD Thesis, University College Cork.
dc.identifier.endpage143
dc.identifier.urihttps://hdl.handle.net/10468/18800
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Professorship Programme/15/RP/2828/IE/Novel applications and techniques for in vivo optical imaging and spectroscopy/
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Research Professorship Programme::Second-Term Funding/22/RP-2TF/10293/IE/Biophotonics@Tyndall phase 2 - Novel applications and techniques for in vivo optical imaging and spectroscopy/
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Research Centres Programme::Phase 2/12/RC/2276_P2/IE/IPIC_Phase 2/
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/860185/EU/Photonics for Healthcare: multiscAle cancer diagnosiS and Therapy/PHAST
dc.relation.projectResearch Ireland (EPSRC Interdisciplinary Research Collaboration, Grant no: EP/K03197X/1)
dc.rights© 2026, Dario Angelone.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectFluorescence lifetime imagingen
dc.subjectSingle-photon avalanche diodeen
dc.subjectChip-on-tip imagingen
dc.subjectTime-gated photon countingen
dc.subjectWide-field FLImen
dc.subjectBiophotonicsen
dc.subjectMiniaturised imaging systemsen
dc.subjectEndoscopyen
dc.subjectTissue diagnosticsen
dc.titleNovel tools for in vivo fluorescence lifetime imaging using miniaturised SPAD arraysen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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