Fluorescence microscopy is a cornerstone of the physical and life sciences, yet its resolution and sensitivity remain limited by the optical diffraction limit and classical photon statistics. This PhD project, hosted within the Applied Quantum Technologies CDT and based in the Photophysics group at the University of Strathclyde, will develop a quantum-enhanced fluorescence lifetime imaging (FLIM) platform that combines time-correlated single-photon detection, photon-statistical quantum contrast, and AI-driven image reconstruction to achieve spatial resolution beyond classical limits.
Unlike conventional super-resolution techniques such as STORM or PALM, which rely on stochastic photoswitching and specialized fluorophores, this project will exploit the intrinsic quantum nature of fluorescence emission. Each fluorophore behaves as a quantum emitter, exhibiting photon antibunching. By analysing second-order photon correlation functions, g²(τ), across time and space, the system will extract quantum signatures that enhance localization precision and reveal nanoscale structural information, reducing dependence on complex switching schemes while remaining compatible with standard fluorescent labeling.
The imaging platform will employ wide-field single-photon avalanche diode (SPAD) arrays capable of detecting and time-tagging individual photons with sub-nanosecond precision. These solid-state detectors are compact, cost-effective, and well-suited for scalable imaging instrumentation. The temporal information contained in photon arrival times will be used not only to measure fluorescence lifetimes but also to extract sub-diffraction spatial information by analysing photon correlations. This multidimensional approach combines spatial, temporal, and photon-statistical information to enhance image resolution, contrast, and sensitivity beyond the limits of classical imaging.
Experimentally, the student will design, build, and characterise a SPAD-based, time-correlated FLIM microscope integrating high-speed timing electronics and machine-learning-based data processing. Initial experiments will use model nanostructures such as 120 nm DNA origami and fluorescent gold quantum dots, which provide well-defined spatial references for calibration and performance benchmarking. The system will then be applied to labelled exosomes and live cells, demonstrating its capability to resolve nanoscale biological features and dynamic molecular interactions. Detector characteristics, including dead time, timing jitter, and photon correlation fidelity, will be systematically assessed to optimise measurement accuracy and throughput.
The novelty of this project lies in its integration of quantum photon correlation analysis, fluorescence lifetime contrast, and AI-based reconstruction, forming a new paradigm in quantum-enhanced microscopy. Rather than relying on chemical modification or complex excitation schemes, it harnesses the intrinsic quantum statistics of fluorescence emission to extract more information per detected photon. This provides a scalable, biologically compatible route to sub-diffraction imaging, bridging the gap between quantum measurement science and applied bioimaging.
This research aligns closely with EPSRC priorities in Quantum Technologies, Artificial Intelligence, and Information and Communication Technologies (ICT), contributing to the Engineering theme and the UK National Quantum Strategy. Through the CDT’s interdisciplinary training, the student will gain expertise across quantum optics, single-photon detection, and computational imaging, preparing them to advance the next generation of quantum-enhanced sensing and bioimaging technologies.