Optical microcavity-enhanced fluorescence detection for single molecules of explosives

Thesis

This thesis investigates the development and application of an open-access optical microcavity-enhanced fluorescence system for single-molecule sensing in the liquid phase, with a specific focus on trace explosive simulant detection. This research presents a novel cavity-based sensor integrated with microfluidics, enabling automated sample injection and dynamic sample switching without disrupting the system’s locking mechanism. The sensor’s performance was systematically characterised under both diffusion and flow conditions, revealing a dynamic concentration range for single-molecule detection between 1 × 10⁻¹⁰ M and 1×10⁻¹⁵M for a 120-second fixed collection time. However, the total dynamic concentration range of the whole system extends beyond this, as the sensor is also shown to operate in the multiple-molecule or "bulk" regime. The system therefore operates in two distinct modes: single-molecule and bulk detection, with the former being the focus of the research presented here. A proof-of concept assay for detecting explosive simulants successfully demonstrated the sensor’s selectivity, although further optimisation of the assay and improved modelling of non-spherical conjugate complexes are needed. Simulations of particle diffusion and flow provided insights into the sensor’s behaviour, though limitations arose due to the application of simplified particle models to the conjugate complexes explored in the assay chapter. The implications of this work extend to a variety of applications, including water quality monitoring, food safety, point-of-care diagnostics, early disease marker detection, and chemical sensing. This research establishes a highly sensitive and selective cavity-based sensor system, addressing key challenges in explosive trace detection, particularly in the presence of interferents.

Authors: Warman, P

• DOI: 10.5287/ora-j27b6w2yq
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English