Optical Theory Group

Abstract : Lensless optical imaging eliminates the need for refractive optics, enabling compact and low-cost cameras with a large field-of-view, supporting point-of-care diagnostics and industrial monitoring. Practical deployments, however, remain constrained by ill-posed image reconstruction pipelines that require multiple measurements, careful calibration or object-specific training, thus limiting robustness and scalability. In this work, we introduce a single-shot lensless imaging framework that reconstructs complex objects from only a single recorded intensity pattern using a genetically programmed iterative algorithm. Our method couples a wave-propagation model with an adaptive meta-optimisation strategy to jointly estimate the object amplitude, object phase, and effective object-detector distance. Experiments demonstrate high-fidelity recovery of amplitude objects, including a USAF target and 2 μm silicon beads on a glass slide, as well as a phase-dominant biological sample consisting of U2OS cells on a glass slide. Across multiple object types, wavelengths, and propagation distances, the same learned policy maintains high reconstruction quality with minimal retuning, indicating strong out-of-distribution generalisation. As a practical demonstration, the framework is integrated with a β-amyloid-based optical digital bead assay under wide field-of-view acquisition. The resulting platform combines single-shot capture, compact hardware, and accurate reconstruction of complex fields, enabling rapid, portable assays in which throughput, alignment tolerance, and cost are critical.

Abstract : Amyloid-β42 assemblies form a dynamic network of oligomers and fibrils, with fibrillar species acting as reservoirs that maintain equilibrium among intermediates. Perturbing a single species shifts the oligomer-fibril balance, highlighting the challenge of selectively targeting toxic species while maintaining the dynamic equilibrium of the amyloid network. Here, we show that the small molecule EPPS (4-(2-hydroxyethyl)-1-piperazine-propanesulfonic acid) fine tunes this network through cooperative, concentration-dependent disaggregation. At optimal concentrations, EPPS efficiently shifts the equilibrium away from the fibrillar structures via multisite, allosteric interactions. At higher concentrations, EPPS self-assembles into supramolecular clusters, depleting free molecules and allowing partially disaggregated amyloid intermediates to reassemble. Notably, at elevated concentrations, interactions transition from molecule-to-molecule to higher-order ensemble-to-ensemble engagement, where EPPS clusters and amyloid fibrils mutually reshape each other's dynamics. Molecular crowding, modeled with polyethylene glycol, further restricts EPPS access to fibrillar surfaces, modulating activity. These findings reveal that small molecule dynamics, including cooperative binding, self-assembly, and environment-dependent accessibility, critically govern amyloid network control, providing a mechanistic blueprint for rational design of next-generation amyloid-targeting therapeutics.

Abstract : Modeling the propagation of light through disordered media is central to understanding and controlling wave transport in diverse optical and mesoscopic applications. Here, we present a random matrix simulation framework for modeling the transport of polarized light through random media composed of arbitrary particulate scatterers. Our approach employs extended scattering channels applied to angular spectral decompositions of the underlying fields, enabling flexible representations of arbitrary illumination and detection profiles. In contrast to previous work, this framework provides a rigorous treatment of scattering matrix correlations and offers novel geometric insights into the optical memory effect. We provide a detailed exposition of the underlying theory and illustrate several key features through numerical simulations. Our work is supported by a free accompanying codebase.