Optical Theory Group

Abstract : We investigate anisotropy in Fourier-domain speckle correlations associated with the optical memory effect in disordered scattering media. Within a single scattering framework, we show that while the conventional memory effect constrains transverse wavevector shifts, the correlation strength also depends non-trivially on differences in the axial wavevector components. Our theory is supported by numerical simulations of a three-dimensional, single scattering medium, which show excellent agreement with theory. We extend the analysis to pseudo-correlations, demonstrating that analogous anisotropic behavior arises in the conjugate memory effect. Our results highlight the often neglected role of axial disorder in scattered field correlations.

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.