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Talon Chandler

Publications and source records attributed to Talon Chandler.

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WaveOrder: A differentiable wave-optical framework for scalable biological microscopy with diverse modalities

Correlative computational microscopy can accelerate imaging and modeling of cellular dynamics by relaxing trade-offs inherent to dynamic imaging. Existing computational microscopy frameworks are either specialized or overly generic, limiting use to fixed configurations or domain experts. We introduce WaveOrder, a generalist wave-optical framework for imaging the architectural order of biomolecules. WaveOrder reconstructs diverse specimen properties from multi-channel acquisitions, with or without fluorescence. It provides a unified representation of linear optical properties and differentiable physics-based image formation models spanning widefield, confocal, light-sheet, and oblique label-free geometries. WaveOrder uses physics-informed ML to auto-tune model parameters and solve blind shift-variant restoration problems. This open-source, PyTorch-based framework enables scalable quantitative imaging across scales from organelles to adult zebrafish, and improves restoration of cellular structures in high-throughput experiments. We validate WaveOrder on diverse imaging applications, demonstrating its ability to recover biomolecular structure beyond the limits of existing approaches.

physics.optics

Spatio-angular fluorescence microscopy III. Constrained angular diffusion, polarized excitation, and high-NA imaging

We investigate rotational diffusion of fluorescent molecules in angular potential wells, the excitation and subsequent emissions from these diffusing molecules, and the imaging of these emissions with high-NA aplanatic optical microscopes. Although dipole emissions only transmit six low-frequency angular components, we show that angular structured illumination can alias higher frequency angular components into the passband of the imaging system. We show that the number of measurable angular components is limited by the relationships between three time scales: the rotational diffusion time, the fluorescence decay time, and the acquisition time. We demonstrate our model by simulating a numerical phantom in the limits of fast angular diffusion, slow angular diffusion, and weak potentials.

physics.optics

Spatio-angular fluorescence microscopy II. Paraxial 4$f$ imaging

We investigate the properties of a single-view fluorescence microscope in a 4$f$ geometry when imaging fluorescent dipoles without using the monopole or scalar approximations. We show that this imaging system has a spatio-angular band limit, and we exploit the band limit to perform efficient simulations. Notably, we show that information about the out-of-plane orientation of ensembles of in-focus fluorophores is recorded by paraxial fluorescence microscopes. Additionally, we show that the monopole approximation may cause biased estimates of fluorophore concentrations, but these biases are small when the sample contains either many randomly oriented fluorophores in each resolvable volume or unconstrained rotating fluorophores.

physics.optics

Spatio-angular fluorescence microscopy I. Basic theory

We introduce the basic elements of a spatio-angular theory of fluorescence microscopy, providing a unified framework for analyzing systems that image single fluorescent dipoles and ensembles of overlapping dipoles that label biological molecules. We model an aplanatic microscope imaging an ensemble of in-focus fluorescent dipoles as a linear Hilbert-space operator, and we show that the operator takes a particularly convenient form when expressed in a basis of complex exponentials and spherical harmonics$-$a form we call the dipole spatio-angular transfer function. We discuss the implications of our analysis for all quantitative fluorescence microscopy studies and lay out a path towards a complete theory.

physics.optics