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Precise characterization of nanometer-scale systems using interferometric scattering microscopy and Bayesian analysis

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Abstract

Interferometric scattering microscopy can image the dynamics of nanometer-scale systems. The typical approach to analyzing interferometric images involves intensive processing, which discards data and limits the precision of measurements. We demonstrate an alternative approach: modeling the interferometric point spread function and fitting this model to data within a Bayesian framework. This approach yields best-fit parameters, including the particle’s three-dimensional position and polarizability, as well as uncertainties and correlations between these parameters. Building on recent work, we develop a model that is parameterized for rapid fitting. The model is designed to work with Hamiltonian Monte Carlo techniques that leverage automatic differentiation. We validate this approach by fitting the model to interferometric images of colloidal nanoparticles. We apply the method to track a diffusing particle in three dimensions, to directly infer the diffusion coefficient of a nanoparticle without calculating a mean-square displacement, and to quantify the ejection of DNA from an individual lambda phage virus, demonstrating that the approach can be used to infer both static and dynamic properties of nanoscale systems.

© 2023 Optica Publishing Group

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Supplementary Material (4)

NameDescription
Supplement 1       Supplemental document and tables.
Visualization 1       Recorded iSCAT images of a stationary 120 nm polystyrene sphere as the focal plane approaches the particle from bottom to top. The focal plane is translated over a total of 1800 nm.
Visualization 2       Recorded iSCAT images of a freely diffusing 79 nm polystyrene sphere, captured at 100 frames per second for a total of 900 ms.
Visualization 3       Recorded iSCAT images of a stationary lambda phage while it ejects its encapsulated DNA, captured at 10 frames per second for a total of 20 s.

Data availability

Data underlying the results presented in this paper are available in Ref. [39]. The source code for the forward model and inference calculations is available at Ref. [40].

39. X. M. de Wit, A. W. Paine, C. Martin, A. M. Goldfain, R. F. Rees, F. Garmann, and V. N. Manoharan, “Data for ‘Precise characterization of nanometer-scale systems using interferometric scattering microscopy and Bayesian analysis’,” Harvard Dataverse, V1, 2023, https://doi.org/10.7910/DVN/N7GJYC.

40. V. N. Manoharan, “Code used for analysis of iSCAT data,” GitHub (2023) https://github.com/manoharan-lab/applied-optics-iscat-code.

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