Particle Localization Using Local Gradients and Its Application to Nanometer Stabilization of a Microscope.

Kashchuk, Anatolii V; Perederiy, Oleksandr; Caldini, Chiara; Gardini, Lucia; Pavone, Francesco Saverio; Negriyko, Anatoliy M; Capitanio, Marco · ACS Nano · 2022

basic_science · Level V

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Abstract

Particle localization plays a fundamental role in advanced biological techniques such as single-molecule tracking, superresolution microscopy, and manipulation by optical and magnetic tweezers. Such techniques require fast and accurate particle localization algorithms as well as nanometer-scale stability of the microscope. Here, we present a universal method for three-dimensional localization of single labeled and unlabeled particles based on local gradient calculation of particle images. The method outperforms state-of-the-art localization techniques in high-noise conditions, and it is capable of 3D nanometer accuracy localization of nano- and microparticles with sub-millisecond calculation time. By localizing a fixed particle as fiducial mark and running a feedback loop, we demonstrate its applicability for active drift correction in sensitive nanomechanical measurements such as optical trapping and superresolution imaging. A multiplatform open software package comprising a set of tools for local gradient calculation in brightfield, darkfield, and fluorescence microscopy is shared for ready use by the scientific community.