Large depth of field real-time drift correction method and system based on programmable point spread function

By employing a real-time drift correction method based on programmable point spread function, and utilizing the maximum likelihood estimation algorithm and the Cramer-Rao lower bound optimization algorithm to switch the PSF, combined with a triaxial nanostage for real-time compensation, the problem of high-precision drift correction over a large axial range was solved, achieving stable and high-resolution imaging in live cell imaging.

CN121740758BActive Publication Date: 2026-06-26ZHEJIANG NORMAL UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZHEJIANG NORMAL UNIV
Filing Date
2026-02-27
Publication Date
2026-06-26

AI Technical Summary

Technical Problem

Existing technologies struggle to achieve high-precision drift correction over a wide axial range, especially in long-term live-cell imaging. Current post-processing correction techniques cannot dynamically adjust the PSF, resulting in poor drift correction performance.

Method used

A real-time drift correction method based on programmable point spread function is adopted. Images are acquired in real time by a high frame rate camera, the drift amount is calculated by the maximum likelihood estimation algorithm, and the optimal PSF is switched based on the Cramer-Rao lower bound optimization algorithm. Combined with a three-axis nanometer displacement stage, real-time closed-loop compensation is performed to achieve a positioning accuracy of 1nm in the 6μm axial range.

Benefits of technology

It achieves high-precision drift correction over a wide axial range, taking into account both the continuity and stability of the correction, adapting to the irregular changes in the axial position of the sample in live cell imaging, and meeting the requirements of ultra-high resolution imaging.

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Abstract

This invention discloses a large depth-of-field real-time drift correction method and system based on a programmable point spread function (PSF). This invention achieves wide-range, high-precision drift correction by dynamically switching different PSF modes, solving the problem of the trade-off between axial correction range and accuracy in existing technologies. This invention includes a marker detection module, a dynamic PSF switching module, and a closed-loop control module. It automatically selects the optimal PSF mode based on the real-time detected drift: astigmatic PSF is enabled when |z|≤1 μm, switching to double-helix PSF when 1μm<|z|≤2μm, Bessel PSF when 2μm<|z|≤3μm, and cloverleaf PSF is activated when |z|>3μm. Through adaptive PSF switching, this invention achieves full closed-loop real-time correction within a 6μm axial range, with a drift suppression error ≤2 nm, making it suitable for long-term super-resolution imaging of live cells.
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