# High-speed blind structured illumination microscopy via unsupervised algorithm unrolling

**Authors:** Zachary Burns, Junxiang Zhao, Ayse Z. Sahan, Jin Zhang, Zhaowei Liu

PMC · DOI: 10.1038/s41467-026-68693-w · Nature Communications · 2026-01-23

## TL;DR

This paper introduces a fast machine learning method for super-resolution microscopy, enabling real-time imaging of live cells with high detail.

## Contribution

The novel UBSIM algorithm uses unsupervised learning to accelerate blind-SIM by two to three orders of magnitude.

## Key findings

- UBSIM achieves similar resolution and image quality as traditional blind-SIM but with significantly faster processing.
- The method enables video-rate super-resolution imaging up to 50 Hz in live cells.
- UBSIM demonstrates superior generalization and reduced hallucinations compared to benchmark networks.

## Abstract

Blind structured illumination microscopy (blind-SIM) is a valuable tool for achieving super-resolution without the need for known illumination patterns. However, in its current formulation the algorithm requires many iterations to converge, leading to long inference times and limited use for real-time or video-rate imaging. We present unrolled blind-SIM (UBSIM), an algorithm which integrates a learnable neural network inside the unrolled iterations of the blind-SIM algorithm. UBSIM delivers a reconstruction speed two to three orders of magnitude faster than that of current iterative blind-SIM methods, while achieving similar resolution and image quality. Furthermore, we demonstrate that UBSIM can be trained in an unsupervised manner that reduces hallucinations and produces superior generalization capability when compared to benchmark super-resolution networks. We test UBSIM experimentally on live cells and present video-rate super-resolution imaging up to 50 Hz. Using our method, we observe dynamic remodeling of the endoplasmic reticulum with high spatiotemporal resolution.

Burns et al. introduce an unrolled, physics-informed machine learning method that speeds up blind structured illumination microscopy by orders of magnitude while preserving generalizability, enabling real-time superresolution imaging in live cells.

## Full-text entities

- **Diseases:** hallucinations (MESH:D006212)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932644/full.md

## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932644/full.md

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Source: https://tomesphere.com/paper/PMC12932644