Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction

Ipek Anil Atalay Appak; Haobijam Johnson Singh; Sanna Korpela; Teemu O. Ihalainen; Erdem Sahin; Christine Guillemot; Humeyra Caglayan

doi:10.1038/s41377-026-02337-y

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Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction

Original Articles

- Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction
- Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction
- Light: Science & Applications 2026年15卷第8期页码：2720-2734
- Affiliations：
  
  1.Physics Unit, Faculty of Engineering and Natural Sciences, Tampere University, Tampere 33720, Finland
  2.INRIA Rennes, Bretagne Atlantique Research Centre, Rennes 35042, France
  3.Bio Unit, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland
  4.Signal Processing Research Centre, Tampere University, Tampere 33720, Finland
  5.Department of Electrical Engineering, Photonic Integration Group, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands
- Author bio：
  
  Humeyra Caglayan (h.caglayan@tue.nl)
- Funds：
- DOI：10.1038/s41377-026-02337-y
  中图分类号：
- 收稿：2025-12-04，
  
  修回：2026-04-12，
  
  录用：2026-04-28，
  
  网络首发：2026-05-19，
  
  纸质出版：2026-08-31
- Accepted：
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Ipek Anil Atalay Appak, Haobijam Johnson Singh, Sanna Korpela, 等. Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction[J]. Light: Science & Applications, 2026,15(8):2720-2734.

Atalay Appak, I. A. et al. Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction. Light: Science & Applications, 15, 2720-2734 (2026).
Ipek Anil Atalay Appak, Haobijam Johnson Singh, Sanna Korpela, 等. Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction[J]. Light: Science & Applications, 2026,15(8):2720-2734. DOI： 10.1038/s41377-026-02337-y.

Atalay Appak, I. A. et al. Multispectral extended depth-of-field fluorescence microscopy with co-designed meta-optics and neural reconstruction. Light: Science & Applications, 15, 2720-2734 (2026). DOI： 10.1038/s41377-026-02337-y.

摘要

Abstract

High numerical aperture fluorescence microscopy provides subcellular resolution

but its depth of field is extremely limited

so thick specimens quickly fall out of focus and typically require axial scanning. Multispectral imaging further compoun

ds this problem because chromatic aberrations shift the best focus plane and distort registration across emission channels

especially in thick samples. In this work

we present MANTIS (Multispectral All-Depth meta-opTic Imaging System)

a co-designed computational microscopy imaging system that achieves extended depth-of-field from a single acquisition without axial scanning. MANTIS combines a learned meta-optic with a physics-guided neural network trained end-to-end to reconstruct sharp multispectral images from depth

and wavelength-dependent blurred sensor measurements. We experimentally demonstrate a 50

m extended depth of field at NA 1.1

corresponding to an 82-fold increase over a conventional wide-field microscope. In addition

simulations show that MANTIS can target different depth-of-field ranges

with the expected trade-off that larger depth-of-field ranges come at a cost in reconstruction fidelity. We validate the approach on biologically relevant fluorescence specimens

including 50

m thick three-dimensional cultured MDCK Ⅱ spheroids

and show that

compared with conventional wide-field fluorescence microscopy

reconstructions maintain contrast and lateral detail across depth

with reduced defocus blur and consistent performance across spectral channels.

关键词

Keywords

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