Chip-based label-free incoherent super-resolution optical microscopy

Nikhil Jayakumar; Luis E. Villegas-Hernández; Weisong Zhao; Hong Mao; Firehun T. Dullo; Jean-Claude Tinguely; Krizia Sagini; Alicia Llorente; Balpreet Singh Ahluwalia

doi:10.1038/s41377-025-01914-x

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Chip-based label-free incoherent super-resolution optical microscopy

Original Articles

- Chip-based label-free incoherent super-resolution optical microscopy
- Chip-based label-free incoherent super-resolution optical microscopy
- LSA 2025年14卷第9期页码：2772-2783
- Affiliations：
  
  1.Department of Physics and Technology, UiT The Arctic University of Norway, Tromsø 9037, Norway
  2.Innovation Photonics and Imaging Center, State Key Laboratory of Space Environment Interation with Matters, Key Laboratory of Ultra-Precision Intelligent Instrumentation of Ministry of Industry and Information Technology, School of Instrumentation Science and Engineering, Harbin Institute of Technology, Harbin 150080, China
  3.SINTEF Digital department of Microsystems and Nanotechnology, Gaustadalleen 23C, 0373 Oslo, Norway
  4.Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
  5.Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello 0379 Oslo, Norway
  6.Department for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway
  7.Department of Clinical Science, Intervention and Technology, Karolinska Institute, Solna, Sweden
- Author bio：
  
  Nikhil Jayakumar (nik.jay.hil@gmail.com)
  Balpreet Singh Ahluwalia (Balpreet.singh.ahluwalia@uit.no)
- Funds：
- DOI：10.1038/s41377-025-01914-x
  中图分类号：
- 收稿日期：2024-09-16，
  
  修回日期：2025-05-27，
  
  录用日期：2025-05-31，
  
  网络出版日期：2025-08-04，
  
  纸质出版日期：2025-09-30
- Accepted：
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Chip-based label-free incoherent super-resolution optical microscopy[J]. LSA, 2025,14(9):2772-2783.

Jayakumar, N. et al. Chip-based label-free incoherent super-resolution optical microscopy. Light: Science & Applications, 14, 2772-2783 (2025).
Chip-based label-free incoherent super-resolution optical microscopy[J]. LSA, 2025,14(9):2772-2783. DOI： 10.1038/s41377-025-01914-x.

Jayakumar, N. et al. Chip-based label-free incoherent super-resolution optical microscopy. Light: Science & Applications, 14, 2772-2783 (2025). DOI： 10.1038/s41377-025-01914-x.

摘要

Abstract

The photo-kinetics of fluorescent molecules have enabled the circumvention of the far-field optical diffraction

limit. Despite its enormous potential

the necessity to label the sample may adversely influence the delicate biology under investigation. Thus

continued development efforts are needed to surpass the far-field label-free diffraction barrier. The statistical similarity or finite coherence of the scattered light off the sample in label-free mode hinders the application of existing super-resolution methods based on incoherent fluorescence imaging. In this article

we present physics and propose a methodology to circumvent this challenge by exploiting the photoluminescence (PL) of silicon nitride waveguides for near-field illumination of unlabeled samples. The technique is abbreviated EPSLON

Evanescently decaying Photoluminescence Scattering enables Label-free Optical Nanoscopy. We demonstrate that such an illumination has properties that mimic the photo-kinetics of nano-sized fluorescent molecules

i.e.

such an illumination permits incoherence between the scattered fields from various locations on the sample plane. Thus

the illumination scheme enables the development of a far-field label-free incoherent imaging system that is linear in intensity and stable over time

thereby permitting the application of techniques like structured illumination microscopy (SIM) and intensity-fluctuation-based optical nanoscopy (IFON) in label-free mode to circumvent the diffraction limit. In this proof-of-concept work

we observed a two-point resolution of

$$ \sim $$

180 nm on super-resolved nanobeads and resolution improvements between 1.9× to 2.8× over the diffraction limit

as quantified using Fourier Ring Correlation (FRC)

on various biological samples. We believe EPSLON is a step forward within the field of incoherent far-field label-free super-resolution microscopy that holds a key to investigating biological systems in their natural state without the need for exogenous labels.

关键词

Keywords

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