Deep-Penetrating and High-Resolution Continuous-Wave Nonlinear Microscopy Based on Homologous Dual-Emission Upconversion Adaptive Optics
Lanthanide-doped upconversion nanoparticles (UCNPs) are emerging as innovative nonlinear probes in biomedical studies, offering the unique capability to simultaneously emit both visible (VIS) and near-infrared (NIR) photons under continuous-wave (CW) NIR excitation. However, deep-tissue high-resolution imaging remains challenging due to the trade-off between VIS emission (higher resolution, limited penetration) and NIR emission (deeper penetration, lower resolution). Here we present a CW nonlinear microscopy based on homologous dual-emission upconversion adaptive optics, leveraging Tm<sup>3+</sup>/Yb<sup>3+</sup> co-doped UCNPs' dual 455 nm/800 nm emission: the 800 nm emission for aberration measurement (guide-star) in deep tissues and the 455 nm emission for high-resolution imaging at matching depths. Using a home-built nonlinear laser scanning microscope with a 975 nm CW laser, we achieved near-diffraction-limited imaging (480 nm laterally) at a 500 μm depth in the mouse brain environment with significant optical aberrations. This strategy expands UCNPs' applications and innovates the exploration of deep-tissue optical features.
Authors
- Jing Yao (ORCID: https://orcid.org/0000-0003-1301-9758)
- Qiuqiang Zhan (ORCID: https://orcid.org/0000-0002-5886-3795)
- Puxiang Lai (ORCID: https://orcid.org/0000-0003-4811-2012)
- Huanhao Li (ORCID: https://orcid.org/0000-0002-1652-6328)
- Wei Zheng (ORCID: https://orcid.org/0000-0002-9651-0915)
- Tianting Zhong (ORCID: https://orcid.org/0000-0002-3925-5903)
- Baoju Wang (ORCID: https://orcid.org/0000-0002-1879-0173)
- Zhiyuan Wang (ORCID: https://orcid.org/0000-0002-1966-2421)
- Hui Hui (ORCID: https://orcid.org/0000-0002-6732-4232)
- Yufeng Gao (ORCID: https://orcid.org/0000-0003-0032-3531)
- Zhipeng Yu (ORCID: https://orcid.org/0000-0002-9866-2672)
- Binxiong Pan
Institutions
- Hong Kong Polytechnic University (HK)
- Shenzhen Polytechnic University (CN)
- Chinese Academy of Sciences (CN)
- Photonics (United States) (US)
- Shandong Institute of Automation (CN)
- Key Laboratory of Guangdong Province (CN)
- Laboratoire d’Imagerie Biomédicale (FR)
- Shenzhen Institutes of Advanced Technology (CN)
Publication Details
- Journal
- Nano Letters
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1021/acs.nanolett.5c01030
- Citations
- 8
- Primary Topic
- Advanced Fluorescence Microscopy Techniques
- Type
- article
- Field-Weighted Citation Impact
- 13.07
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Hong Kong Polytechnic University
- Science, Technology and Innovation Commission of Shenzhen Municipality
- Basic and Applied Basic Research Foundation of Guangdong Province