Citation: Zhaoming Chen, Qinglong Qiao, Yalin Huang, Zhaochao Xu. The promise of bioluminescence as an alternative to fluorescence for surgical guidance and super-resolution microscopy[J]. Chinese Chemical Letters, ;2026, 37(11): 112622. doi: 10.1016/j.cclet.2026.112622 shu

The promise of bioluminescence as an alternative to fluorescence for surgical guidance and super-resolution microscopy

Zhaoming Chen ^a ,
Qinglong Qiao ^a ,
Yalin Huang ^{a, b} ,
Zhaochao Xu ^{a, b, *,}

a.
State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
b.
University of Chinese Academy of Sciences, Beijing 100049, China

zcxu@dicp.ac.cn

Received Date: 8 March 2026
Revised Date: 11 March 2026
Accepted Date: 12 March 2026
Available Online: 13 March 2026

Figures(5)

Fluorescence imaging technologies have revolutionized biomedical research and clinical practice, with fluorescence-guided surgery (FGS) and fluorescence super-resolution microscopy (FL-SRM) representing two landmark applications that have transformed cancer treatment and cellular biology, respectively. Despite these pivotal advances, both modalities share a fundamental limitation: Their dependence on external excitation light, which inevitably leads to insufficient tissue penetration depth, endogenous autofluorescence background interference, and excitation-induced phototoxicity, critical barriers to in vivo deep-tissue imaging in FGS and long-term dynamic observation in FL-SRM. Bioluminescence (BL), which generates photons through luciferase-catalyzed substrate oxidation without any external excitation, offers a compelling alternative that fundamentally circumvents these limitations. In this perspective, we systematically review the state-of-the-art advances and inherent bottlenecks of the two fluorescence imaging frontiers, highlight the disruptive potential of BL imaging to redefine next-generation image-guided surgery and super-resolution microscopy, and critically analyze the key remaining challenges for its clinical translation.
- Fluorescence-guided surgery,
- Bioluminescence,
- Super-resolution microscopy,
- Luciferin substrate engineering,
- Optical imaging
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