Photon-counting Raman spectroscopy at a MHz spectral rate for biochemical imaging of an entire organism

Sicheng Li, Haozheng Li, Yiran Li, Qi Zhang, Shuai Wang, Xin Lv, Shuai Yan, Zhiliang Huang, Xingbo Liu, Qipei Zhou, Bi Zhang, Long Xiao, Yage Chen, Zhe Wang, Wanjun Lu (), Aiguo Shen (), Jianfeng Liu () and Ping Wang ()
Additional contact information
Sicheng Li: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Haozheng Li: Changping Laboratory
Yiran Li: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Qi Zhang: Changping Laboratory
Shuai Wang: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Xin Lv: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Shuai Yan: Changping Laboratory
Zhiliang Huang: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Xingbo Liu: Earthome Technology Inc.
Qipei Zhou: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Bi Zhang: Huazhong University of Science and Technology
Long Xiao: China University of Geosciences
Yage Chen: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Zhe Wang: China University of Geosciences
Wanjun Lu: China University of Geosciences
Aiguo Shen: Wuhan Textile University
Jianfeng Liu: Huazhong University of Science and Technology
Ping Wang: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Raman spectroscopy, which probes fine molecular vibrations, is crucial for interpreting covalent bonds, chemical compositions, and other molecular dynamics in mixtures via their vibrational fingerprint signatures. However, over the past few decades, longstanding barriers have been encountered in both the sensitivity and speed of Raman spectroscopy, limiting its ability to be extended to broader biochemical applications. Here, we introduce a versatile analytical workhorse, the fiber-array Raman engine (termed FIRE). In FIRE, a distinctive fiber array bundle delays the Raman shifts at a scale of 3–960 ns, and a highly dynamic single-channel photon-counting detector achieves spectral measurements that outperform the best commercial confocal Raman microscope. Crucially, FIRE features a major advantage of nonrepetitive single-shot spectra measurement at a MHz repetition rate with a full Raman span (-300-4300 cm-1) covering the fingerprint, silent, C–H, and O–H regions and therefore represents a major step toward overall improving of sensitivity, speed, and spectral span. We demonstrate full Raman spectral imaging of the metabolic activity of intact Caenorhabditis elegans. FIRE exhibits superior performance to a Raman microscope in all aspects, including autofluorescence suppression, and will elucidate a variety of biochemical applications.

Date: 2025
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DOI: 10.1038/s41467-025-59030-8

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