Citation: Hua Guo, Ran Wu, Qichen Hao, Liang Qin, Lulu Chen, Hao Hu, Jie Feng, Lei Wang, Rui Liu, Difan Chen, Anna Wang, Zihan Wang, Xiangrui Cheng, Shuyu Hao, Xiaodong Wang, Huaqing Zhang, Gaopeng Li. Cluster airflow assisted matrix coating enhances high-resolution MALDI imaging of small molecules and lipids in tissues and cells[J]. Chinese Chemical Letters, ;2026, 37(8): 112335. doi: 10.1016/j.cclet.2025.112335 shu

Cluster airflow assisted matrix coating enhances high-resolution MALDI imaging of small molecules and lipids in tissues and cells

Hua Guo ^{a, 1} ,
Ran Wu ^{a, b, 1} ,
Qichen Hao ^{a, 1} ,
Liang Qin ^a ,
Lulu Chen ^a ,
Hao Hu ^a ,
Jie Feng ^c ,
Lei Wang ^a ,
Rui Liu ^a ,
Difan Chen ^a ,
Anna Wang ^a ,
Zihan Wang ^a ,
Xiangrui Cheng ^a ,
Shuyu Hao ^d ,
Xiaodong Wang ^{a, b, *,} ,
Huaqing Zhang ^{e, *,} ,
Gaopeng Li ^{f, *,}

a.
College of Life and Environmental Sciences, Centre for Imaging & Systems Biology, Minzu University of China, Beijing 100081, China
b.
College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
c.
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
d.
Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
e.
Department of Clinical Engineering, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China
f.
General Surgery Department, Shanxi Bethune Hospital, Taiyuan 030032, China

Xiaodong@muc.edu.cn

zhqnature@zju.edu.cn

malone2001@163.com

Received Date: 13 July 2025
Revised Date: 18 November 2025
Accepted Date: 28 December 2025
Available Online: 31 December 2025

Figures(4)

The matrix deposition method is one of the critical factors influencing the performance of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), as it determines matrix crystal sizes and coating uniformity, thereby impacting ionization efficiency and spatial resolution. Currently, automated sprayers are widely utilized for matrix deposition due to their convenience, speed, and robust reproducibility. However, existing automated spraying techniques typically produce micrometer-sized crystal particles, limiting high-resolution imaging quality and sensitivity. To overcome this, we introduce cluster airflow assisted matrix coating (CAAMC), which employs multiple cluster airflows to achieve a more uniform dispersion and atomization of the matrix droplets, resulting in nano-sized crystal particles—an advance beyond traditional deposition methods. This method represented the first successful automatic spray method for nano-matrix crystallization, surpassing regular-one channel pneumatic spraying and sublimation in producing smaller, more homogeneous crystals. Application to rat brain tissues and single cells demonstrates that CAAMC significantly enhances small molecule and lipid detection efficiency and imaging quality (lateral resolution of 5 μm), exceeding the performance of regular-one channel pneumatic spraying and sublimation. Overall, CAAMC significantly broadens the potential of automated matrix spraying techniques in high-resolution MALDI-MSI.
- Cluster airflow,
- Nano-matrix coating,
- Single cell,
- Tissue section,
- MALDI imaging
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