A Single‐Capillary Open Microfluidic Probe for Robust and Versatile Spatial Multi‐Omics Using Ambient Mass Spectrometry Imaging
5 affiliations
- 1Department of Chemistry Hong Kong Baptist University Hong Kong China
- 2School of Marine Sciences Hainan University Haikou China
- 3Single‐Cell Proteomics Research Center, ZJU‐Hangzhou Global Scientific and Technological Innovation Center Zhejiang University Hangzhou China
- 4State Key Laboratory of Soil Pollution Control and Safety Department of Environmental Science Zhejiang University Hangzhou China
- 5School of Chemistry College of Science Eastern Institute of Technology Ningbo Zhejiang China
Abstract
High‐resolution spatial mapping of tissue molecular architecture—from metabolites and lipid isomers to native proteins—remains a central challenge for ambient mass spectrometry imaging (MSI). Existing methods typically rely on multi‐capillary, alignment‐sensitive liquid‐extraction probes, compromising robustness and compatibility with structure‐resolved spatial omics. We mitigate this trade‐off by introducing a monolithic, knot‐shaped open microfluidic probe (Knot‐probe) fabricated from a single capillary. Knot‐probe achieves 40 µm scan‐direction spatial resolution and acquisition throughput up to 0.16 mm s−1, yet can be fabricated in ∼30 min with standard laboratory tools and operated reliably for over one month. Without sacrificing conventional spatial lipidomics and metabolomics, Knot‐probe enables structure‐resolved spatial omics, delivering high‐resolution imaging of phosphatidylcholine sn‐positional isomers via tandem MS and, in a pneumatically‐assisted variant, native MSI of proteins and proteoforms with higher throughput and enhanced sensitivity than with probes lacking pneumatic assistance. These capabilities arise from the integrated knot geometry, which ensures a stable micro‐liquid junction for localized extraction with a minimized sampling footprint and efficient mass transfer, while eliminating intricate probe alignment for robust operation. Readily integrated with standard electrospray ionization MS, Knot‐probe bridges conventional ambient MSI and emerging structural spatial omics, offering a broadly accessible approach across diverse biological and chemical applications.
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BibTeX
@article{zhu2026singlecapillary,
title = {{A Single‐Capillary Open Microfluidic Probe for Robust and Versatile Spatial Multi‐Omics Using Ambient Mass Spectrometry Imaging}},
author = {Xiangyu Zhu and Yunkai Li and Jianing Wang and Chengyi Xie and Lei Guo and Yanyan Chen and Thomas Ka‐Yam Lam and Shao‐Wen Shi and Kun Wang and Baoliang Chen and Zongwei Cai},
journal = {Advanced Science},
year = {2026},
month = nov,
doi = {10.1002/advs.78657},
url = {https://doi.org/10.1002/advs.78657},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Single‐Capillary Open Microfluidic Probe for Robust and Versatile Spatial Multi‐Omics Using Ambient Mass Spectrometry Imaging
AU - Xiangyu Zhu
AU - Yunkai Li
AU - Jianing Wang
AU - Chengyi Xie
AU - Lei Guo
AU - Yanyan Chen
AU - Thomas Ka‐Yam Lam
AU - Shao‐Wen Shi
AU - Kun Wang
AU - Baoliang Chen
AU - Zongwei Cai
PY - 2026
DA - 2026/11/05
JO - Advanced Science
DO - 10.1002/advs.78657
UR - https://doi.org/10.1002/advs.78657
AB - High‐resolution spatial mapping of tissue molecular architecture—from metabolites and lipid isomers to native proteins—remains a central challenge for ambient mass spectrometry imaging (MSI). Existing methods typically rely on multi‐capillary, alignment‐sensitive liquid‐extraction probes, compromising robustness and compatibility with structure‐resolved spatial omics. We mitigate this trade‐off by introducing a monolithic, knot‐shaped open microfluidic probe (Knot‐probe) fabricated from a single capillary. Knot‐probe achieves 40 µm scan‐direction spatial resolution and acquisition throughput up to 0.16 mm s−1, yet can be fabricated in ∼30 min with standard laboratory tools and operated reliably for over one month. Without sacrificing conventional spatial lipidomics and metabolomics, Knot‐probe enables structure‐resolved spatial omics, delivering high‐resolution imaging of phosphatidylcholine sn‐positional isomers via tandem MS and, in a pneumatically‐assisted variant, native MSI of proteins and proteoforms with higher throughput and enhanced sensitivity than with probes lacking pneumatic assistance. These capabilities arise from the integrated knot geometry, which ensures a stable micro‐liquid junction for localized extraction with a minimized sampling footprint and efficient mass transfer, while eliminating intricate probe alignment for robust operation. Readily integrated with standard electrospray ionization MS, Knot‐probe bridges conventional ambient MSI and emerging structural spatial omics, offering a broadly accessible approach across diverse biological and chemical applications.
SN - 2198-3844
ER -