Nanoneedles enable spatiotemporal lipidomics of living tissues
Spatial biology provides high-content diagnostic information by mapping the molecular composition of tissues. However, traditional spatial biology approaches typically require non-living samples, limiting temporal analysis. Here, to address this limitation, we present a workflow using porous silicon nanoneedles to repeatedly collect biomolecules from live brain tissues and map lipid distribution through desorption electrospray ionization mass spectrometry imaging. This method preserves the integrity of the original tissue while replicating its spatial molecular profile on the nanoneedle substrate, accurately reflecting lipid distribution and tissue morphology. Machine learning analysis of 23 human glioma biopsies demonstrated that nanoneedle sampling enables the precise classification of disease states. Furthermore, a spatiotemporal analysis of mouse gliomas treated with temozolomide revealed time- and treatment-dependent variations in lipid composition. Our approach enables non-destructive spatiotemporal lipidomics, advancing molecular diagnostics for precision medicine.
Authors
- Mads S. Bergholt (ORCID: https://orcid.org/0000-0003-3986-8942)
- Leor Ariel Rose (ORCID: https://orcid.org/0000-0001-5542-8002)
- Chenlei Gu (ORCID: https://orcid.org/0009-0006-3034-5319)
- Assaf Zaritsky (ORCID: https://orcid.org/0000-0002-1477-5478)
- Siham Memdouh
- Khuloud T. Al‐Jamal (ORCID: https://orcid.org/0000-0001-5165-2699)
- Alaa Zam (ORCID: https://orcid.org/0000-0001-5485-7307)
- Shiyue Liu (ORCID: https://orcid.org/0000-0002-2582-5055)
- Valeria Caprettini (ORCID: https://orcid.org/0000-0002-2743-5536)
- Maddy Parsons (ORCID: https://orcid.org/0000-0002-2021-8379)
- Davide Alessandro Martella (ORCID: https://orcid.org/0000-0002-7577-1630)
- Magnus T. Jensen (ORCID: https://orcid.org/0000-0002-0544-5215)
- Nadia Rouatbi
- Paul Martin Brennan (ORCID: https://orcid.org/0000-0002-7347-830X)
- Cathleen Hagemann (ORCID: https://orcid.org/0000-0002-9900-3556)
- Andrea Serio (ORCID: https://orcid.org/0000-0002-7271-1878)
- Ciro Chiappini (ORCID: https://orcid.org/0000-0002-9893-4359)
- Vincenzo Abbate (ORCID: https://orcid.org/0000-0002-3300-0520)
- Cong Wang (ORCID: https://orcid.org/0000-0003-0263-1933)
Institutions
- Ben-Gurion University of the Negev (IL)
- King's College London (GB)
- Wenzhou Medical University (CN)
- The Francis Crick Institute (GB)
- London Centre for Nanotechnology (GB)
- Affiliated Eye Hospital of Wenzhou Medical College (CN)
- UK Dementia Research Institute (GB)
- University of Hong Kong (HK)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Nanotechnology
- Published
- 2025-06-16
- DOI
- https://doi.org/10.1038/s41565-025-01955-8
- Citations
- 8
- Primary Topic
- Advanced Electron Microscopy Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 20.39
Funders
- Brain Research UK
- European Commission
- London Centre for Nanotechnology
- China Scholarship Council
- Directorate for Biological Sciences
- Medical Research Council
- Engineering and Physical Sciences Research Council