Nanoneedle Patch Enables Non-Invasive Tissue Sampling Offering Spatiotemporal Insights
By Allison Proffitt
June 19, 2025 | Nanoneedle technology developed by researchers from King’s College London offers the ability to extract molecular information from living tissue without damaging or killing cells—offering spatial and longitudinal molecular insights that Ciro Chiappini describes as a “fundamental scientific breakthrough.” The paper was published in Nature Nanotechnology this week (DOI: https://doi.org/10.1038/s41565-025-01955-8).
The researchers use fabricated porous silicon nanoneedles that can sample the intracellular space of living tissue without perturbing their function. The technology builds on previous work Chiappini published in Nature Materials in 2015 (DOI: 10.1038/nmat4249), which demonstrated that similar nanoneedles could be used in mice without causing inflammatory responses or cell death, providing confidence that the approach could eventually be translated to human applications.
When applied to tissue, these needle arrays create what researchers describe as an imprint or replica that captures proteins, lipids, and mRNA from the cellular environment without perturbing the cell.
“You're sampling the intracellular space in a non-invasive way,” Chiappini explained. “You're managing to extract cytosolic material while keeping your cells alive.”
The nanoneedle replica preserves both the molecular content and the spatial relationships between different tissue regions. Each needle samples from a specific location, maintaining the relative positions and allowing researchers to identify borders and cellular junctions in the data.
Clinical Use Cases
Chiappini’s lab has previously used nanoneedles to deliver gene therapies and CRISPR. “About half of our work is on biosampling, but the other half—because we can access the intercellular space—we can do non-viral, topical delivery very effectively.” However, he noted that optimizing the technology for both sampling and delivery presents challenges, as the requirements for each application can conflict.
The current work focuses on testing glioma biopsies removed from patients, thinly sliced and kept in culture. But Chiappini foresees in vivo uses, particularly during brain surgeries when surgeons need to make critical decisions about tissue removal. Currently, surgeons must remove tissue samples and wait for frozen section analysis, which can take up to an hour and often provides limited information.
“They really need to have a very high certainty about whether that tissue is a tumor or not,” Chiappini noted, because removing healthy brain tissue can result in devastating functional losses. The nanoneedle technology could gather samples from a patient during surgery and when those samples are analyzed, provide more robust information without removing any tissue.
Of course clinical trials will be required before the technology can be used directly on patients, but Chiappini predicted other promising applications as well:
- Atherosclerotic plaques: Traditional sampling would cause dangerous ruptures, but the nanoneedles could gather information during routine stent procedures
- Head and neck cancers: Regular monitoring without repeated biopsies
- Accessible areas: Mouth, neck, and upper gastrointestinal tract examinations
The Real Scientific Breakthrough
Chiappini emphasized that the most significant scientific contribution of the work is the enabled spatiotemporal ‘omics—the ability to repeatedly sample the same tissue over time while maintaining spatial resolution. This capability allows researchers to study how diseases develop and progress at the molecular level over time, something that has been impossible with traditional sampling methods that destroy tissue. He predicts this capability will be particularly valuable for understanding tumor microenvironments and drug resistance pathways.
The nanoneedle patches are manufactured using semiconductor processes and can be produced on wafers up to 18 inches in diameter, though practical medical applications would use much smaller patches. The sampling process takes only about ten seconds, and the collected material can be analyzed using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for lipids or other analytical techniques for proteins and RNA. He says his team is also using the 10X Visium platform.
For longitudinal studies, researchers apply new patches at different time points to the same tissue, then use algorithms to align the spatial data—a common practice in spatial biology research.
“It lays the groundwork for future understanding of longitudinal disease development,” Chiappini said. The research team is currently working with large consortiums to apply the technology to understanding tumor microenvironment dynamics and drug resistance mechanisms.