Nanoneedle arrays map RNA in fresh tissue without sequencing or amplification

Recently, spatial omics has become a powerful tool, enabling researchers to see not only what molecules are present in a tissue, but also where they are located and how they are organized across cells, tissue structures and local microenvironments. This spatial context has deepened our understanding of cancer, neurobiology and immunology. Yet as the field advances, an important question remains: How many of these powerful technologies are ready for routine clinical use?

The most informative technologies are often the most demanding, requiring expensive instruments, sequencing, complicated tissue preparation, lengthy workflows and substantial computational resources. While these requirements are manageable in well-resourced research settings, they can become major obstacles in pathology laboratories, where time-sensitive biopsies, clinical practicality and broad patient access are critical considerations.

Nanoprobes simplify tissue sampling

To address this challenge, a research team led by Shi Peng, a professor in the Department of Biomedical Engineering in the College of Biomedicine at City University of Hong Kong (CityUHK), has presented Spectrum-FISH, a sequencing-free and amplification-free approach to spatial tissue analysis. The method is based on a “touch-and-go” molecular fishing strategy that uses vertically aligned nanoprobes.

Unlike existing spatial omics technologies, which typically require extensive tissue pretreatment, Spectrum-FISH can be applied directly to freshly prepared tissue samples. Spatial information is preserved through a registration strategy that allows researchers to map molecular signals back to tissue structures and individual cells.

Fresh tissues reveal broader potential

Using experiments involving the developing mouse neural tube and olfactory bulb and fresh human colorectal biopsy specimens, the research team investigated whether spatial profiling could be made more accessible by reducing dependence on sequencing, minimizing tissue processing and lowering assay costs while maintaining biologically informative resolution.

Spectrum-FISH’s compatibility with fresh tissues and sequencing-free design offer advantages in affordability and scalability. Its coordinate-preserving sampling strategy also points to new possibilities for spatial analysis in live or minimally processed tissues. Moreover, its ability to profile messenger RNAs (mRNAs), microRNAs (miRNAs) and RNA methylation provides a potential pathway toward spatial multi-omics that are less dependent on large-scale sequencing infrastructure.

Clinical translation gains momentum

The findings were published recently in Nature Biomedical Engineering in a paper titled “Sequencing-free spatial profiling of post-transcriptional regulation in fresh tissues using nanoneedle arrays”. The study aligns closely with the themes discussed in a recent comment article, “Clinical translation of spatial omics”, co-authored by Shi and published in Nature Reviews Bioengineering. Together, the two publications underscore the growing momentum toward the clinical translation of spatial omics.

“This project reminded us that innovation in biomedicine is about more than enabling measurements; it must also ensure they are practical and accessible,” said Shi. “By simplifying workflows and reducing costs while preserving spatial insight, we hope Spectrum-FISH demonstrates how spatial omics technologies can move closer to routine clinical application.

“Ultimately, we believe the future of spatial omics will be defined not only by how deeply we can map tissues, but also by how effectively we can translate those maps into meaningful clinical action.”

Who’s behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021.

Full profile →

Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

Full profile →