Researchers at the National Center for Genomic Analysis (CNAG), located in the Barcelona Science Park, together with St. Jude Children’s Research Hospital (USA) and the University of Adelaide (Australia), have developed a groundbreaking technique called STAMP. This method enables the analysis of millions of individual cells simultaneously using next-generation spatial imaging platforms, without the need for sequencing. The study, published in the journal Cell, has demonstrated a significant reduction in both the time and cost of analysis, while exponentially increasing the number of cells that can be studied at once—from thousands to millions—thus offering an accessible alternative for research laboratories and pharmaceutical companies.

Until now, decoding the complexity of cells within the blood, tissues and organs meant reading millions of letters — A, G, C, and T — by sequencing and assembling them into an instruction book that reveals how a cell functions, whether healthy or diseased. But a revolutionary technique transformed single-cell analysis forever. For the first time, scientists can capture high-resolution snapshots of cells directly from liquid samples—without the need for sequencing.

The full name of this groundbreaking technique—Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging (STAMP)— reveals its key innovations. First, the method enables the study of individual cells from a wide range of sources, including blood samples (such as liquid biopsies), cancer cells, embryonic stem cells, either in the form of whole cells or isolated nuclei. Second, STAMP allows researchers to analyse the transcriptome (the RNA molecules that show which genes are expressed) and the proteome (the proteins that define how a cell functions), either independently or at the same time. Finally, the technique captures this molecular information by imaging the samples—taking snapshots using spatial genomics technologies—instead of sequencing them, additionally giving information on the shape and morphology of the cells.

According to Dr. Holger Heyn, Single-Cell Genomics Group Leader at CNAG and one of the authors of this method: “STAMP can be a game-changer for understanding complex diseases like cancer, neurodegenerative disorders, and autoimmune conditions. By revealing critical changes in cell morphology, RNA and protein profiles of millions of cells or hundreds of samples, STAMP uncovers hidden clues about disease biology and treatment response that were previously impossible to detect. With this technology, we open the door to revolutionary advances in precision medicine, enabling the development of highly targeted diagnostics and therapies that could transform patient outcomes”.

One of the key contributions of STAMP lies in making single-cell analysis faster and more accessible for research laboratories and pharmaceutical organisations. In addition to significantly reducing experimental costs and time, this method provides important molecular information that was difficult to obtain with traditional approaches, such as identifying ultra-rare populations like circulating tumor cells (CTCs), which are crucial for understanding cancer metastasis.

The main innovation of STAMP is its sample preparation. Instead of isolating cells in droplets, STAMP fixes and permeabilises cells in suspension and anchors them onto imaging-compatible glass slides, “stamping” them into uniform monolayers. This approach enables to analyse cells from liquid biopsies or in vitro cell cultures as if they would be tissue sections, using state-ofthe art spatial genomics instruments.

“These imaging-based approaches allow us to see not just what cells are doing at the
molecular level, but also where they are, how they are shaped, and whom they interact with” explains Dr. Anna Pascual-Reguant, Spatial Genomics Team Leader at CNAG and first author of the study. “By combining single-cell profiling with high-throughput imaging instruments, STAMP captures both the inner workings and physical properties of millions of cells in a single experiment. It brings single-cell biology one step further, making it more scalable, cost-effective, and multiplexable, and bridging the gap toward experimental systems such as in vitro co-cultures, and perturbation assays or drug screenings.”

» Article of reference: Pitino, E., Plummer, J., et al. (2025). STAMP: Single‑Cell Transcriptomics Analysis and Multimodal Profiling through Imaging. Cell. Advance online publication. https://doi.org/10.1016/j.cell.2025.05.027

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