Scientists have long faced a major challenge when studying how genes behave inside living cells: to measure gene activity, they usually have to destroy the cells. Traditional methods of RNA extraction rely on cell lysis, a process that breaks open the cell membrane to release its contents. While this allows scientists to analyze RNA, the messenger molecules that reflect which genes are active, it also means that each sample provides only a single snapshot in time. Once a cell is lysed, it’s gone, making it impossible to observe how gene expression changes as cells respond to their environment, treatment, or disease.

Researchers from the National University of Singapore have now introduced an elegant solution to this problem. Their new technique, called nanoelectroextraction (NEE), allows scientists to sample RNA from living cells without harming them. This innovation makes it possible to track changes in gene expression over hours or even days, providing a continuous view of cellular activity that traditional methods simply can’t offer.

So how does NEE work? The system uses a membrane made of tiny, hollow tubes called nanostraws, each just a few hundred nanometers wide, thousands of times thinner than a human hair. When placed against a layer of cells, the nanostraws gently connect to the cell surface. A mild electric pulse is then applied, creating small, temporary openings in the cell membrane. Through these openings, a small amount of RNA is drawn into the nanostraws and collected for analysis.

Because the process is so gentle, the cells remain alive and functional. The researchers confirmed that the technique doesn’t disrupt normal cell behavior or gene expression patterns. The extracted RNA can then be analyzed using powerful molecular biology tools such as RNA sequencing (RNA-seq) and qPCR, giving scientists detailed information about which genes are turned on or off at different times.

To demonstrate the method’s versatility, they applied NEE to several cell systems, including A549 lung cells, primary human lung fibroblasts, monocyte-derived macrophages, and 3D cancer spheroids. Over the course of three days, they were able to repeatedly sample RNA from the same living cultures. This allowed them to monitor dynamic biological events such as cytokine-induced gene reprogramming and gene silencing by siRNA treatment. Remarkably, the RNA profiles obtained through NEE matched closely with those from traditional destructive methods, confirming the reliability and accuracy of the technique.

The ability to perform longitudinal RNA sampling, that is, tracking gene activity in the same cells over time, opens up new opportunities in cell biology, drug discovery, and disease modeling. For instance, researchers can now follow how immune cells respond to infection or how cancer cells adapt to therapies in real time. The technology is also especially valuable when working with rare or hard-to-obtain samples, such as patient-derived tissues or stem cells, where every cell matters.

In essence, nanoelectroextraction provides a powerful new platform for studying the dynamic nature of life at the molecular level. By enabling repeated, non-destructive RNA analysis, it brings scientists closer to understanding how living cells behave, adapt, and communicate—information that could lead to more effective diagnostics and treatments in the future.