Researchers have developed a capsule-based method that makes it possible to analyse the same cell through multiple experimental steps. The technology overcomes a long-standing limitation in cell research and could open new ways to study disease mechanisms at the single-cell level.
In a study published in the journal Science, visiting professor Linas Mazutis at Umeå University in Sweden and his research team present a new technology for analysing individual cells. The method addresses a long-standing technical challenge in cell research: until now, scientists have usually only been able to analyse each cell once, which has made it difficult to study how individual cells change or respond to different experimental conditions.
“All cells are different, and understanding those differences is key to understanding disease,” Mazutis said.
The new technology is based on an innovation that the researchers call semi-permeable capsule technology, using microscopic capsules each containing a single cell. The capsules have a liquid core surrounded by a thin, porous membrane. Small molecules, such as enzymes and chemical reagents, can pass through the membrane, while larger molecules like DNA and RNA are retained inside.
This makes it possible to analyse hundreds of thousands of individual cells simultaneously using standard laboratory equipment. The single cells can be treated and analysed multiple times without being lost or contaminated, something that has not been possible with earlier droplet-based techniques.
“The capsules combine the speed of microfluidics – a technology that works with extremely small liquid volumes – with the flexibility of traditional laboratory workflows,” Mazutis said.
“This makes it possible to carry out advanced molecular biology workflows step by step, while keeping each cell’s genetic material isolated.”
The researchers also show cells can be kept alive inside the capsules for extended periods, or broken down for genetic analysis. In addition, they introduce a new RNA sequencing approach that makes it easier to identify fragile or rare cell types – cells that often disappear when using existing methods.
According to the researchers, the technology is simple and scalable, making it suitable for widespread use in biological and medical research. Long term, it could contribute to deeper insights into how diseases arise at the cellular level and help pave the way for more precise and personalised treatments. For example, researchers could use the method to study how individual cancer cells in the same tumour respond differently to a drug, or to identify rare immune cells that drive disease but are often missed by existing techniques.