A US and Korean research team has developed a chip-like device that could be scaled up to rapidly sort and store thousands of individual living cells.
Researchers at Duke University and Daegu Gyeongbuk Institute of Science and Technology (DGIST) in South Korea hope the cell-sorting system will radically change research by allowing the fast, efficient control and separation of individual cells that could then be studied in vast numbers.
‘Most experiments grind up a bunch of cells and analyse genetic activity by averaging the population of an entire tissue rather than looking at the differences between single cells within that population,’ said Benjamin Yellen, an associate professor of mechanical engineering and materials science at Duke’s Pratt School of Engineering. ‘That’s like taking the eye colour of everyone in a room and finding that the average colour is grey, when not a single person in the room has grey eyes. You need to be able to study individual cells to understand and appreciate small but significant differences in a similar population.’
The study appears online May 14 in Nature Communications.
Yellen and his collaborator, Cheol Gi Kim of DGIST, printed thin electromagnetic components onto a slide. These patterns create magnetic tracks and elements like switches, transistors and diodes that guide magnetic beads and single cells tagged with magnetic nanoparticles through a thin liquid film.
Localised rotating magnetic fields move the beads and cells along specific directions etched into a track, while built-in switches direct traffic to storage sites on the chip. The result is an integrated circuit that controls small magnetic objects much like the way electrons are controlled on computer chips.
In the study, the engineers demonstrate a 3-by-3 grid of compartments that allow magnetic beads to enter but not leave. By tagging cells with magnetic particles and directing them to different compartments, the cells can be separated, sorted, stored, studied and retrieved.
‘You need to analyse thousands of cells to get the statistics necessary to understand which genes are being turned on and off in response to pharmaceuticals or other stimuli,’ Yellen said in a statement. ‘And if you’re looking for cells exhibiting rare behaviour, which might be one cell out of a thousand, then you need arrays that can control hundreds of thousands of cells.’
In HIV or cancer, most afflicted cells are active and can be targeted by therapeutics. A few rare cells, however, remain dormant, and avoid destruction before activating and bringing the disease out of remission. With the new technology, the researchers hope to watch millions of individual cells, pick out the few that become dormant, quickly retrieve them and analyse their genetic activity.
‘Maybe then we could find a way to target the dormant cells,’ said Yellen.
Kim added, ‘Our technology can offer new tools to improve our basic understanding of cancer metastasis at the single cell level, how cancer cells respond to chemical and physical stimuli, and to test new concepts for gene delivery and metabolite transfer during cell division and growth.’
The researchers now plan to demonstrate a larger grid of 8-by-8 or 16-by-16 compartments with cells, and then to scale it up to hundreds of thousands of compartments. If successful, their technology would lend itself well to manufacturing, giving scientists around the world access to single-cell experimentation.