NEW YORK (GenomeWeb News) — Researchers in the US and Korea have devised a microchip-like device that they say can sort single particles and cells for individual analysis, as they reported in Nature Communications today.
This device, which they likened to a random access memory chip included in a computer, traps magnetic particles or cells that have been tagged with magnetic nanoparticles into compartments, isolating single cells in their own slots.
While the researchers, led by CheolGi Kim from the Daegu Gyeongbuk Institute of Science and Technology in Korea, noted that biological applications for the device are still downstream, they said that such a chip, particularly if scaled up, could enable single-cell studies and the examination of rare cells.
"Most experiments grind up a bunch of cells and analyze genetic activity by averaging the population of an entire tissue rather than looking at the differences between single cells within that population," co-author Benjamin Yellen, an associate professor of mechanical engineering and materials science at Duke University, said in a statement. "That's like taking the eye color of everyone in a room and finding that the average color 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 device Yellen and his colleagues developed also draws on the capabilities of magnetic bubble memory technology, in which magnetization bubbles in garnet films are moved along tracks to be stored at certain spots by manipulating the electric and magnetic circuitry of the film.
For this device, the researchers used both magnetic patterns and current lines to control where magnetic particles and tagged cells in aqueous suspension could go.
The magnetic patterns create passive circuitry that the researchers compared to the conductors, capacitors, diodes, and rectifiers of electronic circuits, while the current lines further lead to an active circuitry. Together, these active and passive circuits allow particles and cells to be shunted along various paths.
How the cells move is influenced by rotating magnetic fields of the device, but the researchers can also shift the energy along the device to control just where a particular particle can go.
Kim, Yellen, and their colleagues noted that various pathways could be arranged into closed loops to store particles and cells in certain regions, much like an electronic capacitor. For instance, in a clockwise driving field, they moved single, magnetic nanoparticle-labeled immune cells into the compartments of the device. Then when they reversed the field rotation, the cells were stuck in those spots due to the reverse bias of the diode junction.
Then by taking advantage of both active and passive transport elements, the researchers could alter what track a particle was on and direct it to another. For instance, applying a current line at the edge of a gap created a competing magnetic field that leads that gap to be conductive and move the particle. Further, by timing the current with the rotating magnetic field clock, the researchers could selectively move one particle, but not another.
Additionally, by reversing the rectifier bias by placing a diagonal current line at an angle on the opposite side of the rectifier junction, the researchers could enable a single particle or cell to escape their compartment when a gate current is applied. Again, by synchronizing that step to the magnetic field clock, they could pluck out one cell while leaving others behind.
This capability of allowing certain single cells to be removed, the researchers noted, will enable genome sequencing or other follow-on analyses.
They further multiplexed this system into a three-by-three grid with three horizontal and three vertical current lines that can control the deposition of nine particles or cells.
While the device currently is limited to that small grid of compartments, the researchers said they plan to develop larger grids of eight-by-eight and 16-by-16 before trying to then scale it up to include thousands of compartments.
"Our idea is a simple one," DGIST's Kim said. "Because it is a system similar to electronics and is based on the same technology, it would be easy to fabricate. That makes the system relevant to commercialization."