Tiny ‘Rover’ Explores Cells without Harming Them

When Deblina Sarkar wanted to name her lab’s new creation the “Cell Rover,” her students were hesitant. “They were like, ‘it seems too cool for a scientific technology,’” she says. But Sarkar, a nanotechnologist at the Massachusetts Institute of Technology, wanted the tiny device’s name to evoke exploration of unknown worlds. This rover, however, will roam the inside of a living cell rather than the surface of a planet.

Recent engineering advances have enabled scientists to shrink electronics down to the cellular scale—with hopes of potentially using them to explore and manipulate the innards of individual cells. But such a rover would need to receive instructions and transmit information—and communicating with devices this small can be extremely difficult. “Miniaturizing an antenna to fit inside the cell is a key challenge,” Sarkar says. The problem involves the electromagnetic waves that are used with most conventional antennas, like those in cell phones, to transmit and receive data. Antennas operate best at their so-called “resonant frequencies,” which occur at wavelengths roughly equal to the antenna’s actual length. Because of the mathematical relationship between a wave’s speed, frequency and wavelength, waves with shorter wavelengths have higher frequencies. Unfortunately, subcellular antennas have to be so tiny that they require frequencies in the microwave range. And like the beams in a kitchen microwave, these signals “just fry up the cells,” Sarkar says. But she and her colleagues think they have a solution. In a Nature Communications paper, they describe a new antenna design that can operate safely inside cells by resonating with acoustic rather than electromagnetic waves. A functioning antenna could help scientists power, and communicate with, tiny roving sensors within the cell, helping them better understand these building blocks and perhaps leading to new medical treatments.

Sarkar and her team machined their experimental antenna from a “magnetostrictive” material—one that changes shape when exposed to a magnetic field. The researchers chose a widely available alloy of iron, nickel, boron and molybdenum, a combination already used in other kinds of sensors. When an alternating-current magnetic field is applied to this magnetostrictive antenna, the north and south poles of its molecules align themselves with the changing magnetic field, flipping back and forth, which stretches the material. This motion makes the antenna vibrate like a tiny tuning fork. Like any magnetic material, the antenna produces its own magnetic field in response to the external one, but because it is vibrating, its motion alters its new magnetic field in ways that a receiver can detect. This allows for two-way communication.

The key difference between a conventional antenna and the Cell Rover is the translation of electromagnetic waves into acoustic waves. “Their antenna resonates not based on the wavelength of light, but on the wavelength of sound,” explains Jacob Robinson, a Rice University neuroengineer who was not involved in the study. Like larger traditional antennas, the Cell Rover hits its resonant frequency when waves have a wavelength equal to its length—but the waves that stimulate this frequency are sound waves, which travel much more slowly than electromagnetic waves. Because the relationship between a wave’s wavelength and frequency also depends on its speed, sound waves and electromagnetic waves with the same wavelength will have different frequencies. In other words, the external magnetic field can signal the Cell Rover using waves with frequencies outside the harmful microwave range. “It’s a clever approach,” Robinson says.

The researchers first tested the Cell Rover in air and water, and they found that the antenna’s frequency of operation was 10,000 times smaller than that of an equivalent electromagnetic antenna—low enough to avoid killing live cells. Next the team tested the device within a living system: the egg cell of the African clawed frog, a model organism. Since the Cell Rover was made from a magnetic material, the researchers could use a magnet to pull it into each test cell. After these insertions, the egg cells looked healthy under a microscope and had not sprung any leaks. While inside the egg cell, the Cell Rover was able to receive an electromagnetic transmission and send a responding signal outward, up to a distance of one centimeter. The researchers also added multiple different-sized Cell Rovers to a single cell, and found they could distinguish the transmission signals of individual rovers.

Despite the progress in shrinking the Cell Rover, the prototypes themselves were still relatively large. At just over 400 micrometers (0.4 millimeters) long, they were too sizeable to fit inside many cell types. So the scientists computationally simulated the operation of an antenna about 20 times smaller than the ones they tested. They found these hypothetical rovers could retain a similar communication range—but they have yet to build them. Robinson says the range will also have to be increased to enable such devices to work in living organisms. “I think more work needs to be done to add functionality,” Robinson adds. “They are not yet doing anything biologically relevant.”

So far the scientists have only showed that the Cell Rover can work in principle, using it to send empty signals; this type of transmission can be thought of as being a little like static on a TV. Next they will try to determine what kind of “shows” they can watch by outfitting the rover with tiny instruments that could collect and convey information about the rover’s surroundings. For instance, they might add a simple polymer coating that would bind to nearby ions or proteins. When these substances stick to the polymer they would change the Cell Rover’s mass, and this in turn would alter the acoustic vibrations it produces. By measuring these changes, researchers could assess a cell’s protein or ion levels.

A Cell Rover might also be adapted for more complex applications. It might be possible to someday use such devices to destroy cancer cells, to electrically alter signaling pathways in order to influence cell division or differentiation, or even to serve as a power source for other miniature devices. “We can not only do intracellular sensing and modulate the intracellular activities, but we can power nanoelectronic circuits,” Sarkar says. Such miniscule electronics could also steer the Cell Rover on an exploratory journey, like its much-larger namesakes: they would allow it to analyze sensor data and modify the cellular environment without a scientist’s input. “It will someday be able to make autonomous decisions,” Sarkar says. “The opportunities are just limitless.”