The quiver of tiny cellular hairs called cilia doesn’t do much on its own. But together, these structures often produce biological miracles in the body. Cilia clear inhaled pathogens from the respiratory tract, carry cerebrospinal fluid across the brain cavity, transport eggs from the ovaries to the uterus, and expel mucus from the middle ear into the nasal cavity. These tiny extracellular organelles exert precise microfluidic control over life-sustaining fluids in the body. To better understand how these important natural wonders work, scientists have been trying to mimic them for years.
Now researchers have come close to doing just that, creating a Chips covered with artificial cilia The tiny flow patterns of fluids can be precisely controlled. The developers hope the technology will be the basis for new portable diagnostic devices. Currently, many diagnostic laboratory tests are time-consuming, resource-intensive, and require close human support. The researchers say the cilia-covered chips could be tested in the field, which is easier, cheaper and more effective than lab-based tests — as well as using smaller samples of blood, urine or other test materials.
Humans have achieved amazing feats of large-scale engineering, but “we’re still kind of stuck when it comes to engineering miniaturized machines,” said Itaiken, a Cornell physicist and senior author of the new paper. nature The study describes his team’s cilia chip. Researchers have previously tried to create artificial cilia that work through pressure, light, electricity and even magnets. But a major hurdle remains: Designing extremely tiny actuators — the motion-triggered parts of a machine — that can be controlled individually or in small clusters, rather than all at once.
Cornell researchers jumped that hurdle by drawing inspiration from some of what they learned from their earlier work. In August 2020, Guinness World Records recognized Cohen and his team’s design The world’s smallest walking robot, a machine just a fraction of a millimeter wide that can walk on four bendable legs. Like those legs, the new artificial cilia are made of bendable nanofilms that can respond to electronic control. Each cilia is one-twentieth of a millimeter long (less than half the length of a dust mite) and 10 nanometers thick—thinner than the smallest organelle—with a strip of platinum on one side and a titanium membrane on the other.
The key to electrically controlling these artificial cilia is their metallic composition. Running a low positive voltage through the cilia triggers a chemical reaction: When a drop of test fluid flows past, the charged platinum breaks up the water molecules in the drop. This releases oxygen atoms, which are absorbed by the platinum surface. The added oxygen stretches the strip, causing it to bend in one direction. Once the voltage was reversed, oxygen was expelled from the platinum—and the cilia returned to their original shape. “So by oscillating the voltage back and forth, you can bend and straighten the strip, which will create waves that drive the motion,” Cohen said. At the same time, the electrically inert titanium film stabilizes the structure.
Next, the researchers had to figure out how to pattern the surface with thousands of artificial cilia. By simply bending and straightening one by one, these thin strips can drive tiny amounts of fluid in a set direction. But to guide the droplets to flow in more complex patterns, the researchers had to divide their chip surface into “ciliary units” each consisting of dozens of cilia — each of which could be individually controlled. The Cornell team first planned a control system virtually, working with researchers at the University of Cambridge to digitally simulate in three dimensions how droplets move on a cilia-covered chip.
Once researchers use these computer simulations to examine theoretical aspects of what they do, they go on to produce physical devices. Their centimeter-wide chips are covered with about a thousand tiny platinum-titanium strips, divided into 16 ciliated units, each with 64 cilia. Because each unit is independently connected to a computerized control system, each unit can be individually programmed and then coordinated to move the test fluid in any given direction. Thus, these 16 units work together to create an almost endless combination of flowing patterns.
The team’s first device can drive specific patterns of droplets, but it’s not as efficient as the researchers had hoped. They are now planning next-generation chips with cilia that have more than one “hinge.” This will give them more bending ability, “which allows you to have more efficient fluid flow,” Cohen said.
The research “elegantly enlightens how we can achieve independent, addressable control of artificial ciliary arrays through electronic signals to generate complex programmable microfluidic manipulations,” said Zuankai Wang, a microfluidics researcher at City University of Hong Kong, who was not involved in the new study. Research. “Hopefully, unrestricted mass production of low-cost diagnostic devices will be achievable within the next few years.”
Since the new technology mimics biological structures, it makes sense to use it for medical applications. The researchers envision a cilia-covered chip as the basis for a diagnostic device that could test any sample of water, blood or urine for contaminants or markers of disease. The user puts a drop of blood or urine on the chip, and the artificial cilia carry the sample—along with any chemicals or pathogens in it—from one place to another, where it mixes and reacts with various test reagents. move. Biosensors built into the chip will measure the products of these chemical reactions and then guide the cilia to further manipulate the flow of the fluid, allowing the chip to perform additional tests to confirm the results. “In this way, you can do all the chemistry experiments on a centimeter-sized chip that you would normally do in a chemistry lab,” Cohen explained. “The chip can also operate on its own because it can use a small solar panel mounted on the chip itself.” This self-powered device is ideal for use in the field.
“It’s amazing how they combine microelectronics with fluid mechanics,” said Manoj Chaudhury, a materials scientist at Lehigh University who was not involved in the new study. The researchers have solved a fundamental problem, but further work is needed to put the final product into practice, Chaudhury said. “When they design a reactor system to analyze a drop of blood, there must be local sites, and they may even have to heat or cool the sample,” he said. “So it will be interesting to see how they can integrate all these aspects into one microreactor.”