Cilia are minor miracles, and scientists are finally figuring out how to mimic them

A tiny movement of a microscopic cellular hair known as a cilia can’t do much on its own. But together, these structures routinely pull off biological miracles in the body. Cilia remove inhaled pathogens from the respiratory tract, transport cerebrospinal fluid through the brain cavities, transport eggs from the ovary to the uterus, and drain mucus from the middle ear to the nasal cavity. These tiny extracellular organelles exert precise microfluidic control over the body’s life-sustaining fluids. To better understand how these all-important natural wonders work, scientists have been trying to mimic them for years.

Now researchers have come a step closer, creating a chip covered in artificial cilia that can precisely control the tiny patterns of fluid flow. The developers hope that this technology will become the basis of new portable diagnostic devices. Currently, many diagnostic laboratory tests are time-consuming, resource-intensive, and require immediate human support. A cilia-covered chip, the researchers say, could enable field tests that would be easier, cheaper and more efficient than lab tests, and use much smaller samples of blood, urine or other test material.

Humans have achieved spectacular large-scale engineering feats, but “we’re still kind of stuck when it comes to engineering miniaturized machines,” says Itai Cohen, a physicist at Cornell University and senior author of a new Nature study describing his team’s cilia chip. Researchers have previously tried to make artificial cilia that work using pressure, light, electricity and even magnets. But one big hurdle remains: designing extremely small actuators — the parts of the machine that set the machine in motion — that can be controlled individually or in small clusters, rather than all at once.

The Cornell researchers overcame this hurdle by taking inspiration from some things they learned in their previous work. In August 2020, Guinness World Records recognized Cohen and his team for designing the world’s smallest walking robot, a machine that was only a fraction of a millimeter wide and could walk on four bendable legs. Like those legs, the new artificial cilia are made of a bendable nanometer-thin film that can respond to electrical control. Each cilia is one-twentieth of a millimeter long (less than half the length of a mite) and 10 nanometers thick—thinner than the smallest cell organelle—with a strip of platinum on one side and a coating of titanium film on the other.

The key to the electrical control of these artificial cilia comes from their metallic composition. Running a low positive voltage through the cilia triggers a chemical reaction: when a drop of test fluid flows past it, the electrified platinum breaks down the water molecules in the drop. This releases oxygen atoms, which are absorbed into the platinum surface. The added oxygen stretches the band, causing it to bend in one direction. Once the voltage is reversed, the oxygen is pushed out of the platinum—and the cilium returns to its original shape. “So by oscillating the voltage back and forth, you can bend and unfold the strip, which will generate waves to drive the motion,” says Cohen. Meanwhile, the electrically inert titanium film stabilizes the structure.

Next, the researchers had to figure out how to model a surface with thousands of their artificial cilia. By simply bending and unfolding one after the other, these fine ribbons can propel a microscopic amount of fluid in a set direction. But to direct the droplet to flow in a more complex pattern, the researchers had to divide the surface of their chip into “ciliary units” of several dozen cilia each — each unit individually controllable. The Cornell team first designed a virtual control system by collaborating with researchers at the University of Cambridge to digitally simulate in three dimensions how a droplet would move on a cilia-covered chip.

After researchers have used these computer simulations to verify the theoretical aspects of what they are doing, they move on to produce a physical device. Their centimeter-wide chip is covered with about a thousand tiny platinum-titanium strips, divided into 16 ciliary units with 64 cilia each. Because each module is independently connected to a computer control system, the individual modules can be individually programmed and then coordinated to move the test fluid in any given direction. Working together, the 16 units can create almost endless combinations of flow patterns.

The team’s first device can steer droplets in specific patterns, but it’s not as efficient as the researchers would like. They are already planning next-generation chips with cilia that have more than one “hinge.” This will give them more bending ability, “which can allow you to have much more efficient fluid flow,” says Cohen.

The study “elegantly enlightened us on how independent, addressable control of arrays of artificial cilia can be realized by electronic signals to generate complex programmable microfluidic operations,” said Zuankai Wang, a microfluidics researcher at City University of Hong Kong, who was not involved in the new study. “We hope that mass production of untethered low-cost diagnostic devices can be achievable in the coming years.”

Since the new technology mimics biological structures, it makes sense to use it in medical applications. The researchers envision a cilia-covered chip as the basis of a diagnostic device that could test any sample of water, blood or urine to detect contaminants or markers of disease. The user would place a drop of blood or urine on the chip, and artificial cilia would carry the sample — along with any chemicals or pathogens in it — from one location to another, allowing it to mix and react with various testing agents as it moved. Biosensors built into the chip will measure the products of these chemical reactions and then direct the cilia to further manipulate the fluid flow, allowing the chip to perform additional tests to confirm the results. “This way you can do all the chemical experiments on a centimeter-sized chip that would normally happen in a chemical lab,” explains Cohen. “The chip can also be made to function on its own, as it can use small solar panels mounted on the chip itself.” Such a self-powered device would be ideal for field use.

“It’s amazing how they combined microelectronics with fluid mechanics,” said Manoj Chaudhuri, a materials scientist at Lehigh University who was not involved in the new study. The researchers have solved an important problem, but additional work will be needed to achieve the result, says Chaudhuri. “When they design a reactor system to analyze a drop of blood, there have to be local stations where they may even need to heat or cool the sample,” he says. “So it would be interesting to see how they can integrate all these aspects in a microreactor.”

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