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

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

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

Humans have achieved spectacular engineering feats on a large scale, but “we’re still stuck when it comes to engineering small machines,” says Itai Cohen, a Cornell University physicist and senior author of a new. Nature study describing his team’s eyelash chip. Researchers had previously tried to make artificial eyelashes that worked using pressure, light, electricity and even magnets. But a major hurdle remained: designing extremely small actuators—the parts that cause a machine to move—that can be controlled individually or in small groups rather than all at once.

The Cornell researchers addressed that hurdle by drawing 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 eyelashes are made of bendable, nanometer-thin film that can respond to electrical control. Each cilium is one-twentieth of a millimeter long (less than half the length of a dust mite) and 10 nanometers thick—thinner than the smallest cell organelle—with a strip of platinum on one side and a layer of titanium film. on the other hand. .

The key to the electrical control of these false eyelashes comes from their metallic composition. Driving a low positive voltage through a cilium causes a chemical reaction: as a drop of test liquid passes by, the electrified platinum breaks the water molecules inside the drop. This releases oxygen atoms, which are adsorbed on the platinum surface. The added oxygen stretches the ribbon, causing it to bend in one direction. Once the voltage is reversed, the oxygen leaves the platinum – and the cilium returns to its original shape. “So by swinging the tension back and forth, you can bend and undo the strip, which will generate waves to drive the movement,” 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 eyelashes. By simply bending and removing one after the other, these tiny strips can direct a microscopic amount of fluid in a specific direction. But to direct a droplet to flow in a more complex pattern, the researchers had to divide the surface of their chip into “ciliary units” with several dozen cilia each—with each unit individually controllable. The Cornell team first planned a control system virtually, collaborating with Cambridge University researchers to digitally simulate in three dimensions how a droplet would move over a cilia-covered chip.

After the researchers had used these computer simulations to check the theoretical aspects of what they were doing, they went on to produce a physical device. Their centimeter-wide chip is coated with about a thousand tiny platinum-titanium strips, divided into 16 ciliary units with 64 cilia each. Because each unit is independently connected to a computer control system, the individual units can be programmed separately 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 drive droplets into specific patterns, but it’s not as efficient as researchers would like. They are already planning next-generation chips with eyelashes that have more than one “hang”. This will give them more bending ability, “which can allow you to have much more efficient fluid flow,” says Cohen.

The study “elegantly illuminated how independent and addressable control of artificial arrays of cells could be realized via electronic signals to generate complex programmable microfluidic operations,” says Zuankai Wang, a microfluidics researcher at the City University of Hong Kong. , who was not involved in the new study. “We hope that mass production of low-cost offline diagnostic devices may be achievable in the coming years.”

Because 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 water, blood or urine sample for contaminants or markers of disease. A user would place a drop of blood or urine on the chip, and artificial eyelashes would carry the sample — along with any chemicals or pathogens inside it — from one location to another, allowing it to mix and react with various testing agents. as he moves. Biosensors built into the chip would measure the products of these chemical reactions and then direct the cilia to further manipulate the fluid flow, allowing the chip to run additional tests to confirm the results. “That way, you can do all the chemistry experiments, on a centimeter-sized chip, that would normally happen in a chemistry lab,” explains Cohen. “The chip can also be made to work on its own, as it can use small solar panels located on the chip itself.” Such a self-powered device would be ideal for field use.

“It’s amazing how they’ve combined microelectronics with fluid mechanics,” says Manoj Chaudhury, a materials scientist at Lehigh University who was not involved in the new study. The researchers have solved a fundamental problem, but bringing the resulting product to life will require further work, Chaudhury says. “When they design a reactor system to analyze a drop of blood, there have to be local stations where they might need to heat or cool the sample,” he says. “So it would be interesting to see how they can integrate all these aspects into a microreactor.”

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