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Starfish larva inspires drug delivery microrobot

The new microbot inspired by starfish larva stirs up plastic beads. (Credit: Cornel Dillinger/ETH Zurich)

Researchers have developed a tiny robot that mimics the movement of a starfish larva.

Among scientists, there is great interest in tiny machines that are set to revolutionize medicine. These microrobots, often only a fraction of the diameter of a hair, are made to swim through the body to deliver medication to specific areas and perform the smallest surgical procedures.

Natural microorganisms such as bacteria or algae often inspire the designs of these robots. The new microrobot is an ultrasound-activated synthetic system that mimics the natural arrangements of starfish ciliary bands and leverages nonlinear acoustics to replicate the larva’s motion and manipulation techniques.

Cilia are a key element

At first glance, the microrobots bear only scant similarity to starfish larva. In its larval stage, a starfish has a lobed body that measures just a few millimeters across. Meanwhile, the microrobot is a rectangle and 10 times smaller, only a quarter of a millimeter across. But the two do share one important feature: a series of fine, movable hairs on the surface, called cilia.

The starfish larva creates white swirls against a black background
Depending on whether it is swimming or feeding, the starfish larva generates different patterns of vortices. (Credit: Prakash Lab/Stanford University)

A starfish larva is blanketed with hundreds of thousands of these hairs. Arranged in rows, they beat back and forth in a coordinated fashion, creating eddies in the surrounding water.

The relative orientation of two rows determines the end result: Inclining two bands of beating cilia toward each other creates a vortex with a thrust effect, propelling the larva. On the other hand, inclining two bands away from each other creates a vortex that draws liquid in, trapping particles on which the larva feeds.

These cilia were the key design element for the new microrobot.

“In the beginning, we simply wanted to test whether we could create vortices similar to those of the starfish larva with rows of cilia inclined toward or away from each other,” says Daniel Ahmed, a professor of acoustic robotics for life sciences and health care at ETH Zurich.

 

To this end, the researchers used photolithography to construct a microrobot with appropriately inclined ciliary bands. They then applied ultrasound waves from an external source to make the cilia oscillate. The synthetic versions beat back and forth more than ten thousand times per second—about a thousand times faster than those of a starfish larva.

And as with the larva, these beating cilia can be used to generate a vortex with a suction effect at the front and a vortex with a thrust effect at the rear, the combined effect “rocketing” the robot forward.

In their lab, the researchers showed that the microrobots can swim in a straight line through liquid such as water. Adding tiny plastic beads to the water made it possible to visualize the vortices created by the microrobot. The result is astonishing: both starfish larva and microrobots generate virtually identical flow patterns.

Next, the researchers arranged the ciliary bands so that a suction vortex was positioned next to a thrust vortex, imitating the feeding technique used by starfish larva. This arrangement enabled the robots to collect particles and send them out in a predetermined direction.

The future of microrobots

Ahmed is convinced that this new type of microrobot will be ready for use in medicine in the foreseeable future. This is because a system that relies only on ultrasound offers decisive advantages: ultrasound waves are already widely used in imaging, penetrate deep inside the body, and pose no health risks.

The fact that this therapy requires only an ultrasound device makes it cheap, he adds, and hence suitable for use in both developed and developing countries.

Ahmed believes one initial field of application could be the treatment of gastric tumors. Uptake of conventional drugs by diffusion is inefficient, but having microrobots transport a drug specifically to the site of a stomach tumor and then deliver it there might make the drug’s uptake into tumor cells more efficient and reduce side effects.

But before this vision can be realized, a major challenge remains to be overcome: imaging. Steering the tiny machines to the right place requires that a sharp image be generated in real time. The researchers have plans to make the microrobots more visible by incorporating contrast agents such as those already used in medical imaging with ultrasound.

In addition to medical applications, Ahmed anticipates this starfish-inspired design to have important implications for the manipulation of smallest liquid volumes in research and in industry. Bands of beating cilia could execute tasks such as mixing, pumping, and particle trapping.

The paper appears in Nature Communications.

Source: Rahel Künzler for ETH Zurich

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Magnetic field lets tiny ball robots swim ‘breaststroke’

(Credit: Getty Images)

Scientists have discovered what may be the simplest form of locomotion in the travels of micron-scale particles linked and driven by a magnetic field.

Researchers placed magnetized spheres of different sizes into a solution. When subjected to an “eccentric magnetic field,” the spheres self-assembled and the smaller spheres, attached by virtual hinges, traced rough orbits to one side of their larger partners.

In essence, the small beads replicated the motion of a one-armed swimmer doing the breaststroke. The researchers found they could manipulate the magnetic field to direct swimmers through the fluid at nearly a micron a minute. The ability may eventually make them suitable as drug-delivery vehicles.

Eccentric magnetic fields

“There’s been a great deal of recent interest in active matter and systems that show collective behavior,” says Sibani Lisa Biswal, an associate professor of chemical and bimolecular engineering and of materials science and nanoengineering at Rice University, in whose lab the research took place. “We’re used to seeing this in how birds flock or bacteria swarm, but now we can see it in synthetic materials that also show an ability to couple with each other.

“Magnetic fields have emerged as a way to be able to drive particles to do some interesting things,” she says.

Lead author Di (Daniel) Du discovered the swimmers while studying how paramagnetic colloidal particles respond to a rotating magnetic field, the subject of several recent papers by the Biswal lab.

“We discovered that under some circumstances, especially under an eccentric magnetic field, these particles self-assemble into a swimmer…”

“One day I realized some of them swim,” says Du, a research statistical analyst at the University of Texas MD Anderson Cancer Center. “I was very interested in this, so I looked into this specific locomotion phenomenon under low Reynolds number.” A Reynolds number quantifies how objects move in fluids in relation to their viscosity, he says. “So if you see swimming, it means there’s something going on.

“We discovered that under some circumstances, especially under an eccentric magnetic field, these particles self-assemble into a swimmer and it becomes motive,” Du says.

Eccentric means the focal point of the rotating magnetic field is not the center of a colloid but moves around its circumference. In their experiments, the researchers found they could control the small particle’s orbit by altering the power supply to four computer-controlled electromagnets that surround the solution.

The particles are attached only by the magnetic field, giving the smaller one freedom to move in a swim-like motion with a long driving stroke and a short return stroke. The researchers called that a breaststroke because, as for human swimmers, the stroke does not require it to break the surface of the solution.

The ‘scallop theorem’

To keep with the theme, Du called the large particles “torsos” and the small ones “arms.” The swimmers’ ability to move allowed him to claim they were even simpler than the “simplest possible swimmers” designed by Nobel laureate Edward Purcell. Purcell designed theoretical devices of three rigid rods connected by two hinges, each hinge representing one degree of freedom, and considered them to be the simplest configuration for a device that could swim “if you move the hinges in a specified way,” Du says.

Microbots could deliver drugs by flip-flopping through your body

“But ours is actually simpler,” he says, “as I decreased the number of rigid components from Purcell’s prototype.”

Du says experiments and simulations showed swimmers with multiple torsos and arms could be controlled, though their speed varied depending on the strength of the field and—in the simulations—on Brownian motion, the omnipresent, random push and pull of molecules in gases and liquids.

In tests with multiple-particle swimmers, Du says, some arms would drift a bit further from the torso than others. Because this “arm fragmentation” influenced the swimmer’s speed, it helped Du shake up theories about how particles respond to Brownian motion.

“Only when there is Brownian motion do we see this fragmentation,” he says. “With Brownian motion our simulations match experimental results; sometimes fragmentation drives the swimmers to swim slower, and sometimes faster. Without Brownian motion, there’s a huge difference.”

Previous studies about the “scallop theorem” showed Brownian motion can influence the movement of things with reciprocating motion, like a scallop that simply opens and closes without propelling itself but still moves randomly. The arms in Du’s swimmers move in a nonreciprocal way—the driving stroke is longer than the return stroke—but he showed their velocity is also influenced by Brownian motion.

Du says it will be possible to attach ligands or proteins to the large particles for delivery to cells or other biological locations, and the entire vehicle could be moved with two magnetic coils at 90-degree angles.

Cockroaches teach robots to clamber and scurry

“In that way, swimmers could serve as micro-robots,” he says.

The researchers describe their work in a paper in Soft Matter. The National Science Foundation supported the research.

Source: Rice University