Microrobots can deliver stroke drugs directly to blocked vessels

Every year, strokes hit about 12 million people worldwide. Many do not survive. Many others live with lasting disability, from trouble speaking to paralysis. Treatments exist, but they are far from perfect.

Doctors often use drugs that break up the blood clot blocking a vessel in the brain. These drugs travel through the whole body, not just the clogged vessel.

To make sure enough medicine reaches the clot, doctors have to use high doses, which can cause dangerous side effects such as internal bleeding. Medicines are usually needed in one small area, yet they flood every organ.

Why strokes need a smarter tool

Researchers have chased a simple idea for years: send tiny machines into the body that carry drugs directly to the problem spot.

For stroke, that means steering a drug-filled device right to the clot in the brain instead of dosing the entire body.

This kind of targeted delivery could change more than stroke care. Local treatment could also help with deep infections or tumors while sparing healthy tissue.

To do that, a microrobot has to move inside twisting, narrow, fast-flowing vessels and still deliver its cargo on cue.

A microrobot in a gel shell

At ETH Zurich, a team in the field of microrobotics has built a system that starts with a tiny spherical capsule made of a gel that can dissolve inside the body.

The capsule is packed with iron oxide nanoparticles so that magnets can pull and turn it inside vessels.

Study lead author Fabian Landers is a postdoctoral researcher in the Multi-Scale Robotics Lab at ETH Zurich.

“Because the vessels in the human brain are so small, there is a limit to how big the capsule can be. The technical challenge is to ensure that a capsule this small also has sufficient magnetic properties,” said Landers.

Tracking the capsule in the body

To track the capsule in the body, doctors need to see it on X-ray. The team uses tantalum nanoparticles as a contrast agent, a material already used in medicine but much heavier and harder to control than iron oxide.

Bradley Nelson, a professor of robotics and intelligent systems, has been researching microrobots for decades.

“Combining magnetic functionality, imaging visibility and precise control in a single microrobot required perfect synergy between materials science and robotics engineering, which has taken us many years to successfully achieve,” said Professor Nelson.

Delivering the stroke drugs

The capsules are not empty. The researchers have already loaded them with real drugs used in hospitals, including a clot-busting medicine for stroke, an antibiotic, and a cancer drug.

The shell acts as a container that keeps the drug in place until it reaches the target.

To release the drug, the team uses a high-frequency magnetic field. This field heats the magnetic nanoparticles inside the capsule just enough to melt the gel shell.

Once the shell dissolves, the microrobot breaks apart and the drug diffuses into the surrounding tissue right where it is needed.

Steering the microrobot in the body

Getting the capsule into the body starts with a catheter, a thin tube already common in stroke treatment. The researchers designed a special catheter with an internal guidewire attached to a flexible polymer gripper.

The microrobot sits in the gripper inside the catheter. When the doctor pushes the inner guidewire out a bit, the gripper opens and releases the capsule into the bloodstream or into the cerebrospinal fluid.

Steering the capsule is the hard part. “The speed of blood flow in the human arterial system varies a lot depending on location. This makes navigating a microrobot very complex,” explained Nelson.

To handle this, the team built a modular electromagnetic navigation system suited for an operating room, so that magnetic fields can be shaped and changed in real time around the patient’s head.

Swimming against blood flow

The system combines three magnetic strategies. In one approach, a rotating magnetic field makes the capsule roll along the vessel wall. This allows very fine control over direction at a speed of about 0.16 inches per second.

In another approach, a magnetic gradient pulls the capsule toward the area where the field is stronger, even when blood is flowing fast in the opposite direction.

The microrobot can move upstream against flow speeds of over about 7.9 inches per second.

“It’s remarkable how much blood flows through our vessels and at such high speed. Our navigation system must be able to withstand all of that,” said Landers.

A minimally invasive procedure

Vessels in the head often split into branches where paths turn sharply. At these junctions, the team relies on in-flow navigation.

The magnetic gradient is aimed at the vessel wall so that the flowing blood naturally carries the capsule into the desired branch.

By blending these three strategies, the researchers kept control of the microrobot under many flow and vessel conditions. In more than 95 percent of their tests, the capsule reached the right spot and delivered its drug.

“Magnetic fields and gradients are ideal for minimally invasive procedures because they penetrate deep into the body and – at least at the strengths and frequencies we use – have no detrimental effect on the body,” explained Nelson.

Optimizing the navigation system

Before turning to animals, the team created silicone models that match the exact shape of patient and animal vessels, down to the bends and branches.

These clear models are now sold by ETH spin-off Swiss Vascular and are used for medical training as well as research.

“The models are crucial for us, as we practiced extensively to optimize the strategy and its components. You can’t do that with animals,” explained Professor Salvador Pané, a chemist at the Institute of Robotics and Intelligent Systems.

In these vessel models, the researchers steered a capsule loaded with clot-dissolving drug right into an artificial blockage and watched it break up the clot.

This showed that their navigation system and drug-release trigger could work together under realistic flow conditions.

Testing the system in animals

After extensive model work, the team moved to large animals. In pigs, they showed that all three navigation modes functioned in real arteries and that the microrobot stayed visible for the entire procedure on imaging systems doctors already use.

They then guided capsules through the cerebrospinal fluid in a sheep, a more complex space than blood vessels because the fluid moves differently and the anatomy is intricate.

“This complex anatomical environment has enormous potential for further therapeutic interventions, which is why we were so excited that the microrobot was able to find its way in this environment too,” said Landers.

A new path forward for stroke therapy

The first target for the microrobot is stroke, where faster and more precise clot removal could spare brain tissue and reduce disability.

The same approach could also be adapted to send antibiotics to deep infections or cancer drugs to tumors that are hard to reach with surgery.

The team has tried to design every part of the system with hospital use in mind, from the catheter layout to the electromagnetic hardware. The next big step is to start human clinical trials.

“Doctors are already doing an incredible job in hospitals. What drives us is the knowledge that we have a technology that enables us to help patients faster and more effectively and to give them new hope through innovative therapies,” said Landers.

The full study was published in the journal Science.

Image Credit: Luca Donati/ lad.studio Zurich)

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