The human brain is a fortress. The blood-brain barrier, a selective shield of tightly packed cells, keeps out toxins and infections. However this essential barrier also makes it incredibly difficult for doctors to deliver drugs to the brain when needed.
Now, scientists at ETH Zurich are using an unexpected tool to breach the blockade: microscopic gas bubbles.
Tiny, gas-filled bubbles—smaller than red blood cells—are injected into the bloodstream alongside medication. When activated by ultrasound, they oscillate wildly, creating jets of liquid powerful enough to create microscopic openings in cell membranes so the drugs can reach their target. For the first time, researchers have captured how these bubbles work in real time and published their results in Nature Physics.
Microjets Moving at 200 kph
Until now, how these bubbles punctured cell membranes was a mystery. The microbubbles vibrate up to several million times per second when exposed to ultrasound, a movement too fast for the human eye to track.
To understand what’s happening during this lightning-fast process, physicist Outi Supponen and her team built a microscope capable of capturing ten million images per second. They placed a layer of endothelial cells—mimicking blood vessel walls—inside a small chamber filled with a saline solution. The gas bubbles, naturally rising to the surface, made contact with the cells before being hit with a pulse of ultrasound.
What they saw was stunning.
“At a sufficiently high ultrasound pressure, microbubbles stop oscillating in a spherical shape and start reshaping themselves into regular, non-spherical patterns,” Supponen said.
The lobes of these patterns fold inward, forming jets of liquid that move at an astonishing 200 kilometers per hour (124 mph). These jets act like tiny needles, puncturing the cell membrane with precision—without killing the cell.
Ultrasound’s Role in Guiding Medicine
Scientists are also taking these bubbles one step further—not just for puncturing cells, but steering them through the brain’s blood vessels. In a previous 2023 study published in Nature Communications, the same team of researchers demonstrated that they could control these microbubbles to deliver drugs even though this mechanism wasn’t perfectly understood.
Using a set of transducers (electronic devices that convert energy from one form to another) placed on the skull, the generated ultrasound waves guide the bubbles through the bloodstream. “Since these bubbles, or vesicles, are already approved for use in humans, it’s likely that our technology will be approved and used in treatments for humans more quickly than other types of microvehicles currently in development,” said Daniel Ahmed, a professor of acoustic robotics at ETH Zurich, in 2023.
Since then, scientists have started testing microbubble-mediated drug delivery in clinical settings, especially for brain diseases where traditional drugs struggle to penetrate. Focused ultrasound techniques have been used to temporarily open the blood-brain barrier in patients with Alzheimer’s, Parkinson’s, and glioblastomas, but the process has been largely trial and error.
This breakthrough could also extend beyond neurology. Microbubbles have shown promise in treating solid tumors, where they could help ferry chemotherapy drugs deep into cancerous tissue. Similarly, cardiovascular therapies could benefit from more efficient drug delivery to arteries blocked by atherosclerosis.
A Promising Future
For now, the research remains in its early stages. But scientists are optimistic that ultrasound-controlled microbubbles could one day transform how doctors treat neurological diseases and conditions that require administering drugs in the brain..
It’s a remarkable concept: using sound waves to direct tiny bubbles to deliver life-saving medication to the brain. A method so delicate, so precise, it might just redefine the future of medicine.
“Our work clarifies the physical foundations for targeted administration of drugs through microbubbles and helps us define criteria for their safe and effective use,” Supponen said.
