Cell-Electronic Hybrid Chips Could Enable Surgery-Free Brain Implants

Brain implants can provide important insights into the nervous system and even relieve the symptoms of brain diseases. But getting implants into a patient’s head is an operation fraught with risks of tissue damage and infection.

Some approaches use blood vessels to deliver implants to the fringes of the brain, but these cannot access deep-lying areas at the roots of some of the most stubborn brain disorders. To overcome this, researchers at Massachusetts Institute of Technology, led by bioengineer Deblina Sarkar, took up the challenge of designing an implant with minimal footprint and maximum efficacy.

In a new paper, published in Nature Biotechnology, Sarkar and her colleagues unveiled a novel implant design approach which piggybacks subcellular electronic devices to circulating immune cells. ¹

The team’s wireless electronic-cell hybrids, which are powered by light, are 10 micrometers in diameter, which is smaller than a single droplet of mist. The researchers found that these devices could migrate to areas of inflammation in the mouse brain and then stimulate brain tissue with micrometer-level precision. They called their hybrids the first in a new field of “circulatronic” devices.

“Our tiny electronic devices seamlessly integrate with the neurons and colive and coexist with the brain cells, creating a unique brain-computer symbiosis,” said Sarkar in a press release.

Sneaking Into the Brain

At the start of the project, the team identified access as a huge problem for their implant. If other regions of the body are like a casual bar on a Tuesday night, the brain is like the VIP section of an overpriced club on a Saturday. Implants that want to access the brain need to know where they are going and blend in enough to bypass the blood-brain barrier, which blocks access to unfavorable molecules like a thick red rope manned by a grumpy bouncer.

Sarkar’s team decided to make their devices hard to keep out in two ways: by reducing their size and by chemically welding them to the side of immune cells that the brain always gives access to.

The resulting design is a microscopic sandwich—a layer of organic semiconducting polymers in between an anode and a cathode— attached to an immune cell called a monocyte. When monocytes detect inflammation in the body or brain, they migrate to the site, like a Labrador rushing to the spot where a slice of ham has been dropped.

To put their devices to test, the team infused them intravenously into mice in which they had induced inflammation by injecting proinflammatory molecules into a deep brain area called the ventrolateral thalamic nucleus. The researchers linked the hybrids to a fluorescent dye and followed the glowing signature of the hybrids as they flooded into the deep brain, pulled along by the migrating monocytes. The devices’ entry caused no immune response and didn’t affect the animals’ behavior.

“The living cells camouflage the electronics so that they aren’t attacked by the body’s immune system, and they can travel seamlessly through the bloodstream. This also enables them to squeeze through the intact blood-brain barrier without the need to invasively open it,” said Sarkar.

Applications for Multiple Brain Diseases

Next, they used an external transmitter to send near-infrared light through the mice’s skulls to the device, which could convert it into the energy needed to electrically stimulate nearby neurons.

Sarkar’s devices could, in theory, target a wide range of brain diseases. That’s because conditions like multiple sclerosis, which can be moderated by deep brain stimulation, feature inflammatory side effects that immune-cell hybrids could target.

The researchers even hope that their hybrids could offer a solution to brain diseases that are stubbornly resistant to treatment, including brain cancers like glioblastoma and diffuse intrinsic pontine glioma.

“This is a platform technology and may be employed to treat multiple brain diseases and mental illnesses,” said Sarkar. “Also, this technology is not just confined to the brain but could also be extended to other parts of the body in future.”