New soft implantable probe can monitor changes in chemicals in the brain

New string-like implants can monitor changes in brain chemicals, much like a fitness tracker in the brain.

Imbalances in the chemistry of the brain are at the heart of many neurological disorders. These same brain chemicals also play a role in gut health. So scientists at Stanford University invented the “Neuro String.” This is a soft implantable probe that can seamlessly connect to both brain and intestinal tissue. They describe the probe in a paper published June 2, 2022. Nature.. It may be applicable to depression, Parkinson’s disease, and intestinal disorders.

The mainstream way people are trying to understand the brain is to read and record electrical signals. However, chemical signals play an equally important role in brain communication and are directly related to illness. “

Jinxing Li, the lead author of the paper

Li started and performed as a postdoc in Zhenan Bao’s lab at Stanford University’s Faculty of Chemical Engineering. He is currently an assistant professor of biomedical engineering at Michigan State University.

NeuroString measures dopamine and serotonin, two chemical mediators that modulate the electrical signals of neurons. Dopamine is best known for its role in the brain’s reward system. Serotonin is the target of antidepressants like Prozac. Both are involved in movement, sleep, appetite and digestion.

Implants that measure dopamine and serotonin already exist, but they are made of rigid carbon rods placed in a glass tube. “These are very rigid probes. They are very brittle,” says Li. Not only can the implant shatter, but it can also rub against the fluffy tissue in the brain, inflaming brain cells and degrading the implant.

Bao’s lab designed a soft probe. “My group has been manufacturing soft electronics for quite some time,” said Bao, Professor and Chairman of KK Lee, Department of Chemical Engineering, Faculty of Engineering, Stanford University. The probe is made of graphene, a type of atomically thin carbon. Bao’s team used a laser to engrave what Lee described as “a hairy intertwined network of graphene” on plastic. The plastic contains molecules that turn into nanoparticle dots on the surface of graphene, which can improve the sensitivity and selectivity for simultaneous measurement of dopamine and serotonin. Next, I embedded the network in the rubber matrix. “Graphene itself isn’t very stretchy, but when it’s entwined as a mesh and embedded in rubber, it’s stretchy,” explains Li.

“It’s like kirigami. When you cut and stretch a pattern, you see some kind of hollow connected paper network. Again, the network is made of graphene sheet. NeuroString has the same softness as living tissue. “The sensor is as soft and elastic as a rubber band and doesn’t damage it when it’s embedded in the brain or intestines. It’s not only soft, it’s always moving,” says Bao.

To test the probe, Bao’s team worked with scientists at Stanford University in Biology. Psychiatry, Gastroenterology, and surgery. “I think it’s the most privileged part of Stanford. It’s very open and supportive,” says Li. This work is supported by the Bio-X Seed Grant and the Wu Tsai Neurosciences Institute Big Ideas in Neuroscience Grant, both of which facilitate interdisciplinary collaboration.

In one experiment, the team transplanted NeuroString into the brain and intestines of the same mouse. When they fed the mice chocolate syrup, NeuroString detected dopamine spikes in the brain and serotonin spikes in the intestine-; both expected reactions to chocolate. Dopamine is made in the brain, while serotonin is made primarily in the intestines. In another experiment, NeuroString detected a characteristic pattern of intestinal serotonin in inflamed intestinal mice compared to healthy mice.

“It was at the moment of Eureka that I first saw the signal from the probe,” said co-author Xiaoke Chen, an associate professor of biology. “Chronic recording of dopamine and serotonin signals in free-moving animals is a dream experiment we’ve always wanted to do, and this beautiful collaboration allows us to make it happen. rice field.”

The transplanted mice behaved normally, ate, and had normal defecation. “The exciting thing about this tool was that it didn’t seem to interfere with the normal functioning of the tissue,” said co-author Medical Professor Aida Habtezion. This means that implants could one day be used for real-time monitoring of humans, similar to smartwatches, but she says they can track biochemical levels rather than heart rate or steps. .. Habtezion is currently on leave and she is Pfizer’s Chief Medical Officer, but contributed to her work while she was still in Stanford.

Tracking intestinal serotonin levels may be useful in diagnosing and monitoring intestinal disorders such as irritable bowel syndrome. Tracking dopamine levels in the brain may help Parkinson’s disease caused by dopamine deficiency. Deep brain stimulation, one of the treatments for Parkinson’s disease, works partially by stimulating neurons to produce more dopamine. The combination of deep brain stimulation and NeuroString gives physicians precise control over the amount of dopamine released.

The implant is not yet ready for clinical use. For one thing, the probe is still connected to the wire that reads the signal. People need a wireless version to use it. In the meantime, the probe has many uses in research. For example, antidepressants like Prozac work by regulating serotonin levels. This may explain why they sometimes cause gastrointestinal side effects, says Chen. “Currently, there are tools that can monitor the effects of these agents on serotonin variability in both the brain and intestine of mouse models in real time.”

“We have shown that the probe works, so we have a very long list of biological problems that we want to address,” he adds.