The new string-like implant can monitor fluctuations in chemicals in the brain, as a fitness tracker for the brain.
An imbalance in brain chemistry is the basis of many neurological diseases. These same brain chemicals also play a role in gut health. So Stanford researchers have invented the “NeuroString” – a soft implantable probe that can integrate seamlessly with brain and intestinal tissue. They describe the probe in an article published June 2, 2022 Nature. It has potential use in depression, Parkinson’s disease and intestinal diseases.
The main way people try to understand the brain is to read and record electrical signals. But chemical signals play an equally important role in brain communication and are also directly related to disease. ”
Jinxing Li, the first author of the paper
Li began and performed as a postdoctoral fellow in Zhenan Bao Laboratory at Stanford Department of Chemical Engineering; He is currently an assistant professor of biomedical engineering at Michigan State University.
NeuroString measures dopamine and serotonin, two chemical messengers that modulate electrical signals in neurons. Dopamine is best known for its role in the reward system in the brain; Serotonin is the target of antidepressants such as Prozac. Both are also involved in exercise, sleep, appetite and digestion.
Implants that measure dopamine and serotonin already exist, but are made of rigid carbon rods enclosed in glass tubes. “They’re very rigid probes. They’re very fragile,” says Li. Not only can the implant break, but it also rubs against the crumpled tissue in the brain, which can infect the brain cells and degrade the implant.
Ba’s lab designed a soft probe. “My group has been making soft electronics for some time,” said Bao, Professor KK Lee and chairman of the Department of Chemical Engineering at Stanford School of Engineering. The probe is made of graphene, which is a form of carbon that is atomically thin. Bao’s team used a laser to engrave what Li describes as a “hairy entwined network of graphene” into plastic. The plastic contains molecules that turn into nanoparticle dots on the graphene surface, which can improve sensitivity and selectivity for simultaneous dopamine and serotonin measurements. Then they inserted the net into a rubber matrix. “Graphene itself isn’t very expandable, but when it’s tangled like mesh and embedded in rubber, it becomes expandable,” Li explains.
Bao adds, “It’s like a kirigami. If you cut patterns and then you can stretch it, you’ll see a kind of hollow bonded paper net. It’s the same here, but the net is made of graphene sheets.” NeuroString has the same softness as biological tissue. “The sensor is soft and elastic, like a rubber band that does not cause damage when implanted in the brain or intestine, which is not only soft but also constantly moving,” says Bao.
Bao’s team worked with Stanford scientists in biology, psychiatry, gastroenterology and surgery to test the probe. “I think that’s the most privileged part of Stanford: It’s quite open and cooperative,” says Li. The work was supported by a Bio-X seed grant and a grant from the Wu Tsai Neurosciences Institute Big Ideas in Neuroscience, both of which support interdisciplinary collaboration.
In one experiment, the team implanted a NeuroString in the brain and intestines of the same mice. When the mice were fed chocolate syrup, NeuroString detected dopamine jumps in the brain and serotonin jumps in the gut – both expected reactions to chocolate. Dopamine is formed in the brain, while serotonin is formed predominantly in the gut. In another experiment, NeuroString detected significant patterns of intestinal serotonin in mice with inflammatory bowel compared to healthy mice.
“The first time we saw the signal from the probe was a eureka moment,” says co-author Xiaoke Chen, associate professor of biology. “Chronic recording of dopamine and serotonin signals in free-ranging animals is a dream experiment that we have always wanted to do. And thanks to this beautiful collaboration, we have succeeded.”
The implanted mice behaved and ate normally and had normal bowel movements. “What was exciting about this tool was that it didn’t seem to disrupt normal tissue function,” said co-author Aida Habtezion, a professor of medicine. This means that the implant could one day be used for real-time monitoring in humans, much like a smart watch, but able to monitor biochemical levels rather than heart rate or steps, he says. Habtezion is currently on vacation and serves as Pfizer’s chief physician, but contributed to the work when she was still in Stanford.
Monitoring intestinal serotonin levels could be useful in diagnosing and monitoring intestinal diseases such as irritable bowel syndrome. Monitoring dopamine levels in the brain could be useful in Parkinson’s disease, which is caused by a lack of dopamine. One way to treat Parkinson’s disease, deep brain stimulation, works in part by stimulating neurons to produce more dopamine. If it were possible to combine deep brain stimulators with NeuroString, it would allow doctors to precisely control the amount of dopamine released.
The implant is not yet ready for clinical use. On the one hand, the probe is still connected to the wires that sense the signals; a wireless version would be required for human use. Meanwhile, the probe has many uses in research. For example, antidepressants like Prozac work by modulating serotonin levels, which may explain why they sometimes cause gastrointestinal side effects, Chen says. “We now have a tool that allows us to monitor the impact of these drugs on serotonin fluctuations in the brain and intestines in real time in mouse models.”
He adds: “Now that we have shown that the probe works, there is a very long list of biological issues that we want to address.”
Stanford University School of Engineering
Li, J., et al. (2022) Neurotransmitter tissue sensor for brain and intestine. Nature. doi.org/10.1038/s41586-022-04615-2.
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