Flexible graphene-based probe monitors brain and gut chemistry

Scientists from Michigan State University and Stanford University have invented the “NeuroString” – an implantable graphene-based probe that allows researchers to study the chemistry of brain health and intestine.

Three flexible NeuroString sensors. Credit: Courtesy of Jinxing Li

“The common way people try to understand the brain is by reading and recording electrical signals,” said Jinxing Li, the paper’s first author and assistant professor in MSU’s College of Engineering. “But chemical signals play an equally important role in brain communication, and they are also directly linked to diseases. My lab at MSU focuses on the development of advanced neuroprobes and microrobotics.

The team designed the first iteration of NeuroString to measure dopamine and serotonin present in both the brain and the gut enteric nervous system which also plays a key role in physical health and mental well-being. Dopamine is best known for its role in the brain’s reward system. Serotonin is the target of antidepressants like Prozac. Both neurotransmitters are also involved in sleep, movement, and digestion.

Existing implants that measure dopamine and serotonin are made of stiff, brittle materials, including glass and carbon rods. Implants can not only break, but they also rub against spongy tissue, inflaming the cells and degrading the implant.

“We have developed a flexible probe that can measure the chemical dynamics of soft organs in their natural state,” said Li, who is also a fellow at MSU’s Institute for Quantitative Health Sciences and Engineering, or IQ. . “We are not damaging the biology – or the probe.”

To test the probe, Li worked with scientists from biology, neuroscience, psychiatry, gastroenterology and surgery at Stanford. The work was supported by a Stanford Bio-X Seed Grant and a Big Idea Grant from the Wu Tsai Neuro Institute, which encourages interdisciplinary collaborations. “I think supporting mind-opening collaboration across disciplines is key to the success of this project,” said Li, who is now expanding her network with new collaborators at MSU.

To design the NeuroString probe, Li spent about a year testing different materials. The researchers knew they wanted to use carbon for its electrochemical properties. Carbon can sensitively and selectively detect chemicals of interest while providing attractive electrical properties to connect to sensor circuitry. After careful consideration, the team opted for graphene.

“We found that graphene gave us very good selectivity and sensitivity and we could also embed it in a soft rubber matrix,” Li said. it is entangled like a mesh and embedded in a rubber, then it becomes stretchy.”

“It’s like a kirigami. If you cut patterns out of paper and then you can stretch it out, you see a kind of connected hollow paper network,” Stanford’s Bao said. “It’s the same here, but the network is made of graphene sheets.

“The sensor is soft and elastic, like a rubber band, which does not cause harm when implanted in the brain or intestine, which is not only soft but also in constant motion,” Bao said.

The team already has improvements in mind for NeuroString ahead of human clinical trials: reduced size and wireless communication. Currently, the width of the sensor is comparable to a human hair. The goal is to approach the size of a cell, i.e. a reduction of around 90% in diameter.

As a long-term goal, Li and his colleagues are working on devices that will not only monitor brain and gut chemistry, but can also intervene if the probes detect something is wrong. They envision future NeuroStrings that could, for example, help resynchronize neurons if something causes cells to misfire.

“If we are able to measure molecular concentration and provide stimulation to modulate it with the same device, we could provide truly personalized treatments,” Li said.

In the meantime, however, the team has already demonstrated in preclinical settings and with animal models that NeuroString can be a powerful tool for exploring brain and gut chemistry. For his part, Li is thinking about projects that would better explore the biochemistry of Parkinson’s disease and depression.