NeuroString Sensor Measures Neurotransmitter Activity

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A mouse sits in the palm of an oversized human hand, pictured alongside a rack of filled test tubes.

A soft, stretchable sensor called NeuroString could be used for measuring the activity of neurotransmitters — chemical messengers that nerve cells use to communicate — in the bodies of living animals.

The novel sensor, which may have potential in Parkinson’s disease research, was described in the study, “A tissue-like neurotransmitter sensor for the brain and gut,” and published in Nature.

Neurotransmitters are molecules nerve cells release to send signals to other nerves and to other parts of the body. These chemicals play critical roles in health and disease. For example, Parkinson’s is caused by the death and dysfunction of cells in the brain that make a neurotransmitter called dopamine.

“The mainstream way people are trying to understand the brain is to read and record electric signals, but chemical signals play just as significant a role in brain communication, and they are also directly related to diseases” Jinxing Li, PhD, the study’s first author, said in a press release. Li, who is a professor at Michigan State University, did the post-doctoral research at Stanford University.

Sensors that can detect neurotransmitters like dopamine have been developed before, but existing sensors are made of carbon rods and glass, which makes them rigid and brittle. This makes them ill-suited for implanting in living animals because they can cause damage and inflammation.

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NeuroString is a “soft electronic” designed to sense dopamine, as well as another neurotransmitter called serotonin.

“My group has been making soft electronics for quite some time,” said Zhenan Bao, PhD, a professor at Stanford and the paper’s senior author.

The novel sensor is made of an extremely thin form of carbon called graphene. Using a laser, the team engraved what Li describes as a “hairy entangled network” of graphene onto a plastic that contains nanoparticles to enhance the detection of neurotransmitters. Finally, this network is embedded into a rubber matrix.

“Graphene itself is not very stretchable but if it is entangled as a mesh and embedded in a rubber, then it becomes stretchable,” Li said.

According to Bao, the process is a bit like kirigami — a traditional form a Japanese paper art that involves cutting and folding paper (similar to origami where paper is only folded, not cut).

“If you cut patterns into and then you can stretch it, you see some kind of hollow connected paper network. It’s the same thing here, but the network is made of graphene sheets,” she said.

Because it is soft and flexible, NeuroString can be implanted in the body of a living animal without causing substantial tissue damage — even when the surrounding tissue is moving.

“The sensor is soft and elastic, like a rubber band, which does not cause damage when implanted into the brain or the gut, which is not only soft but also constantly moving,” Bao said.

The researchers conducted a number of proof-of-concept experiments to test the sensor. Results showed the device could be implanted in the brain or guts of mice without disrupting their behavior or bowel movements.

“These results confirmed that the mechanical compliance of the NeuroString is uniquely adequate to reduce disruptions to the physiological state of actively moving organs,” the researchers wrote.

The sensor also could accurately detect changes in dopamine and serotonin levels in the guts and brains of mice and pigs in a number of tests. For example, giving mice chocolate led to an expected response of increased dopamine levels in the brain and serotonin levels in the gut.

Giving the mice drugs that are known to influence these neurotransmitters, including fluoxetine (sold as Prozac, among other names), cocaine, or amphetamines, also led to expected changes that were detectable with NeuroString.

“Combining the excellent mechanical properties with the versatility of chemical sensing provided by the graphene surface chemistry, we predict that the NeuroString platform will be readily adaptable for studying the dynamics of various signalling biomolecules and electrophysiological signals throughout the body,” the scientists concluded.

“The first time we saw the signal from the probe was a eureka moment,” said study co-author Xiaoke Chen, PhD, a professor at Stanford. “Chronic recording of dopamine and serotonin signals in freely moving animals is a dream experiment that we always wanted to do. And with this beautiful collaboration, we were able to make it happen

“We now have the tool to allow real-time monitoring of the impact of those drugs on serotonin fluctuation in both the brain and gut in mouse models,” Chen added. “Now that we’ve shown that the probe works, there’s a very long list of biological questions we want to tackle.”