Ultra-flexible, nanoelectronic thread (NET) brain probes that can achieve more reliable long-term neural recording than existing probes and don’t prompt scar formation when implanted have been developed by researchers at The University of Texas at Austin.
The probes have mechanical compliances approaching that of the brain tissue and are more than 1,000 times more flexible than other neural probes. This ultra-flexibility leads to an improved ability to reliably record and track the electrical activity of individual neurons for long periods of time.
A team led by Chong Xie, an assistant professor in the Department of Biomedical Engineering in the Cockrell School of Engineering, and Lan Luan, a research scientist in the Cockrell School and the College of Natural Sciences, developed the new probes.
Tracking Individual Neurons
There is a growing interest in developing long-term tracking of individual neurons for neural interface applications, such as extracting neural-control signals for amputees to control high-performance prostheses. It also opens up new possibilities to follow the progression of neurovascular and neurodegenerative diseases such as stroke, Parkinson’s and Alzheimer’s diseases.
One of the problems with conventional probes is their size and mechanical stiffness. Their larger dimensions and stiffer structures often cause damage around the tissue they encompass.
Additionally, while it is possible for the conventional electrodes to record brain activity for months, they often provide unreliable and degrading recordings. It is also challenging for conventional electrodes to electrophysiologically track individual neurons for more than a few days.
In contrast, the UT Austin team’s electrodes are flexible enough that they comply with the microscale movements of tissue and still stay in place. The probe’s size also drastically reduces the tissue displacement, so the brain interface is more stable, and the readings are more reliable for longer periods of time.
The researchers conclude in the paper:
“The unprecedented chronic reliability and stability are expected to fundamentally advance both basic and applied neuroscience, as well as lead to substantial improvement in the brain-machine interface which can be applied to neuroprosthetics. Furthermore, the subcellular dimension probes provide new opportunities for high-density electrical recording by overcoming current physical limitations."
Tissue Reaction Suppression
To the researchers' knowledge, the UT Austin probe, which is as small as 10 microns at a thickness below 1 micron, and has a cross-section that is only a fraction of that of a neuron or blood capillary, is the smallest among all neural probes.
“What we did in our research is prove that we can suppress tissue reaction while maintaining a stable recording,” Xie said. “In our case, because the electrodes are very, very flexible, we don’t see any sign of brain damage—neurons stayed alive even in contact with the NET probes, glial cells remained inactive and the vasculature didn’t become leaky."
In experiments in mouse models, the researchers found that the probe’s flexibility and size prevented the agitation of glial cells, which is the normal biological reaction to a foreign body and leads to scarring and neuronal loss.
“The most surprising part of our work is that the living brain tissue, the biological system, really doesn’t mind having an artificial device around for months,” Luan said.
The researchers plan to continue testing their probes in animal models and hope to eventually engage in clinical testing.
Funding for the work came from the UT BRAIN seed grant program, the Department of Defense and National Institutes of Health.
Lan Luan, Xiaoling Wei, Zhengtuo Zhao, Jennifer J. Siegel, Ojas Potnis, Catherine A Tuppen, Shengqing Lin, Shams Kazmi, Robert A. Fowler, Stewart Holloway, Andrew K. Dunn, Raymond A. Chitwood, Chong Xie Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration Science Advances 15 Feb 2017: Vol. 3, no. 2, e1601966 DOI: 10.1126/sciadv.1601966
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