Tag Archives: Chong Xie

Nanoelectronic thread (NET) brain probes for long-term neural recording

A rendering of the ultra-flexible probe in neural tissue gives viewers a sense of the device’s tiny size and footprint in the brain. Image credit: Science Advances.

As long time readers have likely noted, I’m not a big a fan of this rush to ‘colonize’ the brain but it continues apace as a Feb. 15, 2017 news item on Nanowerk announces a new type of brain probe,

Engineering researchers at The University of Texas at Austin have designed ultra-flexible, nanoelectronic thread (NET) brain probes that can achieve more reliable long-term neural recording than existing probes and don’t elicit scar formation when implanted.

A Feb. 15, 2017 University of Texas at Austin news release, which originated the news item, provides more information about the new probes (Note: A link has been removed),

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, have developed new probes that 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. 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. 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 also used advanced imaging techniques in collaboration with biomedical engineering professor Andrew Dunn and neuroscientists Raymond Chitwood and Jenni Siegel from the Institute for Neuroscience at UT Austin to confirm that the NET enabled neural interface did not degrade in the mouse model for over four months of experiments. The researchers plan to continue testing their probes in animal models and hope to eventually engage in clinical testing. The research received funding from the UT BRAIN seed grant program, the Department of Defense and National Institutes of Health.

Here’s a link to and citation for the paper,

Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration by 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, and Chong Xie. Science Advances  15 Feb 2017: Vol. 3, no. 2, e1601966 DOI: 10.1126/sciadv.1601966

This paper is open access.

You can get more detail about the research in a Feb. 17, 2017 posting by Dexter Johnson on his Nanoclast blog (on the IEEE [International Institute for Electrical and Electronics Engineers] website).

Injectable electronics

Having taught a course on bioelectronics for Simon Fraser University’s (Vancouver, Canada) Continuing Studies Program, this  latest work from Harvard University (US) caught my attention. A Harvard research team has developed a technique which could allow doctors to inject us with electronics, should we need them. From a June 8, 2015 news item on phys.org,

It’s a notion that might be pulled from the pages of science-fiction novel – electronic devices that can be injected directly into the brain, or other body parts, and treat everything from neurodegenerative disorders to paralysis.

It sounds unlikely, until you visit Charles Lieber’s lab.

A team of international researchers, led by Lieber, the Mark Hyman, Jr. Professor of Chemistry, an international team of researchers developed a method for fabricating nano-scale electronic scaffolds that can be injected via syringe. Once connected to electronic devices, the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons. …

Here’s an image provided by the researchers,

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

A June 8, 2015 Harvard University new release by Peter Reuell (also on EurekAlert), which originated the news item, describes the work in more detail,

“I do feel that this has the potential to be revolutionary,” Lieber said. “This opens up a completely new frontier where we can explore the interface between electronic structures and biology. For the past thirty years, people have made incremental improvements in micro-fabrication techniques that have allowed us to make rigid probes smaller and smaller, but no one has addressed this issue – the electronics/cellular interface – at the level at which biology works.”

The idea of merging the biological with the electronic is not a new one for Lieber.

In an earlier study, scientists in Lieber’s lab demonstrated that the scaffolds could be used to create “cyborg” tissue – when cardiac or nerve cells were grown with embedded scaffolds. [emphasis mine] Researchers were then able to use the devices to record electrical signals generated by the tissues, and to measure changes in those signals as they administered cardio- or neuro-stimulating drugs.

“We were able to demonstrate that we could make this scaffold and culture cells within it, but we didn’t really have an idea how to insert that into pre-existing tissue,” Lieber said. “But if you want to study the brain or develop the tools to explore the brain-machine interface, you need to stick something into the body. When releasing the electronics scaffold completely from the fabrication substrate, we noticed that it was almost invisible and very flexible like a polymer and could literally be sucked into a glass needle or pipette. From there, we simply asked, would it be possible to deliver the mesh electronics by syringe needle injection, a process common to delivery of many species in biology and medicine – you could go to the doctor and you inject this and you’re wired up.'”

Though not the first attempts at implanting electronics into the brain – deep brain stimulation has been used to treat a variety of disorders for decades – the nano-fabricated scaffolds operate on a completely different scale.

“Existing techniques are crude relative to the way the brain is wired,” Lieber explained. “Whether it’s a silicon probe or flexible polymers…they cause inflammation in the tissue that requires periodically changing the position or the stimulation. But with our injectable electronics, it’s as if it’s not there at all. They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes. They’re what I call “neuro-philic” – they actually like to interact with neurons..”

Despite their enormous potential, the fabrication of the injectable scaffolds is surprisingly easy.

“That’s the beauty of this – it’s compatible with conventional manufacturing techniques,” Lieber said.

The process is similar to that used to etch microchips, and begins with a dissolvable layer deposited on a substrate. To create the scaffold, researchers lay out a mesh of nanowires sandwiched in layers of organic polymer. The first layer is then dissolved, leaving the flexible mesh, which can be drawn into a syringe needle and administered like any other injection.

After injection, the input/output of the mesh can be connected to standard measurement electronics so that the integrated devices can be addressed and used to stimulate or record neural activity.

“These type of things have never been done before, from both a fundamental neuroscience and medical perspective,” Lieber said. “It’s really exciting – there are a lot of potential applications.”

Going forward, Lieber said, researchers hope to better understand how the brain and other tissues react to the injectable electronics over longer periods.

Lieber’s earlier work on “cyborg tissue” was briefly mentioned here in a Feb. 20, 2014 posting.

Getting back to the most recent work, here’s a link to and a citation for the paper,

Syringe-injectable electronics by Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter Kruskal, Chong Xie, Zhigang Suo, Ying Fang, & Charles M. Lieber. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.115 Published online 08 June 2015

This paper is behind a paywall but there is a free preview via ReadCube Access.

One final note, the researchers have tested the injectable electronics (or mesh electronics) in vivo (live animals).

Making nanoelectronic devices last longer in the body could lead to ‘cyborg’ tissue

An American Chemical Society (ACS) Feb. 19, 2014 news release (also on EurekAlert), describes some research devoted to extending a nanoelectronic device’s ‘life’ when implanted in the body,

The debut of cyborgs who are part human and part machine may be a long way off, but researchers say they now may be getting closer. In a study published in ACS’ journal Nano Letters, they report development of a coating that makes nanoelectronics much more stable in conditions mimicking those in the human body. [emphases mine] The advance could also aid in the development of very small implanted medical devices for monitoring health and disease.

Charles Lieber and colleagues note that nanoelectronic devices with nanowire components have unique abilities to probe and interface with living cells. They are much smaller than most implanted medical devices used today. For example, a pacemaker that regulates the heart is the size of a U.S. 50-cent coin, but nanoelectronics are so small that several hundred such devices would fit in the period at the end of this sentence. Laboratory versions made of silicon nanowires can detect disease biomarkers and even single virus cells, or record heart cells as they beat. Lieber’s team also has integrated nanoelectronics into living tissues in three dimensions — creating a “cyborg tissue.” One obstacle to the practical, long-term use of these devices is that they typically fall apart within weeks or days when implanted. In the current study, the researchers set out to make them much more stable.

They found that coating silicon nanowires with a metal oxide shell allowed nanowire devices to last for several months. This was in conditions that mimicked the temperature and composition of the inside of the human body. In preliminary studies, one shell material appears to extend the lifespan of nanoelectronics to about two years.

Depending on how you define the term cyborg, it could be said there are already cyborgs amongst us as I noted in an April 20, 2012 posting titled: My mother is a cyborg. Personally I’m fascinated by the news release’s mention of ‘cyborg tissue’ although there’s no further explanation of what the term might mean.

For the curious, here’s a link to and a citation for the paper,

Long Term Stability of Nanowire Nanoelectronics in Physiological Environments by Wei Zhou, Xiaochuan Dai, Tian-Ming Fu, Chong Xie, Jia Liu, and Charles M. Lieber. Nano Lett., Article ASAP DOI: 10.1021/nl500070h Publication Date (Web): January 30, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.