Tag Archives: brain mapping

Graphene-based neural probes

I have two news bits (dated almost one month apart) about the use of graphene in neural probes, one from the European Union and the other from Korea.

European Union (EU)

This work is being announced by the European Commission’s (a subset of the EU) Graphene Flagship (one of two mega-funding projects announced in 2013; 1B Euros each over ten years for the Graphene Flagship and the Human Brain Project).

According to a March 27, 2017 news item on ScienceDaily, researchers have developed a graphene-based neural probe that has been tested on rats,

Measuring brain activity with precision is essential to developing further understanding of diseases such as epilepsy and disorders that affect brain function and motor control. Neural probes with high spatial resolution are needed for both recording and stimulating specific functional areas of the brain. Now, researchers from the Graphene Flagship have developed a new device for recording brain activity in high resolution while maintaining excellent signal to noise ratio (SNR). Based on graphene field-effect transistors, the flexible devices open up new possibilities for the development of functional implants and interfaces.

The research, published in 2D Materials, was a collaborative effort involving Flagship partners Technical University of Munich (TU Munich; Germany), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; Spain), Spanish National Research Council (CSIC; Spain), The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN; Spain) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2; Spain).

Caption: Graphene transistors integrated in a flexible neural probe enables electrical signals from neurons to be measured with high accuracy and density. Inset: The tip of the probe contains 16 flexible graphene transistors. Credit: ICN2

A March 27, 2017 Graphene Flagship press release on EurekAlert, which originated the news item, describes the work,  in more detail,

The devices were used to record the large signals generated by pre-epileptic activity in rats, as well as the smaller levels of brain activity during sleep and in response to visual light stimulation. These types of activities lead to much smaller electrical signals, and are at the level of typical brain activity. Neural activity is detected through the highly localised electric fields generated when neurons fire, so densely packed, ultra-small measuring devices is important for accurate brain readings.

The neural probes are placed directly on the surface of the brain, so safety is of paramount importance for the development of graphene-based neural implant devices. Importantly, the researchers determined that the graphene-based probes are non-toxic, and did not induce any significant inflammation.

Devices implanted in the brain as neural prosthesis for therapeutic brain stimulation technologies and interfaces for sensory and motor devices, such as artificial limbs, are an important goal for improving quality of life for patients. This work represents a first step towards the use of graphene in research as well as clinical neural devices, showing that graphene-based technologies can deliver the high resolution and high SNR needed for these applications.

First author Benno Blaschke (TU Munich) said “Graphene is one of the few materials that allows recording in a transistor configuration and simultaneously complies with all other requirements for neural probes such as flexibility, biocompability and chemical stability. Although graphene is ideally suited for flexible electronics, it was a great challenge to transfer our fabrication process from rigid substrates to flexible ones. The next step is to optimize the wafer-scale fabrication process and improve device flexibility and stability.”

Jose Antonio Garrido (ICN2), led the research. He said “Mechanical compliance is an important requirement for safe neural probes and interfaces. Currently, the focus is on ultra-soft materials that can adapt conformally to the brain surface. Graphene neural interfaces have shown already great potential, but we have to improve on the yield and homogeneity of the device production in order to advance towards a real technology. Once we have demonstrated the proof of concept in animal studies, the next goal will be to work towards the first human clinical trial with graphene devices during intraoperative mapping of the brain. This means addressing all regulatory issues associated to medical devices such as safety, biocompatibility, etc.”

Caption: The graphene-based neural probes were used to detect rats’ responses to visual stimulation, as well as neural signals during sleep. Both types of signals are small, and typically difficult to measure. Credit: ICN2

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

Mapping brain activity with flexible graphene micro-transistors by Benno M Blaschke, Núria Tort-Colet, Anton Guimerà-Brunet, Julia Weinert, Lionel Rousseau, Axel Heimann, Simon Drieschner, Oliver Kempski, Rosa Villa, Maria V Sanchez-Vives. 2D Materials, Volume 4, Number 2 DOI https://doi.org/10.1088/2053-1583/aa5eff Published 24 February 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.


While this research from Korea was published more recently, the probe itself has not been subjected to in vivo (animal testing). From an April 19, 2017 news item on ScienceDaily,

Electrodes placed in the brain record neural activity, and can help treat neural diseases like Parkinson’s and epilepsy. Interest is also growing in developing better brain-machine interfaces, in which electrodes can help control prosthetic limbs. Progress in these fields is hindered by limitations in electrodes, which are relatively stiff and can damage soft brain tissue.

Designing smaller, gentler electrodes that still pick up brain signals is a challenge because brain signals are so weak. Typically, the smaller the electrode, the harder it is to detect a signal. However, a team from the Daegu Gyeongbuk Institute of Science & Technology [DGIST} in Korea developed new probes that are small, flexible and read brain signals clearly.

This is a pretty interesting way to illustrate the research,

Caption: Graphene and gold make a better brain probe. Credit: DGIST

An April 19, 2017 DGIST press release (also on EurekAlert), which originated the news item, expands on the theme (Note: A link has been removed),

The probe consists of an electrode, which records the brain signal. The signal travels down an interconnection line to a connector, which transfers the signal to machines measuring and analysing the signals.

The electrode starts with a thin gold base. Attached to the base are tiny zinc oxide nanowires, which are coated in a thin layer of gold, and then a layer of conducting polymer called PEDOT. These combined materials increase the probe’s effective surface area, conducting properties, and strength of the electrode, while still maintaining flexibility and compatibility with soft tissue.

Packing several long, thin nanowires together onto one probe enables the scientists to make a smaller electrode that retains the same effective surface area of a larger, flat electrode. This means the electrode can shrink, but not reduce signal detection. The interconnection line is made of a mix of graphene and gold. Graphene is flexible and gold is an excellent conductor. The researchers tested the probe and found it read rat brain signals very clearly, much better than a standard flat, gold electrode.

“Our graphene and nanowires-based flexible electrode array can be useful for monitoring and recording the functions of the nervous system, or to deliver electrical signals to the brain,” the researchers conclude in their paper recently published in the journal ACS Applied Materials and Interfaces.

The probe requires further clinical tests before widespread commercialization. The researchers are also interested in developing a wireless version to make it more convenient for a variety of applications.

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

Enhancement of Interface Characteristics of Neural Probe Based on Graphene, ZnO Nanowires, and Conducting Polymer PEDOT by Mingyu Ryu, Jae Hoon Yang, Yumi Ahn, Minkyung Sim, Kyung Hwa Lee, Kyungsoo Kim, Taeju Lee, Seung-Jun Yoo, So Yeun Kim, Cheil Moon, Minkyu Je, Ji-Woong Choi, Youngu Lee, and Jae Eun Jang. ACS Appl. Mater. Interfaces, 2017, 9 (12), pp 10577–10586 DOI: 10.1021/acsami.7b02975 Publication Date (Web): March 7, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

New tool for mapping neuronal connections in the brain

This work comes from the US Naval Research Laboratory according to a Nov. 17, 2015 news item on Nanowerk (Note: A link has been removed),

Research biologists, chemists and theoreticians at the U.S. Naval Research Laboratory (NRL), are on pace to develop the next generation of functional materials that could enable the mapping of the complex neural connections in the brain (“Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes”). The ultimate goal is to better understand how the billions of neurons in the brain communicate with one another during normal brain function, or dysfunction, as result of injury or disease.

“There is tremendous interest in mapping all the neuron connections in the human brain,” said Dr. James Delehanty, research biologist, Center for Biomolecular Science and Engineering. “To do that we need new tools or materials that allow us to see how large groups of neurons communicate with one another while, at the same time, being able to focus in on a single neuron’s activity. Our most recent work potentially opens the integration of voltage-sensitive nanomaterials into live cells and tissues in a variety of configurations to achieve real-time imaging capabilities not currently possible.”

A Nov. 17, 2015 US Naval Research Laboratory (NRL) news release on EurekAlert, which originated the news item, provides more details,

The basis of neuron communication is the time-dependent modulation of the strength of the electric field that is maintained across the cell’s plasma membrane. This is called an action potential. Among the nanomaterials under consideration for application in neuronal action potential imaging are quantum dots (QDs) — crystalline semiconductor nanomaterials possessing a number of advantageous photophysical attributes.

“QDs are very bright and photostable so you can look at them for long times and they allow for tissue imaging configurations that are not compatible with current materials, for example, organic dyes,” Delehanty added. “Equally important, we’ve shown here that QD brightness tracks, with very high fidelity, the time-resolved electric field strength changes that occur when a neuron undergoes an action potential. Their nanoscale size make them ideal nanoscale voltage sensing materials for interfacing with neurons and other electrically active cells for voltage sensing.”

QDs are small, bright, photo-stable materials that possess nanosecond fluorescence lifetimes. They can be localized within or on cellular plasma membranes and have low cytotoxicity when interfaced with experimental brain systems. Additionally, QDs possess two-photon action cross-section orders of magnitude larger than organic dyes or fluorescent proteins. Two-photon imaging is the preferred imaging modality for imaging deep (millimeters) into the brain and other tissues of the body.

In their most recent work, the NRL researchers showed that an electric field typical of those found in neuronal membranes results in suppression of the QD photoluminescence (PL) and, for the first time, that QD PL is able to track the action potential profile of a firing neuron with millisecond time resolution. This effect is shown to be connected with electric-field-driven QD ionization and consequent QD PL quenching, in contradiction with conventional wisdom that suppression of the QD PL is attributable to the quantum confined Stark effect — the shifting and splitting of spectral lines of atoms and molecules due to presence of an external electric field.

“The inherent superior photostability properties of QDs coupled with their voltage sensitivity could prove advantageous to long-term imaging capabilities that are not currently attainable using traditional organic voltage sensitive dyes,” Delehanty said. “We anticipate that continued research will facilitate the rational design and synthesis of voltage-sensitive QD probes that can be integrated in a variety of imaging configurations for the robust functional imaging and sensing of electrically active cells.”

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

Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes by Clare E. Rowland, Kimihiro Susumu, Michael H. Stewart, Eunkeu Oh, Antti J. Mäkinen, Thomas J. O’Shaughnessy, Gary Kushto, Mason A. Wolak, Jeffrey S. Erickson, Alexander L. Efros, Alan L. Huston, and James B. Delehanty. Nano Lett., 2015, 15 (10), pp 6848–6854 DOI: 10.1021/acs.nanolett.5b02725 Publication Date (Web): September 28, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Brains in the US Congress

Tomorrow, May 24, 2012, Jean Paul Allain, associate professor of nuclear engineering at Purdue University (Illinois) will be speaking to members of the US Congress about repairing brain injuries using nanotechnology-enabled bioactive coatings for stents. From the May 21, 2012 news item on Nanowerk,

“Stents coated with a bioactive coating might be inserted at the site of an aneurism to help heal the inside lining of the blood vessel,” said Jean Paul Allain, an associate professor of nuclear engineering. “Aneurisms are saclike bulges in blood vessels caused by weakening of artery walls. We’re talking about using a regenerative approach, attracting cells to reconstruct the arterial wall.”

He will speak before Congress on Thursday (May 24) during the first Brain Mapping Day to discuss the promise of nanotechnology in treating brain injury and disease.

The May 21, 2012 news release (by Emil Venere) for Purdue University offers insight into some of the difficulties of dealing with aneurysms using today’s technologies,

Currently, aneurisms are treated either by performing brain surgery, opening the skull and clipping the sac, or by inserting a catheter through an artery into the brain and implanting a metallic coil into the balloon-like sac.

Both procedures risk major complications, including massive bleeding or the formation of potentially fatal blood clots.

“The survival rate is about 50/50 or worse, and those who do survive could be impaired,” said Allain, who holds a courtesy appointment with materials engineering and is affiliated with the Birck Nanotechnology Center in Purdue’s Discovery Park.

Allain goes on to explain how his team’s research addresses these issues (from the May 21, 2012 Purdue University news release),

Cells needed to repair blood vessels are influenced by both the surface texture – features such as bumps and irregular shapes as tiny as 10 nanometers wide – as well as the surface chemistry of the stent materials.

“We are learning how to regulate cell proliferation and growth by tailoring both the function of surface chemistry and topology,” Allain said. “There is correlation between surface chemistry and how cells send signals back and forth for proliferation. So the surface needs to be tailored to promote regenerative healing.”

The facility being used to irradiate the stents – the Radiation Surface Science and Engineering Laboratory in Purdue’s School of Nuclear Engineering – also is used for work aimed at developing linings for experimental nuclear fusion reactors for power generation.

Irradiating materials with the ion beams causes surface features to “self-organize” and also influences the surface chemistry, Allain said.

The stents are made of nonmagnetic materials, such as stainless steel and an alloy of nickel and titanium. Only a certain part of the stents is rendered magnetic to precisely direct the proliferation of cells to repair a blood vessel where it begins bulging to form the aneurism.

Researchers will study the stents using blood from pigs during the first phase in collaboration with the Walter Reed National Military Medical Center.

The stent coating’s surface is “functionalized” so that it interacts properly with the blood-vessel tissue. Some of the cells are magnetic naturally, and “magnetic nanoparticles” would be injected into the bloodstream to speed tissue regeneration. Researchers also are aiming to engineer the stents so that they show up in medical imaging to reveal how the coatings hold up in the bloodstream.

The research is led by Allain and co-principal investigator Lisa Reece of the Birck Nanotechnology Center. This effort has spawned new collaborations with researchers around the world including those at Universidad de Antioquía, University of Queensland. The research also involves doctoral students Ravi Kempaiah and Emily Walker.

The work is funded with a three-year, $1.5 million grant from the U.S. Army. Cells needed to repair blood vessels are influenced by both the surface texture – features such as bumps and irregular shapes as tiny as 10 nanometers wide – as well as the surface chemistry of the stent materials.

As I find the international flavour to the pursuit of science quite engaging, I want to highlight this bit in the May 21, 2012 news item on Nanowerk which mentions a few other collaborators on this project,

Purdue researchers are working with Col. Rocco Armonda, Dr. Teodoro Tigno and other neurosurgeons at Walter Reed National Military Medical Center in Bethesda, Md. Collaborations also are planned with research scientists from the University of Queensland in Australia, Universidad de Antioquía and Universidad de Los Andes, both in Colombia.

The US Congress is not the only place to hear about this work, Allain will also be speaking in Toronto at the 9th Annual World Congress of Society for Brain Mapping & Therapeutics (SBMT) being held June 2 – 4, 2012.