Tag Archives: Jose Antonio Garrido

Neurons and graphene carpets

I don’t entirely grasp the carpet analogy. Actually, I have no why they used a carpet analogy but here’s the June 12, 2018 ScienceDaily news item about the research,

A work led by SISSA [Scuola Internazionale Superiore di Studi Avanzati] and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of ion ‘trapping’ by graphene carpets and its effect on the communication between neurons. The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition. Graphene is the thinnest bi-dimensional material available today, characterised by incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.

A June 12, 2018 SISSA press release (also on EurekAlert), which originated the news item, provides more detail,

A study conducted by SISSA – Scuola Internazionale Superiore di Studi Avanzati, in association with the University of Antwerp (Belgium), the University of Trieste and the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now. “It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped. It is this small variation that determines the increase in neuronal excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.

The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices”.

It is a study with a double outcome. Laura Ballerini comments as follows: “This ‘ion trap’ effect was described only in theory. Studying the impact of the ‘technology of materials’ on biological systems, we have documented a mechanism to regulate membrane excitability, but at the same time we have also experimentally described a property of the material through the biology of neurons.”

Dexter Johnson in a June 13, 2018 posting, on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website), provides more context for the work (Note: Links have been removed),

While graphene has been tapped to deliver on everything from electronics to optoelectronics, it’s a bit harder to picture how it may offer a key tool for addressing neurological damage and disorders. But that’s exactly what researchers have been looking at lately because of the wonder material’s conductivity and transparency.

In the most recent development, a team from Europe has offered a deeper understanding of how graphene can be combined with neurological tissue and, in so doing, may have not only given us an additional tool for neurological medicine, but also provided a tool for gaining insights into other biological processes.

“The results demonstrate that, depending on how the interface with [single-layer graphene] is engineered, the material may tune neuronal activities by altering the ion mobility, in particular potassium, at the cell/substrate interface,” said Laura Ballerini, a researcher in neurons and nanomaterials at SISSA.

Ballerini provided some context for this most recent development by explaining that graphene-based nanomaterials have come to represent potential tools in neurology and neurosurgery.

“These materials are increasingly engineered as components of a variety of applications such as biosensors, interfaces, or drug-delivery platforms,” said Ballerini. “In particular, in neural electrode or interfaces, a precise requirement is the stable device/neuronal electrical coupling, which requires governing the interactions between the electrode surface and the cell membrane.”

This neuro-electrode hybrid is at the core of numerous studies, she explained, and graphene, thanks to its electrical properties, transparency, and flexibility represents an ideal material candidate.

In all of this work, the real challenge has been to investigate the ability of a single atomic layer to tune neuronal excitability and to demonstrate unequivocally that graphene selectively modifies membrane-associated neuronal functions.

I encourage you to read Dexter’s posting as it clarifies the work described in the SISSA press release for those of us (me) who may fail to grasp the implications.

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

Single-layer graphene modulates neuronal communication and augments membrane ion currents by Niccolò Paolo Pampaloni, Martin Lottner, Michele Giugliano, Alessia Matruglio, Francesco D’Amico, Maurizio Prato, Josè Antonio Garrido, Laura Ballerini, & Denis Scaini. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0163-6 Published online June 13, 2018

This paper is behind a paywall.

All this brings to mind a prediction made about the Graphene Flagship and the Human Brain Project shortly after the European Commission announced in January 2013 that each project had won funding of 1B Euros to be paid out over a period of 10 years. The prediction was that scientists would work on graphene/human brain research.

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.

Korea

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.

With over 150 partners from over 20 countries, the European Union’s Graphene Flagship research initiative unveils its work package devoted to biomedical technologies

An April 11, 2016 news item on Nanowerk announces the Graphene Flagship’s latest work package,

With a budget of €1 billion, the Graphene Flagship represents a new form of joint, coordinated research on an unprecedented scale, forming Europe’s biggest ever research initiative. It was launched in 2013 to bring together academic and industrial researchers to take graphene from the realm of academic laboratories into European society in the timeframe of 10 years. The initiative currently involves over 150 partners from more than 20 European countries. The Graphene Flagship, coordinated by Chalmers University of Technology (Sweden), is implemented around 15 scientific Work Packages on specific science and technology topics, such as fundamental science, materials, health and environment, energy, sensors, flexible electronics and spintronics.

Today [April 11, 2016], the Graphene Flagship announced in Barcelona the creation of a new Work Package devoted to Biomedical Technologies, one emerging application area for graphene and other 2D materials. This initiative is led by Professor Kostas Kostarelos, from the University of Manchester (United Kingdom), and ICREA Professor Jose Antonio Garrido, from the Catalan Institute of Nanoscience and Nanotechnology (ICN2, Spain). The Kick-off event, held in the Casa Convalescència of the Universitat Autònoma de Barcelona (UAB), is co-organised by ICN2 (ICREA Prof Jose Antonio Garrido), Centro Nacional de Microelectrónica (CNM-IMB-CSIC, CIBER-BBN; CSIC Tenured Scientist Dr Rosa Villa), and Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; ICREA Prof Mavi Sánchez-Vives).

An April 11, 2016 ICN2 press release, which originated the news item, provides more detail about the Biomedical Technologies work package and other work packages,

The new Work Package will focus on the development of implants based on graphene and 2D-materials that have therapeutic functionalities for specific clinical outcomes, in disciplines such as neurology, ophthalmology and surgery. It will include research in three main areas: Materials Engineering; Implant Technology & Engineering; and Functionality and Therapeutic Efficacy. The objective is to explore novel implants with therapeutic capacity that will be further developed in the next phases of the Graphene Flagship.

The Materials Engineering area will be devoted to the production, characterisation, chemical modification and optimisation of graphene materials that will be adopted for the design of implants and therapeutic element technologies. Its results will be applied by the Implant Technology and Engineering area on the design of implant technologies. Several teams will work in parallel on retinal, cortical, and deep brain implants, as well as devices to be applied in the periphery nerve system. Finally, The Functionality and Therapeutic Efficacy area activities will centre on development of devices that, in addition to interfacing the nerve system for recording and stimulation of electrical activity, also have therapeutic functionality.

Stimulation therapies will focus on the adoption of graphene materials in implants with stimulation capabilities in Parkinson’s, blindness and epilepsy disease models. On the other hand, biological therapies will focus on the development of graphene materials as transport devices of biological molecules (nucleic acids, protein fragments, peptides) for modulation of neurophysiological processes. Both approaches involve a transversal innovation environment that brings together the efforts of different Work Packages within the Graphene Flagship.

A leading role for Barcelona in Graphene and 2D-Materials

The kick-off meeting of the new Graphene Flagship Work Package takes place in Barcelona because of the strong involvement of local institutions and the high international profile of Catalonia in 2D-materials and biomedical research. Institutions such as the Catalan Institute of Nanoscience and Nanotechnology (ICN2) develop frontier research in a supportive environment which attracts talented researchers from abroad, such as ICREA Research Prof Jose Antonio Garrido, Group Leader of the ICN2 Advanced Electronic Materials and Devices Group and now also Deputy Leader of the Biomedical Technologies Work Package. Until summer 2015 he was leading a research group at the Technische Universität München (Germany).

Further Graphene Flagship events in Barcelona are planned; in May 2016 ICN2 will also host a meeting of the Spintronics Work Package. ICREA Prof Stephan Roche, Group Leader of the ICN2 Theoretical and Computational Nanoscience Group, is the deputy leader of this Work Package led by Prof Bart van Wees, from the University of Groningen (The Netherlands). Another Work Package, on optoelectronics, is led by Prof Frank Koppens from the Institute of Photonic Sciences (ICFO, Spain), with Prof Andrea Ferrari from the University of Cambridge (United Kingdom) as deputy. Thus a number of prominent research institutes in Barcelona are deeply involved in the coordination of this European research initiative.

Kostas Kostarelos, the leader of the Biomedical Technologies Graphene Flagship work package, has been mentioned here before in the context of his blog posts for The Guardian science blog network (see my Aug. 7, 2014 post for a link to his post on metaphors used in medicine).