Tag Archives: University of Trieste

Calming a synapse (part of a neuron) with graphene flakes

As we continue to colonize our own brains, there’s more news of graphene and neurons (see my Feb. 1, 2016 post featuring research from the same team in Italy featured in this post). A May 10, 2016 news item on ScienceDaily highlights work that could be used for epilepsy,

Innovative graphene technology to buffer the activity of synapses– this is the idea behind a recently-published study in the journal ACS Nano coordinated by the International School for Advanced Studies in Trieste (SISSA) and the University of Trieste. In particular, the study showed how effective graphene oxide flakes are at interfering with excitatory synapses, an effect that could prove useful in new treatments for diseases like epilepsy.

I guess the press release took a while to make its way through translation, here’s more from the April 10, 2016 SISSA (International School for Advanced Studies) press release (also on EurekAlert),

The laboratory of SISSA’s Laura Ballerini in collaboration with the University of Trieste, the University of Manchester and the University of Castilla -la Mancha, has discovered a new approach to modulating synapses. This methodology could be useful for treating diseases in which electrical nerve activity is altered. Ballerini and Maurizio Prato (University of Trieste) are the principal investigators of the project within the European flagship on graphene, a far-reaching 10-year international collaboration (one billion euros in funding) that studies innovative uses of the material.

Traditional treatments for neurological diseases generally include drugs that act on the brain or neurosurgery. Today however, graphene technology is showing promise for these types of applications, and is receiving increased attention from the scientific community. The method studied by Ballerini and colleagues uses “graphene nano-ribbons” (flakes) which buffer activity of synapses simply by being present.

“We administered aqueous solutions of graphene flakes to cultured neurons in ‘chronic’ exposure conditions, repeating the operation every day for a week. Analyzing functional neuronal electrical activity, we then traced the effect on synapses” says Rossana Rauti, SISSA researcher and first author of the study.

In the experiments, size of the flakes varied (10 microns or 80 nanometers) as well as the type of graphene: in one condition graphene was used, in another, graphene oxide. “The ‘buffering’ effect on synaptic activity happens only with smaller flakes of graphene oxide and not in other conditions,” says Ballerini. “The effect, in the system we tested, is selective for the excitatory synapses, while it is absent in inhibitory ones”

A Matter of Size

What is the origin of this selectivity? “We know that in principle graphene does not interact chemically with synapses in a significant way- its effect is likely due to the mere presence of synapses,” explains SISSA researcher and one of the study’s authors, Denis Scaini. “We do not yet have direct evidence, but our hypothesis is that there is a link with the sub-cellular organization of the synaptic space.”

A synapse is a contact point between one neuron and another where the nervous electrical signal “jumps” between a pre and post-synaptic unit. [emphasis mine] There is a small gap or discontinuity where the electrical signal is “translated” by a neurotransmitter and released by pre-synaptic termination into the extracellular space and reabsorbed by the postsynaptic space, to be translated again into an electrical signal. The access to this space varies depending on the type of synapses: “For the excitatory synapses, the structure’s organization allows higher exposure for the graphene flakes interaction, unlike inhibitory synapses, which are less physically accessible in this experimental model,” says Scaini.

Another clue that distance and size could be crucial in the process is found in the observation that graphene performs its function only in the oxidized form. “Normal graphene looks like a stretched and stiff sheet while graphene oxide appears crumpled, and thus possibly favoring interface with the synaptic space, ” adds Rauti.

Administering graphene flake solutions leaves the neurons alive and intact. For this reason the team thinks they could be used in biomedical applications for treating certain diseases. “We may imagine to target a drug by exploiting the apparent flakes’ selectivity for synapses, thus targeting directly the basic functional unit of neurons”concludes Ballerini.

That’s a nice description of neurons, synapses, and neurotransmitters.

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

Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks by Rossana Rauti, Neus Lozano, Veronica León, Denis Scaini†, Mattia Musto, Ilaria Rago, Francesco P. Ulloa Severino, Alessandra Fabbro, Loredana Casalis, Ester Vázquez, Kostas Kostarelos, Maurizio Prato, and Laura Ballerini. ACS Nano, 2016, 10 (4), pp 4459–4471
DOI: 10.1021/acsnano.6b00130 Publication Date (Web): March 31, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Graphene Flagship high points

The European Union’s Graphene Flagship project has provided a series of highlights in place of an overview for the project’s ramp-up phase (in 2013 the Graphene Flagship was announced as one of two winners of a science competition, the other winner was the Human Brain Project, with two prizes of 1B Euros for each project). Here are the highlights from the April 19, 2016 Graphene Flagship press release,

Graphene and Neurons – the Best of Friends

Flagship researchers have shown that it is possible to interface untreated graphene with neuron cells whilst maintaining the integrity of these vital cells [1]. This result is a significant first step towards using graphene to produce better deep brain implants which can both harness and control the brain.

Graphene and Neurons
 

This paper emerged from the Graphene Flagship Work Package Health and Environment. Prof. Prato, the WP leader from the University of Trieste in Italy, commented that “We are currently involved in frontline research in graphene technology towards biomedical applications, exploring the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is a first step in that direction.”

[1] Fabbro A., et al., Graphene-Based Interfaces do not Alter Target Nerve Cells. ACS Nano, 10 (1), 615 (2016).

Pressure Sensing with Graphene: Quite a Squeeze

The Graphene Flagship developed a small, robust, highly efficient squeeze film pressure sensor [2]. Pressure sensors are present in most mobile handsets and by replacing current sensor membranes with a graphene membrane they allow the sensor to decrease in size and significantly increase its responsiveness and lifetime.

Discussing this work which emerged from the Graphene Flagship Work Package Sensors is the paper’s lead author, Robin Dolleman from the Technical University of Delft in The Netherlands “After spending a year modelling various systems the idea of the squeeze-film pressure sensor was formed. Funding from the Graphene Flagship provided the opportunity to perform the experiments and we obtained very good results. We built a squeeze-film pressure sensor from 31 layers of graphene, which showed a 45 times higher response than silicon based devices, while reducing the area of the device by a factor of 25. Currently, our work is focused on obtaining similar results on monolayer graphene.”

 

[2] Dolleman R. J. et al., Graphene Squeeze-Film Pressure Sensors. Nano Lett., 16, 568 (2016)

Frictionless Graphene


Image caption: A graphene nanoribbon was anchored at the tip of a atomic force microscope and dragged over a gold surface. The observed friction force was extremely low.

Image caption: A graphene nanoribbon was anchored at the tip of a atomic force microscope and dragged over a gold surface. The observed friction force was extremely low.

Research done within the Graphene Flagship, has observed the onset of superlubricity in graphene nanoribbons sliding on a surface, unravelling the role played by ribbon size and elasticity [3]. This important finding opens up the development potential of nanographene frictionless coatings. This research lead by the Graphene Flagship Work Package Nanocomposites also involved researchers from Work Package Materials and Work Package Health and the Environment, a shining example of the inter-disciplinary, cross-collaborative approach to research undertaken within the Graphene Flagship. Discussing this further is the Work Package Nanocomposites Leader, Dr Vincenzo Palermo from CNR National Research Council, Italy “Strengthening the collaboration and interactions with other Flagship Work Packages created added value through a strong exchange of materials, samples and information”.

[3] Kawai S., et al., Superlubricity of graphene nanoribbons on gold surfaces. Science. 351, 6276, 957 (2016) 

​Graphene Paddles Forward

Work undertaken within the Graphene Flagship saw Spanish automotive interiors specialist, and Flagship partner, Grupo Antolin SA work in collaboration with Roman Kayaks to develop an innovative kayak that incorporates graphene into its thermoset polymeric matrices. The use of graphene and related materials results in a significant increase in both impact strength and stiffness, improving the resistance to breakage in critical areas of the boat. Pushing the graphene canoe well beyond the prototype demonstration bubble, Roman Kayaks chose to use the K-1 kayak in the Canoe Marathon World Championships held in September in Gyor, Hungary where the Graphene Canoe was really put through its paces.

Talking further about this collaboration from the Graphene Flagship Work Package Production is the WP leader, Dr Ken Teo from Aixtron Ltd., UK “In the Graphene Flagship project, Work Package Production works as a technology enabler for real-world applications. Here we show the worlds first K-1 kayak (5.2 meters long), using graphene related materials developed by Grupo Antolin. We are very happy to see that graphene is creating value beyond traditional industries.” 

​Graphene Production – a Kitchen Sink Approach

Researchers from the Graphene Flagship have devised a way of producing large quantities of graphene by separating graphite flakes in liquids with a rotating tool that works in much the same way as a kitchen blender [4]. This paves the way to mass production of high quality graphene at a low cost.

The method was produced within the Graphene Flagship Work Package Production and is talked about further here by the WP deputy leader, Prof. Jonathan Coleman from Trinity College Dublin, Ireland “This technique produced graphene at higher rates than most other methods, and produced sheets of 2D materials that will be useful in a range of applications, from printed electronics to energy generation.” 

[4] Paton K.R., et al., Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids. Nat. Mater. 13, 624 (2014).

Flexible Displays – Rolled Up in your Pocket

Working with researchers from the Graphene Flagship the Flagship partner, FlexEnable, demonstrated the world’s first flexible display with graphene incorporated into its pixel backplane. Combined with an electrophoretic imaging film, the result is a low-power, durable display suitable for use in many and varied environments.

Emerging from the Graphene Flagship Work Package Flexible Electronics this illustrates the power of collaboration.  Talking about this is the WP leader Dr Henrik Sandberg from the VTT Technical Research Centre of Finland Ltd., Finland “Here we show the power of collaboration. To deliver these flexible demonstrators and prototypes we have seen materials experts working together with components manufacturers and system integrators. These devices will have a potential impact in several emerging fields such as wearables and the Internet of Things.”

​Fibre-Optics Data Boost from Graphene

A team of researches from the Graphene Flagship have demonstrated high-performance photo detectors for infrared fibre-optic communication systems based on wafer-scale graphene [5]. This can increase the amount of information transferred whilst at the same time make the devises smaller and more cost effective.

Discussing this work which emerged from the Graphene Flagship Work Package Optoelectronics is the paper’s lead author, Daniel Schall from AMO, Germany “Graphene has outstanding properties when it comes to the mobility of its electric charge carriers, and this can increase the speed at which electronic devices operate.”

[5] Schall D., et al., 50 GBit/s Photodetectors Based on Wafer-Scale Graphene for Integrated Silicon Photonic Communication Systems. ACS Photonics. 1 (9), 781 (2014)

​Rechargeable Batteries with Graphene

A number of different research groups within the Graphene Flagship are working on rechargeable batteries. One group has developed a graphene-based rechargeable battery of the lithium-ion type used in portable electronic devices [6]. Graphene is incorporated into the battery anode in the form of a spreadable ink containing a suspension of graphene nanoflakes giving an increased energy efficiency of 20%. A second group of researchers have demonstrated a lithium-oxygen battery with high energy density, efficiency and stability [7]. They produced a device with over 90% efficiency that may be recharged more than 2,000 times. Their lithium-oxygen cell features a porous, ‘fluffy’ electrode made from graphene together with additives that alter the chemical reactions at work in the battery.

Graphene Flagship researchers show how the 2D material graphene can improve the energy capacity, efficiency and stability of lithium-oxygen batteries.

Both devices were developed in different groups within the Graphene Flagship Work Package Energy and speaking of the technology further is Prof. Clare Grey from Cambridge University, UK “What we’ve achieved is a significant advance for this technology, and suggests whole new areas for research – we haven’t solved all the problems inherent to this chemistry, but our results do show routes forward towards a practical device”.

[6] Liu T., et al. Cycling Li-O2 batteries via LiOH formation and decomposition. Science. 350, 6260, 530 (2015)

[7] Hassoun J., et al., An Advanced Lithium-Ion Battery Based on a Graphene Anode and a Lithium Iron Phosphate Cathode. Nano Lett., 14 (8), 4901 (2014)

Graphene – What and Why?

Graphene is a two-dimensional material formed by a single atom-thick layer of carbon, with the carbon atoms arranged in a honeycomb-like lattice. This transparent, flexible material has a number of unique properties. For example, it is 100 times stronger than steel, and conducts electricity and heat with great efficiency.

A number of practical applications for graphene are currently being developed. These include flexible and wearable electronics and antennas, sensors, optoelectronics and data communication systems, medical and bioengineering technologies, filtration, super-strong composites, photovoltaics and energy storage.

Graphene and Beyond

The Graphene Flagship also covers other layered materials, as well as hybrids formed by combining graphene with these complementary materials, or with other materials and structures, ranging from polymers, to metals, cement, and traditional semiconductors such as silicon. Graphene is just the first of thousands of possible single layer materials. The Flagship plans to accelerate their journey from laboratory to factory floor.

Especially exciting is the possibility of stacking monolayers of different elements to create materials not found in nature, with properties tailored for specific applications. Such composite layered materials could be combined with other nanomaterials, such as metal nanoparticles, in order to further enhance their properties and uses.​

Graphene – the Fruit of European Scientific Excellence

Europe, North America and Asia are all active centres of graphene R&D, but Europe has special claim to be at the centre of this activity. The ground-breaking experiments on graphene recognised in the award of the 2010 Nobel Prize in Physics were conducted by European physicists, Andre Geim and Konstantin Novoselov, both at Manchester University. Since then, graphene research in Europe has continued apace, with major public funding for specialist centres, and the stimulation of academic-industrial partnerships devoted to graphene and related materials. It is European scientists and engineers who as part of the Graphene Flagship are closely coordinating research efforts, and accelerating the transfer of layered materials from the laboratory to factory floor.

For anyone who would like links to the published papers, you can check out an April 20, 2016 news item featuring the Graphene Flagship highlights on Nanowerk.

Graphene and neurons in a UK-Italy-Spain collaboration

There’s been a lot of talk about using graphene-based implants in the brain due to the material’s flexibility along with its other properties. A step forward has been taking according to a Jan. 29, 2016 news item on phys.org,

Researchers have successfully demonstrated how it is possible to interface graphene – a two-dimensional form of carbon – with neurons, or nerve cells, while maintaining the integrity of these vital cells. The work may be used to build graphene-based electrodes that can safely be implanted in the brain, offering promise for the restoration of sensory functions for amputee or paralysed patients, or for individuals with motor disorders such as epilepsy or Parkinson’s disease.

A Jan. 29, 2016 Cambridge University press release (also on EurekAlert), which originated the news item, provides more detail,

Previously, other groups had shown that it is possible to use treated graphene to interact with neurons. However the signal to noise ratio from this interface was very low. By developing methods of working with untreated graphene, the researchers retained the material’s electrical conductivity, making it a significantly better electrode.

“For the first time we interfaced graphene to neurons directly,” said Professor Laura Ballerini of the University of Trieste in Italy. “We then tested the ability of neurons to generate electrical signals known to represent brain activities, and found that the neurons retained their neuronal signalling properties unaltered. This is the first functional study of neuronal synaptic activity using uncoated graphene based materials.”

Our understanding of the brain has increased to such a degree that by interfacing directly between the brain and the outside world we can now harness and control some of its functions. For instance, by measuring the brain’s electrical impulses, sensory functions can be recovered. This can be used to control robotic arms for amputee patients or any number of basic processes for paralysed patients – from speech to movement of objects in the world around them. Alternatively, by interfering with these electrical impulses, motor disorders (such as epilepsy or Parkinson’s) can start to be controlled.

Scientists have made this possible by developing electrodes that can be placed deep within the brain. These electrodes connect directly to neurons and transmit their electrical signals away from the body, allowing their meaning to be decoded.

However, the interface between neurons and electrodes has often been problematic: not only do the electrodes need to be highly sensitive to electrical impulses, but they need to be stable in the body without altering the tissue they measure.

Too often the modern electrodes used for this interface (based on tungsten or silicon) suffer from partial or complete loss of signal over time. This is often caused by the formation of scar tissue from the electrode insertion, which prevents the electrode from moving with the natural movements of the brain due to its rigid nature.

Graphene has been shown to be a promising material to solve these problems, because of its excellent conductivity, flexibility, biocompatibility and stability within the body.

Based on experiments conducted in rat brain cell cultures, the researchers found that untreated graphene electrodes interfaced well with neurons. By studying the neurons with electron microscopy and immunofluorescence the researchers found that they remained healthy, transmitting normal electric impulses and, importantly, none of the adverse reactions which lead to the damaging scar tissue were seen.

According to the researchers, this is the first step towards using pristine graphene-based materials as an electrode for a neuro-interface. In future, the researchers will investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons, and whether tuning the material properties of graphene might alter the synapses and neuronal excitability in new and unique ways. “Hopefully this will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer unwanted side effects,” said Ballerini.

“We are currently involved in frontline research in graphene technology towards biomedical applications,” said Professor Maurizio Prato from the University of Trieste. “In this scenario, the development and translation in neurology of graphene-based high-performance biodevices requires the exploration of the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is only a first step in that direction.”

“These initial results show how we are just at the tip of the iceberg when it comes to the potential of graphene and related materials in bio-applications and medicine,” said Professor Andrea Ferrari, Director of the Cambridge Graphene Centre. “The expertise developed at the Cambridge Graphene Centre allows us to produce large quantities of pristine material in solution, and this study proves the compatibility of our process with neuro-interfaces.”

The research was funded by the Graphene Flagship [emphasis mine],  a European initiative which promotes a collaborative approach to research with an aim of helping to translate graphene out of the academic laboratory, through local industry and into society.

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

Graphene-Based Interfaces Do Not Alter Target Nerve Cells by Alessandra Fabbro, Denis Scaini, Verónica León, Ester Vázquez, Giada Cellot, Giulia Privitera, Lucia Lombardi, Felice Torrisi, Flavia Tomarchio, Francesco Bonaccorso, Susanna Bosi, Andrea C. Ferrari, Laura Ballerini, and Maurizio Prato. ACS Nano, 2016, 10 (1), pp 615–623 DOI: 10.1021/acsnano.5b05647 Publication Date (Web): December 23, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

There are a couple things I found a bit odd about this project. First, all of the funding is from the Graphene Flagship initiative. I was expecting to see at least some funding from the European Union’s other mega-sized science initiative, the Human Brain Project. Second, there was no mention of Spain nor were there any quotes from the Spanish researchers. For the record, the Spanish institutions represented were: University of Castilla-La Mancha, Carbon Nanobiotechnology Laboratory, and the Basque Foundation for Science.

The yin and the yang of carbon nanotubes and toxicity

 

Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically. From the Jan. 15,2013 news item on ScienceDaily,

In a new study, published January 15 [2013] in the journal Angewandte Chemie, evidence is provided that the asbestos-like reactivity and pathogenicity reported for long, pristine nanotubes can be completely alleviated if their surface is modified and their effective length is reduced as a result of chemical treatment.

First atomically described in the 1990s, carbon nanotubes are sheets of carbon atoms rolled up into hollow tubes just a few nanometres in diameter. Engineered carbon nanotubes can be chemically modified, with the addition of chemotherapeutic drugs, fluorescent tags or nucleic acids — opening up applications in cancer and gene therapy.

Furthermore, these chemically modified carbon nanotubes can pierce the cell membrane, acting as a kind of ‘nano-needle’, allowing the possibility of efficient transport of therapeutic and diagnostic agents directly into the cytoplasm of cells.

Among their downsides however, have been concerns about their safety profile. One of the most serious concerns, highlighted in 2008, involves the carcinogenic risk from the exposure and persistence of such fibres in the body. Some studies indicate that when long untreated carbon nanotubes are injected to the abdominal cavity of mice they can induce unwanted responses resembling those associated with exposure to certain asbestos fibres.

In this paper, the authors describe two different reactions which ask if any chemical modification can render the nanotubes non-toxic. They conclude that not all chemical treatments alleviate the toxicity risks associated with the material. Only those reactions that are able to render carbon nanotubes short and stably suspended in biological fluids without aggregation are able to result in safe, risk-free material.

Here’s a citation and link for this latest  research, from the ScienceDaily news item where you can also read the lead researcher’s comments about carbon nanotubes, safety, and unreasonable proposals to halt production,

Hanene Ali-Boucetta, Antonio Nunes, Raquel Sainz, M. Antonia Herrero, Bowen Tian, Maurizio Prato, Alberto Bianco, Kostas Kostarelos. Asbestos-like Pathogenicity of Long Carbon Nanotubes Alleviated by Chemical Functionalization. Angewandte Chemie International Edition, 2013; DOI: 10.1002/anie.201207664

The article is behind a paywall. I have mentioned long carbon nanotubes and their resemblance to asbestos fibres in several posts. The  Oct. 26, 2009 posting [scroll down about 1/3 of the way] highlights research which took place after the study where mice had carbon nanotubes injected into their bellies; in this second piece of research they inhaled the nanotubes.

ETA Jan. 21, 2013: Dexter Johnson gives context and commentary about this latest research into long multiwalled nanotubes (MWNTs) which he sums up as the answer to this question “What if you kept the MWNTs short?”  in a Jan. 18, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website)