Tag Archives: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

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.

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).

Parvus Therapeutics (Calgary, Canada) and reprogramming immune cells

An international collaboration of Canadian, Spanish, and US scientists has announced a new therapeutic approach which could reverse autoimmune diseases in a Feb. 17, 2016 news item on Nanotechnology Now,

• Nanotechnology Approach Restores Glucose Regulation and Motor Function in In Vivo Preclinical Models of Diabetes and Multiple Sclerosis, Respectively; Joint Swelling and Destruction Resolved in In Vivo Model of Rheumatoid Arthritis
• Parvus’ Approach Can Be Tailored to Treat Diverse Diseases

A Feb. 17, 2016 Parvus Therapeutics news release (also on EurekAlert), which originated the news item, provides more detail and a strong orientation to marketing communication,

Parvus Therapeutics today announced the publication in Nature of a seminal paper describing the discovery and applications of a novel therapeutic approach employing nanomedicines, referred to as “Navacims”TM, to reprogram white blood cells to become regulatory cells capable of blunting autoimmune responses and restoring the equilibrium of the immune system. Navacims are nanoparticles (NPs) coated with disease-relevant peptide-major histocompatibility complexes (pMHCs) that alter the behavior of pathogenic T lymphocytes by binding directly to their antigen receptors. The peer-reviewed article, titled “Expanding antigen-specific regulatory networks to treat autoimmunity” reports on a body of work, including results in multiple in vivo disease models, built on more than eight years of research by Parvus Founder and Chief Scientific Officer, Pere Santamaria, M.D., Ph.D.

Dr. Santamaria commented, “Autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, are extraordinarily complex responses of our immune system against some of our own tissues (e.g. pancreas, brain and joints, respectively), leading to chronic organ inflammation, organ dysfunction, and, in some cases, premature death. Blunting these incompletely understood immune responses without suppressing the normal components of our immune system that protect us against infection and cancer is not currently possible.”

“However, our work offers a pharmaceutical solution to this fundamental problem,” Dr. Santamaria continued. “Navacims essentially re-program disease-causing white blood cells to become disease-suppressing cells, known as regulatory cells, leading to sustained therapeutic effects in various spontaneous and experimental autoimmune diseases, as reported in our article in Nature. Essentially, we have found that Navacims can be tailored to treat a wide range of autoimmune diseases, while sharing a common structure. Importantly, they have been shown to affect human white blood cells in the same manner as they do murine cells. Furthermore, Navacims have shown promising safety findings in preclinical in vivo models. Based on our results to date, we believe Navacims represent a therapeutic platform with broad-ranging health care implications.”

Findings being reported in Nature include:

pMHC class II Navacims expanded cognate CD4+ T-cells that consistently have a TR1-like, regulatory T cell surface phenotype, transcriptional pattern and cytokine profile (mouse=human TR1 cells) systemically.

pMHC class II-Navacims designed to target T cells in newly diabetic nonobese (NOD) mice restored normoglycemia (normal blood sugar regulation) in the majority of the mice tested.

Tailored pMHC class II Navacims restored motor function to paralyzed C57BL/6 mice at the peak of Experimental Autoimmune Encephalomyelitis (a model of Multiple Sclerosis).

pMHC class II Navacims, targeting disease-causing T cells in joints, resolved joint swelling and destruction in arthritic mice.

“The findings being reported in Nature represent a scientific advance for Parvus and also a major achievement in the field of Immunology,” said Janice M. LeCocq, CEO of Parvus. “We believe that Dr. Santamaria’s work has the potential to transform the treatment of many of the more than 80 major autoimmune diseases affecting humankind, alleviating the suffering of millions of patients and their families. Over the coming year, we will be dedicating much of our in-house efforts to the advancement of our two lead programs for type 1 diabetes and multiple sclerosis.”

“Dr. Santamaria’s work to target the immune system dysfunction that causes type 1 diabetes represents the kind of innovative work that JDRF believes will eventually get us to a cure for this disease,” said Juvenile Diabetes Research Foundation Vice President of Discovery Research Julia Greenstein, Ph.D. “He and his colleagues have made exciting progress towards possibly developing a new class of drugs that could rebalance certain T-cells and ultimately provide a cure for type 1 diabetes and other autoimmune diseases as well.” The JDRF has funded the work of Dr. Santamaria and his colleagues at Parvus to explore Navacim-based treatments for diabetes.

Parvus’ strategy is to establish partnerships with major pharmaceutical companies to undertake the clinical and commercial development of many of its product pipeline candidates while also reserving rights to others suitable for its own development and commercialization. Parvus currently is engaged in late stage discussions with multiple pharmaceutical companies with regard to the type 1 diabetes (T1D) program. Manufacturing scale-up is now underway to supply upcoming preclinical and clinical studies.

The work being reported in Nature was led by Dr. Pere Santamaria and largely executed at the University of Calgary, Cumming School of Medicine (animal models of disease) and the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (humanized mouse work), with significant contributions from investigators at Institutions in Europe and the US. Further, Innovate Calgary, the technology-transfer and business-incubation center for the University of Calgary, provided early support for the transfer of the Navacims technology to and incubation of Parvus Therapeutics, which was organized as a separate entity in 2012.

It should be noted that this intervention has been tested on ‘humanized’ mice and, at this point, there don’t seem to have been any human clinical trials. At a guess I’d say we’re still several years away from this therapeutic intervention reaching the market, should it prove to be successful in humans.

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

Expanding antigen-specific regulatory networks to treat autoimmunity by Xavier Clemente Casares, Jesus Blanco, Poornima Ambalavanan, Jun Yamanouchi, Santiswarup Singha, Cesar Fandos, Sue Tsai, Jinguo Wang, Nahir Garabatos, Cristina Izquierdo, Smriti Agrawal, Michael B. Keough, V. Wee Yong, Eddie James, Anna Moore, Yang Yang, Thomas Stratmann, Pau Serra, & Pere Santamaria. Nature (2016) doi:10.1038/nature16962 Published online 17 February 2016

This paper is behind a paywall.