Stiff Biodegradable Needle
Floating Soft Electric Leads Nanostructured Surface
Biodegradation
Biodegradation
Insulating Sheath Microelectrode
Implants that understand the brain
Nanostructured Surface
Brain implants need to be well adapted to the natural brain environment. Researchers in the Brain Micro Snooper project are working to develop improved brain implants, work which brings the prospect of restoring certain functions to disabled people a step closer, as Dr Gaëlle Offranc-Piret explains. An individual who has been paralysed following a traffic accident may retain normal neuronal function, with neurons in the brain still sending signals out to the rest of the body. The problem lies elsewhere in the body. “The problem is in communication to the nerves,” says Dr Gaelle Offranc-Piret, a researcher in the BrainTech research laboratory at Grenoble, part of INSERM. A reliable brain implant could help record information on neural activity at the neuron’s scale, a major step towards effective intervention; this is a topic at the heart of Dr Offranc-Piret’s work in the ERC-funded Brain Micro Snooper project. “We aim to develop brain implants with micro-electrodes that will attach to neurons and detect their action potentials in the long term,” she outlines. “The goal is to bring these implants to the clinic. In order to achieve this we need to pay a lot of attention to the materials that we use, so that it has a higher probability of clinical transfer.” Brain Micro-Snooper This research holds relevance beyond cases of paralysis, as the implant could be adapted to several different pathologies, including epilepsy, neurodegenerative disorders and
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certain types of tumours, while it could also be used in therapeutic brain-computer interfaces. The focus at this stage however The implant before surgical insertion.
A nanostructured electrode.
is on developing an implant to record action potentials, with Dr Offranc-Piret using fairly conventional materials. “We are looking at certain types of insulating polymer such as polyimides or parylenes, and we are also varying the conductor part using gold, platinum or PEDOT:PSS. We are then trying to compare the different possibilities in terms of performance,” she says. The shape of the implant is however the most important consideration. “The aim is really to be as biomimetic as possible when it comes to the shape of the implants so that they are seen by the brain environment just as a brain cell,” continues Dr Offranc-Piret. By minimising the dimensions of the implant, Dr Offranc-Piret aims to reduce the flexibility mismatch between implant and brain materials, and therefore the disruption to surrounding cells once the implant is introduced. Also, researchers are using nanostructured or microstructured materials for the electrode. “Nothing in the brain is really entirely flat, everything is moving around to some extent. The membranes are quite packed,” outlines Dr Offranc-Piret. By modifying the surface of the material, using micro- and nontechnology methods,
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researchers aim to ensure that it can function more effectively in the brain. “These micro/nanostructures are able to improve the adhesion with neural cells, and also encourage the re-growth of neurites, that may be necessary after the surgical insertion of the implant,” says Dr Offranc-Piret. Researchers have used neural cell cultures from rat brains to assess the biocompatibility of the materials used in the implant. This work involves using in vitro tests to look at how neural cells adapt to the presence of an implant, while Dr Offranc-Piret and her colleagues are also conducting in vivo tests. “We check how the tissue around the implant has reacted to the implant. Do we find any glial cell scar for example?” she outlines. The ideal scenario is for the implant itself to be in close contact with the surrounding cells. “If we don’t have good contact then you will have poor recording and if stimulation is needed as a treatment, you will have to put in more current, resulting unfortunately in damage to the neurons,” explains Dr Offranc-Piret. “It’s also good to have several electrodes in contact with several neurons. If you can stimulate several neurons at the same time and individually, you can apply a more complex pattern of stimulation and eventually send more relevant information to another part of the neural chain.”
consideration in terms of stimulating neurons. “With plasticity, it may be that neurons can actually take advantage of a new connection with a device,” outlines Dr Offranc-Piret. This could mean that a patient would be able to find an alternative neural pathway to perform a specific action, rather than the same pathway that they maybe used before the onset of disease, or suffering an injury. “In certain areas of the brain we see that there is some plasticity. This could be interesting, as a potential route to improving the condition of some patients that are wanting to regain certain functions and overcome disability,” continues Dr Offranc-Piret. The focus at this stage in the project however is on improving the implants and bringing them closer to clinical application. Dr OffrancPiret and her team are still working mainly with rodents, and looking to improve the very tiny, thin wires that are used in the implants. “We now know how to assemble those wires to the biodegradable matrix needed during the surgical insertion step. We will also look at the long-term reactions in the rodents after this matrix has degraded, and in the regions around the thin wires,” she says. The implants could also be modified further in future to adapt to specific pathologies. “We can look at the macro-shape of the implants and have sorts of hybridisation between different
The aim is really to be as biomimetic as possible when it comes to the shape of the implants so that they are seen by the brain environment, just as a brain cell. A major challenge here is in establishing a good, reliable connection between a single electrode and the same neuron. Currently it remains very difficult to get long term recording data on the same neuron with a same micro-sensor in vivo, an issue that Dr Offranc-Piret is addressing. This would help researchers understand patterns of neural tissue, which then opens up wider possibilities. “For example, it would be very interesting to look in more depth at the cortical areas that are responsible for the movement of the body, made of so many degrees of freedom” says Dr Offranc-Piret. “We need to gain more information about the patterns of neuronal signals from different areas of the brain, both in healthy and pathologic brain structures.”
implant materials. If it’s going to be implanted deeper in the brain, we may need to assemble our current implant to more stretchable materials,” explains Dr Offranc-Piret. “We will have to adapt the device depending on the pathology that we are aiming at and where it will be implanted.”
BRAIN MICRO SNOOPER A mimetic implant for minimal disturbance, stable stimulation and recording of intra-cortical neural units Project Objectives
One billion people experience some disability making them more susceptible to adverse socioeconomic outcomes such as less education, lower levels employment, and higher poverty rates. These can become more perverse for people who live with some form of paralysis. Gaëlle is now developing flexible, thin and nanostructured brain implants for therapeutic applications that could restore function for disabled people.
Project Partners
• Fannie Darlot • Lionel Rousseau • François Berger
Project Funding
Funded by the European Research Council ERC at 1.5M € over 5 years (2015-2020)
Contact Details
Project Coordinator, Gaëlle Offranc Piret, PhD ERC Brain Micro Snooper Braintech Laboratory U1205 INSERM/UGA/CHU 2280 rue de la piscine, Bât B-3ème étage, 38400 Saint Martin d’Hères, FRANCE E: gaelle.offranc-piret@inserm.fr
Gaëlle Offranc Piret, PhD
Gaëlle Offranc Piret, master in physics (Paris XI - Orsay University) is a permanent researcher at the the French National Institute for Health and Medical Research, Braintech Laboratory (U1205 INSERM UGA, Grenoble, France) whose activities are spread over the CEA-Grenoble and UGA University sites. She obtained her Master in Physics and her PhD in 2010 (IEMN laboratory, Lille University, France) and did a post-doctorate at polytechnique school, Palaiseau-Paris and then at the University of Lund (Sweden). She works on the development of micronanotechnologies, materials and implants.
Tiny electrode wires at the end of each implant “arm”.
Brain models This is a challenging task, as it’s very difficult to get reliable models of the brain, although modern techniques do provide new insights into what can be considered as normal patterns. The plasticity of the brain is also an important
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