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EP-4738475-A2 - AN ELECTROCHEMICALLY ACTIVATED AND REDUCED GRAPHENE OXIDE STRUCTURE

EP4738475A2EP 4738475 A2EP4738475 A2EP 4738475A2EP-4738475-A2

Abstract

The present invention relates to a reduced graphene oxide structure for stimulation and/or recording of the central and/or peripheral nervous system comprising a stack of layered, reduced graphene oxide flakes, wherein the reduced graphene oxide structure is electrochemically activated.

Inventors

  • Viana, Damià
  • Garrido Ariza, José Antonio
  • Walston, Steve

Assignees

  • Fundació Institut Català de Nanociència i Nanotecnologia (ICN2)
  • Institució Catalana de Recerca i Estudis Avançats (ICREA)

Dates

Publication Date
20260506
Application Date
20210603

Claims (15)

  1. A reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system comprising a stack of layered, reduced graphene oxide flakes (22), wherein the reduced graphene oxide structure (20) is electrochemically activated by causing charged ions to permeate into the structure (20), and wherein the graphene oxide structure (20) is obtained by hydrothermal reduction of graphene oxide flakes (22) comprising oxygen-containing functionalizations via subcritical water, causing protons from the water to react with the oxygen-containing functionalizations of the flakes (22).
  2. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to claim 1, characterized in that the reduced graphene oxide structure (20) is obtainable by electrochemical activation in an electrolyte system, preferably an aqueous environment.
  3. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to claim 1 or 2, characterized in that the reduced graphene oxide structure (20) comprises a plurality of holes (26) having a diameter equal to or less than 10 nm.
  4. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to claim 3, characterized in that the holes (26) are permeable for charged ions.
  5. The reduced oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to claim 4, characterized in that the charged ions (24) are arranged between the layers of the reduced graphene oxide flakes (22) and on the outer surfaces of the stack.
  6. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to one of the preceding claims, characterized in that the distance between two consecutive layers (22) is between 0.2 nm and 0.7 nm, preferably between 0.3 nm and 0.5 nm.
  7. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to one of the preceding claims, characterized in that the thickness of the reduced graphene oxide structure (20) is between 20 nm to 5 µm, preferably between 500 nm to 4000 nm.
  8. The reduced graphene oxide structure (20) for stimulation and/or recording of the central and/or peripheral nervous system according to one of the preceding claims, characterized in that the outer surface of the reduced graphene oxide structure (20) has a root square mean roughness of 55 nm.
  9. A method for preparing an electrochemically activated and reduced graphene oxide structure (20), which comprises the following steps: - providing a graphene oxide structure comprising a stack of layered graphene oxide flakes (22), said graphene oxide flakes (22) comprising oxygen-containing functionalizations; - hydrothermally reducing the graphene oxide flakes (22) via subcritical water, causing protons from the water to react with the oxygen-containing functionalizations of the flakes (22); and - electrochemically activating the reduced graphene oxide structure (20) in an electrolyte system, preferably an aqueous environment, wherein electrochemically activating comprises at least partially sweeping cyclically an electrical potential around a potential equilibrium within a plurality of predetermined ranges.
  10. The method for preparing an electrochemically activated and reduced graphene oxide structure (20) according to claim 9, characterized in that the ranges are predetermined such that Faradaic reactions are avoided.
  11. The method for preparing an electrochemically activated and reduced graphene oxide structure (20) according to one of claims 9 or 10, characterized in that electrochemically activating comprises charged ions (24) permeating into the stack, thereby preferably losing their solvation shell.
  12. The method for preparing an electrochemically activated and reduced graphene oxide structure (20) according to one of claims 9 to 11, characterized in that the predetermined ranges are consecutive, wherein each succeeding range is equal to or greater than its preceding range.
  13. The method for preparing an electrochemically activated and reduced graphene oxide structure (20) according to one of claims 9 to 12, characterized in that the number of sweeping cycles within each succeeding range is equal to or greater than the number of sweeping cycles within its preceding range.
  14. An electrode device for stimulation and/or recording of the central and/or peripheral nervous system, preferably for neurostimulation and recording, wherein the electrode comprises the reduced graphene oxide structure (20) according to any of claims 1 to 8.
  15. The electrode device for stimulation and/or recording of the central and/or peripheral nervous system according to claim 14, characterized in that the reduced graphene oxide structure (20) has a diameter of 25 µm or less and provides a charge injection limit from 2 mC/cm 2 to 10 mC/cm 2 and/or an impedance of 10 to 100 kΩ at a frequency of 1 kHz in an electrolyte system.

Description

The present invention relates to a reduced graphene oxide structure for stimulation and/or recording of the central and/or peripheral nervous system, and to a method for preparing an electrochemically activated and reduced graphene oxide structure. The present invention further relates to an electrode device comprising the reduced graphene oxide structure. In practice, it is known that stimulation and/or recording of the central and/or peripheral nervous system is a method for the diagnosis and therapy of neurodegenerative diseases such as inter alia the Parkinson's disease, epilepsy, and chronic pain. In this respect, electrical stimulation by means of leads which were implanted into brain areas or regions like the subthalamic nucleus and/or the globus pallidus internus can e.g. alleviate the tremor symptoms of a patient suffering from a drug-resistant Parkinson's disease. Further, the signals from a brain region or area at which the leads were implanted can be recorded and the condition and/or constitution of the brain tissue can be determined using impedance measurements. In this relation, neuroprosthetic devices are powerful tools to monitor, prevent and treat neural diseases, disorders and conditions by interfacing electrically with the nervous system. They are capable of recording and stimulating electrically neural activity once implanted in the nervous tissue. Currently, most neuroprosthetic technologies base their interface with the neural tissue on electrodes. The interfacing can occur through Faradaic or capacitive currents. One the one hand side, Faradaic currents are associated to redox reactions taking place in the electrode/tissue interface. Those reactions can end up potentially degrading the electrode and damaging the tissue. On the other hand, capacitive currents are due to the charge and discharge of the double layer that appears when an electrical conductor is placed in a liquid environment. For implants, capacitive currents are always preferred over the Faradaic ones since they do not harm the tissue nor degrade the electrode material. Thus, high capacitances are ideal to achieve effective and safe interfacing with the neural tissue. The capacitance sets performance values such as the charge injection limit (CIL) of the material and its impedance. High levels of charge injection and low impedances are desired when recording and stimulating the neural activity of the nervous system. The size of electrodes is limited by the performance of the materials they are made of; materials with high performance, in terms of high capacitance, allow higher levels of miniaturization. Interface precision and device durability, however, are aspects to be improved in order to increase the acceptance of the technology, improve its therapeutic application, and reduce post-operatory complications. The interface precision can be improved by reducing electrodes sizes and increasing the resolution of electrode arrays. Typically, electrodes exhibit miniaturization limitations due to the intrinsic impedance and charge injection limit of the materials they are made of. Additionally, the durability of a device partially depends on the chemical stability of the electrode's material and to some extent on its biocompatibility (including its stability to tissue response) and/or its biodegradability. In turn, the mechanical compliance with the living tissue should be considered to avoid any damage of the affected tissue due to too great a difference in stiffness. The immune response of the body to the materials is another factor to take into account when implanting devices in living tissue. For example, scar tissue formation and inflammation around the implant area can occur. The immune response tends to encapsulate foreign bodies, which decrease the electrical performance of the device over time. Those materials possessing a strong stiffness mismatch with the tissue where are implanted are more aggressively attacked by the body. Therefore, flexible and soft materials are desired over rigid or thick ones. Thin devices are also necessary to minimize the immune response. Long term stability of the material is also a crucial aspect to consider for chronic implants, being required materials with high chemical and mechanical stabilities. Standard commercially available neural interfaces are based on metallic microelectrodes made of platinum Pt, platinum-iridium (Pt/Ir), iridium oxide (IrOx) or titanium nitride (TiN). Those materials interact with the living tissue through a combination of Faradaic and capacitive currents, offer a limited chemical stability and are rigid. Metals performance strongly drops in microelectrodes of tens of micrometres in diameter; further, metals degrade over continuous tissue stimulation. Recently, conductive polymers, such as the polymer mixture poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), have emerged as promising candidates to overcome metallic microelectrodes limitatio