• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Method of manufacturing at least one flexible, biocompatible and implantable neural microprobe, comprising the steps of: providing a layer of a rigid substrate; providing a layer of a soluble polymer on said rigid substrate layer; provide a layer of a first polymer; etch in said first polymer layer at least one aperture; providing a layer of a two-dimensional conductive material on said first polymer layer; recording on said layer of two-dimensional conductive material at least one microelectrode provided with at least one contact area; providing a finishing assembly on said microelectrode assembly; and dissolving said soluble polymer in a solution. The resulting micro-probe is sandwiched between two layers of polymeric material, one of which comprises an opening for accessing said contact area. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2541552A1
    申请号:ES201331895
    申请日:2013-12-20
    公开日:2015-07-21
    发明作者:Rosa Villa；Elisabet PRATS ALFONSO；Gemma Gabriel Buguña；Philippe Godignon；Maria Victoria SANCHEZ VIVES
    申请人:Consejo Superior de Investigaciones Cientificas CSIC；Institucio Catalana de Recerca i Estudis Avancats ICREA；Institut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS；
    IPC主号:
    专利说明:

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    P201331895
    12-20-2013
    In one embodiment of the process, providing a layer of a third polymer further comprises engraving at least one opening therein. Engraving the third polymer can serve to form a microchannel, delineate access to contact areas and microchannel outputs and also the perimeter of the neuronal micro-probe.
    In some embodiments, the first polymer, the second polymer and the third polymer may be of the same polymeric material.
    In some embodiments, the soluble polymer may be poly-acrylic acid (PAA) and the
    The solvent solution thereof may be water. The advantage of using these materials is the relative safety and ease with which the rigid substrate present in the first and second temporary assembly can be discarded without damaging the neuronal micro-probe.
    Other examples of water soluble polymers include polyacrylic acid, dextran,
    15 polymethacrylic acid, polyacrylamide, polyethyleneimine, polyvinyl alcohol and polyethylene oxide.
    Another type of solvent solution may be acetone.
    20 The process allows a wide range of polymers to be used for the different layers but also allows all polymer layers to be of the same material. The polymers can be positive or negative photo-resistant polymers, in which case etching can be done by photolithography.
    In one embodiment, one or more of the polymers may be SU-8 which is a negative photoresin. Another polymer may be the thermoplastic COP polymer, which is an epoxy copolymer of glycidyl methacrylate and ethyl acrylate. Other examples of polymers include, among others: PET (polyethylene terephthalate), PEN (polyethylene naphthalate), PMMA (polymethyl methacrylate), PC (polycarbonate), PE (polyethylene), or PS (polystyrene).
    In some embodiments, one of the polymers may be Polyimide (PI), which may be photosensitive and non-photosensitive. In other embodiments, the polymers may not be photosensitive polymers, such as parylene C, and may be etched by reactive ions (RIE).
    7
    P201331895
    12-20-2013
    In a second aspect, a flexible, biocompatible and implantable neuronal micro-probe comprises at least one layer of a two-dimensional conductive material sandwiched between two layers of polymeric material, said layer of conductive material comprising
    5 two-dimensional at least one microelectrode provided with at least one contact area, such that at least one of said two layers of polymeric material comprises at least one opening for accessing said microelectrode contact area from at least one outer face of the micro probe
    The neuronal micro-probe comprises two key materials, the two-dimensional conductive material, preferably of graphene, and the insulating layer, preferably of SU-8 polymer. Both materials can be provided in ultra-thin layers. They are strong, flexible, compatible for use in magnetic resonance systems, biocompatible, and have a high signal / noise ratio.
    The neuronal micro-probe may comprise one or more layers of microelectrodes, each with one or more contact contact areas on one or more surfaces of the microwave. Therefore, the flexible and implantable biocompatible neuronal micro-probe can be used in a wide range of bio-neuronal applications, including implantation
    20 in-vivo in the short or long term, for simultaneous and precise stimulation and detection of neuronal signals between two or more microelectrodes, or precise multi-neuronal detection located on one or more sides of the same neuronal micro-probe.
    The flexible, biocompatible and implantable neuronal micro-probe is also compatible with
    25 magnetic resonance systems, since it can be used within them for having non-metallic electrodes. The micro-probe can be classified as "conditional on magnetic resonance," which is defined as a device or implant that can contain magnetic components, conductors or radio frequency reagents, which are safe to operate in close proximity to the MRI system. In consecuense,
    30 said neuronal micro-probes can be connected to the instrumentation and control electronics using "zero insertion force" (ZIF) connectors for integrated circuits and magnetic resonance compatible cables.
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    P201331895
    12-20-2013
    In an embodiment of the flexible and implantable biocompatible neuronal micro-probe, the two-dimensional conductive material layer comprises at least two microelectrodes. A minimum of two microelectrodes is necessary to stimulate neurons. A neuronal micro-probe with at least two microelectrodes can stimulate and detect neuronal signals and offer more precise measurements and tight control.
    In one embodiment, the micro-probe comprises at least two layers of the two-dimensional conductive material, each of which in turn comprises at least one microelectrode. The ability to pack multiple microelectrodes within a small surface area or volume offers more precise measurements because, otherwise, it is difficult to specifically identify the location of specific neurons. The micro-probe may comprise two or more layers of microelectrodes with multiple electrodes per layer.
    In another embodiment of the flexible, biocompatible and implantable neuronal micro-probe, each layer of polymeric material comprises at least one opening to access the microelectrode contact area from at least two outer faces of the micro-probe. In this way, the micro-probe can be used to stimulate neurons and detect neuronal signals on two or more faces of the same micro-probe, in order to increase the number of measurement points within a small area with greater precision and accuracy in neuronal research, measurement and control.
    In a preferred embodiment of the micro-probe, the two-dimensional conductive material is graphene. As explained, graphene is a layer with a thickness of a single carbon atom that combines a minimum thickness with high mechanical resistance, high thermal and electrical conductivities, and such flexibility that it can be wrapped around delicate fabrics. It is also biocompatible and does not cause adverse biological reactions when implanted in human or animal living tissue. Graphene is also compatible with magnetic resonance imaging, since it does not cause interference or adverse reactions when used in a magnetic resonance imaging device. This is particularly useful for use with patients with long-term implanted neuronal micro-probes. On the other hand, graphene microelectrodes have a high signal-to-noise ratio since they hardly generate any intrinsic noise, which allows them to detect weak cellular communication signals that are generally below a few hundred micro-volts.
    9
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    P201331895
    12-20-2013
    DETAILED EXHIBITION OF MODES OF EMBODIMENT
    Figure 1 illustrates a first embodiment of a manufacturing process for a flexible, biocompatible and implantable neuronal microsonde, and provided with a layer of 5 microelectrode and at least two openings to access the contact areas of the microelectrode from an outer face of The micro probe.
    A layer of a rigid substrate 100, for example a glass or silicon wafer, is shown in Figure 1 (a). In Figure 1 (b) a layer of a soluble polymer 110 is shown, by
    An example of poly-acrylic acid (PAA), provided on the rigid substrate layer 100. The assembly formed by the rigid substrate layer and the soluble polymer layer will be called temporary assembly 180.
    Figure 1 (c) shows a layer of a first polymer 130, for example SU-8,
    15 provided on the temporary assembly 180. In Figure 1 (d) the first polymer layer 130 has been etched by photolithography (140) to form two openings 151 and 152.
    Figure 1 (e) shows a layer of a two-dimensional conductive material 160, such as graphene, provided on the first polymer layer 130. The assembly formed by
    The first polymer layer and the two-dimensional conductive material layer will be called the microelectrode assembly 190. In Figure 1 (f) the two-dimensional conductive material layer 160 has been etched by photolithography (140) to form one or more microelectrodes. Figure 1 (g) illustrates a microelectrode etched by photolithography in the two-dimensional conductive material layer 160.
    In Figure 1 (h) a layer of a second polymer 170 is represented, for example SU-8, provided on the microelectrode assembly 190. In this embodiment, the second polymer layer 170 is also called finishing assembly 195. Figure 1 (h) also illustrates the immersion of at least temporary assembly 180 in a solution 120, by
    30 example water, to dissolve the soluble polymer layer 110 in order to discard the rigid substrate 100.
    Figure 1 (i) represents a cross-sectional view of a flexible, biocompatible and implantable micro-probe and provided with a microelectrode 160 and at least two openings
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    权利要求:
    Claims (1)
    [1]
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    同族专利:
    公开号 | 公开日
    ES2541552B1|2016-05-04|
    WO2015092109A1|2015-06-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US9907475B2|2010-06-18|2018-03-06|The Regents Of The University Of Michigan|Implantable micro-component electrodes|
    WO2012075120A2|2010-11-30|2012-06-07|University Of South Florida|Graphene electrodes on a planar cubic silicon carbide long term implantable neuronal prosthetic device|
    WO2012103543A2|2011-01-28|2012-08-02|University Of South Florida|Optical neuron stimulation prosthetic using sic |EP3375482A1|2017-03-14|2018-09-19|Scriba Nanotecnologie S.r.l.|Active implantable multifunctional device on a biodegradable/bioresorbable scaffold and its manufacturing processes|
    法律状态:
    2016-05-04| FG2A| Definitive protection|Ref document number: 2541552 Country of ref document: ES Kind code of ref document: B1 Effective date: 20160504 |
    2017-03-01| FA2A| Application withdrawn|Effective date: 20170223 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201331895A|ES2541552B1|2013-12-20|2013-12-20|NEURONAL MICRO-PROBE AND MANUFACTURING PROCEDURE OF THE SAME|ES201331895A| ES2541552B1|2013-12-20|2013-12-20|NEURONAL MICRO-PROBE AND MANUFACTURING PROCEDURE OF THE SAME|
    PCT/ES2014/070940| WO2015092109A1|2013-12-20|2014-12-19|Neuronal microprobe and method for the manufacture thereof|
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