Patent Description:
The implantation into soft tissue, such a nervous or endocrine tissue, of more than one microelectrode at a time is well known.

For instance, at least tree and preferably at least four microelectrodes are required for spatial identification of a neuron by monitoring the electrical signals originating from the neuron.

A requirement for such monitoring is information about the spatial disposition of the microelectrodes in the tissue. In a situation when multiple microelectrodes are spread out in the tissue for stimulattion of excitable cells information about their spatial disposition is required for identification of the cells or groups of cells being stimulated by each electrode. Provided that the spatial disposition of the implanted microelectrodes is known a more efficient stimulation procedure can be designed by combining magnetic resonance imaging (MRI) and knowledge about which structures are capable of producing therapeutic effect on stimulation.

For implantation of two or more microelectrodes at the same time the microelectrodes are bundled by a permanent or temporary means. When bundled by a temporary means the identification of the disposition of a particular microelectrode in the tissue upon its release from the bundling means is problematic, in particular with microelectrodes of identical or substantially identical shape or with microelectrodes that adopt an identical or substantially identical shape during implantation.

Document <CIT> describes a microelectrode for implantation into soft tissue.

A primary object of the present invention is to provide identification of a particular microelectrode inserted into soft tissue of a person or animal amongst a number of microelectrodes of same design or substantially same design.

Another object of the invention is to provide an identifiable microelectrode.

According to the present description is provided a method of identifying, by radiative means, of a microelectrode comprised by a set of two or more microelectrodes of a design that does not allow their identification by radiative means, in particular of same or similar design implanted in soft tissue, in particular nervous or endocrine tissue. Identification comprises identifying a particular microelectrode in a set of implanted microelectrodes, that is, in respect other microelectrodes of the set, but also in respect of its disposition in the tissue. An electrode of a diameter of up to <NUM>, in particular of up to <NUM> is considered to qualify as a microelectrode.

The method comprises providing two or more microelectrodes of same design or of a design that does not allow their identification by radiative means, which are desired to be individually identified upon insertion into soft tissue. In particular, it is desired for a microelectrode to be identifiable both individually and in respect of the position of a distal section thereof providing electrical contact with surrounding tissue. The contact providing distal section can be a section extending from the distal end or disposed in proximity of the distal end of the microelectrode. According to one aspect a microelectrode is one that is inserted into soft tissue simultaneously with other microelectrodes in form of a bundle or array, that is, in a fixed spatial relationship with them, but which loses the fixed spatial relationship upon degradation by dissolution or degradation or both of the means providing the fixed relationship. According to another aspect a microelectrode is one that is inserted into soft tissue consecutively with other microelectrodes or is inserted into soft tissue simultaneously with one or more microelectrodes and consecutively in respect of one or more microelectrodes.

An identifiable microelectrode comprises an electrically conducting oblong electrode body partially covered by a first insulation layer of polymer extending from the proximal end thereof, a unique pattern comprising a metal or metal alloy disposed on a distal portion of the insulation layer, a second insulation layer disposed on the pattern. For insertion into soft tissue the two or more identifiable microelectrodes are comprised by a microelectrode bundle or array disposed in a matrix of a material dissolvable and/or swellable in aqueous body fluid. To facilitate insertion the matrix can be provided with a coat with glidant properties when hydrated, such as a coat of dry gelatin or hyaluronic acid. The microelectrode body is preferably cylindrical. The microelectrode body is electrically conducting and consists or comprises a metal, in particular a noble metal and/or an electrically conducting polymer.

Upon insertion of the bundle or array into the tissue the matrix material is dissolved or swells by contact with aqueous body fluid. The position of the portion of the microelectrode carrying the pattern is thereupon determined by radiative means, in particular by computer tomography (CT) but also by X-ray. Since the geometry of a microelectrode of the invention is known the determination of the position of the pattern also allows determination of neighbouring portions of the microelectrode with good precision. Most important is the precise determination of the position of the contact portion, that is the microelectrode body portion devoid of insulation, which is electrically conducting contact with surrounding tissue. It is therefore preferred to for the unique pattern to be disposed in close proximity of the contact section, preferably on an insulated section proximally adjacent to the contact section.

A bundle or array of microelectrodes comprises three or more microelectrodes, preferably four or more microelectrodes. Each microelectrode comprises at or near its proximal end a means for electric connection to a control unit capable of emitting and/or receiving electrical signals via the microelectrode to or from surrounding tissue. An alternative to forwarding electrical signals arising in the tissue by means of an insulated lead is wireless transmission via an implanted radiofrequency emitter or the like connected with the electrode.

According to one aspect an electrode body comprises a distal terminal portion provided with a polymer bulge or coat and a portion free of insulation extending between the proximal end of the bulge or coat and the distal end of the first insulation layer.

It is preferred for the unique pattern to extend in a longitudinal direction of the electrode body and to comprise three or more sections separated from each other. To provide good visibility by CT or X-ray it is preferred for the elements of the pattern to be axially disposed in regard of each other at distances of <NUM> or more, in particular of <NUM> or more.

According to another aspect a number of microelectrodes or most or all microelectrodes of a bundle or array share a pattern with the same number of sections but differing by the distance between the sections.

The body formed by the matrix enclosing a bundle or array of microelectrodes is preferably of cylindrical form and narrowing towards its distal end. The microelectrodes of a bundle or array are preferably disposed in parallel with the cylinder axis, in particular do not deviate from that axis by more than <NUM> % or <NUM> % in a distal direction, i.e. fan out in that direction. To facilitate insertion the matrix body can be provided with a glidant layer, such as a layer of dry gelatin or hyaluronic acid so as to provide a low-friction surface on contact with aqueous body fluid.

A pattern for identification by radiative means disposed on a non-conducting polymer coat of the electrode body is preferably covered by a second non-conducting polymer coat. A pattern comprises three or more separate sections each comprising a metal, such as in form of metal particles dispersed in a polymer or disposed as a metal layer on the first insulation layer. Preferred metals are noble metal such as gold or platinum, copper, chromium, iridium, tungsten, stainless steel.

Individually identifiable microelectrodes of the invention include those with an electrode body of a thickness of <NUM> and more, such as of up to <NUM> or more or of up to <NUM> or even up to <NUM>, in combination with a thickness of the metal layer of <NUM> or more, such as of <NUM> or more or <NUM> or more. It is preferred for the combined thickness of the metal/metal comprising layer and the electrode body or of the metal/metal comprising layer on an insulation layer of the body to exceed the thickness of the electrode body or the combined thickness of the insulation layer and the electrode body by more than <NUM> %, in particular by more than <NUM> %.

Thus, according to the present disclosure is described a method of identifying, by radiative means, a microelectrode upon its insertion into soft tissue, in particular nervous or endocrine tissue, the microelectrode being comprised by a set of two or more microelectrodes each comprising an electrically conducting electrode body, the microelectrodes being of a design, in particular of same or similar design, that does not allow identification by such means, the method comprising:.

wherein the unique pattern is disposed near the distal end of the electrode body, in particular within a distance from the distal end comprised by <NUM> % or less, in particular by <NUM> % or less, most preferred by <NUM> % or less, of the electrode body length. According to an aspect the unique pattern is either not disposed repetitively on the electrode body or, if disposed repetitively, is disposed in a unique number of repetitions on each electrode body of the set.

A microelectrode for use in the method preferably comprises an electrically conducting oblong electrode body; wherein the electrode body is partially covered by a first polymer insulation layer, the unique pattern being disposed on a distal portion of the first insulation layer and covered by a second insulation layer or wherein the unique pattern is disposed on a distal portion of the electrode body and is covered by an insulation layer.

In particular, the unique pattern is disposed near the distal end of the electrode body, that is, within a distance from the distal end comprised by <NUM> % or less, in particular by <NUM> % or less, most preferred by <NUM> % or less, of the electrode body length.

It is furthermore preferred for the unique pattern to not be disposed repetitively on the electrode body or, if disposed repetitively, to be so in a unique number of repetitions on each electrode body of the set.

The method for simultaneous insertion comprises incorporating the set of two or more microelectrodes into a matrix of a material dissolvable or swellable in aqueous body fluid to form a microelectrode bundle or array; inserting the bundle or the array into soft tissue; upon dissolution or swelling of the matrix material determining the position the unique pattern by radiative means, in particular CT or X-ray.

According to one aspect a method for simultaneous insertion comprises incorporating the set of three or more microelectrodes into a matrix of a material dissolvable or swellable in aqueous body fluid to form a microelectrode bundle or array; inserting the bundle or the array into soft tissue; upon dissolution or swelling of the matrix material determining the position the unique pattern by radiative means, in particular CT or X-ray. The matrix is preferably of cylindrical from narrowing towards its distal end. A bundle or array for use in the method comprises three or more microelectrodes, more preferred four or more microelectrodes.

According to a further aspect an electrode body of a microelectrode for use in the method comprises a distal terminal portion provided with a non-conducting polymer coat or bulge and a portion free of insulation extending between the proximal end of the coat or bulge and the distal end of the first insulation layer or the insulation layer. It is preferred for the unique pattern to comprise three or more sections separated from each other. Preferably all microelectrodes of a bundle or array share a pattern with the same number of sections but differ by the distance between the sections.

It is also disclosed a microelectrode provided with a unique metallic pattern for identification of the microelectrode by radiative means upon implantation into soft tissue, in particular nervous or endocrine tissue, the microelectrode comprising an oblong electrically conducting body and the pattern comprising three or more sections comprising a metal; wherein the pattern is disposed on a first non-conducting polymer coat of an insulating material covering a proximal portion of the microelectrode body, wherein the pattern comprises three or more sections extending in a longitudinal direction of the electrode body and wherein the sections are covered by a second non-conducting coat of a polymer material; or wherein the pattern is disposed on the electrode body and covered by non-conducting coat of a polymer material; with the proviso that the pattern is disposed near the distal end of the electrode body, that is, within a distance from the distal end of comprised by <NUM> % or less, in particular by <NUM> % or less, most preferred by <NUM> % or less, of the electrode body length.

A section of the unique pattern can be formed by metal particles dispersed in a polymer or by a metal layer. It is preferred for a section to be of annular form and to extend around or substantially around the electrode body. A metal for constituting a section or being comprised by a section of the pattern is preferably selected from the group consisting of noble metal such as gold or platinum, copper, chromium, iridium, tungsten, stainless steel.

The body of the microelectrode is preferably cylindrical. The body has a preferred thickness of from <NUM> or <NUM> to <NUM> or <NUM> and the metal layer has a thickness of from <NUM> or <NUM> to <NUM> or <NUM>. A section of the unique pattern has a preferred axial extension of <NUM> or <NUM> or more.

It is also disclosed a bundle or array comprising two or more microelectrodes of the invention, their patterns differing by the distance of their sections in an axial direction. The bundle or array is preferably enclosed by a matrix of a material dissolvable or swellable in aqueous body fluid, in particular one of cylindrical form having a proximal end and a distal end towards which it is narrowing.

It is furthermore disclosed the use of the bundle or array of microelectrodes of the invention for implantation into soft tissue, in particular nervous or endocrine tissue.

Each microelectrode of a set of three or more microelectrodes of the invention is provided with a unique pattern capable of being recognized by CT or X-ray. The set can be used for consecutive implantation of its microelectrodes into soft tissue, in particular nervous or endocrine tissue.

A preferred use of the set of three or more microelectrodes of the invention is for determining the position of one or more neurons in soft tissue.

The microelectrode bundle <NUM> of <FIG> comprises five microelectrodes of which four <NUM>, <NUM>, <NUM>, <NUM> are symmetrically disposed around a central microelectrode <NUM>. At their distal end their metallic or conducting polymer electrode bodies <NUM> are provided with polymer guide elements of which only those for microelectrodes <NUM>, <NUM>, and <NUM> are shown. The guide elements are of two kind: a guide element <NUM> attached to the electrode body <NUM> of the central microelectrode <NUM> in a rotationally symmetric manner and four guide elements <NUM>', <NUM>" (the others not shown) attached to the body <NUM> of the respective microelectrode <NUM>, <NUM>, <NUM>, <NUM> in a non-rotationally symmetric manner. While the distal terminal portions of the microelectrodes <NUM>, <NUM>, <NUM>, <NUM>, <NUM> carry a central guide element <NUM> and peripheral guide elements <NUM>', <NUM>", respectively. The guide elements are electrically insulated by them at those distal terminal portions. Most of the remainder of the microelectrode bodies <NUM> extending from their proximal ends towards the guide elements <NUM>, <NUM>', <NUM>" is insulated by a polymer coat <NUM> of, for instance, polyurethane or Parylene C, except for a short non-insulated section <NUM> extending from the distal end of the coat <NUM> to the proximal end of the guide elements <NUM>, <NUM>', <NUM>". Upon implantation their non-insulated portions <NUM>, <NUM>', <NUM>" can establish electrical contact with surrounding tissue.

The peripheral microelectrodes <NUM>, <NUM>, <NUM>, <NUM> have their guide elements <NUM>', <NUM>" disposed in a manner so as to make the guide element axes G-G, G'-G' diverge in a distal direction from their axes H-H, H'-H' and from the axis K- of the central microelectrode <NUM> extending in parallel and shared by its guide element <NUM>. This disposition of the microelectrodes <NUM>, <NUM>, <NUM>, <NUM>, <NUM> is stabilized by their embedment in cylindrical matrix <NUM> of a biocompatible material dissolvable or degradable in aqueous body fluid such as glucose or gelatin. In <FIG> the distal and proximal ends of the matrix body are indicated by D and P. The electrodes <NUM>, <NUM>, <NUM>, <NUM>, <NUM> are arranged in parallel and their distal ends, which are disposed in a common plane, are indicated by F. At its distal end the matrix <NUM> forms a blunt tip facilitating insertion of the bundle <NUM> into soft tissue. If the matrix is of a high-friction material or prone to dissolve quickly in aqueous body fluid such as glucose it is advantageously covered by a thin layer <NUM> of a material delaying dissolution and acting as a glidant, such as gelatin.

Upon insertion of the bundle <NUM> into soft tissue the matrix <NUM> starts to dissolve in the body fluid. Upon complete dissolution the electrodes <NUM>, <NUM>, <NUM>, <NUM>, <NUM> are no longer restrained in their movement in respect of each other. They may be intentionally or unintentionally individually inserted deeper into the tissue so as to occupy a desired position in respect of a target, in particular a neuron or group of neurons. Their initial orientation upon dissolution in combination with the orientation of their guide elements <NUM>, <NUM>', <NUM>" makes the peripheral microelectrodes <NUM>', <NUM>' fan out from the central axis of the K- of the central microelectrode <NUM>, which coincides with the cylinder axis of the electrode bundle <NUM>. Their disposition in living tissue then can only be determined non-invasively, such as by computer tomography (CT) or X-ray. Microelectrodes of the art are however not suitable for identification by these methods, in particular not suitable for identification by CT. To make them detectable by their polymer coat <NUM> or their guide elements <NUM>, <NUM>', <NUM>" or both they are provided with unique patterns or markers.

In one aspect of the method for marking microelectrodes is provided a polyurethane glue in which sub-micro particles of a noble material such as silver or gold are disposed. Small areas, in particular rings of glue comprising the metal are applied on the polymer coat <NUM> in a pattern differing for each electrode. While a two-ring pattern can be used, a pattern with three or more rings is preferred. The pattern then is covered by a further layer of non-conducting polymer so as to protect the pattern from contact with tissue or body fluid.

<FIG> illustrate the electrodes <NUM>', <NUM>', <NUM>' corresponding to non-marked electrodes <NUM>, <NUM>, <NUM> of <FIG> provided with annular patterns A: <NUM>, <NUM>, <NUM>; B: <NUM>, <NUM>, <NUM>; C: <NUM>, <NUM>, <NUM>, each of which is different by the axial distance between the rings <NUM>, <NUM>, <NUM>; <NUM>, <NUM>, <NUM>; <NUM>, <NUM>, <NUM> of each pattern A, B, C varying in a manner so as to make each pattern unique. While the distance between neighbouring rings <NUM>, <NUM>; <NUM>, <NUM>; of microelectrode <NUM>' is the same, the distance between rings <NUM>, <NUM>; <NUM>, <NUM> and between rings <NUM>, <NUM>; <NUM>, <NUM>, respectively, differs in that the distance between the distal and the central ring is smaller in microelectrode <NUM>' whereas it is greater in microelectrode <NUM>'. The opposite is true for distance between the central ring and the proximal ring of these electrodes, the distance between their distal and proximal rings <NUM>, <NUM>; <NUM>, <NUM> being the same. Other suitable metals for marking of microelectrodes include gold, platinum, iridium but copper, chromium can also be used.

For identification each marked electrode is photographed and the distance between the markings, in particular rings, is determined. The CT software is calibrated to allow automatic identification of each microelectrode.

In another aspect of the method for marking microelectrodes with metal patches or rings a metal beam is sprayed on an insulated portion of the electrode body through slits of a mask, then covered with a layer of non-conducting polymer. Another useful method comprises ion sputtering through a mask.

Microelectrodes presently used in the method have a preferred diameter of about <NUM> including the insulation layer of about <NUM>. A layer of metallic marker of <NUM> thickness disposed on the insulation layer results in a total useful diameter of about <NUM>, well above the CT detection limit, disregarding from the additional insulation layer deposed on the metallic marker layer which does not add detectability.

<FIG> illustrate a set of three microelectrodes <NUM>, <NUM>', <NUM>" provided with unique patterns L, M, N, each comprising three axially disposed metallic elements or elements comprising a metal <NUM>, <NUM>, <NUM>; <NUM>', <NUM>', <NUM>'; <NUM>", <NUM>", <NUM>'' on the electrode body <NUM>, <NUM>', <NUM>". The proximal portion of the electrode body <NUM>, <NUM>', <NUM>'' and the metallic elements <NUM>, <NUM>, <NUM>; <NUM>', <NUM>', <NUM>'; <NUM>", <NUM>", <NUM>'' disposed thereon is covered by a main insulation polymer layer <NUM>, <NUM>', <NUM>'', which extends to near the distal end of the electrode body <NUM>, <NUM>', <NUM>''. The tip of the distal end is covered by a terminal insulation layer <NUM>, <NUM>', <NUM>". A short portion of the electrode body <NUM>, <NUM>', <NUM>'' extending between the proximal end of the terminal insulation layer <NUM>, <NUM>', <NUM>'' and the distal end of the main insulation layer <NUM>, <NUM>', <NUM>'' is naked and in electrical contact with surrounding tissue upon dissolution or degradation of the matrix (not shown) of the electrode bundle in which the microelectrodes <NUM>, <NUM>', <NUM>'' are embedded.

<FIG> shows a first variety <NUM> of the microelectrode <NUM>, <NUM>', <NUM>'' of <FIG>, from which it differs by one metallic element or segment <NUM> of the unique pattern O being disposed at the distal tip of the electrode body <NUM> insulated by an insulating polymer coat <NUM> corresponding to the terminal insulation layer <NUM>, <NUM>', <NUM>'' of the embodiment of <FIG>. The most distally disposed segment <NUM> of the pattern O is covered by an insulation layer <NUM> separate from the main insulation layer <NUM> covering the two other metallic segments <NUM>, <NUM>, the naked portion <NUM> of the electrode body <NUM> extending between them.

Claim 1:
Microelectrode provided with a metallic pattern (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>)for identification of the microelectrode by radiative means upon implantation into soft tissue, in particular nervous or endocrine tissue, the microelectrode comprising an oblong electrically conducting body (<NUM>)and a contact providing distal section (<NUM>, <NUM>', <NUM>", <NUM>, <NUM>', <NUM>", <NUM>, <NUM>) providing electrical contact with surrounding soft tissue being a section extending from a distal end or disposed in proximity of the distal end the microelectrode body, the pattern comprising three or more sections comprising a metal (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>), the sections extending in a longitudinal direction of the microelectrode body near the distal end of the microelectrode body; wherein the pattern is disposed on a first non-conducting coat of polymer material covering a distal portion of the microelectrode body (<NUM>) and the sections of the pattern are covered by a second coat of non-conducting polymer material; or wherein the pattern is disposed on a portion of the microelectrode body (<NUM>) and covered by non-conducting coat of a polymer material.