Patent Application
20190246931
This application claims the priority, under 35 U.S.C. § 119, of European Patent Application EP 1 815 6702.5-1124, filed Feb. 14, 2018; the prior application is herewith incorporated by reference in its entirety.
The present invention relates to a method for producing an implantable multielectrode array, an implantable multielectrode array, as well as a device for producing an implantable multielectrode array.
Such arrays are known in the prior art. For instance, U.S. Pat. No. 5,215,088 A discloses a multielectrode array including electrodes formed of silicon. Furthermore, European Patent EP 2 185 236 B1, corresponding to U.S. Pat. Nos. 8,209,023; 8,489,193; 9,302,107; 9,592,377; and 10,052,478, discloses a multielectrode array including spike electrodes made from metals such as e.g. platinum, iridium, and alloys of platinum and iridium.
Concerning manufacturing of multielectrode arrays of the afore-mentioned kind it has proven generally difficult to manufacture such arrays in a simple and efficient manner. In European Patent EP 2 185 236 B1, corresponding to U.S. Pat. Nos. 8,209,023; 8,489,193; 9,302,107; 9,592,377; and 10,052,478, for example, the spike electrodes are separately produced and then affixed onto the substrate of the multielectrode array.
Therefore, it is an objective to provide a method for producing an implantable multielectrode array, an implantable multielectrode array, as well as a device for producing an implantable multielectrode array which are improved in this regard.
With the foregoing and other objects in view there is provided, in accordance accordance with the invention, a method for producing an implantable multielectrode array, which comprises the steps of:
The result of this method is a first multielectrode array made of the first substrate part with a plurality of tips (electrodes) protruding from its surface and a potential second multielectrode array made of the second substrate part with a plurality of tips (electrodes) protruding from its surface.
Particularly, the present invention allows the production of permanently implantable, and particularly biostable multielectrode arrays, particularly for measuring brain waves, in an efficient manner.
Particularly, due to the principle according to which the respective electrode tip is manufactured, the present invention allows the use of exclusively biocompatible/biostable materials regarding the substrate and the electrodes, such as polymers and metals (see also below).
Furthermore, the method constitutes an efficient process that can be based on printed circuit board techniques and can be used to produce implantable multielectrode arrays in large quantities.
Due to the construction of the implantable multielectrode array, comparatively low production costs can be achieved and particularly the exclusive use of biostable materials is possible.
Furthermore, particularly, the electrodes protruding from the first substrate part and/or the electrodes protruding from the second substrate part can be used as electrodes of the multielectrode array to be produced. Particularly, the multielectrode array can also be a one-dimensional array, in which case each of the substrate parts with the respective electrodes (or only one of the two substrate parts) can form a multielectrode array. Of course, the respective electrodes can be subject to further processes such as cleaning and/or coating with other materials (see e.g. below).
Furthermore, according to an embodiment of the method, the second force points in the first direction and the first force points in a second direction that is opposite the first direction, and wherein particularly the forces are of equal magnitude. This allows pulling the substrate parts and the portions of the conductors on either side of the respective constriction apart in a defined manner.
Furthermore, according to an embodiment of the method, the respective fracture is a ductile fracture. Thus, particularly, the heated sections of the conductors are torn apart at the respective constriction by the opposite forces such that the respective fracture separating the respective section into the respective two electrodes is a ductile fracture. This particularly allows generating electrodes that continuously taper towards the tip of the respective electrode.
Furthermore, according to an embodiment of the method, a plurality of first and second substrate parts are generated by repeating the steps a) to c).
Furthermore, according to an embodiment of the method, for forming the multielectrode array, a plurality of substrate parts (including first and/or second substrate parts) is bonded together to form a substrate of the implantable multielectrode array so that the electrodes protrude from a surface of the substrate of the multielectrode array formed by the plurality of substrate parts bonded together. This can be achieved for example by stacking a plurality of one dimensional multielectrode arrays produced with the method of the present invention on top of each other and by joining them, for example with a low melting LCP. This process allows at the same time hermetically sealing the conductors. The number of one dimensional multielectrode arrays to be stacked on top of each other depends on the number of electrodes and the size of the two dimensional multielectrode array that is to be obtained. The distance between the electrode layers is preferably between 0.02 mm to 0.1 mm. Also here, particularly, each fracture of the conductor sections preferably is a ductile fracture.
In one embodiment, the plurality of conductors with sections disposed in parallel is formed of preferably of at least 2, preferably at least 3, even more preferably at least 5 and most preferably at least 10 parallel conductors. This results in one dimensional multielectrode arrays that respectively include at least 2, 3, 5 or 10 parallel electrodes. The two dimensional microelectrode preferably includes at least 2, preferably at least 3, even more preferably at least 5 and most preferably at least 10 one dimensional electrode microarrays stacked on top of each other.
Furthermore, according to an embodiment of the method, the section of the respective conductor is heated to a temperature in the range from 100° C. to 200° C. for generating the (ductile) fractures under tension.
Furthermore, according to an embodiment of the method, the gap formed in the respective initial substrate extends in a third direction that is perpendicular to the first and/or second direction.
Furthermore, according to an embodiment of the method, each of the sections of the conductors includes a center axis, extending in the first direction, wherein the center axes are equidistantly spaced in the third direction, and wherein a distance between each two neighboring sections (or portions) in the third direction lies within the range from 0.05 mm to 1 mm (grid dimension). This grid dimension corresponds to the density of neurons in the brain. Each of the electrodes is therefore able to, on average, contact one neuron when implanted.
Furthermore, according to an embodiment of the method, the constrictions can be aligned with respect to the third direction. However, alternatively, the constrictions can also be aligned with a pre-defined curved line so that the tips of the respective electrode of a substrate part are located on the line (or on a defined curved surface when considering the whole array).
Furthermore, according to an embodiment of the method, the gap includes a width in the first direction that lies within the range from 1 mm to 5 mm.
Furthermore, according to an embodiment of the method, the respective conductor disposed on the substrate includes a width (e.g. along a surface of the substrate and particularly perpendicular to the first direction) outside the respective constriction that lies in the range from 20 μm to 200 μm.
Furthermore, according to an embodiment of the method, the conductors disposed on the support (e.g. before forming the gap) include a thickness (e.g. perpendicular to the width and/or normal to the surface of the substrate) that lies in the range from 10 μm to 50 μm.
Furthermore, according to an embodiment of the method, the respective constriction includes a length in the first direction that is within the range from 50 μm to 200 μm.
Furthermore, according to an embodiment of the method, a smallest width of the respective constriction (e.g. along a surface of the substrate and particularly perpendicular to the first direction) amounts to 20% to 80% of the width of the respective conductor outside the respective constriction (see above).
Furthermore, according to an embodiment of the method, for forming the gap, the material of the substrate is removed by one of: laser ablation, plasma etching or chemical etching. Other methods are also conceivable.
Furthermore, according to an embodiment of the method, the conductors are formed on the substrate by coating the substrate with a conductive material, particularly with a metal, preferably gold (Au).
Furthermore, according to an embodiment of the method, the substrate includes or is formed of a thermoplastic polymer, particularly a liquid crystal polymer, which is particularly biocompatible and/or biostable.
Furthermore, according to an embodiment of the method, for forming the conductors on the substrate, the substrate (e.g. LCP, see above) can be coated with the conductive material (e.g. gold) using a galvanic process, wherein a layout of the conductors can be defined before using photolithography.
Furthermore, according to an embodiment of the method, the respective conductor is formed from a photolithographically defined conductor track applied to the substrate by galvanic reinforcement of the respective conductor track.
Furthermore, according to an embodiment of the method, each electrode is coated in a further step of the method with a conductive coating.
Particularly, according to an embodiment, the coating includes or is formed of platinum, iridium, or an alloy of platinum and iridium, or a similar conductive material. The advantage of such a coating, for example in the case of gold electrodes, is that the diffusion of gold when implanted in the brain is reduced.
Furthermore, according to an embodiment of the method, each electrode includes a tip that is coated with a conductive coating.
According to a further aspect, a device for performing the method according to the present invention for producing an implantable multielectrode array is disclosed. The device comprises:
Particularly, in an embodiment of the device, the heater can be configured to produce heated air that is directed towards the sections by using a nozzle of the heater.
Furthermore, in an embodiment, the device can include a gear unit or leadscrew via which the two substrate holders are coupled, wherein the actuator (e.g. stepper motor) can be configured to act on the gear unit/lead screw in order to move the substrate holders apart (or closer to one another, particularly for holding the substrate parts when generating the gap).
Yet another aspect relates to an implantable multielectrode array produced by the method according to the present disclosure.
Furthermore, a further aspect relates to a multielectrode array, comprising a plurality of metallic conductors (e.g. wires) embedded in an insulating substrate such that an end section of each conductor protrudes from a surface of the substrate, wherein the respective end section forms an electrode including a drawn tip.
Furthermore, in an embodiment of the implantable multielectrode array, the respective electrode includes a fracture surface of a ductile fracture at the tip of the respective electrode.
Furthermore, according to an embodiment, the respective tip, particularly the fracture surface, is coated with an electrically conductive coating, wherein the coating particularly includes or is formed out of: platinum, iridium, or an alloy of platinum and iridium.
Furthermore, in an embodiment, the electrodes extend parallel to one another, particularly normal to the surface.
Furthermore, according to an embodiment of the implantable multielectrode array, the electrodes of the multielectrode array are disposed on a virtual grid on the surface of the substrate of the multielectrode array.
Particularly, the grid can be e.g. a two-dimensional square lattice having a grid dimension in the range from 20 μm to 0.5 mm. Here, the grid dimension is the distance between each two electrodes that are the nearest neighbors.
Furthermore, according to an embodiment of the implantable multielectrode array, the substrate is a thermoplastic polymer, particularly a liquid crystal polymer.
Furthermore, according to an embodiment of the implantable multielectrode array, the respective conductor has a diameter in the range from 10 μm to 100 μm.
Further, according to an embodiment of the implantable multielectrode array, the respective tip has a radius in the range from 0.2 μm to 5 μm.
Furthermore, according to an embodiment of the implantable multielectrode array, a length of the respective electrode over which the respective electrode protrudes with its tip past the surface of the substrate of the implantable multielectrode array lies in the range from 0.02 mm to 3 mm (e.g. in the range from 0.2 mm to 3 mm).
Furthermore, according to an embodiment of the implantable multielectrode array, a length of the respective electrode over which the respective electrode is tapered lies in the range from 10 μm to 3 mm.
Furthermore, according to an embodiment of the implantable multielectrode array, a region of the respective conductor that protrudes out of the substrate/surface is coated with a metal or an insulator, particularly one of silicon oxide, titanium, titanium oxide, or silicon nitride.
Furthermore, according to an embodiment of the implantable multielectrode array, the tips are disposed in a common plane or in a pre-defined curved surface in order to follow the course of an object in which the electrodes are to be inserted with their tips leading.
According to yet another embodiment of the implantable multielectrode array, the substrate has a curved shape.
Particularly, the substrate can include a first portion integrally connected to a second portion of the substrate, wherein the second portion extends at an angle with respect to the first portion. Particularly, the second portion can extend perpendicular to the first portion.
Particularly, according to an embodiment, the surface of the substrate from which the electrodes of the implantable multielectrode array protrude is formed by a face side of the second portion, so that particularly the electrodes extend parallel to one another at the angle (particularly perpendicular) with respect to the first portion of the substrate.
According to a further embodiment, the implantable multielectrode array includes a multiplexer chip embedded into the substrate for passing electrical signals to individual electrodes.
According to a further embodiment of the implantable multielectrode array, the implantable multielectrode array includes an electrical coil for receiving data and electrical energy transmitted to the implantable multielectrode array. Particularly, the coil is embedded in the substrate of the implantable multielectrode array.
Other features which are considered as characteristic for the invention are set forth in the appended claims.
Although the invention is illustrated and described herein as embodied in an implantable multielectrode array, a method for producing an implantable multielectrode array and a device for performing the method, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims.
The construction and method of operation of the invention, however, together with additional objects and advantages thereof will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
Referring now to the figures of the drawings in detail and first, particularly, to
The conductors 10 can be formed and may include the dimensions as described herein.
Further, a portion of the substrate 2 is removed such that a first and a separate second substrate part 2a, 2b are formed that are separated by an air gap 20, wherein each section 100 extends in the first direction D1 from the first substrate part 2a across the gap 20 to the second substrate part 2b.
Then, as indicated in
As indicated in
The device 1′ is particularly adapted for the controlled application of a tractive force (e.g. Forces F1 and F2) while simultaneously heating the sections 100 of the conductors 10 extending across the gap 20. The two substrate parts 2a, 2b are fixed on two substrate holders 4a, 4b (e.g. between clamping jaws). The substrate holders 4a, 4b can be coupled in the transverse direction via a gear unit 6a (e.g. including a leadscrew) driven by an actuator 6b, which ensures that the substrate holders 4a, 4b can be pulled apart precisely and parallel in the transverse direction (D1, D2), thereby creating a precisely defined tension on the conductor sections 100 (opposite forces F1, F2). At the same time, the constrictions 101 are heated by a suitable heater 5 so that the yield strength in the area of the respective constrictions 101 can be exceeded simultaneously and in a controlled manner for all conductor sections 100. This allows the generation of the ductile fractures 102 at the constrictions 101. The heater 5 can be configured to direct heated air 5a via a nozzle 5b onto the sections 100 of the conductors 10 in order to heat the sections 100.
Furthermore,
Furthermore, the implantable multielectrode array 1 according to
An application of the multielectrode array is shown in
The dimension of the peripheral nerve depends on the number of independent nerve fibers which are combined into one bundle. For nerves which go into an arm or a leg that might be a large number, as every different muscle needs a couple of different nerve fibers. If selective stimulation of a single nerve fiber shall be accomplished, the corresponding electrode has to be thin and stiff to extend from the outside of the nerve bundle to the fascicle inside the nerve bundle.
The present disclosure describes how very thin and long, insulated needles (electrodes) disposed in a row configuration can be produced. With appropriate mechanical construction such rows of thin needles can be made such that they can easily be implanted and protrude from the outside of the nerve bundle into a fascicle as shown in
It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teaching. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 18156702.5-1124 | Feb 2018 | EP | regional |
