DE102023102257A1 - PRODUCTION OF THREE-DIMENSIONALLY STRUCTURED ELECTRODE LAYERS, ESPECIALLY USING THE KIRIGAMI PRINCIPLE - Google Patents

Abstract

The present invention relates to three-dimensionally structured electrode layers, methods for their production and their use, wherein the production is preferably carried out according to the Kirigami principle.

Description

All documents cited in the present application are incorporated by reference in their entirety into the present disclosure.

The present invention relates to three-dimensionally structured electrode layers, methods for their production and their use, wherein the production is preferably carried out according to the Kirigami principle.

State of the art:

1. i. Jede Probe muss einzeln implantiert werden, wodurch sich die Implantationszeit und der Platzbedarf für die Front-End-Verbindungen erhöhen.
2. ii. Beliebige Positionen einzelner 1D- oder 2D-Sonden erhöhen die Komplexität der Rekonstruktion und Analyse des 3D-Raums, insbesondere, weil die implantierte Position einzelner Sonden anfällig für Veränderungen aufgrund von Mikrobewegungen (z. B. durch die Atmung oder des Herz-Kreislauf-Systems) ist.
3. iii. Es kann kein simultaner Zugriff auf den vollständigen 3D-Raum erfolgen.

Flexible neuroimplants are implantable electronic devices that can measure and stimulate the neuronal activity of nerve tissue in the peripheral and central nervous system. Neuroimplants mostly consist of a matrix of microelectrodes, which are usually conductive layers embedded and encapsulated between thin insulating polymer layers. The mostly one-dimensional (1D) or two-dimensional (2D) electrode matrix is either placed on the nerve tissue or penetrates the tissue to measure and/or control various neuronal activities, e.g. of the brain, retina or peripheral nerves. Flexible neural implants can be surface implants that consist of a 2D matrix to map the xy positions on the surface of the neural tissue. In order to be able to address cells at any x and y positions within the nerve tissue, penetrating threads or shafts exist, each consisting of a 1D or 2D electrode matrix. A 1D matrix corresponds to a single shaft to map the z-axis, and a 2D matrix corresponds to a group of shafts with fixed distances between the shafts to map x - z or y - z positions. A standard approach for multi-electrode arrays is the Utah array, which consists of silicon (Si) needles with metal-based or conductive polymer tips and a biocompatible polymer encapsulation. Therefore, the Utah array only allows one recording per needle (x - y positions with a fixed z position). Another approach is the standard design from Michigan, which consists of gold electrodes on Si shafts. Here, several recordings can be made per shaft (multiple z positions), but the design is planar, so only recordings in x - z or y - z are possible. In order to be able to interact with the three-dimensional space of nerve tissue, three-dimensional (3D) neuroimplants with as many electrodes as possible for recording are required. These implants should then penetrate different layers of the tissue to stimulate cells from different layers and record their signals. Existing work with multiple recording in three dimensions currently focuses mainly on in-vitro, ex-vivo, or in-vivo experiments, for example in the cortex. If several 1D or 2D matrices are implanted at different x - y positions, access to 3D space can be ensured. However, this poses the following technical problems:

1. i. Each probe must be implanted individually, increasing implantation time and space requirements for front-end connections.
2. ii. Arbitrary positions of individual 1D or 2D probes increase the complexity of reconstructing and analyzing 3D space, particularly because the implanted position of individual probes is susceptible to changes due to micro-movements (e.g. due to breathing or the cardiovascular system).
3. iii. Simultaneous access to the full 3D space is not possible.

1. i. Stapelung von 2D-Implantaten: Hier werden mehrere 2D-Implantate aufeinandergestapelt, um ein 3D-Implantat zu generieren. Üblicherweise befinden sich zwischen den 2D-Implantaten Platzhalter, um einen genauen Abstand zu definieren (zum Beispiel in Shin, H. et al.: „3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics“, Nat. Commun. 12, 492 (2021), https://doi.org/10.1038/s41467-020-20763-3 ).
2. ii. Kirigami-Technik: Hier werden 2D-Strukturen (aus-)geschnitten und anschließend so gefaltet, dass ein 3D-Implantat entsteht (zum Beispiel in Socia et al.: „A flexible 3-dimensional microelectrode array for in vitro brain models“, Lab Chip., 2020, 20, 901-911. DOI https://doi.org/10.1039/C9LC01148J ). Für das Falten an sich existieren in der Literatur verschiedene Methoden:
   1. a. Nutzen von ferromagnetischen Folien auf der Rückseite der Schäfte, um das 2D-Design mithilfe eines magnetischen Feldes zu falten.
   2. b. Die Schäfte falten sich von selbst (z.B. durch elektrostatische Einwirkungen).
   3. c. Manuelles, mechanisches Falten der einzelnen 2D-Schäfte oder mehrerer zur gleichen Zeit.

Various three-dimensional neuroimplants in the mm and µm size range have already been manufactured using different methods. The two main methods used are the stacking of several 2D implants or the Kirigami technique.

1. i. Stacking of 2D implants: Here, several 2D implants are stacked on top of each other to generate a 3D implant. Usually, there are spacers between the 2D implants to define a precise distance (for example in Shin, H. et al.: “3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics,” Nat. Commun. 12, 492 (2021), https://doi.org/10.1038/s41467-020-20763-3 ).
2. ii. Kirigami technique: Here, 2D structures are cut out and then folded to create a 3D implant (for example in Socia et al.: “A flexible 3-dimensional microelectrode array for in vitro brain models,” Lab Chip., 2020, 20, 901-911. DOI https://doi.org/10.1039/C9LC01148J ). For folding itself, various methods exist in the literature:
   1. a. Using ferromagnetic foils on the back of the shafts to fold the 2D design using a magnetic field.
   2. b. The shafts fold themselves (e.g. due to electrostatic effects).
   3. c. Manual, mechanical folding of individual 2D shafts or several at the same time.

The state-of-the-art solutions are either manual and sometimes very time-consuming processes that require the individual folding of individual shafts or the individual stacking of 2D samples. These processes cannot be parallelized or are difficult to parallelize. In addition, cytotoxic materials, e.g. ferromagnetic metals such as nickel, are used in combination with high-energy magnetic fields (100 - 400 mT), which are considered dangerous. Sometimes shafts fold back again or the folding angle is not always 90° (unreliable results).

Therefore, we are still looking for a method that allows a fast, parallelizable and reliable production of three-dimensional (neuro)implants.

The object of the present invention was therefore, in view of the state of the art, to find methods for producing three-dimensional (neuro) implants or three-dimensionally structured electrode arrangements suitable therefor, which do not have the disadvantages of the state of the art and are in particular fast, parallelizable and reliable, as well as these implants and arrangements themselves.

Further tasks for the specialist arise from the following description.

These and other objects are achieved within the scope of the present invention by the subject matter of the independent claims.

Preferred embodiments emerge from the dependent claims and the following description.

In the context of the present invention, the term "comprise" also includes "consisting of" as a particularly preferred embodiment; that is, a corresponding list can contain (= comprise) other elements in addition to the explicitly mentioned elements, or it can contain exactly these elements (= consist of) (whereby unimportant elements such as screws, markings, etc. are not taken into account).

In the case of relative information such as above, below, left, right or similar, the reference system used in the present invention is an observer standing upright on the ground in front of the object under discussion.

In the context of the present invention, the expression “and/or” means that both elements mentioned in the context are included individually as well as the combination of the elements mentioned in the context.

In the context of the present invention, the term "flexible" means that the elements in question, in particular the 2D electrode structure layer and the n-side electrode structures, can be bent by 90° without being destroyed or losing their functionality, which is achieved by using materials with a corresponding bending stiffness (which depends on the elastic modulus of the materials used and the respective material thickness). The elastic moduli of the materials are known to the person skilled in the art or can be looked up, so that the person skilled in the art can easily determine the necessary bending stiffness. In particular, examples are parylene-C or polyimide with Ti/Au or Ti/Au/Ti conductor tracks on them.

In the context of the present invention, all quantities are to be understood as weights unless otherwise stated.

In the context of the present invention, the term “ambient temperature” means a temperature of 20°C. Temperatures are in degrees Celsius (°C), unless otherwise stated.

Unless otherwise stated, the reactions or process steps mentioned are carried out at atmospheric pressure, i.e. at approximately 1013 kPa.

The present invention relates to a method for producing three-dimensionally structured electrode layers or 3D microelectrode arrays (MEA). These can be used as neural 3D implants based on flexible, polymeric and optionally thermoplastic materials (e.g. parylene-C or polyimides). The implants consist of a 3D microelectrode matrix made of flexible shafts, each of which contains at least one, but preferably several electrode locations in order to be able to establish an electrical coupling, in particular with neural tissue, during implantation. In addition, it is possible to arrange planar electrodes on the surface of the 2D structure of the 3D microelectrode array; in particular, this can be achieved by not raising the relevant electrode structures in the context of the manufacturing method of the present invention, i.e. by not providing elevations in the shaping layer to be used at their locations.

For production, clean room technologies of semiconductor technology are initially used to ensure 2D shape (xy) and cutouts for folding the MEA/implant. This is followed by folding the Kirigami structures. The term Kirigami structures comes from the Japanese art of paper folding, where Kirigami is a variant of Origami. To create Kirigami structures, the two-dimensional material is both cut and folded. This results in a three-dimensional design that stands out from the two-dimensional structure. The term “Kirigami structures” is common in the art and known to the person skilled in the art (see, for example, the abstracts of Liu et al. “Self-Healing Kirigami Assembly Strategy for Conformal Electronics,” Adv. Funct. Mater. 2022, 32, 2109214 or from Guo et al. “A flexible and stretchable Kirigami-inspired implantable neural probe with floating microsites for electrophysiology recordings,” 2020 IEEE 33rd International Conference on Micro Electro Mechanical Systems (MEMS), Vancouver, BC, Canada, 2020, pp. 350-353 ). Within the scope of the present invention, a mechanical shaping process is used to lift all 2D shafts simultaneously and thus form an MEA or a 3D probe with predefined distances between the individual shafts. For this purpose, the 2D electrode structure layer is placed on an array of blocks and structures (the shaping layer) for a type of self-adjustment (key-lock principle) in order to fold the respective electrode shafts upwards at the same time at a previously freely defined angle (depending on the application). In principle, all angles are technically possible. However, according to the invention, angles between 45° and 135° are preferred, particularly preferably 70 to 110°, in particular 90°, in each case based on the plane of the original 2D electrode structure layer. If the structures (electrode structures or their shafts) have a high aspect ratio, predetermined breaking points in the interfaces can be used to stabilize the structures during production and before folding. The MEA or 3D probe is then placed in a heated environment (oven) to stabilize the 3D structures (thermoforming).

Within the scope of the present invention, the 2D structures of the electrode structure layers and the forms for folding (shaping layers) are manufactured in preferred variants in the micrometer range. For this purpose, it is advantageous and therefore preferred if the production is carried out using clean room technology, microfabrication processes, thin film techniques and 3D printing with resolution in the µm range. The folding of the 2D structures within the scope of the present invention is a very precise, self-adjusting process (key-lock principle), which is preferably carried out with µm accuracy.

1. A) Bereitstellen einer flexiblen 2D-Elektrodenstrukturlage umfassend n-seitige Elektrodenstrukturen, von denen eine Seite an der Strukturlage fest ist und die übrigen Seiten ganz oder teilweise von der Strukturlage abgetrennt sind, bevorzugt durch ein- oder durchschneiden sind;
2. B) Bereitstellen einer dreidimensionalen Formgebungslage umfassend hervorstehende Strukturen;
3. C) Ausrichten der flexiblen 2D-Elektrodenstrukturlage und der Formgebungslage, so dass die jeweiligen hervorstehenden Strukturen jeweiligen n-seitigen Elektrodenstrukturen zugeordnet sind;
4. D) Zusammenpressen der 2D-Elektrodenstrukturlage und der Formgebungslage, wobei die n-seitigen Elektrodenstrukturen durch die jeweiligen hervorstehenden Strukturen der Formgebungslage aus der Ebene der 2D-Elektrodenstrukturlage um eine an der 2D-Elektrodenstrukturlage festen Seite rotierend herausgedrückt und angehoben werden (also bis auf die feste Seite);
5. E) Erhitzen der zusammengefügten Lagen, so dass die n-seitigen Elektrodenstrukturen der Elektrodenstrukturlage in der durch die hervorstehenden Strukturen der Formgebungslage vorgegebenen (hervorgerufenen) Lage fixiert werden;
6. F) Trennen der Lagen voneinander.

Firstly, the present invention relates to a method for producing three-dimensionally structured electrode layers, which comprises or consists of the following method steps:

1. A) providing a flexible 2D electrode structure layer comprising n-sided electrode structures, one side of which is fixed to the structure layer and the remaining sides are completely or partially separated from the structure layer, preferably by cutting or cutting through;
2. B) providing a three-dimensional shaping layer comprising protruding structures;
3. C) aligning the flexible 2D electrode structure layer and the forming layer such that the respective protruding structures are associated with respective n-side electrode structures;
4. D) pressing the 2D electrode structure layer and the shaping layer together, wherein the n-side electrode structures are pressed out of the plane of the 2D electrode structure layer by the respective protruding structures of the shaping layer and are raised in a rotating manner about a side fixed to the 2D electrode structure layer (i.e. up to the fixed side);
5. E) heating the joined layers so that the n-side electrode structures of the electrode structure layer are fixed in the position predetermined (caused) by the protruding structures of the forming layer;
6. F) Separating the layers from each other.

Since the material is flexible, the n-sided structures bend as soon as the 2D electrode structure layer is placed in the forming layer. Heating then changes the molecular structure of the material of the 2D electrode structure layer so that the shape is retained after cooling (thermoplastic or thermosetting depending on the material).

In the context of the present invention, n-sided electrode structure means that the respective structure has n sides, where n is a whole natural number and 3 or more. In principle, there is no upper limit for n, but above a certain size of n the side fixed to the structural layer becomes too short to be stable. In this respect, n is preferably 3 and 12, particularly preferably 3 to 8, especially preferably 3 to 6 and even more preferably 3 to 5. Most preferably n = 4 or n = 5.

The end facing away from the fixed side does not necessarily have to be a straight side, but can also be shaped like a point. For example, with n=4, the electrode structure could be elongated and rectangular and the side furthest away from the fixed end (short side) could be shaped like a point, the electrode structure would then have the shape of an obelisk longitudinal section. This is a particularly preferred embodiment according to the invention. This variant could also be referred to as 5-sided if the edges of the point are viewed as sides.

According to the invention, one of the n sides is fixed to the structural layer. Around this side as a rotation axis, a joint acting like a hinge, i.e. with a degree of freedom f=1, the respective n-sided electrode structure is erected in step D) out of the plane of the electrode structure layer by the action of the protruding structures of the shaping layer, whereby the 2D electrode structure layer becomes a layer with a three-dimensional structure of the electrode structures.

The remaining sides are completely or partially separated from the structure layer so that they do not counteract the erection. Depending on the size of the n-sided electrode structure, it may be necessary for the sides to be only partially separated so that the n-sided electrode structures are still sufficiently stable and do not, for example, simply "hang down", as this would make the accuracy of further processing more difficult. In this case, the sides are separated as far as possible and the areas that are not separated remain as predetermined breaking points.

The separation of the sides from the rest of the 2D electrode structure plate preferably takes place during the production of the 2D electrode structure layer. This is preferably not a conventional cutting process, but a dry etching step (reactive ion etching), in which recesses at least 3 µm wide are etched around the sides (except for the side that remains connected to the 2D electrode structure layer and is intended to serve as a "hinge-like" axis of rotation). With high aspect ratios, there are predetermined breaking points in the recesses between the n-side electrode structure and the 2D electrode structure layer. In these cases, the predetermined breaking points are preferably designed in such a way that they break open due to mechanical stress due to the protruding structures of the shaping layer as soon as the 2D electrode structure layer and the shaping layer are pressed together.

The n-side electrode structures have electrode surfaces and conductor tracks, which are conductively connected to other conductor tracks and/or electrodes on the 2D electrode structure layer. The conductor tracks are configured in such a way that they survive the erection without damage. Since the erection takes place in the direction of the conductor tracks, this is usually not a problem and in some variants of the present invention no special measures are required in this regard; in other variants of the present invention, the conductor tracks are preferably designed in the form of meander structures at the points where the largest angles arise during erection, so that the mechanical load is reduced. Another possibility for further variants according to the invention is to reduce the layer thickness of the conductor tracks.

In variants of the present invention, it is preferred if the n-side electrode structures form regular n-corners, for example equilateral ones.

The aspect ratio of the n-side electrode structures is length:width, where the length is the longest distance orthogonal to the fixed side and the width is the longest distance parallel to the fixed side.

In some preferred embodiments, the aspect ratio is 250:1 to 1:1, more preferably 100:1 to 1:1, more preferably 50:1 to 1:1, further preferably 10:1 to 1:1, even more preferably 8:1 to 2:1, particularly preferably 6:1 to 3.1 and in particular 5:1 to 4:1. In a preferred variant, the aspect ratio of a 4-sided electrode structure is 5:1 to 4:1.

• - für KiriCors (siehe dazu weiter unten) 250:1 bis 15:1, zum Beispiel 20:1, etwa 33:1, 40:1, etwa 67:1, 100:1 oder 200:1;
• - für KiriRets (siehe dazu weiter unten) 50:1 bis 3:1, zum Beispiel 4:1, etwa 5:1, 6:1, etwa 8:1, 23:1 oder 45:1.

In further embodiments, the aspect ratios can be selected as follows:

• - for KiriCors (see below) 250:1 to 15:1, for example 20:1, about 33:1, 40:1, about 67:1, 100:1 or 200:1;
• - for KiriRets (see below) 50:1 to 3:1, for example 4:1, about 5:1, 6:1, about 8:1, 23:1 or 45:1.

The protruding structures of the shaping layer can, in principle, have any shape. It must only be ensured that these structures can be pushed away from the n-side electrode structures when the shaping layer is pressed together/pressed against the electrode structure layer without being destroyed. In this respect, it is preferable if the protruding structures are not too sharp and too hard so that they do not damage the n-side electrode structures.

In preferred embodiments, the protruding structures are rectangular blocks with a pyramidal top end, or with a square prismatic top end. In use, the shaping layer is then preferably arranged such that the inclination of the upper surface of the square prismatic top end increases as viewed from the fully solid side of the n-side electrode structure.

Furthermore, the respective protruding structures should be adapted in their dimensions so that they can exert sufficient pressure on the n-side electrode structures, whereby the protruding structures of the forming system should be selected so that, on the one hand, they offer the n-side electrode structures as little contact area as possible, but on the other hand so that they enable the correct folding of the n-side electrode structures.

It is preferred if the width and length of the respective protruding structure on the shaping layer is smaller than the width and length of the respectively associated n-side electrode structure. The protruding structures should therefore in particular not have too great a width and at least not too short a length.

In this case, a width that is not too great means that the width is preferably between 30% and 90%, more preferably between 35% and 80%, particularly preferably between 40% and 70%, especially preferably between 45% and 60% of the width of the respective (assigned) n-side electrode structure. A length that is not too small means that they are the same length or less long than the respective (assigned) n-side electrode structures, but at least long enough to raise the respective n-side electrode structures, wherein ideally the length is at least 50%, preferably at least 70%, particularly preferably at least 85% but less than 100% of the length, preferably less than 95% of the length of the respective n-side electrode structure.

In some variants of the present invention, it is preferred if the length of the protruding structures corresponds to 90% of the n-side electrode structure and the width 50%. In order to reduce the contact areas, the protruding structures can be constructed as cuboids with an undercut.

The height of each of the respective protruding structures is preferably at least half as high, preferably between 55% and 80% as high, as the length of the respective associated n-side electrode structure.

In some preferred embodiments of the present invention, all n-side electrode structures of an electrode structure layer have the same dimensions and also all protruding structures of the shaping layer have the same dimensions, which are adapted in their dimensions and positions to the dimensions and positions of the n-side electrode structures.

In step E), the joined layers are heated to a temperature that causes a permanent shaping of the erected n-side electrode structures. In the case that the 2D electrode structure layer is based on a thermoplastic material, such as preferably parylene-C or polyimide, in particular parylene-C, the temperature is increased to a temperature that is above the glass temperature of the polymer materials but below their melting point.

In the case that thermosets are used, i.e. curing is still to take place, the temperature is increased to a point at which the initiators contained split or at which the cross-linking reaction takes place.

• 1) Bereitstellung einer ersten flexiblen Substratschicht, bevorzugt aus einem thermoplastischen Material, auf einem Trägersubstrat;
• 2) Aufbringen einer strukturierten Basismetallschicht umfassend Leiterbahnen und Elektrodenflächen auf die erste flexible Substratschicht;
• 3) optional Aufbringen einer flexiblen Zwischenschicht, bevorzugt aus einem thermoplastischen Material, auf die strukturierte Basismetallschicht, umfassend die Unterschritte:
  • 3a) Aufbringen einer Maske, bevorzugt Ätzmaske, auf die flexible Zwischenschicht,
  • 3b) Freilegen definierter Bereiche der Basismetallschicht, bevorzugt über reaktives Ionenätzen, der durch die Maske definierten, zu entfernenden Bereiche,
  • 3c) Entfernen der Maske, bevorzugt Ätzmaske,
  • 3d) Einbringen einer zweiten Metallschicht in die freigelegten Stellen der flexiblen Zwischenschicht;
• 4) Aufbringen einer Passivierungsschicht, bevorzugt aus einem thermoplastischen Material, auf die strukturierte Basismetallschicht oder die flexible Zwischenschicht;
• 5) Strukturierung der Passivierungsschicht umfassend die Unterschritte:
  • 5a) Aufbringen einer Maske, bevorzugt Ätzmaske, auf die Passivierungsschicht,
  • 5b) Freilegen definierter Bereiche der Passivierungsschicht, bevorzugt über reaktives Ionenätzen, der durch die Maske definierten, zu entfernenden Bereiche, optional, insbesondere falls Schritt 3) nicht durchgeführt wurde, mehrmalig,
  • 5c) Entfernen der Maske, bevorzugt Ätzmaske;
• 6) Entfernen des Trägersubstrats;
• 7) falls kein Schritt 3) vollführt wurde, Einbringen eines Beschichtungsmaterials in die freigelegten Bereiche der Passivierungsschicht und auf die freigelegten Bereiche der Elektrodenoberflächen.

Within the scope of the present invention, the production of the 2D electrode structure layer preferably comprises or consists of the following process steps:

• 1) providing a first flexible substrate layer, preferably made of a thermoplastic material, on a carrier substrate;
• 2) applying a structured base metal layer comprising conductor tracks and electrode surfaces to the first flexible substrate layer;
• 3) optionally applying a flexible intermediate layer, preferably made of a thermoplastic material, to the structured base metal layer, comprising the substeps:
  • 3a) Applying a mask, preferably an etching mask, to the flexible intermediate layer,
  • 3b) Exposing defined areas of the base metal layer, preferably by reactive ion etching, of the areas defined by the mask to be removed,
  • 3c) Removal of the mask, preferably etching mask,
  • 3d) introducing a second metal layer into the exposed areas of the flexible intermediate layer;
• 4) Applying a passivation layer, preferably made of a thermoplastic material, to the structured base metal layer or the flexible intermediate layer;
• 5) Structuring of the passivation layer comprising the sub-steps:
  • 5a) Applying a mask, preferably an etching mask, to the passivation layer,
  • 5b) Exposing defined areas of the passivation layer, preferably by reactive ion etching, of the areas defined by the mask to be removed, optionally, especially if step 3) has not been carried out, several times,
  • 5c) Removal of the mask, preferably etching mask;
• 6) Removing the carrier substrate;
• 7) If step 3) has not been performed, applying a coating material to the exposed areas of the passivation layer and to the exposed areas of the electrode surfaces.

It is particularly preferred if the production of the 2D electrode structure layer is part of the process for producing the three-dimensionally structured electrode layers.

• 2a) Aufbringen und anschließendes selektives Belichten eines Fotolacks, zum Beispiel mithilfe einer Belichtungsmaske,
• 2b) Entfernen der belichteten oder nichtbelichteten Bereiche, abhängig davon, ob ein positiver oder negativer Fotolack eingesetzt wird,
• 2c) Metallabscheidung in den freigelegten Bereichen.

Step 2) is preferably carried out by

• 2a) Applying and then selectively exposing a photoresist, for example using an exposure mask,
• 2b) Removal of the exposed or unexposed areas, depending on whether a positive or negative photoresist is used,
• 2c) Metal deposition in the exposed areas.

These are standard steps that are readily familiar to the expert and therefore do not need to be described further.

The base metal layer, i.e. the structured conductive layer, can be structured in different ways. Usually there are (more or less) straight conductor tracks that are connected to the electrode surfaces. As already indicated, there can also be meandering structures, for example to better withstand the stress during bending. Other structures possible according to the invention are grid-shaped designs.

In preferred variants of the present invention, the first substrate layer has a thickness of 0.5 µm to 10 µm, particularly preferably 2 µm to 8 µm, further preferably 4 µm to 6 µm and in particular 5 µm.

In preferred variants of the present invention, the intermediate layer has a thickness of 0.1 µm to 4 µm, particularly preferably 0.2 µm to 3 µm, further preferably 0.3 µm to 2 µm and in particular 0.5 µm to 1 µm.

In preferred variants of the present invention, the passivation layer has a thickness of 0.5 µm to 10 µm, particularly preferably 2 µm to 8 µm, further preferably 4 µm to 6 µm and in particular 5 µm.

In preferred variants of the present invention, the first base metal layer has a total thickness of 50 nm to 170 nm, particularly preferably 100 nm to 150 nm, further preferably 110 nm to 140 nm and in particular 120 nm to 130 nm.

In preferred variants of the present invention, the second metal layer has a thickness of 80 nm to 140 nm, particularly preferably 90 nm to 130 nm, further preferably 100 nm to 120 nm and in particular 110 nm.

In preferred variants of the present invention, the applied electrode coating has a thickness of between 50 nm and 1000 nm. It is further preferred if the actual thickness is selected in particular depending on the desired conductivity and the selected material (as well as other desired properties, such as material strength or the like).

In some preferred variants of the present invention, the electrode coating applied by spin coating, especially if it is PEDOT:PSS, has a thickness between 350 nm and 1000 nm, preferably between 400 nm and 950 nm.

In other preferred variants of the present invention, the electrode coating applied by electrodeposition, in particular if it is PEDOT:PSS, has a thickness between 100 nm and 700 nm, preferably between 130 nm and 600 nm.

In further preferred variants of the present invention, the electrode coating applied by galvanic deposition, in particular if it is iridium oxide, has a thickness between 80 nm and 140 nm, preferably between 98 nm and 118 nm.

In still further preferred variants of the present invention, the electrode coating applied by sputtering, in particular when it is SIROF (sputtered iridium oxide films), has a thickness between 200 nm and 550 nm, preferably between 250 nm and 500 nm.

In preferred variants of the present invention, the material of the 2D electrode structure layer is applied to n-1 sides of the respective n-sided electrode structures before or after steps 1) to 8). the material of the 2D electrode structure layer is completely or partially severed, preferably as described above.

In preferred variants of the present invention, the first substrate layer of the electrode structure layer comprises or consists of a thin metal film or a thermoplastic material. It is important here that these materials are moldable when heated to temperatures above their glass transition temperature. Due to the high temperatures, the chain structures of the amorphous regions of the PaC rearrange themselves, softening the material and enabling deformation. The polymeric material will then retain the new shape when cooling and removing the mold (molding layer and optionally pressing layer). Depending on the exact material used, a slow temperature ramp may be necessary during cooling in order to avoid damage to the thermoplastic material due to thermal and mechanical stress. It is important in the context of the present invention that the thermoplastic material has a lower melting temperature than the glass transition temperature of the material of the molding layer.

The materials for the metal films of the electrode structure layer are selected in some preferred variants of the present invention from the group consisting of gold, platinum, titanium, aluminum, and mixtures and alloys thereof.

In this context, it should be mentioned that in various variants of the present invention, to assist in production, the surfaces of the shaping layers can be coated with a thin metal film, water or a soap, a soap such as micro90, or silanes as a non-stick coating so that the separation of the shaping layer and the electrode structure layer following shaping can be carried out more effectively and safely (i.e. in particular without them sticking/adhering to one another).

Furthermore, the thermoplastic material is preferably selected from the group consisting of parylene-C (PaC), polyimide (PI), polyethylene terephthalate (PET), polylactic acid (PLA), polytetrafluoroethylene (PTFE), polystyrene (PS) and mixtures thereof, particularly preferably parylene-C or polyimide, in particular parylene-C. Examples of commercially available products that can be used in the context of the present invention are Parylene Dimer DPX-C from Specialty Coating Systems, Inc., and PI-2611 and PI-2610 from HD Microsystems.

When biomedical applications are considered, it is preferable to use the thermoplastic materials mentioned above, especially PaC and PI due to their proven biocompatibility for invasive medical products.

The materials of the molding layer, in case of polymers, have a glass transition temperature and melting point that are higher than those of the material used for the 2D electrode structure layer (the kirigami design). Other alternative materials for the molding layer are photo-imageable epoxy-based resists such as SU-8. In addition, a metal molding layer can also be used. Other alternative methods for patterning the molding layer are photolithography, stepper lithography, maskless lithography such as electron beam lithography or direct laser writing lithography, nanoimprinting, hot stamping, chemical/photochemical milling or high aspect ratio etching (dry and wet).

However, other materials can also be used within the scope of the present invention, as long as they do not contain any toxic ingredients. Examples of other materials that can be used are quartz, ceramics, and metals.

In preferred variants of the present invention, the shaping layer comprises or consists of metal, plastic or 3D-printed material, preferably starting from material that can be printed by means of 2-photon polymerization, particularly preferably based on (meth)acrylates that cure via radical polymerization or on the basis of photostructurable epoxy resins, in particular bisphenol A novolac epoxies, or also on the basis of mixtures thereof.

Commercially available examples are the photopolymers available under the name IP-S (from NanoScribe GmbH), for example IP-S 780, or SU-8 from Microchem Corp.

In further variants of the present invention, the shaping layer may comprise or consist of materials selected from the group consisting of metal, plastic, quartz, ceramic and mixtures thereof.

In further preferred variants, the photopolymer IP-S can be used in particular for the shaping layer and can be photostructured by means of two-photon polymerization.

The base plane of the shaping layer itself has a thickness of 10 µm to 40 µm, for example 20 µm, in preferred embodiments. The protruding structures have heights (from starting from the plane) depends on the respective n-side electrode structures to be raised and can, in some preferred variants, be between 200 µm and 1200 µm, preferably between 300 µm and 1100 µm.

• B1) Bereitstellen einer Anpresslage.

Furthermore, the method according to the invention can comprise:

• B1) Providing a contact pressure layer.

• C1) Ausrichten der flexiblen 2D-Elektrodenstrukturlage und der Formgebungslage sowie der Anpresslage, so dass die jeweiligen hervorstehenden Strukturen der Formgebungslage jeweiligen n-seitigen Elektrodenstrukturen der 2D-Elektrodenstrukturlage zugeordnet sind und so, dass 2D-Elektrodenstrukturlage zwischen Formgebungslage und Anpresslage angeordnet ist;
• D1) Zusammenpressen der 2D-Elektrodenstrukturlage, der Formgebungslage und der Anpresslage, wobei die n-seitigen Elektrodenstrukturen durch die jeweiligen hervorstehenden Strukturen der Formgebungslage aus der Ebene der 2D-Elektrodenstrukturlage herausgedrückt und angehoben werden.

In this case, steps C) and D) change, i.e. they are extended to include the contact pressure and its use, as follows:

• C1) aligning the flexible 2D electrode structure layer and the shaping layer as well as the pressing layer such that the respective protruding structures of the shaping layer are assigned to respective n-side electrode structures of the 2D electrode structure layer and such that the 2D electrode structure layer is arranged between the shaping layer and the pressing layer;
• D1) Pressing together the 2D electrode structure layer, the forming layer and the pressing layer, wherein the n-side electrode structures are pressed out of the plane of the 2D electrode structure layer and lifted by the respective protruding structures of the forming layer.

Within the scope of the present invention, the materials for the pressing layer can be selected from the same materials that are mentioned for the shaping layer. In preferred variants of the present invention, the pressing layer and the shaping layer are made of the same material.

In preferred embodiments, the base plane of the pressure layer itself has a thickness of 10 µm to 40 µm, for example 20 µm. The protruding elements, i.e. edges, webs, etc., have heights (starting from the plane) depending on the respective n-side electrode structures to be raised and can, in some preferred variants, be between 200 µm and 1200 µm, preferably between 300 µm and 1100 µm.

In preferred variants of the present invention, the electrode structure layer comprises or consists of parylene-C, apart from the metals of the conductor tracks and electrode surfaces, and the shaping layer comprises or consists of IP-S, and, if present, the pressing layer comprises or consists of IP-S.

In variants of the present invention, the electrodes are further coated with materials such as PEDOT:PSS or iridium oxide (IrO _x ) to improve their electrochemical properties. For example, and in some embodiments preferably, these can be sputtered iridium oxide (SIROFs), electrodeposited PEDOT:PSS or electrodeposited IrO _x . However, the invention is not limited to these manufacturing methods and many more are possible, for example, and in some embodiments also preferred, spin coating of PEDOT:PSS, in which for example a stencil process (lift-off technique with sacrificial layer) or a dry etching process can be used.

In preferred variants of the present invention, the electrodes are completely or partially coated with conductive materials, preferably selected from the group consisting of PEDOT:PSS, iridium oxide and mixtures thereof.

Within the scope of the present invention, it is preferred in variants that electrodes or connections are provided on at least one edge of the 2D electrode structure layer in order to enable the connection of the three-dimensionally structured electrode layer obtainable/obtained according to the invention to other instruments. These can be applied during the manufacture of the 2D electrode structure layer as part of the metallization, or also later in addition, for example by soldering, clamping or the like.

Within the scope of the present invention, it is preferred in variants that the n-side electrode structures each independently comprise one or more individual electrode surfaces, for example point-shaped ones. It is preferred if several electrode surfaces are present in each case.

In preferred variants, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 or 32 or even more electrode surfaces per electrode structure (each independently of one another) can be present, preferably 2 to 32, particularly preferably 3 to 20 and in particular 4 or 16.

In particularly preferred variants of the present invention, the three-dimensionally structured electrode layers have 32 4-sided electrode structures of 225 µm length and 50 µm width, each having 4 electrode surfaces, the lowest of the four having a diameter of 25 µm and the remaining three having a diameter of 15 µm.

In other particularly preferred variants of the present invention, the three-dimensionally structured electrode layers have 4-sided electrode structures of 1000 µm to 1500 µm in length, each having 16 electrode surfaces with a diameter of 15 µm.

The present invention further relates to three-dimensionally structured electrode layers produced by a method according to the invention as described above.

Yet another object of the present invention are implants or neuroimplants comprising three-dimensionally structured electrode layers according to the present invention or consisting of these.

Last but not least, the present invention relates to the use of three-dimensionally structured electrode layers according to the present invention as or for implants or neuroimplants, in particular intraretinal 3D implants or intracortical/cortical 3D implants, for measuring electrochemical properties, for measuring physical properties, in biosensing, or for impedance measurement.

The method according to the invention can be used (and has already been used) to produce three-dimensional, flexible neural implants (neuroimplants) for the three-dimensional space of the retina (KiriRet) or the cortex (KiriCor). Parylene-C (PaC) is a material which in some variants can preferably serve as a substrate and for encapsulation in this context. In some preferred variants, the structured base metal layer is structured with Ti/Au/Ti conductor tracks and up to 128 Ti/Au electrodes, which are coated with PEDOT:PSS or iridium oxide at their openings.

With the implants according to the invention (neuroimplants), signals from neuronal cells can be measured in vitro and, in some cases, in vivo and at the same time, cells can be stimulated in a targeted manner.

The design of the KiriRet implant consists in preferred variants of 32 shafts, each 50 µm wide and 225 µm long. In preferred variants, each shaft has four electrodes; with a diameter of 25 µm for the electrode that is furthest away from the electrode structure layer used for electrical stimulation, or 15 µm for the other electrodes. Depending on the application of the implant, the width, length and electrode diameter as well as the number of electrodes can be varied within the scope of the present invention within a wide range. For example, in preferred variants, KiriCor implants are 1000 µm to 1500 µm long and the electrodes have a diameter of 15 µm, so that up to 16 electrodes fit on each shaft. In addition, in some preferred embodiments of the present invention, the implants can contain at least one, preferably exactly one, internal reference electrode in order to carry out electrophysiological or electrochemical measurements.

In the context of the present invention, the implants are preferably manufactured by surface micromachining and microelectromechanical systems (MEMS) to create the 2D shape and the cutouts for folding.

In such preferred embodiments, in particular, a 5 µm thick PaC layer is first applied to a Si wafer and structured with a Ti/Au/Ti layer for conductor tracks, electrodes and contact surfaces. Then a second 5 µm thick PaC layer is applied for encapsulation. In the next step, the folding cutouts and the electrodes and contact surfaces are opened. The 2D sample is then detached from the Si substrate and soldered/fixed to a circuit board; in some preferred variants by flip assembly. An example of this is the flip-chip process. In these variants, the flip-chip process can be carried out in such a way that the circuit board is first heated using a heating plate (to 180°C) and low-temperature solder alloy is applied; the 2D samples are then detached from the Si substrate using water; during this, the heating plate is cooled (to 160°C) and then the 2D probe is fixed with its contact surfaces to the circuit board. Within the scope of the present invention, however, instead of this specific flip-chip method, modified or other similar methods known to the person skilled in the art can also be used.

The folding mold is preferably 3D printed using a 2-photon polymerization technique.

In some preferred variants, the mold consists of two parts. The lower part is then an array of protruding structures, in particular rectangular blocks with a pyramidal end; this is the shaping layer. The protruding structures are further preferably at least half as high as the length of the shafts in order to lift them (a lower height is also possible in principle, but less reliable depending on the material of the shafts). The individual protruding structures are placed in such a way that they are arranged analogously to the corresponding point of the flexible 2D design (the electrode structure layer) (in order to be able to push the shafts up in the first place). In addition, the lower part preferably has a frame on the edges that corresponds exactly to the size of the 2D structure (electrode structure layer) and is used for alignment/adjustment. The The upper part of the 3D mold in this variant of the present invention is a structure made up of a frame and walls in the middle, which, when placed on the lower part and flexible 2D structure, results in the shafts of the electrode structures being folded evenly (as the upper mold ensures even pressing/pressing). This is the optional pressing layer. In further preferred embodiments, the frames of the lower and upper sections fit together like the key-lock principle. Alternatively, and preferred in other variants of the present invention, it is just as possible to use just a one-piece mold that corresponds to the lower part of the mold just described (i.e. the shaping layer). The upper part just described, which serves for pressing, can then be replaced by other means and devices, for example stamp-like devices with only an outer frame or one or more protruding elements - in each case to press the electrode structure layer onto the shaping layer - or also laterally attached (to be attached) (tension) clamps or other devices which are suitable for pressing the electrode structure layer and the shaping layer together in such a way that the n-side electrode structures can be erected by the protruding structures.

After the 3D structure (forming layer) and the 2D sample (electrode structure layer) have been produced, the individual parts are brought together. The 2D sample is placed on the 3D mold to fold all n-sided electrode structures simultaneously. The upper part of the 3D mold (pressing layer) or another device for pressing/compressing helps to fold the shafts in a controlled manner. To simplify the precise alignment/adjustment of the 2D structure and the 3D mold, frames of the 3D mold are used in preferred embodiments.

The assembled layers are then heated together so that the n-side electrode structures are thermally fixed. This can essentially be done by using a thermoplastic material for the base of the electrode structure layer, which accordingly undergoes a thermoplastic deformation that is retained after cooling. Or a not yet cured thermoset or not yet cured thermoset mixture can be used for the base of the electrode structure layer, so that it hardens when heated and then retains its shape after cooling. A combination is also conceivable. In some variants of the present invention, it is preferred if a thermoplastic material is used for the base of the electrode structure layer.

After the shaped, three-dimensionally structured electrode layer is separated from the 3D shape, in further preferred variants of the present invention, the electrodes can be coated with electrolytically deposited conductive substances, particularly preferably PEDOT:PSS or iridium oxide (IrO _x ), in a further manufacturing step in order to improve the electrical properties. The finished three-dimensionally structured electrode layer can then be used as a (neuro)implant in, for example, electrophysiological experiments.

The method according to the invention allows the use of various materials. These include polyimide (PI) and parylene-C (PaC) as examples of thermoplastic materials for the production of the electrode structure layer (2D structure). Various conductive materials that can be deposited by electrodeposition or physical deposition, such as PEDOT:PSS or IrO _x , are also conceivable for the electrodes. The exact designs/configurations of the electrode structure layer, the shaping layer and thus the resulting three-dimensionally structured electrode layer are also flexible. For example, in some preferred embodiments of the present invention, diameters of 10 µm to 25 µm can be used for the electrodes in order to ensure the resolution of individual cells. When using small electrodes and optimized manufacturing processes, however, thinner shafts of less than 50 µm are also possible and are therefore preferred in some other embodiments of the present invention.

The method according to the invention for producing three-dimensionally structured electrode layers can be used to produce three-dimensional Kirigami structures simply, quickly, reliably and at low cost. By using self-adjusting structures, i.e. that the electrode structures are brought into defined positions by pressing the different layers together, it is possible to produce several 3D probes at the same time. Such 3D probes can be used, for example, in electrophysiological experiments for deriving cell signals from different nerve tissues such as the brain, peripheral nerves or retina, and for electrical stimulation of the corresponding nerve cells. Similarly, the structures produced according to the invention can be used, for example, in/for/in 3D cell cultures and organoids. The application is advantageously not limited to electrophysiological applications, but can also be used, for example, if it is desired to measure the electrical properties of a three-dimensional space in the mm or µm range. The terms “flexible substrate layer”, “flexible intermediate layer” and “flexible 2D electrode structure layer” can mean in preferred variants of the present invention: “Substrate layer comprising or consisting of parylene-C or polyimide, optionally with Ti/Au, Ti/Au/Ti, Ti/Pt/Ti, Ti/Au/Pt, Ti/Au/Ti/Pt/Ti, PEDOT:PSS conductor tracks, in particular Ti/Au or Ti/Au/Ti conductor tracks, and electrode surfaces, in particular consisting of parylene-C with Ti/Au or Ti/Au/Ti conductor tracks and electrode surfaces”, “Intermediate layer comprising or consisting of parylene-C or polyimide, in particular consisting of parylene-C”, “2D electrode structure layer comprising or consisting of parylene-C or polyimide with Ti/Au or Ti/Au/Ti conductor tracks and electrode surfaces, in particular consisting of parylene-C with Ti/Au or Ti/Au/Ti conductor tracks and electrode surfaces”.

The three-dimensionally structured electrode layers produced according to the invention could be successfully used as intraretinal 3D implants in in vitro experiments and experiments with cadavers, whereby the functionality was extensively validated.

The method according to the invention advantageously uses neither cytotoxic materials nor high-energy equipment, which could endanger the manufacturer or end user. The purely mechanical forming method according to the invention is fast and reliable because, in contrast to other methods, it folds all (desired) shafts simultaneously and reliably, preferably at an angle of 90°. The highlighted structures of the forming layer and the folded MEA or the folded 3D probe can be placed together in a heating environment in order to fix the positions of the electrode structures using thermoforming.

It is also particularly advantageous within the scope of the present invention that any desired electrode structures for three-dimensional electrode layers can be produced in a very simple, reliable and reproducible manner. By simply adapting the original designs, for example CAD files, electrode structure layers can be produced in which the respective electrode structures can be arranged in any desired position. In addition, the respective dimensions of the individual n-sided electrode structures can be easily changed or adapted to the respective requirements. In this way, electrode layers can be produced which have n-sided electrode structures of different dimensions, for example with regard to the length and/or width of the shafts. The method according to the invention and the three-dimensionally structured electrode layers produced using it are therefore particularly versatile.

The individual parts of the devices/systems according to the invention are operatively connected to one another in a conventional and known manner.

In preferred embodiments of the present invention, this does not relate to the therapeutic treatment of humans or animals.

The various embodiments of the present invention, for example - but not exclusively - those of the various dependent claims or of individual embodiments described in the figures, can be combined with one another in any manner, provided that such combinations do not contradict one another.

Examples:

The invention will now be further explained with reference to the following non-limiting examples.

Example 1 - Fabrication of flexible 2D electrode structure layers:

The fabrication of flexible 2D electrode structure layer with kirigami design (with recesses but not folded) involved the sequential deposition of flexible thin film layer, a metal layer, another flexible thin film layer and an electrode coating. Depending on the electrode coating, six to seven steps were performed as follows. All steps (except PaC deposition) were performed in a certified clean room environment to ensure stable manufacturing.

1. Deposition of the first flexible substrate layer

A first 5 µm thick layer of parylene C (poly(2-chloro-p-xylylene); PaC) was deposited on a silicon wafer by chemical vapor deposition using a PDS 2010 Labcoater 2 (Specialty Coating Systems Inc., USA) using 10 g of PaC dimer and a process vacuum pressure of 3.33 Pa (about 25 mTorr).

2. first metallization

In a second step, metallization was carried out using a lift-off process. The metal base layer for contact surfaces, leads and electrodes was structured. First, a negative photoresist AZ LNR-003 (containing, among other things, hexakis(methoxymethyl) melamine and 1-methoxy-2-propanol acetate; MicroChemicals GmbH, Germany) at 4000 rpm for 45 seconds with a ramp of 500 rpm/s. This was followed by baking at 120°C for 2 minutes on a direct contact hot plate. The photoresist was then exposed to UV light of 375 nm wavelength at 320 mJ/cm ² with a Defoc setting of 2 and a CDB (critical dimension bias) of 800 using a maskless exposure system (MLA 150, Heidelberg Instruments, Germany). After exposure, a heating step at 100°C for 1.5 minutes on a direct contact hot plate, a development step in AZ 326 MIF (MicroChemicals GmbH, Germany) as a developer (a developer based on tetramethylammonium hydroxide) for 1.5 minutes and a cleaning step in deionized water were performed. The wafer was then vapor-deposited with a metal, whereby 20 nm Ti, 100 nm Au and 10 nm Ti were deposited layer by layer in an electron beam assisted evaporation system (Balzer PLS 570, Pfeiffer, Germany) (resulting in a metal layer sequence Ti/Au/Ti). A tungsten crucible and deposition rates of 0.1 nm/s for Ti and 0.5 nm/s for Au were used. A lift-off process in an acetone bath was then carried out for 2.5 hours to wash off the sacrificial material and the photoresist. After lift-off, the wafer was rinsed in isopropanol for 2 minutes and dried with a nitrogen gun.

In other embodiments, the UV exposure step was alternatively performed by standard UV photolithography using a broadband exposure system with mask alignment (Süss MA8/BA8, Germany) with a dose of 100 mJ/cm ² .

3. flexible intermediate layer (optional)

In some designs, step 3 was performed, in others it was not. In cases where it was not performed, step 4 was used. A second flexible PaC layer (PaC interlayer) with a thickness of 0.5 µm to 1 µm (1-2 g PaC dimer) was deposited as described in step 1. The PaC was then etched at the electrode openings by reactive ion etching (RIE). This process is described in detail below in step 5. A second metallization step was then performed to directly add an electrode coating. Here, a resist stack of LOR3B (MicroChem Corp, USA; a resist based on polydimethylglutarimide) and negative photoresist nLOF 2020 (MicroChemicals GmbH, Germany; a negative photoresist containing PGMEA (1-methoxy-2-propanol acetate)) was used to pattern a deposition mask for the electrode openings by photolithography. First, LOR3B was spin-coated at 2000 rpm for 30 seconds with a ramp of 500 rpm/s, then a bake-out step at 150°C for 5 minutes on a direct contact hotplate, followed by spin-coating of nLOF 2020 at 2000 rpm for 30 seconds with a ramp of 500 rpm/s and a bake-out step at 110°C for 1 minute on a direct contact hotplate. The subsequent steps depended on the choice of exposure equipment. Using the MLA150 maskless exposure system, the photoresist was exposed to 375 nm UV light at 670 mJ/cm ² with a Defoc setting of 0. Post-exposure baking was then performed at 102°C for 2 minutes on a direct contact hotplate, followed by a development step in AZ326 MIF for 45 seconds and a cleaning step in deionized water. Using a broadband exposure system with mask alignment, exposure was performed at 40 mJ/cm ² , followed by a post-exposure bake at 110°C for 1 minute, development in AZ325 MIF for 33 seconds to 35 seconds and cleaning in deionized water.

Subsequently, an additional Ti layer of 10 nm thickness and a Pt layer of 100 nm thickness were evaporated (resulting in a metal layer sequence Ti/Pt), followed by 250 nm to 500 nm sputtered iridium oxide layers (SIROFs), which were deposited by sputtering with an Ar/O ₂ gas mixture of 100/6 sccm (standard cubic centimeters per minute) and a DC power of 100 W.

4. Deposition of a flexible passivation layer

A flexible PaC passivation layer with a thickness of 5 µm was deposited analogously as described in step 1.

5. Recesses, shape and passivation openings

In this step, the flexible polymer was structured. This includes the cuts of the kirigami structures (recesses of the n-side electrode structures), the outlines of the shape of the complete probe as well as the openings of the contact surfaces and those of the electrodes. First, an etching mask was structured with a thick positive photoresist of at least 1.5 times the thickness of the polymer to be etched. An etching mask was structured on the last PaC layer by spin-coating the photoresist AZ 12XT (MicroChemicals GmbH, Germany; a photoresist containing PGMEA) at 1000 rpm for 180 seconds with a ramp of 200 rpm/s, baking with a hot plate at 110°C for 4 minutes and exposed to UV light of 375 nm wavelength using a maskless exposure system with a dose of 350 mJ/cm ² , a Defoc setting of 2 and a CDB of -800. Subsequently, after exposure, the wafer was subjected to heating using a hot plate at 90°C for 1 minute, followed by a development step of 2 minutes with AZ 326 MIF. After patterning the etch mask, an RIE step was performed with an O ₂ /CF ₄ gas mixture of 36/4 sccm with RF/ICP (RF = capacitively coupled radio frequency and ICP = inductively coupled plasma) powers of 50/500 W to etch PaC. If step 3 was not performed, a second RIE step was performed to etch the top 10 nm thick Ti layer using an O ₂ /Ar gas mixture of 20/20 sccm and an RF power of 150 W. After RIE, the etch mask was removed with AZ 100 remover (MicroChemicals GmbH, Germany; ethanolamine-based solvent) in a two-bath system. In the first bath, a low-power ultrasonic bath is used for 5 minutes, followed by a second bath with fresh AZ 100 remover without ultrasonication. The wafer was then rinsed in three baths with isopropanol.

6. Detachment and chip assembly

The 2D electrode structure layer was released from the silicon wafer using water drops and tweezers. These were then mounted on a PCB using a flip-chip assembly method. First, the PCB was preheated to 180°C on a direct contact hot plate, and the low-temperature solder alloy Sn42/Bi58 (AMTECH, USA) was applied to the contact pads of the PCB, allowing the formation of liquid bumps on each contact pad. By lowering the temperature to 160°C, the flexible probes were aligned and placed on the liquid solder paste accumulations that solidified after the new chip was quickly removed from the hot plate and cooled to room temperature. The freshly soldered area was sealed with a polydimethylsiloxane (PDMS) coating in a mixing ratio of 1:10 curing agent to prepolymer (for example Sylgard 184, Dow Corning, USA) and cured in an oven at 120°C for 30 minutes. Other epoxy-based polymers could and can also be used as a sealing layer.

7. Applying the electrode coating (optional)

In cases where step 3 was not performed, electrode coating was performed to improve the electrochemical properties of the Au electrodes. In this case, conductive materials such as PEDOT:PSS (poly(3,4-ethylenedioxythiophene:poly(4-styrenesulfonate)) will be electrodeposited.

For this purpose, an EDOT:PSS solution was prepared from 0.1% (w/v) 3,4-ethylenedioxythiophene (EDOT) and 0.7% (w/v) poly(sodium 4-styrenesulfonate) (PSS) in deionized water.

After assembly, the electrode layers were first subjected to electrochemical cleaning in 1x PBS (phosphate buffered saline) at room temperature by performing 10 cycles of cyclic voltammetry on all electrodes with a sweep rate of 100 mV/s and potential limits between -0.6 V and -0.9 V against an Ag/AgCl reference electrode. Then, the surface of the 2D electrode structure layer (can also be called 2D kirigami device) was activated with O ₂ plasma at a pressure of 0.8 mbar and a power of 80 W for 3 min. Electrochemical polymerization of EDOT:PSS on the Au-based electrodes was then performed by chronoamperometry using a constant potential of 1 V for 20 s.

Other conductive materials could also be deposited electrochemically using cyclic voltammetry or chronoamperometry, such as IrO _x . In these cases, an electrolyte solution based on iridium chloride hydrate was used instead of the EDOT:PSS solution. A first adhesion layer of IrO _x was grown after 200 to 400 cycles of cyclic voltammetry with a sweep rate of 50 mV/s and potential limits between 0 V and 0.55 V against an Ag/AgCl reference electrode, followed by the formation of a thicker layer that was grown by chronoamperometry at a constant potential of 0.55 V against an Ag/AgCl reference electrode for 60 minutes to 100 minutes.

Example 2 - Production of the molds (forming layers):

A two-photon polymerization 3D printer Photonic Professional GT2 from NanoScribe GmbH was used to produce the molds. The process used focuses an erbium-doped femtosecond laser source (central wavelength 780 nm) into a liquid drop of photo resin. If the laser power exceeds a certain threshold, the photo resin only polymerizes at the focal point of the laser, making it possible to create really complex structures with high resolution.

1. 1. 3D-Entwurf:
   • Die Formen wurden mit einer CAD-Software entworfen und mit Describe (Software der NanoScribe GmbH) in Druckanweisungen umgewandelt.
2. 2. 3D-Druck:
   • Ein Zeiss 25X NA0.8 Objektiv wurde verwendet und IP-S (NanoScribe GmbH, Deutschland) wurde als Photopolymer-Material verwendet. Mit dem vorgegebenen Druckrezept von NanoScribe, das für die Kombination von 25X-Objektiv und IP-S ausgelegt ist, wurde der Slicing-Abstand auf 1 µm und der Hatching-Abstand auf 500 nm eingestellt. Die Einstellungen Scangeschwindigkeit 100000 µm/s, LaserPower 100% und Power Scaling 1,2 führten zum besten Druckergebnis mit ausreichender Auflösung und Stabilität der gedruckten Struktur. Da die Form viel größer ist als ein einzelner gedruckter Block, der durch das Druckfeld des verwendeten Objektivs (400 µm × 400 µm × 400 µm für das 25X-Objektiv) ohne Tischbewegung definiert ist, wurden viele Blöcke nebeneinander gedruckt, um die gesamte Struktur aufzubauen. Um die Adhäsion zwischen den einzelnen Blöcken zu gewährleisten, wurde die Blocküberlagerung in allen Dimensionen auf 2 µm eingestellt. Die Höhe der einzelnen Blöcke wurde auf 200 µm eingestellt, um zu gewährleisten, dass das Objektiv, welches einen Arbeitsabstand von 380 µm hat, nicht in die Struktur hineinfuhr. Die Formen wurden auf ein 2,5 cm × 2,5 cm großes Glassubstrat gedruckt, das zuvor mit 3 µm PaC beschichtet wurde, wie in Schritt 2 von Beispiel 1 (Herstellung von flexiblen 2D-Elektrodenlagen) beschrieben. Die PaC-Beschichtung gewährleistete eine hohe Haftung des Drucks auf dem Glassubstrat.

To obtain such shapes, three main steps were carried out:

1. 1. 3D design:
   • The shapes were designed using CAD software and converted into printing instructions using Describe (software from NanoScribe GmbH).
2. 2. 3D printing:
   • A Zeiss 25X NA0.8 objective was used and IP-S (NanoScribe GmbH, Germany) was used as photopolymer material. Using the default print recipe from NanoScribe designed for the combination of 25X objective and IP-S, the slicing distance was set to 1 µm and the hatching distance to 500 nm. The settings Scan Speed 100000 µm/s, LaserPower 100% and Power Scaling 1.2 resulted in the best printing result with sufficient resolution and stability of the printed structure. Since the shape is much larger than a single printed block defined by the print field of the objective used (400 µm × 400 µm × 400 µm for the 25X objective) without stage movement, many blocks were printed next to each other to build the entire structure. To ensure adhesion between the individual blocks, the block overlay was set to 2 µm in all dimensions. The height of the individual blocks was set to 200 µm to ensure that the lens, which has a working distance of 380 µm, did not enter the structure. The shapes were printed on a 2.5 cm × 2.5 cm glass substrate that had been previously coated with 3 µm PaC as described in step 2 of Example 1 (production of flexible 2D electrode layers). The PaC coating ensured high adhesion of the print to the glass substrate.

In this step, a raised edge was also printed all around, which will later be important for aligning the different layers with each other.

3. Development:

A post-print development step was used to wash away any remaining photopolymer that had not polymerized. The samples were placed in a bath of fresh Mr-Dev 600 developer (Micro Resist Technology's solvent-based developer for epoxy-based photoresists) for 15 minutes, followed by another 5-minute bath in fresh Mr-Dev 600. Finally, the molds were placed in fresh isopropanol for another 5 minutes and then air dried. All of the above steps were performed in a certified cleanroom environment to ensure a stable manufacturing environment.

Example 3 - Completion of the flexible three-dimensional structured electrode layers

After the flexible 2D electrode layers and the molds (forming layers and pressing layers) had been produced, assembly followed. In order to produce a three-dimensionally structured electrode layer, two molds were used in this example in order to be able to fold the shafts at a 90° angle (however, the mold produced in example 2, i.e. the forming layer, alone is sufficient). First, 2D electrode layers produced according to example 1 were placed on molds produced according to example 2 ( 3A) . This was done either with the help of a micromanipulator or by hand (in the latter case it was helpful to work under a suitable microscope). It was also helpful to use a second pair of tweezers to align the 2D electrode layers with the lower mold. It helped that when the mold was manufactured according to Example 2, outer edges had been formed on which the alignment could be done, because the mold was manufactured in such a way that the 2D electrode layers fit perfectly into the edges of the mold (forming layer) that formed a kind of frame, whereby the 2D electrode layers were held by the edges. In the next step, tweezers were used to grip another, second mold (pressing layer), which was placed on top of the 2D electrode layers with its edges pointing downwards ( 3B) These second molds were produced according to example 2, except that no individual highlights in the form of blocks (which would have been matched to the shafts of the 2D electrode layers) were printed, but rather outer edges that were dimensioned so that the shape with the outside of its edges fit exactly inside the edges of the lower, first mold (i.e. the shaping layer). In addition, the other, second molds (pressing layers) could optionally have further elevations, for example webs or other elevations of any shape. Ideally, and therefore preferred within the scope of the present invention, all elevations of the pressing layers, including the edges, have the same height so that the pressure can be applied as evenly as possible. It is only important that the elevations of the pressing layer are arranged in such a way that when the various layers are pressed together, they do not lie above the elevations of the shaping layer or the shafts of the 2D probes, because otherwise the shafts of the 2D probes could not unfold.

The application of the additional, second forms (pressing layers) was carried out in some cases with the help of a micromanipulator and in other cases with steady hands (if necessary with the help of a microscope). In each case, the upper mold was slowly lowered to facilitate more precise placement. Since the edges of the upper mold fit snugly into the lower mold, alignment was made easier (as explained). Once the second mold (press layer) was in place, it was lowered and all three layers were pressed together until all the shafts rose simultaneously.

In all cases, the different layers were arranged parallel to each other and their parallelism was maintained even when compressed.

In further experiments, a reverse procedure was followed. A 2D electrode layer was produced according to Example 1. This layer was then inserted into a prefabricated holder, which fixed the layer in place ( 4A) . In addition, the frame had cross braces to ensure even pressure distribution during the subsequent folding. The frame was placed on an assembly table (with a recess in the middle) to create space for the shafts to be folded; alternatively, the frame can of course also be designed in such a way that it leaves enough space for the shafts to be unfolded, for example by having appropriately high edges. In the next step, the form (forming layer) produced according to example 2 was placed with the elevations facing forward on the 2D electrode layers ( 4B) . Here too, the edges of the frame helped to improve the alignment. When the mold (forming layer) is correctly placed, it is pressed down onto the 2D electrode layers so that the protrusions of the forming layer pushed the shafts out of the plane of the 2D probe and all shafts were folded simultaneously. In this variant, the prefabricated frame therefore replaces the pressing layer from the first variant; the prefabricated frame can therefore be considered a special case of the pressing layer.

The joined layers were then heated to fix the erected shafts in position. The layers were heated at a ramp as slow as possible of about 5°C/min. The temperature was then held at 150°C to 160°C for 60 minutes. The layers were completely cooled (about 120 minutes) before they were taken apart.

Finally, the layers were separated from each other and the former 2D electrode structure layer was obtained as a new, three-dimensionally structured electrode layer with upright electrode shafts positioned approximately at a 90° angle to the layer plane.

These could then be used, for example, as a neuroimplant. For in vitro and ex vivo applications, these could be used directly as manufactured; for in vivo applications, they still had to be sterilized (for example using ethanol, UV irradiation, ethylene oxide, hydrogen peroxide plasma, autoclaving).

The embodiments of the present invention explained in more detail below with reference to the figures represent various preferred embodiments; many of the features or embodiments shown in individual figures below can be combined with features and embodiments shown in other figures or the rest of the description, especially where the features are described accordingly. The figures are also not to be interpreted as limiting and are not to scale. Furthermore, the figures do not contain all the features that conventional devices/systems have, but are reduced to the features that are essential for the present invention and its understanding; for example, screws, hoses, brackets, etc. are not shown or are not shown in detail.

Identical reference symbols/numbers mean identical or equivalent device parts.

1 shows schematically the sequence of production of 2D electrode structure layers 2DE, as also described above. The layering is shown in a view parallel to the 2D electrode structure layer 2DE after the respective process step. For the sake of simplicity, only one section with an electrode structure is shown here as an example; however, the 2D electrode structure layer (usually) has a large number of these. The numbers 1), 2), 4), 5), 6) and 7) shown on the far left represent the process steps described above with the corresponding numbering. As can be seen, in step 1) the first substrate layer 1S is applied to a carrier substrate T. Also shown is an optional intermediate layer oZ, which is preferably only used if polyimides are used as the substrate. In step 2), the first, structured metal layer (base metal layer) 1M is then applied to this. According to the above description, at the end of step 2) this layer only consists of conductor tracks L and electrode areas EF (regardless of whether a complete metal layer is first applied and then excess metal is removed, or metal is only applied to selected, for example, exposed areas and the remaining areas are then freed of protective polymer, for example; L and EF are not shown separately in this figure for the sake of clarity). Next, the layer sequence after step 4) is shown, in which the passivation layer P remains. In step 5) only the first metal layer 1M is then exposed at selected locations, and in step 6) the carrier substrate T is removed. In step 7) the exposed electrode surfaces are then coated with electrically conductive substances (polymers), resulting in an electrically conductive coating eB, which then remains. The product thus obtained, the 2D electrode structure layer 2DE, can then be subjected to a "kirigami process" (i.e. the inventive process steps A) to F)), for example as in the 3 or 4 shown.

For the sake of clarity, in this figure, as in the other figures, the individual components are not labelled in all steps, but only in some of them; however, identical representations show identical elements.

2 illustrates the same as 1 , but with the difference that a second procedure is shown here, in which step 3) is carried out, but not step 7). Accordingly, for step 3), it is shown that the intermediate layer Z is first applied, whereby the first metal layer 1M remains partially exposed, or is exposed again, so that at the end of step 3) a partially exposed first metal layer 1M results. According to step 3d), a second metal layer 2M is then applied, which then remains. Here it is shown that the second metal layer 2M partially rests on the intermediate layer Z, but this is not necessarily the case. It is also possible to carry out this step in such a way that at the end the intermediate layer Z and the second metal layer 2M merge flush into one another or in such a way that the upper end of the metal layer 2M is slightly lower. The remaining steps correspond to those in 1 The product thus obtained, the 2D electrode structure layer 2DE, can then be subjected to a “kirigami process” (i.e. the process steps A) to F)) according to the invention, for example as shown in the 3 or 4 shown.

The 3 to 5 illustrate the inventive method for producing three-dimensionally structured electrode layers (i.e. a kind of Kirigami process). 3 shows a first possible variant of positioning and bringing together the 2D electrode structure layer 2DE, shaping layer F and pressing layer A. The left half of the figure shows how a 2D electrode structure layer 2DE comprising a large number (four are shown) of n-sided electrode structures n-ES is brought together with a shaping layer F, here placed from above. As can be seen, the shaping layer F comprises a large number (four are shown) of protruding structures hS. The right half also shows a pressing layer A, which comprises an edge and an additional wall or a web on three sides (of course, several walls or webs or other structures as well as edges on all four sides or only on two sides or one are possible). The pressing layer A is then rotated with the edges and the web in the direction of the 2D electrode structure layer 2DE and shaping layer F and all three layers are brought together.

4 shows a second possible variant of positioning and bringing together the 2D electrode structure layer 2DE, shaping layer F and - instead of the pressing layer A - prefabricated socket vF. As can be seen, instead of the shaping layer F, a prefabricated socket vF is shown here, which is designed here in the form of a frame into which the 2D electrode structure layer 2DE can be inserted. In this example, the shaping layer F does not have an edge and in this illustration is inserted from above into the frame of the prefabricated socket vF and placed on the 2D electrode structure layer 2DE. In order to allow sufficient space for unfolding/setting up the n-side electrode structures n-ES, an assembly table is shown here, but this is not always necessary - depending on the height of the frame of the prefabricated socket vF. Furthermore, 4 the same as 3 .

Other, from the representations in 3 and 4 Different variants are possible. 5 then shows schematically the complete method according to the invention - for the sake of simplicity illustrated only by the variant of 3 , which is also preferred in some variants of the present invention. Accordingly, in the middle upper part of the figure it is illustrated that according to 3 the three layers, 2D electrode structure layer 2DE, shaping layer F and pressing layer A, are joined together. If pressing layer A is removed after pressing together, the 2D electrode structure layer 2DE and the shaping layer F are obtained, as shown in the right part. As can be seen there, the n-sided electrode structures n-ES have been pushed out of the plane of the 2D electrode structure layer 2DE and erected by pressing through the protruding structures hS of the shaping layer F upwards. In the lower right part of the figure, the angled arrow with thermometer symbol and °C indication illustrates that these two assembled layers are heated together in order to fix the erected n-sided electrode structures n-ES in their erected position. After removing shaping layer F, the finished three-dimensionally structured electrode layer 3DE is obtained, as shown in the middle, below the 5 you can see.

6 shows three different illustrations for n-side electrode structures, each parallel to the corresponding 2D electro the structural layers. 6a shows a 3-sided electrode structure 3n that is folded out of the plane of the 2D electrode structure layer 2DE. In this illustration, the 3-sided electrode structure 3n has three electrode surfaces EF and correspondingly three conductor tracks L that continue from the electrode surfaces EF. 6b shows a 4-sided electrode structure 4n (with a pointed short side; one could therefore also describe this electrode structure as 5-sided or 4-sided with a point) that is folded out of the plane of the 2D electrode structure layer 2DE. In this illustration, the 4-sided electrode structure 4n has four electrode surfaces EF and correspondingly four conductor tracks L that lead from the electrode surfaces EF. 6c shows a 5-sided electrode structure 5n that is folded out of the plane of the 2D electrode structure layer 2DE. In this illustration, the 5-sided electrode structure 5n has four electrode surfaces EF and correspondingly four conductor tracks L that continue from the electrode surfaces EF.

List of reference symbols:

2EN

2D electrode structure layer

3DE

three-dimensionally structured electrode layer

n-ES

n-side electrode structure

F

Forming position

A

Contact pressure

hS

protruding structures

vF

prefabricated frame (special case of the contact pressure)

M

Assembly table

T

Carrier substrate

1S

first substrate layer

1M

first, structured base metal layer (conductor tracks and electrode surfaces)

2M

second metal layer (optional)

P

Passivation layer

Z

Intermediate layer (optional)

eB

electrically conductive coating

EF

Electrode area

L

Conductor track

oZ

optional intermediate layer (Cr/AU/Cr, especially if 1S is PaC)

3n

3-sided electrode structure

4n

4-sided electrode structure

5n

5-sided electrode structure

QUOTES INCLUDED IN THE DESCRIPTION

This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions.

Cited non-patent literature

• Shin, H. et al.: “3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics,” Nat. Commun. 12, 492 (2021), https://doi.org/10.1038/s41467-020-20763-3 [0004]
• Socia et al.: “A flexible 3-dimensional microelectrode array for in vitro brain models,” Lab Chip., 2020, 20, 901-911. DOI https://doi.org/10.1039/C9LC01148J [0004]
• Liu et al. “Self-Healing Kirigami Assembly Strategy for Conformal Electronics,” Adv. Funct. Mater. 2022, 32, 2109214 [0019]
• Guo et al. “A flexible and stretchable Kirigami-inspired implantable neural probe with floating microsites for electrophysiology recordings,” 2020 IEEE 33rd International Conference on Micro Electro Mechanical Systems (MEMS), Vancouver, BC, Canada, 2020, pp. 350-353 [0019]

Claims (11)

Method for producing three-dimensionally structured electrode layers (3DE), which comprises or consists of the following method steps: A) Providing a flexible 2D electrode structure layer (2DE) comprising n-sided electrode structures (n-ES), one side of which is fixed to the structure layer and the remaining sides are completely or partially separated from the structure layer; B) Providing a three-dimensional shaping layer (F) comprising protruding structures (hS); C) Aligning the flexible 2D electrode structure layer (2DE) and the shaping layer (F) so that the respective protruding structures (hS) are assigned to respective n-sided electrode structures (n-ES); D) Pressing the 2D electrode structure layer (2DE) and the shaping layer (F) together, wherein the n-side electrode structures (n-ES) are pressed out of the plane of the 2D electrode structure layer (2DE) by the respective protruding structures (hS) of the shaping layer (F) and are raised in a rotating manner about a side fixed to the 2D electrode structure layer (2DE); E) Heating the joined layers so that the electrode structures (ES) of the electrode structure layer (2DE) are fixed in the position predetermined by the protruding structures (hS) of the shaping layer (F); F) Separating the layers from one another. Procedure according to Claim 1 , characterized in that the production of the flexible 2D electrode structure layer (2DE) comprises or consists of the following method steps: 1) providing a first flexible substrate layer (1S), preferably made of a thermoplastic material, on a carrier substrate (T); 2) applying a structured base metal layer (1M) comprising conductor tracks (L) and electrode surfaces (EF) to the first flexible substrate layer (1S); 3) optionally applying a flexible intermediate layer (Z), preferably made of a thermoplastic material, to the structured base metal layer (1M), comprising the sub-steps: 3a) applying a mask, preferably an etching mask, to the flexible intermediate layer (Z), 3b) exposing defined regions of the base metal layer (1M), preferably via reactive ion etching, of the regions to be removed defined by the mask, 3c) removing the mask, preferably the etching mask, 3d) introducing a second metal layer (2M) into the exposed areas of the flexible intermediate layer (Z); 4) applying a passivation layer (P), preferably made of a thermoplastic material, to the structured base metal layer or the flexible intermediate layer (Z); 5) Structuring of the passivation layer (P) comprising the sub-steps: 5a) applying a mask, preferably an etching mask, to the passivation layer (P), 5b) exposing defined regions of the passivation layer (P), preferably via reactive ion etching, of the regions defined by the mask to be removed, optionally several times, in particular if step 3) was not carried out, 5c) removing the mask, preferably an etching mask; 6) removing the carrier substrate (T); 7) if step 3) was not carried out, introducing a coating material into the exposed regions of the passivation layer (P) and onto the exposed regions of the electrode surfaces (EF). Procedure according to Claim 2 , characterized in that in the 2D electrode structure layer (2DE) before or after steps 1) to 8), the material of the 2D electrode structure layer (2DE) is completely or partially severed on n-1 sides of the respective n-sided electrode structures (n-ES). Procedure according to one of the Claims 1 until 3 , characterized in that the width and length of the respective protruding structure (hS) on the shaping layer (F) is less than the width and length of the respectively associated n-side electrode structure (n-ES), and wherein the height of each of the respective protruding structures (hS) is in particular half as high as the length of the respectively associated n-side electrode structure (n-ES). Procedure according to one of the Claims 1 until 4 , characterized in that the first substrate layer (S) of the electrode structure layer comprises or consists of a thin metal film or a thermoplastic material, preferably a thermoplastic material, in particular selected from the group consisting of parylene-C, polyimide, polyethylene terephthalate, polylactic acid, polytetrafluoroethylene, polystyrene and mixtures thereof, particularly preferably parylene-C or polyimide, in particular parylene-C. Procedure according to one of the Claims 1 until 5 , characterized in that the shaping layer (F) comprises or consists of metal, plastic or 3D-printable material, preferably material printable by means of 2-photon polymerization, particularly preferably based on (meth)acrylates curing via radical polymerization or based on photostructurable epoxy resins, in particular bisphenol A novolak epoxy resin, or also based on mixtures thereof. Procedure according to one of the Claims 1 until 6 , characterized in that the electrode structure layer comprises or consists of parylene-C, apart from the metals of the conductor tracks (L) and electrode surfaces (EF), and the shaping layer comprises or consists of material based on (meth)acrylates which harden via radical polymerization. Procedure according to one of the Claims 1 until 7 , characterized in that the electrodes are completely or partially coated with conductive materials, preferably selected from the group consisting of PEDOT:PSS, iridium oxide and mixtures thereof. Three-dimensionally structured electrode layers (3DE) manufactured by a process according to one of the Claims 1 until 8th . Implants or neuroimplants comprising three-dimensionally structured electrode layers (3DE) according to Claim 9 or consisting of these. Use of three-dimensionally structured electrode layers (3DE) according to Claim 9 or manufactured according to one of the Claims 1 until 7 as or for implants, neuroimplants, for measuring electrochemical properties, for measuring physical properties, for biosensing, or for impedance measurement.

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