Production, in particular kirigami-inspired production, of three-dimensional structured electrode layers

Abstract

The present invention relates to three-dimensional structured electrode layers, a method for producing them and use thereof, the production being preferably kirigami-inspired.

Description

[0001] Production of three-dimensionally structured electrode layers, especially using the Kirigami principle

[0002] All documents cited in the present application are incorporated by reference in their entirety into the present disclosure.

[0003] 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.

[0004] State of the art:

[0005] Flexible neuroimplants are implantable electronic devices that can measure and stimulate the neuronal activity of neural tissue in the peripheral and central nervous systems. Neuroimplants largely consist of a matrix of microelectrodes, which are usually conductive layers embedded and encapsulated between thin insulating polymer layers. The usually one-dimensional (ID) or two-dimensional (2D) electrode matrix is ​​either placed on the neural tissue or penetrates the tissue to measure and / or monitor various neuronal activities, e.g., of the brain, retina, or peripheral nerves. Flexible neural implants can be surface implants, consisting of a 2D matrix to map the xy positions on the surface of the neural tissue.To address cells at any x- and y-position, even within nerve tissue, penetrating threads or shafts exist, each consisting of an ID or 2D electrode matrix. An ID matrix corresponds to a single shaft to map the z-axis, and a 2D matrix corresponds to a group of shafts with fixed spacing 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 allows only 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.Although multiple recordings can be made per shaft (multiple z-positions), the design is planar, so that only recordings in x-z ​​or y-z are possible. In order to interact with the three-dimensional space of neural tissue, three-dimensional (3D) neuroimplants with as many recording electrodes as possible are required. These implants should then penetrate different layers of the tissue in order to stimulate cells from different layers and record their signals. Existing work with multiple recordings in three dimensions currently focuses mainly on in vitro, ex vivo, or in vivo experiments, for example in the cortex. If multiple ID or 2D matrices are implanted at different x-y positions, access to 3D space can be guaranteed. However, the following technical problems arise: i.Each probe must be implanted individually, increasing implantation time and the space required for front-end connections. ii. Arbitrary positions of individual ID 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 micromovements (e.g., due to respiration or the cardiovascular system). iii. Simultaneous access to the full 3D space is not possible.

[0006] Various three-dimensional neuroimplants in the mm and pm size range have already been manufactured using different methods. The two main methods used are the stacking of multiple 2D implants or the kirigami technique. i. Stacking of 2D implants: Here, multiple 2D implants are stacked on top of each other to generate a 3D implant. Typically, spacers are placed between the 2D implants to define a precise distance (e.g., 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). 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). Various methods exist in the literature for the folding process itself: a. Using ferromagnetic foils on the back of the shafts to fold the 2D design using a magnetic field. b. The shafts fold themselves (e.g., through electrostatic influences). c. Manual, mechanical folding of individual 2D shafts or several at once.

[0007] State-of-the-art solutions are either manual and sometimes very time-consuming processes that require the individual folding of individual shafts or the stacking of 2D samples one on top of the other. These processes are difficult or impossible to parallelize. Furthermore, cytotoxic materials, such as ferromagnetic metals like nickel, are used in combination with high-energy magnetic fields (100-400 mT), which are considered hazardous. Sometimes shafts fold back, or the folding angle is not always 90°, leading to unreliable results.

[0008] Therefore, we are still looking for a method that allows for the fast, parallelizable and reliable production of three-dimensional (neuro)implants.

[0009] 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 suitable three-dimensionally structured electrode arrangements 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.

[0010] Further tasks for the specialist arise from the following description.

[0011] These and other objects are achieved within the scope of the present invention by the subject matter of the independent claims.

[0012] Preferred embodiments emerge from the dependent claims and the following description.

[0013] Within the scope of the present invention, the term "comprise" also includes, as a particularly preferred embodiment, "consisting of"; this means that a corresponding list can contain (=comprise) further elements in addition to the explicitly mentioned elements, or it can contain precisely these elements (=consist of) (whereby unimportant elements such as screws, markings, etc. are not taken into account). For relative specifications such as top, bottom, left, right, or similar, the reference system within the scope of the present invention is assumed to be an observer standing upright on the ground in front of the object in question.

[0014] In the context of the present invention, the term "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.

[0015] In the context of the present invention, the term "flexible" means that the relevant elements, in particular the 2D electrode structure layer and the n-sided electrode structures, can be bent by 90° without being destroyed or losing their functionality. This is achieved by using materials with a corresponding flexural rigidity (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 flexural rigidity. In particular, examples are Parylene C or polyimide with Ti / Au or Ti / Au / Ti conductor tracks thereon.

[0016] In the context of the present invention, all quantities are to be understood as weights unless otherwise stated.

[0017] For the purposes of the present invention, the term "ambient temperature" means a temperature of 20°C. Unless otherwise stated, temperatures are in degrees Celsius (°C).

[0018] Unless otherwise stated, the reactions or process steps mentioned are carried out at atmospheric pressure, ie at approximately 1013 kPa.

[0019] The present invention relates to a method for producing three-dimensionally structured electrode layers or 3D microelectrode arrays (MEAs). These can be used as neural 3D implants based on flexible, polymeric, and optionally thermoplastic materials (e.g., Parylene C or polyimide). The implants consist of a 3D microelectrode matrix composed of flexible shafts, each of which contains at least one, but preferably several, electrode sites to establish an electrical coupling, particularly 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 respective electrode structures in the context of the manufacturing method of the present invention, i.e., by not providing elevations at their locations in the shaping layer to be used.

[0020] For production, cleanroom semiconductor technologies are first used to create the 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 commonly used in the art and known to those skilled in the art (see, for example, the abstracts by Liu et al. "Self-Healing Kirigami Assembly Strategy for Conformal Electronics", Adv. Funct. Mater. 2022, 32, 2109214 or by 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 forming process is used to simultaneously raise all 2D shafts 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 forming layer) for a kind of self-alignment (key-lock principle) in order to simultaneously fold the respective electrode shafts upwards at a previously freely defined angle (depending on the application). In principle, all angles are technically possible.According to the invention, however, angles between 45° and 135° are preferred, particularly preferably 70 to 110°, in particular 90°, in each case relative to the plane of the original 2D electrode structure layer.

[0021] 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 manufacturing and before folding. The MEA or the 3D probe is then placed in a heated environment (oven) to stabilize the 3D structures (thermoforming).

[0022] Within the scope of the present invention, the 2D structures of the electrode structure layers and the molds 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 cleanroom technology, microfabrication processes, thin-film techniques, and 3D printing with resolution in the pm range. Folding the 2D structures within the scope of the present invention is a very precise, self-adjusting process (lock-and-key principle), which is preferably carried out with pm accuracy, especially when the 2D electrode structure layer is pressed between the shaping layer and the pressing layer.

[0023] Firstly, the present invention relates to a method for producing three-dimensionally structured electrode layers, which comprises or consists of the following method steps:

[0024] 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;

[0025] B) providing a three-dimensional shaping layer comprising protruding structures;

[0026] 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;

[0027] D) pressing together the 2D electrode structure layer and the shaping layer, 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 in a rotating manner about a side fixed to the 2D electrode structure layer and are lifted (i.e. up to the fixed side);

[0028] 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;

[0029] F) Separating the layers from each other.

[0030] In preferred embodiments, the n-sided electrode structures (n-ES) are fixed to the structural layer with one side and the remaining sides partially separated from the structural layer and have at least two, preferably two, predetermined breaking points. Particularly preferred in the case of 5-sided electrode structures that have the shape of an obelisk's longitudinal section, two or three predetermined breaking points are preferred, one on each of the long side surfaces and optionally one at the tip. 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).

[0031] In preferred embodiments, the 2D electrode structure layers are self-supporting and therefore do not require any support layers during production or subsequent application. This particularly applies to 2D electrode structure layers with the dimensions specified below, and in particular to those based on / made of Parylene C.

[0032] It should be noted that in addition to Parylene C, other parylenes (e.g. Parylene N, Parylene D) can be used in embodiments of the present invention in addition to or alternatively to Parylene C.

[0033] In the context of the present invention, an n-sided electrode structure means that the respective structure has n sides, where n is an integer and 3 or greater. In principle, there is no upper limit for n, but above a certain value of n, the side fixed to the structural layer becomes too short to be stable. Therefore, n is preferably 3 to 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.

[0034] 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 farthest from the fixed end (short side) could be shaped as a point; the electrode structure would then have the shape of an obelisk's 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 considered sides.

[0035] According to the invention, one of the n sides is fixed to the structural layer. Around this side, which acts as a rotational axis, acting like a hinge, i.e., with a degree of freedom f = 1, the respective n-sided electrode structure is erected out of the plane of the electrode structure layer in step D) by the action of the protruding structures of the forming layer, thereby transforming the 2D electrode structure layer into a layer with a three-dimensional structure of the electrode structures.

[0036] The remaining sides are completely or partially separated from the structural 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 complicate the accuracy of further processing. In this case, the sides are separated as far as possible, and the non-separated areas remain as predetermined breaking points. Due to the partial separation, at least two predetermined breaking points remain; particularly preferred for 5-sided electrode structures that have the shape of an obelisk longitudinal section, two or three predetermined breaking points, one on each of the long side surfaces and optionally one at the tip.

[0037] In preferred variants of the present invention, at least two predetermined breaking points remain due to the partial severing, particularly preferably in the case of 5-sided electrode structures which have the shape of an obelisk longitudinal section, two or three predetermined breaking points, one each on the long side surfaces and optionally one at the tip.

[0038] The separation of the sides from the rest of the 2D electrode structure plate preferably occurs during the production of the 2D electrode structure layer. This preferably involves not a conventional cutting process, but rather 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" rotation axis). With high aspect ratios, predetermined breaking points are located in the recesses between the n-sided electrode structure and the 2D electrode structure layer. In these cases, the predetermined breaking points are preferably designed to break open under mechanical stress due to the protruding structures of the forming layer as soon as the 2D electrode structure layer and the forming layer are pressed together.

[0039] If the n-side electrode structures are long, for example longer than 300 pm, or if thin layers are used, for example a total thickness of 6 pm, it is preferred in some variants according to the invention to attach predetermined breaking points to the sides of the n-side electrode structures, which ensure stability, but which break open when the n-side electrode structures and the shaping layer are brought together and the n-side electrode structures are pressed out of the plane.

[0040] Although predetermined breaking points are common practice in mechanical engineering, for example, they are not used in thin-film processing or in neurotechnology / microtechnology. The use of predetermined breaking points for the production of neural implants is new, and n-sided electrode structures in a 2D electrode structure layer that, in addition to the one side with which they are fixed to the structure layer, are also connected to the 2D electrode structure layer with at least two predetermined breaking points are a subject of the present invention. These structures are an important feature in preferred variants, as they stabilize the 2D electrode layer (before they are fixed / shaped as part of the joined layers and subsequently heated), thus enabling successful production. The predetermined breaking points are points that are intentionally left unseparated when the sides of the n-sided electrode structures are separated from the rest of the 2D electrode structure plate.

[0041] In some preferred variants with 5-sided electrode structures, which have the shape of an obelisk's longitudinal section, two or three predetermined breaking points are present, one on each of the long side surfaces and optionally one at the tip. In preferred variants, these predetermined breaking points have a width, in the direction of the side surface where they are located, of 0.2 to 5 μm, preferably 1 to 2 μm.

[0042] The n-side electrode structures have electrode surfaces and conductor tracks, which are conductively connected to further conductor tracks and / or electrodes on the 2D electrode structure layer. The conductor tracks are configured such that they can withstand the erection without damage. Since the erection occurs in the direction of the conductor tracks, this is usually not problematic, 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 locations where the largest angles arise during erection, thus reducing the mechanical stress. Another possibility for further variants according to the invention is to reduce the layer thickness of the conductor tracks.

[0043] In variants of the present invention, it is preferred if the n-side electrode structures form regular n-corners, for example equilateral ones.

[0044] The aspect ratio of the n-sided 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.

[0045] 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.

[0046] 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.

[0047] The protruding structures of the forming layer can, in principle, have any shape. It must simply be ensured that these structures can push the n-side electrode structures away without being destroyed when the forming layer is pressed together with the electrode structure layer. Therefore, it is preferable for the protruding structures to be neither too sharp nor too hard, so that they do not damage the n-side electrode structures.

[0048] In preferred embodiments, the protruding structures are rectangular blocks with a pyramidal top end, or with a quadrangular prismatic top end. In practice, the shaping layer is then preferably arranged such that the slope of the upper surface of the quadrangular prismatic top end increases as viewed from the fully solid side of the n-side electrode structure.

[0049] 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, they enable the correct folding of the n-side electrode structures.

[0050] It is preferred if the width and length of the respective protruding structure on the forming layer are smaller than the width and length of the respectively associated n-side electrode structure. Thus, the protruding structures should, in particular, not have an excessive width and at least not an excessive length.

[0051] 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-sided electrode structure. A length that is not too small means that they are the same length as or less than the respective (assigned) n-sided electrode structures, but at least sufficiently long to raise the respective n-sided 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-sided electrode structure.

[0052] 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 to 50%. To reduce the contact areas, the protruding structures can be constructed as cuboids with an undercut.

[0053] 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.

[0054] In some preferred embodiments of the present invention, all n-sided 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-sided electrode structures.

[0055] In step E), the joined layers are heated to a temperature that permanently shapes the erected n-sided electrode structures. If the 2D electrode structure layer is based on a thermoplastic material, such as preferably Parylene C or polyimide, especially Parylene C, the temperature is raised to a temperature that is above the glass transition temperature of the polymer materials but below their melting point.

[0056] In the event that thermosets are used, i.e. curing is still to take place, the temperature is increased to a temperature at which the initiators contained split or at which the crosslinking reaction takes place.

[0057] Within the scope of the present invention, the production of the 2D electrode structure layer preferably comprises the following process steps or consists thereof:

[0058] 1) Providing a first flexible substrate layer, preferably made of a thermoplastic material, on a carrier substrate;

[0059] 2) Applying a structured base metal layer comprising conductor tracks and electrode surfaces to the first flexible substrate layer;

[0060] 3) optionally applying a flexible intermediate layer, preferably made of a thermoplastic material, to the structured base metal layer, comprising the substeps:

[0061] 3a) Applying a mask, preferably an etching mask, to the flexible intermediate layer,

[0062] 3b) Exposing defined areas of the base metal layer, preferably by reactive ion etching, of the areas to be removed defined by the mask,

[0063] 3c) removing the mask, preferably an etching mask, 3d) applying a second metal layer into the exposed areas of the flexible intermediate layer;

[0064] 4) Applying a passivation layer, preferably made of a thermoplastic material, to the structured base metal layer or the flexible intermediate layer;

[0065] 5) Structuring of the passivation layer comprising the sub-steps:

[0066] 5a) Applying a mask, preferably an etching mask, to the passivation layer,

[0067] 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,

[0068] 5c) Removing the mask, preferably etching mask;

[0069] 6) Removing the carrier substrate;

[0070] 7) If step 3) has not been performed, applying a coating material into the exposed areas of the passivation layer and onto the exposed areas of the electrode surfaces.

[0071] 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.

[0072] Step 2) is preferably carried out by

[0073] 2a) Applying and then selectively exposing a photoresist, for example using an exposure mask,

[0074] 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.

[0075] These are standard steps that are readily familiar to the expert and therefore do not need to be described further.

[0076] The base metal layer, i.e., the structured conductive layer, can be structured in various ways. Usually, these are (more or less) straight conductor paths connected to the electrode surfaces. As already mentioned, however, they 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.

[0077] In preferred variants of the present invention, the first substrate layer has a thickness of 0.5 pm to 10 pm, particularly preferably 2 pm to 8 pm, further preferably 4 pm to 6 pm, and in particular 5 pm. In preferred variants of the present invention, the intermediate layer has a thickness of 0.1 pm to 4 pm, particularly preferably 0.2 pm to 3 pm, further preferably 0.3 pm to 2 pm, and in particular 0.5 pm to 1 pm.

[0078] In preferred variants of the present invention, the passivation layer has a thickness of 0.5 pm to 10 pm, particularly preferably 2 pm to 8 pm, further preferably 4 pm to 6 pm and in particular 5 pm.

[0079] 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.

[0080] 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.

[0081] In preferred variants of the present invention, the applied electrode coating has a thickness 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, etc.).

[0082] In some preferred variants of the present invention, the electrode coating applied by spin coating, in particular when it is PEDOT:PSS, has a thickness between 350 nm and 1000 nm, preferably between 400 nm and 950 nm.

[0083] 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.

[0084] 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.

[0085] In yet further preferred variants of the present invention, the electrode coating applied by sputtering, particularly 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 completely or partially severed on n-1 sides of the respective n-sided electrode structures before or after steps 1) to 8), preferably as described above.

[0086] 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 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 its new shape upon cooling and removal of the mold (molding layer and optionally contact layer). Depending on the exact material used, a slow temperature ramp may be necessary during cooling 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.

[0087] In some preferred variants of the present invention, the materials for the metal films of the electrode structure layer are selected from the group consisting of gold, platinum, titanium, aluminum, and mixtures and alloys thereof.

[0088] 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 detergent 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 reliably (i.e., in particular, without them sticking / adhering to one another).

[0089] 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.

[0090] When biomedical applications are considered, it is preferable to use the thermoplastic materials mentioned, especially PaC and PI, due to their proven biocompatibility for invasive medical products.

[0091] In preferred embodiments of the method according to the invention, no support layers are used for the 2D electrode structure layer. More preferably, the 2D electrode structure layer is self-supporting.

[0092] The materials of the molding layer, in the 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 photoimageable epoxy-based resists, such as SU-8. A metallic molding layer can also be used. Other alternative methods for patterning the molding layer include 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).

[0093] However, other materials can also be used within the scope of the present invention, as long as they do not contain toxic ingredients. Examples of other usable materials include quartz, ceramics, and metals.

[0094] In preferred variants of the present invention, the shaping layer comprises or consists of metal, plastic or 3D-printed material, preferably starting from 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 epoxies, or also based on mixtures thereof.

[0095] 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 molding layer can comprise or consist of materials selected from the group consisting of metal, plastic, quartz, ceramic and mixtures thereof.

[0096] 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.

[0097] In preferred embodiments, the base plane of the shaping layer itself has a thickness of 10 pm to 40 pm, for example, 20 pm. The protruding structures 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 pm and 1200 pm, preferably between 300 pm and 1100 pm.

[0098] In preferred embodiments of the method of the present invention, the shaping layer comprises a frame whose inner dimensions are matched, preferably exactly, to the outer dimensions of the 2D electrode structure layer, and the alignment in step C) is carried out on this frame.

[0099] In further preferred embodiments of the present invention, the process according to the invention

[0100] Step C) divided into the steps

[0101] C) Aligning the flexible 2D electrode structure layer and the forming layer so that the respective protruding structures are assigned to respective n-side electrode structures,

[0102] CI) Providing a three-dimensional contact layer, preferably comprising elevations, particularly preferably comprising a frame and optionally at least one web,

[0103] C2) Aligning the flexible 2D electrode structure layer between the shaping layer and the pressing layer, so that the respective protruding structures of the shaping layer are assigned to respective n-sided electrode structures, and that the elevations of the pressing layer are assigned to respective regions of the 2D electrode structure layer that are not electrode structures, and wherein preferably the frame of the pressing layer, if present, has outer dimensions that correspond to the inner dimensions of a frame of the shaping layer, if present, in particular correspond exactly, and / or correspond to the outer dimensions of the 2D electrode structure layer, in particular correspond exactly; and

[0104] Step D) changed to

[0105] D) Pressing together the 2D electrode structure layer, the shaping layer and the pressing layer, wherein the n-side electrode structures are pressed out and lifted by the respective protruding structures of the shaping layer from the plane of the 2D electrode structure layer around a side fixed to the 2D electrode structure layer.

[0106] Alternatively, the method according to the invention may comprise:

[0107] Bl) Providing a contact pressure layer.

[0108] In this case, steps C) and D) change, ie they are extended to include the contact pressure and its use, as follows:

[0109] CI) 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;

[0110] Dl) Pressing together the 2D electrode structure layer, the shaping 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 shaping layer.

[0111] Within the scope of the present invention, the materials for the pressure layer can be selected from the same materials as those mentioned for the shaping layer. In preferred variants of the present invention, the pressure layer and shaping layer are made of the same material.

[0112] In preferred embodiments, the base plane of the pressing layer itself has a thickness of 10 pm to 40 pm, for example 20 pm. The protruding elements, i.e. edges, webs, etc., have heights (starting from the plane) depending on the respective n-sided electrode structures to be raised and can, in some preferred variants, be between 200 pm and 1200 pm, preferably between 300 pm and 1100 pm. In preferred variants of the present invention, the electrode structure layer comprises Parylene C or, apart from the metals of the conductor tracks and electrode surfaces, consists thereof, and comprises the shaping layer IP-S or consists thereof, and, if present, the pressing layer comprises IP-S or consists thereof.

[0113] In variants of the present invention, the electrodes are also 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 others 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.

[0114] 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.

[0115] Within the scope of the present invention, it is preferred in variants that electrodes or connectors are provided on at least one edge of the 2D electrode structure layer to enable the connection of the three-dimensionally structured electrode layer obtainable / obtained according to the invention to additional instruments. These can be applied during the metallization process during the production of the 2D electrode structure layer, or additionally later, for example, by soldering, clamping, or similar.

[0116] Within the scope of the present invention, it is preferred in variants that the n-sided 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 may be present per electrode structure (each independently of one another), preferably 2 to 32, particularly preferably 3 to 20, and in particular 4 or 16.

[0117] In particularly preferred variants of the present invention, the three-dimensionally structured electrode layers have 32 4-sided electrode structures of 225 pm length and 50 pm width, each having 4 electrode surfaces, the lowest of the four having a diameter of 25 pm and the remaining three having a diameter of 15 pm.

[0118] In further variants of the present invention, the three-dimensionally structured electrode layers have up to 128 n-sided electrode structures.

[0119] In other particularly preferred variants of the present invention, the three-dimensionally structured electrode layers have 4-sided electrode structures of 1000 pm to 1500 pm length, each having 16 electrode surfaces with a diameter of 15 pm.

[0120] The present invention further relates to three-dimensionally structured electrode layers produced by a method according to the invention as described above.

[0121] 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.

[0122] 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, for 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 that, 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 coated with PEDOT:PSS or iridium oxide at their openings.

[0123] 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 specifically stimulated.

[0124] The design of the KiriRet implant, in preferred variants, consists of 32 shafts, each 50 pm wide and 225 pm long. In preferred variants, each shaft has four electrodes; with a diameter of 25 pm for the electrode furthest from the electrode structure layer used for electrical stimulation, and 15 pm for the remaining 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 the scope of the present invention. Thus, in preferred variants, KiriCor implants are 1000 pm to 1500 pm long, and the electrodes have a diameter of 15 pm, so that up to 16 electrodes fit on each shaft.

[0125] Additionally, in some preferred embodiments of the present invention, the implants may contain at least one, preferably exactly one, internal reference electrode to perform electrophysiological or electrochemical measurements.

[0126] In 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.

[0127] In such preferred embodiments, in particular, a 5 pm thick PaC layer is first applied to a Si wafer and patterned with a Ti / Au / Ti layer for conductor tracks, electrodes, and contact pads. Then, a second 5 pm thick PaC layer is applied for encapsulation. In the next step, the folding cutouts as well as the electrodes and contact pads are opened. Subsequently, the 2D sample is detached from the Si substrate and soldered / fixed to a circuit board; in some preferred variants, this is done by flip-mounting. An example of this is the flip-chip process. In these variants, the flip-chip process can proceed in such a way that the circuit board is first heated using a hot 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 time, the hot plate is cooled (to 160°C), and then the 2D probe is fixed with its contact pads 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.

[0128] The folding mold is preferably 3D printed using a 2-photon polymerization technique.

[0129] 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 shorter height is also possible in principle, but is 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 on 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 exactly corresponds to the size of the 2D structure (electrode structure layer) and is thus used for alignment / adjustment.The upper part of the 3D mold in this variant of the present invention is a structure consisting of a frame and walls (webs) 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 (by the upper mold ensuring 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 and lock principle, i.e. the inner and outer dimensions of the frames of the shaping layer and the pressing layer are preferably coordinated with one another such that the outer dimensions of one frame fit exactly into the inner dimensions of the other.

[0130] Alternatively, and in other preferred variants of the present invention, it is equally possible to use only a one-piece mold, which corresponds to the just-described lower part of the mold (i.e., the forming layer). The just-described upper part, 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 - each for pressing the electrode structure layer onto the forming layer - or also laterally attached (to be attached) (tension) clamps or other devices suitable for pressing the electrode structure layer and the forming layer together in such a way that the n-sided electrode structures can be erected by the protruding structures.

[0131] After fabricating the 3D structure (molding layer) and the 2D sample (electrode structure layer), 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 pressing / compression device helps to fold the shafts in a controlled manner. To facilitate the precise alignment / adjustment of the 2D structure and the 3D mold, frames / protruding edges of the 3D mold are used in preferred embodiments.

[0132] The assembled layers are then heated together to thermally fix the n-side electrode structures. This can essentially be achieved by using a thermoplastic material for the base of the electrode structure layer, which material undergoes a corresponding thermoplastic deformation that is retained after cooling. Or, an as yet uncured thermoset or an as yet uncured thermoset mixture can be used for the base of the electrode structure layer, so that it hardens upon heating 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.

[0133] After the shaped, three-dimensionally structured electrode layer has been separated from the 3D mold, in further preferred variants of the present invention, the electrodes can be coated in a further manufacturing step with electrolytically deposited conductive substances, particularly preferably PEDOT:PSS or iridium oxide (IrO x ) to improve the electrical properties. The finished three-dimensionally structured electrode layer can then be used as a (neuro)implant in electrophysiological experiments, for example.

[0134] The inventive method 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 depositable by electrodeposition or physical deposition, such as PEDOT:PSS or IrO, are also suitable for the electrodes. xconceivable. The precise 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 pm to 25 pm can be used for the electrodes to ensure the resolution of individual cells. However, when using small electrodes and optimized manufacturing processes, thinner shafts of less than 50 pm are also possible and are therefore preferred in some other embodiments of the present invention.

[0135] The inventive method 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-aligning structures, i.e., the electrode structures are brought into defined positions by pressing the various layers together, in particular by precisely coordinated dimensions and frames, it is possible to produce several 3D probes simultaneously. Such 3D probes can be used, for example, in electrophysiological experiments for recording cell signals from various nerve tissues such as the brain, peripheral nerves, or retina, and for electrically stimulating the corresponding nerve cells. Similarly, the structures produced according to the invention can be used, for example, in / with / for 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 pm range.

[0136] 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".Conductor track layers corresponding to Cr / Au, Cr / Ti, Cr / Au / Cr, or Cr / Pt / Cr can also be used within the scope of the present invention.

[0137] The three-dimensionally structured electrode layers produced according to the invention were successfully used as intraretinal 3D implants in in vitro experiments and experiments with cadavers, thus comprehensively validating their functionality.

[0138] 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 process according to the invention is fast and reliable because, unlike 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 to fix the positions of the electrode structures using thermoforming.

[0139] A further particular advantage within the scope of the present invention is 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 using CAD files, electrode structure layers can be produced in which the respective electrode structures can be arranged in any desired positions. Furthermore, 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 thereby are therefore particularly versatile.

[0140] The individual parts of the devices / systems according to the invention are operatively connected to one another in a conventional and known manner.

[0141] In preferred embodiments of the present invention, this does not relate to the therapeutic treatment of humans or animals.

[0142] The various embodiments of the present invention, for example - but not exclusively - those of the various dependent claims or individual embodiments described in the figures, can be combined with one another in any desired manner, provided that such combinations do not contradict one another.

[0143] The invention will now be further explained with reference to the following non-limiting examples.

[0144] 1 - Manufacturing of flexible 2D electrode structure layers:

[0145] The fabrication of flexible 2D electrode structures with a kirigami design (with recesses but not folded) involved the sequential deposition of a 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 the PaC deposition) were performed in a certified cleanroom environment to ensure stable fabrication.

[0146] 1. Deposition of the first flexible substrate layer

[0147] A first 5 pm 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).

[0148] 2. first metallization

[0149] In a second step, metallization was performed using a lift-off process. This involved structuring the metal base layer for contact areas, leads, and electrodes. First, a negative photoresist AZ LNR-003 (containing, among other ingredients, hexakis(methoxymethyl)melamine and l-methoxy-2-propanol acetate; MicroChemicals GmbH, Germany) was spin-coated 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 cured at 320 mJ / cm 2The wafer was exposed to UV light with a wavelength of 375 nm using a maskless exposure system (MLA 150, Heidelberg Instruments, Germany) with a Defoc setting of 2 and a CDB (critical dimension bias) of 800. Following exposure, a heating step at 100°C for 1.5 minutes on a direct contact hot plate was performed, followed by 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. Subsequently, the wafer was evaporated with a metal layer, with 20 nm of Ti, 100 nm Au, and 10 nm Ti being 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.Subsequently, a lift-off process was performed in an acetone bath for 2.5 hours to wash off the sacrificial material and photoresist. After the lift-off, the wafer was rinsed in isopropanol for 2 minutes and dried with a nitrogen gun.

[0150] 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 carried out.

[0151] 3. Flexible intermediate layer (optional) In some designs, step 3 was performed, in others it was not. In cases where it was not performed, the process continued with step 4.

[0152] A second flexible PaC layer (PaC interlayer) with a thickness of 0.5 pm to 1 μm (1-2 g PaC dimer) was deposited as described in step 1. Subsequently, the PaC was etched at the electrode openings by reactive ion etching (RIE). This process is described in detail below in step 5.

[0153] A second metallization step was then performed to directly add an electrode coating. A resist stack consisting of LOR3B (MicroChem Corp, USA; a resist based on polydimethylglutarimide) and negative photoresist nLOF 2020 (MicroChemicals GmbH, Germany; a negative photoresist containing PGMEA (l-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, followed by a bake-out step at 150°C for 5 minutes on a direct-contact hotplate. This was 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 device.In the maskless exposure system MLA150, the photoresist was exposed at 670 mJ / cm. 2 with a Defoc setting of 0 and UV light at a wavelength of 375 nm. Post-exposure heating was then carried out at 102°C for 2 minutes on a direct-contact hot plate, 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 carried out 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.

[0154] Subsequently, a Ti layer with a thickness of 10 nm and a Pt layer with a thickness of 100 nm were additionally 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 / Ch gas mixture of 100 / 6 sccm (standard cubic centimeters per minute) and a DC power of 100 W.

[0155] 4. Deposition of a flexible passivation layer A flexible PaC passivation layer with a thickness of 5 pm was deposited analogously to step 1.

[0156] 5. Recesses, shape and passivation openings

[0157] In this step, the flexible polymer was patterned. 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 pads and those of the electrodes. First, an etch mask was patterned with a thick positive photoresist at least 1.5 times the thickness of the polymer to be etched. An etch mask was patterned 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 using a maskless exposure system with a dose of 350 mJ / cm 2, a Defoc setting of 2, and a CDB of -800 with UV light at a wavelength of 375 nm. Subsequently, after exposure, the wafer was subjected to annealing using a hot plate at 90°C for 1 minute, followed by a 2-minute development step with AZ 326 MIF. After patterning the etch mask, an RIE step was performed with an O2 / CF4 gas mixture of 36 / 4 sccm at 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 Oz / 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.The first bath uses a low-power ultrasonic bath 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.

[0158] 6. Detachment and chip assembly

[0159] The 2D electrode structure layer was detached from the silicon wafer using water droplets and tweezers. These were then mounted on a printed circuit board using the flip-chip assembly method. First, the circuit board 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 circuit board, allowing the formation of liquid bumps on each contact pad. By lowering the temperature to 160°C, the flexible probes were aligned and placed onto the liquid solder paste accumulations, which 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 (e.g. 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.

[0160] 7. Applying the electrode coating (optional)

[0161] 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))) were electrodeposited.

[0162] 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.

[0163] 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 at a sweep rate of 100 mV / s and potential cutoffs between -0.6 V and -0.9 V against a Ag / AgCl reference electrode. Then, the surface of the 2D electrode structure layer (also referred to as a 2D kirigami device) was activated with O2 plasma at a pressure of 0.8 mbar and a power of 80 W for 3 minutes. Electrochemical polymerization of EDOT:PSS on the Au-based electrodes was then performed by chronoamperometry using a constant potential of 1 V for 20 seconds.

[0164] Other conductive materials, such as IrOx, could also be deposited electrochemically using cyclic voltammetry or chronoamperometry. 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 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 grown by chronoamperometry at a constant potential of 0.55 V against an Ag / AgCl reference electrode for 60 minutes to 100 minutes.

[0165] Example 2 - Manufacturing of the molds (molding layers):

[0166] A Photonic Professional GT2 two-photon polymerization 3D printer from NanoScribe GmbH was used to produce the molds. The process involves focusing an erbium-doped femtosecond laser source (central wavelength 780 nm) into a droplet of photoresin. If the laser power exceeds a certain threshold, the photoresin polymerizes only at the laser's focal point, allowing for the creation of truly complex structures with high resolution.

[0167] To obtain such forms, three main steps were carried out:

[0168] 1. 3D design:

[0169] The molds were designed using CAD software and converted into printing instructions using Describe (software from NanoScribe GmbH).

[0170] 2. 3D printing:

[0171] A Zeiss 25X NA0.8 objective lens was used, and IP-S (NanoScribe GmbH, Germany) was used as the photopolymer material. Using NanoScribe's default print recipe, which is designed for the combination of a 25X objective lens and IP-S, the slicing distance was set to 1 pm and the hatching distance to 500 nm. The scan speed of 100,000 pm / s, laser power of 100%, and power scaling of 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 lens used (400 pm x 400 pm x 400 pm for the 25X objective lens) without stage movement, many blocks were printed side by side to build the entire structure. To ensure adhesion between the individual blocks, the block overlay was set to 2 pm in all dimensions.The height of each block was set to 200 pm to ensure that the lens, which has a working distance of 380 pm, did not penetrate the structure. The shapes were printed on a 2.5 cm x 2.5 cm glass substrate that had been previously coated with 3 pm 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.

[0172] In this step, a raised edge was also printed around the entire surface, which will later be important for aligning the different layers to each other.

[0173] 3. Development:

[0174] A development step after the printing process washed away any remaining unpolymerized photopolymer. The samples were placed in a bath of fresh Mr-Dev 600 developer (a solvent-based developer from Micro Resist Technology 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 these steps were performed in a certified cleanroom environment to ensure a stable manufacturing environment.

[0175] Example 3 - Completion of the flexible three-dimensional structured electrode layers

[0176] After fabricating the flexible 2D electrode layers and the molds (forming layers and pressure layers), assembly followed to produce a three-dimensionally structured electrode layer. To allow the shafts to be folded at a 90° angle, two molds were used in this example (however, the mold fabricated in Example 2, i.e., the forming layer alone, is also sufficient). First, 2D electrode layers fabricated according to Example 1 were placed onto molds fabricated according to Example 2 (Fig. 3A). This was done either with the aid 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 outer edges had been formed during the production of the mold according to Example 2, along which the alignment could take place. This was because the mold was manufactured in such a way that the 2D electrode layers fit perfectly into the edges of the mold (forming layer), which formed a kind of frame, whereby the 2D electrode layers were held by the edges. In the next step, tweezers were used to grip a further, second mold (pressing layer), which was placed from above on top of the 2D electrode layers with its edges facing downwards (Fig. 3B). This second mold was manufactured according to Example 2, except that no individual highlighting in the form of blocks (which would have been aligned with the shafts of the 2D electrode layers) was printed, but rather outer edges that were dimensioned so that the mold, with the outer edges of its (frame), fit exactly inside the edges (frame) of the lower, first mold (i.e., the forming layer).In addition, the additional, second shapes (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 essential 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 over the elevations of the shaping layer or the shafts of the 2D probes, because otherwise, the shafts of the 2D probes could not unfold.

[0177] The placement of the additional, second molds (pressure layers) was performed in some cases with the aid of a micromanipulator and in others with steady hands (with the aid of a microscope if necessary). In each case, the upper mold was lowered slowly to facilitate more precise placement. Since the edges of the upper mold fit precisely into the lower mold, alignment was facilitated (as explained). Once the additional, second mold (pressure layer) was in place, it was lowered and all three layers were pressed together until all shafts lifted simultaneously.

[0178] In all cases, the different layers were arranged parallel to each other and their parallelism was maintained even when compressed.

[0179] 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 socket, which fixed the layer in place (Fig. 4A). In addition, the socket had cross braces to ensure even pressure distribution during the subsequent folding. The socket was placed on an assembly table (with a recess in the middle) to create space for the shafts to be folded; alternatively, the socket can of course also be designed to leave sufficient space for the shafts to be unfolded, for example by means of appropriately high edges. In the next step, the mold produced according to Example 2 (forming layer) was placed with the elevations facing forward on the 2D electrode layers (Fig. 4B). Here, too, the edges of the socket helped to improve alignment.Once the mold (forming layer) is correctly positioned, it is pressed down onto the 2D electrode layers so that the protrusions of the forming layer push the stems out of the plane of the 2D probe, and all stems are folded simultaneously. In this variant, the prefabricated socket replaces the clamping layer from the first variant; the prefabricated socket can therefore be considered a special case of the clamping layer.

[0180] The assembled layers were then heated to secure the erected shafts in position. The layers were heated at a ramp rate as slow as possible, approximately 5°C / min. The temperature was then held at 150°C to 160°C for 60 minutes. The layers were allowed to cool completely (approximately 120 minutes) before being separated.

[0181] 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 at approximately a 90° angle to the layer plane.

[0182] These could then be used, for example, as neuroimplants. For in vitro and ex vivo applications, these could be used directly as manufactured; for in vivo applications, they still had to be sterilized (e.g., using ethanol, UV irradiation, ethylene oxide, hydrogen peroxide, plasma, or autoclaving).

[0183] 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, particularly where the features are described accordingly. Furthermore, the figures are not to be interpreted in a limiting manner and are not true to scale. Furthermore, the figures do not contain all features that conventional devices / systems have, but are reduced to the features essential to the present invention and its understanding. For example, screws, hoses, brackets, etc. are not shown or not shown in detail.

[0184] The same reference symbols / numbers mean the same or equivalent device parts.

[0185] Figure 1 schematically shows the sequence for producing 2D electrode structure layers 2DE, as 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 a section with one electrode structure is shown here as an example; however, the 2D electrode structure layer (usually) has a multitude 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 IS 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) IM is then applied thereon.According to the above description, at the end of step 2), this layer only consists of conductor tracks L and electrode surfaces 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, for example, protective polymer; 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 IM is 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 resulting product, 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 shown in Figures 3 or 4. For the sake of clarity, in this figure, as well as in the other figures, the individual components are not labeled in all steps, but only in individual ones; however, identical representations show identical elements.

[0186] Figure 2 illustrates the same as Fig. 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 here the intermediate layer Z is first applied, whereby the first metal layer IM remains partially free, or is exposed again, so that at the end of step 3) a partially exposed first metal layer IM results. According to step 3d), a second metal layer 2M is then applied and remains afterwards. Here it is shown that the second metal layer 2M partially lies 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 its 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 somewhat lower. The remaining steps correspond to those shown in Fig. 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 Figures 3 or 4.

[0187] Figures 3 to 5 illustrate the method according to the invention for producing three-dimensionally structured electrode layers (i.e. a type of Kirigami process).

[0188] Figure 3 shows a first possible variant of the positioning and bringing together of the 2D electrode structure layer 2DE, the shaping layer F and the contact pressure layer A. The left half of the figure shows how a 2D electrode structure layer 2DE comprising a plurality (four are shown) of n-sided electrode structures n-ES is brought together with a shaping layer F, here applied from above. As can be seen, the shaping layer F comprises a plurality (four are shown) protruding structures hS. The right half also shows a contact pressure layer A, which comprises an edge and an additional wall or web on three sides (of course, several walls or webs or other structures as well as edges on all four sides or just on two sides or one are possible). The contact pressure layer A is then rotated with the edges and the web in the direction of the 2D electrode structure layer 2DE and the shaping layer F and all three layers are brought together.Figure 4 shows a second possible variant for positioning and assembling the 2D electrode structure layer 2DE, the shaping layer F, and—instead of the pressing layer A—the prefabricated socket vF, which is a special embodiment of the pressing layer. 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 include 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. To allow sufficient clearance for unfolding / positioning the n-side electrode structures n-ES, an assembly table is shown here, although this is not always necessary depending on the height of the frame of the prefabricated socket vF. Otherwise, Fig. 4 shows the same as Fig. 3.

[0189] Further variants deviating from those shown in Fig. 3 and 4 are possible.

[0190] Fig. 5 then schematically shows the complete method according to the invention - for the sake of simplicity illustrated only using the variant of Fig. 3, which is also preferred in some variants of the present invention. Accordingly, the middle upper part of the figure illustrates that, according to Fig. 3, the three layers, 2D electrode structure layer 2DE, shaping layer F and pressing layer A, are joined together. If the pressing layer A is removed after pressing together, the 2D electrode structure layer 2DE is obtained and the shaping layer F is assembled, as shown in the right-hand part. As can be seen there, the n-sided electrode structures n-ES have been pressed upwards out of the plane of the 2D electrode structure layer 2DE and erected by the protruding structures hS of the shaping layer F being pushed through.In the lower right part of the figure, the angled arrow with the thermometer symbol and the °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 the shaping layer F, the finished three-dimensional structured electrode layer 3DE is obtained, as can be seen in the middle, bottom of Fig. 5. Figure 6 shows three different illustrations for n-sided electrode structures, each seen parallel to the corresponding 2D electrode structure layers. Figure 6a shows a 3-sided electrode structure 3n that has been 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 lead from the electrode surfaces EF.Figure 6b shows a 4-sided electrode structure 4n (with a pointed short side; one could therefore also refer to 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 extend from the electrode surfaces EF. Figure 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 extend from the electrode surfaces EF.

[0191] List of reference symbols:

[0192] 2DE 2D electrode structure layer

[0193] 3DE three-dimensional structured electrode layer n-ES n-sided electrode structure F forming layer

[0194] A contact pressure layer hS protruding structures vF prefabricated frame (special case of the contact pressure layer)

[0195] M assembly table

[0196] T carrier substrate

[0197] IS first substrate layer

[0198] IM first, structured base metal layer (conductor tracks and electrode surfaces) 2M second metal layer (optional)

[0199] P passivation layer

[0200] Z Intermediate layer (optional) eB Electrically conductive coating

[0201] EF Electrode area L Conductor track oZ Optional intermediate layer (Cr / AU / Cr, especially if IS is PaC)

[0202] 3n 3-sided electrode structure

[0203] 4n 4-sided electrode structure 5n 5-sided electrode structure

Claims

Claims:

1. A method for producing three-dimensionally structured electrode layers (3DE), which comprises or consists of the following process 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) such that the respective protruding structures (hS) are assigned to respective n-side 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 and raised by the respective protruding structures (hS) of the shaping layer (F) from the plane of the 2D electrode structure layer (2DE) 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 each other, 2. Method according to claim 1, characterized in that the n-sided electrode structures (n-ES) are fixed with one side to the structural layer and the remaining sides are partially separated from the structural layer and have at least two, preferably two, predetermined breaking points, particularly preferably in the case of 5-sided electrode structures which have the shape of an obelisk longitudinal section, two or three predetermined breaking points, one in each case on the long side surfaces and optionally one at the tip.

3. Method according to claim 1 or 2, characterized in that the shaping layer (F) has a frame which is matched in its inner dimensions to the outer dimensions of the 2D electrode structure layer (2DE), preferably exactly, and the alignment in step C) is carried out on this frame.

4. Method according to one of claims 1 to 3, wherein step C) is divided into the steps C) aligning the flexible 2D electrode structure layer (2DE) and the forming layer (F) so that the respective protruding structures (hS) are assigned to respective n-side electrode structures (n-ES), CI) Providing a three-dimensional pressure layer (A), preferably comprising elevations, particularly preferably comprising a frame and optionally at least one web, C2) Aligning the flexible 2D electrode structure layer (2DE) between the shaping layer (F) and the pressing layer (A) such that the respective protruding structures (hS) of the shaping layer (F) are assigned to respective n-sided electrode structures (n-ES), and that the elevations of the pressing layer (A) are assigned to respective regions of the 2D electrode structure layer (2DE) that are not electrode structures (n-ES), and wherein preferably the frame of the pressing layer (A), if present, has outer dimensions that correspond to the inner dimensions of a frame of the shaping layer (F), if present, and / or correspond to the outer dimensions of the 2D electrode structure layer (2DE), in particular correspond exactly; and Step D) is changed to D) Pressing together the 2D electrode structure layer (2DE), the shaping layer (F) and the pressing layer (A), wherein the n-sided electrode structures (n-ES) are pressed out and lifted by the respective protruding structures (hS) of the shaping layer (F) from the plane of the 2D electrode structure layer (2DE) around a side fixed to the 2D electrode structure layer (2DE).

5. Method according to one of claims 1 to 3, additionally comprising Bl) Providing a contact pressure and changing steps C) and D) into: CI) 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; Dl) Pressing together the 2D electrode structure layer, the shaping 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 shaping layer.

6. Method according to one of claims 1 to 5, 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 (IS), preferably made of a thin metal film or a thermoplastic material, on a carrier substrate (T); 2) Applying a structured base metal layer (IM) comprising conductor tracks (L) and electrode surfaces (EF) to the first flexible substrate layer (IS); 3) optionally applying a flexible intermediate layer (Z), preferably made of a thermoplastic material, to the structured base metal layer (IM), comprising the substeps: 3a) Applying a mask, preferably an etching mask, to the flexible intermediate layer (Z), 3b) Exposing defined areas of the base metal layer (IM), preferably by reactive ion etching, of the areas to be removed defined by the mask, 3c) Removing the mask, preferably 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 areas of the passivation layer (P), preferably by reactive ion etching, of the areas defined by the mask to be removed, optionally, in particular if step 3) has not been carried out, several times, 5c) Removing the mask, preferably etching mask; 6) Removing the carrier substrate (T); 7) if step 3) has not been performed, insert a Coating material into the exposed areas of the passivation layer (P) and the exposed areas of the electrode surfaces (EF).

7. The method according to claim 6, 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).

8. Method according to claim 7, characterized in that at least two predetermined breaking points remain as a result of the partial severing, particularly preferably in the case of 5-sided electrode structures which have the shape of an obelisk longitudinal section, two or three predetermined breaking points, one each on the long side surfaces and optionally one at the tip.

9. Method according to one of claims 1 to 8, 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).

10. Method according to one of claims 1 to 9, characterized in that the first substrate layer (IS) of the electrode structure layer comprises a thin Metal film or a thermoplastic material comprises or consists of, 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.

11. The method according to any one of claims 1 to 10, 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.

12. Method according to one of claims 1 to 11, 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 curing via radical polymerization.

13. Method according to one of claims 1 to 12, 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.

14. Method according to one of claims 1 to 13, characterized in that no support layers are used for the 2D electrode structure layer (2DE), preferably the 2D electrode structure layer (2DE) is self-supporting.

15. Three-dimensionally structured electrode layers (3DE) produced by a method according to one of claims 1 to 13 or 1 to 14.

16. Implants or neuroimplants comprising three-dimensionally structured electrode layers (3DE) according to claim 15 or consisting of these.

17. Use of three-dimensionally structured electrode layers (3DE) according to claim 15 or manufactured according to one of claims 1 to 14 as or for implants, neuroimplants, for measuring electrochemical properties, for measuring physical properties, biosensing, or impedance measurement.

Images