Microelectrodes for insertion into soft tissue

Abstract

The present invention relates inter alia to a microelectrode comprising an electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element being disposed within a casing of electrically insulating non-degradable material comprising a first structural component and optionally a second structural component, the distal non-insulating portion of the conductive element being encased (surrounded) by a casing forming a distal chamber, a void / lumen being present between the insulating portion of the conductive element and the first structural component, the void / lumen allowing the conductive element to slide relative to the casing, and the casing of the distal chamber comprising at least one electrically conductive bridge electrically coupling the distal chamber with adjacent soft tissue.

Description

[Technical field]

[0001] The present invention relates to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, in particular nervous, endocrine, muscular and connective tissue, comprising an elongated (rectangular) electrically conductive element (electrode) with an insulating and non-insulating portion. At least the non-insulating portion of the conductive element is disposed within a casing (envelope, sleeve, sheath) of electrically insulating non-degradable material forming a chamber. The casing of the chamber is configured to electrically couple (connect) the non-insulating portion of the conductive element with the soft tissue. The electrical coupling may be achieved by an electrically conductive bridge, such as a fluid and non-fluid conductive bridge. A distinctive feature of the microelectrode is that the casing is not engaged with the conductive element. Thus, the casing and the conductive element can move relative to each other. The casing is movably disposed around the conductive element by at least a first structural part, which may form part of the casing or be a separate part. The present invention further encompasses a microelectrode probe, an array of microelectrodes and / or microelectrode probes, and a method for manufacturing the microelectrodes / microelectrode probes. The various aspects of the invention are preferably applied for neuromodulation and sensing of neural, endocrine and muscular function, but can also be used for localized drug delivery. [Background technology]

[0002] Implantable microelectrodes and microelectrode sets have a wide range of applications in human and veterinary medicine.

[0003] Microelectrodes implanted in nervous, endocrine or muscular tissues, whether forming a single implant or applying to implants with multiple microelectrodes such as bundles or arrays of microelectrodes, require a connection to a control device located outside the tissue to be monitored and / or stimulated. This connection is generally made by thin, insulated, flexible conductors. The conductors bridge tissues of different types and stiffness, making them subject to the effects of periodic displacements of the tissues relative to each other, caused for example by breathing, heartbeat, head and spinal movement, position of the brain relative to the skull, and age-related changes. This type of tissue movement can affect other thin and flexible implants as well, such as microfibers or microfilaments, especially optical microelectrodes and catheters.

[0004] An example of a situation where the movement of tissues relative to each other may be observed is when the lead bridges the skull and the brain through spaces including the dura, arachnoid, cerebrospinal fluid, and pia mater. Other examples are when the lead bridges the vertebrae and the spinal cord, the muscles and adjacent fibrous sheets and connective tissues, and the peripheral nerves (such as the vagus nerve) and the surrounding tissues. These movements of tissues relative to each other result in various forces (e.g. shear and tear forces) acting between the implanted lead and the tissues in the border areas, with the risk of causing permanent local inflammation and tissue damage. Furthermore, this type of force and e.g. shear forces may affect the position of the electrical contacts (i.e. the non-insulated parts) of the implanted microelectrode relative to the surrounding cells / tissues. Unstable position of the electrode contacts relative to the target tissues may also result in fluctuations of the particular neuronal, endocrine, or muscular elements being recorded or stimulated over time, which is particularly problematic when monitoring and analyzing long-term changes in such signals or when stable long-term stimulation of such elements is required.

[0005] WO 2022 / 005386A1 discloses a microelectrode comprising a casing disposed around a conductive electrode, where a distal non-insulated section of the conductive electrode is encased in the casing forming a distal chamber. The casing is slidably mounted around the conductive electrode. Moreover, the casing has an opening that provides a fluidic electrical connection. WO 2022 / 005386A1 does not disclose an electrical connection between the soft tissue and the encased electrode without an exchange of charged particles (ions) across the casing. Furthermore, WO 2022 / 005386A1 fails to disclose a microelectrode comprising a casing, a first and a second structural part, where the casing, the first and the second structural part form a distal chamber surrounding the non-insulated portion of the electrode, and the casing has an opening distal to the second structural part. Additionally, WO 2022 / 005386 A1 fails to disclose a microelectrode comprising a non-insulated electrode portion confined within a chamber bounded by a casing, a first and a second structural part, said non-insulated electrode portion being disposed within an inner casing of an electrically conductive, non-degradable material.

[0006] The microelectrode of WO 2022 / 005386 A1 provides a configuration in which the conductive element is enveloped from adjacent soft tissue by a casing of a flexible non-degradable material, the casing being provided with one or more openings through which electrical contact with the tissue is established by transfer of charged particles (ions). Furthermore, the casing is decoupled from the conductive element allowing the casing to move relative to the conductive element. Decoupling of the casing from the conductive element significantly improves the positional stability of the opening in the casing relative to the surrounding tissue, and thus also the specificity and resolution of recording and stimulation. Over time, the adjacent tissue still has a tendency to grow inside the chamber to the point where the soft tissue sticks to the non-insulated conductive element, as well as penetrating the casing through the opening. Sticking of the soft tissue to the non-insulated conductive element (which exhibits a sliding movement inside the casing) compromises the positional stability of the tissue to be recorded / stimulated. Movement of the non-insulated portion of the conductive element connected to the tissue also moves the tissue adjacent to the opening and outside the casing, causing variations in the signal-to-noise ratio and waveform of the recorded neuronal signal, as well as variable stimulation efficacy. The casing of the microelectrode of WO 2022 / 005386 A1 is also associated with the conductive element such that the distal tip of the non-insulated portion of the conductive element does not touch or penetrate the casing. An embodiment of the microelectrode of WO 2022 / 005386 A1 comprises first and second structural parts separate from the casing. The casing distal to the second structural part is closed. Movement of the conductive element in the distal direction will increase the pressure in the casing and, if applicable, also in the casing distal to the optional second structural part. Similarly, movement of the conductive element in the proximal direction will decrease the pressure in the volume and, if applicable, also in the casing distal to the optional second structural part. These pressure changes can affect the positional stability of the tissue immediately outside the opening in the casing. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2022 / 005386A1 [Patent Document 2] U.S. Patent Application Publication No. US2020 / 0,086,111(A1) Summary of the Invention

[0008] Some embodiments of the microelectrodes disclosed herein include an elongate electrically conductive element having a proximal end and a distal end, the electrically conductive element having insulated proximal and distal portions, the proximal insulating portion extending distally from the proximal end and the distal insulating portion extending proximally from the distal end, the proximal and distal portions being separated by an uninsulated portion of the conductive element, at least the uninsulated portion of the conductive element being essentially centrally disposed within a casing of an electrically insulating non-degradable material, the microelectrode further comprising first and second structural components extending radially between the casing and the conductive element, the first structural component being movably disposed about the proximal insulating portion and the second structural component being movably disposed about the distal insulating portion, the casing, the first and second structural components forming a distal chamber, the casing having an opening distal to the second structural component, and the casing configured to electrically couple the uninsulated portion of the conductive element with soft tissue. Such embodiments improve the axial adjustability of the conductive element relative to the casing, taking into account the microelectrodes of WO 2022 / 005386 A1, since the opening in the casing distal to the second structural part prevents pressure changes when the conductive element is moving relative to the casing. These embodiments thus improve the freedom of movement of the conductive element relative to the casing, which further improves the positional stabilization of the casing where the non-insulated portion of the conductive element is in contact with adjacent tissue, thereby improving the positional stability of the electrical coupling of the casing to the surrounding tissue, and in particular the specificity and resolution of recording and stimulation.

[0009] The object of the present invention over the prior art, and in particular over WO 2022 / 005386 A1, is to improve or possibly maintain positional stabilization over time of the casing's target tissue and, by inference, the electrical contacts of the implanted microelectrode, preferably maintaining positional stabilization of the electrical contacts over the life of the implantable microelectrode.A further object of the present invention is to provide a microelectrode that can be at least partially embedded (implanted) in soft tissue or placed at least partially adjacent to soft tissue, in particular nervous, muscular or endocrine tissue, and electrically connected to a control device for recording and stimulation that is located outside the target tissue, whereby tissue pain due to tissue movement contacting the microelectrode or contacting leads electrically connecting the microelectrode to the electrode control device that is located outside the tissue of implantation is avoided or at least reduced.

[0010] Another object of the present invention is to prevent or reduce unintended displacement of the electrical contacts of an implanted microelectrode from a target tissue due to forces acting on the electrical leads that electrically connect the microelectrode to an electronic controller for recording and / or stimulation.

[0011] It is yet another object of the present invention to increase the lateral freedom of movement of an implanted microelectrode.

[0012] It is a further object of the present invention to provide a microelectrode probe or an array of such probes for implantation in or placed at least partially adjacent to soft tissue, in particular nervous, muscular, or endocrine tissue, which is capable of being converted into a microelectrode or array of microelectrodes by contact with aqueous body fluids.

[0013] Yet a further object is to provide a microelectrode or array of microelectrodes for placement on (or adjacent to) the surface of the brain, spinal cord, dorsal root ganglion, peripheral nerves, endocrine organs, or muscles for monitoring and / or stimulation of said structures.

[0014] It is an additional object of the present invention to provide methods for manufacturing the microelectrode tips and arrays of microelectrode tips of the present invention.

[0015] A further object is to provide drug delivery to the same, or essentially the same, tissue from a flexible compartment implanted in the soft tissue.

[0016] Another object of the present invention is to avoid or minimize physical contact between the conductive elements, particularly the non-insulated portions of the conductive elements, and adjacent soft tissue, while allowing the conductive elements (including the non-insulated portions and the insulated portions) to move inside the casing and positionally stabilize the casing relative to the surrounding tissue.

[0017] Other objects will be apparent from the following description.

[0018] Explanation of some common terms The following terms are used repeatedly to define embodiments of the present invention.

[0019] The spatial terms "distal" and "proximal" The terms "proximal" and "distal" are used to designate entities of different aspects of the invention relative to another optional device electrically connected to the microelectrode and located outside the target tissue (the target tissue is where stimulation / recording will occur). For example, relative to a microelectrode, a proximal entity or a proximal part / portion / section / region of the entity is closer (in terms of the length of the connecting microelectrode / conductor) to the optional electrical device than a distal entity or a distal part / portion / section / region of the entity. The transition from a proximal part / portion / section / region of the entity to a distal part / portion / section / region of the entity should not be understood to be a very specific region, rather the division of entities into proximal and distal or the designation of entities as proximal and distal is a means to locate such entities relative to each other. Within the context of the present invention, another optional device is typically an electrode control device located outside the tissue of the implant, electrically connected to the microelectrode by a conductor. The connection point of the lead to the microelectrode defines the proximal zone of said microelectrode. The opposite end of the microelectrode to the lead connection point is therefore the distal end of the microelectrode.

[0020] microelectrode Within the context of the present disclosure, a microelectrode is a device for registering / recording / monitoring or stimulating various soft tissues, including nervous tissue, endocrine tissue, exocrine tissue, muscle tissue, cardiac tissue, connective tissue, and retina. A microelectrode comprises a partially electrically insulated longitudinal (rectangular) electrically conductive element (conductive electrode). At least one non-insulating portion of the electrically conductive element is disposed within a casing of electrically insulating non-degradable material, the casing comprising at least one first structural part, the structural part may form part of the casing. The casing, the first and optionally the second structural part surround / enclose the non-insulating portion of the conductive element forming a chamber. The first and optionally the second structural part movably engage the casing with respect to the conductive element. Typically, the first and optionally the second structural part movably engage with the insulating portion of the conductive element. In some embodiments, at least a portion of the first structural part is movably disposed around a proximal insulating portion of the conductive element. In some embodiments, at least a portion of the first structural part is movably disposed around a proximal insulating portion of the conductive element, and at least a second structural part is movably disposed around a distal insulating portion of the conductive element. The inner diameter of the first and optional second structural parts is equal to or preferably greater than the diameter of the insulating portion of the conductive element. The casing, the first and optional second structural parts substantially surround (enclose) the non-insulated portion of the conductive element forming a chamber, which in some embodiments is referred to as the distal chamber. By surrounding or enclosing, it should be understood that the casing, the first structural part and the optional second structural part essentially separate the chamber from the soft tissue when the microelectrode is placed adjacent to or within the soft tissue. Essentially separating the chamber from the soft tissue means that the casing reduces or eliminates the ability of tissue to penetrate the casing and grow inside the distal chamber.

[0021] In some embodiments, the first structural component divides the casing into a distal chamber and a proximal compartment.

[0022] An important feature of the microelectrode is the ability of the casing to move relative to the longitudinal electrically conducting element. Thus, the casing is not permanently affixed to the conducting element. Instead, the casing is decoupled and separated from the conducting element, allowing the casing to move primarily axially relative to the conducting element.

[0023] The microelectrode is preferably flexible. A flexible microelectrode has the ability to accommodate movement of the surrounding tissue. The flexibility of the microelectrode is provided in part by the flexible casing, in part by the decoupling of the casing from the conductive element, and in part by the flexibility of the conductive element. The radial flexibility of the microelectrode is provided in part by the flexibility of the casing and also by the decoupling of the casing from the conductive element, and the axial flexibility of the microelectrode is provided by the ability of the casing to move relative to the conductive element. Typically, flexible microelectrodes are difficult or perhaps impossible to implant in soft tissue without the use of a core providing component. Thus, the term flexibility can also include the inability to successfully implant the microelectrode in soft tissue.

[0024] Preferably, the major axis of the microelectrode is collinear with and appropriately coincides with the elongate conductive element, the conductive element being essentially centrally located within the casing.

[0025] Microelectrode probe Microelectrode probes are typically microelectrodes that are more easily implantable in tissue and include materials that provide enhanced structural rigidity during insertion into soft tissue, but disintegrate and / or dissolve upon insertion into soft tissue.

[0026] Thus, microelectrodes or arrays as disclosed herein generally do not possess structural features that prevent them from collapsing and / or dissolving upon insertion into soft tissue.

[0027] First and optionally second structural components The casing comprises at least a first structural part and optionally a second structural part. In some embodiments, the first and optional second structural parts may form part of the casing and are integral components of the casing. Alternatively, and in some embodiments, the first and optional second structural parts are separate and distinct from the casing. When the first and optional second structural parts are separate from the casing, these structural parts are preferably made from a material different from the material of the casing.

[0028] The first and optional second structural components preferably extend radially between the casing and the conductive element, typically between the casing and an insulating portion of the conductive element.

[0029] If the first and optional second structural parts are an integral part of the casing, there must be a lumen / space, suitably an annular gap, between the first and optionally second structural parts and the conductive element, preferably between the first and optional second structural parts and the insulating part of the conductive element.

[0030] If the first and optional second structural parts are separate from the casing, the first and optional second structural parts may be permanently engaged to the insulating portions of the conductive element, while the casing is decoupled (separated) from the first and optional second structural parts, allowing the casing to move primarily axially relative to the first and optional second structural parts, and by inference also relative to the conductive element. Alternatively, the first and optional second structural parts are permanently affixed to the casing, but decoupled from the insulating portions of the conductive element.

[0031] As used herein, substantially surrounding or encasing the non-insulated portions of the conductive elements means that the casing is configured to minimize, or possibly eliminate, tissue growth inside the distal chamber, while at the same time allowing the non-insulated portions of the conductive elements to electrically engage / couple with the tissue surrounding the casing.

[0032] The centres of the first and second structural components are preferably linearly aligned along the major axis.

[0033] Distal Chamber, Proximal Compartment The distal chamber is a volume defined by a casing (sometimes also called an envelope, sleeve, sheath) of electrically insulating, non-degradable material and at least a first structural component that surrounds or encases the non-insulated (axial) portion of the conductive element. The distal chamber extends distally from the first structural component. In embodiments that include a first and second structural component, the distal chamber is a volume defined (bounded) by the casing and the first and second structural components. In embodiments that include only the first structural component, the distal casing is defined (bounded) by the casing and the first structural component.

[0034] The distal chamber is preferably essentially electrically insulated from adjacent soft tissue, except for electrical connections contained in the casing, such as at least one conductive bridge. As described in further detail herein, when the casing is separated from the conductive element, some electrical current will necessarily leak through gaps between the first and optionally second structural components and the conductive element, or between the first and optionally second structural components and the casing, depending on the embodiment.

[0035] In some embodiments, the first structural part divides the casing into a distal chamber and a proximal compartment, the volume of the proximal compartment extending proximally relative to the first structural part. Suitably, the proximal compartment receives the insulating portion of the conductive element.

[0036] non-degradable material Some parts of the microelectrodes, microelectrode tips, arrays, such as the casing and the insulation of the conductive elements, are non-degradable materials. The microelectrodes are placed in animal and human tissue. The tissue contains various compounds that can affect the material of the microelectrode. A non-degradable material is one that essentially maintains its intended function throughout the life of the implanted microelectrode, which can range from several years to several decades. Thus, a non-degradable material maintains its function throughout the life of the microelectrode, typically at least 1, 2, 3, 4, 5, 10, 15, 20 years.

[0037] Inner casing Some embodiments of the microelectrode include an inner casing. The inner casing is disposed around the non-insulated conductive element and inside the chamber formed by the casing and at least one structural component. The material of the inner casing is electrically conductive and preferably non-degradable. The outer diameter of the inner casing is equal to or less than the inner diameter of the casing. The inner diameter of the inner casing is greater than the diameter of the distal and proximal insulated portions of the conductive element. The inner casing preferably has an annular cross-section. The purpose of the inner casing is to prevent or at least significantly reduce the possibility of tissue sticking to the non-insulated conductive element.

[0038] Electrical Connection Electrical coupling is the ability to electrically couple an electrode enclosed in the casing with soft tissue adjacent to the casing. The enclosed non-insulated portion of the conductive element can electrically interact with the adjacent soft tissue by a conductive bridge selected from either or both of a) an exchange of charged particles across the casing, referred to herein as a fluidic electrically conductive bridge, or b) by electrically coupling the enclosed electrode with the soft tissue in the absence of an exchange of charged particles (ions and electrons) across the casing, referred to herein as an electrically conductive bridge (also referred to as a non-fluidic electrically conductive bridge).

[0039] Electrically Conductive Bridge An electrically conductive bridge as used herein is an entity that allows an enclosed non-insulated portion of a conductive element to electrically interact with adjacent soft tissue without the exchange of charged particles. An electrically conductive bridge may also be configured to exchange charged particles across a casing. An example of an electrically conductive bridge that further exchanges charged particles across a casing is a hollow conductive filament, or a conductive mesh or net. An electrically conductive bridge that does not further have the ability to exchange charged particles across a casing is referred to as a non-fluidic electrically conductive bridge.

[0040] soft tissue In its broadest definition, soft tissue relates to any sentient organism's soft tissue, excluding hard tissues such as bony (bone) tissue. More specifically, soft tissue encompasses any soft tissue that provides an electric fingerprint that can be monitored, and / or any tissue that is sensitive to electrical stimulation. Subgroups of soft tissues of particular interest form nervous tissue, endocrine tissue, muscle tissue, connective tissue, and retina. Soft tissue also encompasses hollow fluid spaces such as the ventricles of the heart.

[0041] The terms "implanted" and "implanted" can be used interchangeably.

[0042] The present invention relates to microelectrodes, microelectrode probes, different arrays of microelectrodes and / or microelectrode probes, and methods for the manufacture of microelectrodes, microelectrode probes and arrays.

[0043] Overview of some embodiments of microelectrodes All of the embodiments of the microelectrodes disclosed herein share the following general features: The non-insulated portion of the elongate conductive element further comprises an insulated portion disposed within a casing of a flexible, non-degradable material. At least the first structural part may form part of the casing, or alternatively the first structural part as an entirely separate entity, separate from the casing. The casing is movably associated with the conductive element.

[0044] Any one and some of the preferred features of any one of the embodiments in this section may be combined with any one of the embodiments unless the preferred features introduce an inconsistency.

[0045] Some embodiments (denoted A) have the following features in addition to the general features. An elongate conductive element includes a distal uninsulated portion and a proximal insulated portion. · The first structural component is present but the second structural component is not. At least the uninsulated portion of the conductive element is disposed within a casing of a flexible, non-degradable material. The casing and the first structural part define a distal chamber. The casing includes an electrically conductive bridge electrically coupling the uninsulated portion of the conductive element with soft tissue adjacent the distal chamber and exterior to the casing.

[0046] Any and all of the following features may be combined with the features of embodiment A above.

[0047] The casing and the first structural component essentially electrically isolate / insulate the distal chamber from adjacent soft tissue, except for the electrically conductive bridge.

[0048] A distal uninsulated portion extends proximally from the distal end to the proximal insulated portion.

[0049] A distal uninsulated portion extending proximally from the distal end to the proximal insulated portion is essentially electrically insulated from the soft tissue by the casing and the first structural component, except for the electrically conductive bridge.

[0050] The conductive element is essentially centrally located within the casing by the first structural part.

[0051] A first structural component extends radially between the casing and the proximal insulating portion of the conductive element.

[0052] The first structural part does not form part of the casing.

[0053] A first structural component is movably disposed about the insulating portion of the conductive element.

[0054] A first structural component is movably disposed about the insulating portion of the conductive element and permanently affixed to the casing.

[0055] A first structural component is permanently affixed to the insulating portion of the conductive element, and a casing is movably disposed about the first structural component.

[0056] A first structural component is permanently engaged with the casing to provide electrical insulation.

[0057] The first structural component has an annular cross-section.

[0058] A first structural part has an annular cross-section with an inner diameter larger than the diameter of the proximal insulating portion of the conductive element and preferably an outer diameter essentially the same as the inner diameter of the casing.

[0059] At least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive, non-degradable material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

[0060] Some embodiments (denoted B) have the following features in addition to the general features. An elongate conductive element includes a distal uninsulated portion and a proximal insulated portion. There are primary and secondary structural components. At least the uninsulated portion of the conductive element is disposed within a casing of a flexible, non-degradable material. The casing, the first and second structural components define a distal chamber. The casing includes an electrically conductive bridge electrically coupling the uninsulated portion of the conductive element with soft tissue adjacent the distal chamber and exterior to the casing.

[0061] Any and all of the following features may be combined with the features of embodiment B above.

[0062] The casing, the first and second structural components essentially electrically isolate / insulate the distal chamber from adjacent soft tissue, except for the electrically conductive bridge.

[0063] A distal uninsulated portion extends proximally from the distal end to the proximal insulated portion.

[0064] A distal uninsulated portion extending proximally from the distal end to the proximal insulated portion is essentially electrically insulated from the soft tissue by the casing and the first structural component, except for the electrically conductive bridge.

[0065] A conductive element is essentially centrally disposed within the casing by the first and second structural parts.

[0066] The first and second structural components do not form part of the casing.

[0067] A first structural component extends radially between the casing and the insulating portion of the conductive element.

[0068] A second structural component extends radially between the casing and the distal uninsulated portion of the conductive element.

[0069] A first structural component is movably disposed about the proximal insulating portion of the conductive element.

[0070] A second structural component is movably disposed about the distal uninsulated portion of the conductive element.

[0071] The first and second structural components are permanently engaged with the casing to provide electrical insulation.

[0072] The first and second structural components have annular cross-sections.

[0073] The centers of the first and second structural components are linearly aligned along the major axis.

[0074] A first structural part has an annular cross-section with an inner diameter larger than the diameter of the proximal insulating portion of the conductive element and preferably an outer diameter essentially the same as the inner diameter of the casing.

[0075] A second structural component has an annular cross-section with an inner diameter greater than the diameter of the distal uninsulated portion of the conductive element, and preferably with an outer diameter essentially the same as the inner diameter of the casing.

[0076] At least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive, non-degradable material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

[0077] Some embodiments (denoted C) have the following features in addition to the general features. an elongate conductive element having proximal and distal ends with insulated proximal and distal portions, the proximal insulated portion extending distally from the proximal end and the distal insulated portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element; There are primary and secondary structural components. At least the uninsulated portion of the conductive element is disposed within a casing of a flexible, non-degradable material. The casing and the first structural part define a distal chamber. The casing includes an electrically conductive bridge electrically coupling the uninsulated portion of the conductive element with soft tissue adjacent the distal chamber and exterior to the casing. The insulated distal portion of the conductive element projects through an opening at the distal end of the casing, the opening at the distal end of the casing serving to radially stabilize the distal insulated portion of the conductive element. The distal end of the casing and the opening act as a second structural part.

[0078] Any and all of the following features may be combined with the features of embodiment C above.

[0079] The casing and the first and second structural components essentially electrically isolate / insulate the distal chamber from adjacent soft tissue, except for the electrically conductive bridge.

[0080] A conductive element is essentially centrally disposed within the casing by the first and second structural parts.

[0081] First and second structural components extend radially between the casing and the proximal and distal insulating portions of the conductive element.

[0082] First and second structural components are movably disposed about the insulating portion of the conductive element.

[0083] The first structural part does not form part of the casing.

[0084] A first structural component is movably disposed about the proximal insulating portion of the conductive element and permanently affixed to the casing.

[0085] A first structural component is permanently affixed to the proximal insulating portion of the conductive element, and a casing is movably disposed about the first structural component.

[0086] A first structural component is permanently engaged with the casing to provide electrical insulation.

[0087] The first structural component has an annular cross-section.

[0088] A first structural part has an annular cross-section with an inner diameter larger than the diameter of the proximal insulating portion of the conductive element and preferably an outer diameter essentially the same as the inner diameter of the casing.

[0089] The diameter of the opening at the distal end of the casing is larger than the diameter of the distal insulating portion of the conductive element.

[0090] At least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive, non-degradable material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

[0091] Some embodiments (denoted D) have the following features in addition to the general features. an elongate conductive element having proximal and distal ends with insulated proximal and distal portions, the proximal insulated portion extending distally from the proximal end and the distal insulated portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element; There are primary and secondary structural components. At least the uninsulated portion of the conductive element is disposed within a casing of a flexible, non-degradable material. The casing, the first and second structural components define a distal chamber. The casing includes an opening distal to the second structural component. The casing includes an electrically conductive bridge electrically coupling the uninsulated portion of the conductive element with soft tissue adjacent the distal chamber and exterior to the casing.

[0092] Any and all of the following features may be combined with the features of embodiment D above.

[0093] A conductive element is essentially centrally disposed within the casing by the first and second structural parts.

[0094] First and second structural components extend radially between the casing and the insulated proximal and distal insulated portions, respectively, of the conductive element.

[0095] The first and second structural components do not form part of the casing.

[0096] First and second structural components are movably disposed about the proximal and distal insulating portions, respectively, of the conductive element.

[0097] The first and second structural components are permanently engaged with the casing to provide electrical insulation.

[0098] The first and second structural components have annular cross-sections.

[0099] The first and second structural components have annular cross-sections with inner diameters larger than the diameters of the proximal and distal insulating portions of the conductive element, and preferably with outer diameters essentially the same as the inner diameter of the casing.

[0100] At least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive, non-degradable material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

[0101] The centers of the first and second structural components are linearly aligned along the major axis.

[0102] Some embodiments (denoted E) have the following features in addition to the general features. an elongate conductive element having proximal and distal ends with insulated proximal and distal portions, the proximal insulated portion extending distally from the proximal end and the distal insulated portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element; at least the uninsulated portion of the conductive element is essentially centrally positioned within a casing of electrically insulating non-degradable material by first and second structural parts extending radially between the casing and the conductive element, the first structural part being movably positioned around the proximal insulating portion and the second structural part being positioned around the distal insulating portion. The casing, the first and second structural components form a distal chamber that encases the uninsulated portion of the conductive element. The casing has an opening distal to the second structural component. The casing is configured to electrically couple the uninsulated portion of the conductive element to the soft tissue.

[0103] Any and all of the following features may be combined with the features of embodiment E above.

[0104] At least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive, preferably non-degradable material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

[0105] The first and second structural components do not form part of the casing.

[0106] The first and second structural components are permanently engaged with the casing to provide electrical insulation.

[0107] An inner casing has an annular cross-section with an inside diameter equal to or greater than the diameter of the insulated proximal and distal portions.

[0108] The first and second structural components have annular cross-sections.

[0109] The first and second structural components have annular cross-sections with inner diameters larger than the diameters of the proximal and distal insulating portions of the conductive element, and preferably with outer diameters essentially the same as the inner diameter of the casing.

[0110] Presentation of some more detailed examples The present invention includes, for example, the following examples.

[0111] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising an electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element being disposed within a casing (envelope, sheath) of an electrically insulating, non-degradable material, the non-insulated portion of the element being enclosed (surrounded) by a casing forming a distal chamber within which the conductive element is axially slidable, the casing of the distal chamber comprising an electrically conductive bridge electrically connecting the distal chamber to adjacent soft tissue, the casing comprising a first structural part along which the electrically insulating portion of the conductive element is axially slidable.

[0112] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, in particular nervous, endocrine, and muscular tissue, the microelectrode comprising an electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element being disposed within a casing (envelope, sheath) of an electrically insulating non-degradable material, the casing comprising a first structural part, the first structural part may form part of the casing, the non-insulated portion of the conductive element being enveloped (surrounded) by a casing forming a distal chamber, the first structural part being separated from the conductive element, the casing of the distal chamber comprising at least one conductive bridge electrically connecting the distal chamber to adjacent soft tissue.

[0113] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising an elongated electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope) of an electrically insulating, non-degradable material, the casing comprising a first structural component, the first structural component may form a part of the casing, the non-insulated portion of the conductive element being encased by the casing and the first structural component forming a distal chamber, the casing and the first structural component essentially separating the non-insulated portion of the conductive element from adjacent soft tissue, the first structural component being separated from the conductive element, the distal chamber comprising an electrically conductive bridge electrically connecting the distal chamber to the adjacent soft tissue.

[0114] A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising a rectangular (longitudinal) electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) comprising an electrically insulating non-degradable material, the non-insulating portion of the element being enveloped (surrounded) by a casing forming a distal chamber, the casing of the distal chamber having a) a hole in the casing, b) a filament-like structure penetrating the casing of the distal chamber, c) a distal chamber having a casing of the ... a transverse member forming part of a casing of the conductive element, the transverse member being selected from one of a sheet comprising a conductive material and an ion permeable membrane (sheet-like structure) allowing ion transfer between the distal chamber and the adjacent soft tissue forming part of the distal chamber, the casing comprising a first structural part slidably mounted [engaged] around at least a portion of the electrically insulating portion of the conductive element, the first structural part allowing the casing to slide axially relative to the electrically conductive element.

[0115] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, in particular neural, endocrine, and muscular tissue, the microelectrode comprising an elongate electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of an electrically insulating, non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, the conductive element being essentially centrally disposed within the casing by at least a first structural part which may form part of the casing, the first structural part extending radially between the casing and the conductive element, the casing and the first structural part forming a distal chamber around the non-insulated portion of the conductive element, the casing and the first structural part essentially partitioning the distal chamber from adjacent soft tissue, the first structural part being detached from the conductive element or the casing being detached from the first structural part, the casing comprising at least one electrically conductive bridge, the bridge being configured to electrically connect the chamber with the adjacent soft tissue.

[0116] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising an elongate electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of an electrically insulating, non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, the conductive element being essentially centrally disposed within the casing by at least a first structural part which may form part of the casing, the first structural part extending radially between the casing and the conductive element, the casing and the first structural part forming a distal chamber around the non-insulated portion of the conductive element, the casing and the first structural part essentially partitioning the distal chamber from adjacent soft tissue, the casing being movably associated with the conductive element, the casing comprising at least one electrically conductive bridge, the bridge configured to electrically connect the distal chamber with the adjacent soft tissue.

[0117] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising an elongate electrically conductive element having a proximal end and a distal end, the electrically conductive element comprising insulated proximal and distal portions, the proximal insulating portion extending distally from the proximal end and the distal insulating portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element, at least the non-insulated portion of the conductive element being made of an electrically insulating, non-degradable material. 1. A microelectrode disposed essentially centrally within a casing, the microelectrode further comprising first and second structural parts, the first and second structural parts extending radially between the casing and the conductive element, the first structural part being movably disposed about a proximal insulating portion and the second structural part being movably disposed about a distal insulating portion, the casing, the first and second structural parts forming a distal chamber, the casing having an opening distal to the second structural part, and the casing configured to electrically couple an uninsulated portion of the conductive element with soft tissue.

[0118] 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising a conductive element having distal and proximal uninsulated portions and an insulated portion between the distal and proximal uninsulated portions, at least the proximal uninsulated portion of the conductive element being essentially centrally disposed within a casing of electrically insulating non-degradable material, the microelectrode further comprising a first structural part which may form a part of the casing, the first structural part being movably disposed about the insulated portion of the conductive element, the casing and the first structural part essentially electrically insulating the proximal uninsulated portion from the soft tissue, the interior of the casing comprising an electrically conductive material electrically coupling the proximal uninsulated section of the conductive element, the electrically conductive material being in electrical communication with an insulated conductor affixed to a proximal end of the casing.

[0119] Disclosure of specific features in more detail Electrical Connection The casing of the microelectrode surrounding the non-insulated portion of the conductive element is configured to electrically couple the non-insulated portion of the conductive element with the soft tissue. The non-insulated conductive element in the distal chamber surrounded by the casing and at least one structural component electrically interacts with the adjacent soft tissue by an electrical coupling / bridge based on one or both of a) an exchange of charged particles across the casing, referred to herein as a fluidic electrical conductive bridge, or b) electrically connecting the surrounded non-insulated portion of the conductive element with the soft tissue in the absence of an exchange of charged particles (ions and electrons) across the casing, referred to herein as an electrical conductive bridge.

[0120] The electrically conductive bridge may also exhibit the ability to exchange charged particles across the casing.

[0121] The distal compartment comprises at least one conductive medium for the non-insulated portion of the conductive element to communicate electrically through an electrical connection contained in the casing. Such a medium may be selected from an aqueous electrolyte and / or a conductive gel, such as a conductive hydrogel. According to one embodiment, the medium may be a combination of an aqueous electrolyte and a conductive gel. The conductive medium may already be contained in the distal chamber before insertion. Alternatively, the conductive medium can be formed upon insertion into the soft tissue by diffusion of soft tissue fluid inside the distal chamber. The soft tissue fluid can diffuse into the distal chamber through a lumen / void / gap between the first structural part and the optional second structural part, between the structural part and the insulating part of the conductive element, or between the structural part and the casing (depending on the particular embodiment). The soft tissue fluid can also diffuse into the distal chamber through a fluid conductive bridge.

[0122] The design of the electrical connection of the casing is governed, inter alia, by the application of the microelectrode. If high specificity and / or resolution is required, the total surface area of ​​the conductive bridge or bridges is limited. A limited area of ​​electrical connection is useful, for example, for monitoring or stimulating individual or a limited number of neurons in a nervous tissue.

[0123] For other applications, it may be beneficial for the electrical coupling to cover multiple areas of the casing, such as multiple conductive bridges, the combined number of which may cover a substantial area of ​​the casing, or alternatively, the electrical coupling may cover a substantial area of ​​the casing with a single conductive bridge.

[0124] The electrical connection of the casing can be obtained by a fluidic and / or an electrically conductive bridge.

[0125] The electrically conductive bridge may also include a fluidic electrically conductive bridge.

[0126] The specific fluidic electrically conductive bridge does not include non-fluidic electrically conductive bridges.

[0127] Some embodiments comprise at least an electrically conductive bridge and may further comprise at least one fluidic electrically conductive bridge.

[0128] Some embodiments include any type of electrical connection disclosed herein.

[0129] The electrical link / bridge is typically disposed transversely to the distal chamber (transversely to the major axis of the conductive element).

[0130] The electrically conductive bridge may be selected from a hollow conductive element, a conductive filament-like structure penetrating the casing of the distal chamber, a transverse member, a transverse sheet-like member, a transverse sheet-like conductive member, a conductive sheet-like structure, and a conductive non-degradable ion-permeable membrane.

[0131] The electrically conductive bridge is preferably non-degradable in tissue fluids.

[0132] The electrically conductive filamentary structure penetrating the distal casing may be selected from hollow conductive filamentary structures (filaments with a central tube). Conductive hollow filamentary structures are representative of electrically conductive bridges with fluidic electrically conductive bridges. Non-conductive hollow filamentary structures are only capable of electrically coupling the non-insulated portion of the conductive element with adjacent soft tissue by exchanging charged particles across the casing, and therefore fall under the definition of a fluidic electrically conductive bridge. Conductive filamentary structures may also be solid.

[0133] The electrically conductive bridge can comprise a metal, a metal alloy, and / or a conductive polymer, and / or a carbon-containing material, such as graphene, graphite, and carbon nanotubes. According to a further aspect, the electrically conductive bridge can be configured to exhibit a significant surface area in contact with the fluid in the distal chamber and in contact with the adjacent soft tissue. An electrically conductive bridge configured with a large surface area in contact with the adjacent soft tissue and the fluid in the distal chamber can provide more effective information transmission between the microelectrodes and the adjacent soft tissue.

[0134] The conductive filamentary electrically conductive bridges are preferably arranged relative to the casing such that the angle of the electrically conductive filaments relative to the normal to the casing surface is greater than 45°, suitably greater than 70°. The angle of the average orbit of the majority of the electrically conductive bridges is greater than 70°, preferably greater than 60°.

[0135] The fluidic-electrical bridge may be an opening, preferably a lateral opening, in the distal casing. The opening may be about 1 μm 2 Preferably, the area of ​​the openings in the distal chamber casing is less than about 1 μm 2 of the openings, up to the combined area of ​​all the openings in the distal chamber casing. 2 From about 150,000 μm 2 The apertures may range from about 20 μm2 to the combined area of ​​all of the above apertures. The apertures are preferably configured to prevent occlusion of the apertures by tissue growth. It has been observed that glial cells can cover the small apertures and then, to some extent, insulate the interior of the distal chamber from the surrounding neurons. The preferred range for the aperture area is about 20 μm2. 2 From about 2000 μm 2 Up to approximately 100 μm 2 From about 1500 μm 2 That is until now.

[0136] According to a further aspect, the casing of the distal chamber comprises a plurality of openings in the distal casing. According to a further aspect, the maximum number of openings in the distal chamber is given by the maximum number of openings that do not significantly compromise the structural rigidity / structure of the distal casing.

[0137] The number of openings is determined in part by the volume of the distal chamber, the type of casing material, and the mode of operation of the microelectrode. When using a microelectrode for soft tissue stimulation, it may be preferred that the microelectrode have a larger total area of ​​openings (a larger number of openings) than when using the microelectrode for soft tissue monitoring. If the microelectrode operates in both stimulation and monitoring modes, the total area of ​​the openings (number of openings) should preferably be within a range that meets the needs of both the stimulation and monitoring modes. The upper number of openings is governed in part by the structural rigidity of the distal chamber (the casing that encases the distal chamber), and the total area of ​​one opening to the combined total area of ​​all openings should be less than about 20 μm 2 From about 150,000 μm 2 The range may be up to this point.

[0138] The electrically conductive bridge may be a transverse member, such as a transverse sheet-like non-degradable conductive member, a non-degradable conductive sheet-like structure, and a conductive non-degradable ion-permeable membrane, forming part of the casing of the distal chamber. By the transverse member forming part of the casing, it is intended that at least a section of the casing is replaced by the transverse member. The transverse member thus typically maintains the three-dimensional shape of the distal casing. The transverse member has an overall sheet-like appearance. The transverse member electrically connects the distal chamber with the adjacent soft tissue. This electrical coupling / connection may be achieved by an electrically conductive material and optionally further by using a transverse member that allows the transport of electrically conductive particles, in particular ions and electrons. The transverse member may therefore be selected from a conductive sheet-type member comprising a conductive material and / or an ion-permeable membrane.

[0139] An ion-permeable membrane is to be understood as a material or configuration that allows the transport of charged particles, such as ions. The ion-permeable membrane may be made of a porous polymeric material. The polymeric material may be non-conductive or conductive. The ion-permeable material may be configured in a mesh, net or web. The mesh, net or web may comprise rods / threads / filaments. The rods / threads / filaments may be conductive. The transverse members may be ion-permeable materials that comprise conductive rods / threads / filaments.

[0140] The lateral members are preferably configured to reduce or eliminate tissue from entering the distal chamber. One way to reduce the ability of tissue to enter the distal chamber is to configure the dimensions (area) of each mass transfer channel such that the risk of tissue entering the distal chamber is reduced or eliminated.

[0141] A further measure to reduce or eliminate tissue from entering the distal chamber is the provision of an inner casing, preferably having an annular shape with an outer diameter that essentially matches the inner diameter of the casing, and more preferably having an inner diameter larger than the diameter of the insulated proximal / distal portions of the conductive element.

[0142] The lateral member (ion permeable membrane) may be selected from any one of the following: a porous polymeric material, a mesh, a net, a web.

[0143] The transverse members may be selected from a mesh, netting, or web comprising a conductive material.

[0144] Microelectrodes in which the casing of the distal chamber consists at least in part of a transverse member are particularly suitable for stimulating soft tissue, such as nerve tissue.

[0145] The area of ​​the transverse members based on the total area of ​​the distal chamber casing that is essentially parallel to the major axis of the elongated conductive element is from about 10%, from about 15%, from about 20%, to about 50%, to about 60%, to about 70%, to about 80%, to about 90%, to 100%.

[0146] The transverse members suitably extend radially up to about 30°, up to about 60°, up to about 90°, up to about 180°, and up to about 360°.

[0147] In some embodiments, the casing of the distal chamber comprises an electrically conductive bridge that electrically couples the distal chamber with adjacent soft tissue.

[0148] In some embodiments, the distal casing comprises at least one electrically conductive bridge electrically connecting the distal chamber with adjacent soft tissue (fluid), selected from any one of: a) an opening in the casing; b) a filamentary structure penetrating the casing of the distal chamber; c) a transverse member forming part of the casing of the distal chamber.

[0149] In some embodiments, the distal casing comprises at least one electrically conductive bridge electrically connecting the distal chamber with adjacent soft tissue (fluid), selected from any one of: a) a filamentary structure penetrating the casing of the distal chamber; or b) a transverse member forming part of the casing of the distal chamber.

[0150] Conductive Elements All aspects of the invention comprise an electrically conductive element. The electrically conductive element can be referred to as a rectangular electrically conductive element or an elongated electrically conductive element. The electrically conductive element may also be referred to as a filament, such as a thin, fine-grained, elongated filament. An electrically conductive element may be understood to be a thin, typically rotationally symmetric, electrically conductive filament that extends on its axis significantly more than its radial extension. The diameter or thickness ranges from about a few microns, e.g., 2 μm, to about 100 μm. Elongated electrically conductive elements (including non-insulated and insulated electrically conductive elements) typically have a length of about 2 mm to about 1 m. The non-insulated part of the conductive element may be roughened or comprised of, for example, nano- or micro-sized particles to reduce impedance. The casing of the microelectrode typically has an elongated shape extending on its axis from about 50 μm to about 20 mm or more, suitably from about 500 μm to about 15 mm, but may be longer. The elongated electrically conductive element may comprise several sub-sections, such as non-insulated and insulated sections. The electrically conductive element may be composed of several electrically connected micro- or nano-wires. The conductive element may be a single rod, or a homogenous rod, or may be designed as a multi-wire element or multi-filament (element), e.g. a twisted multi-wire. Multi-wire electrode elements usually have a larger surface area, and therefore a lower impedance, than a single wire element of the same diameter.

[0151] According to one embodiment, the conductive element comprises a central tube that can be used for the delivery of pharmacologically potent fluids (medicines) to the distal chamber and through a fluid-electrical conductive bridge contained in the casing of the distal chamber.

[0152] The conductive element may also be hollow, i.e., have a central tube. Conductive elements with a central tube can be used for delivery of various biologically active substances to the soft tissue adjacent to the microelectrode.

[0153] First and optional second structural components The first and second structural components may form part of a casing. The first and second structural components are preferably separate from the casing. The first and second structural components preferably have annular cross-sections. The first and second structural components preferably extend radially between the casing and any insulating portion of the conductive element. The first and second structural components essentially center the conductive element with respect to the casing.

[0154] The first and second structural components are preferably made from an electrically insulating, non-degradable material.

[0155] Casing The casing is made from an electrically insulating, non-degradable material. The casing is preferably flexible. The casing may comprise a flexible, soft polymeric material, such as Teflon, silicone, or Parylene C.

[0156] The casing may be configured such that the volume of the casing is variable. Movement of the casing relative to the conductive element (and the insulating section of the conductive element) may affect the pressure inside the casing. The casing is preferably configured to accommodate and thus counteract pressure variations caused by the relative movement of the conductive element and the casing. If the relative movement temporarily increases the pressure inside the casing, the volume of the casing increases. If the relative movement temporarily decreases the pressure inside the casing, the volume of the casing decreases.

[0157] In some embodiments, the conductive element is disposed within a casing, the casing comprising at least a first structural part that divides the casing into a distal chamber and a proximal compartment. The terms chamber and compartment have been chosen in part for added clarity. Additionally, the words "chamber" and "compartment" serve different purposes to some extent, and more importantly, the distal chamber includes / encloses the non-insulated portion of the conductive element, while the insulated portion of the conductive element is primarily or at least partially disposed within the proximal compartment. In some embodiments, the casing, the first and second structural parts form the distal chamber.

[0158] The casing, or at least a portion of the casing, preferably has a rotationally symmetric shape, suitably a cylindrical shape. The radial extensions (diameters) of the casing of the distal chamber and at least a portion of the casing of the proximal compartment (typically the distal portion of the proximal compartment) are preferably similar or essentially the same. Suitably, the radial extensions of the distal chamber and at least a portion of the proximal compartment do not differ by more than 20%, typically not by more than 10%.

[0159] Suitably, the distal section of the casing is preferably narrowed in a manner to facilitate insertion into soft tissue.The transverse cross-section of the distal section of the casing preferably presents a convex line segment.

[0160] In some embodiments comprising first and second structural components, a portion of the casing distal to the second structural component comprises an opening, said opening being preferably symmetrical with respect to a major axis of the microelectrode.

[0161] According to a further aspect, the diameter of the proximal compartment expands in the proximal direction.

[0162] According to some embodiments, the first structural component partitions the casing, thereby forming a distal chamber and a proximal compartment, such that the casing limits part or essentially all of the volume of the distal chamber and the proximal compartment.

[0163] Inner casing It has been pointed out that certain instabilities during recording may occur when using the microelectrodes disclosed in WO 2022 / 005386 A1. A possible reason is that in scientific studies, glial cells and extracellular matrix may settle on the conductive element through the opening in the casing, which is partially supported by the remainder of the tissue inside the casing. Such settling may move the tissue adjacent to the opening into or out of the casing as the conductive element moves, which will affect the amplitude of the recorded neuronal signal. This may also cause pain in the nearby tissue where the neuronal recording is made.

[0164] To further prevent direct physical contact between tissue and the conductive element, it is preferable to provide an electrically conductive, non-degradable inner casing around at least a portion of the uninsulated portion of the conductive element within the distal compartment through which the insulated conductive element can slide. The lumen of the inner casing should be larger than the diameter of the insulated conductive element.

[0165] The inner casing may be deployed in any one of the microelectrodes disclosed herein.

[0166] The inner casing is particularly preferred because the microelectrode has a fluid-electrically conductive bridge such as an opening in the casing, the presence of the inner casing prevents tissue from entering the distal compartment or from sticking to the uninsulated portion of the conductive element when the inner casing engages the inside of the casing.

[0167] Thus, in some embodiments, the non-insulated portion of the conductive element in the distal chamber is disposed within an inner casing comprising an electrically conductive, non-degradable material. The material of the inner casing can be selected from any conductive material, so long as such material substantially inhibits tissue from sticking to the non-insulated portion of the conductive element. The material may be selected from conductive gel-like and non-gel-like materials with porosity that essentially inhibits tissue penetration, as well as other types of biocompatible cross-linked matrix materials with electrically conductive properties. A preferred material for the inner casing is a hydrogel. Hydrogels are cross-linked, water-insoluble, hydrophilic polymers that typically form a three-dimensional network structure. Hydrogels are highly absorbent while essentially maintaining a well-defined spatial structure. Chemical and physical hydrogels may be employed. Chemical hydrogels comprise covalent cross-links, while the integrity of physical hydrogels is based on non-covalent intramolecular attractions between polymeric hydrogen bonds, hydrophobic interactions, and polymer chain entanglements. Hydrogels can be prepared by a variety of natural and synthetic polymers. Natural polymers for hydrogel preparation usually involve cross-linking and include peptides, collagen, gelatin, cellulose, hyaluronic acid, chitosan, heparin, alginate, Pedot, and fibrin, to mention just a few. Common synthetic polymers include polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, acrylate polymers, and their copolymers. Acrylate-siloxane hydrogels may also be applied. The mechanical properties of the hydrogel may preferably be adjusted by the degree of cross-linking.

[0168] The inner diameter of the inner casing is preferably larger than the diameter of the insulating conductive element so as not to impede the axial movement of the conductive element. The conductive inner casing is placed between the first structural component and the optional second structural component. The inner casing is surrounded by the casing. This arrangement is based on the insight that it is a significant advantage to prevent tissue from accumulating inside the distal chamber, since tissue matrix material can adhere to the conductive element, thereby propagating the movement of the conductive element to tissue outside the contacts, thereby causing positional instability of the tissue relative to the contacts.

[0169] Examples D and E These embodiments further reduce the volume / pressure changes of the bodily fluid inside the distal chamber when the conductive element is moving axially. Such changes in volume / pressure may otherwise cause resistance to axial movement of the conductive element and to fluid movement through the contacts (if the contacts include openings), potentially causing positional instability of tissue adjacent to the contacts. This also has the effect of inhibiting tissue growth into the distal chamber.

[0170] This embodiment relates to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising an elongate electrically conductive element having a proximal end and a distal end, the electrically conductive element comprising insulated proximal and distal portions, the proximal insulating portion extending distally from the proximal end and the distal insulating portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulating portion of the conductive element, at least the non-insulating portion of the conductive element being made of an electrically insulating non-degradable material. the microelectrode further comprising first and second structural parts, the first and second structural parts extending radially between the casing and the conductive element, the first structural part being movably disposed about the proximal insulating portion and the second structural part being movably disposed about the distal insulating portion, the casing, the first and second structural parts forming a distal chamber, the casing having an opening distal to the second structural part, and the casing configured to electrically couple the uninsulated portion of the conductive element with soft tissue.

[0171] At least a portion of the non-insulated portion of the conductive element is disposed within an inner casing of electrically conductive, preferably non-degradable material, the inner casing preferably having an outer diameter equal to or smaller than the inner diameter of the distal casing. The inner casing preferably has an annular cross-section with an inner diameter equal to or larger than the diameter of either the insulated proximal or distal portion of the conductive element. The non-insulated portion of the conductive element is preferably disposed within the inner casing to such an extent that tissue inside the distal chamber cannot stick to the non-insulated portion of the conductive element. The entire non-insulated portion of the conductive element is preferably disposed within the inner casing. The inner casing may also be movably disposed around a portion of the proximal insulating portion and / or around a portion of the distal insulating portion of the conductive element.

[0172] The inner casing comprises an electrically conductive, preferably non-degradable, material.

[0173] The first and second structural components are preferably separate entities and preferably have annular cross-sections extending radially between the casing and the insulated distal and proximal portions of the conductive element, the first and second structural components preferably having annular cross-sections with inner diameters larger than the diameters of the insulated proximal and distal portions.

[0174] The first and second structural components are preferably permanently affixed to the casing, and the casing preferably electrically seals the first and second structural components, thereby preventing electrical current between said first and optional second structural components and the casing.

[0175] The electrical connection of the casing of the distal chamber can be any of the electrical connections disclosed herein.

[0176] According to one embodiment, the diameter of the distal insulating portion of the conductive element is larger than the inner diameter of the first structural component, and in some cases is also larger than the diameter of the proximal insulating conductive element. When the microelectrode is removed from the soft tissue, the distal insulating portion is prevented from sliding through the first structural component. The casing is affixed to the first and second structural components so that the entire microelectrode is removed from the soft tissue by pulling on the conductive element or any conductor affixed to the conductive element.

[0177] An alternative solution / embodiment is for the distal insulating portion to comprise a protrusion disposed distally of the second structural component that prevents the distal insulating portion of the conductive element from sliding completely through the second structural component when the conductive element is pulled in the proximal direction.

[0178] Further disclosure of embodiments One embodiment of the present invention is particularly configured for electrical stimulation of soft tissue, the embodiment comprising a casing for delivering electrical current through a tissue volume adjacent to the microelectrode, the casing being completely separate from the conductive element providing the electrical current. This configuration provides efficient electrical stimulation to the same or essentially the same portion of the soft tissue. Microelectrodes for stimulation of soft tissue preferably have an electrically conductive bridge selected from lateral members, such as lateral sheet-like members.

[0179] An advantage of the present invention is that direct physical contact between adjacent soft tissues, particularly neural tissue, but also endocrine, exocrine, muscular, cardiac, connective, and retinal tissues, and the conductive electrodes (referred to herein as conductive elements) of an implanted microelectrode can be avoided by encasing the conductive elements in a casing of electrically insulating, non-degradable material.

[0180] In some examples, the casing is associated with the conductive element such that the distal tip of the uninsulated portion of the conductive element does not touch or penetrate the casing of the distal chamber, which may be beneficial in situations where there is little tissue movement relative to the lead.

[0181] In some embodiments, the elongate electrically conductive element comprises a proximal end and a distal end, the electrically conductive element comprising an insulated proximal portion and a distal portion, the proximal insulated portion extending distally from the proximal end and the distal insulated portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element. The non-insulated portion of the conductive element is preferably disposed within a casing of electrically insulating non-degradable material, the conductive element being essentially centrally disposed within the casing by at least a first structural component that may form part of the casing, the casing and the first structural component preferably forming a distal chamber around the non-insulated portion of the conductive element, the insulated distal portion of the conductive element projecting distally from the distal end of the casing, the distal end of the casing preferably functioning as the second structural component.

[0182] Thus, not only is the proximal portion of the conductive element insulated, but also the distal portion of the conductive element is preferably insulated distal to the distal non-insulated portion of the conductive element (referred to as the distal insulated portion of the conductive element). The distal insulated portion of the conductive element may be arranged inside the distal chamber, but the distal insulated portion of the conductive element may also be arranged such that this portion penetrates the distal end of the casing. Alternatively, the insulated distal portion of the conductive element protrudes through an opening at the distal end of the casing, which serves to radially stabilize the distal insulated portion of the conductive element. In the latter configuration, the casing of the distal chamber can serve to radially stabilize the distal region of the conductive element. The casing, or the distal end of the casing, assumes the function of a second structural part.

[0183] The first and optional second structural parts may also be entirely separate from the casing and present a tubular structure, preferably with an annular cross-section, along which the insulated conductive part of the conductive element can slide. The first and optional second structural parts are preferably made of a non-degradable, electrically insulating material, e.g. Teflon or nylon, that ensures sufficiently low friction against the insulated conductive element. The decoupling of the conductive element from the protective casing, and the potential adhesion of the casing to the surrounding soft tissue, allows the casing to a certain (significant) degree to accommodate any movements of the surrounding tissue, while the electrodes maintain essentially the same areas of soft tissue monitoring and / or stimulating over time.

[0184] Decoupling of the casing from the conductive element (or vice versa) allows the soft tissue surrounding the microelectrode to move, for example by a conductive bridge, without significantly affecting / changing the vertical distance from the non-insulated distal portion of the element to the electrical connection of the casing (FIG. 24, 104), since the vertical distance to the non-insulated portion of the conductive element does not substantially change when the non-insulated portion of the element slides axially. The radially stable non-insulated portion of the conductive element improves the recorded signal pattern (fingerprint) and improves the efficacy of stimulation of the target excitable cells when the microelectrode is used for stimulation. An optional second structural part inside the distal chamber further radially stabilizes the non-insulated distal portion, provided that the vertical distance between the non-insulated distal portion of the element and the conductive bridge (FIG. 24, 104) remains essentially the same over time.

[0185] The first and second structural components facilitate the shortest distance from the electrical bridge to the uninsulated portion of the conductive element remaining essentially the same.

[0186] A further advantage of the present invention is that the casing, once inserted into the soft tissue, may adhere to the soft tissue in a manner that minimizes or perhaps essentially prevents movement of the casing relative to the surrounding soft tissue. As the soft tissue moves, the casing moves with the soft tissue. Separation of the casing from the conductive element inside the casing is an important feature of the present invention to minimize or essentially prevent movement of the casing relative to the surrounding soft tissue.

[0187] Some embodiments of the microelectrodes of the present invention preferably provide a large surface area of ​​uninsulated conductive elements while simultaneously providing stimulation and monitoring of spatially specific regions of soft tissue. The large surface area, e.g., roughened surface of the uninsulated conductive elements, may be provided by any surface that has been subjected to extensive surface modification, e.g., by laser milling.

[0188] The present invention relates, inter alia, to microelectrodes, microelectrode probes, microelectrode arrays, and methods for producing microelectrodes, microelectrode probes, and arrays of microelectrodes. A microelectrode probe forms a version of a microelectrode designed to be inserted into soft tissue. Thus, the microelectrode probe comprises certain components that provide the probe with sufficient rigidity to allow successful insertion into various soft tissues. Once inserted into the soft tissue, certain components of the microelectrode probe dissolve and / or disintegrate upon contact with bodily fluids, gradually transforming the microelectrode or microelectrode array into a microelectrode that is an in situ microelectrode.

[0189] Common to all aspects of the present invention is that the microelectrode / microelectrode probe is at least partially embedded or inserted into the soft tissue or placed at least partially or entirely adjacent to the soft tissue.

[0190] Common to all embodiments of the present invention (microelectrodes, proto-microelectrodes, microelectrode probes, arrays) is that the casing of the distal chamber is configured to electrically couple the uninsulated portion of the conductive element with the soft tissue, e.g., by at least one conductive bridge.

[0191] The microelectrodes may be implanted in the soft tissue or placed adjacent to the surface of the target soft tissue. By adjacent, it should be understood that at least a portion of the microelectrode is not surrounded by the target soft tissue. It may be preferable for certain soft tissues to be monitored and / or stimulated by the microelectrode through adjacent placement to the soft tissue. Sensory tissues such as nerve tissues of the spine, peripheral nerves, dorsal root ganglia, retina, and hearing may be advantageously monitored and / or stimulated by placing a microelectrode or microelectrode array adjacent to the nerve tissue.

[0192] The portion of the casing that forms the proximal compartment may be further referred to as the proximal casing or the casing of the proximal compartment, and the portion of the casing that forms the distal chamber may be further referred to as the distal casing or the casing of the distal chamber.

[0193] The term microelectrode as used herein includes at least a conductive element and a casing as described in any of the aspects / embodiments, including at least a first structural part and further including at least one conductive bridge (in a portion of the casing of the distal chamber).

[0194] In some embodiments, the conductive element is disposed within a casing, the casing comprising a first structural part that divides the casing into a distal chamber and a proximal compartment. The terms chamber and compartment have been chosen in part for added clarity. Moreover, the words "chamber" and "compartment" serve somewhat different purposes, but more importantly, the distal chamber essentially encompasses the non-insulated portion of the conductive element, while the insulated portion of the conductive element is primarily or at least partially disposed within the proximal compartment.

[0195] The microelectrodes or microelectrode probes disclosed herein may also include a proximal bridge arrangement associated with a proximal region of the insulating section of the conductive element. The proximal bridge arrangement is configured to be slidably associated with the proximal region of the insulating section of the conductive element. The proximal bridge arrangement includes a casing with an exposed conductive layer, the casing encasing a proximal non-insulated section of the conductive element proximal to the insulating section of the conductive element. The proximal non-insulated section of the conductive element proximal to the insulating section of the conductive element is not in direct contact with surrounding soft tissue. Thus, bodily fluids inside the casing of the proximal bridge arrangement provide a conductive bridge between the proximal non-insulated section of the conductive element proximal to the insulating section of the conductive element and the conductive layer of the casing.

[0196] Some embodiments relate to a microelectrode (or proximal bridge arrangement) comprising a conductive element comprising distal and proximal uninsulated sections, and further comprising an insulated section between the distal and proximal uninsulated sections, the insulated section of the conductive element being slidably associated with a casing that encases the proximal uninsulated section of the conductive element, the casing further insulating the proximal uninsulated section of the conductive element from direct contact with adjacent soft tissue when the microelectrode is inserted into soft tissue, and the casing, with exposed conductive material, capable of electrically coupling the proximal uninsulated section of the conductive element to a second conductive element that is electrically coupled to the conductive material of the casing.

[0197] An additional example relates to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising a conductive element having distal and proximal uninsulated portions and an insulated portion between the distal and proximal uninsulated portions, at least the proximal uninsulated portion of the conductive element being essentially centrally disposed within a casing of electrically insulating non-degradable material, the microelectrode further comprising a first structural part that may form a part of the casing, the first structural part being movably disposed about the insulated portion of the conductive element, the casing and the first structural part essentially electrically insulating the proximal uninsulated portion from the soft tissue, the interior of the casing comprising an electrically conductive material electrically coupling the proximal uninsulated section of the conductive element, the electrically conductive material being in electrical communication with an insulated conductor affixed to a proximal end of the casing.

[0198] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongated electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of an electrically insulating non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, the conductive element being essentially centrally disposed within the casing by at least a first structural part that may form part of the casing, the first structural part extending radially between the casing and the conductive element, the casing and the first structural part forming a distal chamber around the non-insulated portion of the conductive element, the casing and the first structural part essentially partitioning / restricting the distal chamber from adjacent soft tissue, the casing being movably associated with the conductive element, the casing comprising at least one electrically conductive bridge, the bridge configured to electrically connect the distal chamber with the adjacent soft tissue.

[0199] Some embodiments provide a microelectrode adapted to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine and muscular tissue, comprising an elongate electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of electrically insulating non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, the conductive element being attached to a first structural component which may form part of the casing. Thus, the present invention relates to a microelectrode that is essentially centrally positioned within a casing, a first structural component extending radially between the casing and the conductive element, the casing and the first structural component forming a distal chamber around a non-insulated portion of the conductive element, the casing and the first structural component essentially partitioning / restricting the distal chamber from adjacent soft tissue, the first structural component being decoupled from the conductive element or the casing being decoupled from the first structural component, the casing comprising at least one electrically conductive bridge, the bridge being configured to electrically connect the chamber with the adjacent soft tissue.

[0200] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongated electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element disposed within a casing (envelope) of an electrically insulating non-degradable material, the casing comprising a first structural component, the first structural component may form a part of the casing, the non-insulated portion of the conductive element being encased by the casing and the first structural component forming a distal chamber, the casing and the first structural component essentially partitioning / restricting the non-insulated portion of the conductive element from adjacent soft tissue, the first structural component being separated from the conductive element, and the distal chamber comprising an electrically conductive bridge electrically coupling the distal chamber with the adjacent soft tissue.

[0201] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element disposed within a casing (envelope) of an electrically insulating non-degradable material, the casing comprising a first structural part, the first structural part may form part of the casing, the non-insulated portion of the conductive element is enveloped (surrounded) by a casing forming a distal chamber, the first structural part being separated from the conductive element, and the casing of the distal chamber comprising at least one conductive bridge electrically coupling the distal chamber with adjacent soft tissue.

[0202] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element disposed within a casing (envelope) of an electrically insulating non-degradable material, the non-insulated portion of the element being enveloped (surrounded) by a casing forming a distal chamber within which the conductive element is axially slidable, the casing of the distal chamber comprising an electrically conductive bridge electrically coupling the distal chamber with adjacent soft tissue, the casing comprising a first structural part along which the electrically insulating portion of the conductive element is axially slidable.

[0203] One embodiment of the invention relates to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongate electrically conductive element, the elongate electrically conductive element comprising a proximal electrically insulating portion, a distal non-insulating portion, and optionally a distal insulated portion distal to the non-insulating portion, at least a portion of the conductive element being disposed within a casing (envelope) comprising an electrically insulating non-degradable material, the non-insulating portion of the element being enveloped (surrounded) by the casing, first and optional second structural components, the casing, first and optional second structural components forming a distal chamber within which the conductive element is axially slidable, the casing optionally comprising an opening distal to the second structural component, the casing of the distal chamber comprising an electrically conductive bridge selected from any one of a) a filamentary structure penetrating the casing of the distal chamber, or b) a transverse member forming part of the casing of the distal chamber.

[0204] A further embodiment of the invention relates to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongate electrically conductive element, the elongate electrically conductive element comprising a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element being disposed within a casing (envelope) comprising an electrically insulating non-degradable material, the non-insulating portion of the element being encased (surrounded) by a casing forming a distal chamber, within which the conductive element is axially slidable, the casing of the distal chamber comprising at least one electrically conductive bridge, such as an electrically conductive bridge comprising at least one non-fluidic electrically conductive bridge / element connecting the distal chamber with adjacent soft tissue, selected from filamentary structures penetrating the casing of the distal chamber, the casing comprising a first structural part slidably mounted (engaged) around the electrically insulating portion of the conductive element, the first structural part enabling the casing to slide axially relative to the conductive element.

[0205] A further embodiment is a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongate electrically conductive element, the elongate electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element being disposed within a casing (envelope) comprising an electrically insulating non-degradable material, the non-insulated portion of the element being enveloped (surrounded) by a casing forming a distal chamber within which the conductive element is axially slidable, the casing of the distal chamber comprising a sheet of conductive material, and a distal chamber casing comprising a sheet of conductive material .... The present invention relates to a microelectrode comprising at least one electrically conductive bridge, such as an electrically conductive bridge comprising at least one non-fluidic electrically conductive bridge / element electrically connecting the distal chamber with the adjacent soft tissue, selected from any one of an ion-permeable membrane (in the form of a sheet-like structure) allowing ion transfer between the distal chamber and adjacent soft tissue, selected from a transverse member forming part of the casing of the distal chamber, the casing comprising a first structural part slidably mounted (engaged) around an electrically insulating portion of the conductive element, the first structural part enabling the casing to slide axially relative to the electrically conductive element.

[0206] According to one aspect of the invention, the at least one conductive bridge is arranged laterally with respect to the casing of the distal chamber, preferably arranged laterally such that during axial movement of the conductive element the vertical distance between the non-insulated portion of the conductive element and the conductive bridge does not change by more than 100%, more than 50%, more than 20%, suitably more than 15%, preferably more than 10%.

[0207] The non-insulated portion of the conductive element is disposed within a casing comprising an electrically insulating non-degradable material forming a distal chamber, the casing comprising a first structural part. The first structural part and optional second structural part allow the casing to be axially displaced relative to the conductive element and to maintain the central nature of the conductive element within the casing. For the first structural part and optional second structural part to slide axially relative to the insulating portion of the conductive element, there should be a void / cavity between the insulating portion of the conductive element and the first and second structural parts. Alternatively, the casing is movably disposed around the first and optional second structural parts, while the structural parts are permanently affixed to the insulated distal and proximal portions of the conductive element. The association of the first structural component with the proximal insulated portion of the conductive element should preferably be configured such that the electrical impedance between the non-insulated portion of the conductive element and the soft tissue (adjacent to at least one conductive bridge) is less than the electrical impedance inside the casing between the non-insulated portion of the conductive element and the tissue surrounding the proximal portion of the proximal compartment, or the tissue proximal to the first structural component if there is no proximal compartment.

[0208] In embodiments in which the casing has an opening distal to the second structural component, the impedance on said second structural component (between the uninsulated portion of the conductive element and the tissue surrounding the distal opening of the casing distal to the second structural component) is higher or significantly higher than the impedance between the uninsulated portion of the conductive element and the soft tissue adjacent any (lateral) conductive bridges.

[0209] Some embodiments provide a microelectrode adapted to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongated electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of electrically insulating non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, and the conductive element being enclosed by at least a first structural part, which may form part of the casing. The present invention relates to a microelectrode having a first structural component that is essentially centrally disposed within a casing, a first structural component that extends radially between the casing and the conductive element, the first structural component dividing the casing into a distal chamber and a proximal compartment, the casing and the first structural component forming the distal chamber around an uninsulated portion of the conductive element, the casing and the first structural component essentially dividing the distal chamber from adjacent soft tissue, the casing being movably associated with the conductive element, the casing comprising at least one electrically conductive bridge, the bridge configured to electrically connect the distal chamber with the adjacent soft tissue.

[0210] Some embodiments provide a microelectrode adapted to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine and muscular tissue, comprising an elongated electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element being disposed within a casing (envelope, sleeve, sheath) of electrically insulating non-degradable material, the non-insulated portion of the conductive element being disposed within the casing, the conductive element being essentially centrally positioned within the casing by a first structural part, which may form part of the casing. the first structural component extends radially between the casing and the conductive element, the first structural component divides the casing into a distal chamber and a proximal compartment, the casing and the first structural component form the distal chamber around an uninsulated portion of the conductive element, the casing and the first structural component essentially divide the distal chamber from adjacent soft tissue, the first structural component is decoupled from the conductive element or the casing is decoupled from the first structural component, the casing comprises at least one electrically conductive bridge, the bridge configured to electrically connect the chamber with the adjacent soft tissue.

[0211] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongated electrically conductive element, the electrically conductive element comprising a proximal electrically insulating portion and a non-insulated portion distal to the proximal insulating portion, at least a portion of the conductive element disposed within a casing (envelope) of electrically insulating non-degradable material, the casing comprising a first structural component, the first structural component may form a part of the casing, the first structural component partitioning the casing into a distal chamber and a proximal compartment, the non-insulated portion of the conductive element being encased by the casing and the first structural component forming a distal chamber, the casing and the first structural component essentially partitioning the non-insulated portion of the conductive element from adjacent soft tissue, the first structural component being separated from the conductive element, the distal chamber comprising an electrically conductive bridge electrically coupling the distal chamber with the adjacent soft tissue.

[0212] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element disposed within a casing (envelope) of an electrically insulating non-degradable material, the casing comprising a first structural part, the first structural part may form a part of the casing, the first structural part partitioning the casing into a distal chamber and a proximal compartment, the non-insulated portion of the conductive element being enveloped (surrounded) by the casing forming the distal chamber, the first structural part being separated from the conductive element, and the casing of the distal chamber comprising at least one conductive bridge electrically coupling the distal chamber with adjacent soft tissue.

[0213] Some embodiments relate to a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element disposed within a casing (envelope) of electrically insulating non-degradable material, a first structural part dividing the casing into a distal chamber and a proximal compartment, the non-insulating portion of the element being encased (surrounded) by the casing forming the distal chamber, within which the conductive element is axially slidable, the casing of the distal chamber comprising an electrically conductive bridge electrically coupling the distal chamber with adjacent soft tissue, the casing comprising the first structural part along which the electrically insulating portion of the conductive element is axially slidable.

[0214] For example, if the distal and proximal chambers of the casing are to be placed in different tissues with different aqueous body fluids and if exchange of aqueous body fluids between the tissues is to be minimized, it may be desirable to restrict the passage of charged particles through the lumen between the insulating portion of the conductive element and the first structural component, which is important, for example, when avoiding communication of spinal fluid with neural tissue in the vicinity of the distal element portion that lacks insulation.

[0215] Because the casing is allowed to follow any movement of the surrounding soft tissue, the conductive bridge of the casing of the distal chamber will always essentially be located in approximately the same spatial region in the soft tissue over time. Thus, the microelectrode of the present invention will essentially always monitor or stimulate the exact same region of the soft tissue over time. This property is important for any soft tissue in general, and is particularly relevant for nervous tissue, which is associated with the brain, dorsal root ganglion, spinal cord, and peripheral nerves. The microelectrode design is a significant improvement over previous designs, especially in situations where approximately the same spatial region of the soft tissue is monitored and / or stimulated over time, and even when the soft tissue is displaced.

[0216] Electrically excitable cells, such as neurons, are found in any tissue that is sensitive to electrical stimulation, including nervous, endocrine, muscular, and connective tissue.

[0217] The casing comprises at least a first structural part that allows the casing, i.e. the casing defining the distal chamber, to slide axially relative to the conductive element, and in particular relative to the insulating part of the conductive element. This first structural part may optionally be an integral part of the casing, but can also be provided by an element that is entirely separate from the casing. In the case where the microelectrode comprises only a distal chamber, the first structural part of the casing suitably forms a proximal part of the casing of the distal chamber that is narrowed down to a configuration that provides a slidable connection with the proximal electrically insulating part of the conductive element, while simultaneously minimizing the exchange of charged particles through any voids between the proximal electrically insulating part of the conductive element and the proximal part of the casing of the distal chamber.

[0218] In one embodiment, the casing comprises a first structural part that divides the casing (envelope) into a distal chamber and a proximal compartment. The distal chamber is preferably essentially electrically insulated from the adjacent soft tissue, except for electrical connections included in the casing.

[0219] It should be understood that by encasing the distal chamber, the distal non-insulated portion of the electrically conductive element is essentially electrically insulated from the surrounding tissue by the casing except for the conductive bridge within the casing of the distal chamber. Some leakage current will often be present on the lumen / void / annular channel between the insulated portion of the conductive element and the first structural component.

[0220] Depending on the manufacturing method, the first and second structural components may be an integral part of the casing, or alternatively, the first and second structural components are elements that are entirely separate from the casing, optionally of a material different from that of the casing (FIG. 23).

[0221] Regardless of whether the casing forms only a distal chamber or a distal chamber and a proximal compartment, it is important that the casing be movable relative to the conductive element, particularly in the axial direction. In one aspect of the invention, the casing encases the distal non-insulated portion of the element. Since the casing needs to be movable axially relative to the conductive element, the casing should be slidably connected or engaged to the proximal electrically insulating portion of the conductive element. In a specific embodiment, a portion of the casing is slidably mounted / engaged / positioned around the proximal electrically insulating portion of the conductive element, referred to as the first structural part.

[0222] If the first and optional second structural parts form part of the casing, there must be a void / lumen / gap between the structural parts and the insulating portion of the conductive element, if the first and optional second structural parts are separate from the casing, there is either a void / lumen / gap between the casing and the structural parts, alternatively if the first and optional second structural parts are separate but affixed to the casing, there is either a void / lumen / gap between the structural parts and the insulating portion of the conductive element.

[0223] By "slidably mounted, engaged, or positioned about" it is understood that the mounting or engagement allows axial movement while at least reducing movement of charged particles (such as ions) on the first and optional second structural components, such as between the distal chamber and the proximal compartment or proximal tissue (if the microelectrode does not have a proximal compartment) on the first structural component, and optionally between the distal chamber and soft tissue distal to the distal end of the casing if the casing has a distal opening, which is preferably positioned distal to the second structural component. In other words, the slidable association of the casing to the proximal electrically insulated portion of the element, and optionally the distal insulated portion of the conductive element, should provide a higher impedance between the distal chamber and the proximal compartment (or the surrounding soft tissue, if the casing encases only the distal non-insulated portion of the element) over the attachment distance (across the first and second structural components), or a higher impedance between the soft tissue adjacent the distal opening of the casing and the distal chamber, than the impedance between the non-insulated portion of the conductive element and the soft tissue adjacent the conductive bridge, while simultaneously allowing axial movement.

[0224] According to one embodiment, the void / lumen / annular channel between the first and optional second structural components and the proximal electrically insulating portion of the conductive element and the distal insulating portion of the optional conductive element may comprise a composition that is essentially stable over time in tissue fluids and facilitates axial movement of the casing while minimizing the movement of charged particles (and thus providing a high impedance on the first and optional structural components). According to one embodiment, the composition that is essentially stable over time in tissue fluids and facilitates axial movement of the casing while minimizing the movement of charged particles may be a composition that facilitates movement of the first and optional second structural components relative to the outermost layer of the insulating conductive element or between the outermost layer of the first and second structural components and the inside of the casing, in particular a composition that comprises any one of lipids, silicones (such as silicone oil or silicone grease), and combinations thereof.

[0225] Some embodiments of the microelectrodes, microelectrode tips, and arrays comprise a biocompatible material that provides stiffness to the tips when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids. The term stiffness when dry should be interpreted as a dry state in which the material cracks under load (radial or axial) but not bending.

[0226] Useful biocompatible materials provide sufficient rigidity to the probe when dry for insertion into soft tissue and are soluble or degradable in aqueous body fluids. The biocompatible material, also referred to as the matrix, is suitably selected from protein-based materials, carbohydrate-based materials, and polyethylene glycols of various molecular weights. A suitable protein-based matrix material is gelatin, which is typically derived from collagen. A suitable carbohydrate-based matrix material is dextrose. The biocompatible matrix material may be selected from gelatin, dextrose, and polyethylene glycol.

[0227] According to one embodiment, the microelectrodes or microelectrode tips may be affixed to a non-degradable substrate, thereby forming a non-degradable array.

[0228] When a microelectrode or microelectrode tip is affixed to a non-degradable substrate, it is important that at least some of the capabilities of providing the microelectrode elements (e.g., aperture, electrically conductive bridge) are not compromised by the non-degradable substrate.

[0229] The extension of the non-degradable substrate to the microelectrode has a configuration that does not weaken most of the ability to provide the elements of the microelectrode. The non-degradable substrate is preferably arranged with respect to the microelectrode or microelectrode tip such that most of the openings and / or electrically conductive bridges, preferably more than 50%, more than 60%, more than 70%, suitably essentially all of the openings and / or electrically conductive bridges, are not embedded by the non-degradable substrate. In some versions, the micro- or nanofibers are non-degradable and are attached to the microelectrode with a non-degradable adhesive. A non-degradable material / substrate should be understood to be a material that is essentially unaffected in the presence of body fluids. The non-degradable substrate is preferably flexible. The non-degradable substrate preferably comprises a polymer that is flexible at body temperature. Suitable substrate materials can be selected from silicone and any of the polymers used for casings, but are not limited to these materials. This non-degradable substrate should not be confused with the term "substrate" or "array substrate". The term "substrate" or "array substrate" refers to a substrate that is degradable and / or disintegrates in tissue fluids. The matrices found in the distal and proximal compartments, and defined as array matrices, are considered to be biocompatible materials that provide sufficient rigidity to the probes when dry for insertion into soft tissue, and that are soluble or degradable in aqueous body fluids. Non-degradable matrices do not dissolve or degrade upon insertion into soft tissue. Additionally, non-degradable matrices are suitably flexible or become flexible upon insertion into soft tissue.

[0230] According to certain embodiments, the soft tissue can assume the function of a non-degradable matrix. A number of microelectrodes or microelectrode probes can be arranged in the soft tissue according to a predefined spatial pattern. The soft tissue essentially fixes the arrangement of the microelectrodes over time.

[0231] According to all embodiments, the insulating material of the insulating portion of the conductive element is non-degradable in body fluids. The insulating material may be chosen from any of the materials of the casing, but is not limited to these materials.

[0232] If the first and optional second structural components are distinct from the casing, it is important that the attachment of the first and optional structural components to the casing impedes the movement of charged particles. The materials of the first and optional second structural components must also be essentially electrically non-conductive.

[0233] According to one embodiment, the first and optional structural components extend axially at least about 5 μm to about 10 mm, preferably about 5 μm to about 3 mm.

[0234] According to one embodiment, at least a portion of the electrically insulating portion is localized within the distal chamber.

[0235] According to a further aspect, a lumen / void (allowing axial movement) is provided between the first and optional second structural parts and the electrically insulating portion of the conductive element.

[0236] The lumen / void may also be envisaged as an annular channel formed between the first and optional second structural components and the electrically insulating portion of the conductive element.

[0237] It is preferred that a lumen / void / annular channel between the first and optional second structural components and the electrically insulating element limits radial movement of the conductive element relative to the distal casing, and that the impedance across this lumen / void is higher than the impedance across the opening in the distal casing.

[0238] According to a further aspect, the proximal and optionally distal portions of the distal chamber are narrowed and show an annular structure in which the electrically insulating portions of the conductive element form axially slidable first and optional second structural parts.

[0239] The entire casing is capable of moving, typically axially, relative to the conductive element, so it is important to track the movements of the adjacent soft tissue.

[0240] According to one embodiment, the innermost material of the casing and / or the first and optional second structural components, and / or the outermost material of the proximal electrically insulating portion of the element (respectively) is selected to reduce friction.

[0241] The first and optional structural components may be provided by any shape of casing or non-casing components that allow the casing to move axially relative to the insulated conductive element and suitably provide a high impedance on the first and optional second structural components compared to the impedance between the non-insulated portion of the conductive element and the conductive bridge in the distal casing to facilitate recording and stimulation of electrically excitable cells (neurons) adjacent to at least one opening in the casing of the distal chamber and / or the electrically conductive bridge.

[0242] According to one aspect, the electrical impedance between the uninsulated portion of the conductive element and the soft tissue (at least adjacent the conductive bridge) is less than the electrical impedance within the casing between the uninsulated portion of the conductive element and tissue surrounding the proximal portion of the proximal compartment, or (if there is no proximal compartment) tissue proximal to the first structural component, and optionally adjacent to an opening in the casing distal to the optional second structural component.

[0243] According to a further aspect, the electrical impedance between the uninsulated portion of the conductive element and the soft tissue (adjacent to at least one conductive bridge) is at least 5 times smaller, preferably at least 25 times smaller, preferably at least 100 times smaller than the electrical impedance between the uninsulated portion of the conductive element and the tissue surrounding the proximal portion of the proximal compartment or the tissue proximal to the first structural component and, optionally, adjacent to an opening in the casing distal to the optional second structural component.

[0244] It is preferred that the electrical impedance between the non-insulated portion of the conductive element and the soft tissue (adjacent to at least one conductive bridge) is smaller, preferably at least 5 times smaller, preferably at least 25 times smaller, preferably at least 100 times smaller, than the electrical impedance on the first and optional second structural components.

[0245] Axial movement of the non-insulated portion of the conductive element preferably does not significantly affect its radial positioning within the distal casing. Preferably, the vertical distance between the non-insulated portion of the conductive element and at least one conductive bridge of the casing of the distal chamber (FIG. 24, 104) remains essentially the same during axial movement of the casing relative to the conductive element, optionally by less than 20%.

[0246] Variations in the distance from the non-insulated parts of the conductive elements to the conductive bridges will necessarily lead to variations in the distance to the monitored tissue (adjacent to each conductive bridge), which will affect the fingerprint of the recorded signal. The variations in distance can induce amplitude dispersion in the recorded signal that interferes with the ability to distinguish signals from unique cells.

[0247] According to one embodiment, the distal chamber comprises a second structural part configured to reduce radial movement of the non-insulated portion of the conductive element relative to the distal casing and further configured to allow axial movement of the non-insulated conductive element relative to the second structural part. This second structural part may form part of the casing and thus is an integral part of the casing. Nevertheless, the second structural part may also be entirely separate from the casing. For example, the second structural part may be, for example, Teflon, affixed to the casing and comprises a central channel that allows the non-insulated portion of the conductive element to move axially.

[0248] According to one embodiment, the material of the second structural component is distinct from the material of the casing and is at least partially affixed to the casing and configured to be slidably engaged with the non-insulated conductive element.

[0249] The proximal insulating portion of the conductive element may include segments that facilitate axial and radial bending.

[0250] According to one embodiment, the distal portion of the casing of the distal chamber has a distally narrowing three-dimensional shape, which may be spherical, parabolic (such as an ellipsoid), or conical.

[0251] The casing preferably accommodates soft tissue movement while allowing the conductive elements to move relative to the casing.

[0252] According to one embodiment, the casing comprises means for increasing friction between the casing and adjacent soft tissue (or, alternatively, for fixing the casing to the soft tissue). The means for increasing friction is preferably selected from micro- or nano-fibers applied to the outermost surface of the casing.

[0253] According to one embodiment, the micro- or nano-fibers may be non-degradable to body fluids, so that the material of the micro- or nano-fibers is not degradable when in contact with body tissue.

[0254] Thus, according to one embodiment, the friction between the casing and the adjacent soft tissue is greater than the friction between the innermost material of the casing and / or the first and optional second structural components, and / or the outermost material of the proximal electrically insulating portion of the element.

[0255] A further aspect is that the outermost material and / or outermost surface structure of the casing is selected to increase friction against soft tissue.

[0256] According to a further aspect, the casing comprises two layers of material, an inner layer and an outer layer, the material of the inner layer being different from the material of the outer layer or the surface structure of the inner layer being different from the surface structure of the outer layer. The casing may be configured such that the volume of the casing varies. Movement of the casing relative to the conductive element (and the insulating section of the conductive element) will have a temporary effect on the pressure inside the casing. The casing is preferably configured to counteract pressure variations caused by the mutual movement of the conductive element and the casing. If the mutual movement temporarily increases the pressure inside the casing, the volume of the casing increases. If the mutual movement temporarily decreases the pressure inside the casing, the volume of the casing decreases. The casing may comprise a flexible and stretchable polymeric material, such as silicone.

[0257] A further measure to counteract pressure variations caused by movement of the conductive element relative to the casing is the provision of an opening in the casing distal to the second structural part, where the first and second structural parts, if any, are movably arranged around the distal and proximal insulating parts of the conductive element. Pressure variations in the distal chamber (bounded by the first and second structural parts and the casing) are counteracted by the presence of the first and second structural parts in combination with the insulating parts. Additionally, and importantly, the opening in the casing distal to the second structural part is completely surrounded by the casing, significantly reducing or essentially eliminating pressure variations that would otherwise occur in the cavity distal to the second structural part, induced by axial movement of the distal end portion of the distal insulating part.

[0258] The microelectrode may comprise an engagement element configured to reversibly engage with an elongated rigid pin, such as a needle, configured to insert the microelectrode into or adjacent to the soft tissue. The engagement element is suitably located at the distal tip of the microelectrode, but may also be located along the distal casing. Thus, the engagement element may be located at a distal portion of the casing, such as a distal portion of the distal casing, including the distal tip of the distal casing. When the microelectrode comprises an engagement element, the microelectrode may be inserted into the soft tissue or positioned adjacent to the soft tissue as a rigid pin that reversibly engages with the engagement element, the rigid pin (such as a needle) forming part of a device for inserting the microelectrode into the soft tissue, such as disclosed by U.S. Patent Application Publication No. US2020 / 0,086,111(A1). When the microelectrode is inserted using a rigid pin (reversibly engaged with the engagement element of the microelectrode), the microelectrode does not need to inherently exhibit enhanced intrinsic stiffness during insertion into the soft tissue. Thus, a microelectrode with an engaging element can provide sufficient rigidity to the probe when dry for insertion into soft tissue and can at least partially eliminate the need for any material that provides rigidity to the microelectrode, such as a biocompatible material that is soluble or degradable in aqueous body fluids.

[0259] The engaging element may form a loop or comprise a net. According to one embodiment, the engaging element may also form a non-degradable or degradable micro- or nano-fiber that is adhesively affixed to the microelectrode, typically affixed to the casing, particularly to the distal section of the casing, such as the distal casing. The micro-fiber may be any of the micro- or nano-fibers disclosed herein.

[0260] According to one embodiment, the microelectrode comprises a biocompatible material that provides sufficient rigidity to the probe / microelectrode when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids. The material that imparts structural rigidity to the microelectrode is typically found in the distal chamber, and optionally also in the proximal compartment or around at least a portion of the insulating portion of the conductive element.

[0261] The microelectrode may also be disposed in a material that provides the probe with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids. A microelectrode comprising a casing and a distal chamber and optionally a proximal compartment can be envisioned where the distal chamber and optional proximal compartment do not comprise a biocompatible material that provides sufficient rigidity, but the microelectrode is disposed in a biocompatible material that does provide sufficient rigidity.

[0262] Microelectrodes with biocompatible materials that increase stiffness are also referred to herein as microelectrode tips.

[0263] Also disclosed is a microelectrode (or proximal bridge arrangement) comprising a conductive element comprising distal and proximal non-insulated sections, further comprising an insulating section between said distal non-insulated section and said proximal non-insulated section, the insulating section of the conductive element being slidably associated with a casing encasing at least the proximal non-insulated section of the conductive element, the casing further insulating the proximal non-insulated section of the conductive element from direct contact with adjacent soft tissue when the microelectrode is inserted into soft tissue forming a proximal lumen, the casing exposing the conductive material being capable of electrically coupling the proximal non-insulated section of the conductive element with a second conductive element (conductive lead) electrically coupled to the conductive material of the casing. The casing encasing the proximal non-insulated section of the conductive element can be formed of a conductive material such as a metal or a conductive polymer. The casing engages the insulating section of the conductive element via a fifth structural part. This fifth structural part may be integrated within the casing, or alternatively, the fifth structural part may be entirely separate from the casing. If the fifth structural part is distinct from the casing, the casing is affixed to the distinct fifth structural part. The casing may be covered by a layer of electrically insulating material, which is preferably flexible and may be selected from Parylene C or silicone. The casing or conductive material exposed to the fluid inside the proximal lumen is electrically coupled to a second conductive element (conductive lead) that connects the microelectrode to a suitable electronic device for stimulation and / or recording. The insulating section of the conductive element preferably comprises at least one structural element that limits the axial movement of the conductive element. Such a structural element may increase the radial extension of the insulator at a location close to the proximal end of the insulator. Such a structural element prevents the conductive element from separating from the casing.The microelectrode disclosed in this very paragraph (also referred to as a proximal bridge arrangement) may form part of any of the microelectrodes defined, inter alia, as comprising an electrically conductive element having a proximal electrically insulated portion and a distal non-insulated portion, the distal non-insulated portion of the conductive element and preferably at least a portion of the insulated conductive element being disposed within a casing (envelope) of electrically insulating non-degradable material, the non-insulated portion of the conductive element being enveloped (surrounded) by a casing forming a distal chamber, within which the conductive element is axially slidable.

[0264] The proximal bridge arrangement can also be associated with any microelectrode that comprises a proximal non-insulated electrode (proximal non-insulated conductive electrode).

[0265] Further embodiments of the present invention relate to arrays of microelectrodes and / or microelectrode probes. In its broadest definition, an array is characterized by at least two microelectrodes / microelectrode probes, the array structure being capable of being implanted in or placed adjacent to soft tissue, with several microelectrodes / probes being placed in a set spatial structure without essentially changing their properties during insertion. The array is typically provided by embedding the microelectrodes and / or microelectrode probes in a substrate. The substrate may be a non-degradable substrate or a dissolving and / or degradable substrate. The array may comprise both a non-degradable substrate and a dissolving and / or degradable substrate. When the array comprises both a non-degradable substrate and a dissolving and / or degradable substrate, the non-degradable substrate is suitably in contact with the microelectrodes / microelectrode probes further forming a continuous substrate connecting all the microelectrodes or microelectrode probes. The array may form a plurality of individual microelectrodes and / or microelectrode probes arranged in various three-dimensional shapes.

[0266] According to one embodiment, a plurality of microelectrodes and / or microelectrode tips are attached to a non-degradable substrate and / or adhesively attached to micro- or nanofibers, the non-degradable substrate being preferably arranged relative to the microelectrodes or microelectrode tips such that most of the openings and / or electrically conductive bridges, preferably more than 50%, more than 60%, more than 70%, suitably essentially all of the openings and / or electrically conductive bridges are not embedded by the non-degradable substrate.

[0267] In some versions, the micro- or nanofibers are non-degradable and are affixed to the microelectrode with a non-degradable adhesive. A non-degradable material / substrate should be understood to be a material that is essentially unaffected in the presence of body fluids.

[0268] The non-degradable matrix is ​​preferably flexible. The non-degradable matrix preferably comprises a polymer that is flexible at body temperature. Suitable non-degradable matrix materials can be selected from, but are not limited to, silicone and any of the polymers used for casings.

[0269] According to certain embodiments, soft tissue, and in certain circumstances also hard tissue (such as bony skull tissue), can serve a similar purpose as a non-degradable matrix connecting multiple microelectrodes or microelectrode probes. Multiple microelectrodes or microelectrode probes are arranged in the soft tissue according to a predefined spatial pattern. The soft tissue essentially fixes the arrangement of the microelectrodes over time. The individual microelectrodes / probes may be arranged in any conceivable spatial configuration in an array. The configuration can include axial sections, each section comprising multiple individual microelectrodes having the same ones in different spatial configurations.

[0270] According to an embodiment of the array, the microelectrodes are arranged substantially in parallel.

[0271] According to an embodiment of the array, a plurality of microelectrodes and / or microelectrode probes are arranged essentially in parallel and essentially in one sheet. The microelectrodes and / or microelectrode probes arranged essentially in parallel and essentially in one sheet are preferably attached to a non-degradable substrate and / or adhesively attached to non-degradable micro- or nanofibers, thereby forming an array. The adhesive is suitably non-degradable. The array formed of the sheet may be formed into any three-dimensional configuration adapted to the three-dimensional configuration of the target tissue. For example, the array sheet may be configured as a curved structure for placement adjacent to the spinal cord between the spinal cord and the vertebral column, or as a cuff for placement around a peripheral nerve.

[0272] According to one embodiment, the microelectrodes and / or microelectrode probes of the array, such as an array formed of a sheet or an array in a sheet-like configuration, are arranged such that most of the openings and / or electrically conductive bridges of at least one of the distal chambers face essentially in the same direction. When the array has a sheet-like configuration, most (at least about 50%, 70%, at least about 90%, preferably essentially all) of the openings and / or electrically conductive bridges of the distal chambers of the microelectrodes and / or microelectrode probes face the same side of the sheet-like configuration, such that the openings and / or electrically conductive bridges face the soft tissue to be monitored and / or stimulated.

[0273] According to further embodiments, the microelectrodes are arranged substantially parallel to each other in an array configuration comprising non-degradable micro- and / or nano-fibers and / or a non-degradable substrate. The non-degradable micro- and / or nano-fibers and / or the non-degradable substrate fix the position of the microelectrodes relative to each other over time. The net-like structure also allows for accommodation of volume changes of, for example, peripheral nerves. A plurality of microelectrodes may be arranged in the array to form a three-dimensional configuration, such as a cuff, configured to fit the peripheral nerve. In other words, the array may comprise a plurality of microelectrodes arranged essentially parallel to each other, further comprising non-degradable micro- and / or nano-fibers and / or a non-degradable substrate that fixes the position of the microelectrodes relative to each other over time, the array having a configuration that allows the array to be placed between the vertebrae and the spinal cord (e.g., between the vertebrae body and the spinal cord, or between the dura mater and the spinal cord). The array may have a curved configuration capable of partially surrounding the spinal cord. The array is preferably placed between the vertebrae and the dura mater of the spinal cord. Nevertheless, the array may also be placed in direct apposition to the spinal cord, or between the arachnoid and dura mater, or possibly between the pia and arachnoid mater. The array may also be placed in apposition near the dorsal and ventral roots, dorsal root ganglion, or nerve. The array may also comprise structural elements attached to the surrounding tissue. Such structural elements may be comprised in the micro- and / or nanofibers and / or in the casing of the microelectrodes. The microelectrodes may be essentially arranged in parallel in the distal region of the array comprising the casing of the microelectrodes, but are preferably bundled together at some distance proximal to the casing and proximal to the non-degradable substrate to allow axial movement of the insulating conductive elements.

[0274] When the array comprises multiple microelectrodes, such as three or more, a variation is that the axis of one microelectrode essentially coincides with the major axis of the array with the remaining microelectrodes disposed radially about the axis of the array. Additionally, the distal end of the microelectrode may be disposed in a plane essentially perpendicular to the axis of the microelectrode.

[0275] The array can have a configuration that associates the microelectrodes / probes with each other. One type of association limits the movement of the microelectrodes relative to each other. Adhesive attachment of the microelectrodes with the micro- or nanofibers of the first array is a means for limiting the movement of the microelectrodes with each other. An array configured to associate the microelectrodes may further be referred to as a bundle of microelectrodes. For example, the microelectrodes, such as the casings of the microelectrodes, may be adhesively attached to each other intermittently or permanently (e.g., with a non-degradable material such as a non-degradable glue). Alternatively, the microelectrodes of the array are arranged to move independently after being inserted into the soft tissue. In this variation, the microelectrodes are spatially positioned only by the dissolvable or degradable array substrate.

[0276] According to one embodiment, the array comprises an array cover, and the array substrate may be configured to extend onto a distal surface of the array cover.

[0277] According to further embodiments, the array substrate may be partially covered by an array casing of any of the electrically insulating materials presented herein.

[0278] According to a further embodiment, the array may further comprise an outer array substrate.

[0279] A further aspect of the invention relates to a microelectrode probe. The microelectrode probe comprises features that allow successful implantation of the probe by insertion into soft tissue. Thus, the microelectrode probe comprises components relative to the microelectrode that provide the probe with sufficient rigidity to be inserted into soft tissue. Alternatively, the microelectrode may be converted into a probe by changing the rigidity of the material of the microelectrode, typically a casing, that allows insertion of the microelectrode into soft tissue, for example by temporarily changing the temperature of the material.

[0280] According to one embodiment, the distal section of the distal chamber narrows in a distal direction. The distal section of the distal chamber is preferably of the same material as the casing. The distal section of the distal chamber provides for axial movement of the non-insulated conductive element in a distal direction past the opening and / or the location of the electrically conductive bridge.

[0281] According to one embodiment, the casing comprises a first structural part that divides the casing (envelope) into a distal compartment and a proximal compartment, the distal chamber enclosing the distal non-insulated portion of the element, except for the opening in the casing and / or the electrically conductive bridge. The casing fulfills several purposes. The casing is configured to allow the casing to move axially relative to the conductive element. Furthermore, the casing is configured to divide / divide the casing into a proximal chamber and a distal chamber by the first structural part. The first structural part can form an integral part of the casing. Alternatively, the first structural part can form a separate entity to the casing. In the former, the first structural part shares the same material as the casing. In the latter, the first structural part can be of a different material than the casing. In a particular embodiment, the microelectrode is preferably configured such that physical contact of the conductive element with the casing, and in particular with the distal non-insulated portion of the element, is minimized. The apparent lateral movement of the conductive elements relative to the casing tends to be a function of distance from the tubular structure of the first structural component, such that distal tips of non-insulated elements tend to have more apparent lateral movement relative to the casing than portions of the elements closer to the first structural component.

[0282] In principle, the casing can have any shape, as long as the conductive elements can be placed in the casing. It may be advantageous for the casing to be rotationally symmetrical to avoid the elements coming into contact with the casing. The casing can be rectangular or rhombus-shaped. According to one embodiment, the casing is typically rotationally symmetrical about a central axis that usually coincides with the main axis of the conductive elements. The three-dimensional form of the casing can affect the stiffness of the casing. Thus, the stiffness of the casing can be adjusted by the selection of the casing material as well as the selection of the three-dimensional form of the casing. One preferred three-dimensional form of the casing is cylindrical, optionally with a configuration that facilitates a volume change of the casing, such as an accordion-like configuration. The conductive elements are preferably placed in an essentially cylindrical casing, where the elements essentially coincide with the main axis of the cylindrical casing.

[0283] As alluded to above, the casing is the primary facilitator for preventing significant interference of the conductive elements with the surrounding soft tissue, generally and particularly the distal uninsulated portion of the element present in the distal chamber. The casing may be affixed to the first and optional second structural parts, which may have the form of a tubular structure that allows the passage of charged particles between the distal chamber and adjacent tissue through a lumen / void between the proximal and optional distal insulating portions of the conductive elements and the first and optional second structural parts. If the first and optional second structural parts are entities that are entirely separate from the casing, the first and optional second structural parts suitably abut and / or attach to the casing. The first and optional second structural parts suitably comprise an arrangement such as an elongated tube, preferably having an annular cross-section, and preferably configured to provide a lumen / void between the insulating portion of the conductive element and the elongated tube (tubular structure). The lumen / void volume allows for movement of the first and optional second structural components relative to the conductive element (insulating portion of the conductive element), preferably axial movement of the first and optional second structural components.

[0284] According to one embodiment, the cavity / lumen (defined by the space between the proximal and optional distal electrically insulating portions of the conductive element and the first and optional second structural parts) has an axial extension that satisfies at least one of the following measures: a) allows the first and optional second structural parts (e.g. tubular structures) to move relative to the conductive element; b) allows the first and optional second structural parts to move relative to the conductive element while simultaneously centering the casing with respect to the axis of the conductive element (the first and optional second structural parts allowing an essentially central nature of the conductive element within the casing); c) provides a difference in terms of the electrical impedance appearing between the proximal compartment (on the first and optional second structural parts) and the distal chamber, and the tissue adjacent to the opening in the casing next to the distal chamber and the second structural part, on the one hand, and between the distal uninsulated portion of the conductive element and the (surrounding) soft tissue, on the other hand.

[0285] If the microelectrode probe with proximal and distal chambers is not embedded in a dissolvable and / or degradable embedding matrix, it is preferred to apply a further dissolvable and / or degradable matrix to the space between the proximal compartment and the distal chamber, referred to as the intermediate matrix. The radial extension of the intermediate matrix appropriately follows the radial extensions of the proximal compartment and the distal chamber. The dissolvable and / or degradable embedding and intermediate matrix provide the microelectrode with increased stiffness during insertion into soft tissue.

[0286] The electrical impedance appearing between the proximal compartment and the distal chamber, and between the tissue adjacent to the opening in the casing next to the second structural component and the distal chamber (on the first and optional second structural components) is to some extent a function of the extension of the void / lumen in the axial and radial directions, and the volume of the void / lumen between the first and optional second structural components (tubular structures) and the conductive element, or between the first and optional second structural components and the casing. A reduction in the volume of the void / lumen in a given extension of the first and optional second structural components will increase the electrical impedance between the proximal compartment and the distal chamber, and between the distal chamber and the tissue adjacent to the opening in the casing next to the second structural component.

[0287] The larger the axial extension of the cavity / lumen, the higher the impedance in a given area of ​​the cavity / lumen in a plane perpendicular to the axis of the element (and by implication the microelectrode). Increasing the axial extension of the cavity / lumen also tends to increase friction between the conductive element and the first and optional second structural components. The axial extension of the cavity / lumen must meet a criterion that provides a sufficiently high electrical impedance while allowing the first and optional second structural components to slide relative to the conductive element.

[0288] According to one embodiment, the friction between the casing and the surrounding soft tissue is higher, preferably significantly higher, than the friction between the conductive element and the casing (including the first and optional second structural parts). The difference in friction is at least such that a useful pattern of data can be extracted from the microelectrodes. In particular, the difference in friction is at least such that a useful pattern of data can be extracted from the same region of the soft tissue over time.

[0289] In certain embodiments, the axial extension of the distal casing, which defines the distal chamber, particularly the cavity distal to the non-insulated conductive element, and the axial extension of the first structural component are partially correlated to the normally occurring displacement of the soft tissue adjacent to the conductive bridge in the distal casing associated with the proximal connection, typically localized in the skull or spine. Thus, the cavity / lumen extension of the casing (or first structural component) is determined by the spatial movement of the respective tissue. The axial cavity / lumen extension (i.e., the axial distal chamber extension) can range widely from at least about 300 μm to about 20 mm, but can be longer.

[0290] The material of the casing, as well as the outermost material surrounding the conductive element, or the outermost materials of the first and second structural components (if the structural components are affixed to the insulating portion of the conductive electrode), may be selected to facilitate axial movement of the first and optional second structural components relative to the insulating portion of the conductive element.

[0291] The outermost material surrounding the conductive element at the location of the first and optional second structural parts (or the outermost material surrounding the first and optional second structural parts) can essentially form an electrical insulation. Furthermore, the cavity / lumen between the inner surface of the first and optional second structural parts and the outermost material surrounding the conductive element (or the cavity / lumen between the casing, the first and second structural parts) can comprise a composition (medium) that facilitates axial movement of the first and optional second structural parts (or the casing relative to the first and second structural parts) relative to the conductive element. Such compositions may be selected from compositions comprising lipids, silicones, and polymers of hyaluronic acid and disaccharides, or compositions that mimic the properties of synovial fluid.

[0292] Further embodiments of the microelectrode comprise a second structural part configured to minimize lateral (radial) movement of the distal non-insulated part of the element. The second structural part should also allow the element to move axially. Several second structural parts may be arranged in the distal chamber to centrally position the element. The second structural part may be integrated into the casing, attached to the inner surface of the casing, or optionally made from the same material as the casing and integral with it. Alternatively, the second structural part may be entirely separate from the casing, preferably made from a material other than that of the casing. Lateral movement of the distal non-insulated part of the element relative to the casing, and in particular relative to the conductive bridge, may change the shortest distance between the distal non-insulated part of the element and the soft tissue, and thus imply an impedance between the distal non-insulated part of the element and the soft tissue, which may affect the measurement / stimulation.

[0293] The dimensions of the microelectrodes are such that a material may be used for the casing that is rigid in microscopic dimensions but sufficiently flexible in the dimensions of the microelectrodes. Thus, various crystalline materials may be envisaged as the casing material, such as crystalline materials including silicon dioxide, such as any material called glass. According to a preferred embodiment, the electrically insulating material is an electrically insulating, non-degradable, flexible polymeric material. Suitable electrically insulating, non-degradable, flexible polymeric materials are polymeric materials that can be deposited by dip coating, spray coating, vapor deposition or casting, or any combination thereof. Suitable electrically insulating, non-degradable, flexible polymeric materials include polytetrafluorethene (Teflon), parylene C, polyurethane, polyethylene, and polymers with a backbone of cyclic aromatic moieties, such as aromatic moieties with aromatic six-membered ring structures represented by para benzenediyl moieties. A preferred polymeric material is a polymer obtained by polymerization of paraxylene. Hydrogen atoms of the polymer with a backbone of cyclic aromatic moieties may be substituted with various functional groups. Parylenes are a preferred class of electrically insulating, flexible polymeric materials that share the properties of polymers with a backbone of cyclic aromatic moieties, such as those with aromatic six-membered ring structures represented by the parabenzenediyl moiety. The polymeric materials may be selected from, for example, Parylene C and Parylene M.

[0294] The thickness / diameter of the casing can range from about 0.1 μm, to about 4 μm, to about 10 to 15 μm, to about 300 μm, and in some embodiments, to about 1 mm to 2 mm.

[0295] All materials of the microelectrode in contact with tissue, including the electrically insulating material and the lateral member material, must be biocompatible.

[0296] According to a further embodiment, the proximal electrically insulating portion of the conductive element is configured to accommodate spatial movements of the soft tissue. The proximal electrically insulating portion of the conductive element may comprise at least one section that facilitates bending of the element, in particular bending in a direction partially aligned with the main axis (microelectrode) of the conductive element, and / or a section that facilitates radial curvature. This bending section of the element may be localized proximal to the proximal compartment between the proximal compartment and the holder. Alternatively, the bending section may be localized within the proximal compartment, i.e., completely disposed within the casing of the proximal compartment. The bending facilitating section allows the proximal electrically insulating portion of the conductive element to be elongated by at least about 10% (based on the length of the proximal insulating portion in equilibrium), at least about 20%, at least about 50%, and preferably at least about 100%. The section that facilitates elongation (bending) of the electrically insulating portion of the element may be selected from any of the following formats: spiral, zigzag, serpentine, or any combination of these formats.

[0297] The material of the electrically conductive element can be any electrically conductive material that meets the characteristics of the microelectrode for implantation in soft tissue, particularly in neural, endocrine, or muscular tissue. Various metals are suitable, but conductive non-metallic materials are also suitable. Suitable materials are metals or mixtures of metals in the tissue surrounding the microelectrode, including platinum, iridium, gold, wolfram, stainless steel, and alloys thereof. More preferred metals for the conductive element are selected from materials that do not easily oxidize, such as platinum, iridium, gold, stainless steel, and alloys thereof. Conductive non-metallic materials include various conductive polymers, such as PEDOT, and carbon-containing materials, such as graphene, graphite, and carbon nanotubes.

[0298] The conductive element can be a single metal or comprise two or more portions of different metals. Alternatively, the element can comprise two or more ultra-thin metal wires. The thickness of the wire or wires is preferably from about 100 nm to 1 μm or 10 μm or possibly 100 μm. Two or more ultra-thin wires may be intertwined to maximize surface area.

[0299] The section of the electrically insulating part of the conductive element extending proximally of the proximal compartment can be of one or more materials different from the material of the parts arranged in the proximal compartment and the distal chamber. The non-insulating part of the conductive element present in the distal chamber can present a surface section having a surface area larger than the average surface area of ​​the non-insulating part of the element in the distal chamber. Suitably, the section presenting the larger surface area is localized in the vicinity of the conductive bridge of the distal chamber. Also, the non-insulating part of the element present in the distal chamber can comprise an undulating section or a protrusion near the conductive bridge. The undulating section or protrusion is of micro- or nano-scale.

[0300] As recited in the claims, the distal non-insulated portion of the element is located entirely within the distal chamber.

[0301] According to some embodiments, during operation of the microelectrode, the most distal section of the insulated proximal part of the element should preferably always be contained in the distal chamber. The casing should suitably be arranged in relation to the conductive element such that under normal conditions, regardless of axial movement of the casing, the casing completely encompasses the non-insulated part of the conductive element. Also, according to some embodiments, the conductive element should originally be arranged within the casing such that the distal tip of the non-insulated part of the conductive element never reaches the casing of the distal chamber. Alternatively, the microelectrode can have means for limiting the axial movement of the casing or the conductive element such that the distal tip of the non-insulated conductive element can never contact or puncture the casing.

[0302] According to some embodiments, the first and optionally second structural components may be initially positioned in a location relative to the insulated proximal portion of the conductive element where there is minimal or virtually no probability that the first and optionally second structural components will leave the insulated portion of the element (slide wholly or partially over the non-insulated portion) to any degree.

[0303] The implanted microelectrode may need to be removed from the surrounding tissue. To facilitate removal, the microelectrode may be provided with a flexible filament fixedly affixed to the microelectrode in a location that facilitates removal. The proximal portion of such a flexible filament should be placed such that the filament is easily removable without undue pain to any tissue. Alternatively, the distal portion of the non-insulated conductive element may be equipped with a rounded blob having dimensions that make it impossible to pull through the first or optional second structural parts. In this case, the entire microelectrode may be extracted from the tissue by pulling out the conductive filament.

[0304] In certain embodiments where the microelectrode comprises first and second structural parts, the first and second structural parts forming part of the casing or the first and second structural parts being separate from and affixed to the casing, the diameter of the distal insulating part of the conductive element is larger than the inner diameter of the first structural part, and preferably also larger than the diameter of the proximal insulating conductive element. When such a microelectrode is removed from the soft tissue, the distal insulating part is prevented from sliding through the first structural part. Since the casing is affixed to the first and second structural parts, the entire microelectrode is removed from the soft tissue by pulling on the conductive element or any conductor affixed to the conductive element. An alternative solution is for the distal insulating part to comprise a protrusion located distal to the second structural part that prevents the distal insulating part of the conductive element from sliding completely through the second structural part when the conductive element is pulled in the proximal direction.

[0305] A further aspect of the invention relates to a microelectrode probe. As already alluded to above, a microelectrode probe forms a version of a microelectrode designed to be inserted into soft tissue. The microelectrode probe therefore comprises certain components that provide the probe with sufficient rigidity to be successfully inserted into various soft tissues. Once inserted into the soft tissue, certain components of the microelectrode probe dissolve and / or disintegrate upon contact with bodily fluids, gradually transforming the microelectrode into a microelectrode that is an in situ microelectrode.

[0306] The microelectrode probe comprises a matrix of a biocompatible material that provides the probe with sufficient rigidity when dry for insertion into soft tissue, yet holds the different components of the microelectrode together (casing and conductive element), and is soluble or degradable in aqueous body fluids. The matrix is ​​suitably selected from protein-based materials, carbohydrate-based materials, and polyethylene glycols of various molecular weights. A suitable protein-based matrix material is gelatin, typically derived from collagen. A suitable carbohydrate-based matrix material is glucose. Biocompatible matrix materials may be selected from gelatin, glucose, and polyethylene glycol. The casing-encased distal chamber should preferably comprise a matrix material that does not significantly increase its volume when dissolved in aqueous fluid. The matrix of the distal chamber may have properties such that the increase in the matrix volume upon absorption of aqueous fluid is partially counteracted by dissolution / degradation of the matrix.

[0307] A matrix material that increases its volume when it absorbs aqueous fluid may be used to embed the matrix, or a cavity / compartment provided by a casing material that is sufficiently flexible so as not to suffer structural damage during matrix volume expansion.

[0308] Any of the microelectrode variations / embodiments presented herein may be provided as a microelectrode probe.

[0309] One variation of the microelectrode includes a casing that encases the distal uninsulated portion of the element forming a distal chamber, but does not have a proximal compartment. The microelectrode probe of this "one compartment" variation of the microelectrode includes a distal substrate. It is further preferred to have a proximal substrate around a portion of the proximal insulated portion of the conductive element. This proximal substrate preferably has a spatial radial extension similar to the spatial radial extension of the distal chamber. The proximal substrate may surround a rigid pin / bar used when inserting the microelectrode. The pin preferably has the same major axis as the distal chamber.

[0310] Thus, in one embodiment of the present invention, a microelectrode probe configured for implantation by insertion into soft tissue, particularly neural, endocrine, and muscular tissue, comprises an elongate conductive element having at least a proximal insulated portion and a distal uninsulated portion, at least a portion of the element disposed within a casing of electrically insulating non-degradable material comprising a first structural component, the distal uninsulated portion of the element encased in a casing forming a distal chamber, a void / lumen existing between the insulating portion of the conductive element and the first structural component, the void / lumen allowing the conductive element to slide relative to the casing, the casing of the distal chamber comprising at least one electrically conductive bridge electrically coupling the distal chamber with adjacent soft tissue, the distal chamber comprising a distal substrate providing sufficient rigidity to the probe when dry for insertion into the soft tissue and comprising a biocompatible material that is soluble or degradable in aqueous body fluids.

[0311] A further embodiment is a microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an elongate electrically conductive element having a proximal end and a distal end, the electrically conductive element having insulated proximal and distal portions, the proximal insulating portion extending distally from the proximal end and the distal insulating portion extending proximally from the distal end, the proximal and distal portions being separated by a non-insulated portion of the conductive element, at least the non-insulated portion of the conductive element being essentially centrally disposed within a casing of electrically insulating non-degradable material, the microelectrode being configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrode comprising first and second structural members, the first and second structural members being electrically insulating, the first and second structural members being electrically insulating, the second ... the first and second structural components extend radially between a casing and a conductive element, the first structural component is movably disposed about a proximal insulating portion and the second structural component is movably disposed about a distal insulating portion, the casing, the first and second structural components form a distal chamber, the casing has an opening distal to the second structural component, the casing is configured to electrically couple an uninsulated portion of the conductive element with soft tissue, the distal chamber provides sufficient rigidity to the probe when dry for insertion into soft tissue, and the distal substrate comprises a biocompatible material that is soluble or degradable in aqueous body fluids.

[0312] The first structural component divides the casing into a distal chamber and a proximal compartment, and when at least a portion of the proximal insulating portion of the conductive element is disposed within the proximal compartment, the proximal compartment preferably comprises a distal substrate comprising a biocompatible material that provides sufficient rigidity to the probe when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids.

[0313] The proximal and distal substrates do not have to be the same material. Furthermore, the substrate, whether it be the proximal or distal substrate or any other substrate of the probe or array, can comprise biologically active substances, such as pharmacologically active substances and genetic constructs. According to an embodiment, the distal substrate can comprise biologically active substances.

[0314] The biologically active substances are suitably selected from anti-inflammatory substances, neurotrophic substances, sedatives, transmitter substances such as glutamate, glycine, GABA, dopamine, noradrenaline and acetylcholine, or substances that interfere with synaptic transmission. The pharmacologically active substances are suitably contained in the distal chamber so that they are releasable through the openings and / or electrically conductive bridges that comprise the tubes in the distal chamber. The biologically active substances may be added during the manufacture of the microelectrode probe to any of the substrates, such as the distal, proximal, implanted, array-embedded substrates, to only one substrate, to several of these, or to all of these. According to one embodiment, the biologically active substances are added to the surface of the distal substrate and / or are contained in the distal substrate. The biologically active substances may also be applied to the conductive elements, particularly to the distal uninsulated parts of the conductive elements that are in the distal chamber.

[0315] Drugs may also be delivered to target areas of soft tissue through microelectrodes with hollow conductive elements, i.e. conductive elements with a central tube. Any biologically active substance that can be included in a dissolvable and / or degradable array matrix may also be delivered to target soft tissue areas through the hollow conductive elements. The casing of the microelectrode, separated from the conductive elements, is associated to a large extent with the soft tissue. Thus, microelectrodes with hollow conductive elements can function as catheters for long-term delivery of drugs to precisely targeted areas of soft tissue. Additionally, the impact of drug delivery on the soft tissue can be immediately monitored electrically, allowing drug dosing tailored to immediate soft tissue feedback.

[0316] According to an embodiment, the microelectrode probe may also comprise a further substrate in which a microelectrode is embedded, characterized by a distal and optionally a proximal compartment comprising the substrate. Such a substrate in which a microelectrode is embedded is referred to as an embedding substrate.

[0317] The microelectrode or microelectrode probe may also comprise a holder for the conductive element. In some embodiments, the holder may comprise a proximal casing (e.g., a proximal bridge arrangement as disclosed herein) in which the conductive element can slide. The holder for the conductive element preferably comprises or consists of a rigid material and comprises a distal face and a proximal face. A proximal end section of the proximal insulating part of the conductive element preferably passes through the element holder from the distal face to the proximal face. The holder for the conductive element preferably comprises a cylindrical tube of a diameter smaller than that of the element holder, in particular a cylindrical tube of a diameter equal to or smaller than the diameter of the hole in the bone in which the element holder will be mounted, the tube extending distally from the distal face of the element holder. The tube may be of the same material as the holder or of a different material, which is stable against degradation by aqueous body fluids.

[0318] Further examples relate to arrays of microelectrodes comprising a non-degradable continuous element, also referred to as a non-degradable matrix, and / or a non-degradable discontinuous element, such as a micro- or nano-fiber, to which the microelectrodes are adhesively affixed. Suitably, the non-degradable continuous element or the micro- or nano-fiber is capable of essentially maintaining the mutual spatial arrangement of the microelectrodes of the array over time when the microelectrode array is placed adjacent to or embedded in soft tissue. Arrays of microelectrodes comprising a non-degradable continuous element (non-degradable matrix) and / or a non-degradable discontinuous element may be placed in a robust array matrix of a biocompatible material that provides the array with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids.

[0319] The micro- or nano-fibers for use in the present invention are preferably essentially non-degradable or non-degradable. The micro- or nano-fibers of the present invention are particularly preferably used in the form of a non-woven nano- or micro-fiber assembly. The non-woven micro-fiber assembly consists of randomly entangled micro-fibers and may comprise micro-fibers randomly attached to one another, such as by attachment caused by local melting and / or gluing with a biocompatible glue.

[0320] The non-degradable continuous element capable of essentially maintaining the mutual spatial arrangement of the microelectrodes of the array over time when the microelectrode array is placed adjacent to or embedded in soft tissue is suitably a polymer matrix and / or a non-degradable micro- or nanofiber adhesively affixed to the microelectrodes. A suitable non-degradable polymer matrix material (for the continuous element) is a flexible biocompatible polymer matrix selected from any one of the electrically insulating non-degradable flexible polymeric materials disclosed herein. Additional non-degradable polymers that function as the non-degradable continuous element (non-degradable matrix) include polyurethanes, silicones, polymers with circulating benzene moieties (such as parylene), and other suitable biocompatible flexible polymers that are not essentially degradable upon contact with soft tissue and in typical tissue fluids.

[0321] The time for positional stabilization by integration with non-degradable continuous elements and / or non-degradable discontinuous elements such as nano- and microfibers may range from at least several days to at least two weeks, such as two or five weeks, and more preferably at least several months, preferably at least several years.

[0322] The microfibers of the present invention are in the micro- or nanometer diameter range. Electrospun nano- and microfibers are particularly preferred, with electrospinning being the preferred method for producing the microfibers of the present invention.

[0323] A particularly preferred type of microfiber is electrospun microfiber. According to a preferred embodiment of the invention, the microfiber forms a non-woven irregular structure. Preferably, the microfiber is adhesively attached to the microelectrode and to one or more other microfibers. The microfiber is preferably disposed along at least 50% of the axial extension of the microelectrode. Microfibers for use in the present invention may be of resilient or non-resilient material.

[0324] Another aspect of the invention relates to a process for the manufacture of microelectrodes and microelectrode probes. Depending on the design of the first structural part, two different manufacturing processes are presented. Figures 6 to 16 disclose several manufacturing stages for the manufacture of microelectrodes / microelectrode probes, where the first structural part forms an integral part of the casing. Figure 22 illustrates one stage of the manufacturing process, where the first structural part is not integrated in the casing but is separate from it.

[0325] The present invention encompasses a method for manufacturing a microelectrode, microelectrode tip, or array, comprising: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the conductive element; - forming a distal matrix that is soluble or degradable in aqueous body fluids, extending axially around the distal uninsulated portion of the conductive element, and optionally extending distally from the distal uninsulated portion of the conductive element; - applying a slide-facilitating composition to a section of the insulating element proximal to the distal substrate and distal to the optional proximal substrate, the slide-facilitating composition facilitating axial movement of the first layer of electrically insulating non-degradable material relative to the insulating layer of the conductive element, the medium optionally providing sufficient void / lumen between the insulating layer of the conductive element and the first layer of electrically insulating non-degradable material; - optionally forming a proximal substrate extending axially around at least a portion of the proximal electrically insulating portion of the conductive element; - covering the distal substrate and at least a portion of the proximal electrically insulated portion of the conductive element with a first layer of electrically insulating non-degradable material, thereby providing a casing encasing the distal non-insulated portion of the element forming a distal chamber and a first structural component; - cutting a first layer of electrically insulating non-degradable material near a distal end of the distal substrate comprising an uninsulated portion of the conductive element (preferably a portion of the uninsulated portion of the conductive element) and a distal uninsulated portion of the electrically conductive element, thereby providing a distal opening of the distal chamber; - applying a further distal tip substrate distal to the distal opening; - covering the tip substrate and at least a portion of the first layer with a second layer of electrically insulating non-degradable material and at least a portion of the first layer, thereby forming a distal end cap portion that forms part of a casing of the distal chamber; Including, - The distal and optionally proximal substrates provide structural support to the microelectrode or probe when dry for insertion into soft tissue.

[0326] Additionally, sections of the first and optionally second layers of the casing surrounding the distal substrate are removed by suitable means (e.g., laser milling) and replaced with an electrically conductive bridge, e.g., in the form of a conductive mesh. Alternatively or additionally, a conductive filament may be disposed within the distal substrate protruding essentially radially from the substrate. After the first layer is disposed on the distal substrate, and optionally the second layer is disposed over the first layer, the first and optional second layers of electrically insulating non-degradable material must be removed from the filament such that a portion of the filament can be electrically coupled to the soft tissue outside the distal chamber.

[0327] A further variation of the method for manufacturing a microelectrode, microelectrode tip, or array as disclosed herein comprises: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the conductive element; - forming a distal matrix that is soluble or degradable in aqueous body fluids, extending axially around the distal uninsulated portion of the conductive element, and optionally extending distally from the distal uninsulated portion of the conductive element; - forming a proximal substrate extending axially around at least a portion of the proximal electrically insulating portion of the conductive element, thereby forming an intermediate section of the insulating conductive element with an axial extension, the intermediate section being disposed proximal to the distal substrate and distal to the proximal substrate, the intermediate section not being covered by the distal and proximal substrates; - applying a thin (up to about 5 μm) layer of a first intermediate substrate and / or slide-facilitating composition to the intermediate section of the insulating element, the first intermediate substrate and / or composition providing sufficient void / lumen (annular channel) between the electrically insulating portion of the conductive element and the first layer of electrically insulating non-degradable material, facilitating axial movement of the first layer of electrically insulating non-degradable material relative to the insulating layer of the conductive element; - covering an intermediate section of the distal substrate, the proximal substrate, and the proximal electrically insulating portion of the conductive element, the intermediate section comprising the intermediate substrate and / or the slide promoting composition together with a first layer of electrically insulating non-degradable material, thereby providing a casing comprising a distal chamber, a first structural component, and a proximal compartment; - optionally providing a second intermediate substrate on the first layer of electrically insulating non-degradable material in radial clamping of the first layer between the distal chamber and the proximal compartment; - cutting (a part of) the distal non-insulated portion of the electrically conductive element and the first layer of electrically insulating material near a distal end of the distal substrate (the distal end of the distal chamber), thereby providing a distal opening of the distal chamber; - applying a further distal tip substrate distal to the distal opening; - covering the distal tip substrate and at least a portion of the first layer with a second layer of electrically insulating material, thereby forming a distal end cap that forms part of a casing of the distal chamber; and removing the first layer and optionally the second layer in an annular zone around the proximal substrate. Including, The distal substrate, distal tip substrate, proximal substrate, and optionally the first and second intermediate substrates are of a biocompatible material that provides the probe with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids.

[0328] Additionally, sections of the first layer and optionally the second layer of the casing surrounding the distal substrate are removed by suitable means (e.g., laser milling) and replaced with an electrically conductive bridge, for example in the form of a conductive mesh.

[0329] Further, a further embodiment of a method for manufacturing a microelectrode comprises: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the element; - providing a first structural part configured to allow axial movement of the conductive element relative to a proximal electrically insulating portion; - disposing a first structural part around a proximal electrically insulated portion of the conductive element, suitably at a particular axial distance from a distal non-insulated portion of the element; - applying a proximal matrix that is soluble or degradable in aqueous body fluids around a proximal electrically insulating portion of the conductive element, the proximal matrix extending proximally from a proximal surface of the first structural component; - applying a distal matrix that is soluble or degradable in aqueous body fluids around a distal uninsulated portion of the conductive element, the distal matrix extending distally from the distal surface of the first structural component and extending distally from the distal uninsulated portion of the conductive element; - applying a first layer of electrically insulating, non-degradable material around the proximal and distal substrates and the first structural component, thereby forming a casing having a distal chamber and a proximal compartment. Includes.

[0330] Additionally, a section of the first layer of casing surrounding the distal substrate may be removed by suitable means (eg, laser milling) and replaced with an electrically conductive bridge, for example in the form of a conductive mesh.

[0331] Preparation of Preferred Examples E and D The following example describes the manufacture of one variation in which a cross-linked hydrogel is used to provide a conductive inner casing. Instead of hydrogel, other conductive materials can also be used.

[0332] 1. Provide a straight conductive element (e.g., platinum), insulate the element with a polymer such as Parylene C, and de-insulate, e.g., by laser milling, a defined section of the conductive element such that the conductive element remains insulated distal and proximal to the de-insulated section.

[0333] 2. Provide two electrically insulated tubes, e.g. Teflon or Nylon, with an inner diameter larger than the outer diameter of the insulating conductive element. These are the first and second structural parts. It is preferable to provide the first and second structural parts with transverse grooves on their outer surfaces.

[0334] 3. Providing an inner casing equipped with one or more radial protrusions (having a length greater than the thickness of the casing) and with an inner diameter somewhat larger than the diameter of the first and second structural parts. Cross-linked hydrogels, for example gelatin strongly cross-linked with glutaraldehyde, freeze-dried in a maximally expanded state, can be used as material for the inner casing. Optionally, conductive bridge elements, for example hollow carbon tubes or hollow platinum tubes, are incorporated into or wrapped around the protrusions.

[0335] 4. Align the first structural component, the inner casing, and the second structural component. Insert the conductive element through the first structural component, the inner casing, and the second structural component such that the insulated portion of the distal conductive element is covered by the secondary structural component and the non-insulated portion of the conductive element is surrounded by the second casing. Optionally, glue these parts together with a biocompatible glue that is degradable in body fluids for easy handling. Optionally, coat the second casing with a degradable biocompatible matrix material such as glucose.

[0336] 5. Coat the proximal insulating conductive element protruding proximally from the first structural component with a dissolvable matrix material and add a conical distal tip of the dissolvable matrix material to the distal portion of the secondary structural component. Dip coating or electrospraying are the preferred methods since the thickness of the coating can be easily controlled.

[0337] 6. Provide an appropriate thickness of Parylene C coating on the ensemble using standard methods.

[0338] 7. Cut the Parylene C coating distal to the second structural component to create a hole at the conical distal tip.

[0339] 8. Cut and remove the Parylene C coating at an appropriate distance proximal to the first structural component.

[0340] 9. Cut the protrusion from the distal chamber to provide a hollow protrusion of appropriate length.

[0341] A conductive second casing in a hydrogel can be produced by dip-coating suitably captured pins in a gelatin solution, followed by cross-linking and swelling the hydrogel in water, freeze-drying the hydrogel, and removing the second casing from the pins.

[0342] The non-conductive first and second structural components can be made from stainless steel needles (of suitable size) coated with Teflon by removing the needle after the Teflon has hardened.

[0343] As detailed, the method may include applying a conductive bridge, such as an electrically conductive bridge, for example an electrically conductive bridge comprising at least one non-fluidic electrically conductive bridge, to at least a portion of a surface of the distal substrate. The conductive bridge is suitably applied to the distal substrate with a portion of the electrically conductive bridge submerged by the distal substrate. Also, the conductive bridge is preferably positioned relative to the distal substrate such that it can provide a conductive bridge between the distal chamber and the adjacent soft tissue through the distal casing (of an electrically insulating material) when the microelectrode is operated inside the soft tissue. The electrically conductive bridge is preferably positioned mainly radially relative to the distal substrate.

[0344] Where the microelectrode or microelectrode probe comprises an electrically conductive bridge and the method includes one or more steps of finally covering the electrically conductive bridge with an electrically insulating material, the method preferably includes a step of providing that when the microelectrode is operative and positioned within the soft tissue, the electrically conductive bridge electrically couples the adjacent soft tissue and the distal chamber.

[0345] As alluded to above, the electrically conductive bridge may comprise a central tube, and the electrically conductive bridge may be hollow. If the electrically conductive bridge is hollow, it is preferred to apply a further coating of dissolvable substrate after application of the electrically conductive bridge to the distal substrate, such that the central tube is filled with the dissolvable substrate. Once the first and / or second layer of electrically insulating non-degradable material has been applied, the tip of the hollow electrically conductive bridge partially filled with the dissolvable substrate can be cut, thereby providing that the dissolvable substrate of the hollow electrically conductive bridge is in fluid contact with the soft tissue fluid when the microelectrode is inserted into the soft tissue. The soft tissue fluid will gradually dissolve the dissolvable substrate, thereby providing a hollow electrically conductive bridge that allows for the transfer of charged particles between the distal chamber and the adjacent soft tissue, providing an electrical bridge between the distal chamber and the adjacent soft tissue.

[0346] According to one embodiment, the proximal substrate extends in the proximal direction.

[0347] An array of microelectrodes, e.g., a sheet-form array, in which the microelectrodes are arranged essentially in parallel and the microelectrodes are affixed to a non-degradable substrate and / or adhesively affixed to non-degradable micro- or nanofibers, may be produced by providing a template that mimics the shape of the soft tissue adjacent to which the array will be placed. The microelectrodes are arranged essentially in parallel (relative to the microelectrodes) on the template, with due consideration given to the fact that the openings and / or electrically conductive bridges are arranged such that they engage the soft tissue when the sheet-form array is placed adjacent to the soft tissue. The non-degradable substrate and / or the non-degradable micro- or nanofibers are applied onto the template before or after placing the microelectrodes on the template. The microelectrodes are preferably affixed to the non-degradable substrate and / or the non-degradable micro- or nanofibers along a portion of their axial extension, suitably along a distal section of their axial extension that allows the conductive elements proximal to the non-degradable substrate to be bundled together. [Brief description of the drawings]

[0348] [Figure 1] FIG. 1 is a diagram of an area of ​​neural tissue for implantation of a microelectrode probe of the present invention in a section perpendicular to the bone that protects the area of ​​neural tissue. [Diagram 2] FIG. 2 is a view of the area of ​​FIG. 1 in the same section, after providing a circular hole in the bone. [Diagram 3] FIG. 3b is a diagram of the electrode according to FIG. 3a immediately after implantation. [Figure 3a] FIG. 1 is a schematic diagram of a microelectrode probe of the present invention in axial section. [Figure 4] FIG. 1 is a diagram of a microelectrode of the present invention with multiple electrically conductive bridges in the distal chamber. [Figure 4b] FIG. 1 is a diagram of a microelectrode with a hollow conducting element. [Figure 4c] FIG. 1 is a diagram of a microelectrode with a distal chamber comprising an electrically conductive bridge. [Diagram 5] FIG. 2 is a diagram of a microelectrode of the present invention with a distal chamber but without a proximal compartment proximal to the distal chamber. [Figure 5a] FIG. 1 is a diagram of a microelectrode of the present invention featuring a tubular structure that is distinct from the casing. [Figure 5b] FIG. 1 is a diagram of a microelectrode of the present invention featuring a tubular structure that is distinct from the casing, further comprising a structural element within the distal chamber. [Figure 6] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 7] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 8] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 9] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 10] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 11] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 12] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 13] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 14] 17A-17C are diagrams of a process for the manufacture of a microelectrode probe of the present invention showing successive preliminary stages to the microelectrode probe illustrated in FIG. 16. [Figure 15] FIG. 2 is a view of a microelectrode probe of the present invention in an axial direction. [Figure 16] FIG. 1 is a diagram of various microelectrodes of the present invention with an embedded substrate. [Figure 17] FIG. 1 is a diagram of a microelectrode probe of the present invention implanted in neural tissue prior to dissolution of the embedding matrix and the proximal and distal matrix. [Figure 18] FIG. 2 is a diagram of a proto-microelectrode of the invention implanted in neural tissue, in a state of partial dissolution of the embedding matrix and at a stage of conversion into a microelectrode of the invention. [Figure 19] FIG. 18 is a diagram of a microelectrode of the present invention formed in situ from the microelectrode probe of FIG. 17 (in situ microelectrode). [Figure 19a] FIG. 18 is a diagram of a microelectrode of the present invention formed in situ (in situ microelectrode) from the microelectrode probe of FIG. 17. The casing accommodates spatial movement of the surrounding soft tissue. [Figure 20] FIG. 2 is a diagram of an array of four microelectrode tips of the present invention. [Figure 20a] FIG. 1 is a diagram of a sheet-format array with microelectrodes arranged essentially in parallel. [Figure 20b]FIG. 1 is a diagram of a cuff-like sheet format array with microelectrodes arranged essentially in parallel. [Figure 21] FIG. 13 is a tubular cross-section of the array through the distal chamber of the microelectrode probe. [Figure 22] FIG. 11 is a diagram of a half-mold with a tubular structure for the manufacturing steps to produce a microelectrode featuring a tubular structure that is distinct from the casing. [Diagram 23] FIG. 1 is a diagram of a tubular structure included in a variation of a microelectrode. [Figure 24] FIG. 13 is a diagram of a variation of the microelectrode of the present invention in which the radial extension of the casing of the distal chamber is only slightly wider than the radial extension of the insulating portion of the conductive element. [Diagram 25] FIG. 1 is a diagram of an array of microelectrodes. The individual microelectrodes are held together by a web of micro- or nanofibers. [Figure 26] FIG. 11 is a diagram of a microelectrode with an engaging element and a casing also showing micro- or nano-fibers that increase the friction of the casing against the surrounding soft tissue. [Figure 27] FIG. 1 is a diagram of a microelectrode or proximal bridge arrangement, in accordance with certain embodiments. [Figure 28A] FIG. 13 is a diagram of a microelectrode in which a portion of the casing of the distal compartment has been replaced with a transverse member. [Figure 29a] 29 is a cross-sectional view of the microelectrode of FIG. 28 taken along line AA illustrating several embodiments of radial extensions of the transverse members. [Figure 29b] 29 is a cross-sectional view of the microelectrode of FIG. 28 taken along line AA illustrating several embodiments of radial extensions of the transverse members. [Figure 29c] 29 is a cross-sectional view of the microelectrode of FIG. 28 taken along line AA illustrating several embodiments of radial extensions of the transverse members. [Figure 29d] 29 is a cross-sectional view of the microelectrode of FIG. 28 taken along line AA illustrating several embodiments of radial extensions of the transverse members. [Diagram 30]FIG. 4b is a diagram of a microelectrode with a hollow conductive element similar to that of FIG. 4b but with a transverse member instead of a hole. [Diagram 31] FIG. 2 is a diagram of a microelectrode with a distal chamber comprising a transverse member, where the first structural member forms an integral part of the casing. [Diagram 32] FIG. 2 is a cross-sectional view of a microelectrode comprising first and second structural components, with an uninsulated portion of the conductive element disposed within an inner casing and a distal casing comprising an opening distal to the second structural component. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0349] Some embodiments of the present invention are described in more detail below. The embodiments should not be taken as limiting the overall concept of the present invention.

[0350] Principles of implantation and tissue environment 1, 2, 3a, and 3 illustrate diagrammatically a microelectrode (FIGS. 1 and 2), a microelectrode probe implanted in neural tissue (FIG. 3), and a common portion of the skull without a microelectrode probe (FIG. 3a). The neural tissue (3), here brain tissue, is protected by the skull (1) and separated from the skull (1) by the meninges (2) with several sublayers such as the dura mater, arachnoid mater, pia mater, and cerebrospinal fluid. The neural tissue (3) is subject to spatial displacement relative to the skull (1) due to head movements, which are depicted diagrammatically in a direction parallel (arrows b, b') and perpendicular (arrows a, a') to the skull (1). The tissue (2) intermediate between the skull 1 and the brain tissue 3 is also somewhat displaced in such movements, relative to the skull and brain.

[0351] Prior to implantation of the device according to the invention, access to the desired location of the brain is achieved by drilling a hole (8) in the skull (Figure 2) and, optionally, by providing an opening in the dura using, for example, a diamond knife.

[0352] In a next step, a device of the present invention, such as a microelectrode probe (10) or a microelectrode probe array of the present invention in FIG. 3a, is inserted into the brain tissue (3) through the hole (8) (FIG. 3). Once implanted, the microelectrode probe (10) is converted into a microelectrode of the present invention (in situ microelectrode) by contact with aqueous body fluids. Once the matrix material is completely dissolved or decomposed, a fully functional in situ electrode is formed. The microelectrode probe (10) comprises a cover (7) secured within the skull at the hole (8) that protects the skull and soft tissue. The microelectrode (10) comprises a metal or other electrically conductive element (6) that is affixed to or penetrates the cover (7), and that extends from the proximal face of the cover (7) for electrical communication with a microelectrode control unit (not shown) located outside the body or implanted subcutaneously. The proximal portion of the conductive element (6p) is electrically insulated, while the distal portion of the conductive element (6p) is not insulated. The first structural part (12) divides the casing (13) into a proximal compartment (11p) and a distal chamber (11d). The distal chamber is enclosed by a casing further comprising an electrically conductive bridge in the form of a conductive transverse mesh member (14) that allows electrical current to flow between the distal non-insulated portion (6d) of the conductive element and the neural tissue (3). In this microelectrode, the first structural part is integrated with the casing. The first structural part forms an integral part of the casing. Thus, the casing and the first structural part share the same material. The casing, i.e. the first structural part, is slidably connected to the proximal insulated portion (6p) of the conductive element.

[0353] Figures 4, 5, 5a and 5b show four variations of the microelectrode as configured after complete dissolution of the substrate.

[0354] FIG. 4 shows a variation of the microelectrode as constructed after complete dissolution of a matrix of a biocompatible material that is soluble or degradable in aqueous body fluids. This variation comprises a proximal (11p) compartment and a distal chamber (11d). Between the proximal compartment and the distal chamber there is a first structural part (12) that encompasses the proximal insulating part (6p) of the conductive element (6). As seen in FIG. 4, a casing (13) encases the distal chamber (11d). The first structural part (12) that encompasses the insulating part of the conductive element (6p) is slidably attached to the outermost layer of the proximal insulating part of the conductive element. Here, the outermost layer is identical to the insulating layer (15) of the proximal part of the conductive element (6p). Instead of one opening, the distal chamber has four electrically conductive bridges in the form of conductive transverse mesh members (14). All four openings are axially positioned such that the perpendicular distance from the distal non-insulated portion (6d) of the conductive element to the openings remains essentially constant when the conductive element (6) - i.e., the distal uninsulated portion (6d) of the conductive element and the proximal insulated portion (6p) of the conductive element - moves relative to the first structural component (12) consistent with the movement of the conductive element relative to the casing encasing the distal chamber. The distal tip (16) of the uninsulated conductive element should have sufficient axial travel such that the tip never penetrates the casing of the distal tip cap (17) of the distal chamber casing (11d).

[0355] FIG. 4b shows an embodiment of a microelectrode with a hollow conductive element. In addition to the hollow conductive element, the microelectrode also includes third and fourth structural elements that limit axial movement of the conductive element, particularly the insulated portion of the conductive element. FIG. 4b illustrates a hollow conductive element (406) with a central tube (400) that provides fluid communication between a distal chamber (411d) and a reservoir (not shown) that includes a drug. The distal chamber (411d) includes an electrically conductive bridge in the form of a conductive transverse mesh member (414). The first structural part (412) is distinct from the casing (413). The proximal portion of the conductive element is insulated (415). The third (421) and fourth (420) structural elements are disposed around the insulated portion of the conductive element. The third structural element (421) prevents the tip of the non-insulated conductive element (422) from penetrating the casing (411d) of the distal chamber. A fourth structural element (420) allows for removal of the casing when the microelectrode is removed from the soft tissue by engagement of the conductive element placed proximally and externally of the soft tissue.

[0356] Figure 4c illustrates an embodiment of a microelectrode comprising an electrically conductive bridge (450) electrically coupling the distal chamber (11d) with adjacent soft tissue. The first structural part forms an integral part of the casing (12). Also illustrated are the proximal compartment (11p), the conductive element (6), and the insulator of the conductive element (15).

[0357] FIG. 5 depicts a variant of the microelectrode comprising only a distal chamber (11d) encasing the distal non-insulated portion (6d) of the conductive element (6). The casing gradually transforms into a first structural part (integral tubular structure) (12) which is slidably attached to the proximal electrically insulating portion (6p) of the conductive element. The proximal insulating portion (6p) of the conductive element has an electrically insulating layer (15). The casing of the distal chamber comprises an electrically conductive bridge in the form of a conductive transverse mesh member (14). The electrically conductive bridge in the form of a conductive transverse mesh member (14) is axially positioned such that the perpendicular distance of the opening (14) to the non-insulated portion (6d) of the conductive element remains essentially constant even if the conductive element (6) and thus the non-insulated portion (6d) of the conductive element moves axially.

[0358] FIG. 5a shows a variant of the microelectrode with a first structural part (29) that does not form part (material) of the casing (31), (32). The first structural part may be Teflon® (R) and is provided with a channel for receiving the proximal insulating part (6p) of the conductive element. The first structural part features a recess (30) that may reach around the entire circumference of the first structural part. The recess ensures the attachment of the casing (31) to the first structural part. The void / lumen (annular channel) (29a) between the proximal insulating part of the conductive element and the first structural part is sufficient for the proximal insulating part of the element to slide relative to the first structural part. The casing with the first layer (31) and the second layer (32) can be Parylene C. Alternatively, the first (31) and the second layer (32) can be made of different materials. The second layer (32) can be of a material different from that of the first layer. The second layer (32) may be a layer that exhibits increased friction against the surrounding soft tissue compared to the material of the first layer. Alternatively or additionally, the outer surface of the second layer may exhibit a friction-inducing surface structure. The casing comprises an electrically conductive bridge in the form of a lateral conductive lateral mesh member (14).

[0359] Figure 5b illustrates a variation that shares many of the design elements of the microelectrode of Figure 5a, with the difference that a second structural component (SC) is placed in the distal chamber (11d). The second structural component radially (laterally) stabilizes the distal non-insulated portion (6d) of the element. Even if the soft tissue surrounding the microelectrode moves extensively, displacing the casing relative to the element, the second structural component (SC) stabilizes the radial movement of the distal non-insulated portion (6d) of the element, so that the vertical distance between the distal non-insulated portion 6d of the element and the electrically conductive bridge in the form of the conductive lateral mesh member 14 remains similar over time.

[0360] Fabrication of the Microelectrode of the Invention 6 to 16 show several successive steps of one method of manufacturing a microelectrode probe, characterized in that a first structural part is integrated with a casing.

[0361] A metal filament (conductive element) (18) is fastened at both ends to a frame (19). The metal filament comprises a section (18a) that in particular allows the filament to bend axially (FIG. 6), thereby allowing the conductive element to stretch. FIG. 6a shows a frame (19) with a conductive element (18) that does not comprise a section that allows the element to bend axially. In a subsequent step, a portion (6p) of the filament is covered with an electrically insulating non-degradable material (15), thereby forming the proximal insulating portion (6p) of the conductive element. The distal portion (18) of the conductive element is not covered (6d), thereby providing the prerequisite for forming the distal non-insulated portion of the conductive element. Alternatively, the insulation of the conductive element may be removed by evaporation. Next (FIG. 8), a degradable (degradable in body fluids) distal matrix (20d) is formed radially around the distal portion of the non-insulated conductive element and a portion of the distal section (21) of the proximal insulating portion of the element. It is important that the substrate also covers a portion of the proximal insulating portion (21) of the element. In FIG. 9, the proximal substrate (20p) is applied radially around a portion of the proximal insulating portion (6p) of the element. The intermediate section (22) remains uncovered with a substrate or preferably a thin layer of substrate of a biocompatible material that is soluble or degradable in aqueous body fluids or other compositions / substances, such as compositions that facilitate the movement of the first structural part relative to the insulating portion of the conductive element (FIG. 10: 23), applied to the intermediate section around the element defining a void / lumen (annular channel) (23) between the first layer (24) (FIG. 11) of electrically insulating non-degradable material (such as Parylene C) and the insulating portion of the conductive element. FIG. 10b illustrates an electrically conductive bridge (1000) positioned relative to the distal substrate (20d) such that the bridge is partially submerged in the distal substrate. When a matrix or composition / material is applied around the mid-section of the proximal insulating portion of the conductive element, such composition / material can also facilitate axial movement of the casing (first structural part) and / or adjust the electrical impedance between the proximal compartment and the distal chamber. Figure 11 shows a first layer (24) of electrically insulating non-degradable material applied to the distal matrix (DM), mid-section, and proximal matrix (PM).In a further step (FIG. 12), the non-insulating conductive element (6d), the distal substrate (20d), and the first layer (24) are radially cut at section F-F (FIG. 11) to form a distal opening (25) which is covered in a subsequent step (FIG. 13) by a spherical distal cap (tip) substrate (26). FIG. 14 depicts the second layer (27) of electrically insulating non-degradable material covering the distal cap substrate (26) and the first electrically insulating layer (24) of electrically insulating non-degradable material. An electrically conductive bridge (FIG. 15) in the form of a conductive transverse mesh member (14) is provided through the casing encasing the distal chamber at allocation G (FIG. 14). Furthermore, the first and second electrically insulating layers (24, 27) are removed around a circumferential band of height H forming an annular zone (28, FIG. 15) that is not covered by electrically insulating non-decomposable material. The opening may be achieved by laser vaporization and, optionally, thereafter by laser milling vaporization (FIG. 15).

[0362] The placement of the circumferential band and the axial extension may vary depending on the type of tissue to be penetrated by the microelectrode probe.

[0363] The opening (or openings) is preferably arranged axially relative to the non-insulating element such that the (vertical) distance between the non-insulating element and the opening remains essentially similar when the non-insulating element is moved axially. In the last step (FIG. 16), the proto-microelectrode is covered with an embedding matrix (28) of a biocompatible material that is soluble or degradable in aqueous body fluids. The embedding matrix can be formed by spray coating with gelatin in dry air. Both microelectrodes of FIGS. 15 and 16 are suitable to be inserted into soft tissue. Thus, FIGS. 15 and 16 present a microelectrode probe. FIG. 16 also illustrates a cover (7) applied to the proximal face of the casing, the casing being formed of first and second electrically insulating layers of electrically insulating non-degradable material. The first and second electrically insulating layers are preferably Parylene C.

[0364] Figures 17 to 19 depict the microelectrode probe in various states after introduction into soft tissue (3), such as brain tissue. Figure 17 shows the microelectrode probe immediately after insertion into brain tissue (3) through the skull (1) and intermediate tissues (2) between the skull and brain tissue (3) (neuronal tissue), such as the dura mater, arachnoid mater, cerebrospinal fluid, and pia mater (1), and before dissolution of the matrix. The two discontinuous lines DL illustrate tissue regions that may have different properties, for example with regard to propensity for spatial movement (2 and 3).

[0365] FIG. 18 indicates partial dissolution of the embedding matrix (28).

[0366] FIG. 19 illustrates the state of the microelectrode probe after complete dissolution of the implant matrix and partial dissolution of the distal (DM) and proximal (PM) matrix.

[0367] FIG. 19a is an illustration of the configuration of the microelectrode after complete dissolution of all substrates, showing the spatial movement of the surrounding soft tissue. The casing (13), which may comprise first and second electrically insulating layers of electrically insulating non-degradable material, is affixed (associated) with the surrounding soft tissue to an extent that it can accommodate the spatial movement of the soft tissue. The microelectrode also comprises a structural part SC that stabilizes the movement of the non-insulated distal part (6d) of the element. The structural part SC is configured to allow the distal part 6d of the element to move axially without significant friction, but sufficiently stabilizes the distal ratio radially (laterally) such that the (perpendicular) distance between the distal non-insulated part of the element to the electrically conductive bridge in the form of the conductive lateral mesh member 14 remains essentially the same. When the casing is affixed to the surrounding tissue, the openings in the casing communicate with essentially the same area of ​​the soft tissue over time, even when the soft tissue is moving.

[0368] Figure 20 illustrates an array of four microelectrodes (37a), (37b), (37c), (37d). The microelectrodes are embedded in an array substrate (38). Also illustrated is an insulated conductive element (6) affixed to a cover (2002), the cover comprising microcontacts (2000) to which the conductive elements (2001) are connected.

[0369] FIG. 20a illustrates a sheet-type array (2000) of essentially parallel arranged microelectrodes (2100). The microelectrodes comprise an insulated conductive element (2006+2015) and a non-insulated portion of the conductive element (2006). The microelectrodes comprise a distal chamber (2011d) and a proximal compartment (2011p). The distal chamber comprises an electrically conductive bridge (2014) in the form of a conductive transverse mesh member. A first structural part (2029) is separate from the casing, separating the casing into the distal chamber (2011d) and the proximal compartment (2011p). The microelectrodes are affixed to a non-degradable matrix material (2030). The openings of the distal chamber are positioned so as not to be embedded in the non-degradable matrix material ensuring that the openings engage the soft tissue when the sheet-type array of microelectrodes is placed adjacent to the soft tissue.

[0370] FIG. 20b illustrates a sheet-format array having a cuff-like configuration. The array comprises a non-degradable matrix material (2030) having attached thereto microelectrodes (2100), comprising an insulating conductive element (2006+2015), a non-insulating portion of the conductive element (2006), a first structural part (2029) that divides the casing (2013) into a distal chamber (2011d) and a proximal compartment (2011p). The distal chamber comprises an electrically conductive bridge (2014) in the form of a conductive transverse mesh member. The electrically conductive bridge in the form of a conductive transverse mesh member is not embedded by the non-degradable matrix material and is arranged to engage a peripheral nerve when the cuff-like sheet-format array is placed adjacent to the peripheral nerve.

[0371] FIG. 21 illustrates a cross-section of the array at allocation P showing the array substrate (38), with a casing enclosing the distal chamber (39) and the distal uninsulated portion (40) of the conductive element.

[0372] Figure 22 illustrates a manufacturing step in the manufacture of a microelectrode with a first structural part (29) of a different material than the casing. The first structural part is placed around the proximal insulating portion (36) of the conductive element and placed into one front half of a silicone mold (34). The rear half of the mold is suitably positioned against the front half of the mold. It is preferable to center the element against the mold before casting the proximal and distal substrates.

[0373] FIG. 23 shows a perspective view of the first structural part (29) with the central axis shown as a dashed line.

[0374] FIG. 24 shows a variation of a microelectrode comprising a conductive element (101). A proximal portion (106) of the conductive element is insulated with an electrically insulating non-degradable material (100), while a distal portion of the conductive element is not insulated (105). A casing (107) of a flexible electrically insulating non-degradable material encases the non-insulated portion (105) of the conductive element forming a distal chamber (102). The distal chamber casing comprises an electrically conductive bridge (103) in the form of a conductive transverse mesh member. The radially inward extension of the casing is such as to provide a void / lumen (108) between the casing and the insulated portion (106) of the conductive element to allow axial movement of the casing relative to the conductive element. The numerals (104) visualize what is meant by the vertical distance between the non-insulated portion (105) of the conductive element and the opening (103).

[0375] FIG. 25 presents an array of first microelectrodes affixed to each other by micro- or nanofibers (205). Shown are the conductive element (206), the first structural part (204), the casing (207), the distal chamber (202) and the electrically conductive bridge (203) in the form of a conductive transverse mesh member in the casing of the distal chamber. For the sake of simplicity, the insulation of the conductive element is not indicated. The array of microelectrodes affixed to each other by micro- or nanofibers preferably has an extension that provides a patch. The individual microelectrodes may be arranged essentially parallel in essentially one combined plane that forms an array that presents a patch-like global extension. This type of array may be applied to monitor and / or stimulate nervous tissue of the spinal column.

[0376] FIG. 26 shows a variation of the microelectrode with an engaging element (307). The casing (308) presents a net of micro- or nano-fibers (306) that are preferably adhesively attached to the outer surface of the casing. The micro- or nano-fibers increase the friction of the casing against the surrounding soft tissue. FIG. 26 also shows a void / lumen (annular channel) (305) between the first structural part (304) and the insulator (300) around the conductive element (301) and surrounding the insulating portion (309) of the proximal conductive element. The dimensions of the void are exaggerated for clarity. The engaging element is configured to reversibly engage with an elongated rigid pin, such as a needle (not shown). The pin is further configured to insert the microelectrode into or adjacent to the soft tissue. The casing presents an electrically conductive bridge (303) in the form of a conductive transverse mesh member.

[0377] FIG. 27 illustrates a further embodiment based on the principle of having a casing (2706, 2704) separate from a conductive element (2701). The microelectrode comprises a conductive element (2701) that is insulated (2702) along an axial extension (2708). The insulated portion (2708) of the conductive element is slidably associated with the metal casing (2704) via a first structural part (2705). The dimensions of the first structural part (2705) or the insulated portion (2708) of the conductive element are configured such that an annular gap exists between the first structural part (2705) and the insulated portion (2708) of the conductive element. The metal casing (2704) is affixed to the first structural part (2705). Furthermore, the metal casing (2704) is electrically insulated from the surrounding body fluids by a layer of electrically insulating pliable material such as Parylene C. An insulated conductive wire is electrically connected to the metal casing which connects the microelectrode to appropriate electronics for recording and / or stimulation. A structural element (2703) is disposed at the proximal end of the insulated portion of the conductive element. This structural element (2703) prevents the conductive element from separating from the casing (2704). The uninsulated distal portion (2709) of the conductive element (2701) is in electrical contact with the adjacent soft tissue.

[0378] FIG. 28 illustrates a microelectrode with a conductive bridge in the form of a transverse member of the casing of the distal chamber. The transverse member is a net of conductive material (2803). The net of conductive material extends radially around the conductive element (2804). The microelectrode illustrated by FIG. 28 includes a first structural part (2801) that does not form part of the casing (2806). The first structural part contacts the casing and is slidably disposed around the electrically insulating portion (2802) of the conductive element (2804). The casing around the electrically conductive element forms the distal chamber (2807). There is also a second structural part (2805) in the microelectrode that laterally stabilizes the electrically conductive element. The casing (2806), which is not a transverse member, is made of an electrically insulating non-degradable material, such as Parylene C.

[0379] Figures 29a / 29b / 29c / 29d (2804) illustrate different embodiments of the microelectrode depicted by Figure 28. More specifically, Figures 29a / 29b / 29c / 29d illustrate a cross-sectional view at AA in Figure 28. The embodiments of Figures 29a / 29b / 29c / 29d illustrate microelectrodes with transverse members having different radial extensions. Transverse member radial extensions of 360°, 180°, 90° and 60° are illustrated. (2806) illustrates a casing made of an electrically insulating non-degradable material, while (2803) illustrates a transverse member in the form of a net of conductive material.

[0380] FIG. 30 presents an embodiment of a microelectrode with a hollow conductive element like the microelectrode of FIG. 4b, but with a transverse member as a conductive bridge. In addition to the hollow conductive element, the microelectrode also comprises third (421) and fourth (420) structural elements that limit the axial movement of the conductive element, in particular the insulating portion of the conductive element. FIG. 30 illustrates a hollow conductive element (406) with a central tube (400) that provides fluid communication between the distal chamber (411d) and a reservoir (not shown) that comprises a drug. The distal chamber (411d) comprises a transverse member of a net (414). The first structural part (412) is entirely separate from the casing (413). The proximal portion of the conductive element is insulated (415). The third (421) and fourth (420) structural elements are disposed around the insulating portion of the conductive element. The third structural element (421) prevents the tip of the uninsulated conductive element (422) from penetrating the casing of the distal chamber (411d). The fourth structural element (420) allows for removal of the casing when the microelectrode is removed from the soft tissue, due to engagement of the conductive elements proximal and exterior to the soft tissue.

[0381] Figure 31 illustrates an embodiment of a microelectrode with an electrically conductive bridge (450) in the form of a transverse member presented as a net of conductive material. The transverse member electrically connects the distal chamber (11d) with the adjacent soft tissue. The first structural part forms an integral part of the casing (12). Also illustrated are the proximal compartment (11p), the conductive element (6) and the insulator (15) of the conductive element.

[0382] FIG. 32 illustrates a cross-sectional view of an embodiment of a microelectrode comprising a conductive element having an uninsulated portion (3203) between the distal and proximal insulated portions of the conductive element. The diameter (3205, 3211) of the distal insulated portion of the conductive element is larger than the proximal insulated portion (3204, 2114) of the conductive element. The microelectrode has first (3201) and second (3202) structural components slidably disposed about the proximal (3204) and distal (3205) insulated portions, respectively. The uninsulated portion of the conductive element is disposed within an inner casing having an annular cross-section (3206). The inner casing has an inner diameter (3210) that is larger than the diameter (3211) of the distal insulated portion. The casing has an opening (3209) distal to the second structural component. A conductive bridge (3212) in the form of a transverse conductive sheet, such as a mesh, netting, or ion-permeable membrane, is included in the casing that electrically couples the uninsulated conductive element (2103) with the soft tissue adjacent the conductive bridge when the microelectrode is implanted in the soft tissue. The casing (3213), the first structural component (3201), and the second structural component (3202) form a distal chamber (3207). A portion of the casing forms a proximal compartment (3208) around a proximal insulated portion (3204) of the conductive element proximal to the first structural component.

[0383] Further Examples 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, comprising an electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element disposed within a casing (envelope) of electrically insulating non-degradable material, the non-insulated portion of the element being encased (surrounded) by a casing forming a distal chamber within which the conductive element is axially slidable, the casing of the distal chamber comprising an electrically conductive bridge electrically coupling the distal chamber with adjacent soft tissue, and the casing comprising a first structural part along which the electrically insulating portion of the conductive element is axially slidable.

[0384] 2. The microelectrode of claim 1, wherein a first structural part divides a casing (envelope) into a distal chamber and a proximal compartment.

[0385] 3. The microelectrode of claim 1 or 2, wherein at least a portion of the electrically insulating portion is localized within the distal chamber.

[0386] 4. A microelectrode according to any one of claims 1 to 3, wherein an internal cavity / void (allowing axial movement) is provided between the first structural part and the electrically insulating part of the conductive element.

[0387] 5. The microelectrode of any one of claims 1 to 4, wherein the conductive filament comprises a metal, a metal alloy, and / or a conductive polymer, and / or a carbon-containing material, such as graphene, graphite, and carbon nanotubes.

[0388] 6. A microelectrode according to any one of claims 1 to 5, wherein the conductive filament is partially encased by an electrically insulating, non-degradable material.

[0389] 7. A microelectrode according to any one of claims 1 to 6, wherein the conductive filament, or at least a portion of the conductive filament, comprises a tube that provides fluid contact between the distal chamber and adjacent soft tissue.

[0390] 8. A microelectrode according to any preceding claim, wherein the first structural part has an axial extension of at least about 5 μm to about 10 mm, preferably about 5 μm to about 3 mm.

[0391] 9. A microelectrode according to any one of claims 1 to 8, wherein the innermost material of the casing and / or the first structural part and / or the outermost material of the proximal electrically insulating portion of the conductive element (respectively) are selected to reduce friction.

[0392] 10. A microelectrode as described in any one of claims 1 to 9, wherein the distal chamber comprises a second structural component configured to reduce radial movement of the non-insulated portion of the conductive element relative to the distal casing while further configured to allow axial movement of the non-insulated portion of the conductive element relative to the second structural component.

[0393] 11. The microelectrode of claim 10, wherein the second structural component is an integral part of the casing.

[0394] 12. A microelectrode as described in any one of claims 10 or 11, wherein the second structural component is separate from the casing, is at least partially affixed to the casing, and is configured to be slidably connected to or engaged with the non-insulated portion of the conductive element.

[0395] 13. A microelectrode according to any one of claims 1 to 12, wherein the proximal electrically insulating portion of the conductive element comprises a section which facilitates radial and axial bending, suitably a section which facilitates radial bending.

[0396] 14. A microelectrode according to any one of claims 1 to 13, wherein a distal portion of the casing of the distal chamber has a three-dimensional shape that narrows in the distal direction, such as a spherical shape.

[0397] 15. A microelectrode according to any one of claims 1 to 14, wherein the proximal portion of the distal chamber is narrowed, preferably in an annular form, forming a first structural part, the first structural part and the electrically insulating part of the conductive element being axially slidable.

[0398] 16. A microelectrode according to any one of claims 1 to 15, wherein friction between the casing and adjacent soft tissue is greater than friction between the innermost material of the casing and / or the first structural component and / or the outermost material of the proximal electrically insulating portion of the conductive element.

[0399] 17. A microelectrode according to any one of claims 1 to 16, wherein the outermost material and / or outermost surface structure of the casing is selected to increase friction against soft tissue.

[0400] 18. A microelectrode according to any one of claims 1 to 17, wherein the casing comprises two layers of material, an inner layer and an outer layer, the material of the inner layer being different from the material of the outer layer or the surface structure of the inner layer being different from the surface structure of the outer layer.

[0401] 19. A microelectrode according to any one of claims 1 to 18, wherein the casing of the distal chamber comprises an engagement element, preferably provided in a distal portion of the casing of the distal chamber, configured for reversible engagement with an elongated rigid pin, such as a needle, the pin configured to insert the microelectrode into or place the microelectrode adjacent to soft tissue.

[0402] 20. The microelectrode of claim 19, wherein the engaging element is a loop or a net.

[0403] 21. A microelectrode according to any one of claims 19 or 20, wherein the engaging element is degradable in body fluids.

[0404] 22. A microelectrode according to any one of claims 19 to 21, wherein the engaging element is a net established by micro- or nano-fibers.

[0405] 23. A microelectrode according to any one of claims 1 to 22, wherein the casing comprises means for increasing friction between the casing and adjacent soft tissue.

[0406] 24. The microelectrode of claim 23, wherein the means for increasing friction is selected from micro- or nano-fibers affixed to the outermost surface of the casing.

[0407] 25. A microelectrode described in any one of claims 1 to 24, wherein the void / lumen between the first structural component and the outermost layer of the proximal electrically insulating portion of the conductive element is provided with a composition that facilitates movement of the first structural component relative to the outermost layer, in particular a composition comprising any one of lipids, hyaluronic acid, silicone (such as silicone oil or silicone grease), and polymers of monosaccharides such as glucose, and combinations thereof.

[0408] 26. A microelectrode according to any one of claims 1 to 25, in which the casing has a rotationally symmetric shape, suitably a cylindrical shape.

[0409] 27. A microelectrode according to any one of claims 2 to 26, wherein the diameter of the proximal compartment expands in the proximal direction.

[0410] 28. A microelectrode according to any one of claims 1 to 27, wherein the distal chamber and optionally the proximal compartment comprise at least one biologically active substance, such as a pharma- ceutical active substance.

[0411] 29. A microelectrode as described in any one of claims 1 to 28, wherein a conductive element extending proximally of the proximal compartment is of one or more materials different from the materials of the conductive elements disposed in the proximal and distal compartments.

[0412] 30. A microelectrode according to any one of claims 1 to 29, wherein the conductive element comprises a conductive metal and / or a conductive non-metallic material, such as a conductive polymer.

[0413] 31. A microelectrode according to any one of claims 1 to 30, wherein the electrically conductive element comprises or consists of a material selected from the group of platinum, iridium, gold, wolfram, stainless steel, amalgams of such materials, conductive polymers, graphene, graphite, and carbon-containing materials such as carbon nanotubes.

[0414] 32. A microelectrode according to any one of claims 1 to 31, wherein the electrically insulating material of the casing is a biocompatible, non-degradable, flexible polymeric material, in particular a biocompatible flexible polymer selected from polyurethane, polyethylene, polymers with a backbone comprising benzene (e.g. parylenes such as parylene C and parylene M), and polymers based on the polymerization of tetrafluoroethylene.

[0415] 33. The microelectrode of claim 32, wherein the electrically insulating material around the conductive element is selected from any one of the materials of claim 32 and electrically insulating soft inorganic materials (such as glass or glass-like).

[0416] 34. A microelectrode according to any one of claims 1 to 33, wherein the distal chamber, and optionally the proximal compartment, comprise a biocompatible material that is soluble or degradable in aqueous body fluids and provides structural support to the microelectrode when dry.

[0417] 35. A microelectrode according to any of claims 1 to 34, wherein the casing of the distal chamber has at least one opening that provides (after implantation) a fluid-electrically conductive bridge between the uninsulated portion of the conductive element and the soft tissue, allowing ionic exchange between the distal chamber and the tissue.

[0418] 36. A microelectrode described in any one of claims 1 to 35, wherein the electrical impedance between the uninsulated portion of the conductive element and soft tissue is less than the electrical impedance inside the casing between the uninsulated portion of the conductive element and tissue surrounding the proximal portion of the proximal compartment or (if there is no proximal compartment) tissue proximal to the first structural component.

[0419] 37. A microelectrode according to any one of claims 1 to 36, wherein the electrical impedance between the uninsulated portion of the conductive element and the soft tissue is at least 5 times smaller, preferably at least 25 times smaller, preferably at least 100 times smaller than the electrical impedance inside the casing between the uninsulated portion of the conductive element and the tissue surrounding the proximal portion of the proximal compartment or the tissue proximal to the first structural component.

[0420] 38. A microelectrode described in any one of claims 1 to 37, wherein the first structural component and the proximal electrically insulated portion of the conductive element form an annular channel, the electrical impedance across the channel (when filled with body fluid) being at least 5 times greater, preferably at least 25 times greater, preferably at least 100 times greater than the electrical impedance between the uninsulated portion of the conductive element and the soft tissue, and the channel allowing the first structural component to slide axially relative to the conductive element.

[0421] 39. A microelectrode according to any one of claims 1 to 38, wherein the vertical distance between the uninsulated portion of the conductive element and at least one opening in the casing of the distal chamber and / or the electrically conductive bridge remains essentially the same during axial movement of the casing relative to the conductive element, optionally by up to 100%, preferably by up to 50%, preferably by up to 20%, preferably by up to 15%, preferably by up to 10%.

[0422] 40. At least one opening is at least about 1 μm 2 40. The microelectrode of any one of claims 35 to 39, having an area of

[0423] 41. A microelectrode according to any one of claims 35 to 40, wherein the distal chamber comprises a plurality of openings in the distal casing.

[0424] 42. The total area of ​​all openings in the distal chamber is up to about 150,000 μm 2 A microelectrode according to any one of claims 35 to 41, wherein

[0425] 43. A microelectrode as described in any one of claims 1 to 42, comprising a third structural element suitably affixed to the insulated portion of the conductive element to limit axial movement of the casing relative to the conductive element, the third structural element being positioned and configured to preclude penetration of the tip of the uninsulated portion of the conductive element through the casing.

[0426] 44. The microelectrode of claim 43, wherein the third structural element forms an extension around the periphery of an insulating portion of a conductive element disposed in the insulating portion proximal to the first structural component.

[0427] 45. A microelectrode as described in any one of claims 1 to 44, comprising a fourth structural element suitably affixed to an insulating portion of the conductive element to limit axial movement of the casing relative to the conductive element, the fourth structural element being positioned and configured to allow engagement with the conductive element when the conductive element is removed from the soft tissue.

[0428] 46. ​​A microelectrode probe comprising a microelectrode as defined by any one of claims 1 to 45, wherein the distal chamber and optionally the proximal compartment comprise a biocompatible material that provides structural support to the probe when dry for insertion into soft tissue, the biocompatible material being soluble or degradable in aqueous body fluids.

[0429] 47. A microelectrode according to any one of claims 1 to 45, or a microelectrode probe according to claim 46, wherein the microelectrode or microelectrode probe is embedded in an embedding matrix of a biocompatible material that provides the microelectrode or microelectrode probe with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids.

[0430] 48. A microelectrode according to any one of claims 1 to 45 or a microelectrode probe according to claim 46 or 47, comprising an element holder through which a proximal insulated electrically conductive element extends (proximally), the holder being configured to be fixed to tissue other than soft tissue, in particular bony or connective tissue.

[0431] 49. A microelectrode according to any one of claims 1 to 45 and 47 and 48, or a microelectrode probe according to any one of claims 46 to 48, wherein the electrically conductive element is electrically connected to a device for registering biological signals and stimulating soft tissue.

[0432] 50. The microelectrode probe of any one of claims 46 and 47, wherein the biocompatible matrix material is selected from carbohydrate-based materials, protein-based materials, and non-natural polymeric materials, or mixtures thereof.

[0433] 51. An array of microelectrodes according to any one of claims 1 to 45 and 47 to 50, or an array of microelectrode tips according to any one of claims 46 to 50.

[0434] 52. An array as described in claim 51, wherein the microelectrodes and / or microelectrode tips are preferably affixed to a non-degradable substrate, preferably the distal sections of the microelectrodes and / or microelectrode tips, with the proviso that most, preferably more than 50%, more than 60%, more than 70%, suitably essentially all, of the electrically conductive bridge is not embedded by the non-degradable substrate.

[0435] 53. The array of claim 51 or 52, wherein the microelectrodes and / or microelectrode tips are adhesively affixed to at least some of the micro- or nanofibers.

[0436] 54. The array of claim 53, wherein the micro- or nanofibers are non-degradable.

[0437] 55. An array of microelectrodes and / or microelectrode probes configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrodes and / or microelectrode probes comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element being disposed within a casing (envelope) of electrically insulating non-degradable material, the non-insulating portion of the element being enveloped (surrounded) by a casing forming a distal chamber, the conductive element being axially slidable within the casing, and the casing of the distal chamber providing an interface between the distal chamber and the tissue. an array of microelectrodes and / or microelectrode probes, having at least one opening that provides (after implantation) a fluid electrically conductive bridge between the non-insulated portion of the conductive element and soft tissue enabling on-exchange, the at least one opening being beneficial for recording and stimulating electrically excitable cells, the casing comprising a first structural part along which the electrically insulating portion of the conductive element is axially slidable, the microelectrodes being preferably affixed to a non-degradable substrate, preferably to the distal section of the microelectrodes and / or microelectrode probes, with the proviso that most of the openings, preferably more than 50%, more than 60%, more than 70%, suitably essentially all of the openings are not embedded by the non-degradable substrate.

[0438] 56. An array of microelectrodes and / or microelectrode probes configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, the microelectrodes and / or microelectrode probes comprising an elongated electrically conductive element, the elongated electrically conductive element having a proximal electrically insulating portion and a distal non-insulated portion, at least a portion of the conductive element being disposed within a casing (envelope) of electrically insulating non-degradable material, the non-insulated portion of the element being enveloped (surrounded) by the casing forming a distal chamber, the casing comprising: An array of microelectrodes and / or microelectrode probes, wherein the conductive element is axially slidable, the casing of the distal chamber has at least one opening that provides (after implantation) a fluid electrically conductive bridge between the non-insulated portion of the conductive element and the soft tissue enabling ionic exchange between the distal chamber and the tissue, the at least one opening being beneficial for recording and stimulating electrically excitable cells, the casing comprising a first structural part through which the electrically insulated portion of the conductive element is axially slidable, and the microelectrodes and / or microelectrode probes are adhesively affixed to a non-degradable micro- or nanofiber.

[0439] 57. The array of claim 55 or 56, wherein the first structural component divides the casing (envelope) into a distal chamber and a proximal compartment.

[0440] 58. The array of any one of claims 55 or 56, wherein at least a portion of the electrically insulating portion of the conductive element is localized within the distal chamber.

[0441] 59. An array according to any one of claims 55 to 58, wherein an internal cavity / void (to allow axial movement) is provided between the first structural part and the electrically insulating portion of the conductive element.

[0442] 60. An array as described in any of claims 55 to 59, wherein the electrical impedance between the uninsulated portion of the conductive element and soft tissue is less than the electrical impedance inside the casing between the uninsulated portion of the conductive element and tissue surrounding the proximal portion of the proximal compartment or (if there is no proximal compartment) tissue proximal to the first structural component.

[0443] 61. An array according to any one of claims 55 to 60, wherein the electrical impedance between the non-insulated portion of the conductive element and the soft tissue is at least 5 times smaller, preferably at least 25 times smaller, preferably at least 100 times smaller than the electrical impedance inside the casing between the non-insulated portion of the conductive element and the tissue surrounding the proximal portion of the proximal compartment or the tissue proximal to the first structural component.

[0444] 62. An array as described in any one of claims 55 to 61, wherein the first structural component and the proximal electrically insulated portion of the conductive element form an annular channel, the electrical impedance across the channel (when filled with body fluid) being at least 5 times greater, preferably at least 25 times greater, preferably at least 100 times greater than the electrical impedance between the uninsulated portion of the conductive element and the soft tissue, and the annular channel allowing the first structural component to slide axially relative to the conductive element.

[0445] 63. An array according to any of claims 55 to 62, wherein the first structural component has an axial extension of at least about 5 μm to about 10 mm, preferably about 5 μm to about 3 mm.

[0446] 64. An array according to any one of claims 55 to 63, wherein the innermost material of the casing and / or first structural component and / or the outermost material of the proximal electrically insulating portion of the element (respectively) are selected to reduce friction.

[0447] 65. An array according to any one of claims 55 to 64, wherein the vertical distance between the uninsulated portion of the conductive element and at least one opening in the casing of the distal chamber remains essentially the same during axial movement of the casing relative to the conductive element, optionally by up to 100%, preferably by up to 50%, preferably by up to 20%, preferably by up to 15%, preferably by up to 10%.

[0448] 66. The array of any one of claims 55 to 65, wherein the distal chamber comprises a second structural component configured to reduce radial movement of the non-insulated portion of the conductive element relative to the distal casing while further configured to allow axial movement of the non-insulated conductive element relative to the second structural component.

[0449] 67. The array of claim 66, wherein the second structural component is an integral part of the casing.

[0450] 68. The array of claim 66 or 67, wherein the second structural component is separate from the casing, is at least partially affixed to the casing, and is configured to be slidably connected to or engaged with the non-insulated conductive element.

[0451] 69. At least one opening is at least about 1 μm 2 69. The array of any one of claims 55 to 68, having an area of

[0452] 70. The array of any one of claims 55-69, wherein the distal chamber comprises a plurality of openings in the distal casing.

[0453] 71. An array according to any one of claims 55 to 70, wherein the maximum number of openings in the distal chamber is given by the maximum number of openings that does not significantly compromise the structural rigidity / structure of the distal casing.

[0454] 72. The total area of ​​all openings in the distal chamber is up to about 150,000 μm 272. An array according to any one of claims 55 to 71, wherein

[0455] 73. An array as claimed in any one of claims 55 to 72, wherein the proximal electrically insulating portion of the conductive element comprises a section which facilitates radial and axial bending, suitably a section which facilitates radial bending.

[0456] 74. The array of claim 51, 55, or 56, wherein the microelectrodes are arranged essentially in parallel and essentially in one sheet.

[0457] 75. The array of claim 74, wherein the microelectrodes are arranged such that at least one opening and / or most of the electrically conductive bridges of the distal chamber face essentially in the same direction.

[0458] 76. An array according to any one of claims 51 to 75, wherein the microelectrodes and / or microelectrode tips are partially or wholly embedded in an array substrate of a biocompatible material that provides the array with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids.

[0459] 77. The array of claim 76, wherein the dissolvable or degradable biocompatible material is selected from carbohydrate-based materials, protein-based materials, and non-natural polymeric materials, and mixtures thereof.

[0460] 78. An array according to any one of claims 51 to 77, comprising an array cover.

[0461] 79. The array of claim 78, wherein the array substrate extends onto a distal surface of the array cover.

[0462] 80. The array of any one of claims 51 to 79, further comprising an array casing of a flexible, non-degradable material that encapsulates a portion of the array substrate.

[0463] 81. The array of claim 80, embedded in an outer array substrate of a biocompatible material that is solid when dry and soluble or degradable in aqueous body fluids.

[0464] 82. The array of claim 81, wherein the outer array substrate comprises a biocompatible material selected from carbohydrate-based materials, protein-based materials, and non-natural polymeric materials, and mixtures.

[0465] 83. The array of any one of claims 55 to 73, wherein the casing of the microelectrodes is provided with means for increasing friction between the casing and adjacent soft tissue.

[0466] 84. A method for producing a microelectrode according to any one of claims 1 to 45 and 47 to 50, or a microelectrode probe according to any one of claims 46 to 50, comprising the steps of: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the conductive element; - forming a distal matrix that is soluble or degradable in aqueous body fluids, extending axially around the distal uninsulated portion of the conductive element, and optionally extending distally from the distal uninsulated portion of the conductive element; - applying a slide-facilitating composition to a section of the insulating element proximal to the distal substrate and distal to the optional proximal substrate, the slide-facilitating composition facilitating axial movement of the first layer of electrically insulating non-degradable material relative to the insulating layer of the conductive element, the medium optionally providing sufficient void / lumen between the insulating layer of the conductive element and the first layer of electrically insulating non-degradable material; - applying an electrically conductive bridge to at least a portion of the surface of the uncut distal substrate (20d); - optionally forming a proximal substrate extending axially around at least a portion of the proximal electrically insulating portion of the conductive element; - covering the distal substrate and at least a portion of the proximal electrically insulated portion of the conductive element with a first layer of electrically insulating non-degradable material, thereby providing a casing encasing the distal non-insulated portion of the element forming a distal chamber and a first structural component; - cutting a portion of the non-insulated portion of the conductive element and the first layer of electrically insulating non-degradable material near a distal end of the distal substrate (the distal end of the distal chamber) that comprises a distal non-insulated portion of the electrically conductive element, thereby providing a distal opening of the distal compartment; - applying a further distal tip substrate distal to the distal opening; - covering the tip substrate and at least a portion of the first layer of electrically insulating non-degradable material with a second layer of electrically insulating non-degradable material, thereby forming a distal end cap portion that forms a part of a casing of the distal chamber. Including, - the distal and optionally proximal substrates provide structural support to the microelectrode or probe when dry for insertion into soft tissue; at least an area of ​​each electrically conductive bridge is not covered with the first layer and the optional second layer of electrically insulating non-degradable material; and / or one opening is provided through the first layer and the optional second layer of the casing of the distal chamber; and / or a conductive bridge protruding radially from the casing covered with the first layer and the optional second layer is modified such that (when the microelectrode is positioned within the soft tissue) the conductive bridge provides electrical coupling between the distal chamber and any soft tissue adjacent the microelectrode. method.

[0467] 85. A method for producing a microelectrode according to any one of claims 2 to 45 and 47 to 50, or a microelectrode probe according to any one of claims 46 to 50, comprising the steps of: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the conductive element; - forming a distal matrix that is soluble or degradable in aqueous body fluids, extending axially around the distal uninsulated portion of the conductive element, and optionally extending distally from the distal uninsulated portion of the conductive element; - applying an electrically conductive bridge to at least a portion of the surface of the uncut distal substrate (20d); - forming a proximal substrate extending axially around at least a portion of the proximal electrically insulating portion of the conductive element, thereby forming an intermediate section of the insulating conductive element with an axial extension, the intermediate section being disposed proximal to the distal substrate and distal to the proximal substrate, the intermediate section not being covered by the distal and proximal substrates; - applying a thin (up to about 5 μm) layer of a first intermediate substrate and / or slide-facilitating composition to the intermediate section of the insulating element, the first intermediate substrate and / or composition providing sufficient void / lumen (annular channel) between the electrically insulating portion of the conductive element and the first layer of electrically insulating non-degradable material, facilitating axial movement of the first layer of electrically insulating non-degradable material relative to the insulating layer of the conductive element; - covering the distal substrate, the proximal substrate, and an intermediate section of the proximal electrically insulating portion of the element, the intermediate section comprising the intermediate substrate and / or the slide promoting composition together with a first layer of electrically insulating non-degradable material, thereby providing a casing comprising the distal chamber, the first structural component, and the proximal compartment; - optionally providing a second intermediate substrate on the first layer of electrically insulating non-degradable material in radial clamping of the first layer between the distal chamber and the proximal compartment; - cutting a portion of the distal uninsulated portion of the electrically conductive element and the first layer of electrically insulating material near a distal end of the distal substrate (the distal end of the distal chamber), thereby providing a distal opening of the distal chamber; - applying a further distal tip substrate distal to the distal opening; - covering the distal tip substrate and at least a portion of the first layer with a second layer of electrically insulating material, thereby forming a distal end cap that forms part of a casing of the distal chamber; and removing the first layer and optionally the second layer in an annular zone around the proximal substrate. Including, the distal substrate, the distal tip substrate, the proximal substrate, and optionally the first and second intermediate substrates are of a biocompatible material that provides the probe with sufficient rigidity when dry for insertion into soft tissue and that is soluble or degradable in aqueous body fluids; at least an area of ​​each electrically conductive bridge is not covered with the first layer and the optional second layer of electrically insulating non-degradable material; and / or one opening is provided through the first layer and the optional second layer of the casing of the distal chamber; and / or a conductive bridge protruding radially from the casing covered with the first layer and the optional second layer is modified such that (when the microelectrode is positioned within the soft tissue) the conductive bridge provides electrical coupling between the distal chamber and any soft tissue adjacent the microelectrode. method.

[0468] 86. A method for producing a microelectrode according to any one of claims 1 to 45 and 47 to 50, or a microelectrode probe according to any one of claims 46 to 50, comprising the steps of: - providing an elongated electrically conductive element; - covering a proximal portion of the element with an electrically insulating layer, thereby providing a proximal electrically insulated portion and a distal non-insulated portion of the element; - providing a first structural part configured to allow axial movement of the conductive element relative to a proximal electrically insulating portion; - disposing a first structural part around a proximal electrically insulated portion of the conductive element, suitably at a particular axial distance from a distal non-insulated portion of the conductive element; - applying a proximal matrix that is soluble or degradable in aqueous body fluids around a proximal electrically insulating portion of the conductive element, the proximal matrix extending proximally from a proximal surface of the first structural component; - applying a distal matrix that is soluble or degradable in aqueous body fluids around the distal non-insulated portion of the conductive element, the distal matrix extending distally from the distal surface of the first structural component and suitably extending distally up to several millimeters from the distal non-insulated portion of the element; - applying an electrically conductive bridge to at least a portion of the surface of the uncut distal substrate (20d); - applying a first layer of electrically insulating, non-degradable material around the proximal and distal substrates and the first structural component, thereby forming a casing having a distal chamber and a proximal compartment. Including, at least an area of ​​each electrically conductive bridge is not covered with the first layer and the optional second layer of electrically insulating non-degradable material; and / or one opening is provided through the first layer and the optional second layer of the distal casing; and / or a conductive bridge protruding radially from the casing covered with the first layer and optionally the second layer is modified such that (when the microelectrode is positioned within the soft tissue) the conductive bridge provides electrical coupling between the distal chamber and any soft tissue adjacent the microelectrode; method.

[0469] 87. The method of claim 86, wherein the proximal substrate extends in the proximal direction.

[0470] 88. The method of any one of claims 84 to 87, wherein the electrically conductive bridge applied to at least a portion of the surface of the distal substrate is disposed essentially radially relative to the major axis of the conductive element.

[0471] 89. A microelectrode comprising a conductive element having distal and proximal uninsulated sections, and further comprising an insulated section between the distal and proximal uninsulated sections, wherein the insulated section of the conductive element is slidably associated with a casing that encases at least the proximal uninsulated section of the conductive element, the casing further insulating the proximal uninsulated section of the conductive element from direct contact with adjacent soft tissue when the microelectrode is inserted into soft tissue forming a proximal lumen, and the casing exposing conductive material capable of electrically coupling the proximal uninsulated section of the conductive element with a second conductive element electrically coupled to the conductive material of the casing.

Claims

1. 1. A microelectrode configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, to improve and maintain positional stability of the implanted microelectrode in the target soft tissue over time, the microelectrode comprising an electrically conductive element, the electrically conductive element having a proximal electrically insulating portion and a distal non-insulating portion, at least a portion of the conductive element disposed within a casing of electrically insulating, non-degradable material comprising a first structural component and, optionally, a second structural component, the distal non-insulating portion of the conductive element being enveloped (surrounded) by the casing to form a distal chamber, a void / lumen existing between the insulating portion of the conductive element and the first structural component, the void / lumen allowing the conductive element to slide relative to the casing, and the casing of the distal chamber comprising at least one electrically conductive bridge electrically coupling the distal chamber with the adjacent soft tissue.

2. The microelectrode of claim 1 , wherein the casing of the distal chamber includes at least a fluid-conducting bridge.

3. 3. The microelectrode of claim 1, wherein the electrically conductive bridge is selected from a conductive mesh, net, web, ion-permeable membrane, porous polymeric material, transverse member such as a filamentous structure that penetrates the casing of the distal chamber, the conductive bridge comprising a surface area in electrical contact with fluid inside the distal chamber and adjacent soft tissue, the surface area having sufficient extension to provide efficient electrical coupling.

4. SUMMARY OF THE INVENTION A microelectrode is configured to be at least partially embedded in or placed at least partially adjacent to soft tissue, particularly neural, endocrine, and muscular tissue, to improve and maintain positional stability of an implanted microelectrode in a target soft tissue over time, the microelectrode comprising an elongate electrically conductive element having a proximal end and a distal end, the electrically conductive element having insulated proximal and distal portions, the proximal insulating portion extending distally from the proximal end, the distal insulating portion extending proximally from the distal end, the proximal and distal portions separated by an uninsulated portion of the conductive element, at least the uninsulated portion of the conductive element being essentially centrally disposed within a casing of electrically insulating, non-degradable material, the microelectrode comprising first and second insulating portions, the proximal and distal portions being separated by an uninsulated portion of the conductive element, the uninsulated portion of the conductive element being essentially centrally disposed within a casing of electrically insulating, non-degradable material, the microelectrode comprising: the first and second structural components extend radially between the casing and the conductive element, the first and second structural components preferably being permanently attached to the casing and preventing electrical current between the first and second structural components and the casing, the first structural component being movably disposed around at least a portion of the proximal insulated portion of the conductive element, and the second structural component being movably disposed around at least a portion of the distal insulated portion of the conductive element, the casing, first and second structural components forming a distal chamber, the casing having an opening distal to the second structural component, and the casing configured to electrically couple the uninsulated portion of the conductive element with the soft tissue.

5. 5. The microelectrode of claim 4, wherein at least a portion of the uninsulated portion of the conductive element is disposed within an inner casing of electrically conductive material, the inner casing having an outer diameter equal to or less than the inner diameter of the casing.

6. 6. The microelectrode of claim 5, wherein the inner casing has an annular cross-section with an inner diameter larger than either of the diameters of the insulated proximal and distal portions of the conductive element.

7. The microelectrode of claim 4 , wherein the diameter of the distal insulating portion of the conductive element is greater than the inner diameter of the first structural component.

8. 8. The microelectrode of claim 7, wherein the inner casing has an annular cross-section with an inner diameter greater than the distal insulating portion of the conductive element.

9. 5. The microelectrode of claim 4, wherein the first and second structural components have annular cross-sections such that the inner diameter of the first structural component is larger than the diameter of the proximal insulating portion of the conductive element and the inner diameter of the second structural component is larger than the diameter of the distal insulating portion of the conductive element.

10. The microelectrode of claim 1 , wherein the electrical coupling between the uninsulated portion of the conductive element and the soft tissue is provided by at least one conductive bridge.

11. 11. The microelectrode of claim 10, wherein the conductive bridge is selected from a fluid conductive bridge and / or an electrical conductive bridge.

12. 12. The microelectrode of claim 10 or 11, wherein the conductive bridge is selected from an opening, a conductive filamentary structure penetrating the casing of the distal chamber, a lateral member such as a conductive mesh, net, web, and ion-permeable membrane, or a porous polymeric material.

13. The microelectrode of claim 1 , wherein a first structural component divides the casing into a distal chamber and a proximal compartment.

14. 10. The microelectrode of claim 1, wherein the electrically conductive element comprises or consists of a material selected from the group of platinum, iridium, gold, wolfram, stainless steel, amalgams of such materials, conducting polymers, graphene, graphite, and carbon-containing materials such as carbon nanotubes.

15. 10. The microelectrode of claim 1, wherein the first and optional second structural components are separate from the casing and are preferably made from an electrically insulating, non-degradable material.

16. 2. A microelectrode according to claim 1, wherein the distal section of the casing has a three-dimensional shape that is tapered in a distal direction, preferably distal to the second structural component.

17. 2. The microelectrode of claim 1, wherein the friction between the casing and the adjacent soft tissue is greater than the friction between the proximal insulating portion of the conductive element and the first structural component, and optionally between the distal insulating portion of the conductive element and the second structural component.

18. 10. The microelectrode of claim 1, wherein the casing comprises means for increasing friction between the casing and the adjacent soft tissue, preferably selected from micro- or nano-fibers affixed to the outermost surface of the casing.

19. 10. The microelectrode of claim 1, wherein the distal chamber, and optionally the proximal compartment, comprise a biocompatible material that is soluble or degradable in aqueous body fluids and provides structural support to the microelectrode when dry.

20. 2. The microelectrode of claim 1, wherein, when the microelectrode is implanted, the electrical impedance between the uninsulated portion of the conductive element and the soft tissue adjacent the conductive bridge is less, preferably at least 5 times less, 25 times less, or 100 times less, than the electrical impedance inside the casing between the uninsulated portion of the conductive element and the tissue surrounding the proximal portion of the proximal compartment or tissue proximal to the first structural part (if there is no proximal compartment), and less, preferably at least 5 times less, 25 times less, or 100 times less, than the electrical impedance inside the casing between the uninsulated portion of the conductive element and the tissue surrounding the opening in the casing distal to the second conductive component.

21. 10. The array of microelectrodes of claim 1.

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