Device for the insertion of microfilaments into soft tissue

Abstract

The present invention relates to an implantable microfilament guidance structure comprising spatially arranged channels for the accommodation and movement of microfilaments, such as conductive microelectrodes. The microfilament guidance structure comprises a material that disintegrates and / or dissolves upon exposure to mammalian tissue fluids. The channels of the microfilament guidance structure are spatially arranged such that the distance between at least some of the channels gradually increases in the distal direction. The microfilament guidance structure containing the microfilaments forms part of a proto-electrode, also referred to as a conventional microfilament assembly. The present invention also encompasses methods for fabricating the microfilament guidance structure and proto-microelectrode assembly, as well as methods for implanting microfilaments in soft tissue.

Description

[Technical field]

[0001] The present invention relates to an implantable microfilament guidance structure comprising spatially arranged channels for the accommodation and movement of microfilaments, such as conductive microelectrodes. The microfilament guidance structure comprises a material that disintegrates and / or dissolves when exposed to mammalian tissue fluids. The channels of the microfilament guidance structure are spatially arranged such that the distance between the majority of said channels gradually increases in the distal direction. The microfilament guidance structure containing the microfilaments forms part of a proto-electrode, also referred to as a conventional microfilament assembly. The present invention also encompasses methods for manufacturing the microfilament guidance structure and the proto-microelectrode assembly, as well as methods for implanting microfilaments in soft tissue. [Background technology]

[0002] Electrodes for implantation in the nervous system are widely used to record electrical and chemo-electrical signals of neurons and may also be used for electrical stimulation of the nervous system in specific areas, thereby improving motor symptoms, for example in Parkinson's disease or chronic pain.

[0003] The functionality of an implanted electrode depends on the damage caused by the electrode upon insertion, the severity of the tissue reaction caused by implantation, and the degree of neuronal loss near the implanted electrode. The tissue reaction includes glial reactions (e.g., microglial activation and astroglial proliferation, etc.) that can encapsulate the implant after some time, thereby isolating the electrode(s) from the rest of the brain. As a result, the ability of the electrode(s) to record neuronal signals often deteriorates over time. Although the size of the electrode influences the initial damage caused by insertion, one important trigger of the glial reaction is the microforces between the implanted electrode and the nearby tissue that occur when the electrode cannot follow the movements of the tissue. Examples of movements that can move the neural tissue relative to the implanted electrode are respiratory movements, blood pressure pulsations, or physical movements such as head rotation. To reduce the severity of the tissue reaction, the electrode needs to mechanically fit as much as possible to the target soft tissue so that it can move with pulsations and other movements in the tissue, thereby reducing the tearing forces between the implanted electrode and the tissue. For this reason, highly flexible microelectrodes (defined here as electrodes with a diameter of less than about 100 μm) have been developed. In order to accurately implant a highly flexible microelectrode without substantial deviation from the intended track line, structural support during insertion is necessary. Several methods for providing structural support during insertion into deep structures are known in the art, such as temporarily attaching the microelectrode to a rigid support rod with a dissolvable adhesive, or embedding the microelectrode in a hard but dissolvable material.

[0004] WO 2017 / 095288 discloses a proto-microelectrode comprising individual microelectrodes and a biocompatible solid support material. The solid support material sufficiently stabilizes the proto-microelectrode to allow implantation in soft tissue. According to one embodiment, the microelectrodes can be arranged to extend distally. The individual microelectrodes are firmly embedded in the solid support material. WO 2017 / 095288 does not disclose a solid support material that provides a continuous lumen through the solid support material. The microelectrodes are further firmly embedded in the support material, which prohibits the microelectrodes from moving relative to the solid support.

[0005] US Patent Application Publication No. 2019 / 0298993 relates to a neural probe comprising an electrode assembly with simulation and recording electrodes positioned on a very special carrier similar to a Carpenter's tape spring. The tape spring carrier, once deployed in the body tissue, gives the electrode assembly rigidity along the trajectory line, but a degree of flexibility that allows the electrode assembly to move with the tissue. Each thin-film neural probe electrode assembly includes multiple metal traces and sites. These electrode assemblies cannot be accurately introduced into the tissue without the carrier. More specifically, the probe is not rigid, but has some rigidity provided by the tape spring carrier (inside the probe) that maintains the desired trajectory into the body, but then allows the probe to flex and move in harmony with the movement of the body tissue. Additionally, the probe includes a guide tube that allows the carrier to be deployed in a three-dimensional configuration. As disclosed, the guide tube is made of a rigid material that can be inserted into the tissue without buckling and can maintain a nearly straight trajectory through the tissue. The material of the guide tube is a plastic, such as a medical grade plastic, or a metal, such as titanium. The carrier has the form of a tape-spring carrier in the unstressed state of FIG. 4B. Due to the configuration of the channels of the guide tube, the carrier is forced to bend. At the bend, the carrier under stress is locally transformed to the linear cross section of FIG. 4A. As the carrier passes the bend in the channel, the stress state of the carrier is transformed back to its unstressed concave cross section of FIG. 4B. A rigid guide tube is required to bend and hold the tape-spring carrier with a concave cross section area. Without a rigid guide tube, the tape-spring carrier has an inherent desire to gradually return to its unbent, unstressed linear configuration. Thus, in the absence of a stable guide tube, the carrier will present a constant pressure on the adjacent tissue, which may induce inflammation and eventually encapsulate the carrier and electrode assembly, with the risk of significantly compromising the function of the electrode over time.Replacing the non-transient material of the guide tube with a dissolving and / or degradable material would not only risk compromising the flexion of the unstressed carrier during insertion through the guide tube's channels, but would also fail to keep the flexed, stressed section of the carrier in its proper configuration after dissolution of the guide tube. When the guide tube dissolves, the carrier exerts forces on the adjacent tissue, which over time impairs the functionality of the neural probe. Furthermore, given that the guide tube is described as including flexed channels, and that these are part of the guide tube, one can assume that they are of the same material. The described channels are relatively rigid, flexed tubules fixed to the guide tube, which is intended to be fixed to the skull. The guide tube cannot be explanted without also explanting the electrode, since the hole in the guide tube would simultaneously pull out the electrode. Thus, this structure would remain in the tissue, and there is no explanation to suggest otherwise. If present in the tissue, such a structure would likely cause a substantial tissue reaction that could affect tissue some distance away.

[0006] The combination of a tape spring carrier and the disclosed guide tube would result in significant rupture of the carrier against the surrounding soft tissue if the guide tube were to be removed from the soft tissue leaving the carrier within the soft tissue.

[0007] Specific spatial regions of the brain are usually associated with distinct functions, and functions can shift rapidly over very short distances, such as distances of 100 μm. The exact location of a specific function may vary between individuals due to innate anatomical differences between individuals, use-dependent changes, age-dependent changes, or changes due to degenerative diseases. Therefore, it is usually not possible to predict in advance the exact coordinates in the brain for optimal placement of electrodes. For microelectrodes, this is problematic because the range over which neuronal activity can be recorded with a sufficient signal-to-noise ratio is very limited (typically less than a 70 μm radius from the electrode contact). Microelectrodes also have a relatively limited capacity to emit current within typical safety limits, which means that microelectrodes need to be placed as close to the target neuron as possible.

[0008] Increased precision of brain stimulation with fewer side effects can be achieved by over-provisioning the target area with highly flexible and therefore biocompatible microelectrodes, evaluating which of them provide therapeutic effects and which result in undesirable side effects to stimulation, and then selecting a subgroup of microelectrodes in the implanted cluster that together provide effective symptom relief during stimulation without significant side effects (Forni et al, 3D Microelectrode Cluster and Stimulation Paradigm Yield Powerful Analgesia without Noticeable Adverse Effects, Science Advances 7(41), 2021). However, finding the appropriate subgroup of microelectrodes in a cluster of microelectrodes requires very time-consuming iterative testing. There is a need for an insertion method that improves the regularity of spacing of flexible microelectrodes in the target, so that the location of the best group of implanted microelectrodes can be systematically searched for, providing a map in 3D of the therapeutically effective sites as well as the sites causing adverse effects related to the brain anatomy and the corresponding atlas, which can guide subsequent searches in the subject / patient, and also localize the source of the neuronal signal using multiple cooperating microelectrodes.

[0009] Although single or a few highly flexible microelectrodes can be inserted deep into soft tissues, for example when temporarily attached around a rigid support structure, the damage caused by the insertion is substantially increased by the support structure. When many microelectrodes are implanted, the time consumption of the surgical procedure increases with the number of microelectrodes. It would therefore be advantageous if the individual microelectrodes could be inserted substantially simultaneously through the same guidance system. When guided by a syringe, the exact positioning of each of the multiple microelectrodes in the tissue after ejection from the opening of the syringe is problematic, for example, since the highly flexible electrodes may adhere to each other within the syringe and to the inner wall of the syringe while advancing from the syringe, and thus spread more or less randomly. This makes it very difficult and time-consuming to determine the brain coordinates of each microelectrode, for example using imaging. This can hinder the calculation of the brain signal source when used for recording, and also lead to an increased time consumption to find the optimal microelectrode to stimulate for therapeutic or mapping purposes.

[0010] To at least partially overcome the problem of how to implant ultraflexible microelectrodes precisely with respect to the function being studied or affected by stimulation, methods have been developed in which a bundle of microelectrodes is initially separated and stabilized by a rigid but dissolvable material during insertion, and as the dissolvable material swells / dissolves, the bundle advances further into the target area and spreads out as a cluster of microelectrodes (WO 2007 / 040442, WO 2017 / 095288). However, the track line and separation of individual microelectrodes within the bundle during insertion depends on several parameters, such as the swelling and dissolution time course of the dissolvable material, which may be different for the inner and outer parts of the dissolvable material. This may cause the outer parts to swell / dissolve faster than the inner parts. The heterogeneity of the dissolvable material may also contribute to the heterogeneous swelling. Furthermore, the swelling and dissolution time course often depends on, for example, the brain temperature and the accessibility of body fluids around the probe, which may also indicate regional brain differences and inter-individual differences.

[0011] A related problem is how to regularly and effectively implant flexible microtubes to administer drugs or live cells to a given area in soft tissue over a longer period of time, such as days, weeks, or months. For example, stem cells intended for therapeutic use are usually slowly injected into the target tissue from a single syringe as the syringe is slowly retracted. To obtain a more evenly distributed delivery, several tracks are created one after the other. This is very time-consuming and can result in loss of stem cells and increased tissue damage. A similar problem is to provide a uniform distribution of drugs in soft tissue, for example when dealing with tumors.

[0012] Known channel guidance systems that can be attached to the skull are known for the insertion of electrodes, but they need to be withdrawn after surgery, which runs the risk of dislocating the implanted electrodes and also increases the risk of further damage.

[0013] In general, the present invention relates to a proto-microfilament assembly that includes, inter alia, a microfilament guide structure, an elongated hollow guide member, a pin and a microfilament, and a cover structure. [Prior art documents] [Patent documents]

[0014] [Patent Document 1] International Publication No. 2017 / 095288 Brochure [Patent Document 2] US Patent Application Publication No. 2019 / 0298993 [Patent Document 3] International Publication No. 2007 / 040442 Brochure Summary of the Invention [Problem to be solved by the invention]

[0015] It is an object of the present invention to provide a guidance system for inserting flexible microfilaments, such as flexible microelectrodes or flexible catheters.

[0016] A further object of the present invention is to precisely position clusters of flexible microfilaments simultaneously.

[0017] A further object of the present invention is to precisely position clusters / arrays of flexible microfilaments simultaneously without the need to attach the flexible microfilaments to a support structure along the distal length that is introduced into the soft tissue (such as a carrier).

[0018] A further objective is to improve the spatial precision of simultaneous placement of clusters of flexible microfilaments in soft tissue while reducing tissue damage caused during insertion.

[0019] A further objective is to precisely position clusters / arrays of flexible microfilaments and then detach, dissolve and / or disintegrate as much of the proto-microfilament assembly as possible.

[0020] A further objective is the reduction or even substantial reduction of long term tissue reactions in soft tissue caused by the placement and presence of clusters of flexible microfilaments in the soft tissue which may impair the functionality of the clusters / arrays of flexible microfilaments.

[0021] Another object is to provide an electrode assembly that improves the spatial resolution of recording and stimulation in soft tissue.

[0022] Yet another object is to provide highly ordered clusters / arrays of microfilaments.

[0023] Yet another objective is to allow verification of the intended microfilament clusters / arrays prior to implantation.

[0024] Further objects are apparent or can be extracted from the description and claims. [Means for solving the problem]

[0025] The present invention discloses new guidance tools that at least partially overcome some of the problems of accurately implanting microfilaments into soft tissue, including a microfilament guidance structure for simultaneously inserting multiple flexible microfilaments into soft tissue.

[0026] The present invention relates to a protofilament assembly that includes at least the following structural features: a microfilament guidance structure, a microfilament, an elongated hollow guidance member, and a pin.

[0027] The protofilament assembly may also include a hollow support guide (embodiment Δ).

[0028] The present invention further relates to a microfilament guiding structure.

[0029] Furthermore, the present invention also relates to a method, in particular for the production of a microfilament guiding structure.

[0030] Additionally, the present invention also encompasses methods for disposing clusters / arrays of microfilaments.

[0031] The microfilament may be a microelectrode, a microtube, an optical microfiber, or any other elongated microfiber. Two types of microfilaments are specifically contemplated: hollow microfilaments and microelectrodes including conductive filaments, referred to herein as conductive microelectrodes or simply microelectrodes. Preferably, the material or materials of the microfilament have a level of internal tension(s) that prevents the microfilament from substantially deviating from a straight trajectory in the soft tissue as it exits the channel of the filament guidance structure while being propelled forward into the soft tissue. The microfilament is preferably characterized as having a straight shape, i.e., the microfilament does not exhibit bends that tend to provide a curved path in the soft tissue as it propels the provided microchannel from the guidance system into the tissue. The rational is to allow for precise placement in the tissue. Moreover, the microfilament is preferably flexible enough to accommodate the movement of soft tissue, such as nerve tissue, without significantly affecting the soft tissue. Preferably, the microfilament, or at least a portion of the microfilament (the most distal section), or at least a portion of the microfilament adjacent to and in direct contact with the soft tissue, has a level of internal tension that prevents the microfilament from substantially departing from the trajectory provided by the channel of the filament guidance structure during insertion into the soft tissue, and is flexible enough to accommodate movement of soft tissue, such as neural tissue, without significantly affecting the soft tissue.

[0032] The term "transient" characterizes structures and members (entities) that gradually dissolve and / or disintegrate in body (tissue) fluids. The terms "distal" and "proximal" are used to refer to sections, regions, parts (or any further equivalent terms) of the protofilament assemblies, specifically the microfilament guidance structures, the elongated hollow guidance members, and any pin guidance structures. Distal refers to sections, regions, etc. that are located deeper within the soft tissue than the proximal sections, regions. The terms distal and proximal are relative, not absolute, in location.

[0033] The term "flexible microfilament" is defined as a microfilament that does not have sufficient stiffness to be implanted completely into the target tissue without bending from its intended track line, and thus requires structural support if precise insertion is intended.

[0034] The term "microfilament guiding structure" relates to a structure comprising a channel (lumen) for each microfilament. Also, at least in the distal section of the microfilament guiding structure, the radial distance between at least some of the channels gradually increases in the distal direction. The microfilament guiding structure is typically positioned at the distal end of the elongated hollow guiding member. According to embodiment Δ, the microfilament guiding structure is positioned relative to the elongated hollow guiding member such that the distal part of the microfilament guiding structure is located distally (outside the hollow guiding member) relative to the elongated hollow guiding member, while the proximal part of the microfilament guiding structure is located inside (inside) the elongated hollow guiding member. In the context of embodiment Δ, the term "portion" is used instead of "region" for the microfilament guiding structure.

[0035] The term "pin" refers to a structural member to which the microfilament is removably secured. The pin may be configured such that there is a gap between the pin and the elongated hollow guide member to allow sliding while minimizing lateral movement of the pin. The pin may be made of a temporary material that is dissolvable in bodily fluids. If the pin is made of a temporary material, the dissolution profile should be substantially slower than the dissolution of the microfilament guide structure and optionally the hollow support guide or optional pin guide structure. Preferably, the pin is made of a material that maintains its structural rigidity over time. Suitable pin materials may be selected from metals, metal alloys, polymers, and fiber-reinforced polymers (carbon fiber). According to one embodiment, the pin may be removably attached to the pin guide structure.

[0036] The term "pin guide structure" refers to a structure that fixes a pin in an essentially central position (coincident with the central axis of the elongate hollow guide member) relative to the elongate hollow guide member, particularly as the pin and pin guide structure move distally, as long as the pin is attached to the pin guide structure. The pin guide structure is also configured to be able to slide distally (axially) within the elongate hollow guide member. The pin guide structure preferably dissolves and / or disintegrates in bodily fluids.

[0037] The term "hollow support guide" refers to the temporary guide of embodiment Δ that is located between the microfilament guiding structure and the pin. The hollow support guide preferably dissolves and / or disintegrates in bodily fluids.

[0038] The invention is also based on the insight that flexible microfilaments can also be propelled (inserted) short distances (the distance depending on the insertion speed, flexibility and straightness of the microfilament) into soft tissue without substantially deviating from the intended track, provided that there is no need to traverse mechanically stiffer tissues such as the meninges such as the pia mater and arachnoid mater or other tissues that provide structural support for the soft tissue.

[0039] The present invention is further based on the insight that a microfilament guiding structure (used with an elongated hollow guiding member) for orderly insertion of highly flexible microfilaments should be implanted relatively close to the target tissue, such as 1-20 mm, or preferably 5-12 mm, from the target tissue to provide accurate implantation. To reduce tissue damage, the guiding structure may be implanted through a narrow track, including the gel track provided by the techniques presented in WO 2016 / 032384.

[0040] The present invention is also based on the insight that such an implantable microfilament guidance structure should collapse when the microelectrode is extruded into the target tissue, thereby obviating the need to explant the filament guidance structure from the tissue.

[0041] The microfilament guiding structure represents a structure found in the distal portion of the protofilament array. The function of the microfilament guiding structure is to provide a predetermined spatial arrangement of the microfilaments localized within the channels of the microfilament guiding structure (which may also be called filament guiding channels or guiding channels). It is also important that the microfilaments accommodated by the channels can be moved essentially independently of the microfilament guiding structure. A further feature of the disclosed microfilament guiding structure is that the channels of the microfilament guiding structure represent a spatial configuration of at least some of the channels such that the distance between the distal exit of the channel and the central axis of the filament guiding structure is longer than the distance between the proximal exit of said channel and the central axis of the filament guiding structure.

[0042] The microfilament guidance structure is preferably made of one or more materials that are temporary, so that the material gradually disintegrates and is absorbed by the soft tissue fluids. The microfilament guidance structure may include a material that essentially preserves its configuration over time. Such a material should preferably be flexible (e.g. silicone). Using a temporary material for the microfilament guidance structure is preferred over using a non-temporary material. This spatial configuration of the channels provides for increased separation of the individual microfilaments as they are moved / propelled distally relative to the microfilament guidance structure. The independent movement of the individual microfilaments from the filament guidance structure in the distal direction provides for the formation of a cluster / array of microfilaments in the target tissue with a wider spatial distribution than that of the filament guidance structure. The propulsion of the microfilaments from the filament guidance structure into the target tissue also ensures that each filament is surrounded by tissue at its distal portion. The microfilament guidance structure is also a prerequisite for placing a cluster of microfilaments in the target soft tissue without the need for additional structural support from a rigid extension (a carrier that supports the microfilaments adjacent to the soft tissue), which would substantially increase the likelihood of tissue damage. By using a proto-microfilament assembly with a microfilament guiding structure at its distal end, the microfilament guiding structure can be positioned very precisely at a target area of ​​soft tissue before propelling the microfilaments distally, thereby providing an array of microfilaments at the target area. The microfilament guiding structure also ensures that each microfilament is surrounded by tissue at its distal portion immediately after insertion.

[0043] The microfilament guidance structure may include additional structural features in the proximal section. The microfilament guidance structure including additional proximal structural features may be characterized as including a distal and a proximal section. The distal section or portion of the microfilament guidance structure is a section or portion characterized by a) a number of channels equal to or greater than the number of microfilaments, i.e. each microfilament is accommodated by a separate guidance channel, and / or b) a distance between at least some of the individual channels that increases continuously in the distal direction. In the proximal section of the microfilament guidance structure, the distance between the individual channels that accommodate the microfilaments remains essentially similar in the axial direction. The proximal section of the microfilament guidance structure may also be characterized by including a smaller number of microfilament channels than are present in the distal section. According to one embodiment, the proximal section of the microfilament guidance structure includes one channel for accommodating all the microfilaments, which channel is suitably positioned centrally within the proximal section of the microfilament guidance structure.

[0044] According to one embodiment, at least one channel of a microfilament guiding structure may contain two or more microfilaments, particularly when such microfilaments are microelectrodes.

[0045] According to one embodiment, the distal section of the microfilament guiding structure does not include multiple channels, but one channel that accommodates all the microfilaments. If the microfilament guiding structure is set together in two separate structures, distal and proximal, also referred to in some embodiments as distal and proximal microfilament guiding substructures, the proximal microfilament guiding substructure preferably includes one central conduit having a size that accommodates all the microfilaments. The proximal microfilament guiding substructure with one central conduit is referred to in some embodiments as a hollow support guide.

[0046] If the microfilaments in the gap between the microfilament guidance structure and the pin are bundled together with a material that provides temporary rigidity, such as an adhesive and / or any of the dissolvable or degradable materials disclosed herein, the proximal section of the microfilament guidance structure should include a central conduit / channel having dimensions capable of accommodating the bundle of microfilaments, or a hollow support guide as disclosed herein should be interposed between the microfilament guidance structure and the pin.

[0047] According to one embodiment of the proto-microfilament assembly, at least one channel of a microfilament guiding structure included in the assembly may contain two or more microfilaments, particularly when such microfilaments are microelectrodes.

[0048] The terms "region" and "portion" are used in conjunction with the microfilament guidance structure. The term "portion" is used only in conjunction with the microfilament guidance structure related to embodiment Δ, in which the microfilament guidance structure is partially located outside (distal) the elongated hollow guidance member. According to one embodiment, the microfilament guidance structure may have at least two regions that differ in terms of radial extension, namely a distal region and a proximal region. According to one embodiment, the terms section and region may be equivalent. In this embodiment of the microfilament guidance structure, the channel features and the radial extension features coincide. Thus, the distal section corresponds to the distal region and the proximal section corresponds to the proximal region. According to one embodiment of the microfilament guidance structure, the sections and regions are overlapping. For example, the distal section may include a distal region with one radial extension and a proximal region with a different radial extension.

[0049] The protofilament assembly comprises a pin guide structure or, alternatively, a pin positioned proximal to the microfilament guide structure. The pin guide structure is made of any one or more temporary materials suitable for a microfilament guide structure. According to one embodiment, the temporary materials of the microfilament guide structure and the pin guide structure may be the same, but may also be different. The pin guide structure may comprise a rigid pin suitably centrally located within the pin guide structure and extending proximally from the pin guide structure. Furthermore, the microfilament is typically housed in the center of the pin guide structure, suitably around the rigid pin. The microfilament extends proximally from the pin guide structure. According to one embodiment of the protofilament assembly (embodiment Δ), the pin guide structure is omitted. Instead of attaching the pin to the pin guide structure, the pin is configured to slide inside the elongated hollow guide member. Preferably, there is a gap between the pin and the elongated hollow guide member that allows sliding of the pin and can minimize lateral movement of the pin. This Δ embodiment also comprises a hollow support guide arranged between the microfilament guide structure and the pin.

[0050] One embodiment relates to a proto-microfilament assembly having a distal region and a proximal region comprising a microfilament guiding structure as defined herein, the proto-microfilament assembly further comprising a microfilament disposed within a channel of the microfilament guiding structure, an elongated hollow guiding member, and a pin, the microfilament from the microfilament guiding structure extending in a proximal direction, the microfilament removably (temporarily) attached to the pin, the pin being located proximal to the microfilament guiding structure and configured to be slidably disposed inside the elongated hollow guiding member, the protofilament assembly having sufficient rigidity to be inserted into a target region of soft tissue, the pin being disposed inside the elongated hollow guiding member relative to the microfilament guiding structure to provide a gap between the microfilament guiding structure and the pin, the microfilament guiding structure being temporarily attached to the elongated hollow guiding member, and the microfilament can be urged distally outside the channel by moving the pin in a distal direction essentially without moving the elongated hollow guiding member and the microfilament guiding structure.

[0051] A further embodiment of a proto-microfilament assembly relates to a microfilament guiding structure including a distal portion and a proximal portion, the distal portion of the microfilament guiding structure being positioned distal to an elongated hollow guiding member and the proximal portion being positioned inside the elongated hollow guiding member.

[0052] Yet another embodiment of the proto-microfilament assembly relates to a hollow support guide disposed within an elongated hollow guide member between the microfilament guiding structure and the pin, the hollow support guide including a central conduit that accommodates the microfilament, and the pin disposed inside the elongated hollow guide member relative to the hollow support guide to provide a gap between the hollow support guide and the pin.

[0053] Yet another embodiment of the proto-microfilament assembly is one in which the structural rigidity of the microfilaments is increased along the section between the hollow support guide and the distal end of the pin, inhibiting or essentially inhibiting the individual microfilaments from bending or buckling as the pin is moved distally.

[0054] One embodiment of the proto-microfilament assembly ensures that the microfilament is positioned completely inside the channel of the microfilament guiding structure before the pin is distally engaged.

[0055] The Δ embodiment relates to a proto-assembly for pre-positioning a microfilament guiding structure near a target spatial location in soft tissue, e.g., neural tissue, the proto-assembly comprising a microfilament guiding structure, an elongated hollow guiding member, a hollow support guide, a pin, and at least two microfilaments. The elongated hollow guiding member is preferably circular. In particular, a distal portion of the microfilament guiding structure is disposed distally of the elongated hollow guiding member (outside the elongated hollow guiding member), while a proximal portion of the microfilament guiding structure is disposed inside the elongated hollow guiding member (within the elongated hollow guiding member). Furthermore, the microfilament guiding structure is fixed to the elongated hollow guiding member, which allows a microfilament disposed inside a channel of the microfilament guiding structure to be propelled distally into the soft tissue without significant axial movement of the microfilament guiding structure. The microfilament guiding structure may be attached to the elongated hollow guiding member by a suitable biocompatible adhesive that is degradable or dissolvable in body fluids, such as any one of the adhesives disclosed herein. An alternative attachment of the microfilament guiding structure to the hollow guiding member can be by a thread included in the microfilament guiding structure, which can be attached or fixed by suitable means to the proximal region of the elongated hollow guiding member. The attachment can be done physically or by an adhesive, which can be degradable. The microfilament guiding structure can include a plurality of threads, at least 2, 3, 4, 5, 6 or more. The threads can be integrated within a substantial axial length of the microfilament guiding structure. The threads suitably exit laterally from the microfilament guiding structure before the proximal end of the microfilament guiding structure. This embodiment Δ also comprises a hollow support guide arranged between the microfilament guiding structure and the pin. The hollow support guide is preferably positioned close to the microfilament guiding structure, and the hollow support guide is preferably arranged such that it contacts the microfilament guiding structure.The pin is positioned relative to the elongated hollow guide member such that it can slide while its lateral (radial) arrangement relative to the central axis (of the elongated hollow guide member) remains essentially the same. The pin may be arranged with a small gap between the pin and the elongated hollow guide member, allowing for minimization of sliding and lateral movement of the pin. There is a gap between the distal end of the pin and the proximal end of the hollow support guide. In order for the microfilament to be propelled from its position in the channel of the microfilament guide structure into the soft tissue, the pin must have the ability to move axially in the distal direction. In the proximal portion of the microfilament guide structure, it is preferred that the microfilaments are appropriately arranged along the central axis such that the radial distance of the individual microfilaments remains similar. Preferably, the microfilaments from the proximal exit of the microfilament guide structure to the distal end of the pin are appropriately axially aligned along the central axis of the elongated hollow guide member. The hollow support guide is preferably circular with an outer diameter that allows it to be positioned within the elongated hollow guide member. The diameter of the central channel of the hollow support guide is suitably dimensioned to accommodate all the microfilaments and protect the individual microfilaments with sufficient lateral support to not significantly buckle when moving distally. Along at least the distal portion of the hollow support guide, all the microfilaments are not attached to each other, as each microfilament is assigned its own channel inside the microfilament guiding structure. When the microfilaments are attached to each other near where the individual microfilaments are located in their own channel, the distal movement of the individual microfilaments in the channel is prevented. It is further preferred that the bundle of microfilaments at least between the proximal end of the hollow support guide and the distal end of the pin includes at least an additional component that preferably provides rigidity in the axial direction. The component that provides rigidity may be any of the dissolvable and / or disintegrable materials disclosed herein. In this embodiment Δ, the pin preferably has a recess in which the microfilaments are located.The recess may extend over a portion of the pin, and if so, the recess preferably extends over a distal portion of the pin from the distal end to a position where the microfilament deviates radially (laterally) away from the pin and optionally away from the elongated hollow guide member. The recess may also extend over the entire length of the pin. The rigid pin may have an annular cross section with a lateral partition, gap, preferably with a radial extension of 5°-180°, preferably 10°-170°, preferably 15°-170°. The recess or gap of the pin is preferably in which the filament is disposed. The filament in the recess may be bound by any suitable means, for example any of the adhesives disclosed herein. Preferably, the microfilament is fixably attached to the distal end of the pin with any of the adhesives disclosed herein. This embodiment Δ is preferably combined with the embodiment of the protoassembly that includes a lateral filament deviation. Pins with recesses are particularly preferred when the microfilament is essentially offset laterally with respect to the central axis of the elongated hollow guide member.

[0056] According to one embodiment, the protofilament assembly may include an outer cover or cover structure that serves the purpose of retarding the ingress of bodily fluids, particularly into the channels of the microfilament guiding structure, and thus retarding the dissolution and / or disintegration of any structure or material of the protofilament assembly, including substances that dissolve and / or disintegrate when in contact with bodily fluids. The cover may include three layers, the middle layer acting as a liquid-resistant barrier. The layer facing (or closest to) the elongated hollow guiding member, and the layer adjacent to the surrounding soft tissue (if inserted into the soft tissue) comprise any of the materials disclosed herein that dissolve and / or disintegrate, and gel-forming materials. It is important that the distal portion of the cover does not include a liquid-resistant barrier. Preferably, the liquid-resistant barrier does not extend distally from the distal end of the microfilament guiding structure so as not to impede the movement of the microfilaments out of the microfilament guiding structure. The cover may comprise elongated members, such as wires, strands, threads, etc., suitably integrated into an axially arranged liquid-resistant barrier. The elongated member of the cover may be used to tear the cover when removing it from the soft tissue.

[0057] According to another embodiment, the proto-microfilament assembly may be covered by a water-resistant layer. Such a layer may comprise any one of the degradable or degradable materials disclosed herein.

[0058] The protofilament assembly is preferably inserted into the soft tissue along with the stereotactic instrument. More specifically, a proximal portion of the protofilament assembly may be positioned inside the stereotactic guide of the stereotactic instrument.

[0059] According to one embodiment, the protofilament assembly may be configured such that the microfilaments proximal to the pin guide structure are not essentially arranged around the central axis of the inside of the protofilament assembly, but are arranged proximally from a position proximal to the pin guide structure on the outside of the protofilament assembly, and also on the outside of the stereotactic guide, if applicable, and are suitably essentially parallel to the central axis of the protofilament assembly or the stereotactic guide. The microfilaments are preferably fixed to a member that can be fixed to tissue, e.g. bone tissue, in which the soft tissue can move spatially. By arranging the microfilaments on the outside of the protofilament assembly in the proximal portion, a greater degree of spatial freedom is provided for configuring the microfilaments. The microfilaments on the outside of the protofilament assembly may be configured to improve the inherent ability of the microfilaments to accommodate spatial movements of the soft tissue along the section, particularly movements of the soft tissue essentially parallel to the central axis of the filament assembly (i.e., the filament assembly after dissolution of the filament guide structure, the pin guide structure, and the optional removal of the elongated hollow guide member if the hollow guide member is resistant to dissolution in body fluids).

[0060] The protofilament assembly comprises an elongated hollow guide member. The microfilament guide structure and the pin guide structure are housed by the elongated hollow guide member. The elongated hollow guide member serves several functions. One function is to position the microfilament guide structure in the soft tissue prior to inserting the microfilament into the target tissue. A further function is to sufficiently fix or allow fixation of the microfilament guide structure to the elongated hollow guide member. Fixing the microfilament guide structure to the elongated hollow guide member is important since distal axial movement of the individual microfilaments in the channel should be achieved without significant movement of the microfilament guide structure. A further function of the elongated hollow guide member is to provide the protofilament assembly with sufficient structural rigidity to allow precise axial movement during insertion of the protofilament assembly into the soft tissue. A further function of the elongated hollow guide member is to provide distal axial movement of the pin guide structure. To allow axial movement of the pin guide structure while the microfilament guide structure is essentially fixed to the elongated hollow guide member, a gap must exist between the microfilament guide structure and the pin guide structure.

[0061] The elongated hollow guide member can have any configuration as long as the following criteria are met: proper axial alignment of the microfilament guide structure and the pin guide structure; fixation of the microfilament guide structure (or at least the distal microfilament guide sub-structure); possibility of axial movement of the pin guide structure or pins; sufficient rigidity to enable precise positioning of the protoassembly, specifically the microfilament guide structure, and consequently the array / cluster of microfilaments in the target tissue.

[0062] The elongated hollow guide member is usually rotationally symmetric. Any rotationally symmetric shape is suitable. The various rotationally symmetric shapes offer different surface areas. It is preferable to choose a rotationally symmetric shape that offers a smaller surface area. Thus, elliptical and cylindrical shapes are preferred.

[0063] According to one embodiment, the elongated hollow guide has an annular cross section including lateral partitions, i.e. gaps or openings, along the entire axial length of the elongated hollow guide. Preferably, the lateral partitions can have a radial extension of about 5° to about 180°, about 5° to about 170°, about 5° to about 160°, about 5° to about 90°. Preferably, the lateral partitions can have a radial extension of about 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°. Preferably, the lateral partitions may have a radial extension of up to about 60°, 65°, 70°, 75°, 80°, 85°, 90°, 95°, 100°, 105°, 110°, 120°, 130°, 140°, 150°, 160°, 170°, 180°. Any one of the low ranges may be combined with any one of the high ranges. The radial extension of the gap may vary along the length of the elongated hollow structure. An example is that the extension of the gap is smaller in the distal and proximal directions than in the middle region of the elongated hollow structure. According to one embodiment, the elongated hollow guide member may include a continuous gap from the most distal position to the position where the microfilaments radially deviate from the assembly. Additionally, the radial extension of the side partitions of the distal section of the elongate hollow guide member may be less than the radial extension of the side partitions of the proximal section of the distal section of the elongate hollow guide member.

[0064] According to a further embodiment, the elongate hollow guide has an annular cross-section including an axial side partition along a portion of the axial length of the elongate hollow guide, preferably with a continuous gap from the distal end to the location where the microfilaments are laterally offset, if applicable. The axial side partition may be positioned along the distal section of the elongate hollow guide.

[0065] The elongated hollow guide member is made of a material that is either non-transient, whose structural properties are not structurally affected by soft tissue (or bodily fluids), or that is temporary, but disintegrates substantially slower than the material of the microfilament guide structure of the hollow support guide and pin guide structure. The elongated hollow guide member may also be characterized as having a distal and a proximal region. The division of the elongated hollow guide member in the distal and proximal regions may be governed by the annular cross-sectional configuration of the elongated hollow guide member, more specifically, the width (angular width) of the lateral partitions. According to one embodiment, the distal region of the elongated hollow guide member has a partition width that is smaller than the width of the lateral partitions of the proximal region of the elongated hollow guide member. According to one embodiment, the proximal region of the elongated hollow guide member has a lateral partition having a width corresponding to an angular extension of approximately a semicircle (about 180 degrees). The distal lateral partition may have a width corresponding to an angular extension of between about 5 and about 30 degrees. According to one embodiment, the axial length of the distal region of the microfilament guidance structure is essentially similar to the axial length of the distal region of the elongate hollow guidance member.

[0066] The term "proto-microfilament assembly" refers to a proto-microfilament assembly that has not yet been inserted into soft tissue or has not yet assumed the configuration of a filament array in the soft tissue. Thus, once the proto-filament assembly is properly positioned in the soft tissue and the microfilaments are advanced into the target tissue, the proto-filament assembly gradually develops into a filament array including a bundle of microelectrodes that fans out into the soft tissue as a cluster / array of microfilaments once the non-temporary portions, typically the elongated hollow guide members and pins, are removed.

[0067] A further feature of the proto-microfilament assembly is that the microfilaments must have a form that allows them to transmit the axial force exerted by the pin to which they are attached as they move distally, thereby displacing in a distal direction the individual microfilaments housed in the channels of the microfilament guidance structure. The microfilaments are preferably bundled together in the section defined by the gap between the microfilament guidance structure and the pin or in some embodiments the pin guidance structure. The bundling of the microfilaments themselves increases the general stiffness, which can be further improved by the application of materials that further increase the stiffness. The term stiffness refers to the ability to translate axial forces without significant bending.

[0068] The rigid pin is optionally secured to the pin guide structure. The pin must be appropriately positioned inside the elongated hollow guide member and extend proximally from the elongated hollow member. The pin may be constructed of non-temporary materials including metals (e.g., metal alloys) and reinforced hardenable resins (e.g., carbon fiber), as well as temporary materials that are more resistant to degradation by bodily fluids than the pin guide structure and the microfilament guide structure. The rigid pin may be configured to have an annular cross section and includes a lateral partition of annular cross section. The lateral partition may extend axially along a particular length of the rigid pin or along the entire length of the rigid pin. The partition is preferably configured to be capable of containing the microfilament. The partition also allows for efficient attachment of the microfilament (microfilament bundle).

[0069] The term "soft tissue" includes nervous tissue found in the brain, spinal cord, endocrine organs, and muscle tissue and connective tissue. The present invention may be applicable to nervous tissue, specifically tissues of the nervous system including the brain, spinal cord, and central nervous system.

[0070] In some figures, the letters D and P are shown near the arrows. D and P stand for Distal and Proximal, respectively. The arrow near the D indicates the distal direction and the arrow near the P indicates the proximal direction. [Brief description of the drawings]

[0071] [Figure 1] FIG. 1 is a schematic diagram of a proto-microfilament assembly, for clarity the microfilaments are not shown. [Diagram 2] FIG. 2 is a schematic diagram of a microfilament guiding structure. [Figure 2a] FIG. 2 is a cross-sectional view at AA in the distal region of the microfilament guiding structure. [Figure 2b] FIG. 1 is a cross-sectional view at BB of the proximal region of the microfilament guiding structure. [Diagram 3] FIG. 2 is a schematic diagram of an elongated hollow guide member. [Figure 3a] FIG. 13 is a cross-sectional view at CC of the distal region of the elongate hollow guide member. [Figure 3b] FIG. 5 is a cross-sectional view taken along line DD of the proximal region of the elongated hollow guide member. [Figure 4] FIG. 13 is an axial view of the distal side of the microfilament guidance structure further illustrating the spatial arrangement of several filament guidance channels. [Diagram 5] FIG. 13 is a cross-sectional view of a microfilament guidance structure showing individual guidance channels. [Figure 6] 1 is a cross-sectional view of a microfilament guiding structure having a distal section and a proximal section, the proximal section including one central channel for accommodating individual microfilaments. [Figure 6A] FIG. 13 is a cross-sectional view of a microfilament guiding structure and hollow support guide implemented in a proto-microfilament assembly disclosed, for example, by embodiment Δ. [Figure 6B]1A-1C are cross-sectional views of a microfilament guiding structure and hollow support guide implemented, for example, in a proto-microfilament assembly, as disclosed by embodiment Δ, but with a different configuration of the channels of the microfilament guiding structure. [Figure 7] 7 is a cross-sectional view of a microfilament guiding structure having a distal section and a proximal section. The proximal section includes one central channel for accommodating individual microfilaments. The spatial arrangement of the channels differs from that shown in FIG. [Figure 8] FIG. 1 illustrates the definition of the angle α used to characterize the spatial orientation of the guiding channels in the microfilament guiding structure (distal section of the microfilament guiding structure). [Figure 9] FIG. 2 is a schematic diagram of a pin guide structure including a rigid pin. [Figure 10] FIG. 2 is a cross-sectional view of the proto-microfilament assembly of FIG. 1 at position EE. [Figure 11] FIG. 2 is a cross-sectional view of the proto-microfilament assembly of FIG. 1 at position FF. [Figure 12] 1A-1C show channel positioning members used in the manufacturing process of a microfilament guiding structure. [Figure 13] FIG. 13 illustrates the placement of a channel forming rod / wire between two channel positioning members. [Figure 14] FIG. 13 shows the positioning of the channel forming rods / wires between two channel positioning members after they have been bundled together with a bundling member (35). [Figure 15] FIG. 13 shows a proto-microfilament guiding structure of a temporary material capable of swelling in liquid. [Figure 16] FIG. 16 shows the shape of the microfilament guidance structure of FIG. 15 after a portion of the protoguiding structure has been allowed to swell. [Figure 17] FIG. 13 is a cross-sectional view of an embodiment Δ of a microfilament guide structure disposed within an elongated hollow guide member with a separate hollow support guide. [Figure 17A] FIG. 13 is a cross-sectional view of an embodiment Δ of a microfilament guiding structure disposed within an elongated hollow guiding member together with a separate hollow support guide, with the microfilament being propelled distally from the microfilament guiding structure. [Figure 18] FIG. 18 is a radial cross-sectional view of the assembly of FIG. 17 along the line XX with a positioning guide. [Figure 19] 1 is a schematic axial cross-sectional view of the cover, the assembly including the microfilament guide structure, the pin guide structure and the elongated hollow guide member not shown. [Figure 20] A radial cross-sectional view of the cover taken along the line YY. [Figure 21] FIG. 1 is an axial view of an assembly with a cover, a pin, and microfilaments exiting the assembly radially. [Figure 22] 13A-13C show variations of the elongated hollow guide member. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072] The proto-microfilament assembly may be (or may comprise several temporary items) a temporary instrument for the insertion (implantation) and positioning of the microfilament assembly in the soft tissue. Thus, some parts of the proto-microfilament assembly, in particular the microfilament guidance structure and the optional hollow support guides and pins, and optionally the elongated hollow guidance member, gradually collapse after insertion. The principle is to implant (position) the proto-microfilament assembly, and thus the microfilament guidance structure, in the soft tissue at a distance from the target, and then push out (the microfilaments emerge forward from the microelectrode guidance structure and are inserted into the target soft tissue). Afterwards, parts of the proto-microfilament assembly collapse and / or dissolve and absorb by the tissue and / or are detached. If the elongated hollow guidance member, and possibly also the rigid pins fixed in the pin guidance structure, are disintegrable, the need to extract parts of the proto-microfilament assembly is reduced or effectively omitted.

[0073] The proto-microfilament assembly is intended to be introduced into the soft tissue of a mammal. The distal region of the proto-microfilament assembly is the region that first enters the soft tissue. Thus, the distal region / section / end of the proto-microfilament is usually the region that penetrates the soft tissue the deepest until the microfilament is propelled distally. At the same time, the proximal region of the proto-microfilament is usually closer to the mammalian and environmental boundary. The proximal region of the proto-microfilament assembly may also be outside any mammalian tissue (e.g., the proximal portion of an individual microelectrode). The designations distal and proximal are also used to spatially designate structures / members / guides having axial extensions. Thus, the distance between at least some channels of the microfilament guiding structure is further apart in the distal region than in the proximal region.

[0074] The proto-microfilament assembly is preferably held for a period of time during insertion and after positioning, thereby allowing the flexible microfilament to be extruded from the proto-microfilament assembly (i.e., from the microfilament guiding structure) a fixed distance along a predetermined track line provided by the channels of the microfilament guiding structure. The length to which the microfilament can be extruded without bending from the intended track line depends on the flexibility of the microfilament, the insertion speed and tissue resistance, as well as the internal tension of the filament's material. Since tissue resistance depends on the insertion speed, a higher insertion speed requires a stiffer microfilament.

[0075] The proto-microfilament assembly is the entity / instrument that is inserted into the soft tissue. The proto-microfilament assembly should be configured to allow introduction into the soft tissue or into the channels of biocompatible materials provided in the soft tissue, as disclosed in WO 2016 / 032384. Thus, the proto-microfilament assembly should exhibit design features that allow introduction (insertion) into the soft tissue. The proto-microfilament assembly has an elongated rectangular axial extent and should also exhibit rigidity properties that allow accurate positioning of the distal end of the proto-microfilament assembly, i.e., the microfilament guiding structure. Typically, the cross section of the proto-microfilament assembly is rotationally symmetric, most preferably an ellipse with a circular cross section. The radial extension, diameter of the proto-microfilament assembly is typically less than about 2.5 mm, more preferably less than about 2.0 mm. The radial extension of the proto-microfilament assembly is preferably from about 0.35 mm to about 2.5 mm, preferably from about 0.5 mm to about 2.0 mm. When the cross section of the proto-microfilament assembly is generally circular, the diameter is less than about 2.5 mm, more preferably less than about 2.0 mm. Some structural components of the proto-microfilament assembly, such as the microfilament guide structure and the rigid pin, are housed by an elongated hollow guide member. The axial length of the elongated hollow guide member is typically about 20 mm to about 250 mm, but may be longer.

[0076] It is further beneficial that the proto-microfilament assembly exhibits structural integrity that allows the assembly to be accurately positioned within the soft tissue. Positioning of the assembly is preferably performed by steadily inserting the assembly deeper (distal direction) into the soft tissue until a specific location is reached. The proto-microfilament assembly is appropriately inserted into the soft tissue by application of a stereotactic instrument. For the insertion of the proto-microfilament assembly into animal soft tissue, such as brain tissue, stereotactic instruments such as David Kopf Instruments are practical. High-precision stereotactic instruments for human use are also available, such as the Lexell stereotactic frame.

[0077] The proto-microfilament assembly exhibits a microfilament guiding structure at its distal end. The microfilament guiding structure is accommodated in a distal region of an elongated hollow guiding member. The microfilament guiding structure may have different shapes of cross-section. Preferably, the microfilament guiding structure should exhibit a cross-section that can be efficiently accommodated in the distal region of the elongated hollow guiding member. The microfilament guiding structure comprises at least two filament guiding channels, the channels providing uninterrupted communication between the distal and proximal sides of the microfilament guiding structure, i.e. providing a continuous lumen through the structure. Each guiding channel of the microfilament guiding structure accommodates one microfilament. All microfilaments may be of the same type, or the filament guiding structure may accommodate different microfilament types.

[0078] The channel of the microfilament guiding structure is configured to appropriately guide the microfilament when introduced into / through the microelectrode (microfilament) guiding structure. The diameter of the channel is appropriately adjusted to the diameter of the microfilament. The diameter of the channel (the inner diameter of the channel) is desirably larger than the diameter of the microfilament (i.e. larger than the maximum diameter of the section of the microfilament positioned in the channel). The diameter and length of the channel are preferably sized to facilitate accurate guidance of the microfilament within the channel. Preferably, the inner diameter of the channel is no greater than twice the size of the diameter of the microfilament. Preferably, the inner diameter of the channel is about 105% to about 200% of the diameter of the microfilament, preferably about 110%, about 120%, about 130% to about 150%, about 160%, about 170%, about 180%, about 190% of the extension of the diameter of the microfilament. Any one of the lower ranges may be combined with any one of the upper ranges.

[0079] Thus, the microfilament guidance structure may accommodate conductive microelectrodes, hollow filaments for transport of various liquids, optionally including agents having biological effects, and filaments including additional sensing and stimulating means or optical fibers. The microfilament guidance structure may accommodate any number of channels, from 2 to several hundred. Useful numbers of channels are about 5 to about 250, about 8 to about 100, about 10 to about 80. The diameter of the channels should allow axial movement of the microfilaments. The diameter of the channels of the undegraded microfilament guidance structure should be approximately equal to or larger than the diameter of the microfilaments. The diameter of the channels is suitably about 5 to about 25% larger than the diameter of the microfilaments. The diameter of the channels may range from about 5 μm to about 200 μm, suitably about 10 μm to about 120 μm. Different channels may have different diameters. For example, the most central channel may be wider than the other channels.

[0080] At least some of the channels may have a spatial configuration within the microfilament guiding structure in which the distance of a distal exit of a channel relative to a central axis of the microfilament guiding structure is greater than the distance of a proximal exit of the same channel relative to the central axis.

[0081] According to one embodiment, at least some of the guiding channels of the microfilament guiding structure have a spatial (three-dimensional) configuration in which said channels have an angular spatial arrangement with an acute angle α of about 2 degrees to about 40 degrees, the angle α of the channel being given by the acute angle α of a right triangle having sides defined by a line between the center of the proximal and distal outlets of the channel, a line parallel to the central axis of the microfilament guiding structure and intersecting with the center of the proximal channel outlet, and a line perpendicular to the central axis of the filament guiding structure that intersects with the center of the channel and the distal outlet where the angle α is the angle between the two longest sides. The angle α is suitably in the range of about 1 to about 30 degrees, such as about 2 to about 20 degrees, e.g. 1 to 10 degrees.

[0082] According to one embodiment, the microfilament guiding structure comprises a distal portion positioned distally of the elongated hollow guiding member in the axial direction. This distal portion positioned distally of the elongated hollow guiding member may be referred to as the most distal section of the microfilament guiding structure. This most distal section may also be the distal section of a separate distal subunit of the microfilament guiding structure. If the microfilament guiding structure comprises two separate structures, they are referred to as distal and proximal microfilament guiding substructures. This most distal section of the microfilament guiding structure, or preferably the distal section of the distal microfilament guiding substructure, incorporates a spatial configuration of individual channels that allows the microfilaments to increase in radial distance as they move distally into the soft tissue. The most distal section of the microfilament guiding structure, or the distal section of the distal microfilament guiding substructure, or the distal portion of the microfilament guiding structure, suitably has a diameter similar to the outer diameter of the elongated hollow guiding member. It may also have a concave shape such that the most distal portion has the shape of a cone or a dome. In this case, the diameter referred to is the diameter of the proximal part of the cone or dome. The diameter of the proximal section of the distal microfilament guiding substructure or of the proximal section of the microfilament guiding structure is such that this proximal section can be accommodated inside the most distal part of the elongated hollow guiding member. A similar diameter in this context means a diameter that deviates by less than 10%, preferably less than 5%, from the outer diameter of the elongated hollow guiding member.

[0083] In some embodiments, the distal-most section of the microfilament guiding structure may be equivalent to a distal portion of the microfilament guiding structure, or the distal-most section of the microfilament guiding structure may be the distal section of a distal microfilament guiding sub-structure.

[0084] The radial extent of the microfilament guiding structure ranges from about 250 μm to about 2.5 mm, and the axial extent of the microfilament guiding structure ranges from about 0.5 mm to 25 mm, but can be longer when implemented in deeply located targets.

[0085] The radially fanning channels, characterized by any of the above embodiments, may have a different longitudinal shape between the distal and proximal outlets. Preferably, these channels have a longitudinal shape that facilitates axial movement of the microfilament in the distal direction. The radially fanning channels may have a continuous curvature, such as a concave curvature, between the distal and proximal outlets. The channels may also have a configuration in which the radial deviation is entirely provided in the proximal direction within the distal section of the microfilament guiding structure, or entirely provided within the proximal section of the distal microfilament guiding structure, and in which the channels are essentially straight within the most distal section of the microfilament guiding structure, or in which the channels are essentially straight within the distal section of the distal microfilament guiding sub-structure. According to one embodiment, the channels of the distal part of the microfilament guiding structure (included in embodiment Δ) are preferably essentially straight and fan out radially, with the respective bend of each channel being provided in a distal region of the proximal part of the microfilament guiding structure.

[0086] According to one embodiment, the microfilament guidance structures and optional pin guidance structures and hollow support guides (characterized below) comprise a temporary material including any material or combination of materials that disintegrate and / or dissolve upon contact with mammalian tissue fluids. Suitable materials are described below.

[0087] According to another embodiment, the distal microfilament guiding substructure or the distal microfilament guiding structure of embodiment Δ may comprise a flexible material that does not dissolve and / or disintegrate over time in bodily fluids. Such flexible material may be selected from flexible biocompatible polymers including silicone-type polymers and parylene-based polymers. In this embodiment, the proximal microfilament guiding substructure comprises a temporary material including any material or combination of materials that disintegrate and / or dissolve when contacted with mammalian tissue fluids.

[0088] The channels may be lined with a material that has different properties relative to the bulk material, but that gradually disintegrates and / or dissolves upon contact with mammalian tissue fluids.

[0089] The microfilament guiding structure in some embodiments may be characterized as including a distal, a most distal and a most proximal section, where the distal section (and the most distal section, if applicable) accommodates channels that fan out radially, and the proximal section is characterized as a section that accommodates all microfilaments from one channel to a number of channels equal to the number of channels in the distal section. When the proximal section includes two or more channels, they may be aligned essentially parallel to the central axis. The transition from the proximal section to the distal section may be characterized as the approximate location where at least some of the channels begin to deviate radially. According to embodiment Δ, the axial regions of the microfilament guiding structure are referred to as the distal and proximal portions.

[0090] According to one embodiment, the proximal section of the microfilament guidance structure may be a separate structure, referred to as the proximal microfilament guidance substructure. When the proximal section of the filament guidance structure is a separate structure, it is referred to herein as the proximal microfilament guidance substructure. Conversely, when the filament guidance structure includes two separate structures, one separate structure may be referred to as the distal microfilament guidance substructure and the other may be referred to as the proximal microfilament guidance substructure. As detailed, the distal microfilament substructure may include a distal section and a proximal section. This distal section of the distal microfilament guidance substructure may also be referred to as the most distal section of the distal microfilament guidance structure. In the context of a microfilament guidance structure, a section refers to a particular portion of the microfilament guidance structure or a particular portion of the microfilament guidance substructure.

[0091] All features associated with the proximal section of the filament guiding structure may also be associated with a separate proximal microfilament guiding sub-structure.

[0092] The combined cross-sectional area of ​​the one or more channels in the proximal region of the filament guiding structure is greater than the combined cross-sectional area of ​​all microfilaments passing through the proximal region of the microfilament guiding structure.

[0093] A further feature of the proximal region (or portion) of the microfilament guiding structure is that one or more channels are preferably centrally positioned, and if two or more channels are present, such channels are essentially parallel and their individual axes essentially coincide with the major axis of the distal region of the microfilament guiding structure.

[0094] According to one embodiment, the microfilament guiding structure comprises channels (and optionally one or more channels coincident with or parallel to the central axis) having a spatial arrangement characterized in that the distance of a distal outlet of a channel relative to a central axis of the microfilament guiding structure is greater than the distance of a proximal outlet of the same channel relative to the central axis, and the longitudinal shape of the channel is essentially defined by a straight line between the distal and proximal outlets of the channel. (A microfilament guiding structure having a linear arrangement of channels between the distal and proximal outlets does not exhibit a significantly distal or proximal section.)

[0095] The microfilament guiding structure is preferably rotationally symmetric. As repeated above, the microfilament guiding structure may be characterized in that it comprises at least two regions, a distal and a proximal region.

[0096] According to one embodiment, one parameter that may distinguish the distal and proximal regions of the microfilament guiding structure is the area of ​​the distal and proximal cross sections, the cross-sectional area of ​​the proximal region of the microfilament guiding structure being larger than the cross-sectional area of ​​the distal region.

[0097] According to a further embodiment, the distal region of the microfilament guiding structure has a cross-sectional area that is larger than the cross-sectional area of ​​the proximal region of the microfilament guiding structure, the cross-sectional area being suitably rotationally symmetric, preferably circular.

[0098] According to a further embodiment, the microfilament guiding structure comprises two separate structures, a distal microfilament guiding substructure and a proximal microfilament guiding substructure, and the distal microfilament guiding substructure comprises a distal and a proximal section, the cross-sectional area of ​​the distal section of the distal microfilament guiding substructure being greater than the cross-sectional area of ​​the proximal section of the distal microfilament guiding substructure. Furthermore, the cross-sectional area of ​​the proximal section of the distal microfilament guiding substructure is suitably comparable to the cross-sectional area of ​​the proximal microfilament guiding substructure. All cross-sections of the distal and proximal substructures are preferably rotationally symmetric, suitably a rotationally symmetric cross-section preferably exhibits a smaller area, suitably an elliptical or circular cross-section. The microfilament guiding structure and the elongated hollow guiding member are configured such that the combined assembly is capable of moving the microfilament independently of the microfilament guiding structure. More precisely, the combined assembly is capable of moving the microfilament without significantly displacing the microfilament guiding structure.

[0099] In an embodiment featuring a microfilament guiding structure that includes a section distal to the distal end of the elongated hollow guiding member, the microfilament guiding structure or at least the distal microfilament guiding sub-structure is fixed to the elongated hollow guiding member such that the microfilament guiding structure or the distal microfilament guiding sub-structure does not move essentially radially or axially (distal-axial) when the microfilament is extruded distally from the microfilament guiding structure. One option for attaching the microfilament guiding structure to the elongated hollow guiding member is by a sliding-inhibiting filament included in the microfilament guiding structure and attached to the hollow guiding member. Attachment of the sliding-inhibiting filament to the hollow guiding member can be achieved by an adhesive that preferably dissolves over time in bodily fluids. The sliding-inhibiting filament may be inserted into the microfilament guiding structure during formation of the microfilament guiding structure, e.g., during casting. If the sliding-inhibiting filament is attached to a microfilament guiding structure that includes a material that dissolves and / or disintegrates in bodily fluids, the soluble and / or degradable material of the microfilament guiding structure has the ability to remove the hollow guiding member from the soft tissue.

[0100] According to one embodiment, the first part of the distal region of the filament guiding structure may have a cross section with an essentially uniform radial extension; the distal region of the radial extension: Rd1. Preferably, this first part of the distal region of the microfilament guiding structure has an elliptical or circular cross section. The second part of the distal region of the microfilament guiding structure may present a cross section including radial projections. According to one embodiment, the cross section along the distal region of the microfilament guiding structure may have two different regions / cross sections, for example a circular first region / cross section (first part of the distal region) with a radial extension (Rd1) with a radius rd1 and a second region / cross section (second part of the distal region) with a radius rd2 presenting two different radial extensions (Rd1 and Rd2), these extensions occupying different angular sections. This may be expressed as the distal region having two different radial extensions. In case the radial extension has a circular shape, the axial extension is equal to the diameter (also applicable to the proximal region of the microfilament guiding structure). The radial projection of the cross section of the distal region of the microfilament guiding structure (typically having a radial extension Rd2) may have an angular extension of a few degrees to approximately a value smaller than the angular extension of the wider radial extension of the cross section of the proximal region of the microfilament guiding structure. Typically, the angular extension of the radial projection of the cross section of the distal region is between about 5 degrees and about 90 degrees, preferably about 5 degrees to about 45 degrees, for example about 5 degrees to about 15 degrees. According to one embodiment, the radial extension Rd2 of the projection of the distal region of the guiding system is equal to Rwp (as defined below). According to a further embodiment, the radial extension of the distal region having an essentially uniform radial extension is equal to Rnp.

[0101] The proximal region of the microfilament guiding structure preferably has a uniform cross section along the entire proximal region. Alternatively, the cross section of the proximal region of the microfilament guiding structure has two angular sections exhibiting two different radial extensions, a wide radial (proximal) extension Rwp having a radius rwp and a narrow radial (proximal) extension Rnp having a radius rnp. The radial extension of the proximal cross section is suitably elliptical or circular. Also, the combined angular extension of the two different radial extensions of the cross section of the proximal region of the microfilament guiding structure is preferably 360 degrees. The angular extension of the wide radial extension is suitably from about 90 degrees to about 270 degrees, preferably from about 90 degrees to about 180 degrees. An angular extension of up to about 180 degrees may facilitate the assembly of the proto-microfilament assembly, more particularly the assembly of the microfilament guiding structure and the elongated hollow guiding member.

[0102] The microfilaments may be selected from conductive microelectrodes, hollow filaments for the delivery of biologically potent agents, and filaments containing additional sensing means.

[0103] The microfilament is preferably configured to facilitate guidance through the microelectrode guidance structure. Parameters that can facilitate introduction through the channel of the microfilament guidance structure are the differences in the axial shape and flexibility of the microfilament. The thickness, diameter of the microfilament may vary along the microfilament. The microfilament may be configured such that the diameter of the microfilament gradually increases in the distal direction or gradually decreases in the distal direction. Furthermore, the physical properties, such as the degree of flexibility, of the microfilament may vary along its length. Also, the maximum radial extension of the microfilament should not exceed at least the diameter of the guidance channel. The stiffness of the electrode may be increased along the distal portion of the microfilament. The stiffness increase may be achieved by increasing the diameter and / or changing the properties of the microelectrode material and / or by adding stiffening structural elements.

[0104] According to a further aspect, the distal end of the microfilament may feature a distal end member that serves to reduce or inhibit soft tissue microhemorrhage, as disclosed in WO 2017 / 095288. The member at the very distal end of the microfilament completely surrounds the distal end, forming a blunt distal bulge. The bulge typically has a radial extension greater than the radial extension of the distal end of the microfilament.

[0105] According to one embodiment, the microfilament may be coated with gelatin, and the thickness of the insulating material around the microfilament may vary along its length to provide modulation of the flexibility of the microfilament along its length.

[0106] The conductive microelectrode preferably comprises an electrode body that comprises a noble metal or an alloy of a noble metal, such as gold, silver, platinum, iridium, but also other biologically acceptable metals such as stainless steel and tantalum, as well as gold-plated copper, can be used. The metal surface of the electrode body can be modified by applying a layer of another metal or metal alloy, or a layer that comprises or consists of a conductive non-metallic material. Alternatively, the electrode body may consist of or include a conductive polymer (e.g. poly(3,4-ethylenedioxythiophene) (PEDOT)) and / or a conductive carbon such as graphite or graphene, optionally in the form of nanotubes. Alternatively, the electrode body can be made from a core of a non-conductive polymeric material coated with a metal, in particular a noble metal. The parts of the electrode body that lack insulation may advantageously comprise surface-enlarging elements or structures, such as a roughened surface, a cluster of conductive nanowires, e.g. carbon nanowires, or may be porous. This kind of surface-enlarging structure reduces the impedance of the electrode body. A portion of the electrode body is typically coated with an insulating material that includes or consists of a polymeric material, particularly a polymer selected from the group consisting of parylene, polytetrafluoroethylene (Teflon), polyurethane, and silicone. Other suitable insulating materials include biocompatible polymeric materials, inorganic materials such as hafnium oxide.

[0107] The conductive microelectrodes are preferably oblong / elongated in shape. The term "microelectrode" is also meant to include the insulating layer except in the area in electrical contact with the tissue. The radial extension of the microelectrode (including the insulating layer) may be about a few microns (μm), for example from about 2 μm to about 200 μm, suitably from about 5 μm to about 80 μm. The radial extension of the microelectrode may be from 2, 4, 6, 8, 10, 15, 20 μm to 50, 60, 70, 80, 90, 100, 110, 120, 150, 180 μm. Any one of the lower levels may be combined with any one of the higher levels. A radial extension of about 10 μm to about 60 μm is particularly suitable. The microelectrode is preferably rotationally symmetrical and preferably exhibits an elliptical or circular cross section. The length of the microelectrode is governed in part by the location of the soft tissue to be monitored and / or activated, specifically the depth of the soft tissue to be monitored. The microelectrodes should have a length that allows electrical communication from a location within the soft tissue to a location outside the soft tissue to be tested / monitored, e.g., external to the mammalian body or to an electronic device implanted outside the soft tissue. The length of the microelectrodes may range from a few millimeters (mm) to several centimeters, e.g., from a few mm to 50 mm, or even up to 250 mm or more.

[0108] The proto-microfilament assembly provides for the insertion of a cluster of flexible microfilaments from a microfilament guidance structure into soft tissue. Thus, when the proto-microfilament assembly is positioned in the soft tissue, the cluster of flexible microfilaments housed in the guidance channel of the microfilament guidance structure is carefully pushed out of the channel into the soft tissue. Movement of the microfilament cluster is achieved by movement of a pin in a distal direction to which it is attached. Movement of the pin is possible by applying an axial force to a rigid pin housed in a hollow guidance member, at least distally.

[0109] The flexibility of the microfilament reduces the irritation of the soft tissue during insertion to the extent provided by its limited radial range. Furthermore, the flexibility of the microfilament provides compliance to the soft tissue when the microfilament is properly positioned. The flexibility of the microfilament, which induces compliance, reduces the mechanical forces between the microfilament and the immediately surrounding tissue, thereby reducing the formation of encapsulation tissue between the microfilament and the cells of interest in the soft tissue. Even if the microfilament is highly flexible, the proto-microfilament assembly provides conditions to allow the insertion of the flexible microfilament into the soft tissue, as long as the flexible microfilament does not have to cross stiffer structures such as the meninges as described above.

[0110] A feature of the proto-microfilament assembly is the movement of the microfilament into the soft tissue after the assembly is properly positioned. One function of the pin is to apply a distal axial force to the microfilament. The microfilament guiding structure is essentially fixed in space by the hollow guiding member, and the proto-microfilament assembly should exhibit a gap between the microfilament guiding structure and the pin. The axial extension of the gap depends on various factors, including the flexibility of the microfilament. The maximum extension of the microfilament from the microfilament guiding structure is highly correlated with the extension of the gap. Stiffer microfilaments may extend further into the soft tissue than less stiff (more flexible) microfilaments. Thus, the stiffness or flexibility of the microfilament may affect the placement of the microfilament guiding structure and the pin within the elongated hollow guiding member. The gap (distance) between the filament guiding structure or hollow support guide and the pin is typically from about 500 μm to several millimeters, for example up to about 20 mm, but may be longer, such as up to 60 mm or more, if a hollow guiding structure is disposed between the filament guiding structure and the pin.

[0111] According to one embodiment, the pin is attached to the pin guide structure. Preferably, the pin is suitably positioned centrally within the pin guide structure. The pin and the rod are used interchangeably. The pin / rod are preferably temporarily attached to the pin guide structure. By temporarily attached, it is understood that the rod is fixed to the pin guide structure in the proto state of the microfilament assembly. When the proto microfilament assembly is placed in the soft tissue, the pin guide structure gradually disintegrates and / or dissolves. The pin guide structure may preferably comprise or consist of any of the materials associated with the microfilament guide structure disclosed herein. The rod preferably projects proximally from the pin guide structure and can be attached at its proximal end to a micromanipulator. The microfilament is preferably positioned between the pin guide structure and the rod. The rod, microfilament and pin guide structure may be suitably held together by an adhesive on carbohydrate or protein bases such as alkylated and / or carboxylated cellulose derivatives, amylose, and gelatin, but may also be of a different nature such as polyvinyl alcohol, polyvinylpyrrolidone, and alkali salts of polyacrylic acid. The adhesive should preferably exhibit the property of slowly dissolving and / or disintegrating upon contact with soft tissue (i.e., the aqueous tissue fluids of a mammal) while providing bonding properties when in a dry state.

[0112] The microfilament guidance structure may, for example, include 100 channels for accommodating 100 individual microfilaments. The channels of the microfilament guidance structure have a spatial configuration such that the axis (centerline) of each channel increases in the distal direction. Once the microfilament guidance structure is formed, 100 individual microfilaments are inserted into each of the 100 channels, ultimately providing a proto-microfilament assembly that includes 100 individual microfilaments. The spatial reach of all the microfilaments of the cluster depends in part on the diameter of the proto-microfilament assembly, which governs the number of individual microfilaments that can be accommodated. The diameter of the proto-microfilament assembly is defined by the type of soft tissue. For neural tissue, the proto-microfilament assembly may, for example, have a diameter of 2 mm. This proto-microfilament assembly with a diameter of 2 mm may include a microfilament guidance structure that includes 100 channels and 100 microelectrodes (one microelectrode per channel). The channels of the microfilament guidance structure are configured such that at any given point along the major axis of the microfilament guidance structure, the axis of the channel gradually increases in the distal direction. In this configuration, the proto-microfilament assembly provides a precisely positioned cluster of 100 uniformly distributed microfilaments within mammalian soft tissue, such as neural tissue. This particular example of the proto-microfilament assembly is capable of forming clusters of microfilaments in soft tissue with an average distance between individual microfilaments of about 100 μm to 1 mm apart.

[0113] A further part of the proto-microfilament assembly is an elongated hollow guide member made of a biocompatible material having sufficient structural rigidity to provide the proto-microfilament assembly with sufficient structural rigidity that the distal end of the proto-microfilament assembly, i.e., the microfilament guide structure, may be accurately positioned within soft tissue, for example by application of a stereotactic instrument.

[0114] The elongated hollow guide member suitably comprises two distinct regions, a distal region and a proximal region. The elongated hollow guide member must have a suitable spatial configuration to accommodate the microfilament guide structure. Since the pin is also intended to be accommodated in the elongated hollow guide member and to slide distally relative to the elongated hollow guide member, the elongated hollow guide member preferably exhibits an elliptical cross section or an annular circular cross section (annular can mean circular). However, the distal region of the elongated hollow guide member may exhibit internal design elements that prevent the microfilament guide structure from moving axially relative to the elongated hollow guide member. According to one embodiment, the elongated hollow guide member comprises lateral partitions along the entire length of the elongated hollow guide member. According to a further embodiment, the elongated hollow guide member exhibits an annular cross section with an inner diameter Di and an outer diameter Do. The lateral partitions of the distal part of the elongated hollow guide member are preferably smaller than the lateral partitions of the proximal part of the elongated hollow guide member. According to a further embodiment, the lateral division of the annular cross section of the proximal region of the elongate hollow guide member, expressed as an angular extension, is preferably between about 90 degrees and about 270 degrees. The lateral division of the annular cross section of the distal region of the elongate hollow guide member preferably has an angular extension capable of accommodating the distal region of the microfilament guide structure.

[0115] According to one embodiment, the wide radial (proximal) extension Rwp of the proximal cross section of the microfilament guiding structure is preferably between about -10% to the outer diameter Do of the elongated hollow guiding member. Furthermore, the radial extension of the protrusion of the cross section of the distal region of the microfilament guiding structure is preferably between about -10% to the outer diameter Do of the elongated hollow guiding member.

[0116] According to one embodiment, the length of the distal region of the microfilament guiding structure is between about -10% and about 10%, preferably between about -5% and about 5%, suitably between about -3% and about 3%, for example between about -1% and about 1% of the length of the distal region of the elongate hollow guiding member.

[0117] The elongated hollow guide member should be biologically compatible and, according to one embodiment, not susceptible to degradation by mammalian tissue. The elongated hollow guide member may be composed of any biocompatible material that provides sufficient rigidity for the proto-microfilament assembly. In addition, it is preferable that the elongated hollow guide member has properties that allow the pin to slide. The material of the elongated hollow guide member itself provides sliding properties, or the elongated hollow guide member includes a surface layer that facilitates the sliding of the pin or pin guide structure. Useful materials for the elongated hollow guide member are either metal, polymer, or one of the materials of the transitional microfilament guide structure or pin guide structure or hollow support guide. If temporary materials, i.e. materials that disintegrate and / or dissolve in soft tissue, are used for the elongated hollow guide member, they must provide significant structural rigidity to the elongated hollow guide member so that the proto-microfilament assembly can be precisely spatially positioned in the soft tissue. Thus, the temporary material should typically provide sufficient rigidity for the proto-microfilament assembly to be successfully placed within the soft tissue before dissolution and / or disintegration reaches a point where successful placement of the microelectrode is prohibited. The polymeric material may be reinforced with fibers. Suitable metals for the elongated hollow guide members are surgical grade stainless steels such as austenitic SAE316 and martensitic SAE440, SEA420 and 17-4 stainless steel. Preferred materials for the rigid elongated hollow guide members are carbon fiber or surgical grade stainless steels.

[0118] Any material of the proto-microfilament assembly must be biocompatible.

[0119] The microfilament guide structure, the pin guide structure and optionally the elongated hollow guide member may comprise or consist of a material, in particular a material that forms a gel when contacted with mammalian fluids, i.e. a gel-forming material or a gel selected from the group consisting of low molecular weight carbohydrates, proteinaceous materials or mixtures thereof.

[0120] Gelatin from various animal sources, including recombinant gelatin, is a preferred material for the microfilament guiding structure. Gelatin can be from fish and mammalian sources. The stiffness and degradation of gelatin can be controlled by crosslinking. Examples of gelatin crosslinkers are glyceraldehyde, bis(vinylsulfonyl)methane and 1-ethyl-3(3-dimethylamino-propyl)carbodiimide. Another useful crosslinking method is by UV irradiation. The rate of degradation in the body can be controlled by the degree of crosslinking, which can be controlled by the amount of crosslinker used or by controlling the exposure to UV radiation used to crosslink a given amount of gelatin.

[0121] Other aqueous biocompatible gels of the present invention include carbohydrate gels, which include arabinogalactan gels, arabinoxylan gels, galactan gels, galactomannan gels, lichenan gels, xylan gels, as well as cellulose derivatives such as hydroxymethylpropylcellulose, formed by contacting an aqueous medium, particularly an aqueous body fluid, with a gel-forming agent selected from arabinogalactan, arabinoxylan, galactan, galactomannan, lichenan, xylan, hydroxymethylcellulose and other cellulose derivatives that form a gel in contact with an aqueous medium.

[0122] Further aqueous biocompatible gels of the present invention include protein gels. Protein gels other than gelatin derived from animal sources useful in the present invention include whey protein gels, soy protein gels, and casein gels formed by contacting an aqueous medium, particularly an aqueous body fluid, with a gel-forming agent selected from whey protein, soy protein, and casein.

[0123] Materials useful for any of the temporary portions of the assembly, including the microfilament guide structure and any hollow support guide and pin guide structures, include hyaluronic acid, both natural and cross-linked, whey protein, soy protein, casein; arabinoxylan; galactan; galactomannan; lichenan; xylan; cellulose derivatives such as hydroxymethylpropylcellulose; chitosan; gum arabic; carboxyvinyl polymers; sodium polyacrylate; carboxymethylcellulose; sodium carboxymethylcellulose; pullulan; polyvinylpyrrolidone; karaya gum; pectin; xanthan gum; tragacanth; alginic acid; chitin; polyglycolic acid; polylactic acid; copolymers of polyglycolic acid and polylactic acid; copolymers of polylactic acid and polyethylene oxide; polyethylene glycol; polydioxanone; polypropylene fumarate; poly(ethyl glutamate-co-glutamate); poly(tert-butyloxycarbonylmethyl glutamate); polycaprolactone; poly(caprolactone-co-butyl acrylate); lates;Polyhydroxybutyrates and copolymers thereof;Poly(D,L-lactide-co-caprolactone);Poly(glycolide-co-caprolactone);Poly(phosphate esters);Poly(amino acids);Poly(hydroxybutyrates);Polydepsipeptides;Maleic anhydride copolymers;Polyphosphazenes;Polyiminocarbonates;Poly[(7.5% dimethyl-trimethylene carbonate)-co-(2.5% trimethylene carbonate)];Polyethylene oxide;Polyvinyl alcohol homopolymers;Methacrylic and combinations thereof.

[0124] According to one embodiment, the proto-microfilament assembly, in particular the microfilament guiding structure, may allow the administration of pharmacologically active agents. Such pharmacologically active agents may include coagulants, anticoagulants, antibiotics, osmolytes, anti-inflammatory agents, nutrients, factors stimulating growth, factors stimulating cell differentiation, hormones. The administration of pharmacologically active agents may be performed via microfilaments designed for the administration of pharmacologically active agents. Such microfilaments may, for example, be essentially straight and disposed in a channel positioned essentially along a central axis.

[0125] According to yet further embodiments, the protofilament assemblies may include an outer layer of a material selected from the group consisting of low molecular weight carbohydrates, proteinaceous materials such as proteoglycans or glycoproteins and mixtures thereof, preferably gelatin.

[0126] The invention also encompasses methods for producing microfilament guiding structures and proto-microfilament assemblies. Flexible rods and / or wires and / or filaments may be used in the production. When referring to rods, it is implicitly understood that the rods can be replaced by wires of the filaments.

[0127] The microfilament guiding structure may be fabricated by spatially arranging flexible rods and / or wires and / or filament forming channel forming structures which function as microfilament channel forming structures when positioned in a mold. The channel forming rods and / or wires may be covered by a material which forms the channel surfaces of the microfilament guiding structure.

[0128] After positioning the channel-forming rods in the mold, a suitable material, any one of the materials presented herein usable as a microfilament guiding structure material, is provided in a state that allows casting. After the material transitions to a structurally rigid state, the mold is removed and the rods are removed. Gelatin is one preferred material that can be used to manufacture the microfilament guiding structure. The microfilament guiding structure can be manufactured by providing a solution of dissolved gelatin that is poured into a mold containing flexible rods / wires that function as microfilament channel-forming structures. After the gelatin has solidified and optionally dried, the mold and channel-forming rods / wires are removed. The gelatin may be cooled to near 0°C before the flexible rods are removed. The microfilament guiding structure is suitably freeze-dried at a temperature below -20°C.

[0129] The diameter of the wire / rod must be larger than the diameter of the microfilament that is to be introduced into the channel of the microfilament guiding structure.

[0130] A further method for producing a microfilament guiding structure is to place several wires / rods parallel to each other in a mold (FIG. 15). The mold preferably has a tubular shape with a circular cross section. The wires / rods are appropriately positioned centrally in the mold so that one rod / wire coincides with the central axis of the circular mold. After solidification of the casting material, which may be any one of the fugitive materials specified herein (any material that disintegrates and / or dissolves when in contact with soft tissue, tissue fluids), the mold and the rods / wires are removed. The formed microfilament guiding structure may be cooled to near 0° C. before the rods / wires are removed. In a further manufacturing step, the distal region of the microfilament guiding structure is allowed to swell (FIG. 16). The swelling may be achieved by exposing the distal region of the guiding system to a cold aqueous solution. The swelling of the microfilament guiding structure increases the distance of the axis of the channels in the distal region of the microfilament guiding structure. The resulting microfilament guiding structure, comprising channels having a spatial (three-dimensional) configuration in which the distance between the axes of the individual channels increases in the distal direction, may in a further step be covered by an additional layer of temporary material providing a periphery with a constant radial extension in the axial direction.

[0131] A further method of manufacturing a microfilament guiding structure includes the step of providing first and second channel positioning members including an opening (30). Suitably, but not necessarily, the first (FIG. 13: 32) and second (FIG. 13: 33) channel positioning members have openings (3) positioned at the same location. The first and second channel positioning members are positioned at a suitable distance D from each other. A flexible wire / rod (34) is then positioned through one opening of each channel positioning member. The wire / rod may be fixed to the respective channel positioning member or further away. At a suitable location between the channel positioning members, the wire / rod is bundled together. Bundling may be achieved by a rigid bundling member (FIG. 14: 35) or a flexible wire / filament.

[0132] Advantageously, the first and second channel positioning members may further constitute parts of the mold. The first and second channel positioning members may form the base of a cylindrical mold. After positioning the channel arrangement, i.e. the first and second channel positioning members and the wires / rods bundled together between the first and second channel positioning members, a suitable fugitive material or combination of fugitive materials is injected into the mold. After solidification of the material, the mold is opened, the wires / rods are removed, and a structure including channels is formed. Before separating the structure from the mold, or after separation from the mold but before removing the wires, the structure is suitably cooled to a temperature range of about below 10°C to above 0°C or lower and freeze-dried.

[0133] In a further step, the channel-containing structure is cut in at least two portions, preferably perpendicular to the axis of the channel-containing structure, thereby forming two distal microfilament guiding structures.

[0134] The microfilament may be positioned during formation of the microelectrode (microfilament) guiding structure, but the filament guiding structure is preferably fabricated before the microfilament is inserted. The microfilament may be introduced either distal or proximal to the filament guiding structure.

[0135] According to one embodiment applicable to most production varieties, one microfilament is attached to one rod / wire. The attachment of the microfilament to the rod / wire can be achieved at any stage of the production process, as long as the result is that the microfilament is simultaneously inserted into the guiding channel when the channel-forming rod / wire is pulled out of the solidified microfilament guiding structure. At one end of the rod portion, the rod is chipped axially and laterally to provide a non-circular cross section. The microfilament is attached laterally to the rod with the non-circular cross section. Alternatively, one end of the circular rod is configured such that the microfilament can be attached laterally to the end, for example with an adhesive, so that the rod containing the microfilament does not extend radially beyond the diameter of the rod.

[0136] A further embodiment of the invention relates to a method for manufacturing a microfilament guidance structure comprising a channel and a microfilament arranged inside the channel, the method comprising the steps of positioning channel-forming flexible rods and / or wires in a predetermined spatial arrangement, positioning the flexible rods and / or wires with the predetermined spatial arrangement in a mold, filling the mold with a liquid form of a casting material, allowing the casting material to solidify, forming the channel of the microfilament guidance structure when the flexible rods and / or wires are removed from the microfilament guidance structure, and simultaneously positioning inside the channel a microfilament attached to one end of the flexible rods and / or wires. The material for casting is preferably selected from materials that dissolve and / or disintegrate when exposed to tissue fluids, such as gelatin. The radial extension of the microfilament guidance structure is preferably less than about 2.5 mm. At least some of the microfilaments are microelectrodes with a radial extension of up to about 100 μm.

[0137] Disclosure of Specific Embodiments FIG. 17 shows an embodiment Δ presented herein. FIG. 17 shows a proto-microfilament assembly Δ without a cover structure (200). The microfilament guiding structure (101) includes a distal portion (101a) and a proximal portion (101b). The distal portion of the microfilament guiding structure comprises a channel (lumen) (8). The distal end of the microfilament (6) is disposed inside the channel (8). The distal channel of the distal portion (101a) is essentially straight until it reaches the proximal portion (101b) of the microfilament guiding structure. In the distal region of the proximal portion, the appropriate channel is curved to follow the arrangement of the proximal portion so as to be essentially parallel to the central axis of the elongated hollow guiding member (2). All channels of the proximal portion of the microfilament guiding structure are centrally disposed. A hollow support member (102) is disposed proximally of the microfilament guiding structure. The hollow support guide (102) has a central void (102a) for positioning the microfilament (6). Each microfilament in the hollow support guide is individually movable. The diameter of the conduit (102a) is such that the risk of buckling of the individual filaments when moving distally is significantly reduced or eliminated. The microfilament guide structure and the hollow support guide are made of gelatin among other materials that disintegrate and / or dissolve on contact with tissue fluids. Threads (103) fixed to the microfilament guide structure are attached to the elongated hollow guide member (103a). These threads (103) may be attached to any part of the elongated hollow guide member proximal to the microfilament guide structure. Preferably, the threads are attached to the very proximal part of the microfilament guide structure. In FIG. 17, two threads (103) are shown. The microfilament guide structure may comprise multiple threads. According to one version, the microfilament guide structure may also be attached to the elongated hollow guide member by using a degradable adhesive. Also shown in Figure 17 is a pin (4) including a microfilament. The microfilament is removably attached to the pin. Suitably, the microfilament is removably attached to at least the distal section of the pin.Attachment to the pin may be accomplished with any of the degradable adhesives specified herein. Between the hollow support guide (102) and the pin (4) there is a gap (501) having an axial length (501a). The axial distance of the gap governs how far the microfilaments can be driven into the tissue. To prevent the microfilaments from buckling / bending within the gap (501), the microfilaments are bundled together with a temporary material (502) that provides structural rigidity. This material may be any of the dissolvable or degradable materials and / or adhesives specified herein. Preferably, the material providing structural rigidity extends a small amount into the conduit of the hollow support member (502a). If the material providing structural rigidity does not extend radially into the hollow support guide, there is a risk that the individual microfilaments will bend / buckle and not be supported by the conduit of the hollow support guide. Preferably, the length of the hollow support guide is longer than the gap (501) between the hollow support guide and the pin. Preferably, the length of the hollow support guide distal to the microfilament bundle that comprises the material that makes up the structural support (102b) is greater than the gap (501). Figure 17A shows the microfilament assembly after the microfilament has been advanced into tissue and before the microfilament guiding structure and hollow support guide have dissolved.

[0138] 17A shows a proto-microfilament assembly Δ without a cover structure, with the microfilament (6) protruding distally of the microfilament guiding structure (101). Also shown is a pin (4) positioned proximate to the hollow support guide (102).

[0139] 18 shows a cross-sectional view of the proto-microfilament assembly at XX. The microfilament (6) is positioned inside a pin (4), which is positioned inside an elongated hollow guide member (2), which is further proximally positioned within a guide of a stereotactic instrument (not shown).

[0140] FIG. 19 shows the cover structure (200). Although not shown in FIG. 19 for clarity, this is the proto-microfilament assembly of FIG. 17. The cover includes three layers (201, 202, 203). The layer (202) located between the outer layer (201) adjacent to the tissue (when the assembly is introduced into the soft tissue) and the inner layer (203) is a liquid barrier and does not dissolve in tissue fluids. Preferably, this middle layer (202) is made of a thin layer of Parylene C, but can also be made of other polymers. The outer and inner layers (201, 203) include any one of the dissolving and degrading materials disclosed herein. The inner and outer layers may have the same or different properties with respect to dissolution in tissue fluids, since the outer layer is more exposed to the tissue during implantation and dissolves faster than the inner layer. Also, different parts of the inner and outer layers may have different dissolution profiles. Threads (204) are incorporated into the cover. The cover can be partitioned by engaging the threads laterally. Typically, the cover is partitioned (torn) gradually as the assembly and cover (intermediate layer) are detached from the soft tissue by pulling the threads radially. Part of the thread should be positioned radially inside the intermediate layer (202) as shown in FIG. 19. The thread (204) may be partially integrated into the inner layer (203). It is important that the distal end (201a) of the cover does not contain barrier material, otherwise the microfilaments cannot be driven into the tissue.

[0141] FIG. 6A shows.

[0142] FIG. 20 shows a cross-sectional view of the cover at YY.

[0143] FIG. 21 shows an embodiment of a proto-microfilament assembly in which the microfilament bundle is not positioned inside the entire axial length of the pin. Instead, at certain locations, the microfilament is laterally (radially) offset from the pin, the elongated hollow guide member, the optional cover, and the orientation guide. FIG. 21 shows the microfilament (6), the pin (4), the elongated hollow guide member (2), and the cover (202). Additionally, the microfilament outside the cover has a 3D configuration (601) that corresponds to the movement of the soft tissue, particularly the component of the movement of the soft tissue that coincides with the major axis of the microfilament that is positioned in the soft tissue. Suitable 3D configurations include zigzag, serpentine, and coil spring configurations. FIG. 21 also shows microfilament anchoring points (602) that can be localized inside the soft tissue or skull tissue when the array / cluster of microfilaments is positioned inside the neuronal brain tissue. The anchoring points may comprise electronic circuitry.

[0144] Figure 22 shows an elongated hollow guide member (2) with an axial opening (gap) along the entire length of the guide member. As shown, the width of the gap is not uniform. In the distal section (701) and the proximal section (703), the width of the gap is smaller than along the axial distance (702) between the distal and proximal sections. When the microfilaments are laterally offset as in Figure 21, such lateral offset is preferably coincident with the mid-section (702).

[0145] FIG. 1 shows a proto-microfilament assembly (7) according to the invention. The assembly comprises a microfilament guide structure (1) housed within an elongated hollow guide member (2). A pin guide structure (3) is housed proximally within the elongated hollow guide member. A rigid pin (4) is fixed to the pin guide structure (3) and extends proximally from the pin guide structure. Between the microfilament guide structure and the pin guide structure there is a gap (G) in which a microfilament bundle (5) is shown. A microfilament (6) passes through the pin guide structure and extends proximally (P) from the pin guide structure. D and P indicate distal and proximal, so that the D arrow points in the distal direction and the P arrow points in the proximal direction. DMFS and PMFS indicate the distal and proximal regions of the microfilament guide structure. DHGM and PHGM indicate the distal and proximal regions of the elongated hollow guide member (2). At the distal end of the proto-microfilament assembly, a microfilament guide channel outlet (8) is shown. For clarity, no indication of the microfilament in the microfilament guide structure is shown. The microfilament guide structure (1) houses five microfilament guide channels. One centrally located channel coincides with the central axis of the filament guide structure. The other four channels may have a spatial configuration within the microfilament guide structure, as shown diagrammatically by Fig. 6 or Fig. 7. Figs. 6 and 7 show cross sections of the microfilament guide structure (1) with different spatial configurations of the guide channels (9). For clarity, the channels are shown with lines. In reality, the channels are hollow with radial extensions along their entire length. Figs. 6 and 7 show a variation of the microfilament guide structure (1) in which the microfilament (6) is housed in a single channel (10) housed centrally within the proximal section (PSMFGS) of the microfilament guide structure. The distal section of the microfilament guiding structure (DSMFGS) denotes the section where at least some of the filament guiding channels (9) begin to gradually widen radially.During manufacture, the distal and proximal sections of the microfilament guiding structure may be formed separately and subsequently brought together.

[0146] FIG. 2 shows a perspective view of the microfilament guiding structure (1) showing the outlets of some guiding channels (8). Two distinct regions of the microfilament guiding structure are shown: the distal region of the microfilament guiding structure (DMFS) and the proximal region of the microfilament guiding structure (PMFS). FIG. 2a and FIG. 2b show a cross section of the distal region of the microfilament guiding structure (AA) and a cross section of the proximal region of the microfilament guiding structure (BB). As shown by FIG. 2a, there is a protrusion (11) of the cross section of the distal region of the microfilament guiding structure. Also shown in FIG. 2a is the guiding channel outlet (8). ANGD in FIG. 2a and ANGP in FIG. 2b show the angular extension ANGD of the protrusion (11) of the distal region and the angular extension ANGP of the wide radial extension (Rwp) of the proximal cross section of the proximal region of the filament guiding structure. The sections and regions of the microfilament guiding structure may be coincident, but they may not be coincident. FIG. 2a shows a cross section that can be characterized as having two radial extensions: radial extension 1 (Rd1) with radius rd1 and radial extension 2 (Rd2) with radius rd2. The angular extension of radial extension Rd1 and protrusion (11) with radius rd1 are shown here to be several degrees. According to FIG. 2, the protrusion extends along the entire length of the distal region (DMFS). However, the protrusion may also extend part of the length of the distal region. FIG. 10 shows a cross section of the proto-microfilament assembly of FIG. 1 at EE (distal region of the filament guidance structure and the elongated hollow guiding member) and FIG. 11 shows a cross section of the proto-microfilament assembly of FIG. 1 at FF (proximal region of the filament guidance structure and the elongated hollow guiding member). In FIG. 2, the radial extension (diameter) Rd1 is the same as the radial extension (diameter) of the narrow radial extension Rwp of the proximal cross section of the proximal region of the filament guidance structure.

[0147] FIG. 3 shows a perspective view of an elongated hollow guide member (2) including a distal region (DHGM) and a proximal region (PGHM) of the elongated hollow guide member. FIG. 3a and FIG. 3b show cross-sectional views of the elongated hollow guide member at the distal (CC) and proximal (DD) portions. The elongated hollow guide member includes lateral partitions (13) along the entire length of the elongated hollow guide member. In this configuration, the elongated hollow guide member has an annular cross-section. FIG. 3a shows a cross-section of the distal region of the elongated hollow guide member. The partitions (13) of the distal cross-section are seen at the top. The angular extensions (ANGDH) of the distal partitions are configured to accommodate the protrusions (11) of the distal region of the filament guidance structure (1). FIG. 3a also shows the inner diameter (Di) and outer diameter (Do) of the cross-section of the distal region. FIG. 3b shows a proximal cross-section of the proximal region of the elongated hollow guide member. The angular extension of the proximal partition is approximately 180 degrees. The inner diameter Di of the elongated hollow guide is 1.3 mm and the outer diameter Do is 1.6 mm. The partition in the distal region of the elongated hollow guide is approximately 4 mm. The values ​​shown are for illustrative purposes and may vary significantly.

[0148] Figures 10 and 11 show cross sections of the proto-microfilament assembly according to Figure 1 at positions EE and FF. Figure 10 shows the distal region of the filament guidance structure (1) and the elongated hollow guidance member (2). Several guidance channels (9) are also shown. Figure 11 shows the proximal region of the filament guidance structure (1) and the elongated hollow guidance member (2), as well as the central channel (10) that houses all the microfilaments. For clarity, the microfilaments have been omitted. Figures 10 and 11 show an embodiment in which the angular extension of the cross sections of the filament guidance structure and the elongated hollow guidance member are adjusted so that the combination of the filament guidance structure and the elongated hollow guidance member provides an elongated entity with a uniform circular cross section.

[0149] 9 shows a cross-sectional view of the pin guide structure (3). A rigid rod (4) is fixed in the pin guide structure extending in the proximal direction P. Distal to the pin guide structure is a bundle (5) of individual microfilaments (6). Preferably, the microfilaments between the filament guide structure (1) and the pin guide structure (3) are bundled together with a suitably cross-linked gelatin to provide sufficient stiffness (lateral stiffness) to achieve that a distal axial load on the pin guide structure (3) (imposed by the rigid rod) is translated into a distal axial force component on the individual microfilaments contained in the channels of the filament guide structure to move the microfilaments distally out of the channels and into the soft tissue.

[0150] FIG. 4 shows an axial view of the distal end of the microfilament guiding structure (1) showing the spatial configuration of the outlet of the guiding channel (8).

[0151] FIG. 5 shows a microfilament guidance structure including guidance channels arranged linearly along a line from the proximal end to the distal end. The channels may also be arranged between the proximal and distal ends along a curve. The microfilament guidance structure characterized by FIG. 5 does not show a section including one or more channels arranged parallel to the central axis of the filament guidance structure. The distinction of the filament guidance structure of FIG. 5 in the distal and proximal sections is not useful.

[0152] FIG. 8 shows the definition of angle α used to characterize the radial fanning of the guiding channels of the microfilament guiding structure. In one embodiment, the channels have an angular spatial arrangement with an acute angle α of about 2 degrees to about 40 degrees. FIG. 8 shows a cross-section of a pin guiding structure (3) showing the central axis (CA) and the spatial arrangement of one guiding channel (9). The angle α is given by the acute angle α of a right triangle whose sides are defined by a line (line / side Z) between the centers of the proximal and distal outlets of the channel, a line (line / side X) parallel to the central axis of the filament guiding structure and intersecting the center of the proximal channel outlet (PX), and a line (line / side Y) perpendicular to the central axis of the filament guiding structure intersecting the center of the distal outlet (DX) of the channel, and the angle α is the angle between the two longest sides (lines / sides X and Y).

[0153] Additional non-limiting embodiments are described below. [Clause 1] A microfilament guidance structure comprising channels providing a continuous lumen through the structure configured to accommodate and allow axial movement of microfilaments, the structure gradually disintegrating and / or dissolving upon contact with tissue fluids, at least some of the channels having a spatial (three dimensional) configuration in which the channels have an angular spatial arrangement having an acute angle α of from about 2 degrees to about 40 degrees, the angle α of the channels being given by the acute angle α of a right triangle having sides defined by a line between a center of a proximal and a distal outlet of the channel, a line parallel to a central axis of the guidance structure and intersecting the center of the proximal channel outlet, and a line perpendicular to the central axis of the guidance structure that intersects the channel and the center of the distal outlet where the angle α is the angle between the two longest sides. [Clause 2] 3. The microfilament guiding structure of clause 2, wherein the angle α is from about 2 to about 20 degrees. [Clause 3] 3. A microfilament guiding structure according to clause 1 or 2, comprising a channel lining material different from the material of the structure, the channel lining material gradually disintegrating and / or dissolving on contact with mammalian tissue fluids. [Article 4] 4. The microfilament guiding structure of any one of clauses 1 to 3, having a radial extension (diameter) of from about 250 μm to about 2 mm, preferably from about 300 μm to about 2 mm. [Article 5] 5. The microfilament guiding structure of any one of clauses 1 to 4, wherein the axial height of the guiding structure is at least about 1 mm. [Article 6] 6. The microfilament guiding structure of any one of clauses 1 to 5, wherein the channel has a diameter of from about 5 μm to about 250 μm, suitably from about 10 μm to about 120 μm. [Article 7] 7. A microfilament guiding structure according to any one of clauses 1 to 6, comprising a material selected from the group consisting of low molecular weight carbohydrates, proteinaceous materials and mixtures thereof, preferably gelatin. [Article 8] 8. A microfilament guiding structure according to any one of clauses 1 to 7, wherein the structure comprises at least 2 channels, preferably at least 5 channels, at least 10 channels, at least 15 channels. [Article 9] A microfilament guiding structure according to any one of clauses 1 to 8, wherein the microfilaments are selected from conductive microelectrodes, hollow microfilaments, microfilaments comprising sensing means such as photon sensing means, and any combination of the three types of microfilaments. [Article 10] 10. A microfilament guiding structure according to any one of clauses 1 to 9, wherein the microfilament is a conductive microelectrode. [Article 11] 11. The microfilament guiding structure of any one of clauses 1 to 10, wherein the microfilament guiding structure comprises a distal section and a proximal section, the distal section incorporating the channels having a spatial configuration defined by clause 1, the proximal section comprising from one channel to a number of channels equal to the number of channels included in the distal section, the one or more channels of the proximal section allowing insertion of a number of microfilaments equal to the number of channels of the distal structure and having a combined cross-sectional area capable of accommodating the microfilaments, and the channels of the distal section and the one or more channels of the proximal section are configured to allow individual microfilaments of the proximal section of the guiding structure to move axially. [Article 12] 12. The microfilament guiding structure of claim 11, wherein the proximal section comprises one channel having dimensions capable of accommodating all individual microfilaments and allowing axial movement of each microfilament. [Article 13] 13. A microfilament guiding structure according to any one of clauses 1 to 12, wherein the microfilaments are disposed in at least some of the channels, preferably in all of the channels. [Article 14] 13. A proto-microfilament assembly having a distal region and a proximal region comprising the microfilament guiding structure of any one of clauses 1 to 12, further comprising a microfilament disposed within the channel of the microfilament guiding structure, an elongated hollow guiding member, and a pin, the microfilament extending proximally from the microfilament guiding structure, the microfilament being removably (temporarily) attached to the pin, the pin being located proximal to the microfilament guiding structure and configured to be slidably disposed inside the elongated hollow guiding member, the protofilament assembly having sufficient rigidity to be inserted into a target region of soft tissue, the pin being disposed inside the elongated hollow guiding member relative to the microfilament guiding structure to provide a gap between the microfilament guiding structure and the pin, the microfilament guiding structure being temporarily attached to the elongated hollow guiding member, and the microfilament can be urged distally outside the channel by moving the pin in a distal direction essentially without moving the elongated hollow guiding member and the microfilament guiding structure. [Article 15] 15. The proto-microfilament assembly of claim 14, wherein the microfilament guiding structure comprises a distal portion and a proximal portion, the distal portion of the microfilament guiding structure being positioned distal to the elongated hollow guiding member and the proximal portion being positioned inside the elongated hollow guiding member. [Article 16] 16. The proto-microfilament assembly of claim 15, further comprising a hollow support guide disposed within the elongated hollow guide member between the microfilament guiding structure and the pin, the hollow support guide having a central conduit for accommodating the microfilament, and the pin being disposed inside the elongated hollow guide member relative to the hollow support guide to provide a gap between the hollow support guide and the pin. [Article 17] 17. The proto-microfilament assembly of claim 16, wherein the structural rigidity of the microfilament is increased along a section between the hollow support guide and the distal end of the pin. [Article 18] 17. The proto-microfilament assembly of claim 16, wherein the structural rigidity of the microfilaments is increased along a section between the hollow support guide and the distal end of the pin, thereby inhibiting or essentially inhibiting individual microfilaments from bending or buckling as the pin is moved in a distal direction. [Article 19] 19. The proto-microfilament assembly of any one of clauses 14 to 18, wherein the microfilament is positioned completely inside the channel of the microfilament guiding structure before the pin is distally engaged. [Article 20] 15. The proto-microfilament assembly of claim 14, further comprising a pin guide structure, the pin being temporarily attached to the pin guide structure, the pin guide structure being configured to be slidably disposed inside the elongated hollow guide member. [Article 21] The protofilament assembly of clause 20, or the microfilament guiding structure of any one of clauses 11 and 12, wherein the microfilament guiding structure comprises at least two regions, a distal region and a proximal region, and the cross-sectional area of ​​the proximal region is greater than the cross-sectional area of ​​the distal region. [Article 22] A proto-microfilament assembly according to any one of clauses 14 to 29 and 20, or a microfilament guiding structure according to any one of clauses 11 and 12, wherein the microfilament guiding structure is essentially rotationally symmetric. [Article 23] A proto-microfilament assembly as described in any one of clauses 14 to 19 and 20, or a microfilament guiding structure as described in clauses 11 and 12, wherein the microfilament guiding structure comprises a distal and a proximal region / portion, and at least a portion of the distal region, i.e. the distal portion, comprises an elliptical cross-section, preferably a circular cross-section, and at least a portion of the proximal region, i.e. the distal portion, comprises a double elliptical cross-section, preferably a double circular cross-section. [Article 24] A proto-microfilament assembly as described in clause 20, or a microfilament guiding structure as described in clauses 11 and 12, wherein the microfilament guiding structure comprises a distal and a proximal region, at least a portion of the distal region comprises a double elliptical (preferably double circular) cross-section and at least a portion of the proximal region comprises a double elliptical, preferably double circular, cross-section. [Article 25] 21. A proto-microfilament assembly as described in clause 20, or a microfilament guiding structure as described in clauses 11 and 12, wherein the cross-section of the distal region of the microfilament guiding structure is double elliptical (preferably double circular). [Article 26] 21. A proto-microfilament assembly according to clause 20, or a microfilament guiding structure according to clauses 11 and 12, wherein said cross-section of said proximal region is double elliptical (preferably double circular). [Article 27] 27. The proto-microfilament assembly of any one of clauses 23 to 26, or the microfilament guiding structure of any one of clauses 23 to 26, wherein the proximal region comprises a double circular cross section comprising two different radial extensions, a wide radial extension Rwp (having a radius rwp) and a narrow radial extension Rnp (having a radius rnp). [Article 28] 28. The proto-microfilament assembly of any one of clauses 24 to 27, or the microfilament guiding structure of any one of clauses 24 to 27, wherein the distal region comprises a double circular cross section comprising two different radial extensions, namely radial extension Rs1 (having a radius rd1) and radial extension Rd2 (having a radius rd2). [Article 29] 29. The proto-microfilament assembly of any one of clauses 24 to 28, or the microfilament guiding structure of any one of clauses 24 to 28, wherein the extension Rs1 is essentially similar to the extension Rnp. [Article 30] 30. A proto-microfilament assembly as described in clause 24 or 29, or a microfilament guiding structure as described in clause 24 or 29, wherein the radial extensions Rwp and Rnp of the proximal region and the angular extensions Rs1 and Rd2 of the distal region, respectively, together form an essentially complete circle (360 degrees). [Article 31] 27. The proto-microfilament assembly of any one of clauses 24 to 26, or the microfilament guiding structure of any one of clauses 24 to 26, wherein the angular extensions of the radial extensions Rwp and Rnp are each about 180 degrees. [Article 32] 32. The proto-microfilament assembly of claim 24 or 31, wherein the elongated hollow guide member is configured to accommodate the microfilament guide structure of claim 24 or 31, the guide member including a distal and a proximal region, the guide member including an annular cross-section having an inner diameter (Di) and an outer diameter (Do), Di being from about 102% to about 110% of Rnd and Do being from about 90 to about 100% of Rpw, the elongated hollow guide member having lateral partitions of the annular cross-section throughout the axial length of the guide member, the proximal partition being wider than the distal partition. [Article 33] 33. The proto-microfilament assembly of claim 32, wherein the length of the distal region of the elongate hollow guiding member corresponds to the length of the distal region of the microfilament guiding structure. [Article 34] 34. The proto-microfilament assembly of any one of clauses 14 to 33, wherein the elongated hollow guiding member has sufficient rigidity to provide axial alignment of the proto-filament assembly. [Article 35] A proto-microfilament assembly according to any one of clauses 23 to 34, or a microfilament guiding structure according to any one of clauses 23 and 34, wherein the distal region of the microfilament guiding structure comprises a protrusion. [Article 36] A proto-microfilament assembly as described in clause 35, or a microfilament guiding structure as described in clause 35, wherein the protrusion of the distal region of the microfilament guiding structure has an angular extension for receiving in the lateral partition of the annular cross-section of the distal region of the elongated hollow guiding member. [Article 37] 36. A proto-microfilament assembly as described in clause 35, or a microfilament guiding structure as described in clause 35, wherein the protrusion of the distal region of the microfilament guiding structure extends along the entire length of the distal region of the microfilament guiding structure. [Article 38] 38. The proto-microfilament assembly of any one of clauses 20 to 37, wherein the pin guide structure houses a rigid pin and the individual microfilaments, the rigid pin and the individual microfilaments extending proximally from the pin guide structure, the pin guide structure including a rotationally symmetric cross-section having a radial extension to be housed in the proximal region of the elongate hollow guide member, and the pin guide structure is positioned a short distance from the microfilament guide structure sufficient to move the individual microfilaments through the distal section of the guide system. [Article 39] 39. A proto-microfilament assembly as described in clause 38, wherein the individual microfilaments along the axial section between the microfilament guide structure and the pin guide structure are bundled together and optionally comprise a material that provides structural rigidity in the axial direction, such as gelatin. [Article 40] 40. The proto-microfilament assembly of claim 38 or 39, wherein the individual microfilaments are centrally contained within the pin guide structure and around the rigid pin. [Article 41] 41. The proto-microfilament assembly of any one of clauses 20 to 40, wherein the pin guide structure has the property of gradually disintegrating and / or dissolving when in contact with mammalian tissue fluids. [Article 42] A proto-microfilament assembly described in any one of clauses 14 to 19 and clauses 20 to 41, wherein the elongated hollow guide member comprises one or more insoluble materials that gradually disintegrate and / or dissolve when contacted with mammalian tissue fluids. [Article 43] A proto-microfilament assembly as described in clause 42, wherein the material that slowly disintegrates and / or dissolves when in contact with mammalian tissue fluids does not disintegrate and / or dissolve as rapidly as the microfilament guiding structure and the hollow support guide. [Article 44] The proto-microfilament assembly of any one of clauses 14 to 19 and clauses 20 to 43, wherein the elongated hollow guiding member is made of a material selected from the group consisting of materials including metals and polymers. [Article 45] 45. The proto-microfilament assembly of any one of clauses 20 to 44, wherein the elongated hollow guiding member is made of a metal, such as a metal alloy. [Article 46] A proto-microfilament assembly as described in any one of clauses 14 to 45 or a microfilament guiding structure as described in any one of clauses 1 to 13, wherein the diameter of the channel of the microfilament guiding structure is larger than the diameter of an individual microfilament. [Article 47] 47. The proto-microfilament assembly of any one of clauses 14 to 46 or the microfilament guiding structure of any one of clauses 1 to 13, wherein the diameter of the channel is about 5% to about 150% larger than the diameter of the individual microfilaments, preferably about 10% to about 100% larger. [Article 48] 13. A microelectrode guiding structure according to any one of clauses 1 to 12, wherein the channels in the proximal region of the microfilament guiding structure have dimensions to accommodate and permit axial movement of the individual microfilaments. [Article 49] 49. The protofilament assembly of any one of clauses 13 to 48, wherein the diameter of the individual microfilaments is from about 5 μm to about 120 μm, suitably from about 5 μm to about 70 μm. [Article 50] 50. The proto-microfilament assembly of any one of clauses 14 to 49, wherein the microfilament is a conductive microelectrode comprising a metal, a metal alloy, carbon such as graphite and graphene, a conductive polymer or a mixture thereof. [Article 51] 51. The proto-microfilament assembly of any one of clauses 14 to 50, wherein the individual microfilaments are conductive microelectrodes and are electrically insulated except for a portion extending proximally from their distal end. [Article 52] 52. The proto-microfilament assembly of any one of clauses 14 to 51, wherein the pin comprises a recess (gap) laterally along at least a portion of the pin, preferably from the distal end to a position between the distal end and the proximal end, preferably along the entire length of the pin, the recess preferably configured to accommodate the microfilament. [Article 53] A method for manufacturing a microfilament guiding structure as described in any one of clauses 1 to 12, comprising the steps of providing a number of channel-forming flexible rods and / or channel-forming wires, spatially positioning the channel-forming flexible rods and / or wires to satisfy any one of the channel positioning requirements of clauses 1 to 12, thereby forming a fixed arrangement of flexible rods and / or wires, positioning the arrangement in a mold, and forming the guiding structure by casting using a casting material having the properties of the microfilament guiding structure material defined by any one of clauses 1 to 12, which gradually disintegrates and / or dissolves when contacted with mammalian tissue fluid. [Article 54] A method for manufacturing a microfilament guiding structure as described in any one of clauses 1 to 12, comprising the steps of providing a first distal channel positioning member including an opening, positioning channel-forming flexible rods and / or wires through the opening, spatially arranging the rods such that the distance between the rods increases in the distal direction, positioning the first channel positioning member and the channel-forming flexible rods and / or wires in a mold, filling the mold with a molding material having the characteristics of the microfilament guiding structure material defined by any one of clauses 1 to 12, solidifying the molding material and removing the channel-forming flexible rods and / or wires and the first channel positioning member after solidification, thereby forming a distal microelectrode guiding structure. [Article 55] 13. A method for manufacturing a microfilament guiding structure according to any one of clauses 1 to 12, comprising the steps of providing a first channel positioning member comprising openings and a second channel positioning member comprising (at least) the same number of openings as the first channel positioning member, positioning channel forming flexible rods and / or wires through the openings of both the first and second channel positioning members, bundling the channel forming flexible rods and / or wires into a position between the first and second channel positioning members, and binding the first and second channel positioning members together. positioning the material and the channel-forming flexible rod and / or wire in a mold; filling the mold with a casting material having the properties of the microfilament guidance structure material defined by any one of clauses 1 to 12; solidifying the casting material and after solidification removing the channel-forming flexible rod and / or wire and the first and second channel positioning members, thereby forming a distal microelectrode guidance structure; and optionally cutting the distal microelectrode guidance structure essentially perpendicular to a main axis, thereby forming a distal microelectrode guidance structure. [Article 56] 56. The method of any one of clauses 53 to 55, wherein the channel of the microfilament guiding structure is formed when the flexible rod and / or wire is removed from the microfilament guiding structure. [Article 57] 57. The method of claim 56, wherein one microfilament is attached to each flexible rod and / or wire, and when the flexible rod and / or wire are removed from the microfilament guiding structure, the microfilament is introduced into the channel. [Article 58] A method for manufacturing a microfilament guiding structure comprising a channel and a microfilament disposed inside the channel, the method comprising the steps of positioning channel-forming flexible rods and / or wires in a predetermined spatial arrangement, positioning the flexible rods and / or wires having the predetermined spatial arrangement in a mold, filling the mold with a liquid form of a casting material, allowing the casting material to solidify, forming the channel of the microfilament guiding structure when the flexible rods and / or wires are removed from the microfilament guiding structure, and simultaneously disposing a microfilament attached to one end of the flexible rods and / or wires inside the channel. [Article 59] A method for manufacturing a microfilament guiding structure comprising a channel as described in clause 58, wherein the material for casting is selected from materials that dissolve and / or disintegrate when exposed to tissue fluids, such as gelatin. [Article 60] 60. A method for manufacturing a microfilament guiding structure comprising a channel as defined in clause 58 or 59, wherein the radial extension of the microfilament guiding structure is less than about 2.5 mm. [Article 61] 61. A method for manufacturing a microfilament guiding structure comprising a channel according to any one of clauses 58 to 60, wherein at least some of the microfilaments are microelectrodes having a radial extension of up to about 100 μm.

Claims

1. A proto-microfilament assembly (7) for inserting and controlling placement of a microfilament in soft tissue, such as neural tissue, the proto-microfilament assembly (7) having a distal region and a proximal region, the proto-microfilament assembly (7) comprising: A microfilament guiding structure (1, 101) having a channel; Highly flexible microfilaments, an elongated hollow guide member having an annular cross-section with a lateral partition / gap / opening along at least a distal section; A pin and the highly flexible microfilament (6) is disposed within the channel (8) of the microfilament guiding structure (101), the channel (8) providing a continuous lumen through the microfilament guiding structure configured to accommodate and allow axial movement of the highly flexible microfilament, the diameter and length of the channel being sized to facilitate precise guiding of the microfilament within the channel, the inner diameter of the channel being about 105% to about 200%, preferably about 105% to about 150%, of the diameter of the microfilament; the microfilament guiding structure gradually disintegrates and / or dissolves upon contact with tissue fluids; the microfilaments are not sufficiently stiff to be implanted completely into the target tissue without bending from their intended track line, and thus require structural support if precise insertion is intended; in at least a distal section / portion of the microfilament guiding structure, the radial distance between at least some of the channels gradually increases in a distal direction; The microfilaments from the microfilament guiding structure (101) extend in a proximal direction. The microfilament is removably (temporarily) attached to the pin (4); The pin (4) is located adjacent to the microfilament guiding structure (101) and is configured to be slidably disposed inside the elongated hollow guiding member (2); the proto-microfilament assembly having sufficient stiffness to be inserted into a target area of ​​soft tissue; said microfilament guiding structure (101) being temporarily attached to said elongated hollow guiding member (103, 103a); A proto-microfilament assembly, wherein the microfilament can be urged distally out of the channel by moving the pin in a distal direction, essentially without moving the elongated hollow guiding member and the microfilament guiding structure.

2. A proto-microfilament assembly as described in claim 1, wherein the microfilament guiding structure includes a distal portion (101a) and a proximal portion (101b), the distal portion of the microfilament guiding structure being positioned distal to the elongated hollow guiding member and the proximal portion being positioned inside the elongated hollow guiding member.

3. A proto-microfilament assembly as described in claim 1 or 2, wherein temporary attachment of the microfilament guiding structure (1, 101) to the elongated hollow guiding member can be achieved by a thread included in the microfilament guiding structure and attached to the elongated hollow guiding member.

4. A proto-microfilament assembly as described in any one of claims 1 to 3, further comprising a hollow support guide (102) between the microfilament guiding structure (101) and the pin (4) and disposed within an elongated hollow guide member, the hollow support guide comprising a central conduit (102a) for accommodating the microfilament, the pin being disposed inside the elongated hollow guide member to provide a gap (501a) between the microfilament guiding structure and the pin, and wherein the structural rigidity of the microfilaments is preferably increased along a section between the hollow support guide (102) and the distal end of the pin, such that individual microfilaments are inhibited or essentially inhibited from bending or buckling as the pin is moved in a distal direction.

5. A proto-microfilament assembly as described in any one of claims 1 to 4, wherein the distal section of the microfilament is positioned completely inside the channel of the microfilament guiding structure before the pin engages in the distal direction.

6. The microfilament guiding structure comprises low molecular weight carbohydrates, proteoglycans, glycoproteins and protein materials such as gelatin that can be cross-linked to various degrees, and The proto-microfilament assembly of any one of claims 1 to 5, comprising a material selected from the group consisting of mixtures thereof, said material optionally comprising a pharmacologically active agent.

7. A proto-microfilament assembly as described in any one of claims 1 to 6, wherein the microfilament guiding structure has a radial extension (diameter) of from about 250 μm to about 2 mm, preferably from about 300 μm to about 2 mm, and preferably has an axial extension in the range of from about 0.5 mm to about 25 mm.

8. A proto-microfilament assembly described in any one of claims 1 to 7, wherein the diameter of the channel of the microfilament guiding structure is from about 5 μm to about 250 μm, preferably from about 10 μm to about 120 μm.

9. A proto-microfilament assembly as described in any one of claims 1 to 8, wherein the microfilament is straight and does not exhibit any bends that would provide a curved path within the soft tissue when the provided microfilament is propelled from a guidance system into the tissue.

10. A microfilament assembly as described in any one of claims 1 to 9, wherein the microfilament, at least a portion of the microfilament (the most distal section), or at least a portion of the microfilament adjacent to and in direct contact with soft tissue, has a level of internal tension that prevents the microfilament from substantially departing from the trajectory provided by the channel of the filament guidance structure during insertion into soft tissue and is sufficiently flexible to accommodate movement of the soft tissue, such as neural tissue, without significantly affecting the soft tissue.

11. A protofilament assembly described in any one of claims 1 to 10, wherein the diameter of the individual microfilaments is from about 5 μm to about 120 μm, preferably from about 5 μm to about 70 μm.

12. A proto-microfilament assembly described in any one of claims 1 to 11, wherein the elongated hollow guide member has sufficient rigidity to provide axial alignment of the proto-filament assembly.

13. A proto-microfilament assembly as described in claim 1, further comprising a pin guide structure (3), the pin being temporarily attached to the pin guide structure, and the pin guide structure being configured to be slidably positioned inside the elongated hollow guide member.

14. A protofilament assembly described in any one of claims 1 and 5 to 13, wherein the microfilament guiding structure includes at least two regions, a distal region (DMFS) and a proximal region (PMFS), and the cross-sectional area of ​​the proximal region is larger than the cross-sectional area of ​​the distal region.

15. A proto-microfilament assembly as described in any one of claims 1 and 5 to 14, wherein the microfilament guiding structure comprises a distal (DMFS) and a proximal (PMFS) region, at least a portion of the distal region comprises a double elliptical (preferably double circular) cross-section, and at least a portion of the proximal region comprises a double elliptical cross-section, preferably a double circular cross-section.

16. A proto-microfilament assembly as described in claim 14 or 15, wherein the proximal region (PMFS) of the microfilament guiding structure comprises a double circular cross-section including two different radial extensions, a wide radial extension Rwp (having radius rwp) and a narrow radial extension Rnp (having radius rnp), and preferably the distal region (DMFS) of the microfilament guiding structure comprises a double circular cross-section including two different radial extensions, namely a radial extension Rd1 (having radius rd1) and a radial extension Rd2 (having radius rd2), and preferably the extension Rs1 is essentially similar to extension Rnp.

17. The protomicrofilament assembly of claim 16, wherein the radial extensions Rwp and Rnp of the proximal region and the angular extensions Rd1 and Rd2 of the distal region, respectively, together form an essentially perfect circle (360 degrees).

18. A proto-microfilament assembly as described in claim 16 or 17, wherein the elongated hollow guide member (2) is configured to accommodate the microfilament guide structure (1, 101) of claim 16 or 17, comprising a distal (DMFS) and a proximal (PMFS) region, the elongated hollow guide member comprising an annular cross-section having an inner diameter (Di) and an outer diameter (Do), wherein Di is from about 102% to about 110% of Rnp and Do is from about 90 to about 100% of Rpw, the elongated hollow guide member having lateral partitions (ANGDH, ANGPH) of the annular cross-section throughout the axial length of the guide member, the proximal partition (ANGPH) being wider than the distal partition (ANGDH).

19. A proto-microfilament assembly as described in claim 18, wherein the length (DHGM) of the distal region of the elongated hollow guiding member (2) corresponds to the length (DMFS) of the distal region of the microfilament guiding structure (1).

20. A proto-microfilament assembly as described in any one of claims 14 to 19, wherein a protrusion (11) of the distal region (DMFS) of the microfilament guiding structure (1) has an angular extension (ANGD) for accommodating the lateral partition (13) of the annular cross-section of the distal region of the elongated hollow guiding member (2).

21. A proto-microfilament assembly as described in claim 13, wherein the pin guide structure (3) accommodates the rigid pin (4) and the individual microfilaments (6), the rigid pin and the individual microfilaments extending proximally from the pin guide structure, the pin guide structure including a rotationally symmetric cross-section having a radial extension to be accommodated in the proximal region (PHGM) of the elongated hollow guide member (2), and the pin guide structure (2) is positioned a short distance (G) from the microfilament guide structure sufficient to move the individual microfilaments through the distal section of the guidance system.

22. A proto-microfilament assembly as described in claim 21, wherein the individual microfilaments along the axial section between the microfilament guide structure and the pin guide structure (G) are bundled together and optionally include a material that provides structural rigidity in the axial direction, such as gelatin.

23. A proto-microfilament assembly as claimed in any one of claims 1 to 22, wherein the microfilament is a conductive microelectrode comprising a metal, a metal alloy, carbon such as graphite and graphene, a conductive polymer or mixtures thereof, and is preferably electrically insulated except for a portion extending proximally from its distal end.

24. A proto-microfilament assembly as described in any one of claims 1 to 23, wherein the pin has a recess (gap) laterally along at least a portion of the pin, preferably from the distal end to a position between the distal end and the proximal end, preferably along the entire length of the pin, the recess preferably configured to accommodate the microfilament, and the microfilament preferably bundled with an adhesive.

25. A proto-microfilament assembly as described in any one of claims 1 to 24, wherein at least some of the channels (8) of the microfilament guiding structure have a spatial (three-dimensional) configuration in which the channels have an angular spatial arrangement with an acute angle α of from about 2 degrees to about 40 degrees, preferably from about 2 degrees to about 20 degrees, and the channel angle α is given by the acute angle α of a right triangle having sides defined by a line between the centers of the proximal and distal outlets of the channels, a line parallel to the central axis of the guiding structure and intersecting the center of the proximal channel outlet, and a line perpendicular to the central axis of the guiding structure that intersects the center of the channel and the distal outlet where the angle α is the angle between the two longest sides.

26. A protomicrofilament assembly as described in any one of claims 1 to 25, wherein the elongated hollow guide member and the pin are made of materials that maintain their structural rigidity over time.

27. A protomicrofilament assembly as described in any one of claims 1 to 25, wherein the elongated hollow guide member and the pin gradually collapse after insertion.

28. A cover structure for housing a proto-microfilament assembly as described in any one of claims 1 to 27, the cover structure delaying dissolution and / or disintegration of any structure or material of the proto-microfilament assembly including substances that dissolve and / or disintegrate upon contact with bodily fluids, and comprising elongated members such as axially arranged wires, strands or threads.

29. A method for manufacturing a microfilament guiding structure comprised in a microfilament assembly as claimed in any one of claims 1 to 27, comprising the steps of providing a number of channel forming flexible rods and / or channel forming wires (34), spatially positioning the channel forming flexible rods and / or wires to satisfy any one of the channel positioning requirements of claims 1 to 9, thereby forming a fixed arrangement of flexible rods and / or wires, positioning said arrangement in a mould, and forming the guiding structure by casting using a casting material having the properties of the microfilament guiding structure material defined by any one of claims 1 to 8, which gradually disintegrates and / or dissolves when in contact with mammalian tissue fluids, preferably wherein the channels of the microfilament guiding structure are formed when the flexible rods and / or wires are removed from the microfilament guiding structure, preferably wherein one microfilament is attached to each of the flexible rods and / or wires, preferably wherein the microfilament is introduced into the channels when the flexible rods and / or wires are removed from the microfilament guiding structure.

30. A method for manufacturing a microfilament guiding structure included in a microfilament assembly as defined in any one of claims 1 to 27, comprising the steps of providing a first distal channel positioning member including an opening (31); positioning channel forming flexible rods and / or wires (34) through said opening (30); spatially arranging said rods such that the distance between said rods increases in a distal direction (35); positioning the first channel positioning member and the channel forming flexible rods and / or wires in a mould; and filling the mould with a casting material having the properties of said microfilament guiding structure material as defined by any one of claims 1 to 8. and solidifying the casting material and removing the channel forming flexible rods and / or wires and first channel positioning member after solidification, thereby forming a distal microelectrode guidance structure, preferably the channels of the microfilament guidance structure are formed as the flexible rods and / or wires are removed from the microfilament guidance structure, preferably one microfilament is attached to each of the flexible rods and / or wires, preferably the microfilaments are introduced into the channels as the flexible rods and / or wires are removed from the microfilament guidance structure.

31. A method for manufacturing a microfilament guiding structure included in a microfilament assembly as defined in any one of claims 1 to 27, comprising the steps of providing a first channel positioning member (31) including openings (30) and a second channel positioning member (33) including (at least) the same number of openings (30) as said first channel positioning member, positioning channel forming flexible rods and / or wires (34) through the openings of both said first and second channel positioning members (35), bundling said channel forming flexible rods and / or wires in a position between said first channel positioning member and said second channel positioning member, positioning said first and second channel positioning members and said channel forming flexible rods and / or wires in a mold, and forming a microfilament guiding structure material as defined in any one of claims 1 to 8, the method comprising the steps of: filling the mould with a casting material having said characteristics; allowing said casting material to solidify, and after solidification removing said channel forming flexible rods and / or wires and said first and second channel positioning members, thereby forming a distal microelectrode guidance structure; and optionally cutting said distal microelectrode guidance structure essentially perpendicular to a main axis, thereby forming a distal microelectrode guidance structure, wherein preferably said channels of said microfilament guidance structure are formed when said flexible rods and / or wires are removed from said microfilament guidance structure, preferably one said microfilament is attached to each said flexible rod and / or wire, preferably said microfilament is introduced into said channel when said flexible rod and / or wire is removed from said microfilament guidance structure.

32. A method for manufacturing a microfilament guidance structure comprising a channel and a microfilament disposed inside the channel, the method comprising the steps of positioning channel forming flexible rods and / or wires in a predetermined spatial arrangement, positioning the flexible rods and / or wires having a predetermined spatial arrangement in a mould, filling the mould with a liquid form of a casting material, allowing the casting material to solidify, forming the channel of the microfilament guidance structure when the flexible rods and / or wires are removed from the microfilament guidance structure, and simultaneously positioning a microfilament attached to one end of the flexible rods and / or wires inside the channel, preferably wherein the material for casting is selected from materials that dissolve and / or disintegrate when exposed to tissue fluids such as gelatin, the radial extension of the microfilament guidance structure is preferably no greater than about 2.5 mm, and at least a portion of the microfilaments are microelectrodes having a radial extension of up to about 100 μm.

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