WO2025221201A1

WO2025221201A1 - Protective assembly for insertion of medical objects into soft

Info

Publication number: WO2025221201A1
Application number: PCT/SE2025/050372
Authority: WO
Inventors: Jens SHOUENBORG; Niclas Lindqvist
Original assignee: Neuronano AB
Current assignee: Neuronano AB
Priority date: 2024-04-18
Filing date: 2025-04-18
Publication date: 2025-10-23
Anticipated expiration: 2026-10-18

Abstract

The present invention relates to an assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, the assembly comprising a water-resistant sleeve, accommodating an oblong device comprising at least one rigidity imparting element, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the he sleeve wall having an average thickness of less than 100 µm and comprising a weakness at least in the distal section, said weakness enabling the distal section to rupture when an axial force is exerted on the distal section, such as the region of the distal end, by the oblong device.

Description

PROTECTIVE ASSEMBLY FOR INSERTION OF MEDICAL OBJECTS INTO SOFT TISSUE

FIELD OF INVENTION

The present invention relates to an assembly configured for insertion of medical objects comprising a water-resistant sleeve accommodating an oblong device with a diameter of less than 5 mm, the sleeve comprising at least a weakness inducing an intended breakage of the sleeve after the insertion of the assembly into soft tissue, in particular the nervous tissue.

BACKGROUND OF THE INVENTION

The invention relates to thin objects which are introduced into soft tissue, such as nervous and endocrine tissue. Some objects are so thin (objects with a diameter between 1 to 150 pm) and therefore often so flexible that it is difficult or even impossible to insert such objects into soft tissue. Objects introduced into nervous tissue such as brain tissue for stimulation and monitoring should ideally be flexible enough to accommodate the movement of the brain tissue thereby minimizing tissue irritation and thereby providing the conditions for proper function under an extended period. Thin objects like microelectrodes for stimulation and monitoring of brain tissue should be quite flexible for minimizing tissue damage during insertion but need a certain degree of structural support for introduction into brain tissue. One way of providing structural support to thin objects such as microelectrodes for e.g. deep brain stimulation is to embed the object in a dissolvable matrix where the matrix provides stiffness when dry (WO 2008/091197, WO 2010/1441016). The matrix material must also be biocompatible and regulatorily approved. Thus, a stiffness providing matrix material must either dissolve/disintegrate and/or alter the mechanical properties from stiff to flexible when subjected to soft tissue (soft tissue fluids). It has proven challenging to calibrate the matrix material such that the matrix provides enough stiffness during insertion and a timely dissolution or change of mechanical properties of the matrix once positioned. The present assembly comprising a water-resistant breakable sleeve alleviates many shortcomings of a stiffness providing matrix material for thin and flexible oblong medical devices such as microelectrodes. Once a device is positioned in tissue, blunt smooth contours of an implanted device are preferred to reduce irritation of the tissue and to reduce the risk for puncturing nearby blood vessels by ways of soft tissue movements. Tissue movements are caused by heart beats, respiration and accelerations of body parts. Soft tissue movements are likely to induce shear between implanted device and adjacent tissue often inducing inflammatory processes (Kohler et al, PLOS ONE, 2015). Accordingly, when residing in the tissue the device should be able to follow tissue movement to reduce shear forces. As alluded to above, highly flexible elements such as microelectrodes, can be inserted in soft tissue by embedding them in a stiff but dissolvable/degradable matrix material (WO 2019/03936). Dissolvable matrix materials are known for pharmaceuticals and encapsulations of implantable electrodes with dissolvable materials such as gelatine and Kollicoat® (Etermadi et al, PLOS ONE, 2016). However, when implanting such matrix embedded devices, water may enter the construction immediately on penetrating the tissue, which risk softening the construction before being fully implanted, which in turn risk deviation from the intended insertion track. This risk increases when implanting devices deep into soft tissue such as deep in the brain, since the insertion time gets longer. This challenge can be overcome by using a higher insertion speed, but a higher speed may increase the risk for tissue rupture. However, dissolution time can vary depending on e.g. body temperature, water content of the tissue traversed and local pH. The necessary insertion speed to avoid premature dissolution is therefore difficult to accurately predict.

Another problem is that the performance of a matrix embedded device may be compromised prior to insertion by moisture or water contact.

A further challenge is to have the device operable as soon as the device has been properly positioned. However, the application of a more rapid dissolvable/degradable matrix providing an operable electrode soon after positioning increases the risk of losing rigidity prior to reaching the target position alternatively compromising tissue due to rapid insertion. For devices which comprise components that are dissolvable/degradable in body fluids (or lipids) already during insertion there is therefore a need for a water protection that is not dependent on such parameters as the body temperature, tissue water content or local pH and that can be instantly terminated/removed in a time-controlled manner. As mentioned above, there is also a need for such a water protection to have a shape that cause as little disruption of the tissue as possible during insertion. With the assembly of the invention a stiffening matrix can be applied with e.g. very rapid dissolution properties which are promptly activated immediately after positioning and induced by breakage of the sleeve.

There is a corresponding need for time-controlled water protection of devices containing materials that change physical properties once getting into contact with soft tissue such as materials dissolvable/degradable in body fluids or lipids. Such materials include for example gelling materials or materials that polymerize when brought into contact with body fluids, pharmaceutics or suspensions of pharmaceutics or other materials such as biomarkers, materials providing improved contrast in MRI or in CT, liquid gels, living cells or tissue.

There is also a need for reducing the spreading of the materials to unintended targets during the insertion into soft tissue. Known solutions whereby such materials are injected into tissue comprise a hollow water-tight conduit that is open in the front, e.g. injection needles. Due to the opening, some materials may leak out during insertion thus causing unintended side effects.

Of importance is also to reduce tissue damage during insertion. During insertion into soft tissue, for example the brain or nervous endocrine tissue, a probe will displace tissue or to an extent traverse through the tissue thereby destroying the tissue along the trajectory. Crushing or compression of the tissue can happen when the probe is too blunt preventing the tissue from gliding sideways during insertion or if the tissue to be implanted is tough or resilient such as the fibrous tissue of the arachnoid mater, covering the brain/spinal cord or other parts of the meninges, i.e. dura mater and pia mater. It is known that insertion pressure can provoke severe hypoxia in the tissue to be implanted which can damage nervous tissue if prolonged (Kumosa and Schouenborg, 2021 ). The tip of a probe therefore often needs to be relatively pointed to reduce dimpling of the surface which can result in increased mechanical pressure on the tissue. On the other hand, a too sharp tip may risk puncturing blood vessels during insertion of the probe causing hemorrhage, which can induce tissue reactions. Unless a probe is intended to be inserted into a blood vessel, such as during cannulation of a blood vessel for infusion or blood sampling, tissue reactions induced by hemorrhage may jeopardize the function of the implanted probe. With the assembly, the shape of the distal section and distal end can be optimized for insertion with respect to specific type of soft tissue and/or purpose of the insertion.

Another problem is that the distal opening of injection needles, due to the cutting effect of the most frontal thin walls of the injection needles, can cause injuries along the insertion track and tissue fragments may contaminate the material in the injection needle to be ejected.

A further problem is related to biopsy when samples of tissue or fragments of tissue is to be collected from a particular tissue. In this case, contamination of the biopsy from tissue traversed during probe insertion should be avoided as much as possible.

A further problem is related to cannulation of blood vessels for providing infusions or blood sampling. In the case of fragile blood vessels, which is often seen in elderly people, the procedure of inserting a cannula with a cutting sharp front into a blood vessel can easily result in unintended hemorrhage due to rupture(s) of an excessive number of blood vessels. It would thus be desirable to reduce the risk for unintended ruptures of the wall of blood vessels during the act of inserting a probe. A further problem resides in implanting living cells or aggregates thereof into soft tissues. Known methods to implant cells include the use of a syringe and after placing the syringe in the target tissue injecting the cells into the target tissue. One problem with known methods is that the injected volume dilates the tissue which may cause tissue ruptures. To reduce tissue rupture at the site of injection, the injection should therefore be made slowly. However, in the case of injecting living cells a slow injection risks killing or damaging the cells because of the buildup of anoxic and or energy lacking conditions within the injection cannula.

Another problem when implanting living cells or aggregates thereof is related to the need for optimizing the environment to enhance survival of the inserted cells. It can be problematic to introduce the cells into an environment in which acute tissue reactions have been initiated by the injuries caused by the insertion procedure. The proliferation of living cells in the host tissue can further be enhanced by electric stimulation, e.g. by having a probe providing electrical stimulation to the volume of delivery of the living cells. The present invention offers the conditions for the provision of a device for the delivery of living cells or cell aggregates further comprising means for stimulating the living cells, the device being enclosed by a sleeve of the present invention. The present invention aims at solving or at least mitigating the problems presented herein with an arrangement for inserting and readying a medical object for its intended performance at a target site in soft tissue.

OBJECTS OF THE INVENTION

One objective is to provide water protection of implantable devices that contain materials that are dissolvable, degradable or otherwise affected by contact with body fluids or by contact with the tissue during insertion into soft tissue, wherein the water protection can be controllably discontinued/ by an operator (for example the surgeon or a robot).

A further objective is to provide an arrangement to improve timing of the contact of body fluid with a medical object following insertion into soft tissue.

A still further objective is to provide an arrangement imparting water protection for implantable devices, which reduces insertion-dependent tissue damage.

A further objective is to provide an arrangement for implanting electrodes, materials that polymerize to conductive materials in situ, pharmaceutics, electronic chips, optical wave guides, cells or tissue, or any combination of such medical objects into soft tissue, such as the nervous system, muscles and endocrine organs.

A further objective is to provide an arrangement enabling the spatial- and temporal- controlled delivery of a therapeutic agent, such as a pharmaceutical or cells, without using a conventional injection by means of a needle, thereby reducing injectiondependent tearing of the targeted tissue.

A still further objective is to provide an assembly with a shape that reduces tissue rupture during insertion into blood vessels and that can be transformed into a catheter with a distal opening after its insertion.

A still further objective is to facilitate or enable the insertion into soft tissue of oblong devices with complex shapes and/or having high friction surfaces.

A still further objective is to improve the proliferation of living cells and aggregates of living cells in soft host tissue. A further objective is the delivery of living cells and aggregates of living cells to a target volume within soft tissue while minimizing pressure for delivery or even omit the use of pressure for delivery and preferably reducing cell transferal time.

Other objectives are evident from the description herein.

GENERAL DESCRIPTION OF THE INVENTION

The invention is based on the insight that a water-resistant protective polymer sleeve with a structural weakness allows the sleeve to be controllably ruptured. A controlled rupture of the sleeve particularly in the distal section can be induced by applying axial and/or radial forces from within the sleeve. Radial forces on the water-resistant sleeve can be accomplished by dilation. Axial forces on the distal section of the water-resistant sleeve are preferably induced by the oblong device accommodated by the sleeve. Thus, the assembly comprising a sleeve according to the invention can be used to protect medical objects from premature contact with soft tissue during an insertion procedure and used to enable the controlled exposure of the object to the intended soft tissue when removing the sleeve. That is to say, an assembly of the invention comprising a sleeve provides protection of a medical object, when inserted into soft tissue, from premature contact with tissue and body fluid until the sleeve is ruptured and removed in a controlled way. Provided that the resistance to stretch is higher for the sleeve in general than the weakness zone(s) the latter will break before the rest of the sleeve when sufficiently strong forces are exerted on the sleeve.

The invention is also based on the insight that by adding a sleeve to an oblong device, the distal shape of the oblong device can be provisionally masked reducing tissue damage during insertion while retaining a distal shape designed for minimizing damage once properly positioned. A sleeve may also provide protection of the soft tissue during the insertion procedure if provided with a shape and surface that reduce friction. The surface of the protective sleeve may thus be smooth, slippery and/or coated with materials that reduce friction with soft tissue to reduce tissue disruption during the insertion procedure. The invention thus enables insertion of oblong devices that due to e.g. their complex shapes and/or high friction surfaces would otherwise not be suitable for insertion into soft tissue. The invention is further based on the insight that a removable protection sleeve can be endowed with means to monitor the very insertion procedure and the integrity of the protective sleeve during the insertion procedure.

In general terms, the invention relates to an assembly configured for insertion of medical objects comprising a water-resistant sleeve accommodating an oblong device having a diameter of less than 5 mm, the oblong device comprising at least one oblong rigid element, the assembly preferably adapted to be implanted in soft tissue. For some embodiments the medical object, the oblong device and oblong rigid element may have the same identity, e.g a microelectrode embedded in a matrix providing structural rigidity (stiffness). The assembly must exhibit stiffness allowing the device to be inserted into soft tissue as required for the specific application. If the oblong device comprises two or more objects one being a medical object, it may be sufficient that one object provides adequate stiffness to the oblong medical device.

The oblong device may contain one or several objects/elements and at least one medical object, the medical object needing a) protection from tissue or body fluids during insertion into soft tissue, b) structural support during insertion due to their high mechanical flexibility and/or c) that needs to be precisely administered in the target tissue during the insertion. Examples of such medical objects are: 1 ) objects comprising materials that are dissolvable, degradable or otherwise affected by contact with body fluids or by contact with tissue, 2) electrodes and multichannel electrodes, electronics, optical fibers or other types of filaments such as microcatheters and 3) pharmaceuticals, cells, and other biologically active agents/materials.

A specific feature of the invention is that the sleeve wall is very thin. Thus, the sleeve wall preferably has an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm. For certain applications the sleeve wall may be thicker than 100 pm. The sleeve comprises a water-resistant polymeric material or multiple polymeric materials which collectively provide for a water-resistant sleeve. The water-resistant sleeve at least partly encloses the oblong device during the process of insertion into soft tissue, where the sleeve exhibits structural weaknesses. After the sleeve accommodating the oblong device is correctly positioned, the sleeve is ruptured by exerting axial and/or radial forces on the sleeve. Axial forces on the sleeve, and in particular on the distal end of the sleeve may preferably be provided by moving the distal section of the sleeve in proximal direction while preferably keeping the oblong device stationary. A further option to rupture the sleeve is by dilation, e.g. by increasing the pressure inside the sleeve to cause the sleeve to crack in zones having structural weakness.

The sleeve also comprises at least a withdrawing facilitating element and/or positioning element integrated or attached to the proximal section of the sleeve. A withdrawing facilitating element may be articulated by one or more thin threads integrated or attached to the proximal section of the sleeve. Once positioned, the threads are preferably disposed from the sleeve in a proximal direction enabling an operator or special device to remove the sleeve from the soft tissue by pulling the threads such that the distal section of the sleeve moves in proximal direction.

The sleeve may also be coated with a friction reducing agent. The sleeve may also incorporate one or more sensors, or electrodes connected to electronics to provide information on e.g. premature breach of the water protection.

Additionally, the invention also covers a method for inserting an oblong medical device comprising at least one oblong rigid structural element into soft tissue and a method for manufacturing an assembly.

Further aspects and embodiments will be disclosed and elaborated herein.

DEFINITIONS

The following terms are used to generally describe the invention in its aspects and embodiments.

The terms ‘distal’ and ‘proximal’ are used to denote sections, regions, parts (or any further equivalent term) of elongated/oblong entities of the assembly such as oblong medical device, sleeve, the elements, and objects. Distal denotes a part, section, region, etc. which is located deeper inside soft tissue than a proximal section, region. A distal section extends from the distal end in proximal direction. A proximal section extends from the proximal end in distal direction. The terms distal and proximal are not absolute in position but are relative.

The distal end of the sleeve is defined as the distalmost part of the sleeve. The term “region of the distal end’ defines the part of the distal section where the diameter of the sleeve begins taper towards the distal end including the distal end. The distal section comprises the region of the distal end and the distal end.

In the present context a “medical object” is an object that interacts with the human or animal body following its insertion into human tissue, such as acting diagnostically, therapeutically or in any manner contribute to collect information of a condition in the human or animal body. In the context of the present invention, a medical object needs protection by the protection sleeve at least during an insertion process into soft tissue. The medical object may also be an object in need of a short transferal time such as living cells or cell aggregates. The medical may be selected from medical instruments which can monitor and/or stimulate soft tissue by e.g. electrical, thermal, ultrasound, optogenetic, mechanical monitoring and/or stimulation; and compounds, peptides, proteins, biological macromolecules and microorganisms e.g. pharmaceutics, peptides, proteins, genes, living cells and aggregates of living cells.

The term “oblong” characterizes an entity generally having a significantly longer axial extension than radial extension. An oblong entity may have a length to width ration of more than 10:1 , more than 20:1 , more than 30:1 , more than 50:1 . Typically, the width, diameter, of an oblong device is less than 5 mm and the length less than 15 cm, less than 10 cm, less than 5 cm. An oblong entity such as device, element, object, microelectrode and other medical objects/elements generally has a proximal section and a distal section, wherein the distal part comprises a distal end configured to support an insertion process into soft tissue. The assembly comprises a protection sleeve protectively enclosing an oblong device. The oblong device can in embodiments further comprise an element providing structural support, in oblong rigid element, during the insertion into soft tissue.

An “oblong device” may be the medical object per se. Alternatively, the oblong device comprises at least a medical object. If the oblong device does not by itself provide sufficient structural rigidity for enabling insertion of the assembly into soft tissue, then the oblong device must comprise at least one rigidity imparting element. The oblong device preferably has sufficient structural rigidity (stiffness) to enable breakage of weakness zones of the sleeve such as score lines, frangible lines, tear lines exemplified by slits/slots/indentations. A “rigidity imparting element’ may be the oblong device per se. Alternatively, the oblong device may comprise at least a rigidity imparting element. The rigidity imparting element can be a material providing structural rigidity to an oblong device, such as a water dissolvable, degradable matrix material which is stiff when dry. Alternatively, the rigidity imparting element is an oblong rigid element such as a pin or hollow structure.

An assembly comprises an oblong device and a water-resistant sleeve configured for insertion of a medical object. The assembly, in its totality, needs to be sufficiently rigid to be inserted into soft tissue and preferably follow a controlled trajectory to a predetermined position in soft tissue.

A “sleeve” or a protective sleeve denotes an oblong tubular element that encloses (accommodates) at least a distal section of an oblong device. The sleeve comprises at least a weakness preferably in the form of a longitudinal score zone/frangible zone/tear zone. The weakness may be materialized by a mechanical, thermal, structural, dimensional or chemical weakness in the sleeve. The weakness enables the sleeve to break controllably. The sleeve can have any length but preferably length of the sleeve is no longer than the oblong device.

A “water-resistant polymeric material” is a material which essentially inhibits that tissue fluids can reach the inside of the sleeve for a period at least until the intentional breakage of the sleeve. Minor fluid leaks are tolerable if the overall rigidity of the oblong device (or rigidity imparting element) is not compromised. For some application it is preferable that the material of the sleeve is waterproof meaning that the sleeve material is impervious to water. A waterproof sleeve material can be beneficial if dissolvable and/or degradable matrices are applied for imparting stiffness. For applications where the oblong device has intrinsic stiffness, i.e. stiffness will not degrade on exposure to water, water-resistant sleeve materials can be sufficient. The polymeric sleeve material may also be flexible to a certain extent. The polymeric sleeve material is preferably a Parylene type polymeric material, such as Parylene N, Parylene C, Parylene D and Parylene HT. Parylenes are comparatively stiff compared to flexible elastomers like PDMS of soft polyurethanes. The polymeric sleeve material may have an Elongation at Break of at least 10%, such as from about 10% up to about 250%, such as from about 25% up to about 100%. The sleeve overall may be water-resistant or waterproof or non-water degradable. Waterproof or non-water degradable signifies that the sleeve is fully resistant to degradation, dissolution, or structural breakdown when exposed to water or aqueous environments specifically soft tissue and soft tissue fluids. The sleeve preferably maintains its mechanical integrity, chemical stability, and functional performance over time in the presence of moisture or biological fluids.

A “distal section" of the sleeve is defined as the distal part of the sleeve that narrows in radial extent.

The term “configured for insertion into soft tissue’’ means that the assembly and hence protective sleeve has a suitable shape to penetrate soft tissue without causing unnecessary irritation and with reduced risk for puncturing blood vessels.

A withdrawing facilitating element and/or positioning element is integrated or attached to the proximal section of the sleeve. A withdrawing facilitating element can be a thread or flange attached, adhered to or integrated with the proximal section of the sleeve. A flange has a radial extension. Further to facilitate removal of the sleeve from soft tissue, a flange can also serve the purpose of positioning the assembly in axial direction.

The term that the protection sleeve is “removable in one piece’’ means that following the insertion and rupture of the breakable seal, it should be possible to remove the protection sleeve in its entirety without loose pieces or any other debris remaining in the soft tissue,

The term “transiently and/or permanently rigid component’’ of the oblong device signifies that the oblong device per se or in combination with e.g. a rigidity imparting element provides sufficient structural support to assist with the insertion and in embodiments of the invention have sufficient rigidity to assist in mechanically rupturing the breakable seal. A transient rigidity means temporarily rigid until it dissolves or softens following contact with body fluids.

The term” a connecting means engageable to a guiding system’’ explains that the medical object or its accessories is arranged to directly or indirectly contribute to a necessary displacement of the oblong device when inserting it into soft tissue and/or to a controlled displacement when rupturing the protection sleeve. The term “transferal time" is the time it takes to transfer a medical object such as a suspension with living cells, from an external source to the intended site in the soft tissue.

The term “microelectrode’’ is here defined as an insulated electrically conductive lead (electrically conductive core) preferably with a diameter of less than 100 pm, less than 75 pm, less than 50 pm, with at least one non-insulated section. The lead can be of any material such as a metal or a conductive polymer.

A multichannel microelectrode is a body containing multiple electrically insulated leads with one or more non-insulated active sites per lead.

“Soft tissue” is widely defined as soft tissue of any type including supporting tissue, connective tissue, nervous tissue, endocrine tissue, muscle tissue, vascular and lymphatic tissue, epithelial tissue, retinal tissue, hematopoietic and immune tissue. Nervous tissue may be granulated by functional region, including the central nervous system (CNS), brain including cerebral cortex, white matter deep nuclei, cerebellum, brain stem; spinal cord including central canal, anterior and posterior horns, ascending and descending tracts; peripheral nervous system (PNS) including cranial nerves, spinal nerves; ganglia such as dorsal root ganglia and autonomic ganglia. Nervous tissue may also be characterized by the cellular components including excitable cells such as cell body (soma), dendrites (input) and axon (output); glial cells such as astrocytes, oligodendrocytes, microglia, ependymal cells, Schwann cells, and Satellite cells. Soft tissue excludes hard tissue such as osseous (bone) tissue., Soft tissue may be selected from nervous tissue, endocrine tissue, muscle tissue, connective tissue and retinal tissue. Soft tissue encompasses any soft tissue which provides electric fingerprints which can be monitored and/or any tissue susceptible to electric stimulation. The term soft tissue also includes hollow fluidic spaces such as ventricles.

A “flexible’’ medical object or sleeve is defined such that a structural support is needed to push it through soft tissue, such as the brain without bending significantly.

“Injection free placement” of an object is defined such that no or minimal pressure is exerted on the tissue by the object when the object is entering the tissue.

SUMMARY OF THE INVENTION The invention is defined by the terms of the claims. The invention is also defined by any conceivable combination of features presented herein. Any conceivable combination of features would for the skilled person be obvious and cannot be considered to constitute new knowledge.

The present invention relates to an assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, comprising a water-resistant sleeve accommodating (enclosing) an oblong device; an assembly comprising an oblong device accommodated (enclosed) by a water-resistant sleeve, an oblong device which is enclosed (accommodated) by a water-resistant sleeve, a water-resistant sleeve per se, a method for inserting an oblong device accommodated in a water-resistant sleeve, and a method for manufacturing an assembly comprising an oblong device.

For capturing facets of the invention related to a product one aspect relates to an assembly as articulated in the preceding paragraph, an oblong device which is enclosed (accommodated) by a water-resistant sleeve, and a water-resistant sleeve accommodating (enclosing) an oblong device. The latter aspect highlights linguistically the water-resistant sleeve more than the oblong device. While both the oblong device and the water-resistant sleeve are important features for the inventive concept, the water-resistant sleeve has specific characteristics disclosed herein which are fundamental for the concept to work properly. More specifically, one aspect of the invention relates to an assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, the assembly comprising a water- resistant sleeve, accommodating an oblong device comprising at least one rigidity imparting element, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a withdrawing facilitating element and/or positioning element integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section of the sleeve by way of axial and/or radial forces (when axial and/or radial forces are exerted).

A further aspect of the invention relates to an assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, the assembly comprising a water-resistant sleeve accommodating an oblong device having an average diameter of less than about 5 mm, preferably less than 2 mm, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, the sleeve (sleeve wall) comprising a weakness at least in the distal section, said weakness enabling the distal section to rupture (break) when an axial force is exerted on the distal section, such as the region of the distal end, preferably distal end, by the oblong medical device.

A further aspect of the invention relates to a water-resistant sleeve accommodating an oblong device preferably configured for insertion into soft tissue, such as nervous tissue, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the water-resistant sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a withdrawing facilitating element and/or positioning element integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section of the sleeve by way of axial and/or radial forces (when axial and/or radial forces are exerted). A further aspect of the invention relates to an oblong device configured for insertion into soft tissue, such as neural tissue, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the oblong device accommodated (enclosed) by a water-resistant sleeve, the water-resistant sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a withdrawing facilitating element and/or positioning element integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section of the sleeve by way of axial and/or radial forces (when axial and/or radial forces are exerted).

An additional aspect of the invention relates to a method for inserting an oblong device comprising at least one rigidity imparting element into soft tissue, such as nervous tissue, the oblong medical device having an overall diameter of less than about 5 mm, preferably less than 2 mm, comprising accommodating at least part of the oblong device in a water-resistant sleeve thereby providing an assembly configured for insertion of medical objects in need for protection, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending form the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section when an axial force is exerted on the distal section by the oblong device.

Also encompassed is a method of manufacturing an assembly comprising; providing a removable pin with a shape suitable for forming a sleeve, or an oblong medical device and optionally coating the pin or the oblong medical device with a dissolvable agent; applying a first layer of water-resistant polymeric material on the pin or oblong medical device; forming at least one structural weakness (such as a slit or slot e.g. a longitudinal score zone/frangible zone/tear zone/ such as a score line) in the first, inner layer; optionally applying a second layer of water-resistant polymeric material covering at least the structural weakness such as a slot, the first and optionally second layer providing the sleeve wall; optionally removing the pin and inserting an oblong medical device into the sleeve.

SHORT DESCRIPTION OF THE FIGURES

Fig. 1 and 2A illustrate lateral views of sleeves

Fig. 2B illustrates an axial view of the distal end of a sleeve with three score zones/score lines.

Fig 3A illustrates a cross-section of a part of a sleeve wall of two layers exhibiting a structural weakness (score zone, score line) by way of a slit in the thick layer.

Fig. 3B illustrates a cross-section of the sleeve having two layers and a score zone, score line manifested in a slit in the thicker layer.

Fig. 3C illustrates a cross-section of a part of a sleeve wall exhibiting a structural weakness exemplified by a reduction of the thickness of the sleeve wall.

Fig. 4 illustrates a cross-sectional view of a specific weakness materialized by overlapping sleeve walls forming a breakable score line.

Fig. 4 illustrate

Fig. 5 illustrates a cross-sectional view of a sleeve having two layers where the score line is provided by a slit trough the thick layer covered by a thin layer. The sleeve accommodated a specific oblong medical device.

Fig. 6A-6E illustrate an assembly comprising a hollow cylindrical member within a sleeve. A catheter is inserted inside of the hollow cylindrical member for delivery of a suspension of living cells to the distal end of the sleeve. The sleeve is ruptures enabling the suspension to be absorbed into the surrounding soft tissue. DISCLOSURE OF THE INVENTION

Assembly

The assembly comprises at least an oblong device and a water-resistant sleeve where the sleeve accommodates at least a distal section of the oblong device. By inference the assembly preferably has an oblong shape. The assembly is thin, at least the part to be inserted into soft tissue, as the assembly is designed/configured to be inserted into soft tissue, such as nervous tissue, for the insertion of medical objects in need for protection. The average diameter of the assembly is less than about 5, preferably less than 2 mm. The average diameter of the assembly may for certain applications be less than 100 pm. The oblong device of the assembly may comprise several objects/elements. It is of significance that the oblong device in its totality has sufficient stiffness to allow insertion into various soft tissues. Stiffness can be implemented by a rigidity imparting element such as a single oblong object, alternatively, the overall stiffness of the oblong device can be provided in part by several distinct objects/elements. An oblong flexible object may be stiffened by the application of a material providing stiffness (structural integrity) when the material is dry and disintegrates and/or dissolves and/or changes mechanical properties when subjected to tissue fluids. A particular flexible oblong object/element/device constitutes a microelectrode which is stiffened by the application of a stiffening inducing matrix material when dry, the stiffening inducing matrix material disintegrating and/or dissolving and/or changing mechanical properties when subjected to soft tissue (soft tissue fluid). If the oblong device only constitutes one object/element such element must be sufficiently stiff to allow insertion into soft tissue.

Sleeve material and characteristics

The sleeve is made of one or more polymeric materials having an average sleeve wall thickness of less than 100 pm, less than 50 pm, less than 40 pm, less than 30 pm, less than 20 pm, less than 10 pm. The average sleeve wall thickness can be from 0.1 pm, from 0.2 pm, from 0.5 pm, from 1 pm, from 3 pm from 5 pm. Any lower and upper value may be combined. The average thickness can be from 0.2 pm to 50 pm, from 5 pm to 15 pm, from 1 pm to 2 pm.

The sleeve preferably has an oblong shape accommodating at least a distal section of an oblong device. The sleeve is either water-resistant or waterproof.

The sleeve wall may be made of non-water degradable or dissolving materials

The sleeve is made of a polymeric material. Any polymeric material can be chosen as long as the sleeve is water-resistant, inducing a controllable breakage at sleeve weaknesses and suitable of providing a distal section and distal end with a shape facilitating insertion into soft tissue while minimizing soft tissue damage

The sleeve material is preferably a water-insoluble, preferably flexible, polymer material.

The polymeric material of the sleeve may be selected from polymeric materials which are water-resistant, preferably water-insoluble and can be applied by dip coating, spray coating and vapor deposition such as physical vapor deposition (PVD) and chemical vapor deposition (CVD). Polymeric materials which can be vapor deposited is a preferred class of polymeric materials.

The polymeric material may be selected from polyurethanes, polyvinyl, polyimide, synthetic and natural rubbers, polytetrafluorethylene, silicones, and polymeric materials comprising para-substituted xylylene as backbone including poly(p-xylylene) based polymers.

Poly(p-xylylene) based polymers are particularly preferred as they can be vapor deposited. Examples of poly(p-xylylene) based polymers include Parylenes exemplified by Parylene N, Parylene C, Parylene D, Parylene F (AF-4), and Parylene HT. Parylene C is particularly preferred for some applications.

The polymeric sleeve material may also be flexible to a certain extent. The polymeric sleeve material may have an Elongation at Break of at least 10%, such as from about 10% up to about 250%, such as form about 25% up to about 100%.

The diameter of the distal section of the sleeve is decreasing towards the distal end. The tapering is preferably symmetrical around the central axis

The tapering may be conical, hyperbolic or parabolic. The tapered region of the distal end may be configured with longitudinal ridges and/or flutes evenly distributed around the circumference. The tapered region of the distal end may have any number of ridges, flutes evenly distributed around the circumference such as least three, at least four ridges and/or flutes evenly distributed around the circumference.

The tapering in the distal section of the sleeve, such as the region of the distal end, may have a shape of a half sphere or a dome with a radius of less than 200 urn, more preferred less than 100 urn in its base. The distal end may be blunt.

The weakness in the sleeve wall may be characterized as a score zone/frangible zone/tear zone/breakable seal, alternatively as a score line/frangible line/tear line/breakable seal. Score line/frangible line/tear line/breakable seal are used interchangeably. The weakness may be a reduction of the thickness of the polymeric material, alternatively, executed as an overlap of adjacent wall segments (an overlapping wall segment). A reduction of the thickness has preferably a longitudinal extension. The reduction of the thickness may be continuous or discontinuous such as indentations along a defined path. The width of the weakness in the form of a score line can be any value as long as the sleeve controllably ruptures along the score line. The width of a score line may be less than 500 pm, less than 400 pm, less than 300 pm, less than 200 pm, less than 100 pm, less than 50 pm, less than 15 pm, less than 10 pm, less than 5 pm. The width of a score line can be from 0.1 pm, from 0.2 pm, from 0.3 pm, from 0.4 pm, from 0.5 pm, from 0.6 pm, from 0.7 pm, from 0.8 pm, from 0.9 pm, from 1 .0 pm. The thickness of the score line is less than 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1 %, 0.1 %, 0.01 % of the average thickness of the sleeve wall.

An embodiment of the sleeve wall may comprise two or more layers, preferably two layers. One layer, preferably the inner layer, disposed closest to the central axis of the sleeve, is significantly thicker than the outer layer. The inner layer of preferably 1 ,5 up to 20 times thicker than the outer layer, preferably 2 up to 15 times thicker. The polymeric materials of the two layers may be of the same material or different materials. Preferably, the layers are made from the same polymeric material, so they suitably adhere and integrate. An embodiment of a weakness of the sleeve may be articulated by a sleeve having a sleeve wall formed of one polymeric material comprising at least a through-going slit the slit covered by a material different from the sleeve wall, such as a non-polymeric glue, providing a water-resistant controllably breakable weakness.

A further embodiment of a weakness of a sleeve is exemplified by cutting the sleeve wall thereby forming a slit which is not covered by a further layer or a glue.

The Weakness and positioning of the weakness, score-line

The weakness is preferably localized to a specific area/volume of the sleeve. The weakness can have any extension as long as the weakness induces a controllable breakage of the sleeve while minimizing pieces or even eliminates pieces of the sleeve in the soft tissue after removal of the sleeve. Preferably, the weakness is arranged so that the sleeve can be removed from the soft tissue in one piece. The extension of the weakness may be longitudinal, curved, zigzag shaped or meandering. Presented in two-dimensional space the area of the weakness preferably has an overall longitudinal extension. A weakness may be characterized as a score zones, frangible zone, tear zone, breakable seal inducing a controllable breakage of the sleeve by e.g. a radial and/or an axial force. An axial force is preferably exerted in the distal section of the sleeve preferably on the distal end of the sleeve. A radial force can be applied by dilation of the sleeve. An axial force may be provided by the interaction of the sleeve and oblong device. A score-zone, frangible zone, tear zone, breakable seal may generally refer to a deliberately introduced zone of mechanical weakness that allows for controlled breaking, tearing, or separation of the material along such a zone. The zone has an overall longitudinal extension. The weakness may manifest in several geometrical patters such as zigzag, curved, meandering but still preferably overall follow a longitudinal extension. The weakness may also be continuous or discontinuous in character.

A zone in the context of a weakness has preferably a linear extension. Thus, a score zone may be characterized as a score-line.

A dimensional weakness in the sleeve can be articulated by reducing the thickness of the sleeve wall and for some applications as a through-cut of very limited width. A weakness in the sleeve may also be manifested by a through-going slit, for simplicity herein referred to as a slit. A slit is a very thin (very narrow) and preferably formed by cutting. In the context of the invention, a slit extends completely through the sleeve material (wall), a though-going slit. The width of a slit is usually less than 5 pm, less than 4, 3, 2, 1 pm.

A non-through-going slit, also referred to herein as a slot or groove, can have any width which creates a weakness which is controllably breakable by axial and/or radial forces. A slot can be much wider that a slit because a slot does not extend completely through the sleeve wall. However, there is no lower limit on the value of the width of a slot. Provided the sleeve ruptures controllably the slot can have any width. The width of a slot is typically less than 0.5 mm, less than 0.4 mm, less than 0.3 mm, less than 0.2 mm, less than 0.1 .

In embodiments where a slit is covered with any material such as a thin layer of water- resistant material or glue, the width of the slit can have any value of the width of a slot.

When a sleeve is produced by e.g. deposing two layers on a pin, a first, inner layer and a second, outer layer on the first layer, a slit is cut into the first layer. The slit of the first layer becomes a slot when covered by the second layer. As the slit becomes a slot, the slit can have any width as required of a slot with the caveat that said slit is covered by e.g. a further layer or any other material, e.g. glue.

A slot may provide improved water-resistance compared to a slit. A score line may be represented by a slit or a slot.

The sleeve may be formed by using polymers enabling vapor deposition (chemical vapor deposition (CVD) and physical vapor deposition (PVD)) such a Parylene-type polymers. A first polymer is deposited on a pin or the oblong device of the assembly forming a first, inner layer. At least one through-going slit is cut through the inner layer prior to deposition of a second polymer forming a second, outer layer on the inner layer, or at least covering the slit. A sleeve wall is hereby formed having two layers where the weakness manifests in the combination of the through-going slit in the inner layers combined with the outer layer covering the slit, forming a non-through-going slit, i.e. a slot or groove. A further execution of a weakness of the sleeve, for some applications, is a slit extending completely through the sleeve material, a trough-going slit. Opposite slit surfaces may adhere by means non-covalent forces such as hydrophobic, Van der Waals interaction and/or shape memory effects of the material.

The weakness of the sleeve is preferably controllably breakable by exerting an axial force on the distal section of the sleeve, the distal section comprising at least one weakness, preferably the distal end of the sleeve, the axial force not exceeding 5 N, lower than 5 N, lower than 4 N, lower than 3 N, lower than 2 N. The axial force is exerted by the oblong device in the sleeve preferably by moving at least the distal section of the sleeve in proximal direction.

The weakness of a sleeve comprising at least two layers may be implemented by dissecting completely the inner layer forming a slit before applying an outer layer. The outer layer may not need to be applied fully around the inner layer. It may be sufficient to apply an outer layer at least covering the slit of the inner layer. The trough-going slit in the inner layer in combination with the outer layer covering the slit provides a weakening zone or a score zone/score line in form of a non-trough-going slit, a slot or groove The width of the slit or slot in one of the layers, e.g. an inner layer may be less than 500 pm, less than 200 pm, less than 100 pm, less than 50 pm, less than 40 pm, less than 30 pm, less than 20 pm, less than 10 pm, or even less than 5 pm. After cutting through one of the layers, e.g. the inner layer, the two opposite sides of the wall may still touch each other, i.e. the opposite sides of the wall are in physical contact, providing a slit with a very narrow width of less than 1 pm, prior to applying an outer layer covering the slit.

A weakness may also be generated by cutting the sleeve wall and radially adjusting the two opposing wall segments, so that the wall segments have an overlapping engagement preferably along a longitudinal zone. The overlap may be further secured by a glue such as a non-polymeric glue, providing a water-resistant controllably breakable weakness.

The weakness is positioned in the distal section of the sleeve such as at least one score-line in the distal section of the sleeve, preferably bisecting the distal end, preferably extending proximally preferably on one side of the sleeve preferably essentially disposed along the axis of the sleeve. The sleeve preferably has at least one score line essentially disposed along the entire longitudinal axis of the sleeve dissecting the distal end (taper) essentially symmetrically.

The sleeve preferably comprises at least two weaknesses, score lines, dissecting the distal end and further intersecting each other in the distal end.

According to an embodiment the sleeve comprises at least one cut-out at its proximal end, preferably having a triangular geometry and preferably oriented such that one of its edges (or vertices) points in a distal direction, preferably substantially aligned along the longitudinal axis of the sleeve and preferably associates with a score line in its vertex. The association of the distal vertex of a triangular cut-out facilitates the breakage of a longitudinal score line stretching from the distal section/distal end.

Water dissolvable/degradable materials

In several embodiments, an oblong device comprises water-dissolvable and/or water- degradable materials functioning as a rigidity imparting element. The group of water- dissolvable and/or water-degradable materials are also referred to as matrix materials. The matrix materials are preferably stiff when dry, that is when dry the matrix imparts sufficient stiffness to the oblong device to enable insertion into soft tissue and sufficient structural rigidity for breaking the sleeve.

The matrix material may be gel forming agent preferably in dry state and preferably comprising less than 20 %, less than 10 %, less than 5% by weigh of water.

The matrix material may be selected from gelatin from various animal sources can be used as a gel forming agent, such as bovine, pig skin, poultry skin, and tuna gelatin. Gelatin from mammal sources is preferred due to its superior gelling capacity at body temperature. For increased stiffness the use of chemically cross-linked gelatin is preferred due to its slower rate of degradation in the body. Examples of efficient gelatin cross linking agents are bis(vinylsulfonyl)methane and 1 -ethyl-3(3- dimethylaminopropyl) carbodiimide. Another useful crosslinking method is by UV radiation. The rate of degradation in the body can be controlled by the extent of crosslinking, which in turn can be controlled by the amount of cross-linking agent used or by controlling the exposure to UV radiation used for cross-linking a given amount of gelatin.

Other aqueous biocompatible gels of the invention include carbohydrate gels. Carbohydrate gels useful in the invention include arabinogalactan gel, arabinoxylan gel, galactan gel, galactomannan gel, lichenan gel, xylan gel but also cellulose derivatives such as hydroxymethylpropyl cellulose, and are formed by contact with aqueous media, in particular aqueous body fluid, with a gel forming agent selected from: arabinogalactan, arabinoxylan, galactan, galactomannan, licenan, xylan, hydroxymethyl cellulose and other cellulose derivatives forming gels in contact with aqueous media.

Further aqueous biocompatible gels of the invention include protein gels. Protein gels other than gelatin from animal sources useful in the invention include whey protein gel, soy protein gel, casein gel, which are formed by contact of aqueous media, in particular aqueous body fluid with a gel forming agent selected from whey protein, soy protein, casein.

Still other aqueous gels for use in the invention can be formed by contact of aqueous media, in particular aqueous body fluid, with a gel forming agent selected from the group consisting of: arabinogalactan; arabinoxylan; galactan; galactomannan; lichenan; xylan; cellulose derivatives such as hydroxymethylpropyl cellulose; whey protein; soy protein; casein; hyaluronic acid; chitosan; gum Arabic; carboxyvinyl polymer; sodium polyacrylate; carboxymethyl cellulose; sodium carboxymethyl cellulose; pullulan; polyvinylpyrrolidone; karaya gum; pectin; xanthane gum; tragacanth; alginic acid; polyoxymethylene; polyimide; polyether; chitin; poly-glycolic acid; poly-lactic acid; copolymer of poly-glycolic and poly-lactic acid; co-polymer of poly-lactic acid and polyethylene oxide; polyamide; polyanhydride; polycaprolactone; maleic anhydride copolymer; poly-hydroxybutyrate co-polymer; poly(l,3-bis(p- carbophenoxy)propane anhydride); polymer formed by co-polymerization with sebacic acid or with polyterephthalic acid; poly(glycolide-co-trimethylene carbonate); polyethylene glycol; polydioxanone; polypropylene fumarate; poly(ethyl glutamate-co- glutamic acid); poly(tertbutyloxy carbonylmethyl glutamate); poly-caprolactone; poly(caprolactone-cobutylacrylate); poly-hydroxybutyrate and copolymers thereof; poly(phosphazene); poly(D, L-lactide-co-caprolactone); poly(glycolide-co- caprolactone); poly(phosphate ester); poly(amino acid); poly(hydroxybutyrate); polydepsidpeptide; maleic anhydride copolymer; polyphosphazene; polyiminocarbonate; poly[(7.5% dimethyl-trimethylene carbonate)-co(2.5% trimethlyene carbonate)]; polyethylene oxide; hydroxypropylmethylcellulose, poly(ethylene-co-vinyl acetate); isobutylene-based copolymer of isobutylene and at least one other repeating unit such as butyl acrylate: butyl methacrylate; substituted styrene such as amino styrene, hydroxy styrene, carboxy styrene, sulfonated styrene; homopolymer of polyvinyl alcohol; co-polymer of polyvinyl alcohol and at least one other repeating unit such as a vinyl cyclohexyl ether; hydroxymethyl methacrylate; hydroxyl- or aminoterminated polyethylene glycol; acrylate-based copolymer such as methacrylic acid, methacrylamide, hydroxymethyl methacrylate; ethylene vinyl alcohol copolymer; silicone based copolymer of aryl oralkyl siloxane and at least one repeating unit; polyurethane; heparan sulfate; RGD peptide; polyethylene oxide; chrondroitin sulfate; YIGSR peptides; keratan sulfate; VEGF biomimetic peptide; perlecan (heparan sulfate proteoglycan 2); lleLys-Val-Ala-Val (IKVAV) containing laminin alpha-1 chain peptide; modified heparin; fibrin fragments.

FURTHER EMBODIMENTS OF THE INVENTION

The weakness may be embodied by a sleeve comprising one or at least two layers, preferably two layers, an inner, first and an outer, second layer (inner/outer with respect to the central axis of the sleeve/assembly. The inner layer comprises at least a through- going slit and/or slot forming opposing wall segments which are radially displaced and disposed overlapping each other forming an overlapping wall segment. The wall segment may be further secured by the application of an outer layer covering at least the overlapping wall segment or alternatively water-resistant material such as a non- polymeric glue.

The weakness may be embodied by a sleeve comprising at least two layers, preferably two layers, an inner, first and an outer, second layer (inner/outer with respect to the central axis of the sleeve/assembly. The inner layer comprises a slit, the slit covered by the outer layer thereby forming a slot or groove. The outer layer may be the same or different polymeric material than the inner layer, or another material such as a non- polymeric glue. The weakness may be only arranged in the distal section of the protection sleeve.

The weakness is preferably constituting at least a score zone/score line at least extending around the distal part of the distal section.

The weakness may be embodied by a score line extending in a proximal direction from the distal section.

The weakness of the sleeve may be materialized by at least one score line essentially dissecting the region of the distal end. .

The weakness of the sleeve may be materialized by at least two score lines dissecting the region of the distal end and intersecting each other in the region of the distal end.

The weakness of the sleeve may be materialized by at least two score lines at least extending around the region of the distal end and intersecting each other in the region of the distal end. Preferably, the at least two score lines are essentially uniformly arranged around the circumference at any axial location within the region of the distal end. Preferably, the at least two score lines are arranged (spaced) at approximately equal angular intervals (angles) around the sleeve axis (as axially observed in a proximal direction).

It is generally preferable that all score lines intersect each other in one very confined area which may be characterized as a point (or intersection area/point). The intersection point preferably coincides with the most distal tip of the distal end.

The number of score lines around the sleeve axis as seen from a location distally from the distal end and in proximal direction (referred to as distal end score lines) preferably follows the following equation with at least two score-lines: number of score lines N extending around the region of the distal end equals N+N distal end score lines around the sleeve axis as seen from a location distally from the distal end and in proximal direction (along the central axis). Two score lines provide four distal end score lines. Three score lines provide 6 distal end score lines.

The angle between two distal end score lines preferably varies up to 10°, up to 5°.

The weakness might also be executed by at least three score lines, all extending around the region of the distal end. Preferably, the at least three score lines are essentially uniformly arranged around the circumference at any axial location within the region of the distal end. Preferably, the at least three score lines are arranged (spaced) at approximately equal angular intervals around the sleeve axis (as axially observed in a proximal direction).

It is preferred that at least one score line extends to the proximal end of the sleeve (signifying that the sleeve may be broken up into two pieces). According to an embodiment the at least one score line extending to the proximal end of the sleeve ends (connects to the edge) at the edges (or vertices) of a triangular cut-out in the proximal end of the sleeve pointing in a distal direction.

According to an embodiment, the weakness is executed by at least two score lines, all extending around the region of the distal end. Preferably, the at least two score lines are essentially uniformly arranged around the circumference at any axial location within the region of the distal end. Preferably, the at least two score lines are arranged (spaced) at approximately equal angular intervals around the sleeve axis (as axially observed in a proximal direction), one score line extending to the proximal end of the sleeve. Preferably, only one score line extends from the distal section, distal end to the proximal end of the sleeve, preferably to the distal vertex of a cut-out in the proximal end of the sleeve the cut-out having a predominantly triangular shape.

According to an embodiment, the weakness is executed by three score lines, all extending around the region of the distal end thereby forming six distal end score lines. Preferably, the three score lines (providing six distal end score lines) are essentially uniformly arranged around the circumference at any axial location within the region of the distal end. Preferably, the three score lines are arranged (spaced) at approximately equal angular intervals around the sleeve axis (as axially observed in a proximal direction), one score line extending to the proximal end of the sleeve. Preferably, only one score line is extending from the distal section, distal end to the proximal end of the sleeve, preferably to the distal vertex of a proximal cut-out in the proximal end of the sleeve the cut-out preferably having essentially a triangular shape.

According to an embodiment the sleeve comprises at least one recess at its proximal end, preferably having a triangular geometry and preferably oriented that one of its edges (or vertices) points in a distal direction, preferably substantially aligned along the longitudinal axis of the sleeve. The edge of the recess having a triangular geometry pointing in distal direction is preferably associated with a score line. The weakness may be non-uniform in fragility to break by mechanical forces. A weakness can be designed with selected weaker parts that upon inflation or stretch in a direction transverse to the main axis of a weakness initiate the breakage for an added control of the rupturing process. For example, a score line can be designed to first break in a distal section or distal end (tip) or a region in the vicinity thereof and thereafter in an axial direction, preferably essentially along the axis of the sleeve in a straight line, but also other configurations are conceivable within the inventive scope,

In embodiments, the protection sleeve of the oblong device has a distal section that is generally configured for facilitating the soft tissue to be pushed aside during insertion.

In embodiments of the assembly, the protection sleeve comprises a distal section configured with gradually and distally decreasing radius.

In embodiments, the region of the distal end of the protection sleeve has a blunt configuration that contributes to push away tissue in the insertion process and reduces risks of inadvertently damaging blood vessels.

In embodiments, the protection sleeve has a distal section with a conical shape and at least one score line extending from the distal end to the proximal end of the protective sleeve. A protection sleeve with a conically shaped region of the distal end can have sharp, pointed end or blunt end, dependent on the application of the oblong device.

The distal end of the sleeve may have a shape of a dome or half sphere with a radius less than 200 pm, preferably less than 100pm.

In embodiments, the protection sleeve has a rounded, preferably partially spherical, distal section with at least two intersecting score lines, the intersection preferably in the distal end. Preferably, at least one score line extends proximally towards, but not reaching, the proximal end of the protection sleeve.

In embodiments, the protection sleeve of the assembly has a distal section that is generally configured for facilitating the penetration of and reducing the disruptive effect of penetrating blood vessels, for example to inject pharmaceuticals or other medical objects into the blood stream. In such an embodiment, the distal end can comprise a sharp edge for penetrating blood vessel walls, for example with a medical device serving as an injection needle or as a catheter for drug delivery. This embodiment reduces the risk of bleeding during and after insertion of catheters into blood vessels. By avoiding the cutting effect of the sharp distal part of the state of the art injection needles, injuries to the blood vessels can be reduced. Once inside the blood vessel the protection sleeve is withdrawn leaving the catheter in place inside the blood vessel. A rigid stylet, preferably hollow, may be used to provide structural support during insertion.

In embodiments of the assembly the protection sleeve is configured to be removable from the soft tissue in one piece following rupturing of the weakness zones such as score lines.

In embodiments of the assembly, the protection sleeve comprises at least one flange to control the insertion depth and to facilitate the removal of the protection sleeve after its insertion in soft tissue. The flange is integral with or at least adhering (by for example a glue) to the protective sleeve and is protruding from the protective sleeve. The flange can have any shape such as a rectangular or rounded shape and preferably radially protruding more thanl 0 pm with reference to the outer surface of the sleeve. A suitable radial protrusion is up to 5 mm, preferably up to 10 mm but it can be longer. A suitable axial length of the protrusion (flange) is between 0.1 and 10 mm, preferably between 1 and 5 mm but it can be longer. The flange may be equipped with one or more structures enabling attachments of e.g. any type of wire or handle to facilitate its manipulation.

In embodiments not having a flange, the protection sleeve comprises threads firmly attached, e.g. with a glue, to the proximal part of the sleeve, such that the sleeve can be pulled in a proximal direction. It is preferred that these threads end with a handle to facilitate the removal of the protective sleeve.

In embodiments, the oblong device comprises a connecting means engageable to a guiding system for supporting the insertion into soft tissue.

In embodiments, the assembly further comprises an, at least partially, enclosed rigidity imparting element. A rigidity imparting element can assist with both insertion of the assembly and with rupturing of the protection sleeve. In some embodiments, the rigidity imparting element can have an oblong cylindrical shape, for example made of stainless steel. Preferably, the rigidity imparting element is removable after the oblong device is correctly positioned in soft tissue and in contact with body fluid. In embodiments the oblong device comprises at least one transiently or permanently rigidity imparting element that can provide a support structure for flexible or fragile components of the medical object.

In embodiments of the assembly, the enclosed oblong device contacts the protection sleeve. For example, the protection sleeve and the oblong device can be in friction contact, for example by manipulation of any of their contact surfaces or a suitable part thereof.

In embodiments of the assembly, the oblong device comprises at least one rigidity imparting element selected from biocompatible material that is dissolvable, degradable or otherwise affected by contact with body fluids or by contact with tissue. Dissolvable and/or degradable materials suitable for the purpose of being a part of an implantable oblong device, for example arigidity imparting element supporting insertion of flexible microelectrodes are well known to people skilled in the art. Materials dissolvable in aqueous body fluid including water or degradable by the fluid or water can comprise for example a biocompatible carbohydrate and/or proteinaceous material such as glucose and albumin. Alternatively, the biocompatible material is gelling by contact with aqueous body fluid, such as gelatin or hyaluronic acid or a mixture of gelatin or hyaluronic acid with carbohydrate and/or proteinaceous material. Further examples are available from WO2018/217147 and WO 2022/005386.

In embodiments of the assembly, the enclosed oblong device has an axial extension and has an average diameter of about 5 mm, or less. Preferably, the diameter is less than about 4 mm less than about 3, less than about 2, less than about 1 mm. The length of the oblong device is preferably less than 15 cm, less than 10 cm, less than 5 cm.

In embodiments of the assembly, the enclosed oblong device comprises at least one flexible microelectrode or constitutes a flexible microelectrode, such as microelectrodes in a bundle or an array or multichannel microelectrodes. The microelectrodes/multichannel microelectrodes can be flexible and be embedded in a rigid support structure /matrix material, for example comprising a rigid material soluble in body fluids as outlined above. A microelectrode is an example of a medical object which is oblong in shape and therefore falls in the category of oblong device. In certain embodiments of the assembly, the protective sleeve encloses an oblong device comprising a microelectrode comprising a proximal insulated section and a distal non-insulated section, the microelectrode centrally disposed in an envelope/sleeve/casing of a flexible polymeric material, the casing attached, preferably slidably attached, to the insulated section of the microelectrode by a wall of flexible polymeric material dividing the casing in proximal and distal compartments, the noninsulated section of the microelectrode fully disposed in the in the distal compartment, the distal compartment comprising means allowing the microelectrode electrically monitor or stimulate nervous tissue surrounding the casing without the non-insulated section of the microelectrode directly contacting nervous tissue. Embodiments of such oblong devices are disclosed in WO 2020/141997 and WO 2022/005386. The content of WO 2020/141997 and WO 2022/005386 is incorporated herein by reference. Thus, the content of WO 2020/141997 and WO 2022/005386 should be considered being explicitly disclosed herein.

In certain embodiments of the assembly, the sleeve encloses an oblong device comprising a plurality of microelectrodes arranged in a dissolvable guiding structure connected to a proximal guiding member comprising means to axially and distally displace the microelectrodes to defined tissue contact positions, as described in WO 2022/124957 incorporated herein as a reference.

In embodiments of the assembly, the oblong device can comprise an electronic chip comprising semiconductive materials and serving to for example amplify cellular electrical signals or to transmit signals, an energy source such as a battery, a biocompatible fluid, optionally comprising at least one therapeutically active agent and/or cells. It may also contain toxic materials intended to lesion a particular tissue such as a cancerous tissue or tumor.

In embodiments, the assembly comprises a sensor attached on the inside of the protection sleeve. The sensor can be operably connected to electronics outside the soft tissue capable of processing and communication data received from the sensor. The sensor can detect fluid leakages into the protection sleeve before it is ruptured, or the sensor can be configured to monitor the insertion process. One example of a sensor that can be used to detect fluid leakage comprise two separated electrodes wherein the electrodes are insulated except for their distal ends and wherein the electrodes are in contact with electronics to measure the impedance between the two electrodes. In case of leakage of body fluid in an amount sufficient to short-circuit the two electrodes, a lowered impedance between them will result. This will, in turn, inform the operator that a leakage has occurred.

In embodiments, the assembly comprises markers to improve detection by ultrasound imaging, X-ray, computer tomography (CT) or magnetic resonance imaging (MRI) that can aid the precise positioning of the medical object. Markers can be provided as disclosed in WO 2018/222101 which content is incorporated herein by reference.

In embodiments, the assembly has a smooth shape. The surfaces of the protection sleeve may be coated with a friction reducing agent. In one example, the coating comprises a mucous-like composition comprising glycoproteins and/or proteoglycans, suitable for coating a protection sleeve enclosing a medical object with rough surfaces or that is surrounded by a fibrous net. In another example, the friction reducing agent is a thin layer of ice, which when thawing becomes super slippery.

In embodiments of the assembly, the outer surface of the protection sleeve is coated with degradable materials capable of releasing pharmaceuticals, for example to provide trophic support for the host tissue receiving the implant and or the living cells to be implanted. Such materials include anti-inflammatory agents, trophic factors, neurotransmitter substances such as GABA or glycine or anesthetics such as benzodiazepines to reduce the metabolic need of the local tissue implanted. It may also be coated with antibacterial materials to prevent or at least reduce the risk of infection. It may also be coated with materials that have a pH buffering capacity to reduce the risk of detrimental pH changes during and after the insertion procedure.

Methods for inserting an oblong device

One aspect of the invention relates to a method for inserting an oblong device comprising at least one rigidity imparting element into soft tissue by way of a water- resistant sleeve accommodating at least the distal section of the oblong device.

The assembly comprising an oblong device and a water-resistant sleeve used in the method may be characterized as presented herein. More specifically, the invention relates to a method for inserting an oblong device comprising at least one rigidity imparting element into soft tissue, such as nervous tissue, the oblong device having an overall diameter of less than about 5 mm, preferably less than 1 mm, comprising accommodating at least part of the oblong device in a water-resistant sleeve thereby providing an assembly configured for insertion of medical objects in need for protection, the water-resistant sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section when an axial force is exerted on the distal section by the oblong device.

A further embodiment relates to a method for inserting an oblong device comprising at least one rigidity imparting element into soft tissue, such as nervous tissue, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, comprising accommodating at least part of the oblong medical device in a water- resistant sleeve thereby providing an assembly configured for insertion of medical objects in need for protection, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a withdrawing facilitating element and/or positioning element integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section of the sleeve by way of the application of axial and/or radial forces (when axial and/or radial forces are exerted). The axial force exerted on the distal section of the sleeve is preferably provided by moving at least the distal section of the sleeve in proximal direct by applying an axial force (in proximal direction) on the at least one thread. The thread can be moved in any direction as long as the result is that at least the distal section of the sleeve moves in proximal direction. Preferably the thread is moved such that the move generates an axial force vector.

The axial force is preferably exerted after placement of the assembly within the soft tissue.

According to an embodiment, the axial force exerted on the distal section by the oblong device is lower than 5 N, preferably lower than 2 N such as lower than 1 , lower than 0.6 N.

The method for inserting an oblong device into soft may additionally comprise any one of the following activities: enclosing at least part of the distal section of the oblong object within the sleeve thereby forming an assembly; introducing the assembly into soft tissue; properly positioning the assembly to a predetermined position within soft tissue; rupturing, breaking the at least one weakness of the sleeve thereby at least admitting tissue fluids contacting the medical object by applying radial and/or axial forces on the sleeve; removing the sleeve from the soft tissue.

According to an embodiment, after the breakage of the sleeve, the assembly or parts of the assembly are removed from the soft tissue.

Preferably, weakness zones of the sleeve comprised in the distal section are intentionally broken, ruptured by moving at least the distal section of the sleeve in proximal direction thereby exerting an axial force from the inside of the sleeve in distal direction on the distal end.

In embodiments of the method, an axial or radial pressure is exerted on the protection sleeve by the oblong device to rupture the weakness zone, e.g. score line.

In embodiments of the method, dilation (i.e. radial and/or axial expansion) of the sleeve can generate sufficient force on the sleeve to rupture the weakness zones.

In embodiments of the method the ruptured sleeve is removed in one piece alternatively into any number of pieces corresponding to the number of threads attached to or flanges integrated with the proximal section, preferably proximal end, of the sleeve. An example is a sleeve to which proximal end is attached four threads, the threads attached to sections of the sleeve separated by score lines. The sleeve will rupture to produce four pieces of the sleeve each piece attached to a thread. It is preferred that score lines are arranged such tha the sleeve can be removed in one piece.

In embodiments of the method, the oblong device to be implanted comprises living cells or living tissue fragments or aggregates of living cells. For the application of implanting living cells or tissue fragments, the oblong device preferably comprises a hollow member preferably hollow cylindrical member, preferably provided sufficient rigidity to enable insertion of the assembly, enabling the insertion of a catheter. The medical object, i.e. iving cells or living tissue fragments or any other biological material, is introduced into the sleeve by the catheter. To reduce the risk of premature contact with the tissue or to reduce the transferal time of the cells to be transplanted, one embodiment of the invention is to first insert an assembly of the invention according to any previously described embodiments, comprising a hollow conduit/member such as a rigid cylinder, a catheter and a sleeve. The hollow conduit can comprise living cells or fragments, alternatively, living cells or fragments may be in the distal section, distal end, of an elongated member, e.g. catheter, configured to move axially within the hollow conduit. Living cells or fragments can also be present between an oblong device and the sleeve. After breakage of the sleeve the living cells or fragments are introduced to the soft tissue target volume. By introducing the living cells to an already inserted oblong device, transferal time for the cells can be significantly reduced thereby reducing the risk of detrimental effects on the cells of e.g. decreasing oxygen levels or altered pH inside the hollow conduit. Notably, there is no need to push out (inject) the living cells when removing the sleeve and the oblong device, since they are in direct contact with the target tissue once the protective sleeve and the oblong device are removed. This also means that there are no or minimal pressure on the target tissue when the cells are introduced into the tissue.

After insertion of the assembly of the invention into the target tissue, the cell suspension is quickly transferred to the predetermined soft tissue volume, preferably through a catheter that has been introduced into the stiff cylinder before the insertion, whereafter the sleeve is quickly removed. To further reduce transferal time for the onsite delivery, the hollow conduit is preferably equipped with both a distal opening and one or more open slots or holes in the wall of its distal part through which the suspension of cells or cell aggregates can be exposed to the tissue once the protective sleeve is ruptured and withdrawn. The device comprising a hollow member (cylinder) and optional catheter is then removed leaving the living cells in the intended site in tissue. The suspension of living cells or living tissue fragments (or living cells or cell fragments) can be ejected from the oblong medical device during the withdrawal of the cylinder if necessary. More preferably the living cells, tissue fragments of living cells, preferably in form of a suspension, are delivered to the soft tissue without the need of pressure or at least a minimum of pressure. The suspension of living cells or cell fragments can also be deposited within soft tissue by carefully moving the hollow conduit/member in proximal direct without essentially moving the suspension and without essentially exerting an axial pressure on the suspension. The reduction in transferal time for the living cells corresponds to the duration of inserting the oblong device into soft tissue. The oblong device may have a temperature lower than the body temperature such as below 0 °C and be filled with frozen cell-free solution prior to its insertion and optionally ice coated prior to the insertion.

In an alternative preferred embodiment of the method of delivering cells to soft tissue, the assembly of any previously described embodiment is first inserted into target soft tissue whereafter a pause of up to 7 days or even longer is made, before the living cells are administered through the oblong device. The sleeve is then ruptured thereby exposing living cells to the soft tissue. The purpose of the interruption is to let the tissue reactions (inflammatory reactions) subside thereby providing an environment more conducive for survival of the living cells.

It is within the scope of the invention to combine the insertion of living cells with insertion of further medical objects conducing to the proliferation of the living cells in the soft tissue. Such medical objects can be microelectrodes for electrical stimulation of the implanted living cells or for recording of signals from the implanted or resident cells, and light guides. This is enabled by, for example adding the microelectrodes and/or light guides to the suspension of living cells or cell aggregates before or after the insertion of the oblong device into the target tissue.

In one aspect, the invention relates to a method of manufacturing an assembly according to any previous embodiment. The method comprises providing a pin (or an oblong device) at least partially having a circular, ellipsoid, rectangular, rhomboid cross-section shape and a distal section narrowing in radial direction towards its distal end suitable for forming a sleeve. The pin may also have ridges along its surface. According to an embodiment an oblong device as presented herein can serve as the tool for producing the geometry of the sleeve. The pin can be hollow or solid and for example be made of a polymer, stainless steel, wolfram, glass, crystal or a ceramic. The surface of the pin is preferably smooth to facilitate the subsequent process. Preferably, the pin is coated with a dissolvable agent such as gelatine or hydrocarbon- based material, to support the subsequent process. Next, a water-resistant polymeric layer is applied on the pin or oblong device forming an inner or first layer and a structural weakness such as a slit is formed in the layer with a suitable tool such as a very sharp knife. When the slit has been formed, a second, preferably outer layer of water-resistant material is formed to cover the slit. Preferably, the second, outer layer is significantly thinner than the first, inner layer. Preferably, the first layer has thickness at least two times the thickness of the second layer, at least 3 times, at least 4, 5, 6, 7, 8, 9, 10 times the thickness of the second layer. Preferably, the first and second layer are made from the same polymeric material. However, the use of different materials is within the scope of the invention, for example a glue e.g. a non-polymeric glue covering the slit. If an oblong device is not used as a mold for forming the sleeve, the sleeve is removed from the pin and an oblong device such as presented herein such as a medical object and optionally a rigid element and or a sensing element (e.g. microelectrode and/or light guide) is introduced into the protection sleeve. Alternatively, the second layer can be applied after removal of the pin and insertion of the medical object and the optional structure element.

In embodiments of the method, the weakness is formed by cutting a slit in the one layer preferably the first, inner layer.

In embodiments of the method, the layers are formed from a suitably stretchable Parylene, such as Parylene C. Other polymers such as silicon elastomers, polyurethane, polyethylene are also within the scope of the invention. The application of the layers is made with various conventional techniques including for example dip coating, spray coating and vapor deposition. In embodiments of the method, the pin can be provided with one or more defined radially protruding part(s) serving as a mold for one or more radially extending proximally flange(s) of the protection sleeve continuously formed when applying at least one of the layers of the protective sleeve, preferably the first thicker layer. The flanges can be provided with attachment means for threads serving to support manipulation (withdrawal) of the sleeve.

The protective sleeve formed with the inventive methods will have a final wall thickness of less than 100 pm, less than 50 pm, such as 0.2 to 50 pm preferably from 1 to 25 pm, more preferably from 5 to 15 pm. However, it is within scope of the recited methods to form parts or sections with a higher thickness when necessary for special applications and/or to facilitate its manipulation.

In embodiments of the method, it comprises providing a removable pin with a shape suitable for forming a protection sleeve (as previously described) and optionally coating the pin with a dissolvable agent such as a carbohydrate-based material or gelatine. A layer of water-resistant polymeric material is applied on the pin and a slit with a width of from 5 to 500 pm is formed in the sleeve wall. The slit is then covered by forming an overlapping wall part from the sleeve wall edges and the pin is removed thereby forming a slot or groove, and the oblong medical device which may comprise a medical object and an optional rigid element is introduced into the sleeve. The overlapping wall parts are then covered with a second layer of water-resistant polymeric material, to form a score line. The second layer has a thickness that is substantially thinner than the first layer and, in the range of 0.5 urn to 10 pm, preferably between 0.5 and 5 pm and most preferably between 0.8 urn and 2 pm. Alternatively, a slit is cut through the first layer without forming a wall part overlap, but with the mentioned second layer of water-resistant polymeric material and/or a water-protecting material covering the slit and forming aslot, groove and thereby a score line.

In all embodiments of manufacturing the assembly, the sleeve can be covered with another water-resistant material such as a glue after insertion of the oblong device into the protective sleeve, to reduce risks for leakage of having inadvertently cracked the protection sleeve.

The invention is particularly useful in combination with electrodes embedded in water dissolvable materials but can also be used to protect the tissue from inadvertent cutting at the tip when introducing for example a syringe needle into the tissue. It is within the scope of the invention to implant a bundle or more preferably an array of devices (such as arrays of assemblies) of the invention simultaneously. To this end, a plurality of devices (assemblies) is attached to an insertion system capable of stereotactically implanting the ensemble of the devices. Simultaneous implantation has the advantage of reducing the total time for implantation of a plurality of devices (assemblies) which is of importance in a clinical setting

It is feasible to include structures such as a rigidity imparting element in the devices to be implanted, that facilitate the opening of the weakness. Such rigidity imparting elements could comprise for example a sharp edge that on pulling the protection sleeve backward over the device will focus the tearing forces near the rifts.

Useful embodiments are: 1 ) an oblong device for providing a gel channel as disclosed in WO 2016/032384 2) an oblong medical device comprising dissolvable microchannels and microelectrodes and other filaments as disclosed in WO 2020/141997 and W02022/005386, 3) an oblong medical device serving as a new injection needle having a protection sleeve with a sharp conical tip, a catheter and optionally a stylet.

Use of the invention

The oblong medical device of the invention can be used for delivery into soft tissue of medical objects capable of stimulating, recording or otherwise interact with the targeted soft tissue. Such medical objects include electronics, electrodes, optical fibers, sensors to measure vital parameters such as oxygen, pH, blood pressure, living cells or aggregates of living cells and pharmaceutics. The invention can be used for insertion of a medical device comprising materials that degrade when coming into contact with tissue.

The invention can be used for insertion of catheters into blood vessels.

The invention can be used for therapeutic purposes such as to improve treatment of brain-related disorders such as neurodegenerative diseases, pain, stroke, depression, sleep disorders, blood pressure disorders, obesitas, epilepsy or endocrine disorders. It can also be used for therapeutic purposes to improve treatment of endocrine disorders such as diabetes.

The invention can be used to improve optical visibility when performing endoscopy. For this application the sleeve material is preferably transparent to a degree enabling the use of the optics during insertion.

The invention can be used to reduce the transferal time for time-controlled and on-site delivery in targeted soft tissue of fragile or vulnerable medical objects. Reduction of the transferal time is accomplished by first implanting an oblong device of the invention into the target tissue. The medical object(s) can then be quickly transferred into the intact device without compromising the integrity of the medical objects and after breakage of the seal of the protective sleeve will be in direct contact with the target tissue. One example of use of the invention is to implant living cells, tissue fragments or cell ensembles of any type for cell therapy into an intended site in host soft tissue with the benefits of a reduced transferal time, possibilities to prepare the host tissue for the implant in advance and with possibilities to reduce/elim inate mechanical pressure on the tissue during the actual transferal of the object into the tissue.

DESCRIPTION OF SPECIFIC EMBODIMENTS

Fig. 1 is a schematic illustration in a side view of a sleeve of an assembly 100 of Parylene C according to the invention with a distal conical section providing a sharp distal end 110. A weakness zone in form of e.g. a slot, groove 120 (score line) is arranged along a main axis of the sleeve from the distal end to the proximal end. The inside of the protection sleeve is arranged with sensors 130, 140 that can detect the position of the oblong device and any leakage of water before the insertion into soft tissue is completed to its predetermined position in soft tissue.

Fig. 2A is a schematic illustration in a side view of a sleeve of an assembly 200 with a protection sleeve according to invention with a rounded partially spherical distal end section. The protection sleeve has three score lines 210, 220, 230 intersecting in the region of the distal end part. The score line 210 extends axially from the distal end in proximal direction, but not reaching the proximal end of the protection sleeve. The protection sleeve is provided with flanges 240A and 240B in its proximal part to support its manipulation. The flanges are arranged with manipulation means 242A and 242B, such as attachment means for threads for the surgeon to assist with displacement of the sleeve.

Fig. 2B is a view from an axial position distal of the distal end in proximal direction illustrating tree score lines forming six distal end score lines.

Both arrangements in Fig. 1 and Fig. 2 meet the important requirement that no remnants of the sleeve are left behind in the tissue that risk tissue reactions. It is also necessary that there are no loose fragments of the protection sleeve following its removal, for example in case fragile microelectrodes are to be pushed out from a medical object (not shown) as initially protected by the sleeve.

Figs. 3A to Fig. 3C are cross sections of a protection sleeve walls showing different weaknesses (score lines). Fig. 3A schematically shows a wall part 300A of a protection sleeve of 11 pm wall thickness. A thoroughgoing slit 320A with a width of less than 1 pm is formed in a first layer 310A having thickness of about 10 pm. A second layer 330A with a thickness of about 1 pm is applied on the first layer, covering the slit to form a slot, groove and a breakable score line.

Fig.3B shows the arrangement in Fig 3A in cross-section with an outer protecting layer 330A covering the slit 320A.

Fig. 3C schematically shows a wall part of a protection sleeve 300C with a slit 320C with a width of about 10 pm formed in the first layer 310C having a thickness of 10 pm. A second layer 330C with a thickness of about 1 pm is applied on the first layer covering the slit to form a slot, groove and a breakable score line.

Fig. 4 is a cross-sectional view of another embodiment of a protection sleeve 400 made with an axial slit and walls overlapping to form a breakable score line. A slit 410 is cut in the wall of the layer of polymeric material, such as Parylene C, from the distal end towards the proximal end. Opposite wall segments are radially arranged to form overlapping wall segments. The overlapping wall segment 410 is covered with a second layer of Parylene C or with water-insoluble glue to form a breakable score line.

Fig. 5 is a cross-sectional view of a schematic assembly 500 according to the invention.

It has a protection sleeve with a first layer 510 having a throughgoing slit 520 covered by a second layer 530 providing a slot, groove forming a breakable score line that ruptures in an axial direction from a distal to proximal part. The second layer here is only partly applied to the first layer. Inside the protection sleeve a schematically represented oblong device 540 is schematically shown that both is water sensible and comprise sharp edges and rough surfaces. The assembly can further be coated with a friction reducing material such as gelatine, glycoproteins or a carbohydrate in order facilitate insertion into tissue.

Fig 6a, 6b, 6c and 6c illustrate an assembly for introducing a suspension of living cells. The assembly (600) comprises a sleeve (610) accommodating a hollow cylinder member (620) with a distal rectangular cut-out (621 ). The sleeve has a triangularly formed cut-out at the proximal end (612). A thin thread is also attached to the proximal end of the sleeve (613). Furthermore, a lateral score line (611 ) is disposed axially from the distal end in proximal direction and associated with the distal vertex of the triangular cut-out. The sleeve has further three score lines extending around the region of the distal end (partly obscured) forming six distal end score lines. Fig. 6e illustrates an axial view in proximal direction from a position distally to the distal end of the sleeve. The six dashed lines represent three score lines extending around the distal end and the region of the distal end. After positioning the assembly (600) within soft tissue (640) and inserting the catheter (630) within the hollow member (620) and placing a suspension of living cells (650) within the distal volume of the sleeve, the distal end of the sleeve is ruptured along the score lines extending around the region of the distal end by pulling the thread in mainly axial direction. One score line (611 ) extends on one lateral side of the sleeve engaging the distal vertex of the rectangular cut-out (612) in the proximal end of the sleeve. Fig. 6a illustrates an assembly (600) of a sleeve (610) accommodating a hollow cylindrical member (620) which is positioned within soft tissue (640). Fig. 6b illustrates a catheter (630) which is inserted within the hollow member (620). A suspension of living cells (650) is dispensed inside the catheter (630) to the distal section of the sleeve also filling the gap between the hollow member (620) and the sleeve (610), Fig 6c. Fig. 6d illustrates the suspension of living cells (650) absorbed by the soft tissue (640) after breakage of the distal end (614) of the sleeve along the score lines. The thread (613) is pulled in a proximal direct comprising a radial force vector whereby the sleeve is gradually ruptures along the lateral score line as the sleeve is removed from the soft tissue. EXAMPLES OF MANUFACTURING AN ARRANGEMENT

A cylindrical pin made of solid, smooth stainless steel, having an extension of 10 cm from a proximal end to a distal end, was used as a mold for manufacturing the protection sleeve for an oblong device of the invention. The pin is generally cylindrical with a circular cross-section of 2 mm and a distal section narrowing in radial direction towards its distal end and is provided with proximal. Protrusions in the proximal section of the pin serve as a mold for flanges of the protection sleeve. A 10 pm non-water degradable polymeric layer is then formed on the outer surface of the pin by vapor deposited Parylene C. A suitable sharp tool is then used to form thoroughgoing intersecting slits in the distal part and a slit extending towards the proximal end (see Fig. 2B). A second outer layer of non-water degradable material is then formed to cover the intersecting slits by applying about a 1 urn thick Parylene C layer using vapor deposition (see Fig. 3A). The so formed protection sleeve with breakable score lines is then removed from the pin and a medical object and oblong device can then be inserted in the protection sleeve.

The above-described process was repeated by again applying a non-water degradable polymeric layer of Parylene C with a thickness of about 10 pm on the pin using vapor deposition. A suitable sharp tool was used to form thoroughgoing intersecting slits in the distal part and a throughgoing intersecting slit extending towards the proximal end as depicted in Fig. 2A and Fig. 2B. In a first alternative a second, outer layer of non- water degradable material was formed to cover the slit by applying about a 1 urn thick Parylene C layer using vapor deposition, see Fig. 3C thereby forming a slot, groove. In a second alternative, the opposite wall parts of the slot were arranged to form an overlapping section, see Fig. 4. This structural weakness was coated with a 1 urn thick Parylene C layer using vapor deposition,

Finally in the above-described processes, the protection sleeve is removed from the pin and an oblong medical device can be introduced into the protection sleeve. In the described processes, the second layer can be applied after removal of the pin and insertion of the oblong device.

In the mentioned manufacturing processes, the pin can have at least partially a circular, ellipsoid, rectangular, rhomboid cross-section of the outer shape and has a distal section narrowing in radial direction towards its distal end suitable for forming an oblong protection sleeve. The surface of the pin is preferably smooth to facilitate the subsequent process. The pin can be hollow or solid and for example be made of a polymer, stainless steel, wolfram, glass, crystal or a ceramic. Further when suitable in the manufacturing processes, the pin can be coated with a dissolvable agent such as gelatin or a carbohydrate to support the subsequent process.

The pin can be provided with one or more defined radially protruding part(s) serving as a mold for one or more radially extending proximally flange(s) of the protection sleeve continuously formed when applying at least one of the layers of the protective sleeve, preferably the first thicker layer. In the manufacturing process wires of sufficient strength can be attached to the flanges to be used to facilitate the subsequent manipulation of the protective sleeve.

FURTHER EMBODIMENTS OF THE INVENTION

1. A assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, the assembly comprising a sleeve, accommodating an oblong device comprising at least one rigidity imparting element, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end (i.e. in the region of the distal end), the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the distal section to rupture (break) when an axial force is exerted on the distal section, such as region of the distal end, distal end, by the oblong medical device.

2. The assembly according to claim 1 , wherein axial force exerted on the distal section, in particular on the region of the distal end, such as the distal end, of the sleeve is provided by moving at least the distal section of the sleeve in proximal direct by applying an essentially axial force on the at least one thread.

3. The assembly according to claim 1 or 2, wherein the structural weakness is a score zone/frangible zone/tear zone such as a score zone.

4. The assembly according to any one of the preceding claims wherein the weakness is a score line/frangible line/tear line such as a score line.

5. The assembly according to claim 3, wherein the score zone/frangible zone/tear zone is selected from a reduction of the average thickness of the polymeric material or an overlapping wall segment.

6. The assembly according to claim 3, wherein the longitudinal score zone/frangible zone/tear zone is a reduction of the average thickness of the polymeric material, wherein the width of the (preferably longitudinal) score zone/frangible zone/tear zone is less than 500 pm, less than 400 pm, less than 300 pm, less than 200 pm, less than 100 pm, less than 50 pm, less than 10 pm, less than 5 pm.

7. The assembly according to claim 5, wherein the thickness of the score zone/frangible zone/tear zone is less than 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1 %, 0.5%, 0.1 % of the average thickness of the sleeve wall.

8. The assembly according to any one of the preceding claims, wherein the sleeve material is waterproof, preferably water insoluble.

9. The assembly according to any one of the preceding claims, wherein the sleeve is waterproof, preferably water insoluble.

10. The assembly according to any one of the preceding claims, wherein the sleeve wall comprises at least two layers, preferably two layers) of polymeric water-resistant polymeric material.

11. The assembly according to claim 3, wherein the longitudinal score zone/frangible zone/tear zone has a length to width ratio of at least 10, preferably at least 100, preferably at least 1000, preferably at least 10000.

12. The assembly according to claim 3, wherein the longitudinal score zone/frangible zone/tear zone is continuous or non-continuous.

13. The assembly according to any one of the preceding claims, wherein the axial force exerted on the distal section, such as region of the distal end, distal end, is enabled by moving at least the distal section of the sleeve in proximal direction by pulling at least the one thread in a direction having an axial force vector.

14. The assembly according to claim 4, wherein at least one score line is arranged in the distal section of the protection sleeve.

15. The assembly according to claim 4, wherein at least one score line extends around the distal part of the distal section.

16. The assembly according to claim 14 or 15, wherein the at least one score line extends in a proximal direction from the distal section, preferably on one or both lateral sides of the sleeve. 17. The assembly according to any one of claims 4, 14-16, wherein the at least one score line essentially bisects the region of the distal end.

18. The assembly according to any one of claims 4, 14-17, the sleeve comprising at least two score lines extending around the region of the distal end and intersecting each other in the region of the distal end.

19. The assembly according to claim 18, wherein the at least two score lines are essentially uniformly arranged around the circumference at any axial location within the region of the distal end.

20. The assembly according to claim 18 or 19, wherein the at least two score lines are arranged (spaced) at approximately equal angular intervals around the sleeve axis (as axially observed in a proximal direction).

21. The assembly according to any one of claims 18-20, wherein all score lines intersect each other in one very confined area preferably characterized as a point (or intersection area/intersection point).

22. The assembly according to claim 21 , wherein the intersection point coincides with the most distal tip of the distal end.

23. The assembly according to any one of claims 18-22, wherein the number of score lines around the sleeve axis as seen from a location distally from the distal end and in proximal direction (referred to as distal end score lines) follows the following equation with at least two score-lines: number of score lines N extending around the region of the distal end equals N+N score lines around the sleeve axis as seen from a location distally from the distal end and in proximal direction.

24. The assembly according to claim 23, wherein the angle between two distal end score lines preferably varies up to 10°, up to 5°.

25. The assembly according to any one of the preceding claims, wherein the sleeve comprises at least one cut-out at its proximal end.

26. The assembly according to claim 25, wherein the cut-out has a triangular geometry and preferably oriented that one of its edges (or vertices) points in a distal direction, the distal direction preferably substantially aligned along the longitudinal axis of the sleeve. 27. The assembly according to any one of claims 14-26, wherein at least one score line extends to the proximal end of the sleeve.

28. The assembly according to claim 26, wherein at least one score line extends to the edge of the triangular cut-out.

29. The assembly according to any one of claims 18-28, wherein the sleeve comprises at least three score lines extending at around the region of the distal end and intersecting each other in the region of the distal end, and one score line extending in proximal direction to the proximal end of the sleeve.

30. The assembly according to claim 29, wherein the sleeve comprises two cut-outs preferably only one cut-out, in the proximal end of the sleeve the cut-outs having triangular geometries and preferably oriented that one of its edges (or vertices) points in a distal direction, the distal direction preferably substantially aligned along the longitudinal axis of the sleeve, the one score line extending in proximal direction extends to the edges of the triangular cut-outs.

31 . The assembly according to any one of the preceding claims, wherein the region of the distal end is tapered in distal direction and pointed at the distal end having its most distal end aligned the central axis, preferably sharp tip.

32. The assembly according to claim 31 , wherein the tapering is conical or parabolical.

33. The assembly according to any one of the preceding claims, wherein the region of the distal end is configured with longitudinal ridges and/or flutes evenly distributed around the circumference, preferably configured with any number of ridges, flutes evenly distributed around the circumference such as least three, at least four ridges and/or flutes evenly distributed around the circumference.

34. The assembly according to any one of the preceding claims, wherein the oblong medical device comprises one or more of: or is selected from any one of: hollow oblong medical device such as cannulas, needles, catheters, electrodes, optical guides, guiding tubes, sheaths, rigid oblong elements.

34. The assembly according to any one of the preceding claims, wherein the oblong medical device structural element comprises at least one flexible microelectrode. 35. The assembly according to any one of the preceding claims, wherein the oblong medical device is a flexible microelectrode comprising at least one proximally insulated conductive core.

36. The assembly according to any one of the preceding claims, wherein the oblong medical device is a flexible microelectrode comprising at least one proximally insulated conductive core further comprising a water-dissolvable and/or water-degradable material which material is substantially rigid when dry

37. The assembly according to claim 36, wherein the flexible microelectrode is embedded in the water-dissolvable and/or water-degradable material.

38. A method for inserting an oblong medical device comprising at least one oblong rigid structural element into soft tissue, such as nervous tissue, the oblong medical device having an overall diameter of less than about 5 mm, preferably less than 1 mm, comprising accommodating at least part of the oblong medical device in a water- resistant sleeve thereby providing an assembly configured for insertion of medical objects in need for protection, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section when an axial is exerted on the distal section by the oblong medical device.

39. The method according to claim 38, wherein the axial force exerted on the distal section of the sleeve is provided by moving at least the distal section of the sleeve in proximal direct by applying an axial force on the at least one thread.

40. The method according to claim 38 or 39, wherein the axial force is exerted after placement of the assembly within the soft tissue.

41 . The method according to any one of claims 38-40, further comprising: enclosing at least part of the distal section of the oblong object within the sleeve thereby forming an assembly; introducing the assembly into soft tissue; positioning the assembly within soft tissue; rupturing, breaking the at least one weakness of the sleeve by exerting the axial force thereby admitting tissue fluids contacting the medical objects; removing the sleeve from the soft tissue or optionally the assembly.

42. A method of manufacturing an assembly according to any one of claims 1 -37 comprising:

• providing a removable pin with a shape suitable for forming a sleeve, or an oblong medical device and optionally coating the pin or the oblong device with a dissolvable agent;

• applying a first layer of water-resistant polymeric material on the pin or oblong device;

• forming at least one structural weakness (such as a slit or slot e.g. a longitudinal score zone/frangible zone/tear zone/ such as a score line) in the first, inner layer;

• optionally applying a second layer of water-resistant polymeric material covering at least the structural weakness such as a slot, the first and optionally second layer providing the sleeve wall;

• optionally removing the pin and inserting an oblong m device into the sleeve.

43. The method according to claim 42, wherein the thickness of the first, inner layer is at least two times the thickness of the second layer, at least 3 times, at least 4, 5, 6, 7, 8, 9, 10 times the thickness of the second layer.

44. The method according to claim 42 or 43, wherein the layer(s) are made of Parylene, such as Parylene N, Parylene C, Parylene D, Parylene HT/AF4, preferably Parylene C.

45. The method according to any one of claims 42-44, wherein the structural weakness is formed by cutting the first layer thereby forming a slit, the width of the slit being preferably less than 5 pm, optionally overlapping opposing wall parts forming an overlapping wall segment and applying a second layer covering at least the slit and/or the overlapping wall segment.

Claims

1. An assembly configured for insertion of medical objects in need for protection into soft tissue, such as nervous tissue, the assembly comprising a water-resistant sleeve, accommodating an oblong device comprising at least one rigidity imparting element, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, the sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve comprises a weakness at least in the distal section, said weakness enabling the distal section to rupture when an axial force is exerted on the distal section, such as the region of the distal end, by the oblong device.

2. The assembly according to claim 1 , wherein axial force exerted on the distal section is provided by moving at least the distal section of the sleeve in proximal direct by pulling at least the one thread in a direction having an axial force vector.

3. The assembly according to claim 1 or 2, wherein the structural weakness is a score zone such as a score line.

4. The assembly according to claim 3, wherein the score line is selected from a slit through the sleeve wall, reduction of the average thickness of the polymeric material, and an overlapping wall segment, a reduction of the average thickness of the polymeric material.

5. The assembly according to claim 3, wherein the score line is a slot (groove) comprising a reduction of the average thickness of the polymeric material, wherein the width of the slot (groove) is less than 500 pm, less than 400 pm, less than 300 pm, less than 200 pm, less than 100 pm, less than 50 pm, less than 10 pm, less than 5 pm.

6. The assembly according to claim 5, wherein the thickness of score line is less than 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1 %, 0.5%, 0.1 % of the average thickness of the sleeve wall.

7. The assembly according to any one of the preceding claims, wherein the sleeve material is waterproof, preferably water insoluble, preferably the sleeve is waterproof, preferably water insoluble.

8. The assembly according to any one of the preceding claims, wherein the sleeve wall comprises at least two layers, preferably two layers, of polymeric water-resistant polymeric material.

9. The assembly according to claim 3, wherein at least one score line is arranged in the distal section of the protection sleeve.

10. The assembly according to claim 3, wherein at least one score line extends around the distal part of the distal section.

11 . The assembly according to claim 9 or 10, wherein at least one score line extends in a proximal direction from the distal section, preferably on one lateral side of the sleeve.

12. The assembly according to any one of claims 3, 9-11 , wherein the at least one score line essentially bisects the region of the distal end.

13. The assembly according to any one of claims 3, 9-12, the sleeve comprising at least two score lines extending around the region of the distal end and intersecting each other in the region of the distal end.

14. The assembly according to claim 13, wherein at least two score lines are essentially uniformly arranged around the circumference at any axial location within the region of the distal end.

15. The assembly according to claim 13 or 14, wherein at least two score lines are arranged (spaced) at approximately equal angular intervals around the sleeve axis (as axially observed in a proximal direction).

16. The assembly according to any one of claims 13-15, wherein all score lines intersect each other in one very confined area preferably characterized as a point (or intersection area/intersection point), preferably intersection point coincides with the most distal tip of the distal end.

17. The assembly according to any one of the preceding claims, wherein the sleeve comprises at least one cut-out at its proximal end.

18. The assembly according to claim 17, wherein the cut-out has a triangular geometry and preferably oriented that one of its edges (or vertices) points in a distal direction, the distal direction preferably substantially aligned along the longitudinal axis of the sleeve.

19. The assembly according to any one of claims 9-18, wherein at least one score line extends to the proximal end of the sleeve.

20. The assembly according to claim 18, wherein at least one score line extends to the edge of the triangular cut-out.

21 . The assembly according to any one of claims 9-20, wherein the sleeve comprises at least three score lines extending around the region of the distal end and intersecting each other in the region of the distal end, and one score line extending in proximal direction to the proximal end of the sleeve.

22. The assembly according to claim 21 , wherein the sleeve comprises one cut-out in the proximal end of the sleeve the cut-out having a triangular geometry and preferably oriented that one of its edges (or vertices) points in a distal direction, the distal direction preferably substantially aligned along the longitudinal axis of the sleeve, the one score line extending in proximal direction extends to the distal edge of the triangular cut-out.

23. The assembly according to any one of the preceding claims, wherein the region of the distal end is tapered in distal direction and pointed distal end having its most distal end aligned the central axis, preferably sharp tip, the tapering preferably being conical or parabolical.

24. The assembly according to any one of the preceding claims, wherein the region of the distal end where the diameter of the distal section decreasing towards the distal is configured with longitudinal ridges and/or flutes evenly distributed around the circumference, preferably configured with any number of ridges, flutes evenly distributed around the circumference such as at least three, at least four ridges and/or flutes evenly distributed around the circumference.

25. The assembly according to any one of the preceding claims, wherein the oblong device comprises one or more of: hollow oblong medical device such as cannulas, needles, catheters, electrodes, optical guides, guiding tubes, sheaths, rigid oblong elements.

26. The assembly according to any one of the preceding claims, wherein the oblong device is a flexible microelectrode comprising at least one proximally insulated conductive core further comprising a water-dissolvable and/or water-degradable material which material is substantially rigid when dry, preferably the flexible microelectrode is embedded in the water-dissolvable and/or water-degradable material.

27. The assembly according to claim 1 , wherein the axial force is lower than 5 N, preferably lower than 2 N, lower than 1 , lower than 0.5 N.

28. The assembly according to any one of the preceding claims, wherein the oblong device is a hollow member functioning as rigidity imparting element, the hollow member configured to accommodate a catheter.

29. The assembly according to nay one of the preceding claims, wherein the medical object is selected from medical instruments which can monitor and/or stimulate soft tissue by e.g. electrical, thermal, ultra sound, optogenetic, mechanical monitoring and/or stimulation; and compounds, peptides, proteins, biological macromolecules and microorganisms e.g. pharmaceutics, peptides, proteins, genes, living cells and aggregates of living cells.

30. A method for inserting an oblong device comprising at least one rigidity imparting element into soft tissue, such as nervous tissue, the oblong device having an overall diameter of less than about 5 mm, preferably less than 2 mm, comprising accommodating at least part of the oblong device in a water-resistant sleeve thereby providing an assembly configured for insertion of medical objects in need for protection, the water-resistant sleeve having a proximal and distal section and a distal end, the proximal section extending from the proximal end in distal direction, the distal section extending from the distal end in proximal direction, the diameter of the distal section decreasing towards the distal end, the sleeve comprising a sleeve wall, the sleeve wall comprising a water-resistant polymeric material, the sleeve wall having an average thickness of less than 100 pm, preferably less than 50 pm such as from 0.2 pm to 50 pm, the sleeve further comprising at least a thread integrated or attached to the proximal section of the sleeve, wherein the sleeve (or sleeve wall) comprises a weakness at least in the distal section, said weakness enabling the rupture in the distal section when an axial force is exerted on the distal section by the oblong device.

31 . The method according to claim 30, wherein the axial force exerted on the distal section of the sleeve is provided by moving at least the distal section of the sleeve in proximal direct by applying an axial force on the at least one thread.

32. The method according to claim 30 or 31 , wherein the axial force is exerted after placement of the assembly within the soft tissue.

33. The method according to any one of claims 30-32, wherein the axial force is lower than 5 N, preferably lower than 2 N such as lower than 1 , lower than 0.6 N.

34. The method according to any one of claims 30-33, further comprising: enclosing at least part of the distal section of the oblong object within the sleeve thereby forming an assembly; introducing the assembly into soft tissue; positioning the assembly within soft tissue; rupturing, breaking the at least one weakness of the sleeve by exerting the axial force thereby admitting tissue fluids contacting the medical object; removing the sleeve from the soft tissue or optionally the assembly.

35. A method of manufacturing an assembly according to any one of claims 1 -29 comprising:

• providing a removable pin with a shape suitable for forming a sleeve, or an oblong device and optionally coating the pin or the oblong device with a dissolvable agent;

• forming at least one structural weakness (such as a slit or slot e.g. a longitudinal score zone/frangible zone/tear zone/ such as a score line) in the first, inner layer; • optionally applying a second layer of water-resistant polymeric material covering at least the structural weakness such as a slot, the first and optionally second layer providing the sleeve wall;

• optionally removing the pin and inserting an oblong device into the sleeve.

36. The method according to claim 35, wherein the thickness of the first, inner layer is at least two times the thickness of the second layer, at least 3 times, at least 4, 5, 6, 7, 8, 9, 10 times the thickness of the second layer.

37. The method according to claim 35 or 36, wherein the layer(s) are made of Parylene, such as Parylene N, Parylene C, Parylene D, Parylene HT/AF4, preferably Parylene C.

38. The method according to any one of claims 35-37, wherein the structural weakness is formed by cutting the first layer thereby forming a slit, the width of the slit being preferably less than 5 pm, optionally overlapping opposing wall parts forming an overlapping wall segment and applying a second layer covering at least the slit and/or the overlapping wall segment.