Medical devices, systems, and methods for retrieving thrombus from a blood vessel, and methods for manufacturing the devices - Patents.com

Abstract

The present invention relates to a medical device (1) for retrieving a thrombus (2) from a blood vessel (3). The medical device (1) comprises an attachment element (4) disposed at a distal end (5) of the medical device (1). The attachment element (4) is configured to attach to a proximal surface (6) of the thrombus (2) such that the thrombus (2) can be retrieved by applying a pulling force to the attachment element (4).

Description

[Technical field]

[0001] The present invention relates to a medical device, a system and a method for retrieving thrombus from a blood vessel as described in the preamble of the independent claims, as well as a method for manufacturing the device. [Background technology]

[0002] It is known from the prior art to use medical devices to remove thrombi from blood vessels. For example, U.S. Patent Application Publication No. 2017 / 119407 discloses a suction device for removing blood clots.

[0003] US Patent Application Publication No. 2013 / 060269 discloses a stent device that penetrates and is secured to a material.

[0004] US Patent Application Publication No. 2013 / 289578 discloses a catheter device for surrounding and grasping a blood clot.

[0005] However, devices and methods known in the art have several drawbacks. For example, known devices are typically large, which may limit accessible locations in the vasculature and increase the risk of unwanted interactions with tissue that may lead to injury. Furthermore, large devices may be more difficult for a surgeon to manipulate. Furthermore, known devices may require complex mechanisms to safely remove the thrombus. In addition, procedures using known devices and methods may take a long time and may result in greater patient discomfort and risk associated with the procedure. Summary of the Invention [Problem to be solved by the invention]

[0006] It is therefore an object of the present invention to provide devices, systems and methods for overcoming the shortcomings of the prior art and providing easy, safe and versatile treatment, particularly of blood vessels.

[0007] This and other objects are achieved by the medical device, system and method according to the features of the independent claims of the present invention. [Means for solving the problem]

[0008] A medical device according to the invention is configured for retrieving a thrombus from a blood vessel, the device comprising an attachment element disposed at a distal end of the medical device, the attachment element configured to attach to a proximal surface of the thrombus such that the thrombus can be retrieved by exerting a pulling force on the attachment element.

[0009] In some embodiments, the device comprises more than one attachment element, such as two attachment elements or three attachment elements. Multiple attachment elements can reduce mechanical stress on the thrombus during retrieval, thus making the procedure safer.

[0010] The attachment element may be any element configured to attach to the thrombus, and may in particular comprise a structure for mechanical interaction such as a fork, but also an adhesive or a fiber. Furthermore, the attachment element may be connected to the body, e.g. the magnetic part, in particular via a form-fit connection.

[0011] In one particularly preferred embodiment, the medical device comprises a magnetic part attached to the control line and a connection element for the fixation element, which comprises or consists of an attachment element. The fixation element may be connected to the magnetic part via a form-fit connection, a snap-fit ​​connection, an adhesive connection, a bayonet connection, or any other connection means known in the art. The connection may be reversible or non-reversible.

[0012] In certain embodiments, the medical device comprises or consists of a catheter device and / or a microrobot.

[0013] Proximal attachment of the device at the thrombus is highly advantageous as it allows for rapid attachment without the need for penetration or guidance of device elements around or around the thrombus. In addition, less pulling force is required as pulling force is applied to the proximal face of the thrombus, which can stretch the thrombus and therefore reduce its diameter, reducing friction between the vessel wall and the thrombus.

[0014] The proximal surface of the thrombus may be understood as the most proximal region of the thrombus in the direction towards the device, ie, in the direction of intended removal of the thrombus.

[0015] The attachment element may comprise a biological attachment mechanism. In particular, the biological attachment mechanism may comprise or consist of a thrombogenic element. The thrombogenic element may comprise thrombin, calcium chloride, and / or collagen. The thrombogenic element may be a dried coagulant layer.

[0016] The thrombogenic element may comprise or consist of fibers having thrombogenic properties.

[0017] Biological attachment mechanisms can provide a very simple way to attach thrombi, since they can utilize mechanisms inherent in the human or animal body, for example, thrombogenic elements can form attachment material from blood clots, thus eliminating the need to deliver a portion of the attachment material to the treatment site.

[0018] The biological attachment mechanism may be any mechanism that triggers a biological reaction with tissue and / or blood, such as, for example, clotting.

[0019] The thrombogenic element may be provided in a dry state, for example as a dried clotting layer, which may allow for very easy activation with a bodily fluid such as blood, and the dried clotting layer may thus only become adhesive upon contact with blood or another bodily fluid, or with water or saline delivered to the treatment site.

[0020] The attachment element, preferably the biological attachment mechanism, may comprise an electrical contact that is attached or can be attached to an electrical conductor. Thus, the medical device may particularly preferably comprise an electrical conductor that is attached or can be attached to an energy source. The electrical contact is configured to generate attachment through tissue changes induced by temperature increase and / or current / voltage.

[0021] The energy source may be electrical energy from a building utility, a converter connected thereto, a battery, or any other source of electrical energy known in the art.

[0022] Preferably, the attachment element is configured to provide attachment to the thrombus via cauterization and / or electrothrombosis.

[0023] The attachment element may comprise a chemical attachment mechanism. In particular, the chemical attachment mechanism may comprise an adhesive composition, preferably a dried adhesive composition.

[0024] Chemical attachment mechanisms, such as adhesive compositions, can be highly advantageous, for example, because they can provide instantaneous attachment without requiring a time period for clot formation and / or without requiring additional elements, such as the need to deliver additional / larger elements to the treatment site.

[0025] The adhesive composition may be activatable, in particular the adhesive composition may be activatable by a change in temperature, light, humidity, and / or pH.

[0026] The attachment element may comprise a mechanical attachment mechanism, in particular a mechanical attachment mechanism comprising a shape-changing element. The mechanical attachment mechanism may be selected from the group comprising hooks, forks, springs and spikes.

[0027] Mechanical attachment mechanisms can be particularly safe, since they do not require the introduction of chemical or biological reactive elements into the body. Even when biological or chemical attachment mechanisms are combined with mechanical attachment mechanisms, the mechanical attachment mechanisms can be advantageous, since they can provide more reliable and easily adjustable attachment.

[0028] The shape-changing element may include or be composed of a self-expanding material, particularly to increase the force towards the thrombus, for example to increase mechanical attachment or adhesion.

[0029] Additionally, the shape-changing element may include or be constructed of a shape-memory material, such as, for example, a Nitinol alloy.

[0030] Preferably, the shape-changing element is configured to change from an axial / linear shape to a radial / three-dimensional shape, such as a spiral or hook, Additionally or alternatively, the shape-changing element may be configured to assume an umbrella shape upon shape change.

[0031] Particularly preferably, the mechanical anchor made of a shape memory alloy may be configured to have a straight shape and, upon attachment to the thrombus, to change shape, in particular to a corkscrew or hook shape.

[0032] Any shape known in the art suitable for providing attachment after penetration may be used, particularly a thread shape.

[0033] The medical device may further comprise a suction mechanism. Preferably, the attachment element comprises the suction mechanism.

[0034] The suction mechanism can aid in the attachment of the attachment element to the thrombus. Additionally or alternatively, the suction mechanism can be used to remove fluid and / or tissue from the treatment site. For example, blood may be aspirated from the treatment site to remove thrombus debris and reduce risk to the patient. Additionally or alternatively, softer thrombus portions (such as red thrombus) may be aspirated in order to reach and attach to more solid portions of the thrombus.

[0035] Additionally or alternatively, the suction mechanism may be used to activate the mechanical element, for example by utilizing a gas pressure and / or fluid pressure mechanism. To this end, the medical device may further comprise a canal operably connected to the suction mechanism to provide a line of air pressure or fluid pressure.

[0036] In some embodiments, an electrical element, preferably a ring, is positioned relative to the attachment element so as to be able to apply an electrical current to the thrombus after it has been aspirated by the suction mechanism.

[0037] It will be understood that any combination of biological, chemical, and / or mechanical attachment mechanisms described herein is possible. Furthermore, it will be understood that the attachment mechanism may be biological, chemical, and / or mechanical at the same time. Thus, a reference to one of biological, chemical, or mechanical attachment should not necessarily be understood as excluding the other two mechanisms, unless otherwise specified. For example, the mechanical attachment mechanism may be assisted by adhesion and / or coagulation. However, it is of course possible to configure the attachment mechanism as only mechanical, only biological, or only mechanical.

[0038] Preferably, the medical device comprises an activation mechanism. The attachment element can have an activated state and an inactivated state. In the inactivated state, the attachment element is configured to not interact with a vessel wall or a thrombus. In the activated state, the attachment element is configured to interact with a thrombus. The activation mechanism is configured to bring the attachment element from at least the inactivated state to the activated state.

[0039] An activation mechanism can be advantageous because it can prevent unintended interactions between the attachment elements and tissue and / or blood during delivery, thus resulting in safer procedures, fewer complications, and easier delivery.

[0040] Preferably, the medical device comprises a microrobot with an attachment element. The microrobot may comprise a magnetic portion and / or a control line. The magnetic portion may be preferably configured to interact with an external magnetic field. Additionally or alternatively, the control line may be attachable or attached to a distal portion of the microrobot.

[0041] The control line may be configured to retract the thrombus, in particular to have a minimum strength in the range of 0.5N to 20N, preferably 8N to 12N, by material selection and / or appropriate dimensions.

[0042] The microrobot may further include a retaining line having a higher elastic modulus than the control line, the retaining line having a bending stiffness similar to that of the control line, the retaining line being capable of preventing excessive stretching of the control line without affecting guidance.

[0043] For example, the control line may consist essentially of a hollow tube made of silicone having high flexibility and a breaking strain of about 300%. In such an example, the retention line may be made of polyamide having a breaking strain of about 40%.

[0044] The diameter of the retaining lines may be between 20 μm and 1 mm, preferably between 50 μm and 200 μm.

[0045] The retaining line may comprise or be composed of a polymer, elastomer such as polyamide, polyurethane, or silicone, or may use a silicone-based material with a moderate (less than 100%) or low (less than 10%) breaking strain.

[0046] The retention line may be part of the control line or may be a separate element, and the retention line may have several attachment points with the control line and / or the device.

[0047] The retention lines may be secured to the device by adhesives, knots, adhesives and resins, or a combination of various assembly methods known in the art.

[0048] The retaining line may have a Young's modulus of 0.01 to 50 GPa, preferably 1 to 20 GPa, and particularly preferably 1 to 3 GPa.The retaining line may have a bending rigidity of 0.0001 to 1 N·mm2, and preferably 0.001 to 0.02 N·mm2.

[0049] The retaining lines may have a diameter of 20 μm to 500 μm, preferably 40 μm to 80 μm, particularly preferably 70 μm.

[0050] The medical device may be formed by at least a portion of a catheter device, in addition or instead, a guidewire or any other intravascular device may be used.

[0051] The activation mechanism can include a mechanism configured to release at least the attachment element from the storage region of the medical device.

[0052] For example, the attachment element may be housed in a compartment of a catheter or microrobot. In some embodiments, the medical device comprises a catheter configured to deliver the microrobot. The catheter can comprise a balloon. The microrobot can be configured to be retracted into the catheter after attachment to the thrombus.

[0053] Additionally or alternatively, the attachment elements may be encapsulated. The activation mechanism can include an activatable material.

[0054] The activatable material may be activatable by any of the activation mechanisms described herein or known in the art. For example, the activatable material may be activatable by exposure to a magnetic field, a magnetic gradient, ultrasound, or light (such as a light-curable adhesive). Additionally or alternatively, the activatable material may be activated by an increase in temperature, exposure to humidity / water, a change in pH, a response to salt concentration, activation of inflammatory species, a change in blood flow rate, electricity, etc. The activation mechanism may comprise a protective layer, which may be selected from the group including a protective coating, a protective sheath, a protective frame, and a protective cap.

[0055] Generally, the protective layer can be removed, for example, to bring the attachment element from a non-activated state to an activated state.

[0056] In general, the protective layer may be biodegradable or non-biodegradable and may be a removable cap, a separating layer, or a layer with holes and / or predetermined breaking points.

[0057] The protective coating may be soluble in water or blood, for example, to automatically activate the attachment element after a certain exposure time in blood, which exposure time may be configured to be, for example, in the range of 10 seconds to 20 minutes, preferably 2 to 5 minutes.

[0058] The protective coating may include or consist of biodegradable polymers such as PGA and / or PLGA. In such configurations, the coating is divided into several parts. The natural mechanism of degradation is hydrolysis. Hydrolysis typically occurs within minutes after direct contact with physiological solutions.

[0059] To achieve sufficiently fast degradation, the PGA may have a very low molecular weight. When hydrolysis of the PGA begins, the mechanical strength of the biodegradable coating decreases, thus making the protective coating more easily destroyed.

[0060] Preferably, the protective coating comprises or is composed of a mixture (blend and / or copolymer) of different polymers, so that by adjusting the mixture ratio, the mechanical properties and the degradation rate can be adjusted.

[0061] Degradation can be accelerated under stimuli such as heat. Bioabsorbable coatings can be fabricated from biodegradable polymers loaded with nanoparticles. The polymers exhibit low decomposition temperatures of 40-60°C. The nanoparticles may be made of gold, Fe2O3, Fe3O4, and / or silver. The protective coating is degraded by heat generated by the nanoparticles under stimuli such as light and / or magnetic fields. This causes the coating to break down into small biodegradable pieces that are washed away by the bloodstream.

[0062] In another embodiment, the protective coating comprises a membrane made of magnesium powder acting as a linker embedded in a bioabsorbable polymer. The decomposition of the powder is accelerated by the application of an electric current provided by a control line. The decomposition of the particles can contribute to the destruction of the coating.

[0063] Additionally or alternatively, the biodegradable coating can be made from magnesium or a composite material that degrades by bioerosion. The bioerosion process can be accelerated by applying an electric current.

[0064] The coating may be made of biodegradable and non-biodegradable parts. The non-biodegradable parts remain attached to the device, particularly the attachment element. The biodegradable parts may be removed from the device upon removal / degradation of the protective coating.

[0065] The coating may be made of a non-biodegradable polymer, such as, for example, silicone, polyurethane with a polycarbonate backbone, or PTFE. The non-biodegradable polymer may be destroyed upon opening. Preferably, the non-biodegradable coating is destroyed by tearing so that the coating remains attached to the device and / or attachment element. Preferably, for the capsule, polymers such as PVDF, HDPE, PMMA, LCP, PA46, PI, etc. can be used.

[0066] The protective frame can prevent direct contact between the attachment elements and the surrounding tissue until the protective frame is removed.

[0067] The medical device may further comprise an extension member, which may preferably comprise or consist of a spring, and which may be axially extendable and configured to exert an axial force on the thrombus.

[0068] The extension member may be located at the proximal or distal end of the medical device. The extension member is preferably part of the attachment element.

[0069] In particular, the axial force exerted by the extension member may additionally or alternatively be configured to be used to open and / or remove the protective layer.

[0070] The medical device may further comprise a sensor. Preferably, the sensor is configured to determine incorrect or insufficient attachment of the attachment element to the thrombus.

[0071] The sensor is preferably selected from the group comprising a force sensor, a temperature sensor, a pH sensor, a deposition sensor, a flow sensor, a pressure sensor, and a contact surface sensor.

[0072] For example, the sensor may include a force sensor configured to measure a tensile force acting on the thrombus and / or a sensor configured to measure an interface between the attachment element and the thrombus.

[0073] In particular, the pressure sensor can be used to monitor whether the attachment element is in contact with the thrombus and / or to assess the nature of the thrombus.

[0074] Additionally or alternatively, the sensor may be configured to monitor whether the attachment element is sufficiently attached to the thrombus during retrieval.

[0075] Preferably, the attachment element includes a substantially flat surface configured to adhere to the thrombus.

[0076] Substantially flat can be understood as having a limited maximum curvature (i.e. a minimum radius of curvature). In particular, a substantially flat surface may exhibit a minimum radius of curvature of 3 cm, preferably 5 cm, particularly preferably 50 cm.

[0077] Additionally or alternatively, the attachment element may have a maximum axial extension of the medical device of 5-40 mm, preferably 15-25 mm, particularly preferably 20 mm. For example, the attachment element may be the most distal part of the medical device in its intended use. Alternatively, the maximum extension may be between 1-5 mm, preferably 2 mm.

[0078] Preferably, the size of the attachment element in the activated position when attached to the thrombus is less than 3 mm, particularly preferably less than 1 mm, even more preferably less than 0.8 mm in a direction perpendicular to the longitudinal axis of the medical device. Preferably, this size is the maximum size of the attachment element perpendicular to the longitudinal axis of the medical device.

[0079] Thus, the attachment elements can have a size that allows them to be navigated in small blood vessels, thus providing more versatile treatment options.

[0080] Preferably, the size of the adhesive elements is between 0.2 and 5 mm, particularly preferably between 0.3 and 1 mm.

[0081] Preferably, the attachment element, when attached to the thrombus and / or in an activated state, is smaller than the maximum size and / or size of any other portion of the medical device in a direction perpendicular to the longitudinal axis of the medical device.

[0082] Thus, it can be ensured that any location accessed by the medical device can be treated using the attachment element because the attachment element fits into the vasculature of the treatment location.

[0083] Particularly preferably, the maximum size of the medical device is the size of the magnetic portion in a direction perpendicular to the longitudinal axis of the medical device.

[0084] Preferably, the attachment elements have a maximum size in a direction perpendicular to the longitudinal axis of the medical device that differs by less than 10%, preferably by less than 5%, between the activated and non-activated states, and particularly preferably the maximum size in a direction perpendicular to the longitudinal axis of the medical device remains unchanged.

[0085] If the maximum size of the attachment elements differs between the non-activated and activated state, it is particularly preferred that said maximum size is larger in the activated state compared to the activated state.

[0086] The difference in maximum size may be axial (ie, along the longitudinal axis of the medical device) or radial (ie, perpendicular to the longitudinal axis of the medical device) or both.

[0087] Preferably, the medical device comprises a propulsion member, preferably a chemical propulsion member, for generating an axial propulsive force.

[0088] The medical device, especially the magnetic part with the attachment element, can typically move forward mainly due to the flow force exerted by the blood. If a thrombus is present, the flow may be altered or reduced. To ensure that the medical device can reach the treatment site and the proximal surface of the thrombus, an additional propulsion system may be advantageous. It will be understood that such an additional propulsion system, although highly advantageous, is not essential to the present invention, since the magnetic force exerted by the magnetic field on the magnetic part may be sufficient.

[0089] The additional propulsion system may be mechanical. For example, it may comprise a spring that can be embedded in the control line in a compressed state. The spring may be placed between the control line and the magnetic portion. The spring may be released by removing or deteriorating a physical locking mechanism such as a barrier. The spring may be made of a shape memory alloy, for example Nitinol. The spring may be activated under the influence of a stimulus such as heat or electricity. To activate the spring thermally, it may be coated with a heatable material. An example of such a configuration may be a spring coated with gold nanoparticles that heat up when exposed to, for example, infrared light. Another configuration may be a spring coated with superparamagnetic nanoparticles. These particles may be heated in an alternating magnetic field.

[0090] Alternatively, the additional propulsion system may be chemical. The propulsion member may include reactive species. For example, magnesium may be used, which may react with H2O when in contact with blood, forming a gas used to propel the device. Typically, the additional propulsion force is only required and thus activated in the vicinity of the treatment site, i.e., the clot. Thus, the reactive species may be embedded in the reservoir. As an example, the reservoir may be made of a tube placed around the magnetic portion and attached through the shell. The reservoir may be closed with a plug. The plug may be mechanically removed or may degrade under a stimulus. The plug may be attached to a line fixture connected to a control line. A force acting on this line, for example caused by a control line driver and / or a fluid flow (e.g., air or fluid pressure) in the canal, may remove the plug, thus bringing the contents of the reservoir into contact with the blood. Additionally or alternatively, the plug may degrade under a stimulus, such as electricity (e.g., biocorrosion by electrical current) or exposure to light, as described herein. In such a configuration, the plug may be made of a metal, such as tungsten and / or titanium, or a polymer, such as silicone, PEEK, or any combination thereof. In such a configuration, the outer diameter of the plug may particularly preferably be about 240 μm. The inner diameter of the reservoir may be 100 μm. The outer diameter of the reservoir may be 200 μm. The reservoir may be made of a polymer such as PDMS.

[0091] Preferably, the medical device comprises at least one counterforce member, which may be activatable, the counterforce member being configured to increase the force acting on the medical device.

[0092] The counterforce member may in particular be magnetic and / or hydrodynamic, ie configured to increase the magnetic and / or hydrodynamic forces acting on the medical device.

[0093] For example, the resistance member can include an umbrella element disposed on the magnetic portion or on the control line that can be opened to increase the resistance force exerted by the blood flow on the medical device, thus facilitating transport of the medical device to the treatment site.

[0094] The resistance member may be configured to increase the area of ​​engagement with a fluid, such as blood. The invention further relates to a system comprising a medical device, a control unit and an imaging device. Preferably, the medical device is a medical device as described herein. The control unit is configured to guide the medical device to a target location, in particular a treatment site, within the vasculature.

[0095] The system according to the invention may be particularly suitable for moving a medical device in a vascular network. The medical device may be a catheter device or a microrobot. The device may comprise a balloon. The medical device may comprise a head section having a magnetic portion and a back section having a control line. The medical device may be moved in the vascular network to treat or diagnose a patient. The system may comprise a magnetic actuator, a control unit and a control line driver. The control line may be attached to the control line driver. The control line driver is configured to hold, retrieve and / or release the control line at different speeds when said control line is attached to the control line driver. The magnetic actuator is configured to generate a magnetic field at a predetermined position. Preferably, the magnetic field is predetermined. The magnetic field may exert a force on the medical device, in particular on the magnetic portion of the medical device, pulling the medical device in a predetermined direction. The control unit may be configured to balance at least three forces acting on the medical device. Preferably, the control unit balances the forces in real time.

[0096] Preferably, the three forces include at least one of a drag force acting on the medical device due to a flow of a fluid, e.g. blood in a blood vessel, a force due to a control line, and a magnetic force due to a magnetic actuator. Further, the control unit operates the magnetic actuator and / or the control line driver.

[0097] The balloons used in combination with the device, particularly the microrobot or catheter, may in particular be asymmetrically inflatable, for example it may be possible to selectively inflate the balloon only on one side of the longitudinal axis, or several selectively inflatable balloons may be used, which may allow the device to be detached from tissue to which it has been intentionally or accidentally attached.

[0098] The thickness of the balloon may be between 50 μm and 300 μm, preferably between 80 μm and 150 μm. Furthermore, there may be an activation system for or to enable the expansion. The balloon may have a spherical shape with a diameter between 50 μm and 700 μm, preferably between 200 μm and 400 μm. Thus, the contact surface (and therefore unintentional adhesion) with the tissue wall may be reduced. The balloon wall may be made of any suitable medical grade polymer, such as polyurethane and / or silicone. The activation system may comprise or consist of a solenoid valve and / or may have a shape corresponding to a rotating body.

[0099] The control unit can assist with magnetic guidance. The concepts described herein help to find a good balance between the various forces on the medical device, namely flow forces, gravity, control forces, and magnetic or other potential forces acting on the medical device, to guide the medical device along a trajectory path. The system can automatically calculate the forces and the relationships between the forces, and define the forces generated by the system, especially the control line forces and the magnetic forces, to ensure that the resulting forces move the medical device along a predefined trajectory.

[0100] This balance model can also optimize the distribution of forces induced by the magnetic actuators and the control lines. The force balance can also be beneficial for optimizing system requirements, e.g., weaker magnetic fields and / or smaller control line forces.

[0101] The control line driver may include, and preferably consist of, any one or combination of the following: pulleys, linear actuators, reels, electric motors, spindles, gears, screws and / or nuts, linear gear tracks, and continuous tracks. Additionally, the control line driver may comprise two or more of any one of these elements in combination with one or more of any other elements.

[0102] Further, the control line driver may additionally or alternatively comprise a control line connector configured to provide an operable connection between the control line driver and the control line.

[0103] Preferably, the control unit may comprise a processor and / or a memory. In a particularly preferred embodiment, the control unit is operatively connected to the electric motor and configured to control at least one of the speed, power, and torque of the electric motor.

[0104] The speed may be at least partially predetermined, automatically determined or manually selected. It is also conceivable to use a combination of predefined, automatically determined and manually selected speeds. For example, the control unit may calculate an appropriate speed profile based on the planned trajectory in the vessel, taking into account data on the flow of blood in the vessel, and store the speed profile in memory. Additionally or alternatively, the speed of the control line may be adjusted automatically during the intervention, for example via a feedback loop taking into account the planned trajectory and the actual position data, and / or manually by the user. For this purpose, the system may preferably comprise an interface for the user, for example one or more touch screens, knobs, buttons, levers, configured to allow the input of speed parameters. Using the same interface or additional interfaces, it is possible to input further parameters related to the control of the position and speed of the medical device.

[0105] Preferably, the control unit is configured to calculate the magnetic field at the device position in space and / or the force that said magnetic field exerts on the magnetic element when the magnetic element is located at the device position in space. The control unit may in particular take into account at least one of the position, orientation and / or output of the magnetic actuator. Additionally or alternatively, the control unit may be configured to receive data from a sensor at or near the device position, in particular data relating to the magnetic field and / or magnetic force at the device position.

[0106] Additionally or alternatively, the device may calculate at least one of a position, an orientation, and an output of a magnetic actuator suitable for establishing a magnetic field and / or magnetic force at the device location. The magnetic field and / or magnetic force may be calculated qualitatively (e.g., direction only) or quantitatively.

[0107] Preferably, the control line driver is configured to control at least two control lines attached to the medical device. The two control lines may be released at the same rate. Alternatively, the two control lines may be released at different rates, for example to position and / or orient the medical device in front of a thrombus.

[0108] The control line driver can be equipped with a sensor that allows monitoring of the retrieval of the thrombus. As an example, a dynamometer is used to measure the force during the retrieval (throughout the procedure). The rate of retrieval of the thrombus can be adjusted using the force measured by the control driver and / or the sensor.

[0109] The control unit can monitor physiological data measured by the system and / or data measured by other devices and can adjust commands to various elements of the guidance system based on the monitored data.

[0110] Additionally, the present invention relates to a method of manufacturing a medical device, particularly a medical device as disclosed herein, the method comprising: Providing a flexible line having a magnetic portion and an attachment element attached thereto; - coating at least a portion of the attachment element with a temporary layer; - coating at least a part, preferably the whole, of the medical device with a resin and / or a polymer, preferably carried out by immersion and / or drying; removing the temporary layer; Includes.

[0111] The method is particularly suitable where the attachment element comprises electrical and / or electronic components, for example where the attachment element comprises electrodes for cauterization and / or electrothrombosis as described herein.

[0112] The method may further comprise the step of coating the adhesion layer with a coagulant and drying the coagulant prior to applying the temporary layer.

[0113] The temporary layer protects the attachment elements. A coating applied to at least a portion of a medical device can be easily removed in the areas protected by the temporary layer. The temporary layer thus prevents the attachment elements from becoming covered with the coating. Thus, the method provides a very simple way to produce a medical device having a coating, where portions of the device are selectively left uncoated.

[0114] Additionally, the present invention relates to a method of retrieving a thrombus from a blood vessel using a medical device, preferably the medical device is as disclosed herein. The method comprises: - introducing a distal end of a medical device having an attachment element into a blood vessel; Guiding the medical device to a target location; Optionally, activating the activation mechanism such that the attachment element is transformed from a non-activated state to an activated state capable of attaching to the thrombus, preferably to the proximal side of the thrombus; - attaching an attachment element to the thrombus proximal to the thrombus; Optionally, stretching the thrombus to reduce the diameter of the thrombus in a cross section perpendicular to the longitudinal axis of the blood vessel; removing the thrombus from the target site by pulling the thrombus; Includes.

[0115] Preferably, the withdrawal rate is adjusted to control the force applied to the thrombus. Preferably, the method further comprises the step of providing a vibration or shaking motion to the medical device after attachment of the attachment element to the thrombus to facilitate removal of the thrombus.

[0116] It will be understood that all method steps described herein in the context of medical devices and systems, in particular with respect to the control unit, the control lines and the intravascular guidance using magnetic forces, can be performed in the method according to the invention.

[0117] In the context of this specification, proximal will be understood to refer to the direction along the longitudinal axis of the medical device from the treatment side toward the medical device in its intended use, and distal will refer to the direction from the medical device toward the treatment site.

[0118] Generally, in the context of this specification, a microrobot can be generally understood as a combination of control lines and magnetic parts. The microrobot may be a therapeutic microrobot further comprising a therapeutic tool.

[0119] In some embodiments, the device can include a growth tube that is extendable, for example by filling it with a fluid.

[0120] Suitable fluids are gases, liquids such as saline or viscous solutions, and magnetic fluids (e.g., suspensions of Fe3O4 or Fe2O3 in saline, especially isotonic solutions), which allow access to areas of the body where the flow of bodily fluids is insufficient to exert a drag force on the medical device, such as occluded arteries.

[0121] A growth tube typically comprises a tube of soft material folded inward. The inside of the tube can be moved so that the surface is outward, for example by pressurizing with air or liquid, so that the tube everts and causes unidirectional growth. Growth tubes are well known and are described in U.S. Patent Application Publication No. 2019 / 0217908, the contents of which are incorporated herein by reference.

[0122] The growth tube can have an outer diameter between 0.5 mm and 3 mm, preferably between 0.9 mm and 2 mm. The shell thickness of the growth tube can be between 20 μm and 1 mm, preferably between 100 μm and 400 μm. The tube can be made of polymers such as polyurethane, low density polyethylene, and other medical grade polymers.

[0123] In some embodiments, the medical device is configured to interact with the magnetic field generated by an MRI system. Preferably, the medical device is operable by an MRI system.

[0124] In the following the invention will be explained in detail with reference to the following figures: [Brief description of the drawings]

[0125] [Figure 1a] 1 shows a schematic diagram of a device according to the present invention in a blood vessel having a thrombus and the use of the device to reach and remove the thrombus. [Figure 1b] 1 shows a schematic diagram of a device according to the present invention in a blood vessel having a thrombus and the use of the device to reach and remove the thrombus. [Figure 1c] 1 shows a schematic diagram of a device according to the present invention in a blood vessel having a thrombus and the use of the device to reach and remove the thrombus. [Figure 2a] 1 shows a schematic diagram of an embodiment of a device according to the invention with various attachment elements. [Figure 2b] 1 shows a schematic diagram of an embodiment of a device according to the invention with various attachment elements. [Figure 2c] 1 shows a schematic diagram of an embodiment of a device according to the invention with various attachment elements. [Figure 3a] 4 shows a detailed schematic diagram of the attachment of the attachment elements to the magnetic part of the device according to the invention. [Figure 3b] 4 shows a detailed schematic diagram of the attachment of the attachment elements to the magnetic part of the device according to the invention. [Figure 3c]4 shows a detailed schematic diagram of the attachment of the attachment elements to the magnetic part of the device according to the invention. [Figure 3d] 4 shows a detailed schematic diagram of the attachment of the attachment elements to the magnetic part of the device according to the invention. [Figure 3e] 4 shows a detailed schematic diagram of the attachment of the attachment elements to the magnetic part of the device according to the invention. [Figure 4a] FIG. 1 shows a schematic diagram of the activation of one embodiment of the present invention. [Figure 4b] FIG. 1 shows a schematic diagram of the activation of one embodiment of the present invention. [Diagram 5] 2b shows a detailed view of the embodiment of FIG. 2a. [Figure 6a] FIG. 2b shows a schematic diagram of thrombus retrieval according to the embodiment of FIG. 2a based on biological attachment. [Figure 6b] FIG. 2b shows a schematic diagram of thrombus retrieval according to the embodiment of FIG. 2a based on biological attachment. [Figure 7a] FIG. 13 shows a schematic diagram of an alternative embodiment for bioattachment-based thrombectomy using electrothrombosis. [Figure 7b] FIG. 13 shows a schematic diagram of an alternative embodiment for bioattachment-based thrombectomy using electrothrombosis. [Figure 8a] FIG. 7b shows a detailed view of the device shown in FIG. 7a. [Figure 8b] FIG. 7b shows a detailed view of the device shown in FIG. 7a. [Figure 9] 13 illustrates another embodiment configured for attachment using electrothrombosis. [Figure 10a] FIG. 10 shows a schematic diagram of the manufacturing steps for producing the embodiments of FIGS. 8a, 8b and 9. [Figure 10b] FIG. 10 shows a schematic diagram of the manufacturing steps for producing the embodiments of FIGS. 8a, 8b and 9. [Figure 11a] 1 shows a schematic diagram of an embodiment of a device based on chemical attachment to retrieve thrombus. [Figure 11b]1 shows a schematic diagram of an embodiment of a device based on chemical attachment to retrieve thrombus. [Figure 12a] 1 shows schematic diagrams of various embodiments for mechanical attachment. [Figure 12b] 1 shows schematic diagrams of various embodiments for mechanical attachment. [Figure 12c] 1 shows schematic diagrams of various embodiments for mechanical attachment. [Figure 13a] FIG. 1 shows a schematic diagram of thrombectomy with a mechanical attachment-based device. [Figure 13b] FIG. 1 shows a schematic diagram of thrombectomy with a mechanical attachment-based device. [Figure 13c] FIG. 1 shows a schematic diagram of thrombectomy with a mechanical attachment-based device. [Figure 13d] FIG. 1 shows a schematic diagram of thrombectomy with a mechanical attachment-based device. [Figure 14a] 1 shows a schematic diagram of an embodiment with a spring. [Figure 14b] 1 shows a schematic diagram of an embodiment with a spring. [Figure 15] FIG. 1 shows a detailed schematic diagram of another embodiment based on mechanical attachment with an additional fixation coating (thrombogenic, expandable material). [Figure 16a] 13 shows a schematic diagram of an alternative embodiment of a device having a protective coating. [Figure 16b] 13 shows a schematic diagram of an alternative embodiment of a device having a protective coating. [Figure 17a] 1 illustrates one embodiment for activation of the protective coating. [Figure 17b] 1 illustrates one embodiment for activation of the protective coating. [Figure 18a] 13 illustrates an alternative embodiment for activation of the protective coating. [Figure 18b] 13 illustrates an alternative embodiment for activation of the protective coating. [Figure 18c] 13 illustrates an alternative embodiment for activation of the protective coating. [Figure 19a] 1 illustrates various embodiments of activation of the attachment element. [Figure 19b] 1 illustrates various embodiments of activation of the attachment element. [Figure 19c] 1 illustrates various embodiments of activation of the attachment element. [Figure 19d] 1 illustrates various embodiments of activation of the attachment element. [Figure 20a] 1 shows various embodiments of an attachment element. [Figure 20b] 1 shows various embodiments of an attachment element. [Figure 20c] 1 shows various embodiments of an attachment element. [Figure 20d] 1 shows various embodiments of an attachment element. [Figure 20e] 1 shows various embodiments of an attachment element. [Fig. 20f] 1 shows various embodiments of an attachment element. [Figure 21a] 1 shows diagrammatically different attachment principles of the device; [Figure 21b] 1 shows diagrammatically different attachment principles of the device; [Figure 21c] 1 shows diagrammatically different attachment principles of the device; [Figure 21d] 1 shows diagrammatically different attachment principles of the device; [Figure 21e] 1 shows diagrammatically different attachment principles of the device; [Fig. 21f] 1 shows diagrammatically different attachment principles of the device; [Figure 22a] 1 shows a schematic diagram of an apparatus with a protective frame. [Figure 22b] 1 shows a schematic diagram of an apparatus with a protective frame. [Diagram 23] 1 shows a schematic diagram of a device with an additional propulsion element. [Figure 24a] 1 shows a schematic diagram of an apparatus having a suction mechanism. [Figure 24b] 1 shows a schematic diagram of an apparatus having a suction mechanism. [Diagram 25]FIG. 1 shows a schematic diagram of an apparatus having a mechanical gripper and a shaft. [Figure 26] 1 shows a schematic diagram of a device with a t-PA coating. [Figure 27] 1 shows an alternative device configured to deliver t-PA. [Figure 28] FIG. 1 shows a schematic diagram of a device with fibers. [Figure 29] 13 shows a cross-sectional view of an alternative device having a suction mechanism. [Diagram 30] 1 shows a schematic diagram of a device comprising a balloon. [Figure 31a] 1 shows a schematic diagram of a first embodiment of a device having a sensor; [Figure 31b] 1 shows a schematic diagram of a first embodiment of a device having a sensor; [Figure 32a] 2 shows a schematic representation of a second embodiment of an apparatus having a sensor; [Figure 32b] 2 shows a schematic representation of a second embodiment of an apparatus having a sensor; [Figure 33a] 1 shows a schematic representation of an apparatus with growth elements. [Figure 33b] 1 shows a schematic representation of an apparatus with growth elements. [Diagram 34] 1 illustrates a schematic of an MRI system. [Diagram 35] 1 shows a schematic representation of an apparatus having a retaining line; [Figure 36a] 1 shows a schematic diagram of a device having a catheter and a balloon. [Figure 36b] 1 shows a schematic diagram of a device having a catheter and a balloon. [Figure 37] 1 shows a schematic representation of the device with a suction mechanism and electrical elements. [Figure 38a] 1 shows a schematic of a device having two balloons. [Figure 38b] 1 shows a schematic of a device having two balloons. [Figure 39a] 1 shows a schematic of an apparatus having two retention lines. [Figure 39b] 1 shows a schematic of an apparatus having two retention lines. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0126] Fig. 1a shows a schematic representation of a device 1 according to the invention and its use. The device 1 comprises an attachment element 4 configured to provide attachment to a thrombus 2. It is to be understood that the illustration shown here is general and is only intended to allow the reader to understand the basic principles of the invention, specific embodiments are shown later. The device 1 can be guided to the treatment site where the thrombus 2 is located by magnetic guidance and / or a catheter device (not shown). Once attached to the proximal side 6 of the thrombus 2, a force F can be applied to the device 1, for example to pull the thrombus 2 away from the treatment site in the direction of the force F. The force F is thus sufficient to overcome the frictional forces between the thrombus 2 and the vessel wall 3.

[0127] Fig. 1b shows the device 1 being guided to a treatment site where a thrombus 2 is located between the vessel walls 3 and thus obstructing the blood flow. The device 1 comprises an attachment element 4 for attachment to this thrombus 2. Here, the device 1 comprises a magnetic part 19 attached to a control line 23.

[0128] The control line 19 can be used to control the velocity in the blood flow. The magnetic part 23 can allow guidance by a magnetic field generated by an external magnet. For example, electromagnets and / or coils can be used. Here, the device has reached bifurcation B. A magnet (not shown) can be used to guide the device 1 to the intended branch of bifurcation B for reaching the thrombus 2 at the treatment site.

[0129] Figure 1c shows diagrammatically the removal of a thrombus 2 from a treatment site with a device 1 according to the invention. For clarity, reference numbers for identical features are shown only once. First (panel A) an attachment element 4 is attached to the proximal side 6 of the thrombus 2. To remove the thrombus 2, a force F is applied via a control line 23.

[0130] In general, the device 1 may comprise a magnetic portion 19 and control lines 23. The magnetic portion may be used to control the trajectory of the device 1 in the blood vessel.

[0131] The magnetic portion 19 may comprise or consist of soft ferromagnetic materials such as iron, cobalt, nickel, etc., hard ferromagnetic materials such as Nd-Fe-B alloys, Fe-Pt alloys, ferrimagnetic materials such as iron oxide, etc. The magnetic portion may comprise or consist of an aggregate of magnetic particles, such as superparamagnetic nanoparticles made of iron oxide, among others.

[0132] The magnetic portion 19 may be coated to prevent direct contact with biological fluids and thus avoid corrosion. For example, the coating material against corrosion may be polymeric (such as Parylene C), ceramic (e.g., silica-based, zirconium-based, TiO2), or metallic (gold, silver).

[0133] The control line 23 can be used to control the movement of the device 1. The control line 23 may be attached to a driver (not shown). The driver may be configured to release the control line 23 according to commands provided by a control unit (not shown).

[0134] The control line 23 can be used to slow down, stop movement and / or retract the device 1 being pushed by the blood flow. Additionally or alternatively, the control line 23 can be used to trigger a function of the device 1 by providing a stimulus.

[0135] The control line 23 can be reversibly or irreversibly connected to the magnetic portion 19 by an adhesive. In addition, it is conceivable to immerse the magnetic portion 19 and its connection to the control line in a resin. The resin can increase the stability of the connection between the magnetic portion 19 and the control line 19 by forming a shell that at least partially surrounds the magnetic portion 19 and the distal portion of the control line 23. Furthermore, the adhesion of the adhesive is improved and the adhesive can be functionalized with magnetic particles. The magnetic particles can be attracted to the magnetic portion 19. Thus, the adhesion between the control line 23 and the magnetic portion 19 can be increased due to the magnetic interaction.

[0136] As shown in panel B, the force F acting on the thrombus 2 stretches the thrombus 2 by pulling on it. Therefore, the frictional force between the thrombus 2 and the vessel wall 3 is reduced, and less force is required to remove the thrombus 2 (see panel C).

[0137] Figure 2a shows one particular embodiment of the device 1 according to the invention. The device 1 comprises a magnetic head part 19 attached to a control line 23. The control line 23 is made of nylon with a diameter of 200 μm and a breaking force of 13 N. The attachment element shown here consists of a tool support 102 (see Figures 3a to 3d) arranged on the magnetic head part 19 and equipped with a biological attachment element 7. The magnetic head part 19 is arranged at the distal end 5 of the medical device 1. At the distal end, the device 1 has a substantially flat surface F.

[0138] Here, bioadhesion refers to adhesion between the thrombus 2 and the device 1 by a clot whose formation is induced by the biological adhesive element 7. The biological adhesive element 7 may therefore be any thrombogenic material.

[0139] The biological attachment element 7 is particularly advantageous because it allows a clot to form between the attachment element 4 and the thrombus 2 without requiring any or little compressive force to attach the device 1 to the proximal surface of the thrombus 2.

[0140] To trigger the formation of a clot, the biological adhesive element may preferably contain a thrombogenic agent involved in the coagulation cascade, such as thrombin, the concentration of which in the biological adhesive element can be selected to be sufficient to trigger local clotting despite the presence of anticoagulants typically required in such interventions.

[0141] Here, the thrombogenic material forming the biological attachment elements 7 is attached to the surface of the surface of the tool support 102. The thrombogenic material can be chemically bound to the surface of the tool support 102 by means of a graft.

[0142] Additionally or alternatively, the thrombogenic material may be mixed with a polymer, preferably a non-biodegradable polymer, to form a thrombogenic polymer that ensures permanent attachment. The thrombogenic polymer is allowed to dry on the surface of the tool support 102.

[0143] The thickness of the thrombogenic polymer coated on the biological attachment element 7, in particular on the tool support 102, may be between 10 μm and 500 μm, preferably between 90 and 110 μm.

[0144] Additionally or alternatively, the thrombogenic material may be mixed with a polymer solution, for example polyurethane with a solvent, and then processed as fibers spun onto the surface of the tool support 102 to form the biological attachment elements 7. Preferably, hexafluoroisopropanol (HFIP) is used as the solvent.

[0145] Additionally or alternatively, swelling polymers may be used, for example hydrogels (PVA, PVP, polyacrylamide), porous hydrogels, superabsorbent polymers (poly(acrylic acid (PAA), foams (PU)) can be used as matrix materials in the biological attachment element 4 to increase the contact surface with the thrombus after hydration with blood.

[0146] If the biological attachment element 7 comprises fibres, these fibres may present a core-shell structure. Preferably, the thrombogenic agent is located within the shell. Preferably, a bioabsorbable polymer forms the core and / or the shell.

[0147] The fiber diameter is preferably in the range of 50 nm to 10 μm, and particularly preferably between 800 nm and 3 μm.

[0148] Particularly preferably, biodegradable polymers are used that exhibit a degradation time of more than 2 months. Polymers such as PLGA, PLLA, PDO, PCL, etc. may be suitable.

[0149] Alternatively, the biological adhesive element may include an element configured to react with components of a thrombus, such as fibrin or red blood cells. This reaction may trigger a coagulation cascade that leads to the formation of a clot. For example, the biological adhesive element may include peptides that can react with fibrin in the thrombus 2, in particular cyclic peptides such as Tn6, Tn7, and TnlO.

[0150] Figure 2b shows an alternative embodiment similar to that shown in figure 2a. The device 1 comprises a magnetic head part 19 formed as a microrobot 18 and connected to a control line 23 at the distal end 5 of the device 1. The attachment element 4 comprises a tool support 102. Instead of a biological attachment element, the tool support comprises a chemical attachment element 10. The device 1 has a substantially flat surface F at its distal end.

[0151] The chemical adhesion element 10 can bring about an adhesive force on the proximal surface of the thrombus 2. A compressive force acting on the adhesive and pressing it against the thrombus 2 may be necessary to create sufficient adhesion. The compressive force may be between 0.001 N and 3 N, preferably between 0.02 and 0.08 N. Preferably, the compressive force is applied for at least 30 seconds, particularly preferably between 45 and 120 seconds. The compressive force can be achieved by a magnetic force generated by an external magnetic field and acting on the magnetic head part 19.

[0152] Additionally or alternatively, the compressive force can be achieved by mechanical means, for example a spring can be placed in the control line 23 (see Figures 11a and 11b and similar Figures 14a and 14b). The spring energy can be released once the device 1 is in the proper position for attachment relative to the thrombus 2.

[0153] Additionally or alternatively, a propulsion element (see FIG. 23) may be used. Additionally or alternatively, a counterforce element (see FIGS. 4 a and 4 b ), for example located on the control line 23 , may be activated to force the adhesive against the thrombus surface 6 .

[0154] Additionally or alternatively, any other means known in the art may be used.

[0155] The adhesive material may be n-butyl-2-cyanoacrylate, such as 2-octyl-2-cyanoacrylate. The adhesive may be a medical grade adhesive and may be disposed on a stationary support. Typically, the adhesive strength is sufficient to hold the adhesive on the device 1, preferably the tool support 102. However, it is contemplated that an adhesion promoter, such as an additional surface coating, may be used.

[0156] Additionally or alternatively, the adhesive material may be biological, for example, the adhesive material may be a protein-based (fibrin-, collagen-, gelatin-, albumin-based) and / or polysaccharide-based (chitosan-, alginate- (e.g., SealG), and chondroitin-based) adhesive.

[0157] Additionally or alternatively, the adhesive may be a synthetic adhesive, such as polycyanoacrylate (e.g., n-butyl-2-cyanoacrylate, such as 2-octyl-2-cyanoacrylate), polyurethane (e.g., TissuGlu®), poly(ethylene glycol) (PEG, e.g., DuraSeal™, FoacaSeal®, CoSeal®), polyester, and hyperbranched and dendrimer polymers.

[0158] Additionally or alternatively, the adhesive may be a biomimetic adhesive, such as a mussel-inspired adhesive (eg, dopamine-modified gelatin+Fe3++ genipin), a gecko-inspired adhesive, or the like.

[0159] Additionally or alternatively, the adhesive may exist in an inactive state and be activated by any means known in the art and / or described herein, such as light activation (UV or other wavelengths) or in situ mixing of at least two components. An example of a light-activated adhesive may be a photopolymerizable PEG adhesive or methacrylated tropoelastin. An example of in situ mixing may be mixing of two PEG polymers (such as in CoSeal®) or mixing of a PEG polymer with poly(ethyleneimine) (such as in Adherus).

[0160] Additionally or alternatively, the adhesive may comprise magnetic nanoparticles, for example iron oxide nanoparticles. The nanoparticles may exhibit hard ferromagnetic, soft ferromagnetic, ferromagnetic or superparamagnetic properties. The nanoparticles may have a characteristic size, in particular a diameter, of 5 nm to 400 nm, preferably 10 nm to 50 nm. Additionally or alternatively, the nanoparticles may have a characteristic size, in particular a diameter, of 50 nm to 400 nm. 3 ~3.4·10 7 nm 3 , preferably 400 nm 3 ~5·10 4 nm 3 The feature volume may be in the range of

[0161] The nanoparticles can be dispersed in the adhesive and interact with the adhesive via low-energy van der Waals forces. Alternatively, the nanoparticles can be connected to the adhesive via covalent and / or ionic bonds. Thus, the magnetic nanoparticles can provide magnetic properties to the adhesive dispersion containing these nanoparticles. Thus, magnetic forces can be generated between the adhesive dispersion and the magnetic head portion, resulting in a more reliable attachment of the adhesive to the device 1. These magnetic forces can reduce the risk of detachment of the adhesive from the tool support 102 and at least partially relieve the strain on the adhesive during retrieval of the clot.

[0162] The adhesive is placed on the device 1 so as to have a diameter of 50 μm to 1 mm, preferably 300 μm to 600 μm.

[0163] The adhesive may be a dry adhesive. The adhesive in the dry state has a lower adhesive strength than the wet state. Therefore, the dry adhesive is particularly advantageous when a protective shell is used during the introduction to the treatment site, since it can reduce the risk of accidental and / or permanent adhesion of the attachment element to the protective shell and / or other parts of the device.

[0164] Additionally or alternatively, the adhesive may be impregnated into a porous material disposed on the tool support 102. The porous material may be a fibrous tissue or porous beads.

[0165] For example, a fiber fabric made of PET can be used. The fiber fabric can have fibers with a diameter of 3 μm and a pore size of about 800 nm. The fiber structure can be fixed on the tool support 102 by an adhesive layer in the center and / or on the periphery of the PET fiber fabric. Preferably, the adhesive is allowed to dry on the porous material such as the fiber fabric.

[0166] The use of a fiber fabric that is bonded in the center is particularly advantageous since the peripheral areas remain unattached to the tool support 102 and can therefore increase adhesion by moving towards the thrombus 2.

[0167] Figure 2c shows diagrammatically an embodiment of the device 1, in which the attachment element 4 comprises mechanical attachment means 11. The embodiment shown here is substantially similar to the embodiment shown in figures 2a and 2b, except for the means of attachment. The device 1 has at its distal end a substantially flat surface F.

[0168] Here, the mechanical attachment element 11 is configured to penetrate the proximal surface of the thrombus 2 (see FIG. 1). Optionally, the mechanical attachment element may comprise a thrombogenic coating (not shown), in particular a coating configured to react with components of the thrombus to trigger clotting. It will therefore be appreciated that such an embodiment may combine mechanical and biological attachment means. Additionally or alternatively, the mechanical attachment element may be coated with an adhesive and / or an expandable material as described herein.

[0169] Expandable materials can generally be used to improve adhesion to the thrombus. Here, there are four mechanical attachment elements 11. It will be understood that any number of elements 11 may be used depending on the intended application, in particular the size of the thrombus 2 to be treated. Preferably, between 2 and 8 elements 11 are used. It is also possible to use only one element 11.

[0170] The mechanical attachment element 11 has a Young's modulus greater than that of the thrombus 2, preferably at least above 1 MPa.

[0171] The diameter of the mechanical attachment elements 11, here 100 μm each, may range from 50 μm to 700 μm, preferably from 80 μm to 300 μm.

[0172] The mechanical attachment element 11 preferably comprises or is composed of a polymer such as PET, PE, or PP, or any blend or copolymer thereof.

[0173] In case mechanical and biological attachment means are combined, thrombogenic elements may be mixed with this polymeric material. Thus, the mechanical attachment element 11 may be made of a thrombogenic material.

[0174] Additionally or alternatively, the mechanical attachment element may include or be constructed of a metal, for example, stainless steel (316L), titanium, tungsten, or any alloy thereof.

[0175] Additionally or alternatively, the thrombogenic agent can be coated, for example by dip coating, onto the mechanical attachment element 11. Coatings are advantageous in that they can be used with a wider variety of materials, i.e., suitable for mechanical attachment elements including polymers, metals, or any other material.

[0176] In particular, the surface of the mechanical attachment element 11 can be coated with a thrombogenic agent by CVD, plasma spraying, or physical vapor deposition.

[0177] Exemplary thrombogenic factors that can be used are von Willebrand factor (vWF), laminin, thrombospondin, vitronectin, fibrinogen, or thromboxane A2. These thrombogenic factors can trigger the adhesion of platelets and thus the formation of a clot.

[0178] Thrombin is also suitable and is an enzyme that converts fibrinogen to fibrin by cleavage of fibrinopeptide A. Thus, a fibrin network can be formed to trap red blood cells and platelets, resulting in the formation of a clot.

[0179] 3a to 3e show the device 1, in particular the assembly of the magnetic part 19 and the attachment element 4, in more detail.

[0180] Figure 3a shows a magnetic portion 19 attached to a control line 12 at the distal portion 5 of the device. The magnetic portion 19 comprises an opening 100 which serves as a form-fit connection for a tool support (see Figures 3c and 3d).

[0181] The diameter of the opening 100 is 300 μm in the embodiment shown, however it will be appreciated that the diameter may be anywhere in the range of 50 to 600 μm, preferably 200 to 400 μm.

[0182] The height or depth 106 of the opening 100 may be the same as or smaller than the diameter of the magnetic portion 19. The height may preferably be between 100 and 1000 μm, particularly preferably between 200 μm and 400 μm.

[0183] Figure 3b shows the magnetic part 19 of the device in schematic form. One can see in more detail the magnetic part 19 and the opening 100 in the magnetic part 19 located at its most distal surface for fastening the tool support (see Figures 3c and 3d). For clarity, control lines are not shown in this figure. However, it will be understood that the magnetic part 19 shown here may be connected to any of the control lines 23 disclosed herein.

[0184] The magnetic portion 19 shown here has a substantially spherical shape. Alternatively, the magnetic portion 19 may have any other shape, in particular cubic, flat, elliptical or rod-like. The diameter of the magnetic portion 19 is here 1500 μm, but may range from 50 μm to 2000 μm, preferably from 200 μm to 1000 μm.

[0185] 3c shows the tool support 102 in more detail. The tool support 102 is configured to be mounted to the distal end of the magnetic portion 19.

[0186] The tool support 102 can be connected to the magnetic part 19, for example, by gluing, screwing, clipping, welding or melting. Preferably, the tool support 102 comprises a pin 101 intended to be placed in a form-fitting opening 100 in the magnetic part 19. It will be understood that any of the above mentioned connection methods can be combined with such a form-fitting connection, i.e. glue, screws, clips, welded connections or melted connections can be configured in addition to a form-fitting connection.

[0187] Preferably, the tool support presents a flat surface.The feature size, particularly the diameter, of the tool support 102 may be the same as, larger than, or smaller than the diameter of the magnetic portion.

[0188] The tool support may comprise or consist of a magnetic material, a non-magnetic material, or any combination thereof. For example, a portion of the tool support 102 may be magnetic to improve connection to the magnetic portion 19.

[0189] Suitable non-magnetic materials include: Metals such as titanium, stainless steel, gold, silver, etc. Polymers such as silicone, PEEK, polyurethane, etc. ·ceramic, ·Composite materials It is.

[0190] Tool support 102 may additionally or alternatively include or be composed of agglomerated particles, which may provide enhanced tunability of material properties, such as electrical conductivity. Tool support 102 may optionally be coated with a biocompatible coating (not shown) to improve its biocompatibility.

[0191] FIG. 3d shows the magnetic portion 19 of FIG. 3b in combination with the tool support 102 of FIG. 3c.

[0192] Figure 3e shows the assembled device 1 configured as a microrobot 18. The device 1 comprises a magnetic portion 19 as shown in Figure 3b and a tool support 102 as shown in Figure 3c, connected to control lines 23 at the distal end 5 of the device 1. Although no attachment elements are shown here on the tool support 102, it will be understood that any attachment elements as disclosed herein can be combined with the illustrated embodiment.

[0193] Here, for purposes of illustration, a longitudinal axis L and a direction r perpendicular to the longitudinal axis are shown. The device 1 has a size S in the direction r, which represents the maximum size of the device 1 in the direction r of 2 mm.

[0194] Figures 4a and 4b show an embodiment of the device 1 with an additional counterforce element 25. The device 1 shown here is substantially similar to the device 1 of Figure 2b, with a magnetic part 19 having a tool support 102 constituted by a chemical attachment element 10, here in the form of a droplet of cyanoacrylate glue. The device 1 is configured as a microrobot 18. Furthermore, the device shown here comprises a protective cap 14 constituted by an encapsulation made of a thin foil of PVDF. Additionally or alternatively, PMMA and / or PA66 may be used. The protective cap 14 comprises a ring 108 slidably arranged on a slider 107. The protective cap 14 can be retracted from the microrobot 18 by moving the ring 108 on the slider 107 in a proximal direction. The retraction can tear the protective cap 14, resulting in its opening.

[0195] The protective cap 14 is crimped to a ring 108. The ring 108 may comprise or consist of a polymer, a metal, or any combination thereof. The crimping may prevent the inadvertent ingress of biological fluids, such as blood, into the protective cap 14.

[0196] The ring 108 and slider 107 together form a sliding system and are mounted on the control line 23 .

[0197] The slider 107 can be configured as a straight tube arrangement, optionally with a distal ring (not shown) and a proximal ring 109. The straight tube allows for retraction of the capsule by providing a rail-like guide for the ring 108. Initially, the ring 108 is located at the distal end of the slider 107. To retract the protective cap 14, the ring 108 is moved to the proximal end of the sliding system. The ring can be moved, for example, by a line pulled via a control line driver (not shown). Alternatively, the crimp ring can be moved by contraction of a rigid line disposed between the ring 108 and the distal ring. The rigid line can, for example, comprise or be made of Nitinol that shrinks under electrical stimulation.

[0198] To avoid ingress of liquid, e.g. blood, between the control lines and the sliding system, a valve may be placed inside the proximal ring 109.

[0199] Optionally, to facilitate breaking of the protective cap 14, the protective cap may be provided with a predetermined break point, for example in the form of a reduction in thickness (not shown). The reduction in thickness may be 10-70%, preferably 30-50%. Additionally or alternatively, the breakable portion may comprise or consist of a bioabsorbable material, in particular a bioabsorbable material as described herein. The breakdown may be triggerable by any of the stimuli as described herein.

[0200] Alternatively, the tool support 102 may include a cutting tool (not shown) that is capable of tearing the protective coating 14 upon retraction.

[0201] Preferably, the cutting tool is located at the edge of the tool support 102 . The drag element 25 is disposed on the control line 23. In one configuration, the activatable drag element 25 is made of a Nitinol frame covered with a polymer layer. The polymer layer may comprise or consist of polyurethane and may exhibit a thickness of 50 μm to 300 μm. The Nitinol frame may be activated under a stimulus, such as heat, resulting in opening of the structure. An increase in drag caused by blood flow may provide additional propulsion.

[0202] Figure 4a shows a first configuration of the device 1, where the protective cap 14 is in a delivery configuration, protecting the attachment element 4 from contact with blood, other biological fluids and tissue, and the drag element 25 is in a closed configuration.

[0203] Fig. 4b shows a second configuration of the device 1. Here, the protective cap 14 has been opened by sliding the ring 108 on the slider 107 in a proximal direction. The protective cap 14 is thus torn, thus releasing the attachment element 4 from the protective cap 14 so that the most distal end of the device 1 can attach a thrombus (not shown) to the adhesive attachment element 10. Furthermore, the drag element 15 is in an open configuration, generating additional drag due to blood flow.

[0204] It will be understood that the two configurations shown in Figures 4a and 4b, i.e. the resistance element is closed during delivery and open when the attachment element 4 is released, are exemplary. It is also conceivable that the resistance element 25 is opened and closed independently of the configuration of the protective cap 14 (i.e. the resistance element 25 may be opened and closed during delivery or during attachment of the attachment element to the thrombus). In particular, the resistance element 25 can be used for additional resistance during delivery (i.e. when the protective cap 14 is intact) and / or for providing additional adhesion (i.e. when the attachment element 4 is released). It is also conceivable that the resistance element 25 is only open during delivery and not during attachment.

[0205] Figure 5 shows a more detailed view of the distal end region of a device 1 similar to that of figure 2a. The biological attachment element 7 comprises a porous polymer layer in which a thrombogenic element is arranged. The biological attachment element is mounted as a thin layer on a tool support 102 which is attached to a magnetic part 19. A control line 23 made of thin nylon fibres is attached to the magnetic part 19 and is therefore arranged at the distal end 5 of the device 1.

[0206] 6 a and 6 b show diagrammatically the attachment of a biological attachment element 7 to the proximal surface 6 of a thrombus 2 .

[0207] The device 1 shown here is substantially similar to the device shown in FIGS. FIG. 6a shows the device delivered to a position relatively close to the thrombus 2. The bioadhesive element 7 is oriented towards the proximal surface 6 of the thrombus 2. In this position, the bioadhesive element 7 can be activated. Here, an electrical signal is transmitted through a cable in the control line to release the thrombogenic agent. It will be understood that more than one cable may be used. It will be understood that any of the activation mechanisms disclosed herein may be used in addition or instead, in particular the protective cap (see FIG. 4a and FIG. 4b). Note that the device has been moved close to the proximal surface 6 of the thrombus, but is not in direct contact with it.

[0208] The illustrated embodiment in particular allows for triggering the formation of a thrombus by applying electricity (electrothrombosis).

[0209] Figure 6b shows the device 1 of figure 6a after activation of the biological adhesive element 7. Due to the thrombogenic activity of the biological adhesive element a clot 7' has formed between the biological adhesive element 7 and the proximal surface 6 of the thrombus 2. The clot 7' provides adhesion between the thrombus 2 and the device 1.

[0210] As shown in Figures 6a and 6b, the biological attachment element 7 may be advantageous in that even if the alignment between the attachment element 4 and the thrombus 2 is imperfect, a clot 7' may be formed and fill the entire gap between the device 1 and the thrombus to provide attachment, thus allowing the surgeon to perform the procedure easier, especially when the relative position of the thrombus 2 and the device is not known with sufficient accuracy and / or when the proximal surface 6 of the thrombus 2 is irregularly shaped.

[0211] Figures 7a and 7b show, in schematic form, an alternative strategy for achieving biological fixation using an electric current applied via the tool support 102. It will be appreciated that an apparatus that can be used in the methods shown here is described in further detail below. For clarity, the principles of operation are described here.

[0212] Electric current can result in the formation of a clot by electrothrombosis. Thus, for example, attachment similar to that shown in Figures 6a and 6b can be achieved using electric current.

[0213] Thus, an electric current can be delivered to the tool support 102 to achieve biological attachment to the thrombus 2 .

[0214] Additionally or alternatively, the temperature of the tool support 102 may be increased by an electric current, resulting in adhesion of the tool support 102 by cauterization. The temperature may be increased to a temperature of up to 60° C., preferably between 40-45° C. It is also possible to use a cryogenic probe at the tool support for cauterization. Heating of the tool support may be caused by an internal or external stimulus.

[0215] 7a shows the tool support 102 attached to the magnetic portion 19 of the device 1 and in contact with the proximal surface of the thrombus 2 after delivery, but prior to activation of the attachment mechanism. Those skilled in the art will appreciate that the tool support 102 may penetrate the surface of the thrombus 2 prior to activation. Additionally or alternatively, heating may be combined with the illustrated embodiment to further provide adhesion.

[0216] 7b shows the formation of cauterized tissue 7' within the thrombus 7' after delivering electrical current and / or heat via the tool support 102. The cauterized tissue 7' provides sufficient attachment between the thrombus 2 and the tool support 102 for retrieval of the thrombus.

[0217] Figure 8a shows diagrammatically a device 1 configured as a microrobot 18 according to the invention with a bioattachment mechanism 7 configured to trigger electrothrombosis. Electrical wires (not shown, see Figure 8b) are arranged in a control line 23. The control line 23 is attached to a magnetic part 19 at the distal end 5 of the device 1. A tool support 102 is attached to the magnetic part 19 and configured to deliver an electric current to act as the bioattachment element 7.

[0218] FIG. 8b shows a more detailed view of the distal region 5 of the device 1 of FIG. 8a in cross-section. Here, an electrical wire 9 is embedded in the inner region of the control line 23 and connected to the magnetic portion 19. For clarity, only one wire is shown, but a person skilled in the art will understand that there may be more than one wire 9. An electrical current can be delivered through the magnetic portion 19 to reach the tool support 102. The diameter of each electrical wire 9 is between 10 μm and 500 μm, preferably between 50 μm and 100 μm. The electrical wires 9 may be attached to the magnetic portion 19 by welding, melting or gluing with a conductive adhesive.

[0219] An insulator shell 110 is arranged on the outer surface of the control line 23 to avoid dissipation of electrical current in biological fluids, in particular blood. The insulator shell 110 is preferably made of a flexible polymer with a small Young's modulus. The Young's modulus is preferably between 0.2 GPa and 50 GPa, particularly preferably between 0.5 GPa and 5 GPa. The thickness of the shell is between 20 and 200 μm, preferably between 30 and 80 μm.

[0220] FIG. 9 shows an alternative embodiment of the device 1 comprising a tool support 102 configured as a biological attachment element 7 .

[0221] Here, two electric wires 9, 9' are guided around the magnetic part 19 through the control line 23 and are directly connected to the tool support 102. The connection between the electric wires 9, 9' and the tool support 102 is in this embodiment by welding. The diameter of the electric wires is between 10 μm and 200 μm, preferably between 60 μm and 120 μm. The Young's modulus of these wires is between 0.2 and 50 GPa, preferably between 0.5 GPa and 5 GPa. In the illustrated embodiment, the wires 9, 9' are arranged around the magnetic part 19, thus increasing its diameter. In such an embodiment, the above-mentioned diameters of the wires 9, 9'' are generally advantageous, since an increased size of the magnetic part 19 may make it more difficult to navigate in the vessel.

[0222] It will be appreciated that the electrical wires 9, 9' shown here can be used in any other embodiment disclosed herein to deliver electrical current / voltage.

[0223] Furthermore, to prevent dissipation of electrical current into the magnetic part 19, the magnetic part 19 is covered with a protective shell 111. The protective shell 111 is electrically insulating and can provide additional protection against corrosion. The protective shell 111 here consists of a layer of polyester resin with a thickness of 100 μm. However, in addition to or instead of this, the protective shell 111 may comprise any ceramic, polymer or composite material. For example, epoxy resin, silicone or epoxy-polyurethane blends are suitable materials. Carbon, silica-based ceramic, zirconium nitride or zirconia are also suitable materials. The thickness of the protective shell 111 may be in the range of 50 nm to 200 μm, preferably between 30 μm and 100 μm.

[0224] The tool support 102 can be used as a probe for electrothrombosis or cauterization. It will be understood that the shapes shown are exemplary and that other shapes may be used.

[0225] 10a and 10b show diagrammatically a method for manufacturing a device 1 according to the invention. The method shown here is particularly suitable for manufacturing a device 1 as shown in FIG.

[0226] FIG. 10a shows the device 1 with the magnetic part 19 assembled to the control line 23. The tool support 102 is connected to the magnetic part 19 in a manner substantially as disclosed herein. Here, a temporary layer 105 is arranged on the tool support 102. The temporary layer 105 comprises polyvinyl alcohol (PVA) and has a thickness of 100 μm. The thickness may be any value in the range of 50 μm to 200 μm. The temporary layer 105 completely covers the tool support 102 in the example shown, but does not extend beyond said tool support 102. Thus, the magnetic part 19 and the control line 23 are not covered by the temporary layer. A protective shell (not shown, see FIG. 10b) can be coated on the device 1 including the temporary layer 105.

[0227] Alternatively, the temporary layer 102 may be a silicone cover that may be stretched and placed over the tool support 102. The silicone cover preferably has a thickness of between 100 μm and 300 μm.

[0228] FIG. 10b shows the device 1 after completion of its manufacture. As explained in the context of FIG. 10a, a protective shell 111 is coated on the device 1 while the temporary layer 105 is still present. The protective shell can be cut off in the general area of ​​the tool support 102. The temporary layer 105 (see FIG. 10a) is then removed by dissolution in water. As a result, the protective shell 111 is located exclusively on the magnetic part 19 (where the temporary layer was present, the protective shell 111 is removed together with the temporary layer 105). The tool support 102 is not covered by the protective shell 111. Here, the device 1 is substantially similar to the device 1 shown in FIG. 9, the tool support 102 being configured to deliver an electric current. The absence of the protective shell 111 reduces the overall resistance and therefore makes it easier to deliver the electric current.

[0229] Alternatively, if a silicone cap is used as described above, the cap is cut and removed from the tool support 102 to remove the protective shell 111 .

[0230] The methods described above allow for a simpler and less error-prone way to selectively coat certain portions of a medical device with a protective shell and not other portions, especially since other methods (etching or scratching away the protective coating) can damage the device and increase scrap rates.

[0231] It will be appreciated that the above examples are exemplary in nature and that other portions of the medical device may additionally or alternatively be covered by the temporary layer.

[0232] Fig. 11a shows an embodiment of a device 1 with a chemical attachment element 10 during a procedure to retrieve a thrombus 2 from a blood vessel 3. The device shown here is similar to the device shown in Fig. 2b and is configured as a microrobot 18 with a magnetic part 19, a tool support 102 on which the adhesive 10 is arranged, and a control line 23 attached to the distal end 5 of the device 1. Here, the device further comprises an extendable element 12 configured as a spring. The spring 12 is configured to exert a compressive force of 0.1 N on the thrombus 2 in order to attach the adhesive 10 to the thrombus. The compressive force may be in the range of 0.05 N to 2 N.

[0233] Figure 11b shows a process similar to that shown in Figure 11a. However, the device shown here does not include a spring. Instead, the surgeon can use a magnetic field to exert a distal force on the magnetic element to attach the adhesive attachment element 10.

[0234] FIG. 12a shows a detailed view of the device 1 with the magnetic portion 19 and the control lines, where the mechanical attachment elements 11 are attached to the tool support 102 located at the distal end of the magnetic portion 19. It will be understood that the control lines 23 and the magnetic portion 19 are substantially similar to the control lines and magnetic portions described herein. The tool support 102 is glued to the magnetic elements. Four mechanical attachment elements 11 are placed on the tool support 102 by a screw mechanism (not visible) and comprise a shape memory alloy. Additionally or alternatively, form fitting and / or adhesives can be used. The mechanical attachment elements 11 have a diameter of 60 mpi and a length of 0.5 mm. The diameter may be in the range of 0.3 mm to 0.8 mm. Alternatively, for catheter-based devices, the diameter may be between 1 mm and 3 mm. Here, the mechanical attachment elements 11 are placed perpendicular to the surface of the tool support 102. However, any angle between 10° and 160° is conceivable, with angles between 60° and 120° being preferred.

[0235] Figure 12b shows the device 1 of Figure 12a with the mechanical attachment elements 11 bent outwards. The transition from the straight configuration to the bent configuration shown here can be triggered by a change in temperature, which may be achieved, for example, by delivering an electric current.

[0236] In this design, the mechanical attachment element 11 is based on a rigid wire that can bend in response to any stimulus known in the art. For example, as described above, the wire can comprise or be composed of Nitinol that bends due to an electric current.

[0237] To avoid complete bending of the wire, the wire may be placed inside a rigid shaft. The shaft may be made of polymer (e.g. PEEK) or metal (e.g. stainless steel AISI 316L). The inner diameter of the shaft may be 50 μm to 500 μm, preferably 100 μm to 300 μm. The outer diameter of the shaft may be 90 μm to 600 μm, preferably 140 μm to 350 μm.

[0238] As mentioned above, the wires may be arranged on the tool support 102. The connection between the wires and the tool support may be a through hole or via a matrix fixed to the support. The diameter of the wires may generally be between 50 μm and 300 μm, preferably between 75 μm and 150 μm. The ends of the wires may be shaped to improve the penetration of the proximal surface, in particular they may have a pointed and / or sharp shape.

[0239] FIG. 12c shows another embodiment in which the mechanical attachment elements 11 are bent inwards instead of outwards.

[0240] It will be appreciated that the features shown in Figures 12b and 12c can be combined, for example by configuring some mechanical attachment elements to bend inwards and some other mechanical attachment elements to bend outwards. It will further be appreciated that the shape change shown here, where a portion of the mechanical attachment element 11 bends to form a hook-like shape, is exemplary in nature. It is also contemplated that the mechanical attachment element 11 can be configured to form any other suitable shape, such as a corkscrew shape, a ring, a kink, and / or other shapes.

[0241] Mechanical attachment generally refers to attachment to the proximal surface of a thrombus using a mechanical system. It will be understood that the embodiments illustrated herein are exemplary in nature.

[0242] Generally, mechanical systems are used to penetrate the thrombus. The penetration is gradual, preferably at a speed of 0.01 mm / s to 15 mm / s, particularly preferably 0.1 mm / s to 1 mm / s, to avoid damage to the thrombus structure. An intact thrombus is advantageous, since there is less risk of breakage during retrieval or release of debris into the vasculature.

[0243] The number of mechanical attachment elements 11 arranged on the tool support 102 is generally between 1 and 20, preferably between 2 and 8.

[0244] Figures 13a to 13d show a method of attachment of a thrombus 2 by means of an attachment element 4 with a mechanical hook 11. The device 1 shown here is similar to the device of figure 12b.

[0245] FIG. 13a shows the device 1 in proximity to a thrombus 2 to be retrieved. As mentioned above, the device is substantially similar to the device described in FIG. 12b. In the delivery configuration, the mechanical attachment elements 11′, 11″ are configured to be oriented in a curved shape toward the center of the tool support 102 without a stimulation / trigger mechanism. A stimulation is now used to change the shape of the mechanical attachment elements 11 to a straight shape once the device 1 reaches the general area to be treated. Illustratively, the device 1 is shown here with one element 11′ still curved inwards and another element 11″ already in a straight configuration.

[0246] The mechanical attachment elements 11', 11" may be curved and capable of being actuated separately. To this end, each mechanical attachment element 11', 11" may be connected or connectable to a respective separate electrical connection. Such an arrangement may be advantageous when the thrombus has an irregular shape.

[0247] To provide separate actuation for each mechanical attachment element 11', 11'', the tool support 102 can include four parts glued together with an adhesive that provides electrical insulation. In this way, leakage of electrical current through the adhesive is prevented.

[0248] Each portion of the tool support 102 may be connected to two electrical wires. FIG. 13b shows the device 1 of FIG. 13a, where the mechanical attachment elements are configured in a straight shape as a result of completion of the shape change described in the context of FIG. 13a.

[0249] 13c shows the device of FIGS. 13a and 13b after penetration of the thrombus 2. Here, a magnetic field force exerted on the magnetic portion 19 by an external magnet (not shown) is used to propel the device 1 distally to penetrate the thrombus 2 at the proximal face 6. Generally, penetration of the thrombus 2 is achieved by: Magnetic displacement controlled by an external magnetic field as described herein, and / or Chemical driving forces (see Figure 23), and / or mechanical thrust, achieved for example by a spring (see FIG. 11a), and / or Blood flow propulsion achieved by an additional drag element installed on the control line 23 (see Figures 4a and 4b) This can be achieved by one of the following:

[0250] Penetration can be monitored via the length released by the control line driver. Additionally or alternatively, a pressure sensor can be attached to the control line, specifically a pressure sensor operably connected to the control line driver used to monitor retrieval of the thrombus.

[0251] Additionally or alternatively, penetration may be monitored by any imaging means known in the art, and for this purpose any part of the medical device, in particular the tool support and / or any attachment element, may be configured to be radiopaque and imaged when attached to the thrombus.

[0252] 13d shows the final attachment of the attachment elements 4 to the thrombus 2. Within the thrombus 2, the stimulation value can be increased to orient the mechanical attachment elements 11 outward and thus attached to the thrombus 2.

[0253] It will be understood that the particular shape changes described here are exemplary in nature and that any shape change that allows for initial penetration and subsequent attachment may be suitable. In particular, the attachment element 11 may be bent inwards rather than outwards (see Figures 12b and 12c).

[0254] Figures 14a and 14b show diagrammatically a method of thrombus attachment using a mechanical attachment element 11 substantially similar to the method shown in Figures 13a-13d.

[0255] Here, the device 1 further comprises a spring 12 integrated in a control line 23. The spring 12 is capable of providing a driving force for penetrating the thrombus 2 by the mechanical attachment element 11. It will be understood that any other driving mechanism can be combined with the embodiment shown here, such as the magnetic driving, in particular as described in the context of Figures 13a-13d.

[0256] FIG. 14a shows the device 1 in the general area to be treated, with the spring 12 compressed and locked.

[0257] FIG. 14 b shows the device 1 unlocked and the spring released, providing sufficient distal force to penetrate the thrombus 2 with the mechanical attachment element 11 .

[0258] The release of the spring 12 can be controlled mechanically or electrically. Mechanical release can be performed via a line attached to the spring 12. The spring 12 can be released by applying an external force to the line.

[0259] In particular, the spring 12 may include a shape memory material, such as a Nitinol alloy, and may be triggered to change from a first shape to a second shape.

[0260] The spring 12 may be released by removal or disintegration of a physical barrier. The spring may be made of a shape memory alloy, for example Nitinol, among others. The spring may be activated under a stimulus such as heat or electricity. To heat activate the spring, it may be coated with a heatable material. For example, the spring may be coated with gold nanoparticles that can be heated by exposure to infrared radiation. Another configuration may be a spring coated with superparamagnetic nanoparticles. These particles may be heated in an alternating magnetic field, such as those used in hyperthermia.

[0261] The physical barrier may be a lock. The lock may be set on a frame parallel to the compression spring. The lock is set perpendicular to the longitudinal direction. The lock may be removed by tension or by rapid degradation (bio-corrosion of magnesium under electric current). A part of the control 23 line may be formed by the spring 12, i.e. the control line 23 may be set between a control line driver (not shown) and the spring 12, and a second part of the control line 23 may be set between the spring 12 and the magnetic part 19.

[0262] The spring may have a diameter comprised between 50 μm and 800 μm, preferably between 100 μm and 300 μm. In the extended state as shown in Fig. 14b, the spring may have a length between 1 mm and 30 mm, preferably between 2 mm and 5 mm. In the compressed state as shown in Fig. 14a, the spring 12 may have a length in the range of 0.5 mm to 10 mm.

[0263] Preferably, the spring 12 is configured to change its length by at least 100%, and preferably 200%, when going from a compressed state to an extended state.

[0264] Preferably the spring is configured to exert a force of between 0.05N and 0.6N. The spring 12 may be formed by a control line 23. For example, the control line 23 may comprise a Nitinol wire formed into a helix. Under a stimulus, for example electricity, the Nitinol helix shape may be stretched. The diameter of the Nitinol helix may be between 50 μm and 900 μm, preferably between 100 μm and 300 μm.

[0265] It will be appreciated that the spring 12 shown here may be combined with any other attachment element, in particular a chemical attachment element including an adhesive (see, for example, FIG. 2b).

[0266] Alternatively, the spring 12 may be constructed as a separate element connected to the control line 23. Preferably, the spring is located between the magnetic portion 19 and the control line 23.

[0267] FIG. 15 shows a device 1 substantially similar to that of FIG. 2c when attached to a thrombus 2. Here, three mechanical attachment elements 11 are arranged in a row on the tool support. The attachment elements 11 have a minimum diameter of 120 μm and a maximum diameter of 200 μm towards the distal end of the elements 11. The elements 11 have a length of 300 μm. The mechanical attachment elements are fabricated from surgical grade steel and are coated with calcium chloride to promote thrombus formation which further secures the mechanical attachment elements 11 to the thrombus 2. Generally speaking, any adhesion mechanism (chemical or biological) can be used to provide additional fixation after penetration. Preferably, the adhesion mechanism is located in the proximal region of the elements 11.

[0268] Optionally, element 11 may be coated with an expandable coating, which can provide further fixation to thrombus 2 by expanding once element 11 is located within thrombus 2.

[0269] FIG. 16a shows an embodiment of the device 1 with a chemical attachment element 10 substantially as shown in FIG. 2b. A protective layer 15 is disposed on the attachment element 4 and on a portion of the magnetic portion 19. The protective layer 15 comprises a polymer that is soluble in aqueous solutions and dispersions, such as blood. Preferred polymers are polysaccharides, cellulose, starch and / or starch-based copolymers and derivatives, gelatin, hydroxypropyl methylcellulose (HPMC), gelatin-PEG, and / or PEO. The protective layer 15 is preferably configured in its thickness such that complete dissolution in blood requires a time longer than a typical treatment time. Typically, dissolution occurs within 5-30 minutes, preferably within 5-15 minutes. As a result, the device 1 can be guided through the vascular system to the target site without the chemical attachment element 10 coming into contact with blood. However, once the target site is reached, the protective shell 15 automatically dissolves within a short period of time, for example 5 minutes, after which the chemical attachment element is freed and can attach to the thrombus.

[0270] FIG. 16b shows a device 1 similar to that shown in FIG. 16b. A similar protective cap 15 is placed over the attachment element 4. Here, the attachment element 4 includes an elongated adhesive element 10 having sufficient rigidity to penetrate the thrombus (not shown). The element 10 may be, for example, a metal or polymer element with an adhesive coating. Thus, when released, the chemical attachment element 10 can penetrate the proximal surface of the thrombus, resulting in improved adhesive strength and safer retrieval. Although not shown here, the element 10 may be sharpened to improve penetration into the thrombus.

[0271] Figures 17a and 17b show an embodiment of the device 1 having a mechanical attachment element 11 that comprises a spring.

[0272] Figure 17a shows the device 1 in a delivery configuration. The spring 11 is compressed onto the tool support 102 and has a generally flat shape. A protective cap 14 is attached to the magnetic portion 19 to prevent contact between the spring 11 and body fluids and tissue.

[0273] Figure 17b shows the device 1 after activation, where the spring 11 is used to rupture a film 14' that is part of the protective cap 14. By stretching the spring 11, perforation of the film 14' is achieved.

[0274] Releasing the spring 11 to pierce the protective cap 14 may be accomplished by a locking mechanism that re-extends the spring 11 to its original configuration upon removal.

[0275] A Nitinol piece can be used to maintain the spring 11 in a compressed configuration. By application of an electric current, the Nitinol piece can be heated and change its configuration, thus releasing the spring.

[0276] Here, the protective cap 14 comprises a film 14' and a ring 14''. Preferably, the film 14' is made of a polymer such as PE. The film may be attached to the ring during a process by dip coating. Additionally or alternatively, the film 14' can be glued, fused or welded to the ring 14''. The thickness of the film 14' may be between 20 μm and 500 μm, preferably between 100 μm and 300 μm.

[0277] The ring 14'' can include or be composed of a polymer, such as PEEK (polyetherketone), polysulfone (PSU, PPSU), or polyethylene (HDPE). Additionally or alternatively, the ring 14'' can include a metal, such as stainless steel (304 or 316L), titanium, tungsten, etc.

[0278] The ring 14'' may further include a magnetic material such as iron oxide, iron, Nd-Fe-B, FePt, etc., which gives the ring 14'' magnetic properties. The magnetic ring may provide a magnetic interaction with the magnetic portion 19 used for guidance. This interaction improves the adhesion of the ring to the device 1.

[0279] The ring 14'' may be coated to reduce or prevent corrosion. The spring 11 may be further coated with a thrombogenic or adhesive material to provide additional biological or chemical attachment.

[0280] Additionally or alternatively, a thrombogenic material may be disposed on the tool support 102 .

[0281] It is also conceivable that the spring is used solely for the penetration of the protective cap 14, i.e. for the activation of a separate attachment mechanism.

[0282] For this purpose, a thrombogenic material can be fixed to the scaffold attached to the spring 11 and / or to the spring 11 itself (see FIG. 28). The scaffold can be made of synthetic fibers. The synthetic fibers can be made of bioabsorbable polymers such as polydioxanone (PDO) or poly-ε-caprolactone (PCL) or non-bioabsorbable polymers such as PET or polyurethane. Furthermore, the scaffold can also include or be composed of natural fibers, for example fibers of collagen. It is also conceivable to use a combination of natural and synthetic fibers. The thickness of the scaffold is between 50 μm and 2 mm, preferably between 150 μm and 300 μm.

[0283] In a particular embodiment, the springs 11, 12 may be located between the magnetic portion 19 and the tool support 102. The tool support 102 may be provided with cutting areas for cutting through the protective cap 14. Preferably, four cutting areas are arranged in the peripheral area of ​​the tool support.

[0284] Figures 18a and 18b show an alternative embodiment of an activatable device in a delivery configuration. The protective cap 14 is similar to the protective cap shown in Figure 17a and includes a polymer film 14' attached to a ring 14. The device 1 includes a chemical attachment element 10 formed as an adhesive.

[0285] 18b shows the device 1 in a cross-sectional view in a plane parallel to the longitudinal axis of the device 1. Here, the detailed structure of the device can be seen, in particular the tool support 102, the magnetic part 19 and the attachment of the control lines 23. Furthermore, the activatable break support 112 arranged within the chemical attachment element can be seen.

[0286] Here, the polymer film 14'' is generally placed under tension on the device 1. Thus, upon distal breakage, the polymer film 14'' has a tendency to fold over the ring 14'.

[0287] The thickness of the polymer film 14' may be between 20 μm and 700 μm, preferably between 100 μm and 200 μm. The polymer preferably exhibits a breaking strain of less than 100%. The polymer layer may be attached to the ring 14'' in any manner described herein, particularly in the context of Figures 17a and 17b.

[0288] To create tension in the polymer film 14', an activatable break support 112 is placed on the tool support 102. The polymer layer 14' can be tensioned by the break support 112 as the ring 14'' is moved proximally until it reaches its intended position.

[0289] The activatable fracture supports 112 are configured to change their shape under the action of a stimulus. For example, the activatable fracture supports 112 may be made of Nitinol. Thus, the activatable fracture supports 112 can extend when subjected to an electric current. As a result, additional tension is applied to the protective cap 14, and in particular to the polymer film 14'.

[0290] Alternatively, the activatable rupture support 112 may include a sharp element, such as a needle, that is disposed within the support 112 without contacting the polymeric film 14', but that can be moved to a position where it can contact the film 14' such that the film is punctured. The sharp element may include or be constructed of a metal, such as stainless steel or titanium. The sharp element may have a diameter between 40 μm and 200 μm, preferably between 70 μm and 150 μm. Additionally or alternatively, the sharp element may be configured to be anchored to the thrombus.

[0291] Additionally or alternatively, the activatable rupture support 112 can be configured to trigger a stimulus, such as an electrical current, that can destabilize and thus rupture the polymer film 14'. The electrical current, or heat caused by the electrical current, can destabilize the polymer film 14'.

[0292] The electrical wires can be connected directly to the activatable break support 112. Alternatively, the electrical current can be provided through the tool support 102, particularly if the apparatus is configured substantially similar to the apparatus shown in FIG.

[0293] 18c further illustrates the expansion of a swelling material 113 disposed between the magnetic portion 19 and the tool support 102. Here, the swelling material 113 is a swellable polymer and is configured to provide additional compressive force toward the thrombus (not shown). It will be understood that the swelling material 113, while shown here as an exemplary embodiment, is optional and not necessarily required in conjunction with the activatable break support 112. Additionally, the swelling material as shown here can be combined with any other embodiment disclosed herein.

[0294] In general, the swelling material, in particular any of the above-mentioned polymers, can be used to optimize the contact surface with the proximal surface of the thrombus. For this purpose, an attachment material, such as an adhesive material or a thrombogenic material, can be attached to the swelling material. The size of the material increases under hydration. During the swelling, the adhesive material can cover the activatable support.

[0295] Particularly suitable swelling materials are hydrogels (PVA, PVP, polyacrylamide), porous hydrogels, superabsorbent polymers (poly(acrylic acid (PAA), foams (PU)).

[0296] Figures 19a to 19d show various embodiments of a device 1 according to the invention formed by a catheter device 20. It will be understood that for clarity only the distal part 5 of the catheter device is shown.

[0297] Fig. 19a shows a catheter device 10 with a storage compartment 21. In the storage compartment 21, an attachment element 4 is arranged, which is attached to a guide wire 114. The guide wire 114 has sufficient stiffness to move the attachment element 4 back and forth and to provide a compressive force. Here, the catheter device further comprises a foil 16 made of a biocompatible polymer such as PE. The foil 16 seals the storage compartment 21 from the outside area and prevents the ingress of blood into the storage compartment 21.

[0298] As shown in Fig. 19b, by pushing the guidewire, the attachment element 4 can break the foil 16 and move to a position outside the catheter 20. Thus, the attachment element 4 is activated and can attach to the thrombus.

[0299] In addition to or instead of pushing the guidewire 114, saline injection can be used to move the attachment element 4, particularly by actuation of fluid pressure means.

[0300] Additionally or alternatively, the attachment element 4 attached to the line and / or guidewire may be flushed out of the catheter device 10. The attachment element 4 may be moved into the catheter when the catheter is positioned at the thrombus, or may be stored in the distal portion of the catheter device 10 during delivery.

[0301] The attachment element 4 can be moved out of the catheter device 10 by gas activation (e.g., air), liquid (e.g., saline), heat (e.g., electrical or induction), and / or electricity (e.g., piezoelectric material).

[0302] Figure 19c shows an alternative embodiment of a catheter device 20. The arrangement of the attachment element 4 in the compartment 21 of the catheter device 20 and the closure with the foil 16 are substantially similar to the catheter device of figures 19a and 19b. Here, an expandable element 12 is further arranged between the guidewire and the attachment element 4. The expandable element 12 can be, for example, a spring and is fixedly attached to the catheter 20 with respect to the storage compartment 21.

[0303] As shown in FIG. 19d, the attachment element 4 can be moved outside the catheter 20 by expanding the expandable element 12 without the need to push the guidewire 114, breaking the foil 16 in the process.

[0304] The expansion of the expandable element 12 can be triggered by any of the stimuli disclosed herein, in particular ultrasound, electricity, electromagnetic radiation (preferably UV radiation), heat, hydration.

[0305] It will be appreciated that any of the attachment elements described herein, particularly the biological, mechanical, and chemical attachment mechanisms, may be used in combination with the catheter device shown in Figures 19a-19d.

[0306] Figures 20a-20f show schematic diagrams of various embodiments of the attachment element 4. It will be understood that any of the attachment elements 4 shown herein can be combined with any of the catheter devices of the microrobotic devices disclosed herein.

[0307] FIG. 20 a shows an attachment element 4 comprising an adhesive composition 10 . FIG. 20 b shows an attachment element 4 with a fork-like mechanical attachment mechanism 11 .

[0308] FIG. 20 c shows an attachment element 4 comprising a thrombogenic material 7 . FIG. 20 d shows an attachment element 4 equipped with a suction mechanism 115 .

[0309] Figure 20e shows an attachment element 4 with thrombogenic fibres 7. Thrombogenic fibres 7 may be particularly advantageous as the fibres can adapt to the shape of the proximal surface of the thrombus, providing a very secure attachment.

[0310] FIG. 20f shows an attachment element 4 with electrical contacts 8 that can be used to induce electrothrombosis and / or cauterization.

[0311] Figures 21a-21f show schematic representations of different devices 1 according to the invention, configured as microrobots 18 with a magnetic portion 19 attached to a control line 23 at the distal end of the device 5. All the embodiments shown here comprise a protective layer 17 configured as a biodegradable polymer layer that prevents contact between the attachment element 4 and the blood during delivery. For illustrative purposes, only the delivery configuration is shown, but it will be understood that degradation of the protective layer 17 can release the attachment element 4 and result in attachment to the thrombus in the manner generally described herein. Alternatively, a non-biodegradable polymer may be used as the protective layer 17.

[0312] FIG. 21 a shows an embodiment in which the adhesive composition 10 is disposed on a magnetic portion 19 and protected by a protective layer 17 .

[0313] FIG. 21 b shows an embodiment with a fork-shaped mechanical attachment element 11 attached to a magnetic portion 19 .

[0314] FIG. 21 c shows an embodiment having a thrombogenic element 7 attached to a magnetic portion 19 .

[0315] Fig. 21d shows an embodiment with a screw-like element 116 that is particularly suitable for threading and attaching while forming a hole in the thrombus. A rotating external magnetic field can be used to rotate the drill-like element 116. For example, a permanent magnet can be rotated to generate such a rotating magnetic field.

[0316] FIG. 21e shows an embodiment with fibers 7 acting as biological attachment elements. The fibers 7 can be, for example, PTFE fibers coated with thrombin. Thus, coagulation can be triggered when in contact with blood and the clot formed can attach to the thrombus to be retrieved. The fibers 7 are very advantageous since they can adapt to the shape of the proximal surface of the thrombus to be retrieved. Additionally or alternatively, the fibers 7 can be coated with a dried adhesive composition. The dried adhesive can be reactivated when in contact with a fluid such as blood. Thus, once the fibers 7 come into contact with the thrombus, they can provide adhesive attachment.

[0317] Fig. 21f shows an embodiment in which a canal 117 is arranged in the control line 23. The canal 117 communicates with an opening 118 arranged at the most distal end of the magnetic portion 19. After removal of the protective layer 17, the opening 118 and the canal 117 can be used to provide suction to remove elements from the treatment site. The features of the embodiment shown here are particularly suitable in combination with the embodiment of Fig. 21f. The drill-like element 116 can remove parts of the thrombus, which can be immediately removed and carried away by the suction action provided by the canal 117 and the opening 118.

[0318] Figures 22a and 22b show an embodiment of the device 1 with a frame 22 as a protective element. For the sake of illustration, the device 1 is shown here with a biological attachment element 7. It will be understood that the frame 22 as shown here can be used in combination with any device 1 disclosed herein. Furthermore, it will be understood that further protective elements, such as protective layers and protective caps, can be used in combination with the frame 22 shown here. In particular, a coating can be used on the frame 22 to prevent blood contact.

[0319] Figure 22a shows the device 1 in a delivery configuration. The frame comprises a ring 119 from which four bars 120 extend distally and join together at a distance distal to the device 1. Additionally or alternatively, rods may be used. The frame thus prevents accidental contact between tissue and the attachment elements 4.

[0320] Figure 22b shows the device 1 of figure 22a after the frame 22 has been opened: the bars 120 have been uncoupled from each other and extend away from the ring 119. The attachment elements 4 are therefore exposed and can come into contact with the tissue.

[0321] Frame 22 is preferably activatable. Frame 22 is generally comprised of straight frame elements secured to rings 119 and activatable elements that, when activated, allow the frame to open.

[0322] Preferably, a polymer film is placed on the frame 22. Particularly preferably, a cap as shown in Figure 16 and / or Figure 17 is placed on the frame 22.

[0323] Preferably, the linear element may comprise or consist of a polymer, a ceramic, or a metal. Particularly preferably, stainless steel (316L), Nitinol, and / or titanium are used.

[0324] The diameter of the bars 120 of the frame 22 may be in the range of 80 μm to 300 μm, preferably 100 μm to 200 μm.

[0325] Preferably, the connection between the frame 22, and in particular the bar 120, and the ring 119 is welded.

[0326] The outer diameter of the frame 22 is preferably in the range of 80 μm to 400 μm, particularly preferably in the range of 100 μm to 200 μm. The inner diameter of the hollow frame may be in the range of 50 μm to 300 μm, preferably in the range of 70 μm to 150 μm.

[0327] Preferably, an electric current is used to open the frame 22. As a result, the bars 120 can bend radially away from the tool support 102. For example, the bending of the bars 120 can tear open the polymer layers.

[0328] The bars 120 of the frame 22 can be bent at an angle in the range of 10° to 170°, preferably 80° to 130° relative to the longitudinal axis of the device 1 (ie the axis perpendicular to the plane of the ring 119).

[0329] In some embodiments, a ring may be placed on the end of a protective element, such as the frame 22 and / or a protective cap as described herein, for added protection. The ring may break, for example, when the bar 120 bends. The ring may include or be made of a bioabsorbable polymer, such as PGA or PLGA. Additionally or alternatively, the ring may include or be made of a non-biodegradable or biodegradable polymer. The ring may include a predetermined break point to ensure a smooth break. For example, the predetermined break point may include a localized thickness reduction. The ring may have a diameter ranging from 100 μm to 1000 μm, preferably from 150 μm to 250 μm.

[0330] It is also conceivable that multiple trigger / activation mechanisms may be implemented in one device: for example, one of several activatable elements may be triggered by an electrical current, while another activatable element may be triggered by an increase in temperature.

[0331] Preferably, a protective layer is placed on the frame 22. The protective frame 22 makes it possible to minimize direct contact between the attachment elements and the vessel wall.

[0332] 23 shows an exemplary embodiment of device 1 having an additional propulsion mechanism. For purposes of illustration and clarity, device 1 is shown here without the attachment element. It will be understood that the propulsion mechanisms described herein can be combined with any device 1 disclosed herein.

[0333] An additional propulsion system shown here is a chemical system, the propulsion system including a reactive species configured to react with water or blood to form a gas that can be used to propel the device, here magnesium is used.

[0334] The magnesium (not visible) is embedded in a reservoir 24. The reservoir 24 is here configured as a tube placed around the magnetic portion 19 and attached to a shell 121. The shell 121 may be a protective coating as described herein, such as for example a resin shell. The reservoir 24 is closed with a plug 104. The plug is removably attached to the reservoir 24 and can be mechanically removed and / or decomposed by a stimulus. For example, the plug 104 may be attached to a line associated with the control line 23. A force acting on this line, for example caused by a control line driver, can remove the plug 104 and thus bring the contents of the reservoir, here the magnesium, into contact with the blood. As a result, gas is formed and is forced out through the opening 103 of the reservoir, thus providing a forward force to the device 1.

[0335] Here, plug 104 is made of titanium, however, any metal, such as tungsten or steel, and / or any polymer, such as silicon, PEEK, or any blend or combination thereof, may be used.

[0336] Here, the outer diameter of the plug 104 is 240 μm. The inner diameter of the tank 24 and the opening 103 is 100 μm. The outer diameter of the tank is 200 μm.

[0337] Preferably, the reservoir comprises or consists of a polymeric material such as PDMS, although other polymers may be used, as well as any blends or combinations of polymers.

[0338] 24a and 24b show an alternative embodiment of device 1 with a suction mechanism, which for illustrative purposes is configured as attachment mechanism 4. However, it will be appreciated that the suction mechanism as shown here can be used in combination with any other attachment mechanism disclosed herein, particularly to provide additional attachment in combination with other attachment means and / or to remove debris or thrombus residue to improve the safety of the procedure.

[0339] Here, a variant of mechanical attachment is performed by suction. The suction system comprises a suction surface 122 arranged on the tool support 102. The tool support 102 further comprises an opening 118 by which a suction action can be achieved. The tool support 102 can have a flat and / or curved shape and / or can be provided with peripheral protrusions, in particular to provide a sufficient fit with the shape of the thrombus. Here, the diameter of the opening 118 is 600 μm. The thrombus (not shown) can be pulled to the suction surface 122 and held by suction on the tool support 102. The suction mechanism shown here allows repeated attachment and reattachment of the thrombus, for example until a secure attachment is provided.

[0340] Figure 24b shows the device of Figure 24a in cross-section in a plane parallel to the longitudinal axis of the device. Here one can see the hollow channel 117 arranged through the control line 23 and the magnetic portion 19. The inner diameter of the channel 117 is in the range of 50 μm to 800 μm, preferably 70 μm to 200 μm. When in use, the suction mechanism is preferably activated when in proximity to a thrombus.

[0341] The hollow channel 117 is here configured as a channel within the control line 23, which acts as the suction channel. Alternatively, the suction channel may be configured as a separate element not integrated into the control line, particularly in combination with a catheter device (see Figures 19a-19d).

[0342] It will also be appreciated that hollow line 117 may be used for purposes other than providing a suction mechanism, and in particular may be used for fluid pressure activation, gas compression activation, or delivery of other fluids.

[0343] The Young's modulus of the control line 23 and / or channel 117 (particularly when configured as separate elements) may be in the range of 0.5 GPa to 100 GPa, preferably 0.5 GPa to 5 GPa, suitable for guidance within the vasculature.

[0344] In some embodiment configurations, the suction system, i.e. the tool support 102, may be directly connected to the hollow tube 117, i.e. without the magnetic portion 19 being disposed in between.

[0345] FIG. 25 shows a device 1 configured as a microrobot with a magnetic head portion 19 connected to a control line 23 and a mechanical attachment element 11. The device 1 is similar to the device described in FIG. 12b. The mechanical attachment elements 11 comprise a Nitinol-based shape memory alloy and are configured to bend outward when heated. Furthermore, the mechanical attachment elements 11 each comprise a shaft 130. The shaft 130 is configured to limit the bending of the mechanical attachment element 11. Thus, the shaft 130 can be used to achieve a specific shape for fixation, in particular a straight shape in the region close to the tool support 102. Additionally or alternatively, the shaft 130 may exhibit a higher stiffness than the mechanical attachment element 11. Thus, the shaft can protect the mechanical attachment element 11 during guidance.

[0346] Additionally or alternatively, the shaft 130 may be configured to trigger movement of the mechanical attachment elements 11. For example, the shaft may be connected to an electrical wire (see FIG. 9). Thus, movement of each mechanical attachment element may be controllable by application of an electrical current to the shaft 130.

[0347] Here, the shaft 130 is made of stainless steel and has an inner diameter of 200 μm and an outer diameter of 300 μm.

[0348] FIG. 26 shows a device 1 substantially similar to the device shown in FIGS. 12a-c. Additionally, the mechanical attachment element includes a thrombolytic coating 131, where the thrombolytic coating 131 is configured to release tissue plasminogen activator (t-PA). The t-PA can soften the thrombus tissue and reduce the force required for proximal attachment to the white clot. Additionally, the release of t-PA can reduce the frictional force between the thrombus and the vessel wall, thus reducing the force required for thrombus retrieval.

[0349] It will be appreciated that in addition, or alternatively, the coating 131 may be made of an expandable material that may essentially increase the adhesive force between the thrombus and the device.

[0350] It will be understood that the thrombolytic agents described herein can be used in combination with any other embodiment disclosed herein.

[0351] It will be appreciated that other thrombolytic agents than t-PA may also be used, or may be used alternatively.

[0352] Thrombolytic agents can be grafted directly onto the surface of the medical device, for example, by chemical vapor deposition (CVD) or physical vapor deposition (PVD).

[0353] Furthermore, the thrombolytic agent may be embedded in a matrix, preferably a polymer matrix. Non-biodegradable polymers such as silicone, PDMS, polyurethane, polyethylene-co-vinyl acetate (PEVA), poly(styrene-b-isobutylene-b-styrene), polybutylmethacrylate (PBMA), poly(vinylidene fluoride-co-hexafluoropropylene), phosphorylcholine, or polyester may be used. Biodegradable polymers such as PLGA (any PLA:PGA ratio, preferably 10:90), PDO, PGA, starch, cellulose, and / or chitosan may be used as well.

[0354] The matrix can be made of a gel, in particular a hydrogel. The gel can be degradable or non-degradable. The matrix can be placed on the tool support 102 and held to the tool support 102 by attachment elements, in particular mechanical attachment elements 11.

[0355] The thrombolytic matrix may be disposed on a scaffold on the tool support 102. The scaffold may be adhered onto the tool support. The thrombolytic matrix may exhibit holes for attachment elements. The matrix may have a flat or curved shape. The shape of the thrombolytic matrix may affect the release of the thrombolytic agent, so that the release kinetics may be adjusted by changing the shape of the thrombolytic matrix.

[0356] Typically, flat surfaces result in a relatively slow release of the thrombolytic agent. In contrast, curved surfaces can result in a faster release. For example, a dome shape can be used to achieve this effect, particularly with the apex facing the thrombus.

[0357] A molded scaffold can be used to provide the desired shape. A gel containing a thrombolytic agent can be placed thereon. The curvature can be selected so that the scaffold encompasses an angle between 10 and 45°, preferably 30°, in particular between the surface of the scaffold and the longitudinal axis of the device.

[0358] The thrombolytic matrix is ​​made up of different elements distributed on a tool support. Mixtures of polymers can be used to tailor the release kinetics.Low molecular weight polymers can be used to tailor the release kinetics.

[0359] Typically, low molecular weight polymers may degrade faster resulting in faster release of drugs, thrombogenic agents, thrombolytic agents, etc. Higher molecular weight polymers may degrade at a slower rate. Thus, the release kinetics of the active agent can be tailored by blending polymers with different molecular weights.

[0360] Typically, the ratio (by weight) of thrombolytic agent to polymer is between 0.1% and 50%, preferably between 2% and 15%.

[0361] The thrombolytic matrix can be disposed on any portion of the medical device, such as the mechanical attachment element 11 and / or the tool support 102, and allowed to dry.

[0362] Additionally or alternatively, the thrombolytic matrix may include or consist of particles. For example, the particles may be deposited by electrospraying. The thrombolytic matrix may be molded onto the tool support 102. Alternatively, the thrombolytic matrix may be molded or cast into a part that is placed directly on any portion of the device 1, such as the mechanical attachment element 11, the tool support 102, the shaft 130, etc.

[0363] The thrombolytic agent can be immobilized on any surface of the medical device 1, for example, by a peptide graft or a hydrolyzable linker.

[0364] In one method of attaching a thrombolytic agent to a surface, the thrombolytic agent is mixed with a water soluble polymer, such as PVA or PVP. The polymer solution is coated onto the surface and allowed to dry.

[0365] Any of the thrombolytic matrices described herein can be coated onto the mechanical attachment element 11 to produce a thrombolytic coating 131 .

[0366] 27 shows an alternative embodiment of a medical device 1 configured to release a thrombolytic agent, where the thrombolytic agent is embedded in a thrombolytic matrix 132 disposed on the tool support 102. The mechanical attachment element 11 pierces through the thrombolytic matrix 131.

[0367] The thrombolytic matrix 132 may be any thrombolytic matrix as described herein. Shown here are mechanical attachment elements 11 that substantially correspond to the attachment elements shown in Figures 12a-12c, but it will be understood that they are exemplary in nature. The thrombolytic matrix 132 shown here can be combined with any medical device 1 described herein.

[0368] Any thrombolytic agent can be protected from direct contact with the blood during delivery to the target site. The thrombolytic agent can be activated prior to or simultaneously with the attachment element.

[0369] Once activated, the thrombolytic agent can be delivered by the blood to the thrombus. Fig. 28 shows an embodiment of a medical device 1 with a mechanical attachment element configured as a spring 11. Furthermore, fibers 7 are arranged on the spring. The fibers 7 can be adhesive and / or thrombogenic fibers. The fibers 7 provide favorable attachment since the fibers 7 increase the contact surface with the thrombus (not shown).

[0370] Figure 29 shows a medical device 1, in which the attachment element 4 is provided with a suction mechanism. The embodiment shown is similar to the embodiment shown in figures 24a and 24b. Here, the hollow line 117 in the control line 23 does not pass through the magnetic head part 19. Instead, a Y-fork divides the hollow line 117 into two sub-lines 117', 117'' arranged around the magnetic head part 19. With such an arrangement, no modification of the magnetic head part 19 is necessary. The suction system 117, 118, 122 is connected to at least one hollow line 117.

[0371] It is also conceivable to use more than one hollow line 117. When multiple hollow lines are used, at least one line is used for suction. Other lines can be used to activate additional microrobotic functions, for example for injection of saline. Alternatively, different lines may be connected or connectable to different suction areas. Such a configuration can improve adhesion to the thrombus.

[0372] If there is one suction orifice 118, it may be of progressively larger diameter from proximal to distal to improve adhesion to the thrombus.

[0373] The inner diameter of the hollow sub-lines 117', 117'' is preferably 60 pm and the outer diameter is preferably 90 pm. The diameter of the control lines shown here is 70 pm. The diameter of the suction orifice 118 increases from 100 pm to 200 pm.

[0374] In certain embodiments, the control line 23 may be formed by hollow sub-lines 117', 117''.

[0375] Figure 30 shows a medical device 1 substantially similar to the device of Figure 21b. The device 1 comprises a control line 12, a mechanical gripper 11 and a protective coating 17. The medical device is shown before activation (A), during attachment (B) and during retrieval of a thrombus (2) (B).

[0376] The device 1 shown here further comprises a balloon 133 disposed on the control line 23 distal to the attachment element 4. The interior of the balloon 133 is in fluid communication with a hollow line 117 disposed within the control line and configured to inflate the balloon 133. The balloon 133 comprises a silicone pouch.

[0377] The balloon 133 allows for a reduction in blood flow / pressure in the region of the thrombus 2 before and during attachment to the mechanical gripper 11. To retrieve the thrombus 2, the balloon 133 can be deflated again.

[0378] Those skilled in the art will appreciate that all specific combinations of attachment elements, delivery systems, protective coatings, and activation mechanisms are exemplary in nature and may be used in any other combination.

[0379] Generally, instead of Nitinol, a conductive polymer may be used, the preferred conductive polymers being polythiophene (PT), PA, PPy, PANI, PEDOT.

[0380] In general, the adhesive compositions described herein may be used in an encapsulated form. 31a shows a first embodiment of device 1 having a sensor 134. It will be understood that device 1 is substantially similar to other devices described herein, and that sensor 134 may be combined with any device 1 described herein.

[0381] Here, the sensor 134 is configured as a pressure sensor. The sensor 134 is arranged between the tool support 102 and the magnetic part 19. Thus, when the tool support 102 is pressed against another structure (for example a thrombus), the force 136 exerted on this structure can be measured by the sensor 134. In particular, it is conceivable to measure the force by means of a deformation of the sensor.

[0382] FIG. 31b shows the embodiment of FIG. 31a in cross-section. The sensor 134 may be connected to a cable (not shown) and / or may have a wireless connection to an external device.

[0383] Here, the sensor 134 has an outer diameter of 300 μm, an inner diameter of 200 μm, and a height of 300 μm.

[0384] Fig. 32a shows a second embodiment of the device 1 with a sensor 134. Here, the sensor 134 is configured as a circumferential ring arranged around the tool support 102. The sensor 134 comprises a through hole 135 through which a fluid, e.g. blood, can flow. Here, the sensor 134 is configured as a flow sensor. Preferably, a microturbine (not shown) is arranged in the hole 135 to measure the flow rate of blood relative to the device 1. The sensor 134 can be connected by a cable (not shown) or wirelessly.

[0385] FIG. 32b shows the device 1 of FIG. 32b from a different perspective showing the proximal side of the sensor 134.

[0386] FIG. 33a shows a device 1 similar to other devices shown and described herein. The device 1 comprises a magnetic element 19 and an attachment element 4 configured to pull a thrombus (not shown) proximally. An activation mechanism 201 for the attachment element 4 is disposed in a delivery catheter 20 and operatively connected to the attachment element 4. Here, the device further comprises an in-growth tube 200. The in-growth tube is configured to be deployed by progressively filling it with gas. Alternatively, a liquid such as saline, a viscous solution, or a magnetic fluid may be used. The attachment element 4 may be any of the attachment elements disclosed herein and is attached to the in-growth tube. The in-growth tube may be bendable by the magnetic force exerted on the magnetic element. This may facilitate navigation in curved arteries, for example.

[0387] If the device according to the invention is moved mainly by drag and magnetic forces, the drag may be small in the blocked artery. As a result, the movement of the device 1 may need to be performed by magnetic forces. Depending on the location of the thrombus, especially the distance between the thrombus and the surface of the skull, the magnetic forces may not be sufficiently controlled to move the device 1. The growth tube can provide an alternative means to move the device in the vasculature, thus overcoming this problem.

[0388] FIG. 33b shows the apparatus 1 of FIG. 33a with the growth tube 200 extended. Fig. 34 shows diagrammatically an MRI system 202 that can be used to generate a magnetic field M for guiding a device according to the invention. The relative strength of the magnetic field M is shown diagrammatically. The MRI system 202 can be part of a system with a device (not shown). The magnetic gradients generated by the system can be used. Preferably, the device (not shown) is placed in an area of ​​low field strength of the magnetic field M, in particular by a delivery system.

[0389] FIG. 35 shows a device that can be guided by the MRI system shown in FIG. 34. The device 1 comprises an attachment element 4, a magnetic element 19 and a control line 23. When located in the vicinity of the MRI system, the device 1 may be exposed to strong attractive forces by the MRI system, at least initially. To avoid damage to the control line 23 or its connection to a distal part of the device 1 (e.g. the magnetic part 19), the device 1 may be released at high speed. A high speed in this context may be between 2 cm / s and 100 cm / s, preferably between 10 cm / s and 30 cm / s. Additionally or alternatively, the device 1 may comprise a retention line. The device 1 shown here comprises a first retention line 203′ and a second retention line 203″. The retention line reduces the force exerted by the magnetic force of the MRI system on the control line 23.

[0390] The retention lines 203', 203'' may be detachable from the distal part of the device 1. Detachment can be achieved, for example, by applying an electric current. Here, both retention lines 203', 203'' have a diameter of 100 μm and are made of polyurethane.

[0391] The delivery system may be connected to the delivery catheter via tubing, preferably flexible tubing, which may have an inner diameter between 0.5mm and 4mm, preferably between 0.8mm and 2.5mm.

[0392] Removal of the retention line may be advantageous if the retention line is too rigid for guidance but is necessary to prevent breakage upon initial introduction into the body (due to strong magnetic forces), thus allowing the retention line to be used during introduction and then removed prior to navigation within the vessel.

[0393] Fig. 36a shows a catheter device 20 configured to deliver at least part of a thrombus retrieval device 1. The device 1 may be any device 1 shown herein and comprises a control line 23, an attachment element 4 and a magnetic element 19. The catheter 20 may be controlled by a guidance system. The catheter comprises a balloon 204 that may be inflated upon activation by an activation mechanism 205. When inflated, the balloon 204 may reduce blood flow in the vessel in the area where the balloon is located. The reduced blood flow may be advantageous both during guidance of the device and during retrieval of the thrombus.

[0394] The balloon may not be fully inflated to avoid complete stagnation of the flow. The outer diameter of the catheter may be between 0.8 mm and 5 mm, preferably between 1 mm and 2 mm. The catheter further comprises a diaphragm 206 at the distal opening of the catheter tube. The diaphragm 206 may be closed when the device 1 is housed within the catheter device, either during delivery or after retrieval of the thrombus (see FIG. 36c). In particular, the diaphragm 206 may retain the thrombus within the catheter. When the diaphragm 206 is opened, its opening may have a diameter that may be between 1 mm and 4 mm, preferably between 2 mm and 3 mm.

[0395] Figure 37 shows an embodiment of the device 1 based on and substantially similar to the embodiment of Figures 24a and 24b. Here, the device 1 further comprises an electric ring 208 arranged against the attachment element 4 designed as a suction cup. When the attachment element 4 comes into contact with a thrombus (not shown), a vacuum can be drawn through the opening 118, which draws the thrombus at least partially into the cup and onto the surface 122. Applying an electric current to the electric ring 208 through the electric wire 207 can increase the temperature of the ring 208 and thus promote the attachment of the thrombus to the suction cup, for example by partial and / or localized drying.

[0396] It is contemplated that there may be multiple suction cups, for example three suction cups. In particular, when the device comprises or consists of a microrobot, the device may get stuck during navigation within a blood vessel, for example due to curvature of the arterial wall. Thus, in some embodiments, one or more balloons may be positioned at a distal region of the device (e.g., around the distal region of the microrobot or catheter device).

[0397] FIG. 38a shows an embodiment of the microrobot 1 with two balloons 204′, 204″. Either of the balloons 204′, 204″ can be filled with a gas or a solution. A radiopaque saline solution is then used to inflate the balloons 204′, 204″ via a hollow control line 23. An activation system 205 is connected to the inlets of the first balloon 204′ and the second balloon 204″, allowing selective inflation of either balloon. Both balloons 204′, 204″ have a cylindrical shape, but may also be spherical. The activation system 205 may comprise a membrane or a solenoid valve. The activation system is opened under a stimulus such as electricity, heat or exposure to an alkaline or acidic solution. Both balloons 204′, 204″ have a wall thickness of 120 μm and are substantially made of polyurethane foil. Alternatively, silicone may be used.

[0398] FIG. 38b shows the device 1 of FIG. 38a with the second balloon 204″ inflated but the first balloon 204′ not inflated. To do so, the activation mechanism 205 was selectively activated only for the second balloon 204′ with an electrical pulse. As a result, radiopaque saline is forced into the second balloon 204″, resulting in the second balloon being inflated.

[0399] Additionally, the balloons 204', 204'' may be configured and used for stabilization within the lumen of a blood vessel (eg, an artery) and / or proximal to a thrombus.

[0400] The control lines may be made of highly elastic materials such as silicone, so that they can stretch or lengthen when steering or retracting a device. Increasing the stiffness of the material to reduce stretching increases bending stiffness, and therefore makes the control lines less flexible for steering in tortuous networks.

[0401] Some embodiments therefore include one or more retaining lines, which are particularly advantageous when hollow control lines are used.

[0402] FIG. 39a shows an embodiment of the device 1 with first and second retention lines 203′, 203″. The retention lines 203′, 203″ have a diameter of 70 μm and are arranged separately from the control line 23. The retention lines 203′, 203″ are able to restrain the stretching of the control line 23. Both retention lines are attached to the magnetic part 19 of the device by means of an adhesive.

[0403] FIG. 39b shows an alternative embodiment in which the first and second retention lines 203', 203'' are disposed within the control line 23.

[0404] The embodiment shown in Figures 39a and 39b includes an attachment element 4. However, it will be understood that any device disclosed herein may include one or more retention lines as shown herein.

Claims

1. A medical device (1) for retrieving a thrombus (2) from a blood vessel (3), comprising an attachment element (4) disposed at the distal end (5) of the medical device (1), wherein the attachment element (4) is configured to adhere to the proximal surface (6) of the thrombus (2) such that the thrombus (2) can be retrieved by applying a tensile force (F) to the attachment element (4). Medical device (1).

2. The medical device (1) according to claim 1, wherein the attachment element (4) comprises a biological adhesion mechanism (7), preferably a thrombogenic element, particularly a thrombogenic element containing one of thrombin, calcium chloride, and collagen, particularly preferably a dried coagulant layer.

3. The medical device (1) according to claim 1, wherein the attachment element (4) is attached to, or attachable to, an electrical conductor (9, 9') and comprises an electrical contact (8) configured to cause adhesion through tissue changes caused by a temperature increase and / or current / voltage.

4. The medical device (1) according to claim 1, wherein the attachment element (4) comprises a chemical adhesion mechanism (10), preferably an adhesive composition, particularly preferably a dried adhesive composition.

5. The medical device (1) according to claim 1, wherein the attachment element (4) comprises a mechanical adhesion mechanism (11), particularly a mechanical adhesion mechanism (11) including a shape-changing element (12), preferably a mechanical adhesion mechanism (11) selected from the group including hooks, forks, springs, and spikes.

6. The medical device (1) according to claim 1, further comprising a suction mechanism (13), preferably, the attachment element (4) comprises the suction mechanism.

7. The medical device (1) according to claim 1, further comprising an activation mechanism (14; 15; 16; 17), wherein the attachment element (4) has an activated state and a non-activated state, and in the non-activated state, the attachment element (4) is configured not to interact with the blood vessel wall (3) or the thrombus (2), and in the activated state, the attachment element (4) is configured to interact with the thrombus (2), and the activation mechanism (14; 15; 16; 17; 22) is configured to bring the attachment element (4) at least from the non-activated state to the activated state.

8. The medical device (1) according to claim 1, comprising a microrobot (18) provided with the attachment element (4).

9. The microrobot (18) comprises at least one of a magnetic part (19) and a control line (23), the magnetic part (19) is configured to interact with a magnetic field, preferably an external magnetic field, and / or the control line (23) can be attached to, or is attached to, the distal part of the microrobot (18). The medical device (1) according to claim 8.

10. The medical device (1) according to claim 1, formed by at least a part of a catheter device (20).

11. The medical device (1) according to claim 7, wherein the activation mechanism (14; 15; 16; 17; 22) comprises a mechanism configured to release at least the attachment element (4) from the storage area (21) of the medical device (1).

12. The medical device (1) according to any one of claims 7 or 11, wherein the activation mechanism (14; 15; 16; 17; 22) contains an activatable material.

13. The activation mechanism of the medical device (1) according to claim 7 comprises a protective layer selected from the group consisting of a protective layer (14; 15; 17; 22), preferably a protective coating (17), a protective sheath (14), a protective frame (22), and a protective cap (15).

14. The medical device (1) according to claim 1 further comprises an extension member, preferably a spring (11, 12), which is axially extensible and configured to generate an axial force on the thrombus (2).

15. The medical device (1) according to claim 1 further comprises a sensor (134).

16. The medical device (1) according to claim 1, wherein the attachment element (4) comprises a substantially flat surface (F) configured to attach to the thrombus (2).

17. The size (S) of the medical device (1) in a direction (r) perpendicular to the longitudinal axis of the medical device (1), preferably the maximum size of the attachment element (4), is less than 3 mm, preferably less than 1 mm, and particularly preferably less than 0.8 mm when attached to the thrombus (2).

18. The attachment element (4) is smaller than the maximum size of the medical device (1) in a direction (r) perpendicular to the longitudinal axis (L) of the medical device (1) when attached to the thrombus (2).

19. The maximum size of the attachment element (4) in a direction perpendicular to the longitudinal axis of the medical device is less than 10%, preferably less than 5%, and particularly preferably unchanged, between the activated state and the non-activated state.

20. The medical device (1) according to claim 1 further comprises a propulsion member (24), preferably a chemical propulsion member, for generating an axial propulsion force.

21. The medical device (1) according to claim 1, further comprising at least one resistance member (25), preferably an activatable resistance member configured to increase the force acting on the medical device.

22. A system comprising a medical device (1), preferably the medical device (1) according to any one of claims 1 to 21, a control unit, and an imaging device, wherein the control unit is configured to guide the medical device (1) to a target position within the vascular system.

23. A method of manufacturing a medical device (1), preferably the medical device (1) according to any one of claims 1 to 21, comprising: - providing a flexible line to which a magnetic part (19) and an attachment element (4) are attached; - coating at least a part of the attachment element (4) with a temporary layer; - coating at least a part of the medical device (1), preferably with a resin and / or polymer, particularly preferably including a dipping step and / or a drying step; - removing the temporary layer; and including.

24. A method of retrieving a thrombus (2) from a blood vessel with a medical device (1), preferably using the medical device (1) according to any one of claims 1 to 21, comprising: - introducing the distal end (5) of the medical device (1) provided with the attachment element (4) into the blood vessel; - guiding the medical device (1) to the target position; - optionally activating an activation mechanism (14; 15; 16; 17; 22) such that the attachment element (4) is converted from a non-activated state to an activated state in which it can attach to the thrombus (2), preferably proximal to the thrombus (2); - attaching the attachment element (4) to the thrombus (2) proximal to the thrombus (2); ・Optionally, stretching the thrombus (2) to reduce the diameter of the thrombus (2) in a cross-section perpendicular to the longitudinal axis of the blood vessel (3); ・Removing the thrombus (2) from the target site by pulling the thrombus (2); A method comprising the steps of.

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