Patent Application
20250127531
The present invention relates to a medical device, a system and a method for retrieving a thrombus from a vessel, and to a method of producing a device according to the preamble of the independent claims.
It is known in the prior art to use medical devices to remove thrombi from vessels.
For example, US 2017/119407 discloses aspiration devices for removal of blood clots.
US 2013/060269 discloses a stent device which penetrates a material in order to anchor it.
US 2013/289578 discloses a catheter device for surrounding and gripping blood clots.
However, devices and methods known in the art have several drawbacks. For example, known devices are typically large, which may limit the accessible locations in a vessel system and increase the risk of unwanted interaction with tissue which may lead to injuries. Furthermore, large devices may be more difficult to operate by a surgeon. Furthermore, known devices may require complicated mechanisms for safe removal of a thrombus. In addition, treatments using known devices and methods may take a long time, leading to higher patient discomfort and higher risks associated with the treatment.
Thus, the object of the present invention is to overcome the drawbacks of the prior art, in particular to provide a device, a system and a method to provide easy, safe and versatile treatment of vessels.
This and other objects are achieved by the medical device, the system and the methods according to the characterizing portion of the independent claims of the invention.
The medical device according to the invention is adapted for retrieving a thrombus from a vessel. The device comprises an attachment element arranged at a distal end of the medical device. The attachment element is adapted to attach to a proximal face of the thrombus such that the thrombus is retrievable by exerting a pulling force on the attachment element.
In some embodiments, the device comprises more than one attachment element, for example two attachment elements or three attachment elements. Multiple attachment elements can reduce the mechanical stress on a thrombus during retrieval and thus make the treatment safer.
The attachment element may be any element adapted to attach to a thrombus, in particular it may comprise structure for mechanical interaction such as forks, but also glues, fibers. The attachment element may further be connected to a main body, for example a magnetic part, in particular through a form-fit connection.
In one particularly preferred embodiment, the medical device comprises a magnetic part which is attached to a controlling line, and a connection element for an anchoring element that comprises or consists of the attachment element. The anchoring 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.
In certain embodiments, the medical device comprises or consists of a catheter device and/or a microrobot.
Proximal attachment of the device at a thrombus is particularly advantageous because it enables a quick attachment without the need to penetrate or navigate device elements in our around the thrombus. In addition, because a pulling force is exerted on the proximal face of the thrombus, the thrombus may be stretched, which may lead to a smaller diameter, thus reducing the necessary pulling force, as the friction between the vessel wall and the thrombus may be reduced.
A proximal face of the thrombus may be understood as the proximal-most area of the thrombus in a direction towards the device, i.e. in a direction of intended removal of the thrombus.
The attachment element may comprise a biological attachment mechanism. In particular, the biological attachment mechanisms 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.
The thrombogenic element may comprise or consist of fibers with thrombogenic properties.
Biological attachment mechanisms may provide a particularly simple way of attaching a thrombus as mechanisms inherent in a human or animal body may be capitalized on. For example, thrombogenic elements may form an attachment material from blood coagulation. Thus, a portion of the attachment material does not need to be delivered to a treatment site.
The biological attachment mechanism may be any mechanism which triggers a biological reaction with tissue and/or blood, for example coagulation.
The thrombogenic element may be delivered in a dried state, for example as a dried coagulant layer. This may enable particularly easy activation using a body fluid such as blood. Thus, the dried coagulant layer may become adhesive only when it is in contact with blood or another bodily fluid, or water or saline delivered to the treatment site.
The attachment element, preferably the biological attachment mechanism, may comprise electrical contacts attached or attachable to an electrical conductor. The medical device may thus, particularly preferably, comprise an electrical conductor attached or attachable to an energy source. The electrical contacts are adapted to create attachment through tissue change induced by temperature increase and/or electrical current/voltage.
The energy source may be electrical energy from a building installation, a converter connected thereto, a battery, or any other electrical energy supply known in the art.
Preferably, the attachment element is adapted to provide attachment to a thrombus via cauterization and/or electro-thrombosis.
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.
Chemical attachment mechanisms such as adhesive compositions may be particularly advantageous as they may provide instant attachment, e.g. without time lapse for coagulum formation, and/or without further elements, e.g. it may not be necessary to deliver further/larger elements to the treatment site.
The adhesive composition may be activatable. In particular, the adhesive composition may be activatable by temperature, light, humidity, and/or a change in pH.
The attachment element may comprise a mechanical attachment mechanism, in particular a mechanical attachment mechanism comprising a shape-change element. The mechanical attachment mechanism may be selected from a group comprising a hook, a fork, a spring, and a spike.
Mechanical attachment mechanisms may be particularly safe as no chemically or biologically reactive elements need to be introduced into the body. Even if biological or chemical attachment mechanisms are combined with a mechanical attachment mechanism, mechanical attachment mechanisms can be advantageous because they may provide more secure and easily adjustable attachment.
A shape change element may in particular comprise or consist of a self-expansive material for increasing a force toward a thrombus, for example to enhance a mechanical attachment or an adhesive force.
The shape-change element may also comprise or consist of a shape memory material, for example a Nitinol alloy.
Preferably, the shape-change element is adapted to change from an axial/linear shape to a radial/three-dimensional shape, for example a helix or a hook. Additionally or alternately, the shape-change element may be configured to adopt an umbrella shape upon the change of its shape.
Particularly preferably, a mechanical anchor made of a shape memory alloy may be configured to have a straight shape adapted to change its shape upon attachment to a thrombus, in particular to a cork-screw or hook-shape.
Any shape known in the art suitable to provide attachment after penetration may be used, in particular screw shapes.
The medical device may further comprise a suction mechanism. Preferably, the attachment element comprises the suction mechanism.
The suction mechanism may assist in attachment of the attachment element to the thrombus. Additionally or alternatively, the suction mechanism may be used to remove fluids and/or tissue from the treatment site. For example, blood may be aspirated from the treatment site in order to remove thrombus debris to reduce risks for the patient. Additionally or alternatively, soft thrombus parts (such as red thrombi) may be aspirated in order to reach and attach to a more rigid part of the thrombus.
Additionally or alternatively, a suction mechanism may be used to activate a mechanical element, for example by utilizing a pneumatic and/or hydraulic mechanism. To this end, the medical device may further comprise a canal which is in operable connection with the suction mechanism such as to provide pneumatic or hydraulic line.
In some embodiments, an electric element, preferably a ring, is arranged with respect to the attachment element such that an electric current may be applied to a thrombus after it has been sucked by the suction mechanism.
It will be understood that any combination of biological, chemical and/or mechanical attachment mechanisms described herein is possible. It will also be understood that an attachment mechanism may be biological, chemical and/or mechanical simultaneously. As such, a mention of one of a biological, chemical, or mechanical attachment shall not necessarily be understood as excluding the other two mechanisms unless stated otherwise. For example, a mechanical attachment mechanism may be assisted by adhesion and/or coagulation. However, it is of course possible to configure an attachment mechanism as being only mechanical, only biological, or only mechanical.
Preferably, the medical device comprises an activation mechanism. The attachment element may have an activated state and a deactivated state. In the deactivated state, the attachment element is adapted to not interact with a vessel wall or with the thrombus. In the activated state, the attachment element is adapted to interact with the thrombus. The activation mechanism is adapted to bring the attachment element at least from the deactivated state to the activated state.
An activation mechanism may be advantageous because inadvertent interaction between the attachment element and tissue and/or blood can be prevented during delivery, which may lead to safer treatments and less complications, and easier delivery.
Preferably, the medical device comprises a microrobot equipped with the attachment element.
The microrobot may comprise at least one of a magnetic part and a controlling line. The magnetic part may be adapted to interact with a, preferably external, magnetic field. Additionally or alternatively, the controlling line may be attachable or attached to a distal part of the microrobot.
The controlling line may be adapted to pull back a thrombus. In particular, it may be adapted, by material choice and/or appropriate dimensions, to have a minimum strength in the range of 0.5 N to 20N, preferably 8 N to 12 N.
The microrobot may further comprise a holding line which has a higher elastic modulus than the controlling line. The bending stiffness of the holding line may be similar to the bending stiffness of the controlling line. The holding line can prevent excess stretching of the controlling line without impacting navigation.
For example, the controlling line may substantially consist of a hollow tube made of silicone, having a high flexibility and a breaking strain of approximately 300%. In such an example, the holding line may be made of a polyamide with a breaking strain around 40%.
The diameter of the holding line may be between 20 μm and 1 mm, preferably between 50 μm and 200 μm.
The holding line may comprise or consist of a polymer, for example polyamide, polyurethane or elastomer such as silicone or a silicone-based material with a moderate breaking strain (lower than 100%) or a low breaking strain (lower than 10%) may also be used.
The holding line may be part of the controlling line or a separate element, wherein the holding line may have a few attachment points with the controlling line and/or the device.
The holding line may be fixed to the device by glue, a knot, glue and resin, or a combination of different assembly methods which are known in the art.
The holding line may have a Young's modulus of 0.01-50 GPa, preferably 1-20 GPa, particularly preferably 1-3 GPa. The holding line may have a bending stiffness of 0.0001-1 N·mm2, preferably 0.001-0.02 N·mm2.
The holding line may have a diameter of 20 μm to 500 μm, preferably 40 μm to 80 μm, particularly preferably 70 μm.
The medical device may be formed by at least a part of a catheter device. Additionally or alternatively, a guide wire may also be used, or any other intravascular device.
The activation mechanism may comprise a mechanism adapted to release at least the attachment element from a storage area of the medical device.
For example, the attachment element may be stored in a compartment of a catheter or a microrobot.
In some embodiments, the medical device comprises a catheter which is adapted to deliver a microrobot. The catheter may comprise a balloon. The microrobot may be adapted to be pulled back into the catheter after attachment to a thrombus.
Additionally or alternatively, the attachment element may be encapsulated.
The activation mechanism may comprise an activatable material.
The activatable material may be activatable by any activation mechanism described herein or known in the art. For example, the activatable material may be activatable by exposure to a magnetic field, magnetic gradient, ultrasound, or light (such as light-curable adhesives). Additionally or alternatively, the activatable material may be activated by temperature increase, exposure to humidity/water, change in pH, in response to a salt concentration, activated inflammation species, change in the blood flow velocity, electricity, or others
The activation mechanism may comprise a protection layer. The protection layer may be selected from a group comprising a protection coating, a protection sheath, a protection frame, and a protection cap.
In general, a protection layer may be removed to provide such as to bring the attachment element from a deactivated state to an activated state.
In general, the protection layer may be biodegradable or non-biodegradable, may be a cap that may be removed, or a layer that breaks apart, or comprises a hole and/or a predetermined breaking point.
A protection coating may be soluble in water or blood such as to automatically activate the attachment element after a certain exposure time in blood. The exposure time may be adapted to be in the range of, for example, 10 sec to 20 min, preferably 2 to 5 min.
The protection coating can comprise or consist of biodegradable polymers such as PGA and/or PLGA. In such a configuration, the coating is divided into parts. The natural mechanism for the degradation is the hydrolysis. Hydrolysis typically takes place within several minutes after direct contact with physiological solutions.
To achieve sufficiently fast degradation, PGA may have a very low molecular weight. Once hydrolysis of PGA has started, the mechanical strength of the biodegradable coating decreases and thus breaking of the protection coating is easier.
Preferably, the protection coating comprises or consists of a mixture (blend and/or co-polymer) of different polymers. Thus, mechanical properties as well as the degradation rate may be tuned by adjusting a mixing ratio.
Degradation may be accelerated under stimuli such as heat. A bioresorbable coating can be made of biodegradable polymer loaded with nanoparticles. The polymer exhibits a low degradation temperature of 40-60° C. The nanoparticles can be made of gold, Fe2O3, Fe3O4 and/or silver. The protective coating is degraded by heat generated by the nanoparticles under a stimulus such as light and/or a magnetic field. The coating may then break into small biodegradable parts which are flushed away by the blood flow.
In another embodiment, the protection coating comprises a membrane made of magnesium powder acting as a linker embedded in a bioresorbable polymer. The degradation of the powder is accelerated by applying a current provided by the controlling line. The degradation of the particles can contribute to the breaking of the coating.
Additionally or alternatively, the biodegradable coating can be made of magnesium or a composite which is degraded by biocorrosion. The biocorrosion process may be accelerated by applying a current.
The coating can be made of a biodegradable part and a non-biodegradable part. The non-biodegradable part remains attached to the device, in particular the attachment element. The biodegradable part may be removed from the device during the removal/degradation of the protective coating.
The coating may be made of non-biodegradable polymers such as silicon, polyurethane with polycarbonate backbone or PTFE, for example. The non-biodegradable polymer may be broken during the opening. Preferably, the non-biodegradable coating is broken by tearing in order that the coating remains attached to the device and/or the attachment element. Preferably, for a capsule, polymers such as PVDF, HDPE, PMMA, LCP, PA46, PI can be used.
A protection frame may prevent direct contact between the attachment element and a surrounding tissue until removal of the protection frame.
The medical device may further comprise an extension member. The extension member may preferably comprise or consist of a spring. The extension member may be extendable in an axial direction and may be adapted for the generation of an axial force on the thrombus.
The extension member may be arranged at a proximal or distal end of the medical device. The extension member preferably is part of the attachment element.
In particular, the axial force provided by the extension member may additionally or alternatively be adapted to be used to open and/or remove the protection layer.
The medical device may further comprise a sensor.
Preferably, the sensor is adapted to determine incorrect or insufficient attachment of the attachment element to the thrombus.
The sensor is preferably selected from the group comprising a force sensor, a temperature sensor, a pH sensor, an attachment sensor, a flow sensor, a pressure sensor, and a contact surface sensor.
For example, the sensor may comprise force sensor adapted to measure a pulling force acting on the thrombus and/or a sensor adapted to measure the contact surface between the attachment element and the thrombus.
In particular, a pressure sensor may be used to monitor whether or not a the attachment element is in contact with the thrombus and/or evaluate the nature of the thrombus.
Additionally or alternatively, the sensor may be adapted to monitor whether the attachment element is sufficiently attached to the thrombus during retrieval.
Preferably, the attachment element comprises a substantially flat surface which is adapted for attachment to the thrombus.
Substantially flat may be understood as having a limited, maximum curvature (i.e. a minimum radius of curvature). In particular, the substantially flat surface may exhibit a minimum radius of curvature of 3 cm, preferably 5 cm, particularly preferably 50 cm.
Additionally or alternatively, the attachment element may have a maximum extension in an axial direction of the medical device of 5 to 40 mm, preferably 15 to 25 mm, particularly preferably 20 mm. For example, the attachment element may be the distal-most portion of the medical device in its intended use. Alternatively, the maximum extension may be between 1 and 5 mm, preferably 2 mm.
Preferably, a size of the attachment element in its activated position when attached to the thrombus is smaller than 3 mm, particularly preferably smaller than 1 mm, even more preferably 0.8 mm, in a direction perpendicular to a longitudinal axis of the medical device. Preferably, this size is the maximum size of the attachment element perpendicular to a longitudinal axis of the medical device.
Thus, the attachment element may have a size which allows for navigation even in small vessels and thus provides more versatile treatment options.
Preferably, the size of the attachment element is between 0.2 and 5 mm, particularly preferably between 0.3 and 1 mm.
Preferably, the attachment element is smaller, in a direction perpendicular to the longitudinal axis of the medical device, than a maximum size and/or a size of any other portion of the medical device, when attached to the thrombus and/or in the activated state.
Thus, it can be ensured that any location that is accessed by the medical device can be treated using the attachment element as the attachment element will fit into the vasculature at the treatment location.
Particularly preferably, the maximum size of the medical device is a size of the magnetic part in a direction perpendicular to the longitudinal axis of the medical device.
Preferably, the attachment element is configured such that a maximum size of the attachment element in a direction perpendicular to a longitudinal axis of the medical device differs by less than 10%, preferably 5%, between the activated and the deactivated state. Particularly preferably, the maximum size of the attachment element in a direction perpendicular to a longitudinal axis of the medical device remains constant.
If the maximum size of the attachment element differs between the deactivated and the activated state, it is particularly preferred that said maximum size is larger in the activated state compared to the activated state.
The difference in said maximum size may be in an axial (i.e. along the longitudinal axis of the medical device) or radial (i.e. perpendicular to the longitudinal axis of the medical device) direction, or both.
Preferably, the medical device comprises a, preferably chemical, propulsion member generating an axial propulsion force.
The medical device, in particular the magnetic part with the attachment element, may typically be moved forward mainly by a flow force exerted by blood. When a thrombus is present, the flow can be modified 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 is particularly advantageous, but not necessary to the invention, as a magnetic force exerted by a magnetic field on the magnetic part may be sufficient.
The additional propulsion system may be mechanical. For example, it may comprise a spring which can be compressed and embedded into the controlling line. The spring may be arranged between the controlling line and the magnetic part. The spring can be released by removing or degrading a physical locking mechanism such as a barrier. The spring can be made of a shape memory alloy, for example nitinol. Under the influence of a stimulus, such as heat or electricity, the spring may be activated. To activate the spring by heat, it can be coated with a material which can be heated. An example of such configuration can be a spring coated with gold nanoparticles which will be heated when exposed to, for example, infrared light. Another configuration can be a spring coated with superparamagnetic nanoparticles. These particles can be heated in an alternating magnetic field.
The additional propulsion system may alternatively be chemical. The propulsion member may comprise a reactive species. For example, magnesium may be used which, when in contact with blood, can react with H2O by forming a gas which is used to propel the device. Typically, the additional propulsion is only required and thus activated near the treatment site, i.e. the thrombus. Hence, the reactive specie may be embedded into a tank. As an example, a tank can be made of a tubing setup around the magnetic part and attached via a shell. The tank may be closed with a plug. The plug can be mechanically removed or degraded under a stimulus. The plug can be attached to a line setup connected with the controlling line. A force acting on this line, induced for example by a controlling line driver and/or via fluid flow in a canal (e.g. pneumatic or hydraulic pressure), may remove the plug and thus the content of the tank can come in contact with blood. Additionally or alternatively, the plug may be degraded under a stimulus such as electricity (e.g. biocorrosion due to a current) or exposure to light as described herein. In such a configuration the plug may be made of metal such as tungsten and/or titanium or 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 tank may be 100 μm. The outer diameter of the tank may be 200 μm. The tank may be made of a polymer such as PDMS.
Preferably, the medical device comprises at least one drag member. The drag member may be activatable. The drag member is adapted for increasing forces acting on the medical device.
The drag member may, in particular, be magnetic and/or hydrodynamic, i.e. adapted to increase magnetic and/or hydrodynamic forces acting on the medical device.
For example, the drag member may comprise an umbrella-like element arranged on the magnetic part or on the controlling line. Opening of the umbrella-like element may increase the drag force exerted on the medical device by blood and thus enhance transport of the medical device to the treatment site.
The drag member may be adapted to increase an engagement area with a fluid such as blood.
The invention is further directed to a system comprising a medical device, a controlling unit, and an imaging device. Preferably, the medical device is a medical device as described herein. The controlling unit is adapted to navigate the medical device to a target location in a vasculature, in particular a treatment site.
The system according to the invention may be particularly suited for moving a medical device in a vascular network. The medical device maybe a catheter device or a microrobot. The device may comprise a balloon. The medical device may comprise a head section with a magnetic part and a back section with a controlling line. The medical device may be moved in the vascular network in order to treat or diagnose a patient. The system may comprise a magnetic actuator, a controlling unit and a controlling line driver. The controlling line may be attached to the controlling line driver. The controlling line driver, when said controlling line it attached to the controlling line driver, is adapted to hold, to retrieve and/or release a controlling line at different speeds. The magnetic actuator is adapted to generate a magnetic field at a predetermined location. Preferably, the magnetic field is predetermined. The magnetic field may exert a force on the medical device, in particular the magnetic part of the medical device, such as to pull the medical device in a predetermined direction. The controlling unit may be adapted to balance at least three forces applied on the medical device. Preferably, the controlling unit balances the forces in real time.
Preferably, the three forces include at least one of a drag force acting on the medical device by a fluid flow, for example blood in a vessel, a force by the controlling line, and a magnetic force by the magnetic actuator. The controlling unit further operates the magnetic actuator and/or the controlling line driver.
A balloon used in combination with the device, in particular a microrobot or a catheter, may in particular be inflatable asymmetrically. For example, the balloon may be selectively inflatable only on one side with respect to a longitudinal axis. Alternatively, several selectively inflatable balloons may be used. This may allow to detach the device from a tissue to which it has been attached deliberately or by accident.
The thickness of the balloon may be between 50 μm and 300 μm, preferably 80 μm and 150 μm. Furthermore, an activation system for inflating or enabling inflation may be present. 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 with a tissue wall (and thus inadvertent adhesion) 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 have a shape corresponding to a solid of revolution.
The controlling unit can help the magnetic navigation. The concept described here helps to find a good equilibrium on the different forces applied on the medical device: flow force, gravity force, controlling force and the magnetic force or other potential forces acting on the medical device in order to navigate the medical device along the trajectory path. The system may automatically compute the forces and the relations between the forces and define the forces generated by the system, especially the controlling line force and the magnetic force, to ensure that the resulting force moves the medical device along a predefined trajectory.
This balancing model may allow also to optimize the distribution of forces induced by the magnetic actuator and the controlling line. The balancing of forces may also be beneficial for optimizing system requirements, such as e.g. lower magnetic fields and/or lower controlling line forces.
The controlling line driver may comprise, preferably consist of, any one of or a combination of a pulley, a linear actuator, a reel, an electric motor, a spindle, a gear, a screw and/or a nut, a linear gear track, and a continuous track. The controlling line driver may also comprise two or more of any one of these elements, also in combination with any one, two, or more of any other element.
The controlling line driver may also comprise, additionally or alternatively, a controlling line connector adapted for providing an operable connection between the controlling line driver and the controlling line.
Preferably, the controlling unit may comprise a processor and/or a memory. In a particularly preferred embodiment, the controlling unit is in operable connection with an electric motor and is adapted to control at least one of speed, power, and torque of the electric motor.
The speed may be at least partially predetermined, automatically determined or manually chosen. It is conceivable to use a combination of predetermined, automatically determined, and manually chosen speeds. For example, the controlling unit may calculate a suitable speed profile based on a planned trajectory in a vessel taking into account data about the flow of blood in said vessel and save the speed profile in a memory. Additionally or alternatively, the speed of the controlling line may be adapted during an intervention automatically, for example via feedback loop taking into account a planned trajectory and actual position data, and/or manually by a user. To this end, the system may preferably comprise an interface for a user, for example one or more touch screens, knobs, buttons, levers, adapted for allowing input of speed parameters. It is possible to use the same or additional interfaces for inputting further parameters related to control of position and speed of the medical device.
Preferably, the controlling unit is adapted to calculate a magnetic field at a device position in space and/or a force exerted on a magnetic element by said magnetic field when the magnetic element is positioned at the device position in space. The controlling unit may in particular take into account at least one of a position, an orientation, and/or a power of the magnetic actuator. Additionally or alternatively, the controlling unit may be adapted for receiving data from a sensor at or close to the device position, in particular data related to the magnetic field and/or force at the device position.
Additionally or alternatively, the device may calculate at least one of a position, an orientation, and a power of the magnetic actuator suitable to achieve a magnetic field and/or a magnetic force at the device position. The magnetic field and/or magnetic force may be calculated qualitatively (e.g. only a direction) or quantitatively.
Preferably, the controlling line driver is adapted to control at least two controlling lines attached the medical device. The two controlling lines may be released at the same velocity. Alternatively, the two controlling lines may be released at different velocities such as to position and/orient the medical device in the front of the thrombus.
The controlling line driver may comprise a sensor allowing to monitor the retrieving of the thrombus. As an example, a dynamometer is used to measure the force during the thrombus retrieving (entire procedure). The retrieving velocity of the thrombus may be regulated using a force measured by the controlling driver and/or the sensor.
The controlling unit may monitor physiological data measured by the system and/or data measured by other devices. The controlling unit may adapt the instructions to the different elements of the navigation system based on the monitored data.
The invention is further directed to a method of producing a medical device, in particular a medical device as disclosed herein. The method comprises the steps of
The method is particularly suitable if the attachment element comprises electric and/or electronic component, for example if the attachment element comprises electrodes for cauterization and/or electrothrombosis as described herein.
The method may further comprise a step of, prior to providing the temporary layer, coating the attachment layer with a coagulant and drying said coagulant.
The temporary layer protects the attachment element. The coating which is coated on at least a part of the medical device can be easily removed in areas that are protected with a temporary layer. Thus, the temporary layer prevents that the attachment element is coated with a coating. Thus, the method provides a particularly simple way of producing a medical device with a coating wherein a portion of the device is selectively not coated.
The invention is further directed to a method of retrieving a thrombus from a vessel using a medical device. Preferably, the medical device is a medical device as disclosed herein. The method comprises the steps of
Preferably, a retrieving velocity is adapted such as to control a force applied on the thrombus.
Preferably, the method further comprises a step of, after attachment of the attachment element to the thrombus, providing a vibration or shaking motion to the medical device to facilitate removal of the thrombus.
It will be understood that all method steps described herein in the context of medical devices and systems, in particular with respect to navigation in a vessel using the controlling unit, the controlling line and magnetic force, may be performed in the method according to the invention.
It will be understood, in the context of the present description, that proximal refers to a direction along the longitudinal axis of the medical device generally from the treatment side toward the medical device in its intended use, and distal from medical device toward the treatment site.
In general and in the context of the present description, a microrobot may generally be understood as a combination of a controlling line and a magnetic part. The microrobot may be a therapeutic microrobot further comprising a therapeutic tool.
In some embodiments, the device may comprise a growing tube which is extendable, for example by filling with a fluid.
Suitable fluids are gases, liquids such as saline or viscous solutions, and magnetofluids (e.g. suspension of Fe3O4 or Fe2O3 in saline solution, in particular an isotonic solution). This allows to reach areas of the body, for example an occluded artery, where flow of a bodily fluid is insufficient for exerting a drag force on the medical device.
A growing tube typically comprises a tube of soft material which is folded inside itself. The inside of the tube can be moved right-side-out, for example by pressurization with air or liquid, such that the tube everts, leading to growth in one direction. Growing tubes are generally known and described in described in US 2019/0217908 A1, the contents of which are incorporated here by reference.
The growing tube may have an outer diameter between 0.5 mm to 3 mm, preferably from 0.9 mm to 2 mm. The thickness of a shell of the growing tube may be between 20 μm and 1 mm, preferably between 100 μm and 400 μm. The tube may be made of polymers such as polyurethane, low-density polyethylene, and other medical-grade polymers.
In some embodiments, the medical device is adapted to interact with a magnetic field created by an MRI system. Preferably, the medical device is steerable by an MRI system.
In the following, the invention is described in detail with reference to the following figures, showing:
In general, the device 1 may comprise a magnetic part 19 and a controlling line 23. The magnetic part can be used to control the trajectory of the device 1 in a blood vessel.
The magnetic part 19 can comprise or consist of soft ferromagnetic material such as iron, cobalt, nickel, hard ferromagnetic material such as Nd—Fe—B alloy, Fe—Pt alloys, ferrimagnetic material such as iron oxide. The magnetic part can comprise or consist of an aggregation of magnetic particles, particularly superparamagnetic nanoparticles made of iron oxide.
The magnetic part 19 may be coated to prevent direct contact with a biological fluid and thus avoid corrosion. For example, coating materials against corrosion can be polymers (such as Parylene C), ceramics (such as silica based, zirconium based, TiO2) or metals (gold, silver).
The controlling line 23 may be used to control the displacement of the device 1. The controlling line 23 may be attached to a driver (not shown). The driver may be adapted to release the controlling line 23 according to instructions provided by a controlling unit (not shown).
The controlling line 23 may be used to slow down the velocity of the device 1 pushed by the blood flow, to stop the displacement and/or to move back the device 1. Additionally or alternatively, the controlling line 23 can be used to trigger a function in the device 1 by providing a stimuli.
The controlling line 23 can be connected reversibly or irreversibly to the magnetic part 19 by means of an adhesive. It is conceivable to additionally dip the magnetic part 19 and its connection to the controlling line into a resin. The resin may form a shell at least partially around the magnetic part 19 and a distal part of the controlling line 23, thus increasing the stability of the connection between the magnetic part 19 and the controlling line 19. Furthermore, improved adhesion the gluing, the glue can be functionalized with magnetic particles. The magnetic particles may be attracted to the magnetic part 19. Hence, the adhesion between the controlling line 23 and the magnetic part 19 can be increased due to magnetic interactions.
As shown in panel B, pulling of the thrombus by means of the force F exerted on the thrombus 2 leads to a stretching of the thrombus 2. Accordingly, a friction force between the thrombus 2 and the vessel wall 3 is reduced and less force is necessary to remove the thrombus 2 (see panel C).
Here, biological attachment refers to adhesion between a thrombus 2 and the device 1 by means a blood clot whose formation is induced by the biological attachment element 7. Thus, the biological attachment element 7 may be any thrombogenic substance.
Biological attachment elements 7 are particularly advantageous because a blood clot can be formed between the attachment element 4 and the thrombus 2 completely without or with a reduced need of a compression force to attach the device 1 to the proximal surface of the thrombus 2.
To trigger the blood clot formation, the biological attachment element may preferably comprise thrombogenic agents involved in the coagulation cascade, such as thrombin. The concentration of the thrombogenic agent in the biological attachment element may be chosen such that it is sufficient to trigger local coagulation despite the presence of anticoagulant agents typically required during such interventions.
Here, the thrombogenic material which forms the biological attachment element 7 is attached to the surface of the surface of the tool support 102. The thrombogenic material may be chemically bonded to the surface of the tool support 102 by grafting.
Additionally or alternatively, the thrombogenic material may be mixed with a polymer, preferably a non-biodegradable polymer, to form a thrombogenic polymer which ensures a permanent attachment. The thrombogenic polymer may be dried on the surface of the tool support 102.
The thickness of the biological attachment element 7, in particular of the thrombogenic polymer coated onto the tool support 102, may be between 10 μm to 500 μm, preferably 90 to 110 μm.
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 on the surface of the tool support 102 such as to form a biological attachment element 7. Preferably, hexafluorisopropanol (HFIP) is used as the solvent.
Additionally or alternatively, swelling polymers may be used. For example, hydrogels (PVA, PVP, Polyacrylamide), porous hydrogels, superabsorbent polymers (Poly(acrylic acid (PAA), foams (PU) may be used as a matrix material in a biological attachment element 4 to increase the contact surface with the thrombus after hydration by the blood.
If the biological attachment element 7 comprises fibers, said fibers may exhibit a core-shell structure. Preferably the thrombogenic agent is arranged in the shell. Preferably, a bioresorbable polymer forms the core and/or the shell.
The fiber diameter is preferably in the range of 50 nm to 10 μm, particularly preferably between 800 nm and 3 μm.
Particularly preferably, biodegradable polymers are used which exhibit a degradation time higher than two months. Polymers such as PLGA, PLLA, PDO, PCL may be suitable.
Alternatively, the biological attachment element may comprise an element adapted to create a reaction with a component of the thrombus, for example fibrin or red blood cells. Said reaction may trigger a coagulation cascade which will lead to the formation of a blood clot. For example, the biological attachment element may comprise peptides, in particular cyclic peptides such as Tn6, Tn7 and Tn10, which may react with fibrin in a thrombus 2.
The chemical attachment element 10 may provide an adhesive force to a proximal surface of the thrombus 2. A compression force acting on the adhesive and compressing the adhesive on the thrombus 2 may be necessary to create sufficient adhesion. The compression force may be between 0.001 N to 3 N, preferably between 0.02 to 0.08 N. Preferably, the compression force is applied at least during 30 s, particularly preferably between 45 s and 120 s. The compression force can be achieved with a magnetic force generated by an external magnetic field and acting on the magnetic head portion 19.
Additionally or alternatively, the compression force can be achieved by mechanical means. For example, a spring can be setup within the controlling line 23 (see
Additionally or alternatively, a propulsion element (see
Additionally or alternatively, an drag element (see
Additionally or alternatively, any other means known in the art may be employed.
The adhesive material may be a n-Butyl-2-cynoacrylate such as 2-octyl-2-cyanoacrylate. The adhesive is a medical grade adhesive and may be arranged onto the anchoring support. Typically, the adhesive force of the adhesive is sufficient to hold the adhesive on the device 1, preferably the tool support 102. However, it is also conceivable to use adhesive enhancers such as an additional surface coating or the like.
Additionally or alternatively, the adhesive material may be biological. For example, the adhesive material may be a protein-based (fibrin-based, collagen-based, gelatin-based, albumin-based) and/or polysaccharide-based adhesive (chitosan-based, alginate-based (e.g., SealG), and chondroitin-based).
Additionally or alternatively, the adhesive may be synthetic, such as polycyanoacrylates (e.g. n-Butyl-2-cynoacrylate such as 2-octyl-2-cyanoacrylate, polyurethanes (e.g., TissuGlu®), poly (ethylene glycol) (PEG, e.g., DuraSeal™, FoacaSeal®, CoSeal®), polyesters, as well as hyperbranched and dendrimer polymers.
Additionally or alternatively, the adhesive may be biomimetic, such as mussel-inspired adhesives (e.g., dopamine-modified gelatin+Fe3++genipin), gecko-inspired adhesives.
Additionally or alternatively, the adhesive might be present in an inactive state, and activated via any means known in the art and/or described herein, such as light activation (UV or other wavelength), or in situ mixing of at least two components. An example of light-activated glue may be a photo-polymerizable PEG glue, or a methacrylated tropoelastin. An example of in situ mixing may be a mix of two PEG polymers (such as in CoSeal®), or of a PEG polymer and a poly(ethyleneimine) (such as in Adherus).
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, between 5 nm to 400 nm, preferably 10 nm to 50 nm. Additionally or alternatively, nanoparticles may have a characteristic volume in the range of 50 nm3 to 3.4.107 nm3, preferably 400 nm3 to 5.104 nm3.
The nanoparticles may be dispersed in the adhesive and interact with the adhesive via low-energy Van der Waals forces. Alternatively, the nanoparticles may be connected to the adhesive via covalent and/or ionic bonds. The magnetic nanoparticles may thus provide magnetic properties to the adhesive dispersion comprising said nanoparticles. Thus, magnetic forces between the adhesive dispersion and the magnetic head part may arise and provide more secure attachment of the adhesive to the device 1. These magnetic forces may reduce the risk of detachment of the adhesive from the tool support 102 and at least partially counteract the strain applied on the adhesive during the retrievement of the thrombus.
The adhesive is arranged on the device 1 such as to have a diameter between 50 μm to 1 mm, preferably between 300 μm and 600 μm.
The adhesive may be a dried adhesive. A dried adhesive has a reduced adhesive strength compared to its wetted state. Thus, a dried adhesive is particularly advantageous if a protective shell is used during navigation to the treatment site, as the risk of accidental and/or permanent adhesion of the attachment element to the protective shell and/or other parts of the device may be reduced.
Additionally or alternatively, the adhesive may be impregnated into a porous material arranged on the tool support 102. The porous material may be fibrous tissue or porous beads.
For example, a fibrous fabric made of PET may be used. The fibrous fabric may comprise fibers with a diameter of 3 μm and a pore diameter of about 800 nm. The fibrous tissue can be fixed on the tool support 102 by means of a glue layer at the center and/or on the perimeter of the PET fibrous fabric. Preferably, the adhesive may be dried on the porous material such as the fibrous fabric.
It is particularly advantageous to use a fibrous fabric which is glued at a center as a circumferential area may remain unattached to the tool support 102 and thus provide increased attachment by moving toward the thrombus 2.
Here, the mechanical attachment element 11 is adapted to penetrate the proximal surface (see
Expansive materials may generally be used to improve attachment to the thrombus.
Here, four mechanical attachment elements 11 are present. 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 two and eight elements 11 are used. It is also possible to use exactly one element 11.
The mechanical attachment elements 11 have a higher Young's modulus than the thrombus 2 and is preferably at least above 1 MPa.
The diameter of the mechanical attachment element 11 here is 100 μm each, but may be in a range of 50 μm to 700 μm, preferably 80 μm to 300 μm.
The mechanical attachment element 11 preferably comprises or consists of a polymer, such as PET, PE or PP, or any blends or co-polymers thereof.
If mechanical and biological attachment means are combined, a thrombogenic element may be mixed with said polymer material. Thus, the mechanical attachment elements 11 may be made of a thrombogenic material.
Additionally or alternatively, the mechanical attachment element can comprise or consist of a metals. For example, stainless steel (316 L), titanium, tungsten, or any alloy thereof may be used.
Additionally or alternatively, a thrombogenic agent can be coated onto the mechanical attachment elements 11, for example by dip coating. Coating is advantageous in that it can be used with a wider variety of materials, i.e. is suitable with mechanical attachment elements comprising polymers, metals, or any other material.
In particular, the surface of the mechanical attachment elements 11 may be coated with a thrombogenic agent by means of CVD, plasma spraying, or physical vapor deposition.
Exemplary thrombogenic elements which may be employed are Von Wilerbrand factor (vWF), laminin, thrombospondin, vitronectin, fibrinogen or Thromboxane A2. These thrombogenic elements may trigger platelet adhesion and thus clot formation.
Thrombin is also suitable and is an enzyme which converts fibrinogen, by cleavage of fibrinopeptide A, into fibrin. Thus a fibrin network may be formed to capture erythrocytes and platelets leading to formation of a blood clot.
The diameter of the opening 100 is 300 μm in the shown embodiment. However, it will be understood that the diameter may be anywhere in the range of 50 to 600 μm, preferably 200 μm to 400 μm.
A height or depth 106 of the opening 100 can be equal or smaller to the diameter of the magnetic part 19. The height may preferably be between 100 to 1000 μm, particularly preferably between 200 μm to 400 μm.
The magnetic part 19 shown here has a substantially spherical shape. Alternatively, the magnetic part 19 may have any other shape, in particular cubic, flat, elliptic or rod-like. The diameter of the magnetic part 19 here is 1500 μm, but may be in the range of 50 μm to 2000 μm, preferably between 200 μm to 1000 μm.
The tool support 102 may be connected to the magnetic part 19 by gluing, screwing, clipping, welding or melting, for example. Preferably, the tool support 102 comprises a pin 101 intended for being arranged in the form-fit opening 100 of the magnetic part 19. It will be understood that any of the above connection methods may be combined with such a form-fit connection, i.e. an glue, a screw, a clip, a welded connection or a molten connection may be configured in addition to the form-fit connection.
Preferably, the tool support exhibits a flat surface. A characteristic size of the tool support 102, in particular the diamemter, may be equal, higher or lower than the diameter of the magnetic part.
The tool support may comprise or consist of a magnetic material, a non-magnetic material, or any combination thereof. For example, a part of the tool support 102 may be magnetic to improve its connection to the magnetic part 19.
Suitable non-magnetic materials are:
The tool support 102 may, additionally or alternatively, comprise or consist of agglomerated particles. Agglomerated particles can provide enhanced tuneabity of material properties, for example the conductivity. The tool support 102 may optionally be coated with a biocompatible coating (not shown) to improve its biocompatibility.
Here, illustratively, a longitudinal axis L and a direction r perpendicular to the longitudinal axis is shown. The device 1 has a size S in a direction r which represents the maximum size of the device 1 in the direction r of 2 mm.
The protective cap 14 is crimped on the ring 108. The ring 108 may comprise or consist of a polymer, a metal, or any combination thereof. Crimping may prevent unintended penetration of biological fluids, such as blood, into the protective cap 14.
The ring 108 and the slider 107, which together form a sliding system, are setup on the controlling line 23.
The slider 107 may be configured as a configuration a straight tube, optionally with a distal ring (not shown) and a proximal ring 109. The straight tube allows the retractation of the capsule by providing a rail-like guide for the ring 108. Initially, the ring 108 is positioned at a distal end of the slider 107. To retract the protective cap 14, the ring 108 is moved to a proximal end of the sliding system. The ring may, for example, be moved by a line pulled via a controlling line driver (not shown). Alternatively, the crimping ring may be moved by contraction of a rigid line arranged between the ring 108 and the distal ring. The rigid line may, for example, comprise or consist of nitinol compressed under an electrical stimulus.
To avoid penetration of a liquid, for example blood, between the controlling line and the sliding system, a valve may be arranged inside the proximal ring 109.
Optionally, to facilitate the breaking of the protective cap 14, the protective cap may comprise a predetermined breaking point, for example in the form of a reduction of the thickness (not shown). The reduction of the thickness can be between 10 to 70%, preferably 30% to 50%. Additionally or alternatively, the breakable part can comprise or consist of a bioresorbable material, in particular a bioresorbable material as described herein. The degradation may be triggerable with any stimulus as described herein.
Alternatively, the tool support 102 may comprise a cutting tool (not shown). The cutting tool may tear the protective coating 14 during the retraction.
Preferably, the cutting tool is arranged on an edge of the tool support 102.
The drag element 25 is arranged on the controlling line 23. In one configuration, the activable drag element 25 is made of a nitinol frame covered with a polymer layer. The polymer layer may comprise or consist of polyurethane and exhibit a thickness between 50 μm to 300 μm. The nitinol frame can be activated under a stimulus such as heat leading to the opening of the structure. The increased drag caused by the blood flow can provide an additional propulsion force.
It will be understood that the two configurations shown in
The device 1 shown here is substantially similar to the device shown in
The shown embodiment in particular allows to trigger the formation of a thrombus by applying electricity (electro-thrombosis).
As shown in
An electric current can lead to the formation of a blood clot by electro-thrombosis. Thus, similar attachment as, for example, shown in
Thus, an electrical current can be delivered to the tool support 102 in order to achieve biological attachment to the thrombus 2.
Additionally or alternatively, an electrical current may also increase the temperature of the tool support 102, and thus lead to attachment of the tool support 102 by cauterization. The temperature can be increased up to 60° C., preferably to a temperature between 40 to 45° C. It is also possible to use a cryogenic probe at or on the tool support for cauterization. Heating of the tool support may be provided by an internal stimulus or an external stimulus.
An insulator shell 110 is arranged on an outer surface of the controlling line 23 in order to avoid dissipation of electrical current in the biological fluids, in particular the blood. The insulator shell 110 is preferably made of a flexible polymer with a low Young 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 to 200 μm, preferably between 30 to 80 μm.
Here, the two electrical wires 9, 9′ are guided through the controlling line 23 and around the magnetic part 19 and connected directly to the tool support 102. The connection between the electrical wires 9, 9′ and the tool support 102 is welded in this embodiment. The diameter of the electric wire is between 10 μm to 200 μm, preferably between 60 μm to 120 μm. The Young modulus of these wires is between 0.2 to 50 GPa, preferably between 0.5 GPa and 5 GPa. In the shown embodiment, the wires 9,9′ are arranged at a circumference of the magnetic part 19 and thus increase the diameter of the magnetic part. The described diameters of the wires 9,9″ are generally advantageous in such embodiments as navigation in blood vessels may be more challenging with increasing size of the magnetic part 19.
It will be understood that the electric wires 9,9′ shown here may be used in any other embodiment disclosed herein to deliver an electrical current/voltage.
Furthermore, in order to prevent dissipation of current into the magnetic part 19, the magnetic part 19 is coated with a protective shell 111. The protective shell 111 is electrically insulating and may provide additional protection against corrosion. The protective shell 111 here consists of a layer of polyester resin with a thickness of 100 μm. Additionally or alternatively, the protective shell 111 may, however, comprise any ceramic, polymer or a composite material. For example, epoxy resins, silicones, or epoxy-polyurethane blends are suitable materials. Carbon, silica-based ceramics, zirconium nitride or zirconia are suitable materials as well. The thickness of the protective shell 111 may be in the range of 50 nm to 200 μm, preferably between 30 μm to 100 μm.
The tool support 102 may be used as a probe for the electrothrombosis or cauterization. It will be understood that the shown shape is exemplary and that other shapes may be employed.
Alternatively, the temporary layer 102 may be a silicone cover which may be stretched and placed over the tool support 102. The silicone cover preferably has a thickness of 100 μm to 300 μm.
Alternatively, where a silicone cap as described above is used, said cap is cut and removed from the tool support 102 such as to remove the protective shell 111.
The method as described above allows for an simple and less error-prone way of selectively coating certain parts of the medical device with a protective shell, but not others. In particular, other methods (etching or scratching the protective coating) may damage the device and increase scrap rates.
It will be understood that the example above is exemplary in nature and other parts of the medical device may be covered by a temporary layer in addition or as an alternative.
In this design, the mechanical attachment elements 11 are based on rigid wires which can be bent according to any stimulus known in the art. For example, as described above, the wires can be comprise or consist of nitinol which is bent due to an electrical current.
To avoid a complete bending of the wire, the wire may be setup inside a rigid shaft. The shaft can be made of a polymer (PEEK for example) or a metal (stainless steel AISI 316L, for example). The internal diameter of the shaft may be between 50 μm and 500 μm, preferably 100 μm to 300 μm. The external diameter of the shaft may be between 90 μm to 600 μm, preferably 140 μm to 350 μm.
As described above, the wires may be arranged on the tool support 102. The connection between wires and tool support may be through holes, or via a matrix which is fixed to the support. The diameter of the wires generally may be between 50 μm and 300 μm, preferably 75 μm and 150 μm. The extremity of the wire can be shaped in order to improve the penetration of the proximal surface, in particular have a pointy and/or sharp shape.
It will be understood that the features shown in
Mechanical attachment generally refers to the attachment to the proximal surface of the thrombus using a mechanical system. It will be understood that the embodiments shown herein are of exemplary nature.
In general, mechanical systems are used to penetrate the thrombus. Penetration is preferably progressive at a rate between 0.01 mm/s to 15 mm/s, particularly preferably 0.1 mm/s to 1 mm/s, in order to avoid a damage to the thrombus structure. An intact thrombus is advantageous as it reduces the risk of breaking during retrieval or debris being released into the vessel system.
The number of mechanical attachment elements 11 arranged on the tool support 102 is generally between 1 to 20, preferably 2 to 8.
The mechanical attachment elements 11′, 11″ are bent and may be separately activatable. To this end, each mechanical attachment element 11′, 11″ may be in connected or connectable to a separate electrical connection each. Such an arrangement may be advantageous when the thrombus has an irregular shape.
In order to provide separate activation to each mechanical attachment element 11′, 11″, the tool support 102 may comprise four parts glued together with an adhesive providing electrical insulation. Thus, current leakage through the glue is prevented.
Each part of the tool support 102 may be connected with two electrical wires.
The penetration may monitored via the length released by the controlling line driver. Additionally or alternatively, a pressure sensor may be attached to the controlling line, in particular a pressure sensor in operable connection with the controlling line driver used to monitor the retrieval of the thrombus.
Additionally or alternatively, the penetration may be monitored by any imaging means known in the art. To this end, any part of the medical device, in particular the tool support and/or any attachment element, may be configured to be radiopaque and thus imaged when attached at or in a thrombus.
It will be understood that the specific shape change described here is of exemplary nature and any shape change that allows for penetration initially and attachment subsequently may be suitable. In particular, the attachment elements 11 may be bent inwardly instead of outwardly (see
Here, the device 1 additionally comprises a spring 12 incorporated into the controlling line 23. The spring 12 can provide a propulsion force to penetrate the thrombus 2 with the mechanical attachment elements 11. It will be understood that any other propulsion mechanism may be combined with the embodiment shown here, in particular magnetic propulsion as described in the context of
Release of the spring 12 may be mechanically or electrically controlled. Mechanical release may be performed via a line attached to the spring 12. Application of an external force on the line may release the spring 12.
In particular, the spring 12 may comprise a shape memory material, for example a Nitinol alloy and may be triggered to change from a first shape to a second shape.
The spring 12 may be released by removing or degrading a physical barrier. The spring may in particular be made of a shape memory alloy, for example nitinol. Under a stimuli such as heat or electricity, the spring may be activated. To activate the spring by heat, it can be coated with a material which can be heated. For example, a spring may be coated with gold nanoparticles which can be heated when exposed to infrared irradiation. Another configuration can be a spring coated with superparamagnetic nanoparticles. These particles can be heated in an alternative magnetic field such as the one use for hyperthermia.
The physical barrier may be a lock. The lock can be setup with a frame parallel to the compressed spring. The lock is setup perpendicularly to the longitudinal direction. The lock may be removed by pulling or by fast degradation (biocorrosion of magnesium under a current). A part of the controlling 23 line may be formed by the spring 12, i.e a controlling line 23 may be set up between the controlling line driver (not shown) and the spring 12 and a second portion of the controlling line 23 may be set up between the spring 12 and the magnetic part 19.
The spring may have a diameter comprised in the range of 50 μm to 800 μm, preferably 100 μm to 300 μm. In the extended state as shown in
Preferably, the spring 12 is adapted to change its length, when transitioning from the compressed to the extended state, by at least 100%, preferably 200%.
Preferably, the spring is adapted to apply a force between 0.05 N and 0.6 N.
The spring 12 may be formed by the controlling line 23. For example, the controlling line 23 may comprise a nitinol wire which is formed in a helical shape. Under a stimuli, for example electricity, the helical nitinol shape may be elongated. The diameter of the nitinol helix may be between 50 μm to 900 μm, preferably 100 μm to 300 μm.
It will be understood that the spring 12 shown here may be combined with any other attachment element as well, in particular a chemical attachment element comprising an adhesive (see
Alternatively, the spring 12 may be configured as a separate element connected to the controlling line 23. Preferably, the spring is arranged between the magnetic part 19 and the controlling line 23.
Optionally, the elements 11 may be coated with an expansive coating. Such a coating may provide additional anchoring to the thrombus 2 by expanding once the elements 11 are placed within the thrombus 2.
Release of the spring 11 in order to perforate the protective cap 14 may be done by a locking mechanism that lets the spring 11 expand back to its original configuration when removed.
To maintain the spring 11 in a compressed configuration, nitinol parts can be used. By application of a current, the nitinol parts may be heated up and change their configuration and thus they may release the spring.
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 its processing by dip coating. Additionally or alternatively, the film 14′ can be glued, melted or welded on the ring 14″. The thickness of the film 14′ may be between 20 μm and 500 μm, preferably between 100 μm and 300 μm.
The ring 14″ can comprise or consist of a polymer such as PEEK (polyetherkeytone), polysulfones (PSU, PPSU) or polyethylene (HDPE). Additionally or alternatively, the ring 14″ may comprise a metal such as stainless steel (304 or 316L), titanium, tungsten.
The ring 14″ may further comprise a magnetic material such as iron oxide, iron, Nd—Fe—B, FePt, thus giving the ring 14″ magnetic properties. A magnetic ring can lead to magnetic interaction with the magnetic part 19 used for the navigation. This interaction improves the adhesion of the ring with the device 1.
The ring 14″ may be coated to reduce or prevent corrosion.
The spring 11 may additionally be coated with a thrombogenic material or an adhesive material in order to provide further biological or chemical attachment.
Additionally or alternatively, a thrombogenic material may be arranged on the tool support 102.
It is also conceivable to use the spring solely for penetration of the protection cap 14, i.e. for activation of a separate attachment mechanism.
To this end, a thrombogenic material may be fixed to a scaffold which is attached to the spring 11 and/or to the spring 11 itself (see
In certain embodiments, a spring 11,12 may be setup between the magnetic part 19 and the tool support 102. The tool support 102 may comprise a cutting area in order to cut the protective cap 14 open. Preferably, four cutting areas are arranged on a circumferential area of the tool support.
Here, in general, the polymer film 14″ is arranged on the device 1 under tension. Thus, once broken distally, the polymer film 14″ has a tendency to fold onto the ring 14′.
The thickness of the polymer film 14′ may be between 20 μm and 700 μm, preferably 100 μm to 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 way as described herein, in particular in the context of
In order to create a tension in the polymer film 14′, the activable breaking support 112 is setup on the tool support 102. The polymer layer 14′ may be strained by the breaking support 112 while the ring is moved in a proximal direction until the ring 14″ reaches its intended position.
The activable breaking support 112 is adapted to change its shape by action of a stimulus. For example, the activable breaking support 112 may be made of nitinol. Thus, the activatable breaking support 112 may extend when subjected to an electrical current. As a result, further strain is applied to the protective cap 14, in particular the polymer film 14′.
Alternatively, the activable breaking support 112 may comprise a sharp element, such as a needle, which is arranged within the support 112 without contact to the polymer film 14′, but movable to a position where it can be brought in contact with the film 14′ such that the film is perforated. The sharp element may comprise or consist of a metal, such as stainless steel or titanium. The sharp element may have a diameter between 40 μm to 200 μm, preferably 70 μm to 150 μm. Additionally or alternatively, the sharp element may be adapted for anchoring to the thrombus.
Additionally or alternatively, the activatable breaking support 112 may be adapted to trigger a stimulus, for example an electric current, which can destabilize and thus break the polymer film 14′. The current, or heat caused by the current, may destabilize the polymer film 14′.
Electrical wires can be directly connected to the activable breaking support 112. Alternatively, the current can be provided via the tool support 102, in particular if the device is configured substantially similarly as shown in
In general, swelling materials, in particular any of the polymers mentioned above, may be used to optimize the contact surface with the proximal surface of the thrombus. To this end, an attachment material such as the adhesive material or the thrombogenic material can be attached to the swelling material. The size of the material will increase under hydration. During the expansion, the adhesive material can cover the activable support.
Particularly suitable swelling materials are hydrogels (PVA, PVP, Polyacrylamide), porous hydrogels, superabsorbent polymers (Poly(acrylic acid (PAA), foams (PU).
As shown in
Additionally or alternatively to pushing of the guidewire 114, injection of saline solution may be used to move the attachment element 4, in particular by activation of hydraulic means.
Additionally or alternatively, the attachment element 4, which is attached to a line and/or guidewire, may be flushed outside of the catheter device 10. The attachment element 4 may be moved into the catheter when the catheter is located at the thrombus or may be stored in a distal part of the catheter device 10 during delivery.
The attachment element 4 may be moved out of the catheter device 10 by means of a gas activation (e.g. air), liquid (e.g. saline solution), heat (e.g. electrical or induction) and/or electricity (e.g. piezoelectric material).
As shown in
Expansion of the expandable element 12 may be triggered by any stimulus disclosed herein, in particular ultrasound, electricity, electromagnetic radiation (preferably UV radiation), heat, hydration.
It will be understood that any attachment element described herein, in particular biological, mechanical and chemical attachment mechanisms, may be used in combination with the catheter devices shown in
The frame 22 is preferably activatable. The frame 22 is generally composed of a straight frame element fixed to the ring 119 and an activable element which may open the frame upon activation.
Preferably, a polymer film is arranged on the frame 22. Particularly preferably, a cap as shown in
Preferably, the straight elements can comprise or consist of a polymer, a ceramic or a metal. Particularly preferably, stainless steel (316 L), nitinol and/or titanium are used.
The diameter of the bars 120 of the frame 22 may be in the range of 80 μm and 300 μm, preferably 100 μm and 200 μm.
Preferably, the frame 22 is welded, in particular the connections between bars 120 and ring 119.
An external diameter of the frame 22 is preferably in the range of 80 μm to 400 μm, particularly preferably 100 μm to 200 μm. An inner diameter of the hollow frame may be in the range of 50 μm to 300 μm, preferably 70 μm and 150 μm.
Preferably, an electrical current is used to open frame 22. As a result, the bars 120 can bend towards a radial direction of the tool support 102. For example, the bending of bars 120 may tear and open the polymer layer.
The bars 120 of the frame 22 can be bent at an angle in the range of 10° to 170°, preferably 80° to 130°, with respect to a longitudinal axis of the device 1 (i.e. an axis perpendicular of a plane of ring 119).
In some embodiments, the ring may be arranged at an extremity of a protective element, for example the frame 22 and/or a protective cap as described herein, for reinforcement of the protection. Said ring may break upon bending of the bars 120, for example. Said ring may comprise or consist of bioresorbable polymers such as PGA or PLGA. Additionally or alternatively, the ring comprise or consist of a non-biodegradable polymer or a biodegradable polymer. Said ring may comprise a predetermined breaking point to ensure a smooth breaking. For example, the predetermined breaking point may comprise a local thickness reduction. Said ring may have a diameter in the range of 100 μm and 1000 μm, preferably 150 μm and 250 μm.
It is conceivable that multiple triggers/activation mechanisms are realized in one device. For example, one of several activable elements may be triggered with an electric current whereas other activatable elements may be triggered by an increase in temperature.
Preferably, a protective layer is arranged on the frame 22. The protective frame 22 allows to minimize direct contact of the attachment element with blood vessel walls.
The additional propulsion system shown here is chemical. The propulsion system comprises a reactive specie, which is adapted to react with water or blood to form a gas may be used to propel the device. Here, magnesium is used.
The magnesium (not visible) is embedded into a tank 24. The tank 24 here is configured as a tubing setup around the magnetic part 19 and attached to a shell 121. The shell 121 may be a protective coating as described herein, for example a resin shell. The tank 24 is closed with a plug 104. The plug is removably attached to the tank 24 and can be removed mechanically and/or degraded by means of a stimulus. For example, the plug 104 may be attached to a line associated with the controlling line 23. A force exerted on said line, induced for example by a controlling line driver, may remove the plug 104 and thus the content of the tank, here magnesium, can come in contact with blood. As a result, a gas is formed and propelled through opening 103 of the tank, thus providing a forward force on the device 1.
Here, the plug 104 is made of titanium. However, any metal, for example tungsten or steel, may be used, and/or any polymer such as silicon, PEEK, or any blend or combination thereof.
Here, an outer diameter of the plug 104 is 240 μm. An inner diameter of the tank 24 and opening 103 is 100 μm. An outer diameter of the tank is 200 μm.
Preferably, the tank comprises or consists of a polymer material such as PDMS. Other polymers may be used, as well as any blend or combination of polymers.
Here, a variant of mechanical attachment is performed by suction. The aspiration system comprises a suction surface 122 arranged on the tool support 102. The tool support 102 further comprises an opening 118 through which a suction action can be achieved. The tool support 102 may in particular have a flat shape, a curved shape, and/or comprise peripheral protrusions to provide sufficient fit with a shape of the thrombus. Here, a diameter of the opening 118 is 600 μm. The thrombus (not shown) can be pulled onto the suction surface 122 and be held by means of the suction on the tool support 102. A suction mechanism as shown here allows to attach and reattach a thrombus repeatedly, for example until secure attachment is provided.
The hollow channel 117 here is configured as a channel within the controlling line 23, the controlling line 23 serves as a suction channel. The suction channel may, alternatively, be configured as a separate element not incorporated in the controlling line, in particular when combined with a catheter device (see
It will also be understood that the hollow line 117 may be used for other purposes than to provide a suction mechanism. In particular, it may be used for hydraulic activation, activation by gas-compression, or delivery of other fluids.
The Young's modulus of the controlling line 23 and/or the channel 117 (in particular if configured as a separate element) may be in the range of 0.5 GPa and 100 GPa, preferably 0.5 GPa and 5 GPa, in order to be compatible with navigation within a vessel system.
In some embodiments configuration, the aspiration system, i.e. the tool support 102, may be directly connected with a hollow tube 117, i.e. without an magnetic part 19 arranged intermediately.
Additionally or alternatively, the shaft 130 may be configured to trigger the movement of the mechanical attachment elements 11. For example, the shaft may be connected to electric wires (see
Here, the shafts 130 are made of stainless steel and have an internal diameter of 200 μm and an outer diameter of 300 μm.
It will be understood that the coating 131 might, additionally or alternatively, be made of an expansive material, which can inherently increase the adhesion force between the thrombus and the device.
It will be understood that thrombolytic agents as described here may be used in combination with any other embodiment disclosed herein.
It will be understood that another thrombolytic agents than t-PA may be used in addition or as an alternative.
Thrombolytic agents may be directly grafted on a surface of the medical device, for example chemical vapor deposition (CVD) or physical vapor deposition (PVD).
The thrombolytic agent may also 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), polybutyl methacrylate (PBMA), poly(vinylidene fluoride-co-hexafluoropropylene), phosphorylcholine or polyesters may be used. Biodegradable polymers such as PLGA (in any PLA:PGA ratio, preferably 10:90), PDO, PGA, starch, cellulose, and/or chitosan may be used as well.
The matrix can be made of a gel, in particular a hydrogel. The gel may be degradable or non-degradable. The matrix may be arranged on the tool support 102 and held the tool support 102 by the attachment elements, in particular mechanical attachment elements 11.
The thrombolytic matrix may be arranged on a scaffold on the tool support 102. The scaffold may be glued on the tool support. The thrombolytic matrix can exhibit holes for attachment elements. The matrix may have a flat or a curved shape. The shape of the thrombolytic matrix may have an influence on the release of the thrombolytic agent and thus, the release kinetics may be tuned by changing the shape of the thrombolytic matrix.
Typically, a flat surface will lead to comparably slow release of a thrombolytic agent. By contrast, curved surfaces may provide for faster release. For example, a dome shape may be used, in particular with the top oriented toward the thrombus, to achieve this effect.
A shaped scaffold may be used to provide the desired shape. A gel containing the thrombolytic agent can be arranged on it. The curvature may be chosen so that the scaffold encompasses an angle between 10 to 45°, preferably 30°, in particular between a surface of the scaffold and the longitudinal axis of the device.
The thrombolytic matrix is made of different elements distributed on the tool support surface.
A mix of polymers can be used to tune the release kinetics. Low molecular weight polymers can be used to tune the release kinetic.
Typically, polymers with low molecular weight may degrade faster and provide faster release of drugs, thrombogenic agents, thrombolytic agents, or others. Polymers with higher molecular weight may degrade at a slower rate. Thus, the kinetics of release of an active agent may be tuned by mixing polymers with different molecular weights.
Typically, the ratio of thrombolytic agent to polymer (weight by weight) is between 0.1% and 50%, preferably between 2% and 15%.
The thrombolytic matrix may be arranged on any part of the medical device, for example the mechanical attachment elements 11 and/or the tool support 102, and dried.
Additionally or alternatively, the thrombolytic matrix may comprise or consist of particles. For example, the particles may be deposited by electro-spraying. The thrombolytic matrix may also be molded onto the tool support 102. Alternatively, the thrombolytic matrix can be shaped, by molding or casting, into a part to be arranged directly on any part of the device 1, for example on a mechanical attachment element 11, the tool support 102, shaft 130 or others.
The thrombolytic agent can be fixed on any surface of the medical device 1 by, for example, peptide grafting or hydrolysable linkers.
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 a surface and dried.
Any thrombolytic matrix as described herein may be coated onto the mechanical attachment elements 11 in order to create a thrombolytic coating 131.
The thrombolytic matrix 132 may be any thrombolytic matrix as described herein. It will be understood that the mechanical attachment elements 11 shown here, which substantially correspond to the ones shown in
Any thrombolytic agent may be protected from direct contact with blood during the navigation to a target site. The thrombolytic agent may activated before or at the same time as the attachment element.
Once activated, the thrombolytic agent may be carried by blood up to the thrombus.
It is conceivable to use more than one hollow line 117. If several hollow lines are used, at least one line is used for suction. Other lines may be used to activate additional microrobot features, for example for the injection of saline solution. Alternatively, different lines may be connected or connectable to different suction areas. Such a configuration may improve the adhesion to the thrombus.
If one suction orifice 118 is present, a progressive increase of the diameter from the proximal side to the distal side may improve the adhesion to the thrombus.
The inner diameter of hollow sublines 117′, 117″ is preferably 60 μm, and the outer diameter is preferably 90 μm. The diameter of the controlling line shown here is 70 μm. The diameter of the suction orifice 118 increases from 100 μm to 200 μm.
In certain embodiments, the controlling line 23 may be formed by the hollow sublines 117′, 117″.
The device 1 shown here further comprises a balloon 133 arranged at a distal position of the attachment element 4 on the controlling line 23. An inside of the balloon 133 is in fluid communication with a hollow line 117 arranged within the controlling line and adapted to inflate the balloon 133. The balloon 133 comprises a silicone pouch.
The balloon 133 allows to reduce the blood flow/blood pressure in an area of the thrombus 2 before and during attachment to mechanical gripper 11. For retrieval of the thrombus 2, the balloon 133 may be deflated again.
The person skilled in the art will understand that all specific combinations of attachment elements, delivery systems, protective coatings and activation mechanisms are of exemplary nature and may be used in any other combination.
In general, conducting polymers may be used instead of Nitinol. Preferred conducting polymers are polythiophene (PT), PA, PPy, PANI, PEDOT.
In general, adhesive compositions as described herein may be used in an encapsulated form.
Here, the sensor 134 is configured as a pressures sensor. The sensor 134 is arranged between the tool support 102 and the magnetic part 19. Thus, when the tool support 102 is pushed against another structure (for example a thrombus), the force 136 exerted on said structure may be measured by means of the sensor 134. It is in particular conceivable to measure the force via a strain of the sensor.
The sensor 134 may be connected to cables (not shown) and/or comprise a wireless connection to an external device.
Here, the sensor 134 has an external diameter of 300 μm, an internal diameter of 200 μm and a height of 300 μm.
When a device according to the invention is predominantly moved by drag and magnetic forces, the drag force may be reduced in an occluded artery. As a result, the displacement of the device 1 may need to be conducted with magnetic force. Depending on the localization of the thrombus, especially the distance between the thrombus and the surface of the skull, magnetic forces may be controllable insufficiently to move the device 1. A growing tube may provide an alternative means to move the device within a vasculature and thus overcome this problem.
The holding lines 203′, 203″ may be detachable from the distal part of the device 1. The detachment may be done by applying a current for example. Here, both holding lines 203′, 203″ have a diameter of 100 μm and are made of polyurethane.
The delivery system may be connected to a delivery catheter-through a tubing, preferably a flexible tubing. The flexible tubing may have an inner diameter between 0.5 mm to 4 mm, preferably between 0.8 mm and 2.5 mm.
Detachment of a holding line may be advantageous where the holding line is too rigid for navigation but required to prevent breaking during initial introduction into the body (due to high magnetic forces). Thus, the holding line may be used during introduction but then detached before navigation in a vessel.
The balloon may be only partially inflated to avoid a total 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 a distal opening of a catheter tube. The diaphragm 206 may be closed when the device 1 is housed within the catheter device, either during deliver or after retrieval of a thrombus (see
It is conceivable that multiple suction cups are present, for example three suction cups.
In particular when the device comprises or consists of a microrobot, the device may get stuck during navigation in a vessel, for example due to curvature on an artery wall. Hence, in some embodiments, one or several balloons may be arranged at a distal region of the device (e.g. around the microrobot or a distal region of a catheter device).
The balloons 204′, 204″ may also be adapted for and used to be stabilize inside a lumen of a vessel (e.g. an artery) and/or a proximal side of the thrombus.
The controlling line may be made of highly elastic material such as silicon. Thus, the controlling line may be stretched or elongated during navigation or retractation of the device. If the rigidity of the material is increased to limit the stretching, the bending stiffness is increased and thus the controlling line is less flexible to navigate in tortuous network.
Some embodiments therefore comprise one or several holding lines. A holding line is particularly advantageous where a a hollow controlling line is used.
The embodiments shown in
| Number | Date | Country | Kind |
|---|---|---|---|
| 21315103.8 | Jun 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/067180 | 6/23/2022 | WO |
