Device, in particular a robot, system comprising such device and method for controlling such device

Abstract

The invention relates to a device, in particular a robot, arranged to be inserted into a human or animal body, for example in a vessel or tissue thereof, and to move through said human or animal body, said device comprising at least one magnet or magnetizable element for cooperating with an externally applied magnetic field so as to control the movement of said device in the human or animal body by a magnetic field.

Description

[0001] DEVICE, IN PARTICULAR A ROBOT, SYSTEM COMPRISING SUCH DEVICE AND METHOD FOR

[0002] CONTROLLING SUCH DEVICE

[0003] The invention relates to a device, in particular a robot, arranged to be inserted into a human or animal body, for example in a vessel or tissue thereof, and to move through said human or animal body, said device comprising at least one magnet or magnetizable element for cooperating with an externally applied magnetic field so as to control the movement of said device in the human or animal body by a magnetic field.

[0004] The device is in particular a robot or robotic device, more in particular an untethered robotic device, more in particular an untethered micro-robotic device.

[0005] The device is particularly a wireless magnetically actuated device comprising at least one magnet or magnetizable element arranged to cooperate with an externally applied magnetic field to generate propulsion, thereby enabling the device to swim through non-Newtonian biological fluids such as blood and to screw or drill through viscoelastic environments including tissue or tumors. The device may be configured to penetrate or drill through a vessel wall, including an arterial wall, without causing infection, due to its biocompatible construction and the absence of an external tether or incision.

[0006] The size of the device is chosen such that it can be inserted into the human or animal body, in particular in vessels thereof. The size may for example be in the range of some millimetres, for example between 1 - 10 mm, more in particular between 1 - 8 mm, even more in particular between 1 - 5 mm, most in particular between 3 - 8 mm, or in the range of microns, for example between 20 - 1000 micron, more in particular between 20 - 500 micron. Other sizes are possible as well. For example, the device may have a minimal length of 20 micron, 40 micron, 60 micron, 80 micron, 100 micron, 150 micron, 200 micron, 250 micron, 300 micron, 350 micron, 400 micron, 450 micron, 500 micron, 600 micron, 700 micron, 800 micron, 900 micron, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm. For example, the device may have a maximum length of 10 mm, 9 mm, 8 mm, 7 mm, 6 mm 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, 900 micron, 800 micron, 700 micron, 600 micron, 500 micron, 450 micron, 400 micron, 350 micron, 300 micron, 250 micron, 200 micron, 150 micron, 100 micron, 80 micron, 60 micron, 40 micron.

[0007] Examples of vessels include blood vessels such as veins or arteries, lymphatic vessels, urinary system vessels such as the urethra or ureters, seminal vessels, saliva ducts, bile ducts and more.

[0008] Examples of tissue include organs such as the liver, pancreas, kidney, and brain, as well as soft connective structures including muscle tissue, adipose tissue, and glandular tissue. These biological environments differ significantly in mechanical and rheological characteristics: for example, liver and pancreas tissue exhibit viscoelastic and highly heterogeneous compositions; kidney tissue presents fibrous regions with localized stiffness variations; and brain tissue represents an ultra-soft, gelatinous viscoelastic medium.

[0009] The device is capable of navigating and mechanically penetrating such tissues and organs, enabling local delivery of drugs or radioactive agents directly within or adjacent to pathological regions such as ischemic clots, tumors, fibrotic lesions, and necrotic zones. More in particular, the device may for example be used to dissolve a material part, such as a blood clot or any other occlusion, from a human or animal body.

[0010] For example, the device of in particular any of claims 25 - 26 can be used to be inserted into the human or animal body, for example into a vessel thereof, and can be controlled to move towards the material part and optionally enters the material part. Once the device is located close to or within the material part, the device is able to chemically dissolve the material part. After dissolving the material part, the device can be removed from the human or animal body by controlling the device to move in a reverse direction, or the device or part thereof may be dissolvable in the human or animal body.

[0011] In otherwords, the device can comprise blood-dissolving medication and can be moved into the blood clot.

[0012] Alternatively or additionally, the device may for example be used to treat a tumor. For example, the device can be used to be inserted into the human or animal body and can be controlled to move towards the tumor. Once the device is located close to or within the tumor, the device is able to treat the tumor by means of radioactive radiation provided by labelling with / or implanting radioactive materials. The Materials can contain for example beta emitters or alpha emitters like but not limited to the radioisotopes Lutetium-177, Therbium-161 , Holmium- 166, Yttrium-90, Rhenium-186, Rhenium-188, Actinium-225 or diagnostic isotopes like Technetium-99m. After treating the tumor, the device can be removed from the human or animal body by controlling the device to move in a reverse direction, or the device may stay in the tumor. The applicant has found out, that leaving the device in the tumor has no harmful effect on the human or animal body.

[0013] In otherwords, the device can be equipped with or can comprise radioactive cancer drugs like beta and / or alpha emitters and can be moved precisely to the tumor.

[0014] The device may be moved in the human or animal body by applying said external magnetic field. External means external to the human or animal body. By applying the magnetic field the device can be controlled to move forward, in particular by rotating the device along its longitudinal axis in a first direction, for example clockwise, or backward, in particular by rotating the device along its longitudinal axis in a second, opposite direction, for example anti-clockwise, and / or to make a turn. The speed of the device may also be controlled. Because the device is externally controlled, the device may be relatively small for insertion into the body.

[0015] An embodiment of the device that is used for removing clots by dissolving clots is described below in more detail. The device may have any one or more of the below described features, alone or in any suitable combination. None of the described features is essential. This embodiment is provided only as an example.

[0016] Problem Statement: Current methods for clot (refers to blood clots and other occluding materials) retrieval in vessels interventions, such as catheter-based techniques, face significant limitations in terms of invasiveness, manoeuvrability, and dependency on tethered systems. These limitations often result in incomplete clot removal, prolonged procedure times, and increased risk of complications. Effective and efficient treatment of vascular occlusions, which can lead to critical conditions like strokes, and heart attacks and limbs amputations, remains a major medical challenge.

[0017] Examples of vessels include blood vessels such as veins or arteries, lymphatic vessels, urinary system vessels such as the urethra or ureters, seminal vessels, saliva ducts, bile ducts and more.

[0018] Occlusions are any flow limiting blockages in the vessel which are caused by local buildup of atherosclerotic material, atherosclerotic emboli, migrating blood clots, biological stones or the like

[0019] Invention Overview: The system comprises an untethered robotic device designed to revolutionize the approach to clot retrieval in vascular interventions. By using advanced magnetic actuation technology, this invention addresses the key limitations of traditional catheter-based methods, providing a wireless, highly manoeuvrable solution that enhances procedural efficiency and patient safety. The system operates by using external magnetic fields to induce controlled motion and rotation in the robotic device. External is with reference to the human or animal body. The device is composed of a flexible, biocompatible material embedded with magnetic nanoparticles and ferromagnetic cores. The device is coated with LipoCoat 4AC to prevent any coagulation during the locomotion in the bloodstream. When subjected to an external magnetic field, the magnetic material generate torque, causing the device to rotate and propel through the bloodstream. The rotational motion is precisely controlled by adjusting the magnetic field's strength and orientation, allowing the device to navigate through intricate vascular structures and reach the site of the clot. Once the device reaches the clot, it can dissolve the clot by means of the anticoagulant drug.

[0020] Comparison to Other Inventions. The device stands out from other clot removal methods due to its wireless, magnetic actuation system. Traditional catheter-based systems rely on manual navigation, which can be limited by the operator's skill and the vascular anatomy's complexity. These systems often struggle with reaching clots in tortuous or narrow vessels, posing a risk of vessel damage.

[0021] The device according to this explanatory embodiment of the invention is the first device capable of swimming untethered toward a blood clot and to dissolve the blood clot. The helical body of the device has an optimal helical pitch based on its diameter, ensuring optimal swimming speed when deployed within a confined space.

[0022] Components and Functionality

[0023] Untethered Micro-Robotic Device: The system comprises a compact, untethered robotic device capable of navigating through the intricate vascular pathways. Its small size and wireless nature allow it to reach locations that are difficult or impossible for traditional catheters.

[0024] Scalability: The optimal combination of helical pitch relative to the diameter of the elongated body enables the device to be scaled according to the vessel diameter between the point of deployment and the location of the blood clot.

[0025] Magnetic Actuation Mechanism: The device is equipped with magnetic elements that enable precise control and manoeuvrability via an external magnetic field. This allows the device to be steered accurately through the bloodstream, avoiding obstacles and reaching the site of the clot with minimal disruption to the surrounding tissues.

[0026] The magnetic actuation works in sync with the unique body design, enabling propulsive thrust to be generated by the screw-shaped body.

[0027] The device may be fabricated using a composite material of resin and magnetic nanoparticles, offering a unique dual functionality. The magnetic nanoparticles not only enhance the magnetic moment during wireless magnetic actuation, providing superior control and manoeuvrability, but also significantly increase radiation absorption and reflection. This dual enhancement ensures exceptional visibility and accuracy during X-ray-guided or ultrasound-guided imaging, making the device distinctly more effective for precise navigation and clot removal.

[0028] The specific ratio of resin to nanoparticles in the device can be optimized to ensure optimal buoyancy in blood. This precise balance is beneficial for maintaining effective propulsion and stability within the vascular environment.

[0029] Novelty and Advantages

[0030] Minimally Invasive: Unlike traditional catheter-based systems, the device is untethered, significantly reducing the invasiveness of the procedure. This leads to shorter recovery times and lower risk of complications for patients. Enhanced Manoeuvrability: The wireless and magnetically actuated nature of the device allows for superior manoeuvrability, enabling the device to navigate complex and narrow vascular pathways that are challenging for conventional methods.

[0031] Improved Efficiency and Efficacy: The precise control afforded by the magnetic actuation mechanism ensures efficient and accurate clot retrieval, potentially reducing procedure times and improving overall outcomes.

[0032] Interdisciplinary Innovation: The proposed device represents a convergence of robotics, micro-robotics, magnetic actuation, and advanced imaging techniques. This interdisciplinary approach brings together expertise from various fields, resulting in a highly innovative and effective solution for vascular interventions.

[0033] As described above, this was an example of using the device for blood clot removal by dissolving the blood clot. As described above, the system and device according to the invention may be used for any suitable purpose and the inventions is only limited to the claims. Below the claims and features thereof or features relating thereto will be explained in further detail with respect to embodiments of the device.

[0034] In an embodiment of the device according to the invention, the device comprises a helical vane. The helical vane is configured to generate propulsion torque under the applied magnetic field, thereby enhancing swimming in non-Newtonian blood and enabling drilling or screwing motion through viscoelastic tissue or vessel walls. The helical vane may be an integral part of the device.

[0035] As a result of the helical vane, the device may be substantially screw or helical shaped.

[0036] In some embodiments, the device may comprise two or even more helical vanes, such that for example, the device may have a substantially double helical shape. If hereafter reference is made to the helical vane, it may refer to one helical vane of the device, to two or more helical vanes of the device, or to one out of two or more helical vanes of the device.

[0037] In an embodiment of the device according to the invention the helical vane has a pitch that is determined in accordance with a desired movement of the device through the body. The pitch may be optimized not only for swimming efficiency in non-Newtonian blood and for drilling or screwing penetration through viscoelastic tissue or vessel walls, but also to define the device’s magnetic step-out frequency, thereby enabling motion differentiation between multiple devices actuated simultaneously for targeted delivery or treatment, including treatment of a tumor.

[0038] Said pitch may be constant over a length of the device, wherein said pitch is for example between 0.5 - 8 mm, more in particular between 1 - 3 mm, or is for example between 20 - 1000 micron, more in particular between 20 - 500 micron, and / or wherein said pitch is for example between 10% and 30% of the length of the device. Other pitches are possible as well. For example, the device may have a minimal pitch of 20 micron, 40 micron, 60 micron, 80 micron, 100 micron, 150 micron, 200 micron, 250 micron, 300 micron, 350 micron, 400 micron, 450 micron, 500 micron, 600 micron, 700 micron, 800 micron, 900 micron, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm. For example, the device may have a maximum pitch of 8 mm, 7 mm, 6 mm 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, 900 micron, 800 micron, 700 micron, 600 micron, 500 micron, 450 micron, 400 micron, 350 micron, 300 micron, 250 micron, 200 micron, 150 micron, 100 micron, 80 micron, 60 micron, 40 micron.

[0039] From experiments it was found that a pitch within such range allows the device to travel through blood and / or tissue.

[0040] Alternatively said pitch may vary over a length of the device, said pitch for example varying between 0.5 - 8 mm, more in particular between 1.8 - 6 mm, or varying between 20 - 1000 micron, more in particular between 20 - 500 micron, and / or wherein said pitch may for example vary between 10% and 100% of the length of the device. Other varying pitches are possible as well. For example, the device may have a minimal pitch of 20 micron, 40 micron, 60 micron, 80 micron, 100 micron, 150 micron, 200 micron, 250 micron, 300 micron, 350 micron, 400 micron, 450 micron, 500 micron, 600 micron, 700 micron, 800 micron, 900 micron, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm. For example, the device may have a maximum pitch of 8 mm, 7 mm, 6 mm 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, 900 micron, 800 micron, 700 micron, 600 micron, 500 micron, 450 micron, 400 micron, 350 micron, 300 micron, 250 micron, 200 micron, 150 micron, 100 micron, 80 micron, 60 micron, 40 micron. The pitch may vary between any of these minimum and maximum values.

[0041] From experiments it was found that a pitch varyingwithin such range allows the device to travel through blood and / or tissue. In particular a device designed to “swim” through blood may have such a varying pitch.

[0042] Said pitch may gradually increase over the length of the device, in particular as seen in one length direction thereof. It will be clear that as seen in the opposite direction the pitch decreases over the length of the device. By gradually increasing the pitch of the helical vane along the length of the device, the forward propulsion in non-Newtonian blood at lower rotation speeds is enhanced, and it also increases the drilling efficiency in viscoelastic tissue or vessel walls at higher rotation speeds, while providing smoother transition between swimming and penetration modes.

[0043] In an embodiment of the device according to the invention, the device comprises at least one sharp tip, at least at one longitudinal end thereof, optionally at two longitudinal ends thereof. Such a sharp tip may allow the device to enter for example the blood clot or other material part or occlusion. Alternatively or additionally, such a sharp tip may allow the device to drill through tissue and / or vessel walls.

[0044] In this respect it is noted that in this and other embodiments the device may have a substantially cylindrical shape, having two longitudinal ends.

[0045] The sharp tip may alternatively be referred to as a pointy or tapered tip or end.

[0046] In an embodiment of the device according to the invention, the device comprises at least one fin-shaped element at least at one longitudinal end thereof, optionally at two longitudinal ends thereof.

[0047] Such a fin-shaped element may enhance the swimming or propagation properties of the device through a fluid such as blood.

[0048] In an embodiment the device may have a sharp tip at one end thereof, and a fin-shaped element at the other end thereof.

[0049] In an embodiment the device may have both a fin-shaped element and a sharp tip at one or both longitudinal ends of the device.

[0050] The fin-shaped element may be defined by the free end of the helical vane.

[0051] The longitudinal end may comprise two such fin-shaped elements, for example defined by the free ends of a double helical vane of the device.

[0052] In an embodiment of the device according to the invention, said device comprising a substantially cylindrical body, optionally wherein said cylindrical body comprises said helical vane, optionally wherein said cylindrical body and said helical vane are formed by one integral part.

[0053] A cylindrically shaped body is streamlined for moving through the human or animal body.

[0054] The substantially cylindrical body comprising said helical vale can also be referred to as a substantially helical or screw shaped body, optionally a double helical body.

[0055] In an embodiment of the device according to the invention, said cylindrical body is a hollow body.

[0056] Such a hollow body provides an internal accommodation space or chamber, for example for accommodating certain components of the device.

[0057] The hollow space of the hollow body may be in communication with the outside of the device, i.e. the hollow space may be accessible from outside, or it may be fully enclosed by the body.

[0058] The hollow space defined by the hollow body may extend in the longitudinal direction of the cylindrical body and may be concentric therewith, such that it is a substantially hollow cylinder. In other embodiments, the hollow space of the hollow body may just be defined by a hollow chamber of any suitable shape at any suitable location.

[0059] In an embodiment of the device according to the invention, said device comprises a pinshaped element, said pin-shaped element extending at least partly through the hollow body.

[0060] In such an embodiment the pin-shaped element is located in the hollow space of the hollow body, in particular of the hollow cylindrical body, and may optionally completely fill the hollow space.

[0061] In an embodiment of the device according to the invention, the pin-shaped element comprises said at least one sharp tip, wherein the pin-shaped element extends out of at least one of the longitudinal ends of the hollow body such that the sharp tip defines a first end of the device.

[0062] In such an embodiment the sharp or pointy tip of the pin-shaped element defines the sharp or pointy end or tip of the device, for penetrating or drilling through occlusions, tissue or vessel walls.

[0063] In an embodiment of the device according to the invention, said at least one magnet or magnetizable element is arranged within a hollow space defined by the hollow body.

[0064] For example, the at least one magnet or magnetizable element may be located in a centrally located hollow space and may be fully enclosed by said body.

[0065] Alternatively, said at least one magnet or magnetizable element substantially has the shape of a hollow cylinder, wherein the at least one magnet or magnetizable element is positioned between the pin-shaped element and the hollow body. In this case the magnet surrounds the pin-shaped element and thereby providing a more balanced magnetic torque for propulsion.

[0066] In such an embodiment the magnet or magnetizable element extends around the pinshaped element, and the hollow body extends around the magnet or magnetizable element. In such an embodiment the magnet or magnetizable element may extend over the full length of the pin-shaped element and / or hollow space defined by the hollow body, or over only a part thereof.

[0067] In an embodiment two such magnets or magnetizable elements may be provided, which are each positioned between the pin-shaped element and the hollow body at two opposing longitudinal ends of the pin-shaped element and / or hollow body. In such an embodiment the magnets or magnetizable elements may close off the hollow space defined by the hollow body.

[0068] In an embodiment of the device according to the invention, said at least one magnet or magnetizable element comprises a plurality of magnetic or magnetizable particles embedded in at least part of the device, for example in at least part of the cylindrical body thereof. For example, such magnetic or magnetizable particles may comprise metal particles, for example iron particles.

[0069] The particles may be powder.

[0070] Such an embodiment comprising magnetic or magnetizable particles may in particular be advantageous if the device or part thereof is dissolvable, as will be explained later. In such a case only small magnetic or magnetizable particles remain in said human or animal body, which is not harmful forthe human or animal body.

[0071] In an embodiment of the device according to the invention, said at least one magnet is a permanent magnet.

[0072] In an embodiment of the device according to the invention, said at least a portion of the device, in particular at least a portion of the cylindrical body and / or helical vane thereof, is coated with a lipid-based biocompatible layer and / or an anti-inflammatory drug layer.

[0073] Such lipid-based biocompatible coating will ensure long-term stability and effectiveness within biological environments. An anti-inflammatory drug layer may be provided to minimize inflammation as the device travels through the body and for example transitions from the arteries to the tumor site, further enhancing its safety and compatibility. The coating may be configured to modulate the biodegradation rate of the device or part thereof, thereby enabling controlled timing of therapeutic and / or radioactive material release within the body.

[0074] In an embodiment of the device according to the invention, said device or part thereof, for example the cylindrical body and / or helical vane, is dissolvable.

[0075] An advantage of such a dissolvable device or part thereof is that the device may dissolve in the human or animal body and does not need to be retrieved.

[0076] Practically said device or part thereof is dissolvable in blood or tissue.

[0077] In other words, in such an embodiment the device or part thereof is made of a material that dissolves in blood or tissue.

[0078] Practically said device of part thereof is dissolvable in blood or tissue within a time period of less than 10 minutes, thereby enabling rapid release of the embedded therapeutic and / or radioactive material directly at the target site.

[0079] Practically said device or part thereof is made of a dissolvable material, said dissolvable material for example comprising a biocompatible sugar-based matrix including sucrose. Sucrose is a material that allows said device or part thereof to be manufactured by any suitable manufacturing process, such as for example molding or 3D-printing, and allows for handling of the device or part thereof, and it is dissolvable in the human or animal body within suitable time range without causing any harm to the human or animal body. In addition, said device or part thereof may further comprises ethylenediaminetetraacetic acid (EDTA) and / or alginic acid and / or water. These additional components may tailor the dissolution rate of the material in blood or tissue and to stabilize the embedded therapeutic and / or radioactive agent during fabrication and release. As an example, such a device may be manufactured by mixing and heating sucrose, ethylenediaminetetraacetic acid (EDTA), alginic acid and water, and pouring this mixture into a mould having a suitable shape. After cooling down and thereby curing, the device is obtained. Optionally insert elements, such as wires, are arranged into the mixture before it is cured, thereby creating the hollow space of the device.

[0080] In an embodiment of the device according to the invention, the device comprises a drug. Such a drug may be any desired drug for treating a specific decease, tumor or disorder.

[0081] Examples of drugs, but not limited to that for lung tumors are Cisplatine, gemcitabine, Carboplatine, Pembrolizumab, Nivolumab, Durvalumab. For liver tumors: Sorafenib, Bevacizumab, Doxorubicine etc. For brain tumors: Temozolomide, Bevacizumab.

[0082] For example, said drug may be arranged to dissolve a material part, such as a blood clot.

[0083] In an embodiment of the device according to the invention, the drug comprises an anticoagulant, such as heparin, warfarin, dabigatran, apixaban, or rivaroxaban, or any combination thereof. Practically the drug may be embedded in the device.

[0084] In an embodiment of the device according to the invention, said device is a 3D-printed device, wherein the drug is embedded in the 3D-printing material.

[0085] In an embodiment of the device according to the invention, the device comprises a polymer matrix, wherein the drug is embedded in the polymer matrix.

[0086] In an embodiment of the device according to the invention, the device comprises a container for containing said drug.

[0087] In an embodiment of the device according to the invention, the container is defined by an internal chamber or cavity of the device, wherein said chamber or cavity is closed or sealed, for example by soldering iron.

[0088] Such an internal chamber or cavity may be defined by a hollow space of the device.

[0089] If the device is at least partly dissolvable, the drugs may be released as the device or part thereof dissolves.

[0090] If the device is not dissolvable, the device may be retrieved after releasing the drug.

[0091] In an embodiment of the device according to the invention, the device comprises a radioactive material. Preferably, a distribution of the radioactive material within the device is spatially configured to define a tailored radiation dose profile within a tumor. Such a radioactive material may be used for treating a tumor. In such a case the device may be moved such that it is positioned close to the tumor or may drill into the tumor.

[0092] For example, the radioactive material may comprise holmium, for example holmium 163 or holmium 166, or gold, for example gold 198.

[0093] The radioactive material may optionally be radioactive only after activation thereof, for example in a reactor.

[0094] In an embodiment of the device according to the invention, said pin-shaped element comprises said radioactive material.

[0095] In such an embodiment the pin-shaped element may have substantially the same length as the hollow body, optionally slightly longer and comprising a sharp or pointy tip to define the sharp or pointy end or tip of the device.

[0096] Alternatively or additionally, the device comprises a radioactive coating.

[0097] Alternatively or additionally, the radioactive material element is attached or labelled to said device. The radioactive material element can be incorporated using two fabrication methods. In a first method, referred to as Radioactivation inside the robot, a stable isotope such as165HO is embedded directly into a 3D-printed robot during fabrication. After printing, the entire RUMAR (i.e. device) is placed inside a neutron activation facility close or in the core of a research nuclear reactor, where the embedded isotope is neutron-activated into166Ho, making the robot radioactive. After activation, a magnetic core is attached to enable steering.

[0098] In a second method, referred to as Radioactive layer added after fabrication, the device is first manufactured with its magnetic core. Then a radioactive compound (e.g., holmium-166 chloride or gold-198 chloride, oryttrium-90 chloride or other salts and ion compounds that can be used for labelling) is labelled, coated, or clicked onto the surface of the RUMAR. This creates a controlled radioactive layer while keeping the robot steerable.

[0099] In both scenarios, the labelled / activated radioactive material remains fixed to the device during navigation and treatment. The surface is then protected with antifouling and antiinflammatory coatings to prevent coagulation and inflammation.

[0100] In an embodiment of the device according to the invention, the device or part thereof, in particular the cylindrical body and / or helical vane, comprises a biocompatible resin.

[0101] A biocompatible resin is a suitable material for insertion into the human or animal body.

[0102] The invention further relates to a system, comprising a device as described above and a source for creating a magnetic field, said source being controllable for controlling a direction and / or magnitude of the magnetic field. In an embodiment, the system comprises a robotic manipulator comprising an endeffector that carries a rotatable magnetic source comprising a single rotating magnet or a plurality of magnets distributed along the circumference of a rotatable disk, and a control system configured to control the rotation, position, and orientation of the magnetic source so as to steer and actuate the device within a vessel or tissue.

[0103] In an embodiment, the rotation of the plurality of magnets produces an effective magnetic field frequency that is a multiple of the rotation frequency of the disk.

[0104] The rotating magnet(s) may be a rotating permanent magnet(s). Alternatively, the rotating magnet(s) may be a rotating electro-magnet(s) comprising a coil(s).

[0105] In an embodiment, the controlling system is arranged to drive the device when being in a bodily fluid or tissue, by way of suitably manoeuvring the rotating magnet in the vicinity of the device. The rotating magnet(s) enables a propulsion of the device in non-Newtonian fluids such as blood and drilling or penetration through viscoelastic tissue without requiring a tether or physical contact.

[0106] In an embodiment, the robotic manipulator is a 6-degrees-of-freedom (DOF) manipulator. Such a robotic manipulator enables flexibility in steering the device by way of controlling the location and orientation of the rotatable magnet.

[0107] In an embodiment, the system comprises detecting means for detecting the device in the bodily fluid or tissue. The detecting means may comprise at least one of an X-ray or CT imaging system, an ultrasound system, a magnetic resonance imaging system, a magnetic particle imaging system, or a scintigraphy or SPECT or PET systems configured for radioactive dose mapping.

[0108] In an embodiment the controlling system is arranged to receive information from the detecting means and to control the device using the received information.

[0109] By integrating real-time imaging techniques into the system, real-time visualization of the device's position and the surrounding vascular environment is possible. Also, computational modelling may be used to simulate various vascular conditions, optimizing the design and functionality of the device for different clinical scenarios.

[0110] In an embodiment, the controlling system is arranged to receive a backward instruction, and drive the device in a backward direction by reversing the rotation direction of the rotating magnet.

[0111] In an embodiment, the detecting means are arranged to provide feedback of radio-active dose distribution, and the control system is arranged to adjust a device position or dissolution rate based on the measured dose distribution. In an embodiment, the control system is loaded with an algorithm configured to autonomously plan a navigation path to a clot or tumor and to confirm target engagement before release of a therapeutic or radioactive dose.

[0112] The invention further relates to a method for controlling the movement of a device as described above in a human or animal body by a controlling a magnetic field, in particular a direction and / or magnitude of the magnetic field.

[0113] In an embodiment, the direction of the magnetic field causes the device to rotate along its longitudinal axis either in a first direction or in a second, opposite direction, and wherein the rotation of the device in the first direction causes the device to move in a first, substantially longitudinal direction and the rotation of the device in the second direction causes the device to move in a second, opposite direction.

[0114] In an embodiment, geometric and / or magnetic properties of the device are selected to produce a distinct magnetic step-out frequency, thereby enabling simultaneous navigation of multiple devices in the same patient through frequency-based motion differentiation.

[0115] In an embodiment, the device remains magnetically steerable during partial dissolution of the material, enabling navigation and controlled release of a therapeutic and / or radioactive agent while the device degrades.

[0116] In an embodiment, drilling by means of the device through a vessel wall or tissue triggers accelerated dissolution of an antimicrobial and / or anti-inflammatory coating to reduce infection or inflammatory response at the penetration site.

[0117] The invention also relates to a method for dissolving a material part, such as a blood clot or any other occlusion, from a human or animal body, said method comprising the use of the device as described above.

[0118] The invention also relates to a method for treating a tumor, said method comprising the use of the device as described above.

[0119] In an embodiment, the method comprise magnetically actuating the device of any of the preceding claims to drill into the target tissue and releasing a therapeutic or radioactive agent through controlled dissolution at the drilled location.

[0120] Finally, the invention also relates to a method of delivering a spatially distributed radiation dose into a tumor of a human or animal body, the method comprising simultaneously navigating multiple devices of distinct step-out frequencies and allowing them to dissolve at different positions within the tumor.

[0121] The invention will be described with respect to the following figures: Fig. 1 shows a schematic view of the device according to a first embodiment of the invention and the use of the device as it is controlled to move through a human or animal vessel in order to dissolve a blood clot;

[0122] Fig. 2 shows the device of the first embodiment in a schematic perspective view.

[0123] Fig. 3 shows an exemplary method for making the device of figure 2;

[0124] Fig. 4 shows how the device of figure 2 may dissolve in time;

[0125] Fig. 5 shows a schematic view of the device according to a second embodiment of the invention and the use of the device as it is controlled to move through a human or animal vessel and tissue in order to treat a tumor;

[0126] Fig. 6 shows four embodiments of a device for treating a tumor in a perspective view;

[0127] Fig. 7 shows two exemplary methods for making any of the devices of figures 5 or 6;

[0128] Fig. 8 schematically shows a system according to an embodiment of the invention.

[0129] Figure 1 shows a device 10, in particular a robot, more in particular an untethered micro- robotic device (UMR) that is inserted into a human or animal body. Figure 1 also shows a cross sectional view of two lungs 21 and a heart 22 of a human or animal. At the right side Figurel shows three exploded views of a part of one of the lungs 21 in which a blood clot 20 is present. The three exploded views show three different moment in time to explain the working of the device 10.

[0130] First, the UMR 10 is inserted into a vessel, optionally using a superficial vein, and is controlled by an external, in this case rotating, magnetic field to move through the vessels of the human lungs 21 into the direction of the blood clot 20 that occludes one of the vessels of one of the lungs 21 and to drill into the blood clot 20, such that the UMR 10 is located within the blood clot 20. Within the blood clot 20 the UMR 10 releases a drug that dissolves the blood clot. The release of the drug may be controlled in time, for example by using a UMR 10 that dissolves itself within a chosen time period and upon dissolving gradually releases the drug. The time period in which the UMR 10 dissolves may be chosen by choosing a suitable material and / or size and / or shape of the UMR 10.

[0131] Figure 2 shows the device 10 in more detail. This figure shows that the device 10 comprises a substantially cylindrical body 11 including in this case a double helical vane 12 that is spread around said body 11 . In this embodiment the body 11 and double helical vane 12 are formed by one integral part. Within the body 11 and / or within the double helical vane 12 iron particles are distributed, which iron particles are magnetizable for controlling the movement of the device 10 within the human or animal body by means of the external magnetic field. The external magnetic field will make the device 10 rotate around its rotation axis 13. Within a hollow space (not shown) within the body 11 a drug is present, which drug is released when the device 10 dissolves. The drug may be an anticoagulant, such as heparin, warfarin, dabigatran, apixaban, or rivaroxaban, or any combination thereof. The body 11 and vane 12 may be made from a material comprising sucrose, optionally combined with ethylenediaminetetraacetic acid (EDTA) and / or alginic acid and / or water. Such a body 11 and vane 12 are dissolvable in the human or animal body without causing any harm to the human or animal body. Only the iron nanoparticles remain in the human or animal body, and due to their size being significantly smaller than blood cells, they do not obstruct vessels or interfere with normal physiological functions. Figure 3 shows how the device 10 of figure 2 is manufactured in an experimental setup. This figure 3 shows, see step 1 , that first sucrose, ethylenediaminetetraacetic acid (EDTA), alginic acid, water and iron oxide nanoparticles are provided, which are heated and stirred until the mixture obtains a temperature of 130 °C, see step 2. The mixture is then scooped or poured into a lower part of a mold, in particular a silicon mold, see step 3. Next, wires are inserted in the mixture in the mold, one per device, and a top part of the mold is placed on top of the mixture and lower part of the mold, see step 4. The mixture dries and cures in the mold. Next, the wires are removed from the cured mixture, leaving a hollow space in the cylindrical bodies. The hollow space is filled with said drug and after filling the hollow space is sealed or closed. Optionally the device is cleaned with tweezers. Step 5 shows four simultaneously produced devices.

[0132] It will be clear that the manufacturing method of figure 3 is provided by means of example only and is in particle suitable for manufacturing a small amount of devices. In a production process, similar or different production steps may be performed using suitable machines that allow mass production.

[0133] Figure 4 shows six photos to show the dissolvement of the device in time. The photos show that the device dissolves gradually and so also the drug is released gradually through time. During dissolving the device may break into multiple parts.

[0134] Figure 5 shows a device 110, in particular a robot, more in particular a radio-active untethered micro-robotic device (RUMAR) that is inserted into a human or animal body. In this case the RUMAR 110 is inserted into a vessel and is controlled by an external, in this case rotating, magnetic field to move through the vessels of the human brains into the direction of a tumor 120, such that the RUMAR 110 is located close to the tumor 120. As a result of locating the radio-active device 110 near the tumor 120, the tumor is effectively treated, while causing little harm to the remainder of the human or animal body.

[0135] Figure 6 shows four different types of RUMARs. From left to right, the first RUMAR is of the so-called drill type and comprises a pointy or sharp end at both longitudinal ends of the substantially cylindrical body, such that the RUMAR is able to drill through vessel walls and / or tissue. The first RUMAR has a length of about 6.8 mm, and the helical vane thereof has a constant of about 2 mm. The second RUMAR is also of the drill type and only differs from the first RUMAR in that it has a length of 5.3 mm and a constant pitch of 1 mm. The third RUMAR is of the so-called swim type, which differs from the drill type in that is has a fin-shaped element at both longitudinal ends of the substantially cylindrical body and has a varying pitch that varies between 1.8 - 6 mm over the length of the substantially cylindrical body. The fin-shaped element is defined by the free end of the helical vane. The fourth RUMAR is again of the drill type and differs only from the first RUMAR in that it has a length of 7 mm and a constant pitch of 1 mm. It will be clear that the four RUMARs are exemplary only and that other RUMARs may have same or different sizes, pitches, pointy or non-pointy ends, less or more fin-shaped elements.

[0136] Figure 7 schematically shows two methods for making any of the RUMARs of figures 5 or 6, or any other desired RUMAR. It shows that the RUMAR in essence comprises three components, namely a body, in this case a substantially cylindrical body comprising at least one helical vane, a radioactive source that is optionally only radioactive after activation thereof, and at least one magnet or magnetizable element.

[0137] Figure 8 schematically shows a system 500 according to an embodiment of the invention. The system 500 comprises a robotic manipulator 501 comprising an end-effector 502. A rotating magnet 503 is rotatably arranged at the end-effector 502. The rotating magnet 503 creates a rotating magnetic field. The system further comprises a controlling system 504 for controlling rotation, position and orientation of the rotating magnet 503. Preferably, the rotating magnet is a rotating permanent magnet. In this embodiment, the system also comprises detecting means 505. A human body 506 is lying on a table in the vicinity of the rotating magnet 503. A device 510 as described above has been inserted into the human body 506, for example into the vessels. The controlling system 501 is arranged to drive the device 510 when being in a bodily fluid or tissue, by way of suitably manoeuvring the rotating magnet 503 in the vicinity of the device 510.

[0138] The robotic manipulator 501 may be a 6-degrees-of-freedom (DOF) manipulator. Such a manipulator is preferred so as to be able to manoeuvre the magnet 503 over the body 506 in any possible way.

[0139] The detecting means 505 are arranged for detecting the device 510 in the bodily fluid or tissue of the body 506. Examples of such detecting means are optical detection means using reflection or fluorescence, ultra-sound detection means, radiation detection means, such as X- ray or CT, and magnetic detection means using MRI, MPI or other magnetic techniques. The controlling system 504 may be arranged to receive information from the detecting means 505 and to control the device 510 using the received information. This enables real time control of the device 510, and even automatic control of the device 510. Although the invention is elucidated above on the basis of a number of specific examples and embodiments, the invention is not limited thereto. Consequently, the scope of the invention is defined by the following claims.

Claims

Claims1 . Device, in particular a robot, arranged to be inserted into a human or animal body, for example in a vessel or tissue thereof, and to move through said human or animal body, said device comprising at least one magnet or magnetizable element for cooperating with an externally applied magnetic field so as to control the movement of said device in the human or animal body by a magnetic field.

2. Device according to claim 1 , wherein the device comprises a helical vane.

3. Device according to claim 1 or 2, wherein the helical vane has a pitch that is determined in accordance with a desired movement of the device through the body.

4. Device according to claim 3, wherein said pitch is constant over a length of the device, wherein said pitch is for example between 20 micron - 8 mm, or between 0.5 - 8 mm, or between 1 - 3 mm, or between 20 - 1000 micron, or between 20 - 500 micron, and / orwherein said pitch is for example between 10% and 30% of the length of the device..

5. Device according to claim 3, wherein said pitch varies over a length of the device, said pitch for example varying between 20 micron - 8 mm, or between 0.5 - 8 mm, or between 1.8 - 6 mm, or between 20 - 1000 micron, or between 20 - 500 micron, and / orwherein said pitch may for example vary between 10% and 100% of the length of the device.

6. Device according to claim 5, wherein said pitch gradually increases over the length of the device.

7. Device according to any of the preceding claims, wherein the device has a length between 20 micron - 10 mm, or between 1 mm - 10 mm, or between 1 - 8 mm, or between 1 - 5 mm, or between 3 - 8 mm, or between 20 - 1000 micron, or between 20 - 500 micron.

8. Device according to any of the preceding claims, wherein the device comprises at least one sharp tip, at least at one longitudinal end thereof, optionally at two longitudinal ends thereof.

9. Device according to any of the claims 1 - 8, wherein the device comprises at least one fin- shaped element at least at one longitudinal end thereof, optionally at two longitudinal ends thereof.

10. Device according to any of the preceding claims, said device comprising a substantially cylindrical body, optionally wherein said cylindrical body comprises said helical vane, optionally wherein said cylindrical body and said helical vane are formed by one integral part.11 . Device according to claim 10, wherein said cylindrical body is a hollow body.

12. Device according to claim 11 , comprising a pin-shaped element, said pin-shaped element extending at least partly through the hollow body.

13. Device according to claim 12, wherein the pin-shaped element comprises said at least one sharp tip, wherein the pin-shaped element extends out of at least one of the longitudinal ends of the hollow body such that the sharp tip defines a first end of the device.

14. Device according to at least claim 11 , wherein said at least one magnet or magnetizable element is arranged within a hollow space defined by the hollow body.

15. Device according to at least claims 12 and 14, wherein said at least one magnet or magnetizable element substantially has the shape of a hollow cylinder, and wherein the at least one magnet or magnetizable element is positioned between the pin-shaped element and the hollow body.

16. Device according to any of claims 1 - 13, wherein said at least one magnet or magnetizable element comprises a plurality of magnetic or magnetizable particles embedded in at least part of the device, for example in at least part of the cylindrical body thereof.

17. Device according to any of the preceding claims, wherein the at least one magnet is a permanent magnet.

18. Device according to any of the preceding claims, wherein at least a portion of the device is coated with a lipid-based biocompatible layer and / or an anti-inflammatory drug.

19. Device according to any of the preceding claims, wherein said device or part thereof is dissolvable.

20. Device according to claim 19, wherein said device or part thereof is dissolvable in blood or tissue.21 . Device according to any of claims 19 - 20, wherein said device of part thereof is dissolvable in blood or tissue within a period of 10 minutes.

22. Device according to any of claims 19 - 20, wherein said device or part thereof is made of a dissolvable material, said dissolvable material for example comprising a biocompatible sugar- based matrix including sucrose.

23. Device according to claim 22, wherein said device or part thereof further comprises ethylenediaminetetraacetic acid (EDTA) and / or alginic acid and / or water.

24. Device according to any of the preceding claims, wherein the device comprises a drug.

25. Device according to claim 14, wherein said drug is arranged to dissolve a material part, such as a blood clot.

26. Device according to claim 24 or 25, wherein the drug comprises an anticoagulant, such as heparin, warfarin, dabigatran, apixaban, or rivaroxaban, or any combination thereof.

27. Device according to any of claims 24 - 26, wherein the drug is embedded in the device.

28. Device according to claim 27, wherein said device is a 3D-printed device, wherein the drug is embedded in the 3D-printing material.

29. Device according to claim 27 or 28, wherein the device comprises a polymer matrix and wherein the drug is embedded in the polymer matrix.

30. Device according to any of claims 24 - 29, wherein the device comprises a container for containing said drug.2131 . Device according to claim 30, wherein the container is defined by an internal chamber or cavity of the device, wherein said chamber or cavity is closed or sealed, for example by soldering iron.

32. Device according to any of the preceding claims, wherein the device comprises a radioactive material, preferably wherein a distribution of the radioactive material within the device is spatially configured to define a tailored radiation dose profile within a tumor.

33. Device according to claim 31 , wherein the radioactive material comprises holmium, for example holmium 163 or holmium 166, or gold, for example gold 198 or for example Lutetium- 177, Therbium-161 , Holmium-166, Yttrium-90, Rhenium-186, Rhenium-188, Actinium-225 or diagnostic isotopes like Technetium-99m.

34. Device according to claim 32 or 33, wherein the radioactive material is radioactive upon activation thereof, for example in a nuclear research reactor.

35. Device according to any of claims 32 - 34, wherein said pin-shaped element comprises said radioactive material.

36. Device according to at least claims 12 and 35, wherein the pin-shaped element has substantially the same length as the hollow body.

37. Device according to any of claims 32 - 36, wherein the device comprises a radioactive coating.

38. Device according to any of claims 32 - 37, wherein the radioactive material element is attached or labelled to said device.

39. Device according to any of the preceding claims 1 - 18 and 25 - 28, wherein the device or part thereof comprises a biocompatible resin.

40. System, comprising a device according to any of claims 1 - 39 and a source for creating a magnetic field, said source being controllable for controlling a direction and / or magnitude of the magnetic field.2241 . System according to claim 40, comprising a robotic manipulator (501) comprising an endeffector (502) that carries a rotatable magnetic source comprising a single rotating magnet or a plurality of magnets distributed along the circumference of a rotatable disk, and a control system (504) configured to control the rotation, position, and orientation of the magnetic source so as to steer and actuate the device within a vessel or tissue.

42. System according to claim 41 , wherein the rotation of the plurality of magnets produces an effective magnetic field frequency that is a multiple of the rotation frequency of the disk.

43. System according to any one of claims 41 - 42, wherein the controlling system is arranged to drive the device when being in a bodily fluid or tissue, byway of suitably manoeuvring the rotating magnet in the vicinity of the device.

44. System according to any one of claim 41-43, wherein the robotic manipulator is a 6-degrees- of-freedom (DOF) manipulator.

45. System according to any one of claim 41-44, wherein the system comprises detecting means for detecting the device in the bodily fluid or tissue.

46. System according to any one of claim 41-45, wherein the controlling system is arranged to receive information from the detecting means and to control the device using the received information.

47. System according to any one of claims 41 - 47, wherein controlling system is arranged to:- receive a backward instruction, and- drive the device in a backward direction by reversing the rotation direction of the rotating magnet.

48. System according to any of the claims 41 -47 and at least claim 45, wherein the detecting means are arranged to provide feedback of radio-active dose distribution, and the control system is arranged to adjust a device position or dissolution rate based on the measured dose distribution.2349. System according to any of the claims 41 - 48, wherein the control system is loaded with an algorithm configured to autonomously plan a navigation path to a clot or tumor and to confirm target engagement before release of a therapeutic or radioactive dose.

50. Method for controlling the movement of a device according to any of claims 1 - 39 in a human or animal body by a controlling a magnetic field, in particular a direction and / or magnitude of the magnetic field.51 . Method according to claim 50, wherein the direction of the magnetic field causes the device to rotate along its longitudinal axis either in a first direction or in a second, opposite direction, and wherein the rotation of the device in the first direction causes the device to move in a first, substantially longitudinal direction and the rotation of the device in the second direction causes the device to move in a second, opposite direction.

52. Method according to any of the claims 50 - 51 , wherein geometric and / or magnetic properties of the device are selected to produce a distinct magnetic step-out frequency, thereby enabling simultaneous navigation of multiple devices in the same patient through frequencybased motion differentiation.

53. Method according to any of the claims 50 - 52, wherein the device remains magnetically steerable during partial dissolution of the material, enabling navigation and controlled release of a therapeutic and / or radioactive agent while the device degrades.

54. Method according to any of the claims 50 -53, wherein drilling by means of the device through a vessel wall or tissue triggers accelerated dissolution of an antimicrobial and / or antiinflammatory coating to reduce infection or inflammatory response at the penetration site.

55. Method for dissolving a material part, such as a blood clot or any other occlusion, from a human or animal body, said method comprising the use of the device as claimed in any of claims 1 - 39 and at least claim 19.

56. Method for treating a tumor, said method comprising the use of the device as claimed in any of claims 1 - 39 and at least claim 32.

57. Method according to claim 56, said method comprising magnetically actuating the device of any of the preceding claims to drill into the target tissue and releasing a therapeutic or radioactive agent through controlled dissolution at the drilled location.

58. Method of delivering a spatially distributed radiation dose into a tumor of a human or animal body, the method comprising simultaneously navigating multiple devices of distinct step-out frequencies and allowing them to dissolve at different positions within the tumor.

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