Propeller and method of moving the propeller

Abstract

A method of causing a propeller (1) to move relative to a medium (2) at least partially surrounding the propeller (1), wherein an actuator causes the propeller (1) to rotate relative to the medium (2) and about an axis of rotation (4) of the propeller (1), and the propeller (1) converts its rotational motion into a motion of the propeller (1) relative to the medium (2). The aspect ratio of at least one section (5) of the propeller (1) is 3 or more, wherein the section (5) is a section (5) related to the axis of rotation (4) of the propeller (1), or the aspect ratio of at least one section of a rotating body is 3 or more, wherein the rotating body includes the propeller (1) and a portion (10) of the medium that is separated from the remaining portion of the medium (2) due to the rotation of the propeller (1) and rotates with the propeller (1), the section being a section related to the axis of rotation (4) of the rotating body.

Description

[0001] This application is a divisional application of an application with an application date of April 11, 2018, application number 201880038191.7 (corresponding PCT application number PCT / EP2018 / 059331), and invention name “Propeller and method for moving a propeller”. Technical Field

[0002] The invention relates to a method for moving a propeller relative to a medium at least partially surrounding the propeller, wherein an actuator causes the propeller to rotate relative to the medium and about an axis of rotation of the propeller, and wherein the propeller converts its rotational movement into a movement of the propeller relative to the medium. Furthermore, the invention relates to a propeller of a helix or modified helix for converting the rotational movement of the propeller into a movement of the propeller relative to the medium. Furthermore, the invention relates to a method for manufacturing a propeller. Background Art

[0003] In many applications in medicine and biology, being able to penetrate biological media including biological fluids and soft tissues can be advantageous. For example, in minimally invasive procedures, such as targeted delivery of substances or minimally invasive surgery, it may be desirable to move a small, untethered device to penetrate the media because this approach is potentially less invasive and provides better control than approaches using larger or tethered devices.

[0004] Small untethered devices have been reported in the literature. For example, A Ghosh and P Fischer demonstrated in "Controlled Propulsion of Artificial Magnetic Nanostructure Propellers" (Nano Letters, vol 9, pp 2243 to 2245, 2009) and in the supporting information published with the paper that the rotation of a corkscrew shape can produce forward propulsion in a fluid. The rotation is affected by a rotating magnetic field. This concept is also described in US 8 768 501 B2. A slightly different shaped swimmer is disclosed in the publication "Artificial Bacterial Flagella: Fabrication and Magnetic Control" (Applied Physics Letters, vol 94, p 064107, 2009) by L Zhang, JJ Abbott, L XDong, BE Kratochvil, D Bell and BJ Nelson. This swimmer is also driven by a rotating magnetic field. K Ishiyama, M Sendoh, A Yamazaki and K I Arai in "Swimming microcomputer driven by magnetic torque" (Sensors and Actuators A: Physical, vol 91, pp 141 to 144, 2001) describe a screw several millimeters in length that penetrates bovine tissue (meat) samples when rotated by a rotating magnetic field.

[0005] T Qiu, J Gibbs, D Schamel, A Mark, U Choudhury and P Fischer in "Small-Scale Robotics, From Nano-to-Millimeter-Sized Robotic Systems and Applications, vol 8336, I Paprotny and S Bergbreiter, 1st ed Berlin: Springer, pp53 to 65, 2014" describe the fabrication of corkscrew-type propellers by means of a grazing angle deposition method (GLAD) and propellers more similar to conventional screws by means of microinjection molding. They also describe the motion of the propeller in an agarose gel when the propeller is actuated by means of a rotating magnetic field.

[0006] In all of the above disclosures, a portion of the thruster has a permanent magnetic moment orthogonal to its long axis, or the thruster is attached to a permanent magnet. Application of an external rotating magnetic field produces a torque that turns the untethered thruster and causes it to translate through the medium.

[0007] WO 2008 / 090549 A2 discloses a medical device for insertion into a patient's organ, which can be repeatedly moved by an external magnetic field. WO 2016 / 025768 A1 discloses nanoparticles that can move along the gradient of a magnetic field originating from a permanent magnet or an electromagnet. The nanoparticles have a high tendency to attach to target cells, and an electric field can be applied to the nanoparticles to produce an effect sufficient to cause the death of the target cells. WO 2011 / 073725 A1 discloses a handheld automatic biopsy device with a drill-like end. The device can be rotated by an actuator.

[0008] EP 2 674 192 A1 discloses a medical implantable device that can be implanted in a human or animal body. It comprises spirals wound together, one of which will be screwed into tissue when rotated. US 2012 / 0010598 A1 discloses a catheter insertion system that is provided with an external thread and can enter a body passage by means of rotation. US 2009 / 0248055 A1 discloses a tissue penetrating surgical device. The distal end of the device is at least partially covered by a fabric, and the device can drill into tissue by means of rotating the fabric.

[0009] Further miniaturization of existing devices may be challenging. Moreover, it has been proven difficult to obtain propulsion in viscoelastic media using existing devices. Known corkscrew shapes work well in viscous liquids such as water and glycerol, and elastic solids such as agarose and meat. However, many important tissues in the biomedical field are neither pure viscous fluids nor pure elastic solids. Instead, they are viscoelastic media that exhibit the combined properties of both liquids and solids. The inventors have found that known propeller shapes may be ineffective in viscoelastic media. Summary of the invention

[0010] Problem that the invention aims to solve

[0011] The object of the present invention is to provide an improved method for moving a propeller relative to a medium at least partially surrounding the propeller, wherein an actuator causes the propeller to rotate relative to the medium and around the propeller's axis of rotation, and the propeller converts its rotational motion into motion of the propeller relative to the medium. Another object of the present invention is to provide an improved helical or modified helical propeller, which is used to convert the rotational motion of the propeller into motion of the propeller relative to the medium. It is also an object of the present invention to provide an improved propeller. It is a further object of the present invention to provide an improved method for manufacturing a propeller. What can be achieved by using the present invention is to solve one or more of the above-mentioned problems in the prior art.

[0012] Solution according to the present invention

[0013] In one aspect of the invention, the problem is solved by providing a method for moving a propeller relative to a medium at least partially surrounding the propeller. An actuator causes rotation of the propeller relative to the medium and about an axis of rotation of the propeller, and the propeller converts its rotational motion into motion of the propeller relative to the medium. At least one cross section of the propeller has an aspect ratio of 3 or more, wherein the cross section is a cross section related to the axis of rotation of the propeller.

[0014] The inventors have discovered that such a large aspect ratio can significantly increase propulsion, particularly in viscoelastic media. Without being bound by a particular theory, the inventors believe that the present invention utilizes a newly discovered propulsion mechanism that utilizes elastic deformation of the medium caused by propeller rotation. A high aspect ratio can cause large deformations, thereby causing strong propulsion.

[0015] In the context of the present invention, the term "propeller" refers to a propulsion structure that is capable of achieving its own movement relative to a medium or the movement of a load attached to it relative to a medium. In the context of the present invention, the "aspect ratio" of a cross section is the maximum radius of the cross section divided by the minimum radius of the cross section, with the radius extending from the center of the cross section to the point at the periphery of the cross section. The center of the cross section is the point at which the axis "associated with" the cross section passes through the cross section. In addition, the cross section is perpendicular to the axis "associated with" the cross section. The periphery of the cross section is the outer boundary of the cross section. Therefore, if the cross section is associated with the axis of rotation of the propeller, the radius used to determine the aspect ratio extends from the point at which the axis of rotation passes through the cross section perpendicularly to the point at the periphery of the cross section. Similarly, if the propeller is a helicoid (see below) and the cross section is associated with the helical axis of the propeller, the radius used to determine the aspect ratio extends from the point at which the helical axis passes through the cross section perpendicularly to the point at the periphery of the cross section.

[0016] In another aspect of the invention, the problem is again solved by providing a method for moving a propeller relative to a medium at least partially surrounding the propeller. The actuator causes the propeller to rotate relative to the medium and around the axis of rotation of the propeller, and the propeller converts its rotational movement into movement of the propeller relative to the medium. In this aspect of the invention, the aspect ratio of at least one section of the rotating body is 3 or more, wherein the rotating body includes the propeller and the part of the medium that is separated from the residual part of the medium due to the rotation of the propeller and rotates with the propeller, and the section is a section related to the axis of rotation of the rotating body. Advantageously, using this aspect of the invention, it can be achieved that the part of the medium that is separated from the residual medium due to the rotation of the propeller rotates at the same speed as the propeller.

[0017] This embodiment of the invention is based on the inventors' discovery that part of the media can be separated from the residual media, for example due to adhesion, and thus rotate with the propeller. The inventors have found that this co-rotation can significantly hinder propulsion, but strong propulsion can still be achieved by means of the high aspect ratio of the rotating body of the co-rotating portion including one or more propellers and the media. Again without being bound by a particular theory, the inventors believe that in the newly discovered propulsion mechanism, propulsion is mainly caused by elastic deformation of the media that does not rotate with the propeller, and therefore the aspect ratio of the rotating body of the co-rotating portion including the propeller and the media is crucial to achieve strong propulsion.

[0018] In yet another aspect of the invention, the problem is solved by a helical or modified helical propeller for converting a rotational motion of the propeller into a motion of the propeller relative to a medium at least partially surrounding the propeller, wherein at least one cross section of the propeller has an aspect ratio of 3 or more, wherein the cross section is a cross section related to the helical axis of the propeller.

[0019] In the inventor's experiments, spiral and modified spiral shapes have been shown to be particularly suitable for achieving propulsion. In addition, spiral and modified spiral shapes have been shown to be easy to manufacture.

[0020] In the context of the present invention, a propeller is "helical" (hereinafter further referred to as a "helicoid") if its three-dimensional shape can be obtained by extending a two-dimensional shape along a curve while rotating the two-dimensional shape. The two-dimensional shape extends along a curve (hereinafter also referred to as the "helical axis") so that any two sections of the propeller can coincide with the two-dimensional shape if each section is intercepted perpendicular to the curve at the point where the curve passes through the section. The helical axis is the curve along which the two-dimensional shape extends. The helicoid is chiral. In the context of the present invention, a propeller is "chiral" if its shape is distinguishable from its mirror image shape; in other words, a propeller has chirality if the image of the propeller in a plane mirror (an ideal realization) cannot be made to coincide with itself. A propeller can also be chiral due to the orientation of its magnetic moment relative to the body of the propeller; in the context of the present invention, such a propeller is defined as "generalized chirality". This includes objects with an achiral bulk shape but with a magnetic moment appropriately oriented to make the propeller chiral.

[0021] In the context of the present invention, a "modified spiral" (hereinafter further referred to as a "modified helix") differs from a spiral in that the two-dimensional shape does not remain the same, but changes as it extends along a curve. The evolution of the two-dimensional shape is continuously differentiable (in a mathematical sense, as opposed to being discontinuous or non-differentiable). For example, the two-dimensional shape can be stretched or compressed in one dimension, it can be bent, or it can be scaled down or enlarged in both dimensions. As a result of the latter, for example, a part of the propeller or even the entire propeller can have a cone shape.

[0022] In another aspect of the present invention, this problem is solved by a method for manufacturing a propeller, which includes the following steps: (1) defining a straight helical axis; (2) providing a plate extending along the helical axis, wherein at least one cross-section of the plate (preferably all cross-sections) has an aspect ratio of 3 or greater, wherein the cross-section is a cross-section relative to the helical axis; and (3) applying a torque to the plate along the helical axis to twist the plate into a helical shape.

[0023] The method exploits the inventors' insight that the high ratio of width or length to thickness inherent in the definition of a plate can be converted into an aspect ratio of the helix if the helix is ​​twisted by applying a torque. The inventors have found that this forms a method for easily and reliably manufacturing screw propellers with high aspect ratios.

[0024] In another aspect of the present invention, the problem is solved by a method for manufacturing a propeller, which includes the following steps: (1) providing a first structure having a defined geometric shape; (2) molding the first structure in a second material, removing the first structure from the second material to produce a negative replica of the first structure; (3) injecting one or more molding materials into a negative mold and curing the molding materials under given physical and chemical conditions to form a second solid structure; and (4) releasing the second solid structure from the negative mold to obtain a defined propeller.

[0025] The present invention can be advantageously used for medical diagnosis and treatment, including endoscopy, biopsy, delivery of drugs or implants or radioactive materials, local heat generation. For example, the thruster can carry a payload attached to the thruster and release the drug at the disease location. In tumor treatment, the thruster can be pushed through normal tissue to the tumor tissue, and if the thruster is made of or includes metal and magnetic materials, heat can be generated in the material by induction heating to kill tumor cells. In addition, the thruster can drag a thin flexible tube to the tumor site, and the drug can be continuously delivered to the tumor through the tube. Similarly, the thruster can drag electrodes connected to wires and move to specific areas of the brain to measure neuronal electrical signals or apply electrical stimulation.

[0026] Preferred Embodiments of the Invention

[0027] Further preferred features of the invention, which can be used alone or in combination, are described in the dependent claims, the following description and the drawings.

[0028] In a preferred embodiment of the invention, at least one cross-section of the propeller (preferably all cross-sections) has an aspect ratio of 2 or more, more preferably 3 or more, more preferably 5 or more, more preferably 10 or more, more preferably 20 or more, more preferably 50 or more, more preferably 100 or more; one or more cross-sections are associated with the axis of rotation of the propeller, or optionally with the helical axis of the propeller. This embodiment of the invention makes use of the inventors' discovery that particularly high aspect ratios can result in particularly powerful propulsion. The cross-section is preferably a continuous shape.

[0029] Preferably, at least one section (more preferably each section) of the propeller relative to the axis of rotation of the propeller has a cross-sectional area that is at least 50%, more preferably 100%, more preferably 300%, more preferably 1000% of the cross-sectional area of ​​the portion of the media (in the same section) that is separated from the residual media due to the rotation of the propeller and rotates with the one or more propellers. This embodiment makes use of the inventors' discovery that co-rotating media can impede propulsion and that this impediment can be limited by limiting the amount of co-rotating material.

[0030] Preferably, in the case of at least one section of the propeller (more preferably in the case of all sections), the rotation axis of the propeller passes through the area of ​​the section, i.e. through the inside of the periphery of the section; one or more sections are associated with the rotation axis of the propeller, or alternatively with the helical axis of the propeller. In other words, in a preferred embodiment of the invention, the rotation axis or the helical axis at least partially passes through the propeller.

[0031] Preferably, at least 20%, more preferably at least 50%, more preferably at least 80%, more preferably at least 95% of the surface area of ​​the propeller has a surface roughness Ra (according to Deutsche Institut für Normung DIN 4760) of less than 3.2 μm, more preferably less than 1.6 μm, more preferably less than 0.4 μm, more preferably less than 0.025 μm, more preferably less than 0.006 μm. With this embodiment of the invention, it is advantageously possible to achieve a reduction in the adhesion of media such as biological tissue to the propeller, which adhesion could hinder movement. The surface roughness of the propeller is low, thereby minimizing the adhesion of media to the propeller surface.

[0032] Preferably, in order to minimize adhesion, the material of the propeller (at least at the surface of the propeller) is a metal, an anti-adhesion polymer and / or a biocompatible polymer. A coating can be applied to the surface of the propeller to minimize the adhesion of the medium on the propeller surface. A special actuation method can be applied to minimize the adhesion of the medium, which actuation method causes large shear forces on the surface, such as sudden start or stop of large angle rotation, large angle vibration. For example, before the propeller rotates a full circle, the vibration of the propeller can be applied with an amplitude gradually increasing from 10° to 300° and / or a frequency gradually increasing from 0.1 Hz to 10 Hz. Due to the viscoelasticity of the medium (e.g., shear-thinning effect), this actuation method reduces the starting torque required for the propeller to rotate a full circle.

[0033] In a particularly preferred embodiment of the invention, the low surface roughness is achieved by at least partially coating the surface of the propeller, more preferably coating the entire surface of the propeller. Preferred coating materials include Teflon, PEG (polyethylene glycol), titanium or a combination thereof.

[0034] In a preferred embodiment of the invention, at least one section (preferably all sections) of the rotating body including the propeller and part of the medium, wherein the part of the medium is separated from the residual medium due to the rotation of the propeller and rotates with the propeller, has an aspect ratio of 2 or more, more preferably 3 or more, more preferably 5 or more, more preferably 10 or more, more preferably 20 or more, more preferably 50 or more, more preferably 100 or more. The one or more sections are sections related to the axis of rotation of the rotating body. This embodiment of the invention makes use of the inventors' discovery that although co-rotation can hinder propulsion, powerful propulsion can still be achieved with the help of the high aspect ratio of the rotating body including the co-rotating part of one or more propellers and the medium. The cross section of the rotating body is preferably a continuous shape.

[0035] Preferred propellers are chiral. More preferably, the propeller is helical or modified helical. This embodiment of the invention is based on the following discovery of the inventors: chiral shapes (especially helical and modified helical shapes) can be particularly effective for achieving propulsion. In addition, helical and modified helical shapes have been shown to be easy to manufacture. Preferably, the helical axis is straight. If the propeller or propeller is a helicoid or a modified helicoid, the axis of rotation preferably coincides with the helical axis. Preferred helical or modified helical propellers have a constant pitch.

[0036] The preferred propeller has a forward taper at at least one end (more preferably at two opposite ends). In the context of the present invention, "forward taper" means that the propeller gradually becomes smaller or thinner towards the end of the propeller. Preferably, the front end of the propeller is provided with a forward taper. In the context of the present application, the "front end" is the leading side of the propeller relative to the direction of movement. The achievable advantage of this embodiment of the present invention is that the cone can reduce the area of ​​contact with the medium at the front end of the propeller. It can be achieved (especially when the medium has viscoelasticity) that the pressure applied by the propeller on the medium is greater than the tensile strength of the medium.

[0037] In one embodiment, if the propeller is a helicoid, the end of the cone is located on the axis of rotation and / or the spiral axis of the propeller. In another embodiment, if the propeller is a helicoid, the end is located eccentrically, i.e. away from the axis of rotation and / or away from the spiral axis. Particularly preferably, the end is located near the periphery relative to the axis of rotation or the spiral axis of the propeller. This embodiment can take advantage of the fact that many media have shear-thinning properties, so that a large shear rate can help the propeller to move forward. Since the speed is greatest at the periphery of the propeller, the end located there can achieve the maximum shear rate.

[0038] The maximum radius of any cross-section of the propeller perpendicular to the rotation axis or screw axis of the propeller is preferably 5 mm or less, more preferably 3 mm or less, more preferably 1 mm or less, more preferably 500 μm or less, more preferably 300 μm or less, more preferably 100 μm or less, more preferably 50 μm or less, more preferably 30 μm or less.

[0039] The minimum radius of any cross-section of the propeller perpendicular to the rotation axis or screw axis of the propeller is preferably 300 μm or less, more preferably 100 μm or less, more preferably 50 μm or less, more preferably 30 μm or less, more preferably 10 μm or less, more preferably 5 μm or less, more preferably 3 μm or less.

[0040] The length of the propeller divided by the maximum radius of any cross section of the propeller perpendicular to the axis of rotation or helical axis of the propeller is preferably 0.5 or greater, more preferably 1 or greater, more preferably 3 or greater, more preferably 5 or greater.

[0041] Preferably, the propeller is untethered. In the context of the present invention, "untethered" means that the propeller has no material connection (e.g., a connection in the form of a wire, tube, or rod) to the space outside the medium that at least partially (preferably completely) surrounds the propeller. Optionally, the propeller is minimally tethered, and the driving torque for the propeller is applied wirelessly, but the propeller is connected to a passive element, such as to pull the end of a tube and / or wire (the other end being outside the medium) into a specific position inside the medium. The tether can be used for material transport, signal measurement, or stimulation, but the tether is passive (it does not provide an active driving force or torque to the propeller). Optionally, the propeller is tethered, for example, the driving torque is input to the propeller by a rope, wire, or rod, and the rotation of the rope, wire, or rod causes the propeller to move with the tether.

[0042] The rotation of the propeller is preferably caused remotely. In the context of the present invention, "acting remotely" means that the component causing the rotation of the propeller is at a distance of at least 5 times the maximum diameter of the propeller from the propeller in any dimension. In a preferred embodiment of the present invention, the rotation of the propeller is caused remotely by means of a magnetic field. Therefore, the magnetic field source is at a distance of at least 5 times the maximum diameter of the propeller from the propeller in any dimension and the magnetic field source acts as an actuator to cause the rotation of the propeller. Preferably, the magnetic field source is outside the medium, which medium at least partially (preferably completely) surrounds the propeller.

[0043] The magnetic field is preferably caused to rotate, thereby inducing rotation in the thruster. Since the magnetic moment of the thruster tends to align with the external magnetic field, and the thruster rotates along the axis that presents least resistance, the orientation of the thruster is determined by the rotating external magnetic field. The magnetic field can be applied, for example, by a set of electrical coils (e.g., Helmholtz coils) or permanent magnets.

[0044] Preferably, if the magnetic field exerts a magnetic gradient force on the thruster in the direction of motion, the force is so weak that it alone cannot affect the motion of the thruster. More preferably, the magnetic field has no gradient component in the direction of motion. The preferred magnetic field is stronger than 1 G (Gauss), more preferably stronger than 10 G, more preferably stronger than 50 G. The preferred magnetic field is weaker than 10 000 G, more preferably weaker than 1 000 G, more preferably weaker than 500 G, for example 100 G.

[0045] Preferably, in order to cause rotation by means of a magnetic field, the thruster is at least partially magnetized, or a component connected to the thruster material is at least partially magnetized. The magnetization is preferably permanent. To this end, the thruster comprises a magnetized or magnetizable material; for example, the thruster consists of a magnetized or magnetizable material, or contains a magnetized or magnetizable material, or is coated with a magnetized or magnetizable material. Suitable materials include Fe, Co, Ni or magnetic alloys, preferably including some or all of the above metals. The preferred magnetizable material of the thruster is magnetized in its cross section in the direction of the greatest length.

[0046] Additionally or optionally, an actuator is provided which, like the propeller, is at least partially (preferably completely) surrounded by the medium and is materially connected to the propeller. For example, the actuator may be an electric motor or a molecular motor; the material connection may include a drive shaft. An energy reservoir (such as a battery) for the actuator may likewise be at least partially (preferably completely) surrounded by the medium; preferably, in this case, a material connection (e.g. a wire or a tube) is provided between the reservoir and the actuator to provide an energy source to the actuator, such as electrical energy or chemical energy stored in the energy reservoir. Additionally or optionally, the actuator is preferably provided with an energy receiver to receive energy from an energy transmitter located in a space outside the medium in an untethered manner, i.e., there is no material connection between the energy transmitter and the energy receiver.

[0047] Preferably, the torque applied to the propeller when causing the one or more propellers to rotate is less than 100 mN·mm (millinewton millimeters), preferably less than 50 mN·mm, 10 mN·mm, 5 mN·mm, 1 mN·mm.

[0048] Preferably, the thruster is operated at a speed lower than 0.9 times (more preferably lower than 0.8 times, more preferably lower than 0.7 times, more preferably lower than 0.5 times) its step-out frequency. Preferably, the thruster is operated at a speed higher than 0.05 times (more preferably higher than 0.1 times, more preferably higher than 0.2 times, more preferably higher than 0.3 times) its step-out frequency. In the context of the present invention, a "step-out frequency" is a frequency at which the torque is insufficient to overcome the resistance of the medium. The step-out frequency can be measured, for example, by driving the thruster with a rotating magnetic field; if the magnetic field rotates slowly enough, the thruster rotates synchronously with the magnetic field. However, there is a field rotation frequency above which the applied magnetic torque is not strong enough to keep the thruster synchronous with the field. This is the step-out frequency.

[0049] In a preferred method according to the invention, the propeller is completely surrounded by the medium. With this embodiment of the invention, a particularly powerful propulsion can be achieved, since all parts of the propeller are in permanent contact with the medium.

[0050] Preferred media are viscoelastic. In the context of the present invention, "viscoelastic" refers to a medium that exhibits both viscous and elastic properties when undergoing deformation. Particularly preferred media are viscoelastic fluids, where viscosity is more prominent than elasticity at an applied shear frequency (or shear stress), such as synovial fluid, vitreous humor, mucus. Another particularly preferred medium is a viscoelastic solid, where elasticity is more prominent than viscosity at an applied shear frequency (or shear stress), such as connective tissue, brain tissue,

[0051] Preferred media are biological tissues. Particularly preferred biological tissues are brain tissue, kidney, prostate, bladder, blood vessels, liver, pancreas, breast, lung, skin, adipose tissue, connective tissue, vitreous humor, mucus or tumor tissue.

[0052] Preferably, the rotation of the propeller induces a strain in the medium, whereby the strain induces a change in the elastic energy of the medium, which in turn induces a translation of said propeller.

[0053] In a preferred embodiment of the present invention, the load is attached to the propeller to move relative to the medium by the propeller. Preferred loads may include molecules, nanoparticles, porous polymer matrices, porous silicon and / or one or more circuits attached to the propeller. Advantageously, the one or more circuits may control the motion of the propeller. Alternatively or additionally, one or more tubes and / or wires pulled from the outside of the medium to the inside may be attached to the propeller.

[0054] Preferably, the motion trajectory is remotely controlled, for example by changing the direction and / or rotation frequency of the magnetic field or by changing the direction, rotation axis, rotation direction and / or rotation frequency of an actuator at least partially surrounded by the medium. Moreover, a plurality of thrusters according to the invention may be combined into one device, and in this case, changing the rotation frequency of the thrusters alone can be used to control the propulsion direction of the device. Preferably, a controller, for example a suitably equipped and programmed PC, is connected to the actuator (e.g., a magnetic field source or an actuator at least partially surrounded by the medium) to control the motion trajectory.

[0055] The motion trajectory is preferably imaged and / or measured, for example, by one or more or the following imaging methods: optical microscopy, fluorescence imaging, x-ray imaging, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), infrared imaging, ultrasound imaging.

[0056] The thruster can be, for example, made of one or more metals (e.g., copper, gold, cobalt, nickel, iron, steel, titanium) and / or one or more polymers (e.g., Teflon, PLA, PMMA, PC) and / or one or more semiconductors (e.g., silicon) or a combination of these materials or include one or more metals and / or one or more polymers and / or one or more semiconductors or a combination of these materials. In a particularly preferred embodiment of the present invention, the thruster can be made of a biodegradable material. The achievable advantage of this embodiment of the present invention is that it does not need to be retrieved after being arranged in the tissue because it can be degraded and absorbed by the body. The thruster can, for example, be made of two or more parts, a rigid part for propulsion and a biocompatible part for drug carrying and release.

[0057] Suitable methods for manufacturing the thruster include molding (particularly injection molding), electrodeposition, direct writing, 3D printing and machining. A preferred manufacturing method comprises the following steps: (1) defining a straight spiral axis; (2) providing a plate extending along the spiral axis, wherein at least one cross-section (preferably all cross-sections) of the plate has an aspect ratio of 2 or greater, wherein the one or more cross-sections are cross-sections associated with the spiral axis; and (3) applying a torque to the plate along the spiral axis, thereby twisting the plate into a spiral shape. In a next step, the spiral can be cut into one or more individual thrusters of the desired length. A realizable advantage of this method is that the thruster can be manufactured easily and reliably.

[0058] Another particularly preferred manufacturing method comprises the following steps: (1) providing a first structure having a defined geometry; (2) molding the first structure in a second material, removing the first structure from the second material to produce a negative copy of the first structure; (3) injecting a molding material into a negative mold and curing the molding material under given physical and chemical conditions to form a second solid structure; and (4) releasing the second solid structure from the negative mold to obtain a defined thruster, wherein the molding material is a mixture of at least two component materials. Preferred component materials include polymer materials, magnetic materials, drug molecules, radioactive materials. Thus, the molding material can, for example, consist of a polymer material and a magnetic material.

[0059] The curing conditions preferably include at least one of the following conditions: temperature, pH value, magnetic field, electric field, acoustic field, optical field and radiation. For example, the mixture is an epoxy resin mixed with ferromagnetic particles, and the polymer is cured at room temperature in a magnetic field in a direction perpendicular to the helical axis.

[0060] The drug can be incorporated into the mixture in step (3) above, or can be adsorbed to the pusher material after release in step (4) above. Using this method, the structure, magnetization and functionalization of the pusher can be achieved in a single process. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] The invention is explained in more detail with the aid of a schematic diagram:

[0062] Figure 1 (a) is a perspective view of an embodiment of a propeller according to the present invention;

[0063] Figure 1 (b) is Figure 1 (a) a cross-sectional view of a propeller;

[0064] Figure 2 is an optical microscope image of a thruster according to the present invention, the thruster having a magnet attached and embedded in soft tissue;

[0065] Figure 3 Shows penetration of Figure 2 Two optical microscope images of the thruster. The bottom image was acquired 18 seconds after the top image.

[0066] Figure 4 (a) to (d) schematically compare Figure 4 The cross-sectional shape of the propeller according to the present invention shown in (a) is similar to that shown in Figure 4 The cross-sectional shapes of the prior art propellers shown in (b) to (d);

[0067] Figure 5is a schematic cross-sectional view of a propeller according to the present invention, wherein the medium rotates together with the propeller;

[0068] Figure 6 (a) shows a frame from a video of a propeller in a viscoelastic medium, where tracer particles are embedded in the medium to visualize the deformation of the medium;

[0069] Figure 6 (b) shows the trajectory of a tracer particle during multiple rotations of the propeller; large normalized deformation provides large axial propulsion force;

[0070] Figure 7 A propeller according to the invention is shown in cross section rotating in a viscoelastic medium, and the effective deformation area of ​​the medium caused by the rotation of the propeller is marked with hatching;

[0071] Figure 8 A prior art propeller design rotating in a viscoelastic medium is shown in cross-section, with the effective deformation area of ​​the medium caused by the propeller's rotation marked with shading;

[0072] Fig. 9 Another prior art propeller design rotating in a viscoelastic medium is shown in cross-section, with the effective deformation area of ​​the medium caused by the propeller's rotation marked with shading;

[0073] Fig.10 is a force diagram of a short portion on the edge of a propeller according to the present invention;

[0074] Fig.11 shows penetration into pig brain tissue Figure 2 Two optical microscope images of the thruster, with the bottom image taken 300 seconds after the top image.

[0075] Fig.12 A method of manufacturing a propeller according to the present invention is shown;

[0076] Fig.13 Another method of manufacturing a propeller according to the present invention is shown; and

[0077] Fig.14 is a perspective view of two propellers according to the present invention, both of which have a forward taper at both ends. DETAILED DESCRIPTION

[0078] Propellers move in tissue model

[0079] An achievable advantage of the propeller 1 according to the invention is that it is able to effectively self-propel through viscoelastic media (such as biological tissue). Figure 2 In the figure, a propeller 1 according to the invention is shown, which is completely embedded in The hydrogel was used as a tissue model to verify the propulsion mechanism. Life Obtained It is the trade name for a gelatinous mixture of proteins secreted by mouse sarcoma cells. It is similar to the complex extracellular matrix (ECM) found in many tissues and is widely accepted as an in vitro model for cell 3D culture, tumor cell metastasis research, and cancer drug screening. Here, Gel medium 2 used as a model of connective tissue penetrated by propeller 1. Use as is The solution was thawed on ice and gelled in an incubator at 37°C for 1 hour.

[0080] The propeller 1 is inserted into the gel medium 2 with the help of tweezers. A magnetic field with uniform size (adjustable from 50 to 1000 Gauss) and continuous rotation direction (frequency in the range of 1 to 100 Hz (Hertz)) is applied, and the magnetic field rotates at a speed of 10 Hz. At one end of the propeller 1, a cylindrical magnet 3 of neodymium iron boron (NdFeB) material with a diameter of 200 μm (micrometers), a length of 400 μm and magnetized in the diameter direction is mounted in a torsion-proof manner. The magnet has a permanent magnetic moment and rotates with the external rotating magnetic field. Due to the special shape design of the propeller, it couples rotation with translational motion (forward or backward propulsion) and achieves a net displacement in the gel medium 2 or biological tissue.

[0081] from Figure 1 As can be best seen in (a) of FIG. 1 , the propeller 1 has a chirality, more precisely a helical shape. It is left-handed, but of course a right-handed design would also work. The axis of rotation 4 and the helical axis are in Figure 1 The direction of motion v is indicated by the rightward arrow v. The direction of rotation is indicated by the semicircular arrow ω. Figure 1 As can be seen in the cross-sectional view (b) of the propeller 1, the aspect ratio of any section 5 perpendicular to the screw axis is significantly greater than 5. The aspect ratio is obtained by dividing the maximum radius 6 of the section by the minimum radius 7 of the section 5. The radii 6, 7 extend from the point 8 where the axis of rotation 4 passes perpendicularly through the section 5 to a point on the periphery 9 of the section.

[0082] from Figure 3 The image in the figure shows how thruster 1 propagates through Gel medium 2. The bottom image was acquired 18 seconds after the top image. The dotted line indicates the initial position of the magnet 3. A speed of about 45 μm / s (micrometers per second) along the propeller's helical axis was observed at a rotation frequency of 10 Hz. By selecting the direction of rotation clockwise or counterclockwise, the propeller 1 can be moved forward or backward.

[0083] exist Figure 4 In (a) to (d), the cross-sectional shape of the propeller 1 according to the present invention is schematically compared with the cross-sectional shape of the propeller 1 according to the aforementioned publication ( Figure 4 (b) are publications by L Zhang, JJ Abbott, LX Dong, BE Kratochvil, D Bell and BJ Nelson, Figure 4 (c) A Ghosh and P Fischer and Figure 4 (d) is a cross-sectional shape of a propeller known from a publication by T Qiu, J Gibbs, D Schamel, A Mark, U Choudhury and P Fischer). In the top row, a 3D view is provided, while in the bottom row, the cross-sectional shape is shown. It can be seen that, based on its radii 6' and 7', the section 5 of the propeller of the present invention has a much larger aspect ratio than the section 5' of the propeller 1' of the prior art.

[0084] Furthermore, when the propeller 1 rotates in and moves through the viscoelastic medium 2, a portion 10 of the medium 2 may adhere to the surface of the propeller 1 and rotate with the propeller 1. Figure 5 It is schematically shown in Figure 5 In the example of , the aspect ratio of the cross section of the body of rotation comprising the propeller 1 and the portion 10 of the medium 2 rotating with the propeller 1 is still greater than 3. In this case, the aspect ratio is obtained by dividing the maximum radius 11 of the cross section of the body of rotation by the minimum radius 12 of the cross section of the body of rotation. The radii 11, 12 extend from the point 8 of the cross section perpendicularly through the axis of rotation 4 to the point of the periphery 9 of the cross section of the body of rotation.

[0085] Propulsion mechanism of the thruster

[0086] The inventors believe, without prejudice, that the propeller 1 according to the invention, when used in a viscoelastic medium, employs a new propulsion mechanism which is different from previously disclosed propulsion mechanisms in viscous fluids. Figure 6 (a) and Figure 6 (b) shows the results of a particle imaging velocimetry (PIV) experiment. In this experiment, fluorescent polystyrene beads with a diameter of 15 μm ( Life Technologies) as tracer particles and mixed in The gel medium 2 is formed to show the movement (particularly deformation) of the gel medium 2. A green laser beam with a wavelength of 532 nm (nanometers) is expanded to the laser plate through a cylindrical lens and is directed to the laser plate. A thin sheet of gel medium 2. The motion of propeller 1 and tracer particles was recorded by a microscope with a long pass filter (OD4-550nm, Edmund Optics) and a video camera. The position of the tracer particles was analyzed by a custom script in Matlab (R2014b, Mathworks) and circled in each frame of the video. Figure 6 (a) and enlarged Figure 6 In (b), circles can be seen. Figure 6 In (b) of FIG. 1 , the trajectory of one tracer particle 13 is shown. The particle 13 follows a closed, substantially elliptical trajectory 14 over many rotation periods of the propeller 1. The normalized deformation can be calculated as the quotient of the radial displacement d and the distance r from the axis of rotation.

[0087] The experiments show that the motion (deformation) of the viscoelastic medium 2 is significantly different from the flow around a propeller in a viscous fluid. In the fluid, the particle rotates with the propeller for a full revolution, and the difference in the fluid dynamic drag in two perpendicular directions at low Reynolds numbers results in a forward propulsion force, which has been explained in the literature. However, with the propeller 1 disclosed here, a different motion trajectory of the particles was observed, indicating that the new design of the propeller 1 enables a new propulsion mechanism in a viscoelastic medium, which has not been reported before.

[0088] The relaxation time of viscoelastic solids, including most biological tissues, is usually on the order of several minutes, and the propeller typically rotates at a frequency of 1 to 10 Hz. Since the cycle time (0.1 to 1 s) of one revolution of the propeller is much shorter than the relaxation time, only the elastic response of the gel needs to be considered. As an example, Figure 7 As shown, the section 5 of the propeller 1 is modeled as a rectangular solid rotating in an initial rectangular hole 15 in the medium 2. Note that Figure 7 In (b), when the propeller 1 rotates, the medium 2 does not flow but deforms. The large deformation (strain) of the medium 2 is caused by the rotation of the propeller 1. The effective deformation of the medium 2 around the propeller 1 is much larger than that of the prior art propeller design (e.g. Figure 8 (the corresponding element is the propeller 1' in the form of a screw reported in the prior art) and Fig. 9 (The corresponding element is a propeller 1' in the form of a conventional screw. The medium 2', the gap 15' and the effective deformation area (shaded) are also shown in the figure). The medium 2 is considered to be elastic, that is, a spring whose resilience is positively correlated with the deformation. Therefore, a greater deformation of the medium 2 requires a greater rotational torque and exerts a greater forward propulsion force. These two phenomena were observed in the experiment.

[0089] To further illustrate, Fig.10The force diagram for a small part of a propeller 1 (left-handed, the front edge of the propeller rotates upwards to move to the right) is shown in FIG. The direction of rotation is indicated by the upward arrow v. It can be clearly seen from the force diagram that there is a propulsion force component F_p pointing to the right. Figure 7 Similar to the situation shown, the greater the deformation, the greater the forward propulsion force. Therefore, the proposed propulsion mechanism of the propeller 1 according to the present invention can be summarized as the following three aspects: First, the rotation of the propeller 1 causes a large deformation of the gel medium 2. More specifically, the large aspect ratio on the cross section 5 of the propeller 1 causes a large deformation of the gel medium 2, which results in a large forward propulsion force F_p. Second, the pressure on the end 16 of the propeller 1 should be higher than the tensile strength of the gel medium 2 in order to cause it to break. It is necessary that the area of ​​the end 16 is as small as possible, for example, a sharp end 16 is preferred. In addition, the new cut area (crack) 15 of the medium 2 caused by the forward movement of the end 16 of the propeller also has a high aspect ratio, such as a rectangular shape, as shown in FIG. Figure 7 This again allows large deformations of the medium 12 when the propeller 1 rotates. This is different from the following design of a conventional propeller 1', in which the crack 15' is almost circular (see Fig. 9 (a)), and the deformation of the medium 2' caused by the conventional propeller 1' is small. Third, the medium 2 may be attached around the propeller 1 (such as Figure 5 ) after the above two conditions should still be met. This standard ensures the continuous movement of the propeller 1 in the tissue.

[0090] The conventional propeller 1' is designed with a hollow opening in the middle, such as Figure 4 (b) and Figure 4 The published design shown in (c) of FIG. 1 cannot be effectively propelled in a viscoelastic medium. The reason is that the opening is filled with the viscoelastic medium during the propeller rotation, and when considering that the medium rotates with the propeller, the overall structure does not have a high aspect ratio in any cross section, such as Figure 8 As shown in (b). In other words, the gel plug changes the shape of the conventional propeller to an almost cylindrical shape, causing very limited deformation of the surrounding medium, so that the conventional propeller can only rotate at the same position in the viscoelastic medium and cannot achieve net displacement. In a preferred embodiment, the present invention is significantly different from the design of the prior art in that, on at least one section perpendicular to the helical axis of the propeller (preferably on all sections), the axis passes through the propeller. Or in other words, on at least one section (preferably on all sections), the center of rotation is inside the propeller.

[0091] For certain types of viscoelastic media (such as yield stress fluids), the propeller can destroy (or liquefy) part of the medium due to the shear stress caused by the rotation of the propeller. Moreover, the backward transport of the destroyed (or liquefied) part of the medium can also cause the forward propulsion of the propeller.

[0092] Preferably, the propeller 1 should be actuated with a rotation speed that results in the highest propulsion speed. This value, which depends on both the geometry of the propeller 1 and the rheology of the medium, can be experimentally determined by sweeping the frequency and measuring the propulsion speed. It has been found that the optimal frequency in the viscoelastic medium 2 of the propeller 1 disclosed herein can be well below the step-out frequency. When the frequency is increased above the optimal value, the propeller 1 continues to rotate, but the propulsion speed drops sharply until it reaches zero. On the contrary, in viscous fluids with low Reynolds numbers, the optimal frequency of the propeller 1 is very close to the step-out frequency, and the propulsion speed increases linearly with the driving frequency before reaching step-out. This observation also shows that the present propeller 1 can realize a new propulsion mechanism in a viscoelastic medium.

[0093] Propellers move through brain samples

[0094] Fig.11 The optical microscope photograph in Figure 1 shows a propeller 1 according to the present invention penetrating a pig brain tissue to demonstrate its ability to move through real biological soft tissue. Fresh pig brains were stored on ice and obtained from a local slaughterhouse. A 25×25×8 mm 3 (cubic millimeters) volume of brain was then inserted into the propeller 1 by forceps. Due to the relatively thin tissue and the use of bright white light backlighting, the movement of the propeller was observed inside the brain tissue. The dotted line represents the initial position of the propeller 1. An average propulsion speed of approximately 35 μm / s was measured at a rotational frequency of approximately 1 Hz. Due to the shape of the propeller 1, the rotation of the propeller 1 can be actuated with a limited magnetic torque. In the experiments, a magnetic field of 100 to 300 G was sufficient to drive the propeller 1 through the brain tissue sample. This magnetic field is suitable for use with common magnetic field generators, such as electric coils or permanent magnet arrangements as described in further detail below.

[0095] Propulsion device manufacturing

[0096] exist Fig.12 The method for manufacturing the propeller 1 according to the invention is shown in FIG. The propeller 1 is made of copper using a machining method. A copper wire with a diameter of 50 μm is mechanically rolled into a flat plate 17 with a width of 255 μm and a thickness of 13 μm. Fig.12As shown, the plate 17 is mounted between two concentric clamps 18, 19 that can rotate relative to each other. The plate 17 is twisted into a chiral structure by rotating one of the clamps 18 and keeping the other clamp 19 stationary. During the twisting, a normal force is generated in the axial direction v, so the distance between the two clamps 18, 19 is adjusted accordingly. In this process, sensors can be used to measure the force and torque, and the distance and angular position of the clamps can be controlled by a computer through a motor. The pitch size and chirality of the thruster can be controlled in this way. The long twisted plate 17 is then cut into individual thrusters 1 of the desired 2 mm length. Finally, a small magnet with a diameter of 200 μm and a length of 400 μm is mounted to one end of the thruster 1.

[0097] The cutting process can be done by machining, laser etching, (focused) ion etching or chemical etching. Masks for etching can be made by photolithography on both sides of the plate before the twisting process. In this way, a batch manufacturing process of the thrusters can be realized.

[0098] exist Fig.13 Another method of manufacturing a propeller 1 according to the invention is shown in FIG. The structure of the propeller 1 is first obtained in copper material, for example by the above method or by 3D printing ( Fig.13 (a)); the structure is then molded into a second material such as a soft polymer (e.g., PDMS) ( Fig.13 (b)); for example, by rotating the pusher 1 in the right direction and driving out the mold 20 or by expanding the soft polymer mold 20 to remove the first structure from the female mold 20 ( Fig.13 (c)); injecting the liquid polymer material or mixture into the female mold 20 ( Fig.13 (d)), for example, a mixture of epoxy resin and ferromagnetic particles (average diameter 40 μm) is injected into the female mold 20, Fig.13 The polymer is solidified at room temperature under the condition of the external magnetic field indicated by the arrow in (d); finally, the propeller 1 is released from the female mold 20 to obtain the propeller 1 ( Fig.13 (e)), the release is achieved by destroying the mold 20 or by rotating the pusher 1 in the right direction and driving it out of the mold 20. The pusher 1 has a rightward magnetic moment M (such as Fig.13 The magnetic particles in the structure are aligned in the right direction when an external magnetic field B is applied (as shown by the arrow in (f)). The drug can be incorporated into the polymer mixture in the above molding step or adsorbed to the pusher material after being released in the above final step.

[0099] Fig.14It is shown how the two ends 16 of the propeller 1 can be cut or etched or formed into a designed shape, preferably a sharp end. In this way, the pressure at the end 16 can be increased by reducing the contact area; moreover, the shear rate in the medium 2 in front of the propeller can be increased. Since many biological media are shear-thinning, the larger shear rate also helps the forward propulsion of the propeller. In this case, the sharp end of the propeller is preferably at the edge of the propeller end 16 and away from the axis of rotation.

[0100] Actuation of the thrusters

[0101] Suitable devices for inducing rotation in a thruster by means of a rotating magnetic field are known, for example, from the aforementioned publications of T Qiu, J Gibbs, D Schamel, A Mark, U Choudhury and P Fischer. The relevant parts of this document are incorporated into the present disclosure by reference.

[0102] The magnetic field may be spatially uniform or have a magnetic gradient in space, but preferably the direction of the pulling force on the thruster generated by the magnetic gradient is the same as the direction of the self-propulsion force of the thruster 1. The magnetic field can be generated by electric coils. For example, three pairs of Helmholtz coils can achieve motion control of the thruster in three-dimensional space by changing the phase and magnitude of the current in different coils. The magnetic field can also be generated by the rotation of one or more permanent magnets, which can be multiple magnets specially configured in space or just one magnet at a desired distance from the thruster. In order to control the propulsion trajectory using a permanent magnet device, the rotation axis of the device should be changed.

[0103] In order to realize the present invention, in various embodiments, the features disclosed in the description, claims and drawings can be combined individually or in any combination.

Claims

1. A propeller (1) of a spiral or modified spiral, for converting a rotational motion of the propeller (1) into a motion of the propeller (1) relative to a medium at least partially surrounding the propeller (1), characterized in that: The aspect ratio of at least one section (5) of the propeller (1) is 3 or more, wherein the section (5) is a section (5) related to the helical axis of the propeller (1), and in at least one section perpendicular to the helical axis of the propeller, the axis passes through the propeller, The propeller is at least partially magnetized or the propeller further comprises a magnetized component materially connected to the propeller, so that a rotation of the propeller can be induced by means of a magnetic field source located outside the medium.

2. The propeller (1) according to claim 1, characterized in that The maximum radius (6) of any cross section (5) of the propeller (1) perpendicular to the axis of rotation (4) of the propeller (1) is 5 mm or less.

3. The propeller (1) according to claim 1, characterized in that The minimum radius (7) of any cross section (5) of the propeller (1) perpendicular to the rotation axis (4) of the propeller (1) is 300 μm or less.

4. A method for manufacturing a propeller (1) according to claim 1, characterized in that: The method comprises the following steps: defining a straight helical axis; providing a plate (17) extending along the screw axis, wherein at least one section (5) of the plate (17) has an aspect ratio of 3 or more, wherein the section (5) is a section related to the screw axis; and applying a torque to the plate (17) along the spiral axis, thereby twisting the plate (17) into a spiral shape; the method further comprising the steps of: The twisted plate (17) is cut into a desired length of the propeller (1) and / or the tip (16) of the propeller (1) is cut or etched into a sharp tip (16).

5. A method for manufacturing a propeller (1) according to claim 1, characterized in that: The method comprises the following steps: providing a first structure having a defined geometry; molding the first structure in a second material, removing the first structure from the second material to produce a negative replica of the first structure; Under given physical and chemical conditions, injecting a molding material into the negative mold and curing the molding material to form a second solid structure; releasing the second solid structure from the negative mold so as to define the pusher; and The tip (16) of the thruster (1) is cut or etched into a sharp tip (16).

6. The method according to claim 5, characterized in that The molding material is a mixture of at least two component materials.

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