Magnetic-field driven colloidal microbots, methods for forming and using the same

Abstract

The invention relates to a magnetic-field driven colloidal microbot that employs wall-based propulsion, method of forming the microbot and a method of using the microbot. The microbot can be formed in situ with the use of magnetic fields, and the magnetic fields can be used to translate the microbot to a specified location in a patient. The microbot does not depend on swimming or flow currents within a patient to move, but instead can propel itself along a surface using a magnetic field. Once the magnetic field is removed, the microbot disassembles into colloidal particles.

Claims

1. A microbot system for use in a biological system, comprising: at least two colloidal particles comprising magnetic properties; and a magnetic field activating the at least two colloidal particles to form the microbot system, and propelling the microbot system by rolling the microbot system on a surface that is external to the rotating microbot system with the magnetic field, wherein at least two of the at least two colloidal particles are in contact with each other and remain in contact with each other during the propelling.

2. The microbot system of claim 1, wherein the at least two colloidal particles comprise a paramagnetic material, a superparamagnetic material, a non-magnetic material comprising a magnetic material or combinations thereof.

3. The microbot system of claim 1, wherein the microbot applies a force of between about 250 fN to about 25 pN to a surface.

4. The microbot system of claim 1, further comprising a surface coating.

5. The microbot system of claim 4, wherein the surface coating is at least one of an antimicrobial material, an antiplatelet material, a fibrinolytic material, a tactifying material, an antibacterial material, a cancer therapeutic medicine, or at least one ligand.

6. The microbot system of claim 1, wherein between 2 and 500 of the at least two colloidal particles are joined in the magnetic field to form the microbot.

7. The microbot system of claim 1, further comprising at least one ligand for receptors expressed on an endothelial cell.

8. The microbot system of claim 1, further comprising an anionic surface.

9. The microbot system of claim 1, wherein the at least two colloidal particles vary in size, and wherein a diameter of the at least two colloidal particles vary between about 1 micron and 10 mm.

10. The microbot system of claim 1, wherein the rolling converts rotational energy to translational energy using wall friction.

11. A method to form a rotating microbot, comprising: applying a magnetic field to at least two colloidal particles of a diameter between about 1 m and about 4 m; forming the rotating microbot comprising the at least two colloidal particles in a biological system of a patient in the presence of the magnetic field; rotating the rotating microbot by rolling propulsion on a surface that is external to the rotating microbot in the presence of the magnetic field; and disassembling the rotating microbot to the at least two colloidal particles when the magnetic field is removed, wherein at least two of the at least two colloidal particles are in contact with each other and remain in contact with each other during the rolling propulsion.

12. The method of claim 11, wherein the magnetic field is between about 1 mT and about 20 mT.

13. The method of claim 11, wherein the microbot forms in between about 1 second and about 20 seconds, and wherein a speed of the rotating microbot is between about 10 m/s and about 100 m/s.

14. The method of claim 11, wherein the at least two colloidal particles do not form the microbot in the absence of the magnetic field.

15. A method for using a microbot in a biological system to treat a patient, comprising: inserting at least one particle in the biological system of the patient; applying a magnetic field to the at least one particle to form the microbot; and rolling the microbot to a predetermined location in the biological system of the patient by propelling the microbot as a result of a rotational force created by the magnetic field on a surface that is external to the microbot in the biological system, wherein at least two of the at least one particle are in contact with each other and remain in contact with each other during the propelling.

16. The method of claim 15, further comprising disassembling the microbot by removing the magnetic field.

17. The method of claim 15, wherein the biological system is a cardiovascular system, a lymphatic system, a reproductive system, or a gastrointestinal system.

18. The method of claim 15, wherein the microbot provides a cancer therapeutic medicine to the patient.

19. The method of claim 15, wherein the microbot is directed to the predetermined location in the biological system of the patient with the magnetic field.

20. The method of claim 15, wherein the microbot induces localized hyperthermia.

21. The method of claim 15, wherein the microbot is used to remove at least one occlusion in the patient.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

(2) FIG. 1 illustrates an example application where an external magnetic field is used to assemble microbots, then used for a blood clot removal in a blood vessel;

(3) FIG. 2 illustrates the potential speed of several devices compared to the microbot of the present invention;

(4) FIG. 3 illustrates the rolling velocity for microbots created from 1 (n=25), 2 (n=168), 3 (n=140) and 7 (n=35) colloidal particles as a function of weighted angular frequency;

(5) FIG. 4 illustrates three seconds of translation under identical field conditions demonstrate that larger microbots roll faster;

(6) FIG. 5A illustrates the formation of a microbot initially;

(7) FIG. 5B illustrates the particles after the B.sub.x and B.sub.y magnetic fields are turned on and time elapses;

(8) FIG. 5C illustrates two additional particles joining together continued from FIG. 5B;

(9) FIG. 5D illustrates the formation of a four particle microbot continued from FIG. 5C;

(10) FIG. 5E illustrates the formation of a five particle microbot continued from FIG. 5D;

(11) FIG. 5F illustrates the two remaining microbots joining together to form a two particle microbot near the five particle microbot of FIG. 5E;

(12) FIG. 5G illustrates a seven particle microbot continued from FIG. 5F;

(13) FIG. 6A illustrates seven colloidal particles as they form a microbot;

(14) FIG. 6B illustrates the assembly and rotation of the microbot;

(15) FIG. 6C illustrates the translation of the microbot;

(16) FIG. 6D illustrates the camber angle function of the magnetic field in the direction perpendicular to the wall.

(17) FIG. 7 illustrates the camber angle curves as a function of microbot projected area as viewed from above for several configurations of microbots;

(18) FIG. 8A illustrates a side view and of a translating microbot modeled as a disk;

(19) FIG. 8B illustrates a front view of a translating microbot modeled as a disk;

(20) FIG. 9A illustrates heading angle as a function of camber angle;

(21) FIG. 9B illustrates the heading angle of 27;

(22) FIG. 9C illustrates a heading angle of 5;

(23) FIG. 10A illustrates automated patterns of a microbot;

(24) FIG. 10B illustrates a manual pattern of a microbot;

(25) FIG. 10C illustrates a stepwise microbot assembly;

(26) FIG. 11A illustrates a microbot comprising three colloidal particles at a first position;

(27) FIG. 11B illustrates a microbot comprising three colloidal particles at a second position;

(28) FIG. 11C illustrates a microbot comprising three colloidal particles at a third position;

(29) FIG. 12A illustrates a microbot comprising two colloidal particles at a first position;

(30) FIG. 12B illustrates a microbot comprising two colloidal particles at a second position;

(31) FIG. 12C illustrates a microbot comprising two colloidal particles at a third position;

(32) FIG. 12D illustrates a microbot comprising two colloidal particles at a fourth position;

(33) FIG. 12E illustrates a microbot comprising two colloidal particles at a fifth position;

(34) FIG. 12F illustrates a microbot comprising two colloidal particles at a sixth position;

(35) FIG. 12G illustrates a microbot comprising two colloidal particles at a seventh position;

(36) FIG. 12H illustrates a microbot comprising two colloidal particles at an eighth position; and

(37) FIG. 13 illustrates an experimental set up of the invention where the magnetic field system consists of five air-cored solenoid coils.

DETAILED DESCRIPTION

(38) The present invention relates to a precise and controllable device and method suitable for exploring the body of a patient, delivering medication to a location in a patient, or treating a patient (for example by removing or reducing an occlusion in a patient) that moves in a system by rolling on surfaces. This mechanism can be used to translate microbots at speeds that are an order-of-magnitude greater than other propulsion mechanisms in similarly sized bots. The advantages of this approach include; (i) the microbots are fast and could achieve about 1 mm/s speeds necessary for practical application, (ii) by moving along surfaces the microbots translate in low velocity regions of arterial flow allowing the microbots to move upstream, and (iii) the microbots translation direction can be tightly controlled allowing for targeted applications.

(39) An aspect of the invention is a microbot for use in a biological system. The microbot includes at least one colloidal particle, which is paramagnetic or superparamagnetic. The colloidal particles are activated when a magnetic field is applied to the colloidal particles to form the microbot.

(40) The colloidal particle can be any suitable magnetic material including, but not limited to, iron oxide, iron or iron containing compounds, magnesium or magnesium containing compounds, molybdenum or molybdenum containing compounds, lithium or lithium containing compounds, tantalum or tantalum containing compounds, sodium or sodium containing compounds, aluminum or aluminum containing compounds, calcium or calcium containing compounds, titanium or titanium containing compounds, manganese or manganese containing compounds, strontium or strontium containing compounds, zirconium or zirconium containing compounds, ruthenium or ruthenium containing compounds, rhodium or rhodium containing compounds, palladium or palladium containing compounds, tin or tin containing compounds, barium or barium containing compounds, cerium or cerium containing compounds, neodymium or neodymium containing compounds, samarium or samarium containing compounds, europium or europium containing compounds, terbium or terbium containing compounds, dysprosium or dysprosium containing compounds, holmium or holmium containing compounds, erbium or erbium containing compounds, thulium or thulium containing compounds, tungsten or tungsten containing compounds, osmium or osmium containing compounds, iridium or iridium containing compounds, platinum or platinum containing compounds, or any other paramagnetic or superparamagnetic material. The materials of the colloidal particles allow for the microbot to disassemble to the colloidal particles once the magnetic field is removed. In other words, the materials of the colloidal particles do not produce a microbot that cannot be disassembled. The material can be a non-magnetic material that is later coated, doped, implanted with a material, or otherwise manipulated to become magnetic. For example, the material can be polystyrene doped with iron oxide. Other suitable materials include Dynabeads (polystyrene doped with iron oxide) available from ThermoFischer Scientific. In some embodiments, the colloidal particles are approved for use within a patient. In some embodiments, the material can be biodegradable such as polylactic acid. In some embodiments, the material of the colloidal particles can have a hardness of less or equal to or greater than polystyrene, when measured in accordance with ASTM E18 or similar method. The colloidal particles can contain a therapeutic material. The therapeutic material can be imbedded into the colloidal particle and slowly released from the colloidal particle as the particle breaks down. In some embodiments, the material of the microbots can be used to provide radiation therapy to a location within the patient. For example, the magnetic field can be altered to heat the particles of the microbot causing localized hyperthermia.

(41) The colloidal particles can be coated. Suitable coating materials include, but are not limited to an antimicrobial material, an antiplatelet material, a fibrinolytic material, a tactifying material, an antibacterial material, a cancer therapeutic, at least one ligand and combinations thereof. Suitable antimicrobial materials include but are not limited to silver containing compounds, lincosamides (for example clindamycin), tetracyclines (for example doxycline or minocycline), fluoroquinolones (for example ciprofloxacin, oflozacin, levofloxacin or norfloxacin), aminoglycosides (for example streptomycin, tobramycin, gentamycin, or amikacin), and other antimicrobial materials. Suitable antiplatelet or anticoagulation materials include, but are not limited to, dextran, abciximab, clopidogrel, aspirin or other suitable antiplatelet materials. Suitable fibrinolytic materials include, but are not limited to, tissue plasminogen activator, plasmin, urokinase plasminogen activator or other fibrinolytic materials. Suitable tactifying materials include, but are not limited to, hydrophilic and hydrophobic, positively or negative charged or uncharged, moieties to enhance interaction with surface. Suitable antibacterial materials include, but are not limited to, surfactants, rifampin, chlorhexidine, sulfadiazine, erythromycin, or other antibacterial materials. In some embodiments, ligands for receptors expressed on the endothelial cells can be conjugated to the microbots. Suitable ligands include, but are not limited to, selectins, fibrinogen. The ligands can be conjugated to the microbot by physical adsorption or covalent coupling. Chemotherapy materials can be used to provide localized chemotherapy to a patient. One skilled in the art would understand that they type of cancer therapeutic material provided to the patient will depend upon multiple factors, including the type of cancer, the biology of the cancer and the biology of the patient. Thus, while an exhaustive list is not included, one skilled in the art would understand that any conjugated medicine can be used. The colloidal particles can also include a material or coating, or be treated, to change the charge associated with the surface. By way of example, the charge of the microbot can be treated to make it anionic, cationic or neutral.

(42) The surface of the colloidal particles, and thereby the microbot, can be smooth. In some embodiments, the surface of the colloidal particles can be decorated with other materials to increase the surface area of the microbot, thereby increasing traction of the microbot. The decoration materials can be adhered to the surface of the colloidal particles. In some embodiments, the decoration materials can have smaller dimensions from the dimension of the colloidal particle that it covers. The surface of the colloidal particles can also be manipulated during the formation of the particles to increase the surface area. For example, the surface of a colloidal particle can be adjusted by changing the synthesis of the particle. The surface of the colloidal particles can also be removed to roughen the surface by chemical etching or by surface roughening (e.g. abrasive blasting, or particle on particle roughening).

(43) A single colloidal particle can form a microbot, but in some embodiments, at least two colloidal particles are joined together to make the microbot. The number of colloidal particles will depend upon the application of the microbots. While there is no maximum limit on the number of colloidal particles used to form a microbot, in some embodiments, between 1 to about 500 colloidal particles are joined to make the microbots. In some embodiments, three colloidal particles are joined to make the microbot. Multiple colloidal particles of the same size or of different sizes can be used to form a microbot. The dimensions of the microbot can dependent upon the number and size of the colloidal particles used. The dimensions of the colloidal particles are limited by the use of the microbots. For example, if the microbot will be used in a vascular system of a patient, the dimensions of the colloidal particles are limited by the dimension of the vein or artery along which the microbot travels. The diameter of the colloidal particles can be between about 1 m to about 4 m. In some embodiments, the diameter of the colloidal particles can be between about 10 nm to 10 m. In some embodiments, the microbot can have a diameter between about 10 nm and about 10 mm. The thickness of the microbot can be between about 10 nm and about 10 m.

(44) The magnetic fields can have a magnitude between about 1 mT to about 20 mT, however fields outside that range can also be effective. The magnitude can be local to the colloidal particles. One skilled in the art would understand that the magnetic field is dictated by the susceptibility of the colloidal particles. Thus, if a colloidal particle is receptive to a magnetic field, then a lower magnetic field can be used, while if the colloidal particle is not receptive to the magnetic field, then a higher magnetic field should be used. The magnetic field can be used to form, power and direct the microbot. The microbots form quickly after the magnetic field is applied, in some embodiments in less than about 20 seconds. In some embodiments, the microbot forms in between about 0.1 second to about 20 seconds. Furthermore, the colloidal particles can closely pack together (similar to a hexagonal crystalline structure) once the magnetic field is applied. Once the magnetic field is applied to the colloidal particles to form the microbot, the microbot can move (i.e. translating along the surface) at a rolling or translation velocity (V) of between about 1 m/s and about 1 mm/s. In some embodiments, the microbot can move at a speed greater than about 1 mm/s. The microbot can be moved using a propulsion system. In some embodiments, the propulsion system can be a wall-based propulsion system. The microbot can advance through the patient at a camber angle relative to the wall or tissue, theta. Theta can be between about 0 (i.e. upright orientation compared to the surface) and 90 (i.e. laying flat on the surface). Notably, the microbot can roll along a surface regardless of the camber angle. However, larger camber angles allow the microbots to roll on round surfaces, such as the inner surface of a tube or vessel. The angle for theta can be set using the magnetic field, understanding that the camber angle can change as the microbot travels along a surface that changes (i.e. bumps, turns, etc.). The microbot can apply a force to the surface which it travels on of between about 250 fN to about 25 pN. The coefficient of friction as the microbot is moving within the patient can be between zero and unity.

(45) Important parameters influencing the rolling velocity (V) include the number of particles comprising the microbot (n), its angular frequency (), and, as the mirobot rotates, the outer circumferential velocity Vo>R.

(46) The microbot can rotate between about 1 hertz and about 100 hertz (). Thus, the microbot can be used to remove material with rotational advancement of the microbot.

(47) The magnetic field can be applied using any suitable device. By way of example only, the device can be large, similar to a CT or MM. In some embodiments, the microbot can be observed in situ using a MRI or other magnetic imaging device. Magnets within these devices can be used to control the microbots. In some embodiments, the magnetic field device can be small, such that it can be used in remote areas or for ease of use. A plurality of electromagnetic coils can be used to apply a magnetic field. The phase angle, , of the field applied to the microbot can be controlled by a user, for example with a device similar to a joystick, or directional keys. Application of the magnetic field can also direct the microbot. Thus, the magnetic field can control the rotational speed, the advancing speed, the angle relative to the wall, theta and the direction of the microbot. Once the magnetic field is removed from the microbots, they can return to the colloidal particle form, and can be absorbed or broken down by macrophages in the patient.

(48) An aspect of the invention is a method to form a microbot. The method includes applying a magnetic field to at least one colloidal particle. The colloidal particles form the microbot in the presence of the magnetic field. In the absence of the magnetic field, the colloidal particles do not form a microbot.

(49) The colloidal particle can be any suitable magnetic material including, but not limited to, iron oxide, iron or iron containing compounds, magnesium or magnesium containing compounds, molybdenum or molybdenum containing compounds, lithium or lithium containing compounds, tantalum or tantalum containing compounds, sodium or sodium containing compounds, aluminum or aluminum containing compounds, calcium or calcium containing compounds, titanium or titanium containing compounds, manganese or manganese containing compounds, strontium or strontium containing compounds, zirconium or zirconium containing compounds, ruthenium or ruthenium containing compounds, rhodium or rhodium containing compounds, palladium or palladium containing compounds, tin or tin containing compounds, barium or barium containing compounds, cerium or cerium containing compounds, neodymium or neodymium containing compounds, samarium or samarium containing compounds, europium or europium containing compounds, terbium or terbium containing compounds, dysprosium or dysprosium containing compounds, holmium or holmium containing compounds, erbium or erbium containing compounds, thulium or thulium containing compounds, tungsten or tungsten containing compounds, osmium or osmium containing compounds, iridium or iridium containing compounds, platinum or platinum containing compounds, or any other paramagnetic or superparamagnetic material. The materials of the colloidal particles allow for the microbot to disassemble to the colloidal particles once the magnetic field is removed. In other words, the materials of the colloidal particles do not produce a microbot that cannot be disassembled. The material can be a non-magnetic material that is later coated, doped, implanted with a material, or otherwise manipulated to become magnetic. For example, the material can be polystyrene doped with iron oxide. Other suitable materials include Dynabeads available from ThermoFischer Scientific. In some embodiments, the colloidal particles are approved for use within a patient. In some embodiments, the material can be biodegradable such as polylactic acid. In some embodiments, the material of the colloidal particles can have a hardness of less or equal to or greater than polystyrene, when measured in accordance with ASTM E18 or similar method. The colloidal particles can contain a therapeutic material. The therapeutic material can be imbedded into the colloidal particle and slowly released from the colloidal particle as the particle breaks down. In some embodiments, the material of the microbots can be used to provide radiation therapy to a location within the patient. For example, the magnetic field can be altered to heat the particles of the microbot causing localized hyperthermia.

(50) The colloidal particles can be coated. Suitable coating materials include, but are not limited to an antimicrobial material, an antiplatelet material, a fibrinolytic material, a tactifying material, an antibacterial material, a cancer therapeutic, at least one ligand and combinations thereof. Suitable antimicrobial materials include but are not limited to silver containing compounds, lincosamides (for example clindamycin), tetracyclines (for example doxycline or minocycline), fluoroquinolones (for example ciprofloxacin, oflozacin, levofloxacin or norfloxacin), aminoglycosides (for example streptomycin, tobramycin, gentamycin, or amikacin), and other antimicrobial materials. Suitable antiplatelet or anticoagulation materials include, but are not limited to, dextran, abciximab, clopidogrel, aspirin or other suitable antiplatelet materials. Suitable fibrinolytic materials include, but are not limited to, tissue plasminogen activator, plasmin, urokinase plasminogen activator or other fibrinolytic materials. Suitable tactifying materials include, but are not limited to, hydrophilic and hydrophobic, positively or negative charged or uncharged, moieties to enhance interaction with surface. Suitable antibacterial materials include, but are not limited to, surfactants, rifampin, chlorhexidine, sulfadiazine, erythromycin, or other antibacterial materials. In some embodiments, ligands for receptors expressed on the endothelial cells can be conjugated to the microbots. Suitable ligands include, but are not limited to, selectins, MAC-1. The ligands can be conjugated to the microbot by physical adsorption or covalent coupling. Chemotherapy materials can be used to provide localized chemotherapy to a patient. One skilled in the art would understand that they type of cancer therapeutic material provided to the patient will depend upon multiple factors, including the type of cancer, the biology of the cancer and the biology of the patient. Thus, while an exhaustive list is not included, one skilled in the art would understand that any conjugated medicine can be used. The colloidal particles can also include a material or coating, or be treated, to change the charge associated with the surface. By way of example, the charge of the microbot can be treated to make it anionic, cationic or neutral.

(51) The surface of the colloidal particles, and thereby the microbot, can be smooth. In some embodiments, the surface of the colloidal particles can be decorated with other materials to increase the surface area of the microbot, thereby increasing traction of the microbot. The decoration materials can be adhered to the surface of the colloidal particles. In some embodiments, the decoration materials can have smaller dimensions from the dimension of the colloidal particle that it covers. The surface of the colloidal particles can also be manipulated during the formation of the particles to increase the surface area. For example, the surface of a colloidal particle can be adjusted by changing the synthesis of the particle. The surface of the colloidal particles can also be removed to roughen the surface by chemical etching or by surface roughening (e.g. abrasive blasting, or particle on particle roughening).

(52) A single colloidal particle can form a microbot, but in some embodiments, at least two colloidal particles are joined together to make the microbot. The number of colloidal particles will depend upon the application of the microbots. While there is no maximum limit on the number of colloidal particles used to form a microbot, in some embodiments, between 1 to about 500 colloidal particles are joined to make the microbots. In some embodiments, three colloidal particles are joined to make the microbot. Multiple colloidal particles of the same size or of different sizes can be used to form a microbot. The dimensions of the microbot can dependent upon the number and size of the colloidal particles used. The dimensions of the colloidal particles are limited by the use of the microbots. For example, if the microbot will be used in a vascular system of a patient, the dimensions of the colloidal particles are limited by the dimension of the vein or artery along which the microbot travels. The diameter of the colloidal particles can be between about 1 m to about 4 m. In some embodiments, the diameter of the colloidal particles can be between about 10 nm to 10 m. In some embodiments, the microbot can have a diameter between about 10 nm and about 10 mm. The thickness of the microbot can be between about 10 nm and about 10 m.

(53) The magnetic fields can have a magnitude between about 1 mT to about 20 mT, however fields outside that range can also be effective. The magnitude can be local to the colloidal particles. One skilled in the art would understand that the magnetic field is dictated by the susceptibility of the colloidal particles. Thus, if a colloidal particle is receptive to a magnetic field, then a lower magnetic field can be used, while if the colloidal particle is not receptive to the magnetic field, then a higher magnetic field should be used. The magnetic field can be used to form, power and direct the microbot. The microbots form quickly after the magnetic field is applied, in some embodiments in less than about 20 seconds. In some embodiments, the microbot forms in between about 0.1 second to about 20 seconds. Furthermore, the colloidal particles can closely pack together (similar to a hexagonal crystalline structure) once the magnetic field is applied. Once the magnetic field is applied to the colloidal particles to form the microbot, the microbot can move (i.e. translating along the surface) at a rolling or translation velocity (V) of between about 1 m/s and about 1 mm/s. In some embodiments, the microbot can move at a speed greater than about 1 mm/s. The microbot can be moved using a propulsion system. In some embodiments, the propulsion system can be a wall-based propulsion system. The microbot can advance through the patient at a camber angle relative to the wall or tissue, theta. Theta can be between about 0 (i.e. upright orientation compared to the surface) and 90 (i.e. laying flat on the surface). Notably, the microbot can roll along a surface regardless of the camber angle. However, larger camber angles allow the microbots to roll on round surfaces, such as the inner surface of a tube or vessel. The angle for theta can be set using the magnetic field, understanding that the camber angle can change as the microbot travels along a surface that changes (i.e. bumps, turns, etc.). The microbot can apply a force to the surface which it travels on of between about 250 fN to about 25 pN. The coefficient of friction as the microbot is moving within the patient can be between zero and unity.

(54) Important parameters influencing the rolling velocity (V) include the number of particles comprising the microbot (n), its angular frequency (), and, as the mirobot rotates, the outer circumferential velocity Vo>R.

(55) The microbot can rotate between about 1 hertz and about 100 hertz (). Thus, the microbot can be used to remove material with rotational advancement of the microbot.

(56) The magnetic field can be applied using any suitable device. By way of example only, the device can be large, similar to a CT or MRI. In some embodiments, the microbot can be observed in situ using a MRI or other magnetic imaging device. Magnets within these devices can be used to control the microbots. In some embodiments, the magnetic field device can be small, such that it can be used in remote areas or for ease of use. A plurality of electromagnetic coils can be used to apply a magnetic field. The phase angle, , of the field applied to the microbot can be controlled by a user, for example with a device similar to a joystick, or directional keys. Application of the magnetic field can also direct the microbot. Thus, the magnetic field can control the rotational speed, the advancing speed, the angle relative to the wall, theta and the direction of the microbot. Once the magnetic field is removed from the microbots, they can return to the colloidal particle form, and can be absorbed or broken down by white blood cells in the patient.

(57) An aspect of the invention is a method for using a microbot. The method includes inserting at least one particle in a biological system of a patient. A magnetic field is applied to the particles to form the microbot. The microbot is directed to a location in the biological system of the patient.

(58) The microbot can be used to provide material to a location within a patient. Medications can include, but are not limited to, an antimicrobial material, an antiplatelet material, a fibrinolytic material, a tactifying material, an antibacterial material, a cancer therapeutic, at least one ligand and combinations thereof. Suitable antimicrobial materials include but are not limited to silver containing compounds, lincosamides (for example clindamycin), tetracyclines (for example doxycline or minocycline), fluoroquinolones (for example ciprofloxacin, oflozacin, levofloxacin or norfloxacin), aminoglycosides (for example streptomycin, tobramycin, gentamycin, or amikacin), and other antimicrobial materials. Suitable antiplatelet or anticoagulation materials include, but are not limited to, dextran, abciximab, clopidogrel, aspirin or other suitable antiplatelet materials. Suitable fibrinolytic materials include, but are not limited to, tissue plasminogen activator, plasmin, urokinase plasminogen activator or other fibrinolytic materials. Suitable tactifying materials include, but are not limited to, hydrophilic and hydrophobic, positively or negative charged or uncharged, moieties to enhance interaction with surface. Suitable antibacterial materials include, but are not limited to, surfactants, rifampin, chlorhexidine, sulfadiazine, erythromycin, or other antibacterial materials. In some embodiments, ligands for receptors expressed on the endothelial cells can be conjugated to the microbots. Suitable ligands include, but are not limited to, selectins, MAC-1. The ligands can be conjugated to the microbot by physical adsorption or covalent coupling. Chemotherapy materials can be used to provide localized chemotherapy to a patient. One skilled in the art would understand that they type of cancer therapeutic material provided to the patient will depend upon multiple factors, including the type of cancer, the biology of the cancer and the biology of the patient. Thus, while an exhaustive list is not included, one skilled in the art would understand that any conjugated medicine can be used. The microbot can also include a material or coating, or be treated, to change the charge associated with the surface. By way of example, the charge of the microbot can be treated to make it anionic, cationic or neutral.

(59) In some embodiments, the microbot can be used to remove a blockage or occlusion within a patient. The microbot can be used to remove the blockage or can be used to supply medication to the blockage. Advantageously, the materials of the microbots can be broken down by white blood cells within the patient after use.

(60) The magnetic fields can have a magnitude between about 1 mT to about 20 mT, however fields outside that range can also be effective. The magnitude can be local to the colloidal particles. One skilled in the art would understand that the magnetic field is dictated by the susceptibility of the colloidal particles. Thus, if a colloidal particle is receptive to a magnetic field, then a lower magnetic field can be used, while if the colloidal particle is not receptive to the magnetic field, then a higher magnetic field should be used. The magnetic field can be used to form, power and direct the microbot. The microbots form quickly after the magnetic field is applied, in some embodiments in less than about 20 seconds. In some embodiments, the microbot forms in between about 0.1 second to about 20 seconds. Furthermore, the colloidal particles can closely pack together (similar to a hexagonal crystalline structure) once the magnetic field is applied. Once the magnetic field is applied to the colloidal particles to form the microbot, the microbot can move (i.e. translating along the surface) at a rolling or translation velocity (V) of between about 1 m/s and about 1 mm/s. In some embodiments, the microbot can move at a speed greater than about 1 mm/s. The microbot can be moved using a propulsion system. In some embodiments, the propulsion system can be a wall-based propulsion system. The microbot can advance through the patient at a camber angle relative to the wall or tissue, theta. Theta can be between about 0 (i.e. upright orientation compared to the surface) and 90 (i.e. laying flat on the surface). Notably, the microbot can roll along a surface regardless of the camber angle. However, larger camber angles allow the microbots to roll on round surfaces, such as the inner surface of a tube or vessel. The angle for theta can be set using the magnetic field, understanding that the camber angle can change as the microbot travels along a surface that changes (i.e. bumps, turns, etc.). The microbot can apply a force to the surface which it travels on of between about 250 fN to about 25 pN. The coefficient of friction as the microbot is moving within the patient can be between zero and unity.

(61) The microbot can be used in multiple biological systems in a patient. Systems can include the cardiovascular system, the gastrointestinal system, the lymphatic system, the reproductive system, or other systems within a patient. By way of example, the microbot can be used to remove or reduce a clot (blood, fat, gas, or foreign material) in a patient's artery or vein, or junction between the cardiovascular system and an organ. In some embodiments, the microbot can be used to remove an occlusion in the fallopian tubes of the reproductive organs. In some embodiments, the microbots can be used to remove fluid or metabolic waste from tissues of the lymphatic system. Similar to the vascular system, the microbot would be injected into the lymphatic system. Microbots can also be used to remove a clot in a gastrointestinal system, for example a blockage or occlusion in the small or large intestine. The microbot can also be used within tissue rather than a vessel wall. The patient can be any animal, including a human, dog, cat, horse, cattle, mouse, hamster, or the like.

(62) The microbot can be used to provide medication or treatment to a location in the patient. The medication can be an antimicrobial material, an antiplatelet material, a fibrinolytic material, a tactifying material, an antibacterial material, a cancer therapeutic, at least one ligand or combinations thereof. By way of example, the microbot can provide a cancer therapeutic to a tumor within a patient.

(63) In some embodiments, the microbot can induce localized hyperthermia with a patient. Babincova et al., Selective treatment of neoplastic cells using ferritin-mediated electromagnetic hyperthermia, Medical Hypothesis, 54, 179 (2000), which is incorporated by reference in its entirety, discusses hyperthermic approaches to cancer treatment. The microbots can also be used as paramagnetic particles. Lanza et al., Magnetic resonance molecular imaging with nanoparticles, J. Nucl Cardiol, 11, 733, (2004), which is incorporated by reference, discusses use of iron oxide based materials as contrast enhancers in magnetic imaging.

(64) FIG. 1 illustrates an example application where an external magnetic field is used to assemble microbots, then used for a blood clot removal in a blood vessel. The colloidal particles 102 are joined to make a microbot 104. The colloidal particles rapidly assemble and rotate and employ available surfaces to translate to the clot site 106 in a blood vessel 108. After mechanical or chemical clot dissolution, the applied field is removed and the microbot 108 disassembles into the colloidal particles 102, which quickly disperse.

(65) FIG. 2 illustrates the potential translation velocity of several devices compared to the microbot of the present invention. The microbot of the present invention can have 1-2 orders of magnetite faster speed of the device compared to current technologies. Furthermore, the present invention has much better directional control compared to prior art methods. Thus, as illustrated in FIG. 2, the present invention provides both better directional control and higher speed compared to prior art devices.

EXAMPLES

(66) FIG. 3 illustrates the rolling velocity for microbots created from 1 (n=25), 2 (n=168), 3 (n=140) and 7 (n=35) colloidal particles as a function of weighted angular frequency. Weighted angular frequency is represented in Equation 1.
*.Math.n.Math.cos(.sub.c)(1)
Data points oriented upright (0) to lying nearly flat (90). Line indicates the slope (3 mg/32) (where is viscosity) based on wet friction scaling arguments. To compare results for spherical monomers with those for disk-like wheels, the drag force (F.sub.d) was used for spheres at low Reynolds number (Re) (Equation 2). V, which is related to the friction coefficient, was determined from Equation 3.
F.sub.d=6RV(2)
V=(mg/6)(/hP).Math..Math.n.Math.cos(.sub.c)(3)
where R is the radius of the microbot, h is the gap between the microbot and the surface with pressure P (load/area). The monomer results are scaled by 32/(3.Math.6)=16/9 inset shows unscaled monomer data. FIG. 4 illustrates three seconds of translation under identical field conditions demonstrate that larger microbots roll faster. The increased angular frequency and lower camber angles lead to increased speeds as well. The weighted angular frequency illustrated in FIG. 3 accounts for microbot size and angular frequency. The data illustrates good agreement with this scaling for weighted angular frequencies below 200 rad s/l. Above this amount, the scaling deviates from the data, likely because the assumption that the microbot velocity is much greater than the fluid velocity is no longer valid. Microbots roll along the surface at speeds of up to 90 m/s with applied field frequencies up to 50 Hz over the 0<.sub.c<90. Even single particles roll as long as the surface-parallel component of the rotational axis is not zero. Microbots comprising 2, 3, 7 and even 19 particles, though not strictly round, exhibit smooth motion as they rapidly spin and translate across flat surfaces as illustrated in FIG. 4. At higher values, motion becomes unstable. Velocities of greater than 120 m/s were achieved with dimers and 19-mers at higher amplitude fields, but observation times were limited due to the size of the field-of-view. The data condense to a single line at low to moderate as illustrated in FIG. 3, which supports the conclusion that friction is not stick-slip and microbot speeds increase with size for a given angular frequency due both to the increased load and increased fluid velocities near the wall. A useful feature of this approach is that different sized microbots, and thus different speeds for a given field rotation frequency, can be assembled from the same building blocks by changing the bulk colloid concentration. In fact, microbots of other particle sizes roll well. However, structural isomers in these systems make quantification difficult.

(67) FIGS. 5A-G illustrate the forming of a microbot. Seven colloidal particles are illustrated in these figures. Three magnetic fields B.sub.x, B.sub.y, and B.sub.z are initially off as illustrated in FIG. 5A. FIG. 5B illustrates the particles after the B.sub.x and B.sub.y magnetic fields are turned on and time elapses. Two particles have joined in FIG. 5B (illustrated as 502). While not illustrated in these figures, the particles are rotating at a rotational velocity (). FIG. 5C illustrates two additional particles joining together (illustrated as 504) after additional time elapses. FIG. 5D illustrates the joining of 502 and 504 to form a four particle microbot (illustrated as 506) after additional time elapses. FIG. 5E illustrates an additional particle joining the microbot 506 to form a five particle microbot (illustrated as 508) after additional time elapses. FIG. 5F illustrates the two remaining microbots joining together to form a two particle microbot 510 after additional time elapses. Finally, FIG. 5G illustrates a seven particle microbot 512 formed from the joining of 510 and 508 after additional time elapses. The B.sub.z magnetic field has also been activated. A total of about 12 second elapsed from the time that the magnetic field was applied (illustrated in FIG. 5B) to the forming of the seven-mer microbot (illustrated in FIG. 5G).

(68) FIGS. 6A-D illustrates field induced assembly and rotation of a seven-mer microbot. Superparamagnetic beads assemble into a microbot by isotropic interactions induced by the in-plane rotating magnetic field (FIG. 6A-B) with microbot size controlled by local bead density. Spinning microbots lying flat on a surface have no net motion. For translation to occur they must be inclined relative to the surface. A normal component is introduced to the magnetic field to orient the field rotation axis towards the surface plane and propel the microbot. With addition of a field in the z direction, both symmetric and asymmetric microbots reorient off the surface to a defined camber angle, .sub.c (FIG. 6C-D), and begin to translate. Advantageously, the camber angle can vary from lying flat, (90), and spinning without translation to fully upright, (0), and rolling (FIG. 6B-C). FIG. 6A illustrates the formation of the microbot. Seven colloidal particles join together to form the microbot. With application of the rotating magnetic field B.sub.x+B.sub.y in the surface plane, colloids assemble via isotropic interactions and sit and spin (scale bar, 20 m) as illustrated in FIG. 6B. FIG. 6C illustrates the field rotation axis oriented towards the surface plane resulting in the microbots standing up at a camber angle, .sub.c, and roll along the surface with addition of a normal variable-phase component (B.sub.z). FIG. 6D illustrates .sub.c measured during microbot translation as a function of the applied field rotation axis set via tan.sup.1(B.sub.0/B.sub.z0). Data points (n=368) are illustrated by the magnetic field magnitude, from low to high. The magnetic field magnitude is represented by Equation 4.
B.sub.Total=(B.sub.0.sup.2+B.sub.z0.sup.2).sup.1/2(4)
The black line corresponds to perfect alignment between microbot and field rotation axis. The inset identifies total field magnitudes as field ratios are varied.

(69) FIG. 7 illustrates the camber angle curves as a function of microbot projected area as viewed from above for several configurations of microbots.

(70) FIGS. 8A and 8B illustrate a side view and front view, respectively, of a translating microbot modeled as a disk. The important parameters include F.sub.d, drag force; F.sub.f, friction force; L, load; N, normal force from wall; M, mass of the microbot; .sub.c, camber angle; , angular frequency; g, gravitational constant; and R, radius.

(71) FIGS. 9A-C illustrates the heading angle. Targeting applications require not only microbot propulsion but also the ability to direct them to desired locations. Unlike tires, microbots can be oriented at very high .sub.c and, as a result, can experience significant lateral forces and heading slip. Defining the heading slip angle, .sub.h, as the difference between the rolling direction (heading) and the microbot rotation plane (pointing) directions, lateral forces can be observed to push microbots towards the microbot rotational axis (FIG. 9A). As .sub.c increases, heading and pointing directions separate as characterized by increasing microbot heading angle .sub.h (n=343) as illustrated in FIG. 9A. FIG. 9B illustrates a microbot where .sub.h is 27, .sub.c is 76, and V is 14 m/s. FIG. 9C illustrates a microbot where the heading angle is 5, .sub.c is 28 and V is 39 m/s.

(72) FIGS. 10A-C illustrate directional control of the microbots. FIG. 10A illustrates automated patterns that can be formed with the microbots of the invention (scale bars, 10 m). FIG. 10B illustrates manual control of the microbots using a keypad over time. FIG. 10C illustrate a stepwise microbot assembly.

(73) FIGS. 11A, 11B and 11C illustrate a microbot comprising three colloidal particles that have been moved from a first position (FIG. 11A) to a second position (FIG. 11B) to a third position (FIG. 11C).

(74) FIGS. 12A-H illustrate a microbot comprising two colloidal particles that have been moved from a first position (FIG. 12A) to a final position (FIG. 12H) and intermediate positions (FIGS. 12B-G). For clarity, the path of the microbot has been illustrated by spelling the word key.

(75) FIG. 13 illustrates an experimental set up of the magnetic field system consisting of five air-cored solenoid coils. These cores are used to apply the magnetic field to the microbots. Each coil had an inner diameter of 50 mm, 51 mm length, 400 turns and current capacity 3.5 A. The field generated at the center of experiments had three components, B.sub.x, B.sub.y and B.sub.z (equations represented in Equations 5-7, respectively):
B.sub.x=/B.sub.x0 cos(.sub.ft)(5)
B.sub.y=B.sub.y0 cos(.sub.ft/2)(6)
B.sub.z=B.sub.z0 cos(.sub.ft.sub.z)(7)
B.sub.x was generated by coils C.sub.x1 and C.sub.x2, B.sub.y was generated by C.sub.y1 and C.sub.y2, B.sub.z was generated by coil C. Sinusoidal voltage waveforms were generated using Matlab (Mathworks, Inc., Natick, Mass., USA) and an analog-output card (National Instruments, NI-9263) and then amplified (Behringer EP2000) before being applied to individual solenoids. To monitor coil currents, an analog input data acquisition card was used (National Instruments, NI-USB-6009). The resulting magnetic fields were estimated using a custom Matlab code solving the fields of the solenoids for a given current. Predictions of the code were validated by exciting the coils with constant currents and measuring the field with a gaussmeter (VGM Gaussmeter, Alphalab Inc.).

(76) The effect of rotational speed () on translation velocity tested. Table 1 illustrates the velocity for two-mer microbots.

(77) TABLE-US-00001 TABLE 1 Number of colloidal Rotational Speed Translation Theta Sample particles (n) ( - rotations/s) velocity (m/s) () 1 2 45 17 17 2 2 64 28 17 3 2 126 52 17 4 2 253 87 17 5 2 126 22 53 6 2 126 33 44 7 2 126 47 24 8 7 16 14 76 9 7 19 21 65 10 7 21 25 53 11 7 24 28 44 12 7 28 34 35 13 7 33 39 28

(78) Ranges have been discussed and used within the forgoing description. One skilled in the art would understand that any sub-range within the stated range would be suitable, as would any number within the broad range, without deviating from the invention.

(79) The foregoing description of the present invention has been presented for purposes of illustration and description. Furthermore, the description is not intended to limit the invention to the form disclosed herein. Consequently, variations and modifications commensurate with the above teachings, and the skill or knowledge of the relevant art, are within the scope of the present invention. The embodiment described hereinabove is further intended to explain the best mode known for practicing the invention and to enable others skilled in the art to utilize the invention in such, or other, embodiments and with various modifications required by the particular applications or uses of the present invention. It is intended that the appended claims be construed to include alternative embodiments to the extent permitted by the prior art.