Aggregation and control of magneto-responsive entities

• US 9,905,347 B2
• Filed: 06/13/2012
• Issued: 02/27/2018
• Est. Priority Date: 06/13/2012
• Status: Active Grant

• Current Assignee: Polyvalor LP
• Original Assignee: Polyvalor LP
• Inventors: Martel, Sylvain, Felfoul, Ouajdi
• Primary Examiner(s): Talpalatski, Alexander
• Application Number:
  US14/406,371
• Publication Number:
  US 20150243425A1
• Time in Patent Office: 2,085 Days
• Field of Search: 335219
• CPC Class Codes: A61B 2090/374 NMR or MRI
• CPC Class Codes: A61B 34/70 Manipulators specially adapted for use in surgery
• CPC Class Codes: A61B 34/73 Manipulators for magnetic surgery
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 47/69 the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01R 33/0023 Electronic aspects, e.g. circuits for stimulation, evaluation, control; Treating the measured signals; calibration G01R33/0017 takes precedence
• CPC Class Codes: H01F 7/0273 Magnetic circuits with PM for magnetic field generation
• CPC Class Codes: H01F 7/064 Circuit arrangements for actuating electromagnets circuit arrangements for obtaining special operating characteristics H01F7/18; driving circuits for electromagnets making use of a switching regulator H01H47/325

Abstract

Applicants have discovered a novel apparatus and method to aggregate and displace a plurality of magneto-responsive entities (steerable self-propelled entities or SSPEs) in three dimensions using time-multiplexing. The apparatus for controlling aggregation of SSPEs in a body comprises at least three sets of magnetic field sources arranged in three axes for generating a controlled magnetic field and a controller connected to at least one of said magnetic field sources to create a three dimensional convergence point. The method for aggregating the entities can comprise using a first set and a second set of said magnetic field sources to generate opposed magnetic field gradients in each said set to cause aggregation of said magneto-responsive entities in two axes and wherein the controller is configured to reverse a direction of said magnetic field gradient in a third set of magnetic field sources in a third axis according to a first predetermined program.

Claims

1. An apparatus for controlling aggregation of magneto-responsive self-propelled entities in a body comprising:

at least three sets of magnetic field sources arranged in three axes for generating a magnetic field; and

a controller connected to at least one of said magnetic field sources configured to create a three dimensional convergence point to which following the direction of said magnetic field said self-propelled entities will move to and aggregate, wherein surrounding said convergence point the effective field points from all directions to said convergence point, and at least one of said magnetic field sources is time varied to cause said self-propelled entities to move toward said convergence point and stay close to said convergence point, wherein said controller causes one of;

any two axes of said three axes to maintain a constant magnetic field while changing the direction of the other axis of said three axes depending upon said two axes of said three axes being maintained constant; and

one axis of said three axes to maintain constant while changing the direction of the other two axes of said three axes in a time multiplexing fashion at the same time or with a phase delay; and

to change the direction of all of said three axes in a time multiplexing fashion simultaneously or with a delay between each axis of said three axes,

wherein the direction of the magnetic field gradient of at least one axis of said three axes is changed in a time multiplexed fashion with a switching speed appropriate with the reaction time of said self-propelled entities.

2. The apparatus of claim 1, wherein a first set and a second set of said magnetic field sources generate an opposed magnetic field gradients in each said set to cause aggregation of said magneto-responsive entities in two axes and wherein said controller is configured to reverse a direction of said magnetic field gradient in a third set of magnetic field sources in a third axis according to a first predetermined program.

3. The apparatus of claim 1, wherein said controller is configured for one of:

sequentially actuating all combinations of two sets of magnetic field sources according to a second predetermined program;

controlling said magnetic field sources to cause displacement of said magneto-responsive entities;

targeting said entities to a location in said body by moving said convergence point with respect to said sets of magnetic field sources;

changing a size of said convergence point to increase pathfinding capability of magneto-responsive entities;

changing a shape of said convergence in order to increase pathfinding capability of magneto-responsive entities; and

controlling an actuation of said magnetic field source in order to increase pathfinding capability of magneto-responsive entities.

4. The apparatus of claim 2, wherein said first set and said second set of magnetic field sources each comprise two coils having current flowing in opposite directions in each set.

5. The apparatus of claim 1, wherein said axes are orthogonal with respect to each other.

6. The apparatus of claim 1, further comprising a platform for receiving said body, wherein a location of said convergence point is changed by moving said platform.

7. The apparatus of claim 3, wherein said targeting comprises a combination of a directional mode and an aggregation mode.

8. The apparatus of claim 2, wherein said first and said second predetermined programs provide a frequency at which a predetermined proportion of said magnetotactic bacteria are able to realign to said field following change in said magnetic field.

9. The apparatus of claim 1, wherein a top of an aggregation zone is modulated in order to increase pathfinding capability of magneto-responsive entities.

10. The apparatus of claim 1, further comprising a magneto-responsive entity detector for detecting the location of said magneto-responsive entities.

11. The apparatus of claim 1, further comprising a platform for moving between a first station having a magneto-responsive entity detector and a second station having said magnetic field sources.

20. The apparatus of claim 4, further comprising means for positioning said coils to be around said body and means for releasing said body form the coils.

12. A method of aggregating therapeutic carrying magneto-responsive self-propelled entities at a target location in a body, wherein said self-propelled entities comprise a steering system and a propulsion system, comprising:

introducing said therapeutic carrying magneto-responsive self-propelled entities in said body at an injection site;

generating in said body a magnetic field having a three dimensional convergence point at said target location or near said target location to which, following the direction of said magnetic field, said self-propelled entities will move to and aggregate, wherein said magnetic field is sufficient to induce a directional torque that influences said steering system;

maintaining said generating to allow said entities in said body to move toward and aggregate at or near said convergence point by using said propulsion system of said entities for their self-propulsion and said steering system of said entities, said steering system influenced by said directional torque, for guiding said self-propelled entities; and

delivering said therapeutic-carrying self-propelled entities to said target location in said body.

13. The method of claim 12, wherein generating said convergence point further comprises keeping a constant magnetic field gradient in two axes and alternating a direction of said magnetic field gradient in a third axis according to a first predetermined program.

14. The method of claim 12, wherein generating said convergence point further comprises sequentially actuating all combinations of two opposed magnetic field sources according to a second predetermined program.

15. The method of claim 12, further comprising changing a location of said convergence point by changing said magnetic field.

16. The method of claim 12, wherein said body is a non-living body.

17. The method of claim 15, wherein said location is reached by one of a continuous and a sequential movement of said convergence point.

18. The method of claim 12, further comprising targeting said magneto-responsive entities to a location in said body using a directional mode.

19. The method of claim 12, wherein said magneto-responsive entities comprise magnetotactic bacteria.

21. The method of claim 12, wherein said generating in said body a magnetic field having a three dimensional convergence point is performed by time varying at least one magnetic field source of at least three sets of magnetic field sources arranged in three axes for generating said magnetic field, wherein surrounding said convergence point the effective field points from all directions to said convergence point, causing said self-propelled entities to move toward said convergence point and stay close to said convergence point, wherein said convergence point is further generated by causing one of:

maintaining any two axes of said three axes with a constant magnetic field while changing the direction of the other axis of said three axes depending upon said two axes of said three axes being maintained constant;

maintaining one axis of said three axes constant while changing the direction of the other two axes of said three axes in a time multiplexing fashion at the same time or with a phase delay; and

changing the direction of all of said three axes in a time multiplexing fashion simultaneously or with a delay between each axis of said three axes, and

wherein the direction of the magnetic field gradient of at least one axis of said three axes is changed in a time multiplexed fashion with a switching speed appropriate with the reaction time of said self-propelled entities.

22. The method of claim 12, wherein said generating in said body a magnetic field having a three dimensional convergence point comprises inserting a magnetotaxis probe, configured to generate a magnetic field, into said body.