Apparatus for mixing magnetic particles

• US 20060207944A1
• Filed: 05/17/2006
• Published: 09/21/2006
• Est. Priority Date: 02/21/1995
• Status: Active Grant

• Current Assignee: Sigris Research Incorporated
• Original Assignee: Iqbal Waheed Siddiqi
• Inventors: Siddiqi, Iqbal Waheed
• Granted Patent: US 7,476,313 B2
• Time in Patent Office: Days
• US Class Current: 210/695
• CPC Class Codes: B01F 33/451 wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
• CPC Class Codes: B01F 33/81 Combinations of similar mixers, e.g. with rotary stirring devices in two or more receptacles
• CPC Class Codes: B01F 33/813 mixing simultaneously in two or more mixing receptacles
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for microtitration plates
• CPC Class Codes: B03C 1/01 by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/12 with magnets moving during operation; with movable pole pieces
• CPC Class Codes: B03C 1/14 with non-movable magnets
• CPC Class Codes: B03C 1/24 with material carried by travelling fields
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

An apparatus and method for carrying out the affinity separation of a target substance from a liquid test medium by mixing magnetic particles having surface immobilized ligand or receptor within the test medium to promote an affinity binding reaction between the ligand and the target substance. The test medium with the magnetic particles in a suitable container is removably mounted in an apparatus that creates a magnetic field gradient in the test medium. This magnetic gradient is used to induce the magnetic particles to move, thereby effecting mixing. The mixing is achieved either by movement of a magnet relative to a stationary container or movement of the container relative to a stationary magnet. In either case, the magnetic particles experience a continuous angular position change with the magnet. Concurrently with the relative angular movement between the magnet and the magnetic particles, the magnet is also moved along the length of the container causing the magnetic field gradient to sweep the entire length of the container. After the desired time, sufficient for the affinity reaction to occur, movement of the magnetic gradient is ended, whereby the magnetic particles are immobilized on the inside wall of the container nearest to the magnetic source. The remaining test medium is removed while the magnetic particles are retained on the wall of the container. The test medium or the particles may then be subjected to further processing.

Claims

1. Apparatus for mixing and separating magnetic particles in a plurality of containers with liquid and said particles therein, said apparatus comprising:

a. first support means for holding said containers in substantially straight parallel rows which are spaced apart;

b. second support means for holding magnets in substantially straight parallel rows separated by sufficient distance to place said rows of containers there between to dispose magnets alternately on opposite sides of each container in close proximity wherein said rows of magnets are mounted on at least two separate supports which are independently moveable substantially upwardly or downwardly to alternately position said magnets on the opposite sides of said containers rows;

c. means for providing an oscillating movement to said two independent supports successively in substantially linear path in the vertical plane to dispose said magnets alternately on opposite sides of each container to disperse said magnetic particles in liquid inside said containers; and

d. means for stopping said motion in vertical plane and moving said two independent supports to position said magnets in said magnet rows in close proximity to each container of said container rows to aggregate said magnetic particles on the inner wall of said containers.

2. The apparatus of claim 1 wherein acceleration of movements in vertical plane is at a rate of about 0.2 m/s² to about 1 m/s² with a delay time of about 0.25 s to about 120 s or over 120 seconds between successive movements of said two support means.

3. The apparatus of claim 2 wherein said oscillating movement is started and stopped by at least one electric motor operated and controlled by electrical means.

4. The apparatus of claim 1 wherein said magnetic particles are non-colloidal paramagnetic or super paramagnetic.

5. The apparatus of claim 1 wherein said containers is a 96-well microplate held on a support means and one of said two independently movable supports carries a 6×

4 array of evenly spaced magnets and the other of said two independently movable supports carries a 7×

5 array of evenly spaced magnets wherein alternate oscillating movement of said two independently movable supports alternately positions their respective magnets on the opposite sides of wells of said 96-well microplate.

6. The apparatus of claim 1 constructed and arranged to purify molecular and cellular entities by affinity binding on magnetic, paramagnetic or super paramagnetic particles and separation of said magnetic particles from liquid by magnets.

7. Apparatus for mixing and separating magnetic particles in containers with liquid and said particles therein comprising;

a. a first support means for mounting one or more containers in a ring configuration;

b. a second support means for mounting magnets in at least two concentric magnet rings spaced apart to position said container ring there between;

c. said first support means and said second support means aligned in the apparatus to make said container ring and said two magnet rings concentric on a common axis;

d. said two magnet rings constructed and configured to dispose a magnet of each ring alternately on opposites sides each container;

e. means for providing rotary motion to either said first support or said second support in the horizontal plane to alternately displace each magnet of said magnet rings at opposite sides of each container in said container ring to disperse said magnetic particles in liquid inside said containers; and

f. means for stopping said rotary motion to position each magnet in said two magnet rings in close proximity to each container of said container ring to aggregate said particles on the inner wall of said containers.

8. The apparatus of claim 7 wherein the said magnets are permanent magnets and magnets in said two concentric rings have similar poles opposite one another.

9. The apparatus of claim 7 wherein said rotary motion is started and stopped by at least one electric motor operated and controlled by electrical means.

10. The apparatus of claim 7 wherein said magnetic particles are non-colloidal paramagnetic or super paramagnetic.

11. The apparatus of claim 9 wherein said rotary motion is stepwise angular displacement at an angular acceleration of about 21 rads/s² or higher.

12. The apparatus of claim 11 wherein said stepwise rotary motion has a delay time of about 0.25 seconds to 120 seconds, and over 120 seconds between successive steps.

13. The apparatus of claim 11 wherein said stepwise rotary motion is in steps of about 10 degrees to 30 degrees and unidirectional or bidirectional oscillating between clockwise or anticlockwise directions.

14. The apparatus of claim 7 constructed and arranged to purify molecular and cellular entities by affinity binding on magnetic, paramagnetic or super paramagnetic particles and separation of said magnetic particles from liquid by magnets.

15. Apparatus for mixing and separating magnetic particles comprising:

a. at least one said container held in a fixed upright position in the said first support; and

b. at least two magnets mounted in orthogonal positions on two separate second supports facing each other and sufficiently spaced to position said container in the middle;

c. said two second supports rotatable in unison on a common axis by to successively dispose magnets on the opposite sides of said container; and

d. said container and the said two second supports being orientated in substantially vertical orientation.

16. The apparatus of claim 15 wherein said rotary motion is by at least one electric motor operated and controlled by electronic means.

17. The apparatus of claim 15 wherein said magnets are separated by an angular position of 180 degrees or less.

18. The apparatus of claim 15 wherein said rotary motion is stepwise at an angular acceleration of about 21 rads/s² or higher with a delay time of about 0.25 seconds to 120 seconds, and over 120 seconds between successive steps.

19. The apparatus of claim 15 wherein said magnetic particles are non-colloidal paramagnetic or super paramagnetic.

20. The apparatus of claim 15 constructed and arranged to purify molecular and cellular entities by affinity binding on magnetic, paramagnetic or super paramagnetic particles and separation of said magnetic particles from liquid by magnets.