Magnetic separation device and methods for use in heterogeneous assays

• US 4,988,618 A
• Filed: 05/03/1989
• Issued: 01/29/1991
• Est. Priority Date: 11/16/1987
• Status: Expired due to Term

• Current Assignee: Amoco Corporation (BP PLC)
• Original Assignee: Gene Therapy Systems, Inc.
• Inventors: Bach, David T., Li, May K., Kessler, Jack
• Primary Examiner(s): Price, Carl D.
• Application Number:
  US07/347,544
• Time in Patent Office: 636 Days
• Field of Search: 435/173, 435/301, 435/6, 210/222, 210/695, 209/9, 269/8, 422/104, 436/808, 436/809, 436/526
• US Class Current: 435/6.13
• CPC Class Codes: B03C 1/0332 using permanent magnets
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/26 for use in medical or biological applications
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/54326 Magnetic particles
• 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: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays

Abstract

Magnetic separation devices are described for use in immunoassay or hybridization assay procedures. The most preferred embodiments comprise a defined relationship between microtube and microtiter plate receiving orifices and rare earth cobalt magnets having predetermined magnetic field orientations.

Claims

1. A magnetic separation apparatus for use in assays employing solid phases comprising magnetic particles, said apparatus comprising:

(a) base means having a plurality of orifices for receiving nonferrous containers adapted to contain said magnetic particles; and

(b) a plurality of magnet means mounted on said base and spaced about the periphery of each receiving orifice wherein each of said magnet means possess a north-south magnetic field orientation in a direction which is coplanar with a cross-sectional plane through said receiving orifices and wherein each of said north-south magnetic fields of said magnet means are oriented in a common direction and wherein said magnet means are mounted in a fixed relation with respect to themselves and to said base whereby each nonferrous container, when placed in receiving relationship with each of said orifices, has four magnet means about its periphery.

2. The apparatus of claim 1 wherein said magnet means is a rare earth cobalt magnet.

3. The apparatus of claim 2 wherein said magnet means is a 33H Neodymium Iron Boron magnet.

4. The apparatus of claim 1 further comprising tube transfer means adapted to receive nonferrous microtube containers and to mateably engage said base means whereby each nonferrous microtube container is received by a receiving orifice and is surrounded by a plurality of magnets.

5. A process for detecting a ligand in a fluid sample by immunoassay or hybridization with a ligand specific binding substance which utilizes a ferrous solid phase microparticle wherein the improvement comprises employing the magnetic separation apparatus of claim 1 for effecting separation of solid phase bound ligands or ligand specific binding substances from unbound ligands or ligand specific binding substances present in said fluid sample.

6. A magnetic separation apparatus for use in assays employing solid phases comprising magnetic particles, said apparatus comprising:

(a) a base means having a plurality of orifices for receiving nonferrous containers adapted to contain said magnetic particles; and

(b) a plurality of magnet means mounted on said base spaced about the periphery of each receiving orifice and wherein said magnet means are mounted in a fixed relation with respect to themselves and to said base and wherein each of said magnet means possess a north-south magnetic field orientation in a direction which is coplanar with a cross-sectional plane through said receiving orifices and wherein the north-south magnetic field direction orientation, moving in a common direction about the periphery of each of said receiving orifices, alternates approximately 180°

from the north-south field direction orientation of the preceding magnet whereby each nonferrous container, when placed in receiving relationship with each of said orifices, has four magnet means about its periphery.

7. The apparatus of claim 6 wherein said magnet means is a rare earth cobalt magnet.

8. The apparatus of claim 7 wherein said magnet means is a 33H Neodymium Iron Boron magnet.

9. The apparatus of claim 8 wherein said base means has 96 receiving orifices, said apparatus comprises 117 33H Neodymium Iron Boron magnets and said base means is made of a material selected from the group consisting of aluminum and plastic.

10. The apparatus of claim 9 wherein said magnets have a dimension of approximately 0.13×

0.13×

0.5 inches.

11. The apparatus of claim 6 further comprising tube transfer means adapted to receive nonferrous microtube containers and to mateably engage said base means whereby each nonferrous microtube container is received by a receiving orifice and is surrounded by a plurality of magnets.

12. A process for detecting a ligand in a fluid sample by immunoassay or hybridization with a ligand specific binding substance which utilizes a ferrous solid phase microparticle wherein the improvement comprises employing the magnetic separation apparatus of claim 6 for effecting separation of solid phase bound ligands or ligand specific binding substances from unbound ligands or ligand specific binding substances present in said fluid sample.

13. The apparatus of claim 12 wherein said magnet means is a rare earth cobolt magnet.

14. The apparatus of claim 13 wherein said magnet means is a rare earth cobolt magnet.

15. A magnetic separation apparatus for use in assays employing solid phases comprising magnetic particles, said apparatus comprising:

(a) base means adapted to receive microwell tray means of nonferrous composition adapted to contain said magnetic particles; and

(b) a plurality of magnet means mounted on said base in spatial alignment with said microwell tray means whereby each well in said microwell tray means has adjacent thereto at least one magnet means possessing a north-south magnetic field orientation in a direction which is coplanar with a cross-sectional plane through said well and wherein each of said north-south magnetic fields of said magnet means are oriented in a common direction and wherein said magnet means are mounted in a fixed relation with respect to themselves and to said base whereby each nonferrous container, when placed in receiving relationship with each of said wells, has four magnet means about its periphery.

16. A magnetic separation apparatus for use in assays employing solid phases comprising magnetic particles, said apparatus comprising:

(a) base means adapted to receive microwell tray means of nonferrous composition adapted to contain said magnetic particles and having a plurality of wells; and

(b) a plurality of magnet means mounted on said base in spatial alignment with said microwell tray means wherein said magnet means are mounted in a fixed relation with respect to themselves and to said base and wherein each of said magnet means possess a north-south magnetic field orientation in a direction which is coplanar with a cross-sectional plane through said microwell tray means and wherein the north-south magnetic field direction orientation, moving in a common direction about the periphery of each well in said microwell tray means, alternates approximately 180°

from the forth-south field direction orientation of the preceding magnet thereby each well of said microwell tray means, when placed in receiving relationship with said base means, has four magnet means about its periphery.

17. A magnetic separation apparatus for use in assays employing solid phases comprising magnetic particles, said apparatus comprising:

a. base means for receiving a nonferrous tray containing a plurality of microwells adapted to contain said magnetic particles;

b. base means comprising a plurality of magnet means mounted on said base spaced on said base whereby engagement of said base and said tray results in the juxtapose placement of a plurality of magnet means about the periphery of each well wherein each of said wells is surrounded about the perhiphery by four magnet means wherein the north-south magnetic field direction orientation, moving in a common direction about the periphery of each of said wells, alternates approximately 180°

from the north-south field direction orientation of the preceding magnet.