Magnetic separation method

• US 5,458,785 A
• Filed: 09/24/1993
• Issued: 10/17/1995
• Est. Priority Date: 09/24/1992
• Status: Expired due to Fees

• Current Assignee: Amersham International Plc (General Electric Company)
• Original Assignee: Amersham International Plc (General Electric Company)
• Inventors: Howe, Roland P., Reeve, Michael A., Bischof, Daniel
• Primary Examiner(s): Savage, Matthew O.
• Application Number:
  US08/125,811
• Time in Patent Office: 753 Days
• Field of Search: 210/222, 210/695, 422/100, 422/101, 436/177, 436/178, 436/526, 335/302, 335/304, 335/306
• US Class Current: 210/695
• CPC Class Codes: B03C 1/0332 using permanent magnets
• CPC Class Codes: B03C 1/0335 using coils
• CPC Class Codes: B03C 1/035 Open gradient magnetic separators, i.e. separators in which the gap is unobstructed, characterised by the configuration of the gap
• 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: 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: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

Biological assay systems often involve suspending magnetically attractable particles in a liquid, and later bringing down the particles from suspension and separating the formed pellet from the supernatant liquid. The invention provides magnetic systems for this purpose, shaped to form an annular or part-annular pellet close to the bottom of the vessel. The systems are suitable for automation.

Claims

1. A magnet system comprising:

a carrier plate of non-magnetizable material;

a back flow plate of magnetizable material overlying the carrier plate;

a row of permanent magnets each having opposed first and second ends, the first end of each said magnet being positioned on the back flow plate with a N-S axis oriented perpendicular to the back flow plate, the polarity of each permanent magnet being opposite to that of its neighbor or neighbor, the permanent magnets being spaced apart to define between them one or more work stations;

a field concentrator plate of magnetizable material overlying said second ends of the permanent magnets; and

a cover plate of nonmagnetizable material overlying the field concentrator plate;

there being provided a hole through the field concentrator plate and the overlying cover plate for locating a vessel at the work station.

2. A magnetic separation method which comprises the steps of:

a) bringing a vessel having a bottom end and containing a liquid suspension of magnetically attractable particles into proximity with a magnet system whereby there is formed an annular or part-annular pellet comprising the magnetically attractable particles close to, but not at, the bottom end of the vessel;

b) removing supernatant liquid from the vessel; and

c) adding fresh liquid to the vessel;

d) using the magnet system to draw the magnetically attractable particles to the bottom of the vessel;

e) removing the magnet system;

f) and re-suspending the magnetically attractable particles in the fresh liquid;

g) wherein the magnet system comprises a carrier plate of non-magnetizable material;

a back flow plate of magnetizable material overlying the carrier plate;

a row of permanent magnets each having opposed first and second ends, the first end of each said magnet being positioned on the back flow plate with a N-S axis oriented perpendicular to the back flow plate, the polarity of each permanent magnet being opposite to that of its neighbor or neighbors, the permanent magnets being spaced apart to define between them one or more work stations;

a field concentrator plate of magnetizable material overlying said second ends of the permanent magnets; and

a cover plate of non-magnetizable material overlying the field concentrator plate;

there being provided a hole through the field concentrator plate and the overlying cover plate for locating a said vessel at the work station.

3. The method as claimed in claim 2, wherein during step c) sufficient fresh liquid is added to the vessel to submerge the annular or part-annular pellet.

4. The method as claimed in claim 2, wherein the vessel is a round-bottom or conical-bottom vessel.

5. A method of treating a solution of a polymer in a vessel having a bottom end, by the use of magnetically attractable particles which do not specifically bind the polymer, comprising the steps of:

a) suspending the magnetically attractable particles in the solution so as to form a liquid suspension of the magnetically attractable particles;

b) precipitating the polymer out of solution whereby it becomes non-specifically associated with the magnetically attractable particles;

c) bringing the vessel into proximity with a magnet system whereby there is formed an annular or part-annular pellet comprising the magnetically attractable particles and the precipitated polymer, said pellet being positioned close to, but not at, the bottom of the vessel;

d) removing a supernatant liquid from the vessel;

e) adding fresh liquid to the vessel;

f) using the magnet system to draw the magnetically attractable particles to the bottom of the vessel;

g) removing the magnet system;

h) redissolving the polymer in the fresh liquid; and

k) wherein the magnet system comprises a carrier plate of non-magnetizable material;

a back flow plate of magnetizable material overlying the carrier plate;

a row of permanent magnets each having opposed first and second ends, the first end of each said magnet being positioned on the back flow plate with a N-S axis oriented perpendicular to the back flow plate, the polarity of each permanent magnet being opposite to that of its neighbor or neighbors, the permanent magnets being spaced apart to define between them one or more work stations;

a field concentrator plate of magnetizable material overlying said second ends of the permanent magnets; and

a cover plate of non-magnetizable material overlying the field concentrator plate;

there being provided a hole through the field concentrator plate and the overlying cover plate for locating a said vessel at the work station.

6. The method as claimed in claim 5, wherein the polymer is a nucleic acid.

7. The method as claimed in claim 5, wherein during step e) sufficient fresh liquid is added to the vessel to submerge the annular or part-annular pellet.

8. The method as claimed in claim 5, wherein the vessel is a round-bottom or conical-bottom vessel.

9. Apparatus which comprises:

an array of vessels each to contain a liquid suspension of magnetically attractable particles;

a pipetting system for transferring liquid to and from the array of vessels;

and a magnet system; and

means for movably mounting the magnet system relative to the array of vessels, said means being adapted to bring the magnet system to any one of three positions and hold the magnet system in that position, the positions being;

i) engaged with the array of vessels in an annular separation position;

ii) engaged with the array of vessels in a pull-down separation position; and

iii) free of the array of vessels;

wherein the magnet system comprises;

a carrier plate of non-magnetizable material;

a back flow plate of magnetizable material overlying the carrier plate;

a row of permanent magnets each having opposed first and second ends, the first end of each said magnet being positioned on the back flow plate with a N-S axis oriented perpendicular to the back flow plate, the polarity of each permanent magnet being opposite to that of its neighbor or neighbors, the permanent magnets being spaced apart to define between them one or more work stations;

a field concentrator plate of magnetizable material overlying said second ends of the permanent magnets; and

a cover plate of non-magnetizable material overlying the field concentrator plate;

there being provided a hole through the field concentrator plate and the overlying cover plate for locating a said vessel at the work station.