Method for treating magnetic particles and biological analysis device using magnets

• US 20040235196A1
• Filed: 06/07/2004
• Published: 11/25/2004
• Est. Priority Date: 07/09/2001
• Status: Active Grant

• Current Assignee: Biomerieux SA (Compagnie Merieux Alliance SAS)
• Original Assignee: Biomerieux SA (Compagnie Merieux Alliance SAS)
• Inventors: Colin, Bruno
• Granted Patent: US 7,396,690 B2
• Time in Patent Office: Days
• US Class Current: 436/526
• 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 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

Abstract

A method for treating magnetic particles present in a solution in a container by redispersion, rinsing or displacement, the particles having novel characteristics under the effect of a specific magnet and being associated or not with biological entities. The magnetic particles undergo at least one low-intensity magnetization where they are disposed in filaments oriented according to the north-south axis of the magnet; the magnetization source and/or container is/are displaced while the magnetic effect is maintained on the magnetic particles; the magnetization source and/or container is/are displaced or the, magnetization is stopped, in order to suppress the magnetic field on the magnetic particles. Preferably, the invention can be used in the field of biology.

Claims

1-17. -17. (Canceled)

18. A method for treating magnetic particles present in solution in a vessel, magnetic particles being associated or not to biological entities, the method comprising:

subjecting said magnetic particles to a constant magnetic field in the form of magnetisation which is a function essentially of two values, T and D, where;

T corresponds to the magnetic induction of the magnetisation source, expressed in milliTesla (mT), and

D corresponds to the distance separating this magnetisation source from the bottom of the vessel, expressed in millimetres (mm), such that when T is between 5 and 400 mT, D is less than or equal to 50 mm for magnetic particles having a diameter substantially less than 1μ

, such that said magnetic particles are disposed in filaments oriented along the north-south axis of the magnetisation source,

moving the magnetisation source and/or the vessel, while maintaining magnetisation on the magnetic particles, and

suppressing magnetisation on the magnetic particles by moving said magnetisation source and/or the vessel and/or stopping the magnetisation source.

19. The method of claim 18, wherein magnetic induction T of the magnetisation source is between 10 and 50 mT, and the distance separating this magnetisation source from the vessel is between 3 and 15 mm.

20. The method of claim 18, wherein magnetic induction T of the magnetisation source is less than 5 mT when the distance separating this magnetisation source from the bottom of the vessel is zero.

21. The method of claim 18, allowing washing of the magnetic particles, wherein the movement of the magnetisation source and/or the vessel, while maintaining the magnetic effect on the magnetic particles, is achieved by the variation between −

90° and

+90°

of the angle between the north-south axis of said magnetisation source and the axis of said vessel.

22. The method of claim 18, allowing the resuspension of the magnetic particles, wherein the magnetisation of the magnetisation source is maintained on the magnetic particles during the injection of a liquid for recovering said magnetic particles within the vessel, then is cut off after this injection.

23. The method of claim 22, wherein the magnetic particles are disposed in filaments oriented along the north-south axis of the magnetisation source and parallel to the injection motion of the recovery liquid.

24. The method of claim 18, allowing the movement of magnetic particles, wherein movement of the magnetisation source and/or the vessel, while maintaining magnetisation on the magnetic particles, is achieved by the 360°

rotation of the angle between the north-south axis of said magnetisation source and the axis of said vessel.

25. The method of claim 24, wherein the 360°

rotation is effected a plurality of times so as to obtain an appropriate movement of the magnetic particles.

26. A biological analysis apparatus, the apparatus including guiding and moving means for reaction vessels over at least one path including a predetermined number of positions, wherein it comprises a configuration of magnets for each path, the configuration of magnets comprising:

upstream, a plurality of high-intensity magnetisation sources, such that the magnetic particles are agglomerated against the wall of the vessel, and

downstream, a low-intensity magnetisation source, according to claim 18, such that said magnetic particles are disposed in filaments oriented along the north-south axis of the magnetisation source.

27. The apparatus of claim 26, wherein each high-intensity magnetisation source has a magnetic induction which is 20 to 100 times greater than the low-intensity magnetisation source, and each high-intensity magnetisation source is at a distance from the vessel which is 5 to 20 times less than the distance from the low-intensity magnetisation source.

28. The apparatus of claim 26, wherein each high-intensity magnetisation source is in a perpendicular position to the low-intensity magnetisation source, in relation to the vessel.

29. The apparatus of claim 26, wherein each high-intensity magnetisation source is in a lateral position to the axis passing through the opening and the bottom of the vessel, and the low-intensity magnetisation source is located beneath said bottom of said vessel.

30. The apparatus of claim 26, wherein the closer the position of the high-intensity magnetisation source, along the path including a predetermined number of positions, to the low-intensity magnetisation source, the closer the position of said high-intensity magnetisation source to the bottom of the vessel.

31. The apparatus of claim 26, wherein the high-intensity magnetisation source comprises:

a row of magnets located on the same side of the vessels, or

two rows of magnets located on either side of the vessels, the magnets of a same row being positioned side-by-side, with the north-south poles identically oriented.

32. The apparatus of claim 31, wherein the high-intensity magnetisation source comprises at least one reversed polarisation magnet (reverse field) which promotes the “

release”

of the magnetic particles.

33. The method of claim 18, wherein said biological entities are selected from the group consisting of antibodies, antigens and nucleic acids.

34. The apparatus of claim 27, wherein each high-intensity magnetization source has a magnetic induction which is 30 to 60 times the low-intensity magnetization source.

35. The apparatus of claim 27, wherein each high-intensity magnetization source is at a distance from the vessel which is 10 to 15 times less than the distance from the low-intensity magnetization source.