System and method for manipulating magnetically responsive particles fluid samples to collect DNA or RNA from a sample

• US 20020014443A1
• Filed: 05/17/2001
• Published: 02/07/2002
• Est. Priority Date: 05/19/2000
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Hansen, Timothy Roy, Collis, Matthew P., Thomas, Bradley Scott, Bianco, John Joseph
• Granted Patent: US 6,672,458 B2
• Time in Patent Office: Days
• US Class Current: 209/213
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• 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: C12N 15/1013 by using magnetic beads
• CPC Class Codes: G01N 2035/103 using disposable tips
• 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 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates

Abstract

A system and method for manipulating magnetically responsive particles in a solution to separate nucleic acid molecules from cell components in a cell solution. The system and method employ a device capable of receiving a plurality of tubes, each of which contain respective sample and magnetically responsive particles. The device includes heating and cooling devices to facilitate a lysing step to release the nucleic acid molecules from the cells in the cell solution. The device further includes moveable magnets which can be moved proximate to and away from the tube to hold the magnetically responsive particles to which the nucleic acid molecules become bound, so that the molecule-bound particles can be separated from the remainder of the solution, and washed as appropriate. The system also employs an electromagnet which is capable of demagnetizing the particles to allow the particles to freely mix with solution, such as elution solutions which are used to unbind the molecules from the particles.

Claims

1. A system for manipulating magnetically responsive particles having nucleic acid molecules bound thereto and being in a solution contained in at least one tube, said system comprising:

a tube receiver having at least one tube opening adapted to receive said tube therein;

at least one first magnet;

a magnet moving device, adapted to selectively move said first magnet between a first location with respect to said tube to attract said magnetically responsive particles toward an inner wall of said tube, and a second location with respect to said tube to allow said magnetically responsive particles to be suspended in said solution; and

a second magnet, adapted to apply a magnetic field to said magnetically responsive particles when said first magnet is positioned at said second location, to remove a magnetization imposed on said magnetically responsive particles by said first magnet.

2. A system as claimed in claim 1, wherein:

said second magnet comprises an AC electromagnet, and said magnetic field comprises an AC magnetic field.

3. A system as claimed in claim 1, wherein:

said second magnet is substantially stationary with respect to said tube.

4. A system as claimed in claim 1, wherein:

said first and second magnets are disposed on substantially opposite sides of said tube.

5. A system as claimed in claim 1, wherein said magnet moving device comprises:

a cam and cam driver, said cam driver being adapted to drive said cam to move said first magnet between said first and second locations.

6. A system as claimed in claim 1, wherein said magnet moving device comprises:

at least one first panel having a first opening therein;

at least one second panel having at least one second opening therein, extending transverse to said first opening; and

an extension which is coupled to said first magnet and passes through said first and second opening;

said second panel being adapted to move with respect to said first panel to apply a driving force to said extension to cause said extension to move along said first and second openings between said first and second locations.

7. A system as claimed in claim 6, further comprising:

a motor, adapted to drive said second panel to move with respect to said first panel.

8. A system as claimed in claim 1, wherein:

said tube receiver has a plurality of said tube openings for receiving a plurality of said tubes therein;

said system comprises a plurality of said first magnets, each being positioned with respect to at least one of said tube openings; and

said magnet moving device is adapted to move said plurality of said first magnets between respective said first and second locations.

9. A system as claimed in claim 8, further comprising:

a plurality of second magnets, each being adapted to apply a magnetic field to said magnetically responsive particles in at least one of said tubes when a respective one of said first magnets is positioned at a respective said second location to substantially remove a magnetization imposed on said magnetically responsive particles by said respective first magnet.

10. A system as claimed in claim 1, further comprising:

a thermal element, adapted to at least one of apply thermal energy to said solution in said tube and extract thermal energy from said solution in said tube.

11. A system as claimed in claim 1, wherein:

said magnet moving device is adapted to move said magnet between said first and second locations in a first direction which is substantially parallel to a longitudinal axis of said tube.

12. A system as claimed in claim 1, further comprising:

at least one pair of said first magnets; and

wherein said magnet moving device is adapted to selectively move each said first magnet of said pair of first magnets between respective said first locations with respect to said tube to attract said magnetically responsive particles toward an inner wall of said tube, and respective said second locations with respect to said tube to allow said magnetically responsive particles to be suspended in said solution.

13. A system as claimed in claim 12, wherein:

said tube receiver has a plurality of said tube openings for receiving a plurality of said tubes therein;

said system comprises a plurality of said pairs of first magnets, each being positioned with respect to at least one of said tube openings; and

said magnet moving device is adapted to move said plurality of said pairs of first magnets between respective said first and second locations.

14. A system as claimed in claim 13, further comprising:

a plurality of second magnets, each being adapted to apply a magnetic field to said magnetically responsive particles in at least one of said tubes when a respective one of said pairs of said first magnets is positioned at a respective said second location to substantially remove a magnetization imposed on said magnetically responsive particles by said respective pair of said first magnets.

15. A system as claimed in claim 1, wherein:

said second magnet is disposed below a bottom of said tube opening.

17. A method as claimed in claim 16, wherein:

said magnetic field comprises an AC magnetic field.

18. A method as claimed in claim 16, wherein:

said first magnet is coupled to a cam; and

said selectively moving step comprises the step of driving said cam to move said first magnet between said first and second locations.

19. A method as claimed in claim 16, wherein:

said tube receiver has a plurality of said tube openings for receiving a plurality of said tubes therein; and

said moving step comprises the step of moving a plurality of said first magnets between respective said first and second locations with respect to respective said tubes.

20. A method as claimed in claim 19, wherein:

said applying step applies a respective magnetic field to said magnetically responsive particles in each of said tubes when a respective one of said first magnets is positioned at a respective said second location to substantially remove a magnetization imposed on said magnetically responsive particles by said respective first magnet.

21. A method as claimed in claim 16, further comprising:

at least one of applying thermal energy to said solution in said tube and extracting thermal energy from said solution in said tube.

22. A method as claimed in claim 16, wherein:

said magnet moving step moves said magnet between said first and second locations in a first direction which is substantially parallel to a longitudinal axis of said tube.

23. A method as claimed in claim 16, wherein:

said applying step applies said magnetic field to said magnetically responsive particles from a side of said tube substantially opposite to a side adjacent to said first location.

24. A method as claimed in claim 16, wherein:

said magnet moving step maintains said magnet at said first location for a time sufficient for removal of said solution from said tube.

25. A method as claimed in claim 16, wherein:

wherein said selectively moving step selectively moves each said first magnet of a pair of first magnets between respective said first locations with respect to said tube to attract said magnetically responsive particles toward an inner wall of said tube, and respective said second locations with respect to said tube to allow said magnetically responsive particles to be suspended in said solution.

26. A method as claimed in claim 16, wherein:

said tube receiver has a plurality of said tube openings for receiving a plurality of said tubes therein; and

said selectively moving step selectively moves said plurality of said pairs of first magnets between respective said first and second locations.

27. A method as claimed in claim 26, wherein:

said applying step applies a respective said magnetic field to said magnetically responsive particles in each of said tubes when a respective one of said pairs of said first magnets is positioned at a respective said second location to substantially remove a magnetization imposed on said magnetically responsive particles by said respective pair of said first magnets.

28. A method as claimed in claim 16, wherein:

said applying step applies said magnetic field from below a bottom of said tube opening.

16. A method for manipulating magnetically responsive particles having nucleic acid molecules bound thereto and being in a solution contained in at least one tube, said method comprising:

receiving said tube in a tube receiving opening of a tube receiver;

selectively moving a first magnet to a first location with respect to said tube to attract said magnetically responsive particles toward an inner wall of said tube, and to a second location with respect to said tube to allow said magnetically responsive particles to be suspended in said solution; and

applying a magnetic field to said magnetically responsive particles when said first magnet is positioned at said second location, to substantially remove a magnetization imposed on said magnetically responsive particles by said first magnet.