Device and method for manipulating and mixing magnetic particles in a liquid medium

• US 8,870,446 B2
• Filed: 01/23/2013
• Issued: 10/28/2014
• Est. Priority Date: 06/21/2006
• Status: Active Grant

• Current Assignee: Spinomix SA
• Original Assignee: Spinomix SA
• Inventors: Rida, Amar
• Primary Examiner(s): Del Sole, Joseph S
• Assistant Examiner(s): Sultana, Nahida
• Application Number:
  US13/748,336
• Publication Number:
  US 20130217144A1
• Time in Patent Office: 643 Days
• Field of Search: 366/273, 366/274, 366/341, 422/186.1, 422/129
• US Class Current: 366/273
• 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: C12N 15/1013 by using magnetic beads
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples
• 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

Abstract

A device for manipulating and mixing magnetic particles (3) in a surrounding liquid medium, comprises at least one couple of magnetic poles (1,1′) facing each other across a gap, the facing poles diverging from a narrow end of the gap to a large end of the gap, the poles (1,1′) forming part of an electromagnetic circuit and being arranged to provide a magnetic field gradient in the gap region; and a reaction chamber (2) that is a part of a fluidic network for containing the said magnetic particles in suspension and placed in the gap of the said electromagnets poles (1,1′). The reaction chamber (2) preferably has at least one part which has a diverging cavity, arranged co-divergently in the diverging gap between the poles.

Claims

1. A method of mixing magnetic particles designed to capture at least one target substance from a surrounding liquid medium, wherein said particles are contained in suspension within a reaction chamber that is a part a microfluidic network, wherein the reaction chamber comprises a narrow end and a large end that are connected to inlet and outlet ends for introducing and removing the liquid medium into and from the reaction chamber, and at least two electromagnetic poles face each other across the reaction chamber and retain the particles within the reaction chamber under fluid flow conditions, the method comprising:

a) applying from the electromagnetic poles magnetic field sequences having polarity and intensity that vary in time;

said varying magnetic field sequences being effective to break and inhibit particle claim aggregates and to maintain the particles in suspension as a fog of particles in relative dynamic movement; and

b) combining the magnetic fields from different magnetic poles in a sequence to induce continuous time variations of the position of the magnetic field gradient maxima across the reaction chamber,

wherein the combination of steps a) and b) causes the particles in use to be in relative translational and rotational motion as a fog of particles homogeneously covering substantially the whole reaction chamber volume to allow an effective binding to take place between the particle surfaces and the sample in the reaction chamber, thereby forming a complex of the target substances and the magnetic particles.

2. The method according to claim 1, which further comprises the step of combining the magnetic fields from different magnetic poles in a sequence to separate or confine the particles so the particles occupy a sub-volume in the volume of the reaction chamber.

3. The method according to claim 1, wherein the particle homogeneity of mixing the particles are controlled by varying respectively the frequency and the amplitude of the magnetic field.

4. The method of mixing particles according to claim 1, wherein the reaction chamber comprises a cavity with at least one segment with diverging/converging parts, and at least one couple of electromagnetic poles face each other across the reaction chamber and geometrically arranged in a way to be co-diverging/co-converging with diverging/converging parts of the reaction chamber.

5. The method according to claim 4, wherein the magnetic poles form a quadrupole configuration.

6. The method of mixing magnetic particles with surrounding liquid according to claim 1, wherein the particles are designed to selectively bind the particle with at least one target molecule or with other particles carried in the reaction chamber by a fluid flow.

7. The method according to claim 1, wherein the fog of particles occupies substantially the whole reaction chamber volume quasi-instantaneously.

8. The method according to claim 1, wherein the fog of particles occupies substantially the whole reaction chamber volume over a period of time.

9. The method according to claim 1, wherein the volume of the reaction chamber is between 0.1 μ

l to 500 μ

l.