Method for manipulating magnetic particles in a liquid medium
First Claim
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1. A method of mixing magnetic particles with a reagent in a reaction chamber that is part of a microfluidic device and that contains the particles in suspension, comprises the steps:
- a. providing an electromagnetic means to generate magnetic field sequences having polarity and intensity that vary in time and a magnetic field gradient that covers the whole space of the reaction chamber;
b. applying a first magnetic field sequence to separate or confine the particles so the particles occupy a sub-volume in the volume of the reaction chamber;
c. injecting a defined volume of the said reagent in the reaction chamber;
d. applying a second magnetic field sequence having polarity and amplitude that vary in time to induce continuous time variations of the position of the magnetic field gradient maxima across the reaction chamber thereby causing the particles in use to be in relative translation and rotational motion as a fog of particles covering substantially the whole reaction chamber volume;
e. leaving the fog of particles in a homogenous state for a defined period of time to allow a reaction to take place between the particle surfaces and the reagent injected in the said reaction chamber, thereby forming a complex; and
f. repeating the steps (b)-(e) until a given reagent volume has passed through the reaction chamber.
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Abstract
The invention relates to a method of handling and mixing magnetic particles within a reaction chamber that is part of a microfluidic device and that contains the said particles in suspension. More particularly, the invention concerns a method of handling magnetic particles in a way to improve the mixing of the particles with the surrounding liquids medium and where the liquid is carried by a fluid flow as part of an automated system. Further, the invention describes the use of the method for conducting biological and chemical assays.
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Citations
23 Claims
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1. A method of mixing magnetic particles with a reagent in a reaction chamber that is part of a microfluidic device and that contains the particles in suspension, comprises the steps:
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a. providing an electromagnetic means to generate magnetic field sequences having polarity and intensity that vary in time and a magnetic field gradient that covers the whole space of the reaction chamber; b. applying a first magnetic field sequence to separate or confine the particles so the particles occupy a sub-volume in the volume of the reaction chamber; c. injecting a defined volume of the said reagent in the reaction chamber; d. applying a second magnetic field sequence having polarity and amplitude that vary in time to induce continuous time variations of the position of the magnetic field gradient maxima across the reaction chamber thereby causing the particles in use to be in relative translation and rotational motion as a fog of particles covering substantially the whole reaction chamber volume; e. leaving the fog of particles in a homogenous state for a defined period of time to allow a reaction to take place between the particle surfaces and the reagent injected in the said reaction chamber, thereby forming a complex; and f. repeating the steps (b)-(e) until a given reagent volume has passed through the reaction chamber. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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18. A method to extract target molecule(s) that enter in a composition of intracellular complexes in a sample volume, said method comprises:
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a. providing a reaction chamber that is part of a microfluidic device and that contains a first type of magnetic particles in suspension;
wherein the first type of particles have a surface coating designed to selectively bind with the target molecules;b. providing an electromagnetic means to generate magnetic field sequences having polarity and intensity that vary in time and a magnetic field gradient that covers the whole space of the reaction chamber; c. applying a first magnetic field sequence to separate or to confine the first type of particles so the particles occupy a sub-volume in the volume of the reaction chamber; d. injecting in the reaction chamber a defined volume of the said sample, wherein the cells were previously bound to a second type of magnetic particles; e. applying a second magnetic field sequence to cause the first type of particles to be homogenously distributed and dynamically moving as a fog of first particles over a substantial portion of the whole reaction chamber volume; f. leaving the fog of the first type of particles in the homogenous state for a defined period of time to allow strong contact between the surfaces of the first type of particles and the said magnetically labelled cells injected in the reaction chamber, thereby forming by means of dipolar interaction a complex composed of the first type of particles and the magnetically labelled cells; g. applying a further magnetic field sequence to separate or to confine the complex in a specific area of the reaction chamber; h. repeating the steps (c)-(g) until a given sample sub-volume is passed through the reaction chamber; and i. lysing the complex to release the target molecules in the reaction chamber to capture the target molecules on the first particles types surfaces. - View Dependent Claims (19, 20, 21, 22, 23)
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Specification