Method for processing a biological sample with magnetic particles

Inventors

Korner, Stephan • Sarofim, Emad • Savatic, Goran • Simic, Marko

Assignees

Roche Molecular Systems Inc

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Publication Number

US-12544757-B2

Patent

Publication Date

2026-02-10

Expiration Date


Abstract

The present disclosure relates to a method for isolating a biological target material from a liquid sample in a multiwell plate using magnetic particles, wherein high efficiency and low elution volumes are achieved by specific movements of the multiwell plate and a magnetic separation plate in relation to each other. Also disclosed is a pre-analytical system suitable for carrying out the method.

Core Innovation

The invention relates to a method for isolating a biological target material from a sample by associating the biological target material with magnetic particles homogeneously suspended in a liquid in at least one well of a multiwell plate. The multiwell plate includes recesses in positions corresponding to a predetermined geometrical arrangement of a plurality of magnets of a magnetic separation plate, and the association is performed when the multiwell plate and the magnetic separation plate are in an incubation position in which the magnets do not impose a magnetic field on the magnetic particles.

Magnetic particles are then pelletized on an inner wall of the well by moving the magnets into the recesses to a first peripheral collection position, positioning the pellet at a first specific height along the inner wall. The method further includes sliding the formed pellet along the inner wall from the first specific height to a second specific height by moving the multiwell plate and/or the magnetic separation plate relatively to each other to a second peripheral collection position, where the relative movement comprises both vertical and lateral movement components.

After sliding, the method includes withdrawing at least a portion of the liquid, and eluting the biological target material from the magnetic particles by suspending the magnetic particles in an elution buffer. The magnetic particles are suspended by introducing the elution buffer to the well and moving the magnets to the incubation position, then the pellet is re-formed by moving the magnets back into the recesses and the eluate including the isolated biological target material is withdrawn from the well.

Claims Coverage

The document includes three independent claims. Across these claims, the core inventive coverage centers on incubation with no magnetic field, forming and laterally/vertically sliding a pellet along the inner wall using magnets positioned in recesses, elution by resuspending magnetic particles via magnet movement, and a pre-analytical system using a guiding screen with rails that moves the multiwell plate and/or magnetic separation plate in combined vertical and lateral manner, coupled to an actuator and a slide.

Incubation without magnetic field in a multiwell with magnet recesses

Associating the biological target material with magnetic particles homogeneously suspended in a liquid in at least one well of a multiwell plate, wherein the multiwell plate includes recesses in positions corresponding to a predetermined geometrical arrangement of a plurality of magnets of a magnetic separation plate, and the association is performed when the multiwell plate and the magnetic separation plate are in an incubation position where the plurality of magnets do not impose a magnetic field on the magnetic particles.

Pellet formation at a first specific height using magnet recess entry

Forming a pellet of magnetic particles on an inner wall of the at least one well by moving the plurality of magnets into the recesses of the multiwell plate and to first peripheral collection position, wherein the formed pellet is positioned at a first specific height along the inner wall of the at least one well.

Sliding the pellet with combined vertical and lateral relative movement to a second height

Sliding the formed pellet along the inner wall from the first specific height to a second specific height by moving the multiwell plate and/or the magnetic separation plate relatively to each other to a second peripheral collection position, wherein the relative movement comprises both vertical and lateral movement components.

Elution by resuspending magnetic particles using incubation-position magnet movement

Eluting the biological target material from the magnetic particles by suspending the magnetic particles in an elution buffer, wherein the magnetic particles are suspended by introducing the elution buffer to the at least one well and moving the magnets to the incubation position.

Re-forming the pellet and withdrawing eluate without disturbing pellet position

Re-forming the pellet of magnetic particles on the inner wall by moving the magnets into the recesses of the multiwell plate, and withdrawing the eluate including the isolated biological target material from the at least one well of the multiwell plate.

Guiding screen with perpendicular rails enabling combined vertical and lateral movement

A pre-analytical system for isolating a biological target material from a liquid sample comprising a multiwell plate having wells with an open top and closed bottom and one or more recesses corresponding to a predetermined geometrical arrangement of a plurality of magnets of a magnetic separation plate, and a magnetic separation device including a guiding screen perpendicular to the multiwell plate and/or to the magnetic separation plate and including one or more guiding rails adapted to move the multiwell plate and/or the magnetic separation plate relative to each other in a combined vertical and lateral manner.

Magnetic separation device coupled to actuator and slide

The pre-analytical system further comprising a magnetic separation device wherein the magnetic separation device is coupled to both an actuator and a slide.

Overall, the claims cover a pre-analytical workflow and system in which a pellet of magnetic particles on a multiwell inner wall is formed using magnets moved into recesses, slid along the inner wall using combined vertical and lateral relative movement, and then eluted by resuspending magnetic particles through magnet movement back to an incubation position with no magnetic field. The system uses a guiding screen with guiding rails arranged perpendicular to the plates to drive the combined motion, and is coupled to both an actuator and a slide.

Stated Advantages

High efficiency.

Low elution volume.

Compatibility with small volumes and nanobeads.

Minimized particle loss.

Reduced interference in downstream steps.

Documented Applications

Pre-analytical workflow for isolating a biological target material from a liquid biological sample using a magnetic-particle magnetic separation plate and a multiwell plate workflow in wells.

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