Non-linear magnetophoretic separation device, system and method

Patent metadata

Field	Value
Publication number	US-9421555-B2
Application number	US-201113809091-A
Country	US
Kind code	B2
Filing date	Jul 7, 2011
Priority date	Jul 8, 2010
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

A flow enhanced method and system for flow non-linear magnetophoresis (F-NLM) is described. By tuning an external field frequency and the flow rate the migration velocities of different bead types may be caused to differ by several orders of magnitude over an extended range of frequencies to allow for separation of particles. Use of such efficiency in separation in bio-separation and similar assays is described.

First claim

The invention claimed is:

1. A separation system for flow enhanced non-linear magnetophoretic separation of magnetic particles of a first and second type of a sample, comprising:
a chip assembly device comprising:
a flow chamber having an inlet for the introduction of the sample as a flowing sample and an outlet, the flow chamber having a flow path in a first direction between the inlet and the outlet,
the flow path comprising a first fluid path and a second fluid path located side by side and having fluid communication therebetween to allow for magnetic particles of the first and second type to be transported from the first fluid path to the second fluid path, and
a micro magnet array provided in the first fluid path defining a magnetic separation fluid path;
the second fluid path defining a flow separation channel;
a flow controller configured to apply flow to the flow chamber such that the particles within the sample travelling in the first and second fluid paths experience hydrodynamic forces affecting their movement in the direction of the flow path, wherein the flow controller provides control of the rate of the flow in each of the first and second fluid paths and wherein the flow is applied continuously;

a magnetic module comprising electromagnets and a controller, the magnetic module configured to apply a rotating magnetic field to the first fluid path of the chip assembly device such that particles within the sample travelling in the first fluid path operably experience an induced magnetic field based on interaction of the rotating magnetic field and the magnetic field of first micro magnet array proximal the first fluid path; the magnetic module further configured to apply the rotating magnetic field in a second direction, substantially perpendicular to the direction of flow, and the rotating magnetic field is selected to effect transport of particles of the second particle type from the first fluid path to the second fluid path; and
a system controller, wherein taking account of the properties of the particles of the first type and second type, and the critical and threshold frequencies at which the particles of the first and second type are responsive to the rotating magnetic field, the system controller is configured to:
(1) control the frequency of the rotating magnetic field, and
(2) control the rate of flow of the sample in the first fluid path

wherein the frequency of the rotating magnetic field and the rate of flow of the sample are tuned relative to each other to effect a retention of particles of the first type in the first fluid path and transport of particles of the second type to the second fluid path and to provide separation of the particles of the first type from particles of the second type in the first fluid path.

2. The system as claimed in claim 1 wherein the particles of the first and second type are responsive to a predefined frequency of operation of the rotating magnetic field, the particles of the first type having a critical frequency, ω c at which particles of the first type are trapped in the micro magnet array, the particles of the first type having a threshold frequency Ω t at which a majority of particles of the first type are trapped in the micro magnet array, the micro magnet array being tuneable to allow selection of at least one of the critical and threshold frequency.

3. The system of claim 2 wherein the particles of the second type have a different critical and threshold frequency to the particles of the first type.

4. The system of claim 2 wherein the threshold frequency is greater than the critical frequency for each of the particles of the first and second types.

5. A system as claimed in claim 1 wherein the frequency ω of the rotating magnetic field is greater that the critical frequency ω c of the particles of the first type and less than the critical frequency ω c of the particles of the second type.

6. A system as claimed in claim 1 wherein each of the flow control and the magnetic control effects a variance in an induced force on the particles within the device and wherein each of the flow control and magnetic control are tuneable to effect separation of the particles of the first and second types.

7. A system as claimed in claim 1 wherein the frequency of the rotating magnetic field is controllable to effect transport of the particles of the second type to an intermediary region adjacent to each of the first and second fluid paths in the direction of the rotating magnetic field.

8. A system as claimed in claim 7 wherein the rate of flow in the second fluid path is operably controlled to provide a hydrodynamic force to effect movement of the particles of the second type which have been transported to an intermediary region adjacent to each of the first and second fluid paths.

9. A system as claimed in claim 7 wherein the frequency of rotation of the external magnetic field is controllable to operably provide that particles of the second type oscillate in phase with the external magnetic field at the intermediary region.

10. A system as claimed in claim 1 wherein the flow controller effects a variance on the flow based on properties of the particles of the first and/or second type.

11. A system as claimed in claim 1 further comprising a sensor or detector configured to sense or detect particles wherein the sensor or detector comprises an impedance sensor, a micro-coulter detector, an optical microscope, or a fluorescent detector.

12. A system as claimed in claim 1 configured for use in-line with linear magnetophoresis, the linear magnetophoresis effecting a first separation of particles.

13. A system as claimed in claim 1 wherein the particles are provided in the form of micro-beads and/or wherein the particles are functionalised prior to introduction into the chip-assembly device.

14. A system as claimed in claim 1 wherein the frequency of rotation and flow rate are controllable to provide a continuous separation.

15. A method of flow-enhanced non-linear magnetophoretic separation of magnetic particles of a first and second type of a sample, the method comprising:
providing a separation system in accordance with claim 1 comprising a chip assembly device including a first fluid path comprising a micro magnet array and a second fluid path comprising a flow separation channel, an electro magnet, and a flow controller;
introducing a sample including particles of the first and the second type to be separated into the system;
applying flow continuously to the sample in the chip assembly device;
applying a rotating magnetic field proximate to the first fluid path;
controlling the frequency of the rotating magnetic field,
controlling the rate of flow in the first fluid path;
wherein the frequency of the rotating magnetic field and the rate of flow are tuned relative to each other to effect a retention of particles of the first type in the first fluid path and to transport particle of the second type to the second fluid path to provide separation of said particles of the second type from said particles of the first type.

16. A method as claimed in claim 15 further comprising controlling the rate of flow in first and second fluid paths.

17. A method as claimed in claim 15 further compromising operating the rotating magnetic field at a frequency of rotation above the critical frequency of the particles of the first type and below a threshold frequency of particles of the second type to effect a separation thereof.

18. A method as claimed in claim 17 further comprising transporting

Assignees

• Lee Gil
• Li Peng
• Platt Mark
• Cannon Gemma
• Univ College Dublin Nat Univ Of Ireland

Inventors

• Lee Gil
• Li Peng
• Platt Mark
• Cannon Gemma

Classifications

• B03C1/288

  disposed at the outer circumference of a recipient · CPC title

• B03C2201/26

  for use in medical or biological applications · CPC title

• B03C1/02 Primary

  acting directly on the substance being separated · CPC title

• G01N27/44756

  Apparatus specially adapted therefor · CPC title

• B03C2201/18

  Magnetic separation whereby the particles are suspended in a liquid · CPC title