# US 2008/0187472 A1 · Magnetic bead-based arrays

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- Number: US 2008/0187472 A1
- Document ID: US20080187472A1
- Status: Published application
- Kind: A1
- Application number: 12/004,806
- Filed: 2007-12-22
- Published: 2008-08-07
- Earliest claimed: 2000-05-12
- Inventors: Chong H. Ahn; Hyoung J. Cho; Jin-Woo Choi
- Web page: https://patentgrep.com/patent/US20080187472A1

## CPC

- B01F 33/3031: using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
- B01F 25/31: in conduits or tubes through which the main component flows
- B01F 33/05: Mixers using radiation, e.g. magnetic fields or microwaves to mix the material ({B01F23/2133, B01F23/238, B01F23/55,} B01F33/3031, B01F33/3032 take precedence)
- B01F 33/052: {the energy being electric fields for electrostatically charging of the ingredients or compositions for mixing them}
- B01F 33/3032: using magneto-hydrodynamic [MHD] phenomena to mix or move the fluids
- B01J 19/0046: {Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays (synthesis methods per se C40B50/00)}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B03C 1/00: Magnetic separation
- B03C 1/0332: {using permanent magnets}
- B03C 1/034: characterised by the matrix elements
- B03C 1/28: Magnetic plugs and dipsticks
- H01F 10/16: containing cobalt ({H01F10/126} , H01F10/13 take precedence)
- H01F 41/16: the magnetic material being applied in the form of particles, e.g. by serigraphy {, to form thick magnetic films or precursors therefor} (H01F41/18 {-H01F41/24} take precedence)
- H01F 41/26: using electric currents {, e.g. electroplating}
- H01F 41/34: in patterns, e.g. by lithography
- B01F 23/40: Mixing liquids with liquids; Emulsifying
- B01F 2101/23: Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
- B01J 2219/00459: Beads
- B01J 2219/00466: in a slurry
- B01J 2219/005: Beads
- B01J 2219/0054: Means for coding or tagging the apparatus or the reagents
- B01J 2219/00585: Parallel processes
- B01J 2219/00596: Solid-phase processes
- B01J 2219/00648: by the use of solid beads
- B01J 2219/00655: the compounds being bound to magnets embedded in or on the solid supports
- B01J 2219/00659: Two-dimensional arrays
- B01J 2219/00689: using computers
- B01J 2219/0072: Organic compounds
- B01J 2219/00722: Nucleotides
- B01J 2219/00725: Peptides
- B01J 2219/0074: Biological products
- B01L 3/502707: {characterised by the manufacture of the container or its components}
- B01L 2200/0668: Trapping microscopic beads
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0877: Flow chambers
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/0487: fluid pressure, pneumatics
- B03C 2201/18: Magnetic separation whereby the particles are suspended in a liquid
- B03C 2201/26: for use in medical or biological applications
- C40B 40/06: Libraries containing nucleotides or polynucleotides, or derivatives thereof
- C40B 40/10: Libraries containing peptides or polypeptides, or derivatives thereof
- C40B 70/00: Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
- G01N 30/6095: {Micromachined or nanomachined, e.g. micro- or nanosize}
- 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)}
- G01N 2030/347: {mixers}
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B03C: MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS (separating isotopes B01D59/00; combinations of magnetic or electrostatic separation with separation of solids by other means B03B, B07B)
- H01F: MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to magnetic particle separators using micromachined magnetic arrays and more particularly, to magnetic particle separators or manipulators using controlled magnetization on micromachined magnetic arrays for the separation of cells and other biological materials. The present invention also pertains to using such devices for the separation and analysis of biological materials for immunoassays, DNA sequencing, protein analysis, and biochemical detection applications. The present invention can also be viewed as a novel method for fabricating fully integrated permanent magnet components within any microelectromechanical system (“MEMS”) structures. The present invention also provides a magnetic particle separation and manipulation system for rapid separation and accurate manipulation of magnetic particles in two-dimensional electromagnetic arrays, which utilize high throughput biological analyses. A disposable cartridge can be produced in low cost using a low cost substrate such as plastic or other polymer, glass, or metal. Magnetic flux is generated by conventional or micromachined electromagnets a platform system consisting of magnetic flux sources, magnetic flux guidance, and a microprocessor control interface. By controlling direction of electric currents into inductors on the platform system, arbitrary magnetic poles can be generated on Permalloy structures of the cartridge to separate and manipulate magnetic particles. The magnetic particle separator and manipulator in the present invention can be easily combined with automated detection systems such as a fluorescent monitoring system.

## Claims

### Claim 1

A system for collecting biological target particles from a fluid medium, the system comprising: a) a tag for dispersing in the fluid medium and comprising a magnetically responsive material having at least one binding molecule immobilized upon an exterior surface for binding to the biological particles; b) a magnetic field generator having a substantially planar surface with a spatially distributed array of magnetic field elements for generating within the fluid medium a magnetic field to establish a flow of biological particles coupled to the tag; c) a cartridge having a spatially distributed array on a surface of the cartridge of Permalloy structures that will work as magnetic poles for positioning within said flow for collecting the target particles thereon wherein the surface forms a fluid barrier and wherein the cartridge is substantially planar and adapted for placement upon the magnetic field generator; d) wherein the magnetic field generator is arranged relative to the plate to direct the flow to selected portions of the surface for collecting particles thereon; and e) a controller for controlling the magnetic field of one or more of the elements in the array wherein said controller turns said magnetic fields on or off.

### Claim 2 (depends on 1)

A system of claim 1 wherein the controller further comprises a microprocessor control interface and an optical monitoring system for selectively moving the magnetic field source means relative to the surface for spatially distributing the particles collected thereon.

### Claim 3 (depends on 2)

A system of claim 2 further comprising transfer means, coupled to the cartridge, for withdrawal of the target particles collecting thereon.

### Claim 4 (depends on 2)

A system of claim 2 wherein the cartridge further comprises a housing for containing fluids.

### Claim 5 (depends on 1)

A system according to claim 1 wherein the magnetically responsive material comprises one or more materials selected from the group consisting of paramagnetic, superparamagnetic, ferromagnetic, and ferromagnetic materials.

### Claim 6 (depends on 5)

A system according to claim 5, wherein the magnetically responsive material is iron oxide-impregnated polymer beads.

### Claim 7 (depends on 1)

A system according to claims 1 wherein the magnetic field generator is a device selected from the group consisting of an electromagnet, an air-cored coil, a wire coil, a straight wire, a conductive microfabricated trace, and a permanent magnet.

### Claim 8 (depends on 7)

A system according to claim 7, wherein the magnetic field generator is an inductor connected to a magnetic guidance.

### Claim 9 (depends on 3)

A system according to claim 3, wherein the system further comprises a device to remove nonspecifically-bound label particles.

### Claim 10 (depends on 1)

A system according to claim 1 wherein the binding molecules are molecules selected from the group consisting of antibodies, polynucleotides, oligonucleotides, peptides, polypeptides, proteins, receptors, chelators and fragments thereof.

### Claim 11 (depends on 10)

A system according to claim 10, wherein the target molecules are selected from the group consisting of antibodies, polynucleotides, oligonucleotides, peptides, polypeptides, proteins, receptors, chelators, polymers, metal ions, low molecular weight organic species, cells, and fragments thereof.

### Claim 12 (depends on 1)

A system according to claim 1 wherein the tag comprises a magnetic bead having at least one selected antibody bound on the exterior bead surface and having a specificity for an epitope on one or more particle subpopulations dispersed within the fluid medium.

### Claim 13 (depends on 12)

A system according to claim 12 wherein the tag comprises a selected quantity of the magnetic beads.