Arrays of magnetic particles

• US 20050272049A1
• Filed: 08/03/2004
• Published: 12/08/2005
• Est. Priority Date: 06/21/2000
• Status: Active Grant

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Seul, Michael, Banerjee, Sukanta, Li, Alice X.
• Granted Patent: US 8,486,720 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: 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
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 2563/107 fluorescence
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: C12Q 2563/155 : Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/513 : characterised by the pattern of the arrayed oligonucleotides
• CPC Class Codes: G01N 2035/00564 : Handling or washing solid phase elements, e.g. beads
• CPC Class Codes: G01N 2035/00762 : magnetic code
• CPC Class Codes: G01N 2446/20 : the magnetic material being present in the particle core
• CPC Class Codes: G01N 2446/64 : Magnetic material dispersed in oil drop
• CPC Class Codes: G01N 27/745 : for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01N 33/5434 : using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/54346 : Nanoparticles
• CPC Class Codes: G01N 33/587 : Nanoparticles
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis

Abstract

The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interactions of a number of analyte molecules in a sample.

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41. An array comprising a plurality of magnetic particles comprising at least two different particle populations distinguishable by a chemical characteristic associated therewith, wherein the magnetic particles are suspended in a fluid, are magnetically polarizable and are assembled in a planar array on one or more chips using a magnetic field.

42. The array of claim 41 wherein the particles are randomly placed in the array.

43. The array of claim 41 wherein a plurality of arrays are assembled on a plurality of chips.

44. The array of claim 42 wherein the magnetic particles are immobilized on the chips by trapping them within the microwells which have been patterned on the chips.

45. The array of claim 42 wherein the magnetic particles are immobilized on the chips by forming a composite gel-particle film for immobilization.

46. The array of claim 45 wherein the gel-particle film is formed following assembly of the array by a monomer, a crosslinker and initiator in the fluid phase.

47. A method of performing a bioassay comprising:

48. A method for performing a bioassay involving integration of sample preparation and parallel molecular interaction assay analysis, comprising:

providing an apparatus comprising a sample preparation compartment and an assay compartment, and fluidic connection for the sample preparation and the assay compartments;

providing, in the sample preparation compartment, a biological fluid containing a biomolecule of interest and a plurality of magnetic particles capable of binding to the biomolecule of interest under conditions wherein the magnetic particles to bind the biomolecules of interest;

removing the biological fluid along with unbound components of said fluid, while retaining the magnetic particles and the biomolecules bound to said particles; and

releasing said biomolecules from said magnetic particles and transporting said biomolecules from the sample preparation compartment to the assay compartment through the fluidic connection; and

performing a bioassay wherein the analyte in the bioassay comprises transported biomolecules of interest.

49. The method of claim 48, further comprising transforming the biomolecules of interest, which are then used as analytes in the bioassay.

50. The method of claim 49, wherein the biomolecule of interest comprises mRNA and the transformation comprises reverse transcription of said mRNA to produce cDNA, and wherein the analyte in the bioassay comprises said cDNA and the binding comprises oligonucleotides or other DNA probes.

51. The method of claim 48, wherein the reverse transcription occurs in the sample preparation compartment, while said mRNA is bound to the magnetic particles, and the cDNA is released from said magnetic particles after the reverse transcription and transported to the assay compartment and used as an analyte in the bioassay.

52. A method of integrating sample preparation and bioassay using magnetic particles comprising:

providing a plurality of magnetic particles comprising at-least two different particle populations, each population having a recognition molecule attached thereto, wherein the particles are distinguishable a chemical characteristic that uniquely identifies a biomolecule that selectively binds to the recognition molecule;

providing a biological fluid containing biomolecules and allowing said biomolecules to interact with the recognition molecules on the magnetic particles;

removing the fluid along with unbound components thereof;

transforming the biomolecules bound to the magnetic particles to produce transformed biomolecules, wherein the transformed biomolecules remain attached to the magnetic particles on which they are synthesized;

performing a bioassay using the transformed biomolecules.

53. The method of claim 52, wherein the biomolecules are mRNA and the transforming comprises reverse transcribing the mRNA to produce cDNA, which is attached to the magnetic particles.

54. The method of claim 52, wherein the sample preparation and the bioassay occur in the same compartment.