CA2387788A1 - Systems and methods for performing magnetic chromatography assays - Google Patents

Systems and methods for performing magnetic chromatography assays Download PDF

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Publication number
CA2387788A1
CA2387788A1 CA002387788A CA2387788A CA2387788A1 CA 2387788 A1 CA2387788 A1 CA 2387788A1 CA 002387788 A CA002387788 A CA 002387788A CA 2387788 A CA2387788 A CA 2387788A CA 2387788 A1 CA2387788 A1 CA 2387788A1
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CA
Canada
Prior art keywords
magnetic
chromatography method
test strip
magnetic field
chromatographic
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002387788A
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French (fr)
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CA2387788C (en
Inventor
Christopher Feistel
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Wavesense Inc
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Individual
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Publication of CA2387788C publication Critical patent/CA2387788C/en
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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G01N33/54333—Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/803—Physical recovery methods, e.g. chromatography, grinding
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/805—Test papers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/81—Packaged device or kit
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/97—Test strip or test slide
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/806—Electrical property or magnetic property
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/824—Immunological separation techniques

Abstract

Novel magnetic assay methods and systems. According to a preferred embodimen t, a chromatographic medium, which preferably comprises a test strip, is provid ed that is designed to be contacted with a test solution having activated magnetic particles such that the solution flows bilaterally thereacross. A magnetic field, generated by a magnet or electromagnet, is selectively appli ed to the medium which causes the charged particles to become substantially bou nd at a site on the medium specified by the position of the magnet, to thus for m a captured line or zone. In one preferred embodiment, the magnetic field is applied at the site on the medium at which the test solution is contacted. T he degree of magnetic force applied to the membrane may be selectively adjusted to vary the width or surface area of the capture line or zone.

Claims (49)

1. A magnetic chromatography method for performing a bioassay comprising the steps:
a) providing a chromatographic medium;
b) providing a magnetic field;
c) providing a reaction mixture suspected of containing an analyte, a reporter ligand that binds to said analyte and a quantity of magnetic particles with capture ligands for binding said analyte immobilized thereon suspended therein;
d) contacting said chromatographic medium with said reaction mixture such that said reaction mixture flows laterally across said chromatographic medium;
e) applying said magnetic field at a site upon said chromatographic medium, said magnetic field being so applied such that said magnetic particles suspended within said reaction mixture are caused to become substantially captured upon said medium at said site where said magnetic field is applied;
and f) analyzing said majority magnetic particles captured upon said chromatographic medium.
2. The magnetic chromatography method of Claim 1 wherein in step b), said magnetic field is generated by a magnet.
3. The magnetic chromatography method of Claim 1 wherein in step b), said magnetic field is generated by an electromagnet.
4. The magnetic chromatography method of Claim 1 wherein in step e), said magnetic field is applied by positioning a magnet in close proximity said chromatographic medium.
5. The magnetic chromatography method of Claim 1 wherein in step c), said magnetic particles having an analyte, receptor, and label complexed therewith.
6. The magnetic chromatography method of Claim 5 wherein said label comprises a detectable chemical moiety selected from the group consisting of radioactive, flourescent, enzymatic, and dye moieties.
7. The magnetic chromatography method of Claim 2 wherein in step b), said magnetic field is provided by a magnetic rail having a width between 0.003 inches and 3.0 inches, and having a length between 0.010 inches and 100 inches.
8. The magnetic chromatography method of Claim 1 wherein in step b), said magnetic field is provided by a least two (2) magnets.
9. The magnetic chromatography method of Claim 1 wherein in step c), said magnetic particles have a diameter ranging between 1 nm to 10 microns.
10. The magnetic chromatography method of Claim 1 wherein in step a), said test membrane includes a zone of immobilized receptors bound thereto.
11. A magnetic chromatography test strip for performing a bioassay comprising:
a) a test strip having a liquid receiving end, test membrane and liquid absorbent end formed thereon in a generally linear fashion, said test membrane being disposed intermediate said liquid receiving end said liquid absorbent end such that said liquid receiving end, test membrane and liquid absorbent end cooperates to define a lateral direction of flow; and b) at least one magnet bound to said backing of said test strip.
12. The magnetic chromatography test strip of Claim 11 wherein said assay includes a plurality of magnets bound to said backing of said test strip.
13. The magnetic chromatography test strip of Claim 11 wherein said test membrane of said test strip further includes a zone of receptors bound thereupon.
14. The magnetic chromatography test strip of Claim 11 wherein said test strip further has formed thereon a reagent pad for storing at least one reagent for performing said assay.
15. A multimode photometer for analyzing the presence of a chemical entity identified in a chromatographic medium comprising:
a) a base member having a channel formed therein for receiving said chromatographic medium, said base member further having a magnetic source disposed therein; and b) an opaque optical canopy formed upon said base, said optical canopy having at least one first surface through which electromagnetic radiation emanating from an external source may be transmitted, said first surface being designed to align with said chromatographic medium and said magnetic source disposed within said base such that said electromagnetic radiation may be focused thereupon, said optical canopy having at least one second surface through which electromagnetic radiation reflected or emitted from said chromatographic medium received within said channel of said base may be detected.
16. The multimode photometer of Claim 15 wherein said chemical entity sought to be analyzed is bound to a magnetic particle susceptible to magnetic attraction.
17. The multimode photometer of Claim 15 wherein said chromatographic medium is selected from the group consisting of test membranes and chromatographic plates.
18. The multimode photometer of Claim 15 further comprising:
c) a source for transmitting electromagnetic radiation.
19. The multimode photometer of Claim 18 wherein said source for transmitting electromagnetic radiation is selected from the group consisting of LED, incandescent, mercury vapor, laser, laser diode, and xenon.
20. The multimode photometer of Claim 15 further comprising:
c) a photodetector for detecting said electromagnetic radiation reflected from said test strip.
21. The multimode photometer of Claim 20 wherein said photodetector is selected from the group consisting of photodiodes, photodiode arrays, photo multipliers, charge coupled devices, x-ray film, and photographic film.
22. The magnetic chromatography method of Claim 1 wherein in step a), said chromatographic medium comprises a test membrane.
23. The magnetic chromatography method of Claim 1 wherein in step a), said chromatographic medium comprises a chromatographic plate.
24. The magnetic chromatography method of Claim 1 wherein in step a), said chromatographic medium comprises a test strip, said test strip comprising a backing having a liquid receiving end, test membrane and liquid absorbent end formed thereon in a sequential fashion, said test membrane being disposed intermediate to said liquid receiving end and said liquid absorbent end such that said liquid receiving end, test membrane and liquid absorbent end cooperates to define a lateral direction of flow.
25. A magnetic chromatography method for sequentially performing a multiplicity of bioassays comprising the steps:
a) provide a multiplicity of chromatographic mediums;
b) providing a magnetic field;
c) providing at least one reaction mixture suspected of containing at least one analyte, at least one reporter ligand that binds to said at least one analyte and a quantity of magnetic particles with capture ligands for binding to at least one of said analytes immobilized thereon suspended therein;
d) contacting said multiplicity of chromatographic mediums with said at least one reaction mixture such that said at least one reaction mixture flows laterally across such respective one of said mediums;
e) applying said magnetic field at dedicated sites upon respective ones of said multiplicity of chromatographic mediums, said magnetic field being so applied such that a majority of said magnetic particles suspended within said at least one reaction mixture is caused to become captured upon a respective one of said multiplicity of chromatographic mediums at said sites where said magnetic field is applied;
f) analyzing said majority of magnetic particles captured upon said chromatographic mediums.
26. The magnetic chromatography method of Claim 25 wherein in step a), said chromatographic medium is selected from the group consisting of test membranes and chromatographic plates.
27. The magnetic chromatography method of Claim 25 wherein in step b), said magnetic field is generated by a magnetic rail.
28. The magnetic chromatography method of Claim 27 wherein in step b), said magnetic rail is situated in close proximity to dedicated sites upon respective ones of said multiplicity of chromatographic mediums.
29. The magnetic chromatography method of Claim 1 wherein in step c), said reaction mixture further includes a reporter ligand.
30. The magnetic chromatography method of Claim 1 wherein in step c), said capture ligand is covalently bound to said magnetic particles.
31. The magnetic chromatography method of Claim 1 wherein in step c), said capture ligand is absorbed to the surface of said magnetic particles.
32. The magnetic chromatography method of Claim 1 wherein in step c), said analyte is present in the sample and said analyte is selected from the group consisting of a control analyte and a calibrator analyte.
33. A magnetic chromatography method for performing a bioassay comprising the steps:
a) providing a chromatographic medium;
b) providing a magnetic field;
c) providing a reaction mixture having a quantity of magnetic particles suspended therein;
d) contacting said chromatographic medium with said reaction mixture at a site thereon such that said reaction mixture flows bi-laterally across said chromotographic medium;
e) applying said magnetic field at said site upon said chromatographic medium corresponding to where said reaction mixture is contacted in step d), said magnetic field being so applied such that a majority of said magnetic particles suspended within said reaction mixture are caused to become captured upon said medium at said site; and f) analyzing said magnetic particles captured upon said chromatographic medium.
34. The magnetic chromatography method of Claim 33 wherein in step b), said magnetic field is generated by a magnet.
35. The magnetic chromatography method of Claim 33 wherein in step b), said magnetic field is generated by an electromagnet.
36. The magnetic chromatography method of Claim 33 wherein in step e), said magnetic field is applied by positioning a magnet in close proximity to the chromatographic medium.
37. The magnetic chromatography method of Claim 33 wherein in step c), said magnetic particles have an analyte, receptor, and label complexed therewith.
38. The magnetic chromatography method of Claim 37 wherein said label comprises a detectable chemical moiety selected from the group consisting of radioactive, fluorescent, enzymatic, and dye moieties.
39. The magnetic chromatography method of Claim 34 wherein in step b), said magnetic field is provided by a magnetic rail having a width between 0.003 inches and 3.0 inches, and having a length between 0.010 inches and 100 inches.
40. The magnetic chromatography method of Claim 33 wherein in step c), said magnetic particles have a diameter ranging between 1 nm to 100 microns.
41. The magnetic chromatography method of Claim 33 wherein in step a), said chromatographic medium comprises a test strip, said test strip comprising:
a) an elongate backing having first and second opposed ends and an intermediate portion;
b) first and second absorbent pads formed upon respective ones of said first and second ends of said backing;
c) a lateral flow mesh formed upon said intermediate portion of said backing and between said first and second absorbent pads; and d) a vertical flow mesh formed upon said lateral flow mesh.
42. The magnetic chromatography method of Claim 41 wherein in step c), said reaction mixture is contacted with said chromatic graphic medium via a sample well such that said sample well causes said reaction mixture to flow sequentially from said vertical flow mesh, to said lateral flow mesh, and to said absorbent pads.
43. A magnetic chromatography test strip for performing a bioassay comprising:
a) an elongate backing having first and second opposed ends and an intermediate portion;
b) first and second absorbent pads formed upon respective ones of said first and second opposed ends of said backing;
c) a lateral flow mesh formed upon said intermediate portion of said backing and between said first and second absorbent pads; and d) a vertical flow mesh formed upon said lateral flow mesh.
44. The magnetic chromatography test strip of Claim 43 wherein said vertical flow mesh and said lateral flow mesh are fabricated from a polymer selected from the group consisting of nylon and polyester.
45. The magnetic chromatography test strip of Claim 43 wherein said lateral flow mesh is formed to have a generally perpendicular orientation relative said vertical flow mesh.
46. The magnetic chromatography test strip of Claim 43 wherein said lateral flow mesh is formed to have a generally diagonal orientation relative said vertical flow mesh.
47. The magnetic chromatography test strip of Claim 43 further comprising:
a) sample well for introducing a test solution to said test strip, said sample well being configured to disperse said test solution upon said vertical flow mesh.
48. The magnetic chromatography test strip of claim 43 further comprising:
a) a magnet disposed underneath said intermediate portion of said backing.
49. The magnetic chromatography test strip of claim 48 wherein said magnet is disposed beneath said vertical flow mesh and said lateral flow mesh.
CA2387788A 1999-10-15 2000-10-05 Systems and methods for performing magnetic chromatography assays Expired - Lifetime CA2387788C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US09/418,864 US6136549A (en) 1999-10-15 1999-10-15 systems and methods for performing magnetic chromatography assays
US09/418,864 1999-10-15
US09/668,966 2000-09-25
US09/668,966 US6713271B1 (en) 1999-10-15 2000-09-25 Systems and methods for performing magnetic chromatography assays
PCT/US2000/027452 WO2001029559A1 (en) 1999-10-15 2000-10-05 Systems and methods for performing magnetic chromatography assays

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CA2387788A1 true CA2387788A1 (en) 2001-04-26
CA2387788C CA2387788C (en) 2011-06-14

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US (3) US6136549A (en)
EP (1) EP1226434B8 (en)
JP (1) JP4683806B2 (en)
AU (1) AU772407B2 (en)
CA (1) CA2387788C (en)
DE (1) DE60037268T2 (en)
DK (1) DK1226434T3 (en)
NO (1) NO331708B1 (en)
WO (1) WO2001029559A1 (en)

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