Magnetic nanoparticles, magnetic detector arrays, and methods for their use in detecting biological molecules

• US 8,318,093 B2
• Filed: 05/17/2007
• Issued: 11/27/2012
• Est. Priority Date: 11/12/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Wang, Shan X., White, Robert L., Webb, Chris D., Li, Guanxiong
• Primary Examiner(s): Shibuya, Mark
• Assistant Examiner(s): DO, PENSEE T
• Application Number:
  US11/804,583
• Publication Number:
  US 20120122732A1
• Time in Patent Office: 2,021 Days
• Field of Search: 422/50
• US Class Current: 422/50
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00563 Magnetic means
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00655 the compounds being bound to magnets embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00734 Lipids
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 25/00 Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2446/10 : the magnetic material being used to coat a pre-existing polymer particle but not being present in the particle core
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: G01N 33/5434 : using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/553 : Metal or metal coated
• CPC Class Codes: H01F 1/0054 : Coated nanoparticles, e.g. nanoparticles coated with organic surfactant
• CPC Class Codes: H01F 10/3254 : the spacer being semiconducting or insulating, e.g. for spin tunnel junction [STJ]
• CPC Class Codes: H01F 10/3272 : by use of anti-parallel coupled [APC] ferromagnetic layers, e.g. artificial ferrimagnets [AFI], artificial [AAF] or synthetic [SAF] anti-ferromagnets
• CPC Class Codes: Y10T 428/2991 : Coated

Abstract

Magnetic nanoparticles and methods for their use in detecting biological molecules are disclosed. The magnetic nanoparticles can be attached to nucleic acid molecules, which are then captured by a complementary sequence attached to a detector, such as a spin valve detector or a magnetic tunnel junction detector. The detection of the bound magnetic nanoparticle can be achieved with high specificity and sensitivity.

Claims

1. A spin valve detector array useful for the detection of magnetic nanoparticles, the detector array comprising:

a plurality of detection sites, wherein each of the plurality of detection sites comprise;

a first ferromagnetic layer;

a non-magnetic layer facially contacting the first ferromagnetic layer;

a second ferromagnetic layer facially contacting the non-magnetic layer;

an ultrathin passivation layer facially contacting the second ferromagnetic layer; and

a binding molecule bonded to the passivation layer, wherein the binding molecule is at least one of a nucleic acid, a natural DNA, a synthetic DNA, a natural RNA, a synthetic RNA, a peptide, a protein, an antibody, a lipid, a virus, a polymer, a toxin compound, a pharmaceutical compound, a biohazard compound, or an explosive compound;

a DC bias field source; and

an AC tickling field source.

2. The array of claim 1, wherein the first ferromagnetic layer comprises Co, Co alloys, Iron, Iron alloys, Fe—

N, Fe₃O₄, Fe—

Zr—

Nb—

B, Ni, Ni alloys, or mixtures thereof.

3. The array of claim 1, wherein the first ferromagnetic layer is pinned by an exchange-bias layer or a synthetic ferromagnetic layer.

4. The array of claim 1, wherein the second ferromagnetic layer comprises Co, Co alloys, Iron, Iron alloys, Fe—

N, Fe₃O₄, Fe—

Zr—

Nb—

B, Ni, Ni alloys, or mixtures thereof.

5. The array of claim 1, wherein the passivation layer is about 1 nm to about 10 nm in thickness.

6. The array of claim 1, wherein the passivation layer comprises gold, tantalum, or glass.

7. The array of claim 1, further comprising an aperture on the top of the passivation layer to confine the binding molecule.

8. The array of claim 1, wherein the non-magnetic layer comprises ruthenium, a ruthenium alloy, chromium, a chromium alloy, gold, a gold alloy, a noble metal, a noble metal alloy, or mixtures thereof.

9. The array of claim 1, wherein each of the detection sites comprises a spin valve detector or detectors with a line width of between about 0.01 μ

m and about 1 μ

m.

10. The array of claim 1, further comprising microfluidic circuits.

11. The array of claim 1, wherein the ultrathin passivation layer has a thickness of 10 nm or less.

12. The array of claim 1, further comprising a row decoder, a column decoder, a preamplifier, and at least one current source.

13. The array of claim 1, further comprising one or more leads disposed under the first ferromagnetic layer.

14. The array of claim 1, wherein the array comprises a bridge circuit.

15. The array of claim 1, wherein the detection sites have a magnetoresistance ratio of 5% or more.

16. The array of claim 1, wherein the AC tickling field source is configured to produce an AC tickling field orthogonal to a DC bias field produced by the DC bias field source.

17. A spin valve detector array useful for the detection of magnetic nanoparticles, the detector array comprising:

a plurality of detection sites, wherein each of the plurality of detection sites comprise;

a first ferromagnetic layer;

a non-magnetic layer facially contacting the first ferromagnetic layer;

a second ferromagnetic layer facially contacting the non-magnetic layer;

an ultrathin passivation layer facially contacting the second ferromagnetic layer; and

a binding molecule bonded to the passivation layer, wherein the binding molecule is at least one of a nucleic acid, a natural DNA, a synthetic DNA, a natural RNA, a synthetic RNA, a peptide, a protein, an antibody, a lipid, a virus, a polymer, a toxin compound, a pharmaceutical compound, a biohazard compound, or an explosive compound; and

a reference detector, wherein the reference detector comprises a polymer coating.