US4672040A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Magnetic particles for use in separations
Assignee: Amag Pharmaceuticals Inc
•
Filing: 1985-06-28
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Granted: 1987-06-09
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Expires: 2005-06-28
Abstract
Abstract Methods are provided for the use of magnetically responsive particles in systems in which the separation of certain molecules, macromolecules and cells from the surrounding medium is desirable. The magnetically responsive particles may be coupled to a wide variety of molecules. The magnetic particles can be dispersed in aqueous media without rapid settling and conveniently reclaimed from media with a magnetic field. Preferred particles do not become magnetic after application of a magnetic field and can be redispersed and reused.
Inventors
- 👤 Lee Josephson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 06:26
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/54313; G01N33/54326; G01N33/5434; B; B01; B01D; B01D15/00; B01D15/08; B01D15/10; B01D15/18; B01D15/1807; B01D15/26; B01D15/38; B01D15/3804; B01J; B01J20/00; B01J20/02; B01J20/0203; B01J20/0225; B01J20/0229; B01J20/06; B01J20/22; B01J20/26; B01J20/262; B01J20/28; B01J20/28002; B01J20/28009; B01J20/30; B01J20/32; B01J20/3202; B01J20/3204; B01J20/3214; B01J20/3217; B01J20/3219; B01J20/3231; B01J20/3242; B01J20/3244; B01J20/3246; B01J20/3257; B01J20/3261; B01J20/3268; B01J20/3272; B01J20/3274; B01J20/3291; B01J20/3293; B01J20/34; B01J20/3425; B01J20/345; B03; B03C; B03C1/00; B03C1/005; B03C1/01; C; C12; C12Q; C12Q1/00; C12Q1/34; C12Q1/42; C12Q1/54; C12Q1/68; C12Q1/6813; C12Q1/6834; B01J2220/00; B01J2220/50; B01J2220/54; G01N2446/00; G01N2446/20; G01N2446/80; G01N2446/90
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
210 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a magnetic metal oxide core generally surrounded by a coat of polymeric silane, a mass of such uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, the magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 2
Independent Claim
210 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a magnetic metal oxide core generally surrounded by a coat of polymeric silane, a mass of such uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, the magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 3
Independent Claim
254 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically-responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 4
Independent Claim
254 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically-responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 5
Independent Claim
255 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a ferromagnetic metal oxide core generally surrounded by a coat of polymeric silane, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 6
Independent Claim
255 words
A method for carrying out nucleic acid hybridization which comprises: (a) contacting a first nucleic acid molecule covalently coupled to a magnetically-responsive particle with a solution or suspension containing a complementary nucleic acid molecule in a reaction vessel; (b) allowing the first nucleic acid molecule and the complementary nucleic acid molecules to hybridize; (c) magnetically separating the magnetically responsive particles with complementary nucleic acid molecules bound thereto from the solution or suspension; and (d) recovering the bound nucleic acid molecule from the magnetically-responsive particles, wherein the magnetically-responsive particle of step (a) comprises a ferromagnetic metal oxide core generally surrounded by a coat of polymeric silane, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 7
Dependent Claim
17 words
The method according to claim 1, 2 or 3 wherein the nucleic acid molecule is deoxyribonucleic acid.
Claim 8
Dependent Claim
17 words
The method according to claim 1, 2 or 3 wherein the nucleic acid molecule is ribonucleic acid.
Claim 9
Dependent Claim
18 words
The method according to claim 1, 2 or 3 wherein the nucleic acid molecule is a homopolymeric oligonucleotide.
Claim 10
Dependent Claim
26 words
The method according to claim 6 wherein the homopolymeric oligonucleotide is selected from the group consisting of polyuridylic acid, polythymidylic acid, polyadenylic acid, and polyguanidylic acid.
Claim 11
Independent Claim
90 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution or suspension of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and
Claim 12
Independent Claim
90 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution or suspension of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and
Claim 13
Dependent Claim
135 words
(d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a magnetic metal oxide core generally surrounded by a coat of polymeric silane, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, the magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 14
Dependent Claim
135 words
(d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a magnetic metal oxide core generally surrounded by a coat of polymeric silane, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, the magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 15
Independent Claim
268 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and (d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 16
Independent Claim
268 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and (d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 17
Independent Claim
268 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and (d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a ferromagnetic metal oxide core generally surrounded by a coat of polymeric silane, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 18
Independent Claim
268 words
A method for selecting a subpopulation of cells, bacteria or viruses from a heterogeneous population which comprises: (a) incubating a solution or suspension of the heterogeneous population with a ligate which specifically binds to the subpopulation; (b) reacting magnetically-responsive particles to which a ligand which specifically binds to the ligate in solution or suspension of step (a) is covalently coupled with the solution of step (a) for a sufficient time to form a ligand/ligate complex; (c) magnetically separating the magnetic particle-ligand/ligate-subpopulation complexes from the solution or suspension; and (d) recovering the subpopulation from the magnetically-responsive particles, wherein the magnetically-responsive particles of step (b) individually comprise a ferromagnetic metal oxide core generally surrounded by a coat of polymeric silane, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (i) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (ii) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 19
Dependent Claim
14 words
The method of claim 8, 9 or 10 wherein the ligand is an antibody.
Claim 20
Dependent Claim
14 words
The method of claim 8, 9 or 10 wherein the ligand is protein A.
Claim 21
Dependent Claim
15 words
The method of claim 8, 9 or 10 wherein the ligand is a fluorescent dye.
Claim 22
Dependent Claim
14 words
The method of claim 8, 9 or 10 wherein the ligand is a lectin.
Claim 23
Dependent Claim
20 words
The method of claim 8, 9 or 10 wherein the ligand is protein A and the ligate is an antibody.
Claim 24
Dependent Claim
22 words
The method of claim 8, 9 or 10 wherein the ligand is an antibody specific for fluorescein and the ligate is fluorescein.
Claim 25
Dependent Claim
129 words
A coupled magnetically-responsive particle comprising a magnetic metal oxide core generally surrounded by a coat of polymeric silane to which a nucleic acid molecule is covalently coupled, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 26
Dependent Claim
129 words
A coupled magnetically-responsive particle comprising a magnetic metal oxide core generally surrounded by a coat of polymeric silane to which a nucleic acid molecule is covalently coupled, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 27
Dependent Claim
177 words
A coupled magnetically-responsive particle comprising a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane to which a nucleic acid molecule is covalently coupled, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 28
Dependent Claim
177 words
A coupled magnetically-responsive particle comprising a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane to which a nucleic acid molecule is covalently coupled, the iron oxide core including a group of crystals of iron oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m 2 /gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 29
Dependent Claim
177 words
A coupled magnetically-responsive particle comprising a ferromagnetic metal oxide core generally surrounded by a coat of polvmeric silane to which a nucleic acid molecule is covalently coupled, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m /2 gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 30
Dependent Claim
177 words
A coupled magnetically-responsive particle comprising a ferromagnetic metal oxide core generally surrounded by a coat of polvmeric silane to which a nucleic acid molecule is covalently coupled, the metal oxide core including a group of crystals of metal oxide, the uncoupled particle having a mean diameter as measured by light scattering between about 0.1μ and about 1.5μ and a surface area as measured by nitrogen gas adsorption of at least about 100 m /2 gm, a mass of the uncoupled particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninety-five-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.
Claim 31
Dependent Claim
21 words
The coupled magnetically-responsive particle according to claim 17, 18 or 19 wherein the nucleic acid molecule is a deoxyribonucleic acid molecule.
Claim 32
Dependent Claim
21 words
The coupled magnetically-resoonsive particle according to claim 17, 18 or 19 wherein the nucleic acid molecule is a ribonucleic acid molecule.
Claim 33
Dependent Claim
20 words
The coupled magnetically-responsive particle according to claim 17, 18 or 19 wherein the nucleic acid molecule is a homopolymeric oligonucleotide.
Claim 34
Dependent Claim
28 words
The coupled magnetically-responsive particle according to claim 22 wherein the homopolymeric oligonucleotide is selected from the group consisting of polyuridylic acid, polythymidilic acid, polyadenylic acid and polyguanidylic acid.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-06-08 | 1990-12-08 | 1991-06-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-06-08 | 1994-12-08 | 1995-06-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-06-08 | 1998-12-08 | 1999-06-09 | $7700.00 | Window Closed / Lapsed |