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US 2002/0001855 A1Published application
Methods and apparatus for parallel magnetic biological analysis and manipulation
OwnerMara G. Prentiss, Gary Zabowinventors
Life of this patent
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Abstract
The invention relates to a new method for conducting parallel manipulations of biological entities with emphasis on measurements of binding strengths between, or elastic strengths of, various biological molecules. In particular, the invention involves the generation and use of high magnetic fields and in particular high magnetic field gradients over extended areas using electromagnetic or permanent magnets in one- or two-dimensional grids, which can be used to measure simultaneously multiple binding interactions. The binding interactions may all be the same or may each be different from the others.
Claims115
A method for measuring a binding strength between at least one binding member and a cognate receptor comprising
- contacting a magnetically-labeled cognate receptor with an at least one binding member conjugated to a first surface,
- applying a magnetic force to the magnetically-labeled cognate receptor by positioning the first surface in proximity to a second surface having a magnetic field and magnetic field gradient, and
- determining whether the magnetically-labeled cognate receptor remains in contact with the at least one binding member,
- wherein the magnetic field and the magnetic field gradient are produced by an arrangement selected from the group consisting of an antiparallel adjacent array of permanent magnets, an antiparallel array of electric current carrying wires, a magnetic media with a one- or two-dimensional periodic pattern, a permanent magnet with a regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field.
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A method for measuring an elastic strength of a biological molecule comprising
- binding a biological molecule which is labeled with a magnetic particle at one end to a first surface,
- applying a magnetic force to the biological molecule by positioning the first surface in proximity to a second surface having a magnetic field and a magnetic field gradient, and
- determining a distance between the first surface and the magnetic particle as a measure of the elastic strength of the biological molecule after the magnetic force has been applied,
- wherein the magnetic field and the magnetic field gradient are produced by an arrangement selected from the group consisting of an antiparallel adjacent array of permanent magnets, an antiparallel array of electric current carrying wires, a magnetic media with a one- or two-dimensional periodic pattern, a permanent magnet with regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field.
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A method for measuring a binding strength between at least one binding member and a cognate receptor comprising
- contacting a magnetically-labeled cognate receptor with an at least one binding member conjugated to a first surface,
- applying a magnetic force to the magnetically-labeled cognate receptor by positioning the first surface in proximity to a second surface having a magnetic field and a magnetic field gradient, and
- determining whether the magnetically-labeled cognate receptor remains in contact with the at least one binding member,
- wherein the second surface has an area of at least 1 mm2, and a magnetic field magnitude produced is approximately uniform throughout planes parallel to the first surface and the second surface.
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A method for measuring an elastic strength of a biological molecule comprising
- binding a biological molecule which is labeled at one end with a magnetic particle to a first surface,
- applying a magnetic force to the biological molecule by positioning the first surface in proximity to a second surface having a magnetic field and a magnetic field gradient, and
- determining a distance between the first surface and the magnetic particle as a measure of the elastic strength of the biological molecule after the magnetic force has been applied,
- wherein the second surface has an area of at least 1 mm2, and a magnetic field magnitude produced is approximately uniform throughout planes parallel to the first surface and the second surface.
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A method of mixing magnetically-labeled biological molecules comprising:
- transporting a first type and a second type of magnetically-labeled biological molecule in a fluid stream, and
- mixing the first type and a second type of magnetically-labeled biological molecule within the fluid stream by applying a magnetic force using an arrangement selected from the group consisting of an antiparallel adjacent array of permanent magnets, an antiparallel array of electric current carrying wires, a magnetic media with a one- or two-dimensional periodic pattern, a permanent magnet with a regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field.
An apparatus for measuring a biological parameter comprising
- a first surface comprised of a magnetic field and a magnetic field gradient generated by an arrangement selected from the group consisting of a planar, adjacent, antiparallel array of a plurality of permanent magnets, a planar, adjacent antiparallel array of magnetizations recorded onto a magnetic recording media, a permanent magnet with regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field, and
- a second surface,
- wherein the magnetic field and magnetic field gradient is periodically modulated over an area of the first surface and decays non-linearly with distance from the first surface,
- wherein each of the plurality of permanent magnets, magnetizations or embossed surface structure has an area of less than 1 cm2.
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An apparatus for measuring a biological parameter comprising
- a first surface comprised of a magnetic field and a magnetic field gradient generated by a planar, adjacent, antiparallel array of a plurality of permanent magnets, or a planar, adjacent antiparallel array of magnetizations recorded onto a magnetic recording media,
- wherein the magnetic field is approximately uniform over an area of the first surface and decays non-linearly with distance from the first surface,
- wherein each of the plurality of permanent magnets or magnetizations has an area of less than 1 cm2, and wherein the first surface has an area of at least 2 cm2.
An apparatus for measuring a biological parameter comprising
- a first surface with a magnetic field and a magnetic field gradient comprised of a first planar, antiparallel array of electric current carrying wires,
- wherein the magnetic field is a periodically modulated throughout an area of the first surface and decays non-linearly with distance from the first surface, and wherein the first surface has an area of at least 2 cm2.
An apparatus for measuring a biological parameter comprising
- a first surface with a magnetic field and a magnetic field gradient comprised of a first planar, antiparallel array of electric current carrying wires,
- wherein the magnetic field is one-dimensional and approximately uniform throughout an area of the first surface and decays non-linearly with distance from the first surface and wherein the first surface has an area of at least 2 cm2.
An apparatus for measuring a biological parameter comprising
- a periodic magnetic array with an area of at least 2 cm2 in close proximity to at least one biasing magnetic field,
- wherein the biasing magnetic field is produced by a permanent magnet of area greater than the array, or by electric current carrying wires,
- wherein a resultant magnetic field in the plane of the periodic magnetic array has a regular periodic variation in field strength.
An article comprising
- a one- or two-dimensional antiparallel array of magnetizations defining a surface comprised of alternating magnetic poles, the surface having an area of at least 2 cm2.
A method for measuring a plurality of elastic strengths simultaneously comprising
- contacting a first surface to a plurality of biological molecules which are labeled at one end with a magnetic particle,
- applying a magnetic force to the plurality of biological molecules by positioning the first surface in proximity to a second surface having a magnetic field and a magnetic field gradient, and
- determining a distance between the first surface and the magnetic particle as a measure of the elastic strength of the biological molecule after the magnetic force has been applied,
- wherein the magnetic field is produced by an arrangement selected from the group consisting of an antiparallel adjacent array of permanent magnets, an antiparallel array of electric current carrying wires, a magnetic recording material with a one- or a two-dimensional periodic pattern, a permanent magnet with regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field.
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A method for determining a plurality of biological strengths simultaneously comprising
- contacting a plurality of binding members conjugated to a first surface to at least one magnetically-labeled cognate receptor,
- applying a magnetic force to the at least one magnetically-labeled cognate receptor by positioning the first surface in proximity to a second surface having a magnetic field and a magnetic field gradient, and
- determining whether each of the plurality of binding members remains in contact with the at least one magnetically-labeled cognate receptor,
- wherein the magnetic field is produced by an arrangement selected from the group consisting of an antiparallel adjacent array of permanent magnets, an antiparallel array of electric current carrying wires, a magnetic recording material with a one- or a two-dimensional periodic pattern, a permanent magnet with regularly embossed one or two dimensional surface structure, and a magnetizable material formed in a one or two dimensional grid, or with an embossed one or two dimensional surface structure in the presence of an externally applied uniform magnetic field.
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Dependencies are inferred from the claim text.