Individually addressable micro-electromagnetic unit array chips

• US 6,355,491 B1
• Filed: 09/17/1999
• Issued: 03/12/2002
• Est. Priority Date: 03/15/1999
• Status: Expired due to Term

• Current Assignee: AVIVA Biosciences Corporation
• Original Assignee: AVIVA Biosciences Corporation
• Inventors: Zhu, Xiaoshan, Tan, Zhimin, Li, Zhiming, Wang, Jia, Chen, Depu, Liu, Xiumei, Chen, Ken, Xu, Junquan, Liu, Litian, Zhou, Yuxiang, Liu, Zewen, Xie, Wenzhang, He, Xuezhong
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/399,299
• Time in Patent Office: 907 Days
• Field of Search: 436/518, 436/526, 436/149, 436/150, 436/151, 436/806, 435/4, 435/6, 435/7.1, 435/287.1, 435/287.2, 422/82.01
• US Class Current: 436/518
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00614 Delimitation of the attachment areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00639 the compounds being trapped in or bound to a porous medium
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 : Electrodes
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/089 : Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property

Abstract

This invention provides electromagnetic chips and electromagnetic biochips having arrays of individually addressable micro-electromagnetic units, as well as methods of utilizing these chips for directed manipulation of micro-particles and micro-structures such as biomolecules and chemical reagents. An electromagnetic biochip comprises an individually addressable micro-electromagnetic unit chip with ligand molecules immobilized on its surface. By controlling the electromagnetic field at each unit of the array and combining this control with magnetic modification of biomolecules, these chips can be used for directed manipulation, synthesis and release of biomolecules in order to increase sensitivity of biochemical or chemical analysis and reduce assay time. Other advantages with these chips include minimized damages to biological molecules and increased reproducibility of assay results.

Claims

1. An electromagnetic chip with individually addressable micro-electromagnetic units comprising:

a substrate;

a plurality of micro-electromagnetic units in whole or in part within said substrate, each of said micro-electromagnetic units structured to produce a magnetic field upon application of electric current thereto; and

means for selectively applying an electric current to any one or more of said plurality of micro-electromagnetic units to produce a magnetic field therein.

2. The electromagnetic chip of claim 1, wherein each of said micro-electromagnetic units comprises a magnetic core and means for conducting an electric current about the magnetic core.

3. The electromagnetic chip of claim 2, wherein said means for conducting an electric current about said magnetic core comprises single or multiple loops of electric conductive traces around said magnetic core.

4. The electromagnetic chip of claim 3, wherein said loops of electric conductive traces are of a circular, a square, an elliptical, a triangular, a spiral, or a squared-spiral shape.

5. The electromagnetic chip of claim 3, further comprising means for modulating a magnitude and a polarity of the electric current selectively applied to one or more of said plurality of micro-electromagnetic units.

6. The electromagnetic chip of claim 2, wherein said magnetic core comprises ferromagnetic material or a ferrimagnetic material.

7. The electromagnetic chip of claim 1, wherein said micro-electromagnetic units are arranged in a regular, repetitive pattern with substantially equal distances between neighboring units.

8. The electromagnetic chip of claim 1, wherein said micro-electromagnetic units have dimensions of width and length ranging between 0.1 micrometer and 1 centimeter.

9. The electromagnetic chip of claim 1, wherein said means for selectively applying comprises conductive connections between each micro-electromagnetic unit and a source of electric current and switch means for alternately interrupting and establishing a flow of electric current through said conductive connections.

10. The electromagnetic chip of claim 9, wherein said switch means are either mechanical or electronic switches.

11. An electromagnetic chip with individually addressable micro-electromagnetic units comprising;

a substrate;

a plurality of micro-electromagnetic units in whole or in part within said substrate, each of said micro-electromagnetic units structured to produce a magnetic field upon application of electric current thereto;

means for selectively applying an electric current to any one or more of said plurality of micro-electromagnetic units to produce a magnetic field therein; and

a functional layer for immobilizing ligand molecules.

12. The electromagnetic chip of claim 11, wherein said functional layer comprises material selected from the group consisting of a hydrophilic molecular monolayer, a hydrophilic molecular monolayer with functional groups, a hydrophobic molecular monolayer, a hydrophobic molecular monolayer with functional groups, a hydrophilic membrane, a hydrophilic membrane with functional groups, a hydrophobic membrane, a hydrophobic membrane with functional groups, a hydrophilic gel, a hydrophilic gel with functional groups, a hydrophobic gel, a hydrophobic gel with functional groups, a porous material, a porous material with functional groups, a non-porous material and a non-porous material with functional groups.

13. The electromagnetic chip of claim 12, wherein said functional groups are selected from the group consisting of aldehydes, carbodimides, succinimydyl esters, antibodies, receptors and lectins.

14. An electromagnetic chip with individually addressable micro-electromagnetic units comprising;

a substrate;

a plurality of micro-electromagnetic units in whole or in part within said substrate, each of said micro-electromagnetic units structured to produce a magnetic field upon application of electric current thereto;

means for selectively applying an electric current to any one or more of said plurality of micro-electromagnetic units to produce a magnetic field therein;

a functional layer for immobilizing ligand molecules; and

ligand molecules immobilized by said functional layer.

15. The electromagnetic chip of claim 14, wherein said ligand molecules are selected from the group consisting of oligonucleotides, DNA molecules, RNA molecules, proteins, antibodies, lectins and receptor molecules.

16. An electromagnetic chip having an array of individually addressable micro-electromagnetic units comprising:

a substrate;

an array of cavities in the substrate, arranged in columns and rows, each of said cavities comprising a ferromagnetic core;

a first layer of conductive traces, each separate trace of said first layer of conductive traces running adjacent to one of said columns;

a second layer of conductive traces insulated from said first layer of conductive traces, with each separate trace of said second layer of conductive traces perpendicular to said first layer of conductive traces and running adjacent to one of said rows.

17. The electromagnetic chip of claim 16, wherein a first layer of insulating material separates said first layer of conductive traces from said second layer of conductive traces.

18. The electromagnetic chip of claim 17, wherein the material of said first insulating layer is selected from the group consisting of silicon dioxide, silicon nitride, plastic, glass, ceramic and rubber.

19. The electromagnetic chip of claim 16, wherein a second layer of insulating material is deposited on a top surface of said second layer of conductive traces and on a top surface of said ferromagnetic cores.

20. The electromagnetic chip of claim 19, wherein the material of said second insulating layer is selected from the group consisting of silicon dioxide, silicon nitride, plastic, glass, ceramic, photoresist and rubber.

21. The electromagnetic chip of claim 16, further comprising an additional layer of conductive traces, each separate trace of said additional layer of conductive traces running adjacent to one of the columns and insulated from other layers of conductive traces.

22. The electromagnetic chip of claim 16 further comprising a further layer of conductive traces, each separate trace of said further layer of conductive traces running adjacent to one of the rows and insulated from other layers of conductive traces.

23. The electromagnetic chip of claim 16, wherein the substrate is a material selected from the group consisting of silicon, glass, ceramic, silicon dioxide and plastic.

24. The electromagnetic chip of claim 16, wherein said conductive traces comprise a material selected from the group consisting of aluminum, gold, silver, tin, copper, platinum, palladium, carbon and semiconductor material.

25. The electromagnetic chip of claim 16, further comprising a functional layer.

26. The electromagnetic chip of claim 25, wherein said functional layer comprises material selected from the group consisting of a hydrophilic molecular monolayer, a hydrophilic molecular monolayer with functional groups, a hydrophobic molecular monolayer, a hydrophobic molecular monolayer with functional groups, a hydrophilic membrane, a hydrophilic membrane with functional groups, a hydrophobic membrane, a hydrophobic membrane with functional groups, a hydrophilic gel, a hydrophilic gel with functional groups, a hydrophobic gel, a hydrophobic gel with functional groups, a porous material, a porous material with functional groups, a non-porous material and anon-porous material with functional groups.

27. The electromagnetic chip of claim 26, wherein said functional groups are selected from the group consisting of aldehydes, carbodiimides, succinimydyl esters, antibodies, receptors and lectins.

28. The electromagnetic chip of claim 16, further comprising a fluidic chamber.

38. The electromagnetic chip of claim 28, wherein said substrate comprises a material selected from the group consisting of silicon, glass, ceramic, silicon dioxide and plastic.

29. An electromagnetic chip comprising an array of individually addressable micro-electromagnetic units comprising:

a substrate;

an array of cavities in said substrate, arranged in columns and rows, each of said cavities comprising a ferromagnetic core; and

a first layer of conductive traces, each separate trace of said first layer of conductive traces extending at least 90°

around at least one of said ferromagnetic cores.

30. The electromagnetic chip of claim 29 further comprising an additional layer of conductive traces, each separate trace of said additional layer of conductive traces extending at least 90°

around at least one of said ferromagnetic cores and being separated from said first set of conductive traces by an insulating layer penetrated by a vertical conductive connection between traces of said first layer of conductive traces and traces of said additional layer of conductive traces.

31. The electromagnetic chip of claim 30, wherein a first layer of insulating material separates said first layer of conductive traces from said additional layer of conductive traces.

32. The electromagnetic chip of claim 31, wherein said first insulating layer comprises a material selected from the group consisting of silicon dioxide, silicon nitride, plastic, glass, ceramic, photoresist and rubber.

33. The electromagnetic chip of claim 29, wherein a second layer of insulating material is deposited on a top surface of the array.

34. The electromagnetic chip of claim 33, wherein said second insulating layer comprises a material selected from the group consisting of silicon dioxide, silicon nitride, plastic, glass, ceramic, photoresist and rubber.

35. The electromagnetic chip of claim 29, further comprising a functional layer.

36. The electromagnetic chip of claim 35, wherein said functional layer comprises material selected from the group consisting of a hydrophilic molecular monolayer, a hydrophilic molecular monolayer with functional groups, a hydrophobic molecular monolayer, a hydrophobic molecular monolayer with functional groups, a hydrophilic membrane, a hydrophilic membrane with functional groups, a hydrophobic membrane, a hydrophobic membrane with functional groups, a hydrophilic gel, a hydrophilic gel with functional groups, a hydrophobic gel, a hydrophobic gel with functional groups, a porous material, a porous material with functional groups, a non-porous material and anon-porous material with functional groups.

37. The electromagnetic chip of claim 36, wherein said functional groups are selected from the group consisting of aldehydes, carbodiimides, succinimydyl esters, antibodies, receptors and lectins.

39. The electromagnetic chip of claim 29, wherein said conductive traces comprise a material is selected from the group consisting of aluminum, gold, silver, tin, copper, platinum, palladium, carbon and semiconductor materials.

40. The electromagnetic chip of claim 29 further comprising a fluidic chamber.