Microdevices having a preferential axis of magnetization and uses thereof

• US 20020187501A1
• Filed: 03/21/2002
• Published: 12/12/2002
• Est. Priority Date: 01/26/2001
• Status: Active Grant

• Current Assignee: AVIVA Biosciences Corporation, CapitalBio Corporation, Tsinghua University
• Original Assignee: CapitalBio Corporation
• Inventors: Wang, Xiaobo, Wu, Lei, Xu, Junquan, Huang, Mingxian, Rothwarf, David M., Tao, Guo Liang
• Granted Patent: US 7,015,047 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00457 Dispensing or evacuation of the solid phase support
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00502 Particles of irregular geometry
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00542 Alphanumeric characters
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00556 Perforations
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00592 Split-and-pool, mix-and-divide processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00655 the compounds being bound to magnets embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00729 : Peptide nucleic acids [PNA]
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01J 2219/00734 : Lipids
• CPC Class Codes: B01J 2219/0074 : Biological products
• CPC Class Codes: B01J 2219/00743 : Cells
• CPC Class Codes: B01L 2200/0647 : Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/043 : magnetic forces
• 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: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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: B03C 5/028 : using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]
• CPC Class Codes: B82Y 10/00 : Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• 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: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G06K 19/06009 : with optically detectable marking G06K19/063, G06K19/08 take precedence
• CPC Class Codes: G06K 19/06046 : Constructional details
• CPC Class Codes: G06K 19/06196 : Constructional details
• CPC Class Codes: Y10T 428/24917 : including metal layer

Abstract

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) a magnetizable substance; and b) a photorecognizable coding pattern, wherein said microdevice has a preferential axis of magnetization. Systems and methods for isolating, detecting and manipulating moieties and synthesizing libraries using the microdevices are also provided.

Claims

1. A microdevice, which microdevice comprises:

a) a magnetizable substance; and

b) a photorecognizable coding pattern,

wherein said microdevice has a preferential axis of magnetization.

2. The microdevice of claim 1, wherein the magnetizable substance is selected from the group consisting of a paramagnetic substance, a ferromagnetic substance and a ferrimagentic substance.

3. The microdevice of claim 1, wherein an induced magnetization in its absolute magnitude along the preferential axis of the magnetization of the microdevice is at least 20% more than an induced magnetization of the microdevice along at least one other axis.

4. The microdevice of claim 1, wherein an induced magnetization in its absolute magnitude along the preferential axis of the magnetization of the microdevice is at least 50%, 75%, or 100% more than an induced magnetization of the microdevice along at least one of any other axes.

5. The microdevice of claim 1, wherein an induced magnetization in its absolute magnitude along the preferential axis of the magnetization of the microdevice is at least one-, two-, five-, ten-, twenty-, or fifty-times more than an induced magnetization of the microdevice along at least one of any other axes.

6. The microdevice of claim 1, wherein the preferential axis of magnetization is substantially aligned with the major axis of the microdevice.

7. The microdevice of claim 1, wherein the microdevice is in the form of a thin round disc with the preferential axis of the magnetization substantially in the plane of the major surface of the disc.

8. The microdevice of claim 1, wherein the microdevice has a thin rectangular shape with the preferential axis of the magnetization substantially in the direction of the length of the microdevice.

9. The microdevice of claim 1, wherein the magnetizable substance comprises a metal composition.

10. The microdevice of claim 9, wherein the metal composition is a transition metal composition or an alloy thereof.

11. The microdevice of claim 10, wherein the transition metal is selected from the group consisting of iron, nickel, copper, cobalt, manganese, tantalum, zirconium and cobalt-tantalum-zirconium (CoTaZr) alloy.

12. The microdevice of claim 9, wherein the metal composition is Fe₃O₄.

13. The microdevice of claim 1, further comprising a non-magnetizable substrate.

14. The microdevice of claim 13, wherein the substrate comprises a material that is selected from the group consisting of silicon, plastic, glass, ceramic, rubber, polymer, silicon dioxide, aluminum oxide, titanium, aluminum, gold and a combination thereof.

15. The microdevice of claim 14, wherein the silicon is silicon dioxide or silicon nitride.

16. The microdevice of claim 13, wherein the substrate comprises a surface that is hydrophobic or hydrophilic.

17. The microdevice of claim 1, wherein the photorecognizable coding pattern is the material composition of the microdevice itself, a structural configuration in the microdevice or an optical labeling substance.

18. The microdevice of claim 17, wherein the versatility of the photorecognizable coding pattern is caused by the shape, number, position distribution, optical refractive property, material composition, or a combination thereof, of the microdevice, the structural configuration(s), or the optical labeling substance(s).

19. The microdevice of claim 17, wherein the photorecognizable coding pattern comprises a plurality of the structural configurations and/or a plurality of the optical labeling substances.

20. The microdevice of claim 1, wherein the photorecognizable coding pattern is fabricated or microfabricated on the microdevice.

21. The microdevice of claim 1, wherein the photorecognizable coding pattern is lithographically patterned.

22. The microdevice of claim 21, wherein the lithographical pattern is selected from the group consisting of photolithography, electron beam lithography and X-ray lithography.

23. The microdevice of claim 17, wherein the optical labeling substance is deposited on the microdevice.

24. The microdevice of claim 17, wherein the optical labeling substance is comprised within the microdevice.

25. The microdevice of claim 17, wherein the optical labeling substance is deposited by evaporation or sputtering.

26. The microdevice of claim 17, wherein the optical labeling substance is selected from the group consisting of a fluorescent substance, a scattered-light detectable particle and a quantum dot.

27. The microdevice of claim 26, wherein the quantum dot comprises a Cd-X core, X being Se, S or Te.

28. The microdevice of claim 27, wherein the quantum dot is passivated with an inorganic coating shell.

29. The microdevice of claim 28, wherein the coating shell comprises Y-Z, Y being Cd or Zn, and Z being S or Se.

30. The microdevice of claim 26, wherein the quantum dot comprises a Cd-X core, X being Se, S or Te, a Y-Z shell, Y being Cd or Zn, and Z being S or Se, and the microdevice is further overcoated with a trialkylphosphine oxide.

31. The microdevice of claim 17, wherein the photorecognizable coding pattern comprises an 1-D and/or a 2-D bar coding pattern.

32. The microdevice of claim 1, further comprising a binding partner that is capable of binding to a moiety.

33. The microdevice of claim 32, wherein the binding partner is an antibody or a nucleotide sequence.

34. The microdevice of claim 32, which comprises a plurality of binding partners, each binding partner is capable of binding or specifically binding to a different moiety.

35. The microdevice of claim 1, further comprising an element that facilitates and/or enables manipulation of the microdevice and/or a moiety/microdevice complex.

36. The microdevice of claim 35, wherein the element is selected from the group consisting of a conductive or insulating material, a material having high or low acoustic impedance and a charged material.

37. The microdevice of claim 35, wherein the element facilitates and/or enables manipulation of the microdevice and/or a moiety/microdevice complex by a physical force selected from the group consisting of a dielectrophoresis, a traveling-wave dielectrophoresis, an acoustic, an electrostatic, a mechanical, an optical radiation and a thermal convection force.

38. The microdevice of claim 35, which comprises a plurality of the elements, each of the elements facilitates and/or enables manipulation of the microdevice and/or the moiety/microdevice complex by a different physical force.

39. The microdevice of claim 8, which has a major axis to minor axis ratio of at least about 1.2.

40. The microdevice of claim 8, which comprises at least two rectangular structures of the paramagnetic substance.

41. The microdevice of claim 40, wherein the at least two rectangular structures of the paramagnetic substance are separated by a metal layer.

42. The microdevice of claim 41, wherein the metal layer comprises aluminum.

43. The microdevice of claim 41, which has unequal number of the paramagnetic substance rectangular structure(s) on each side along the major axis of the microdevice.

44. The microdevice of claim 8, which comprises two rectangular structures of the paramagnetic substance along the major axis of the microdevice.

45. The microdevice of claim 8, wherein the paramagnetic substance forms a rectangular structure along the major axis of the microdevice and said rectangular structure has fingers on both ends.

46. The microdevice of claim 44, wherein the two rectangular structures of the paramagnetic substance have fingers on both ends.

47. The microdevice of claim 1, further comprising a functional group suitable for synthesis, conjugation, or binding.

48. The microdevice of claim 47, wherein the functional group is selected from the group consisting of a carboxyl, an amino, a hydroxyl, a sulfhydryl, an epoxy, an ester, an alkene, an alkyne, an alkyl, an aromatic, an aldehyde, a ketone, a sulfate, an amide, an urethane group and a derivative thereof.

49. The microdevice of claim 17, wherein the structural configuration is a hole.

50. The microdevice of claim 40, wherein the at least two rectangular structures of the paramagnetic substance are in the form of strips.

51. A system for forming a microdevice array, which system comprises:

a) a plurality of the microdevices of claim 1;

and

b) a microchannel array comprising a plurality of microchannels, said microchannels are sufficiently wide to permit rotation of said microdevices within said microchannels but sufficiently narrow to prevent said microdevices from forming a chain when the major axis of said microdevices is substantially perpendicular to the major axis of said microchannels.

52. The system of claim 51, wherein the height of the microchannels and/or the constraint on the microdevices by a magnetic field does not allow the microdevices to stand up within the microchannels.

53. The system of claim 51, wherein the height of the microchannels is less than about 70% of the major axis of the microdevices.

54. The system of claim 51, wherein the microchannel array further comprises a staging area where the microdevices can be manipulated.

55. The system of claim 51, wherein the microchannel array further comprises an outlet channel.

56. The system of claim 51, which further comprises a magnetic field generator capable of generating a magnetic field suitable for manipulating the microdevices into, within and/or out of the microchannel array.

57. The system of claim 56, wherein the magnetic field generator comprises a ferromagnetic material or a microelectromagenetic unit.

58. The system of claim 56, wherein the magnetic field generator is located below, within and/or above the microchannel array.

59. A method for forming a microdevice array, which method comprises:

a) providing a plurality of the microdevices of claim 1;

b) providing a microchannel array comprising a plurality of microchannels, said microchannels are sufficiently wide to permit rotation of said microdevices within said microchannels but sufficiently narrow to prevent said microdevices from forming a chain when the major axis of said microdevices is substantially perpendicular to the major axis of said microchannels;

c) introducing said plurality of microdevices into said plurality of microchannels; and

d) rotating said microdevices within said microchannels by a magnetic force, whereby the combined effect of said magnetic force and said preferential axis of magnetization of said microdevices substantially separates said microdevices from each other.

60. The method of claim 59, wherein the height of the microchannels and/or the constraint on the microdevices by a magnetic field does not allow the microdevices to stand up within the microchannels.

61. The method of claim 59, wherein the height of the microchannels is about less than 70% of the major axis of the microdevices.

62. The method of claim 59, wherein the microdevices are introduced into the microchannels by a magnetic force, a fluidic force or a combination thereof.

63. The method of claim 59, wherein the microdevices are introduced into the microchannels by a magnetic force at a direction such that the angle between the major axis of the microdevice and the major axis of microchannel is about less than 45 degrees.

64. The method of claim 59, further comprising a step of breaking a chain formed among the microdevices prior to or concurrent with introducing the microdevices into the microchannels.

65. The method of claim 59, wherein the microdevices are rotated at least 45 degrees.

66. The method of claim 65, wherein the microdevices are rotated 90 degrees.

67. The method of claim 59, wherein at least one of the microdevices binds to a moiety and the method is used to manipulate said moiety.

68. The method of claim 59, wherein a plurality of the microdevices bind to a plurality of moieties and the method is used to manipulate said plurality of moieties.

69. The method of claim 67, wherein the manipulation is selected from the group consisting of transportation, focusing, enrichment, concentration, aggregation, trapping, repulsion, levitation, separation, fractionation, isolation and linear or other directed motion of the moiety.

70. The method of claim 67, further comprising a step of assessing the identity of the manipulated moiety by photoanalysis of the photorecognizable coding pattern on the microdevice to which the moiety binds.

71. The method of claim 59, wherein a plurality of the microdevices bind to a plurality of moieties and the method is used to quantify moieties by detecting a physical property of said moieties or of labeling moiety attached to or interacting with said moiety.

72. The method of claim 71, wherein the physical or labeling property is fluorescence, radioactivity, mass, refractive index, absorbance, chemiluminescence, or response to a secondary molecule that alters one of said properties.

73. The method of claim 72, wherein the secondary molecule is an enzyme.

74. The method of claim 67, further comprising a step of collecting the microdevice to which the moiety binds through an outlet channel.

75. The method of claim 74, further comprising a step of recovering the moiety from the collected microdevice.

76. A method for forming a microdevice array, which method comprises:

a) providing a plurality of the microdevices of claim 1 on a surface suitable for rotation of said microdevices; and

b) rotating said microdevices on said surface by a magnetic force, whereby the combined effect of said magnetic force and said preferential axis of magnetization of said microdevices substantially separates said microdevices from each other.

77. The method of claim 76, wherein the surface comprises grooves or channels whose width is substantially narrower than the width of at least one dimension of microdevice.

78. The method of claim 76, wherein the microdevices are introduced onto the surface in a liquid suspension and further comprising removing the liquid via the grooves or channels on the surface after the microdevices are introduced.

80. The method of claim 79, wherein the microdevices are sorted through a microchannel array comprising a plurality of microchannels, said microchannels are sufficiently wide to permit rotation of said microdevices within said microchannels but sufficiently narrow to prevent said microdevices from forming a chain when the major axis of said microdevices is substantially perpendicular to the major axis of said microchannels, and a combined effect of a magnetic force and the preferential axis of magnetization of the microdevices substantially separates the microdevices from each other.

81. The method of claim 80, wherein the height of the microchannels and/or the constraint on the microdevices by a magnetic field does not allow the microdevices to stand up within the microchannels.

82. The method of claim 80, wherein the height of the microchannels is about less than 70% of the major axis of the microdevices.

83. The method of claim 79, wherein each of the microdevices contains a single synthesized entity.

84. The method of claim 79, wherein the synthesized entities are selected from the group consisting of peptides, proteins, oligonucleotides, nucleic acids, vitamins, oligosaccharides, carbohydrates, lipids, small molecules, or a complex or combination thereof.

85. The method of claim 79, wherein the synthesized library comprises a defined set of entities that are involved in a biological pathway, belongs to a group of entities with identical or similar biological function, expressed in a stage of cell cycle, expressed in a cell type, expressed in a tissue type, expressed in an organ type, expressed in a developmental stage, entities whose expression and/or activity are altered in a disease or disorder type or stage, or entities whose expression and/or activity are altered by drug or other treatments.

86. The method of claim 79, wherein the synthesized library comprises a defined set of oligonucleotide or nucleic acid fragments.

87. The method of claim 86, wherein each of the nucleic acid fragments in the synthesized library comprises at least 2, 10, 15, 20, 25, 50, 75, 100, 200 or 500 nucleotides.

88. The method of claim 79, wherein the synthesized library comprises a defined set of protein or peptide fragments.

89. The method of claim 88, wherein each of the protein or peptide fragments in the synthesized library comprises at least 2, 10, 15, 20, 25, 50, 75, 100, 200 or 500 amino acids.

90. A library that is synthesized according to the method of claim 79.

79. A method for synthesizing a library, which method comprises:

a) providing a plurality of microdevices, each of said microdevices comprises a magnetizable substance and a photorecognizable coding pattern, wherein said microdevices have a preferential axis of magnetization and wherein said photorecognizable coding pattern corresponds to an entity to be synthesized on said microdevice; and

b) synthesizing said entities on said microdevices, wherein said microdevices are sorted after each synthesis cycle according to said photorecognizable coding patterns,

whereby a library is synthesized, wherein each of said microdevices contains an entity that corresponds to a photorecognizable coding pattern on said microdevice and the sum of said microdevices collectively contains a plurality of entities that is predetermined before the library synthesis.

91. A method for synthesizing a library, which method comprises:

a) providing a plurality of microdevices, each of said microdevices comprises a magnetizable substance and a unique photorecognizable coding pattern, wherein each of said microdevices has a preferential axis of magnetization and wherein said unique photorecognizable coding pattern on each of said microdevices corresponds to an entity to be synthesized on each of said microdevices; and

b) synthesizing said entities on said microdevices, wherein said microdevices are identified after each synthesis cycle according to said unique photorecognizable coding patterns,

whereby a library is synthesized, wherein each of said microdevices contains an entity that corresponds to said unique photorecognizable coding pattern on each of said microdevices.

92. The method of claim 91, wherein the microdevices are identified after each synthesis cycle according to the unique photorecognizable coding patterns after the microdevices are arrayed with the aid of a magnetic field interacting with the preferential axis of magnetization.

93. A library that is synthesized according to the method of claim 91.