Encoded beads having oligonucleotides attached and formed in arrays
First Claim
1. A method for manipulating particles suspended at an interface between an electrode and an electrolyte solution, the method comprising the following steps:
- generating an electric field at an interface between an electrode and an electrolyte solution;
patterning either the surface or interior of said electrode to modify its electrochemical properties; and
illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.
1 Assignment
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Accused Products
Abstract
A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.
146 Citations
66 Claims
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1. A method for manipulating particles suspended at an interface between an electrode and an electrolyte solution, the method comprising the following steps:
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generating an electric field at an interface between an electrode and an electrolyte solution;
patterning either the surface or interior of said electrode to modify its electrochemical properties; and
illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps:
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providing a light-sensitive electrode and an electrolyte solution;
generating an electric field at an interface between said electrode and said electrolyte solution; and
illuminating said electrode with a predetermined light pattern to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said illumination pattern in a direction substantially orthogonal to the direction of said electric field.
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20. A method of transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps:
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providing an electrode and an electrolyte solution;
generating an electric field at an interface between said electrode and said electrolyte solution; and
patterning said electrode to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said pattern created in said electrode in a direction substantially orthogonal to the direction of said electric field.
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21. A sorting apparatus for implementing the differential lateral displacement of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising:
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an electric field generator which generates an electric field at said interface;
an electrode;
an electrolyte solution having a substantially continuous flow which effects the displacement of said particles in a direction substantially parallel to said interface;
said electrode being patterned and having its electrochemical properties modified;
an illumination source which illuminates said electrode with an adjustable, predetermined light pattern; and
a plurality of particles located in said electrolyte solution, said particles being acted upon by a combination of forces arising from said substantially continuous electrolyte flow and from said electric field in accordance with said predetermined light pattern and said electrode electrochemical properties, said particles being displaced in accordance with variations in the physical and chemical properties which determine the mobility of said particles. - View Dependent Claims (22, 23, 24, 25)
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26. A method of dynamically assembling and disassembling an array of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps:
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providing an electrode, an electrolyte solution and an interface therebetween;
providing a plurality of particles located in said electrolyte solution;
patterning said electrode to include at least one area of modified electrochemical properties;
illuminating said electrode with a predetermined light pattern;
generating an electric field at said interface to cause the assembly of an array of particles in accordance with the predetermined light pattern and the electrochemical properties of said electrode; and
removing said electric field to cause the disassembly of said array of particles. - View Dependent Claims (27, 28)
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29. A method of forming a spatially encoded array including multiple types of particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps:
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providing an electrode and an electrolyte solution;
providing multiple types of particles, each type being stored in accordance with chemically or physically distinguishable particle characteristics in one of a plurality of reservoirs, each reservoir containing a plurality of like-type particles suspended in said electrolyte solution;
providing said reservoirs in the form of an M×
N grid arrangement;
patterning said electrode to define M×
N compartments corresponding to said M×
N grid of reservoirs;
depositing M×
N droplets from said M×
N reservoirs onto said corresponding M×
N compartments, each said droplet originating from one of said reservoirs and remaining confined to one of said M×
N compartments and each said droplet containing at least one particle;
positioning a top electrode above said droplets so as to simultaneously contact each said droplet;
generating an electric field between said top electrode and said M×
N droplets;
using said electric field to form a particle array in each of said M×
N compartments, each said particle array remaining spatially confined to one of said M×
N droplets;
illuminating said M×
N compartments on said patterned electrode with a predetermined light pattern to maintain the position of said particle arrays in accordance with said predetermined light pattern and the pattern of M×
N compartments; and
positioning said top electrode closer to said electrode thereby fusing said M×
N droplets into a continuous liquid phase, while maintaining each of said M×
N particle arrays in one of the corresponding M×
N compartments. - View Dependent Claims (30)
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31. A method of forming an optical lens array including particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps:
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providing an electrode and an electrolyte solution having an interface therebetween;
providing a plurality of particles located in said electrolyte solution;
patterning said electrode to include at least one area of modified impedance; and
generating an electric field at said interface to cause said particles to assemble into an ordered array within said area of modified impedance. - View Dependent Claims (32, 33, 34)
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35. A diffraction grating formed using particles suspended at an interface between an electrode and an electrolyte solution, said grating comprising:
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an electrode and an electrolyte solution having an interface therebetween;
a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;
said electrode being patterned to include at least one area of modified impedance; and
an electric field generator which generates an electric field at said interface causing said large and small particles to assemble into an array, said small particles being located between said large particles to create a large particle separation distance corresponding substantially to the size of said small particles, said large particle separation distance also determining the spatial frequency characteristics of said diffraction grating, said frequency characteristics being adjustable in dependence on the size of said small particles.
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36. An optical display formed using particles suspended at an interface between an electrolyte solution and an electrode, said display comprising:
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an electrode and an electrolyte solution having an interface therebetween;
a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;
said electrode being patterned to include at least one area of modified impedance;
an electric field generator which generates an electric field at said interface causing said large particles to assemble in accordance with the impedance of said patterned electrode, said electric field generator generating a time varying electric field causing said small particles to selectively move under said large particles to form an on-pixel, and also causing said small particles to selectively move away from said large particles to form an off-pixel in accordance with a selected frequency of said time varying electric field.
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37. A bioanalytical assay implemented using at least one array of particles, said particles being suspended at an interface between an electrode and an electrolyte solution, said assay comprising:
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an electrode and an electrolyte solution therebetween;
a plurality of molecules located in said electrolyte, said molecules including a first type of molecule and a second type of molecule;
a biochemical protocol implementation unit which effects a biochemical interaction between said first and second types of molecules, said interaction resulting in the formation of paired entities, and said implementation unit operating to detect the formation of said paired entity;
plurality of particles located in said electrolyte solution;
an electric field generator which generates an electric field at said interface;
said electrode being patterned to include at least one area of modified electrochemical properties; and
an illumination source positioned to illuminate said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.
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38. A method of implementing a bioanalytical assay using at least one array of particles, said particles being suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps:
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providing an electrode and an electrolyte solution therebetween;
providing a plurality of molecules, said molecules including a first type of molecule and a second type of molecule;
performing a biochemical protocol to effect the biochemical interaction between said first and second types of molecules, said interaction resulting in the formation of paired entities, said protocol including the additional step of detecting the formation of said paired entities;
providing a plurality of particles in said electrolyte solution;
generating an electric field at said interface;
patterning said electrode to include at least one area of modified electrochemical properties; and
illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode. - View Dependent Claims (39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)
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51. A method for performing multiple chemical and biochemical analytical procedures using at least one particle array, said method comprising the following steps:
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providing an electrode and an electrolyte solution having an interface therebetween;
generating an electric field at an interface between an electrode and an electrolyte solution;
patterning said electrode to modify the electrochemical properties of said electrode;
illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode;
performing a first procedure on a portion of said particles to produce a first reaction set of particles;
isolating said first reaction set of particles in accordance with said predetermined light pattern; and
performing a second procedure on said first reaction set of particles to produce a second reaction set of particles. - View Dependent Claims (52, 53)
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54. A method of manipulating nucleic acid, including DNA or RNA, comprising the following steps:
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providing an electrode, an electrolyte solution and an interface therebetween;
providing a plurality of nucleic acid molecules in said electrolyte solution, said nucleic acid molecules being in a coiled configuration;
generating an electric field at said interface to cause the movement of said particles;
patterning said electrode to include areas of modified electrochemical properties which in conjunction with said electric field create controlled gradients in the flow velocity across the nucleic acid, said velocity gradient causing different portions of the nucleic acid to move at different velocities such that the nucleic acid is stretched in the direction of the local velocity gradient; and
maintaining a stagnation point of zero velocity such that the nucleic acid is substantially fixed in position. - View Dependent Claims (55, 56)
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57. An apparatus for the manipulation of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising:
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an electrode and an electrolyte solution;
an electric field generator for generating an electric field at an interface between said electrode and said electrolyte solution;
said surface or interior of said electrode being patterned to modify its electrochemical properties; and
an illumination source which illuminates said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.
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58. An apparatus for the transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, said apparatus comprising:
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a light-sensitive electrode and an electrolyte solution;
an electric field generator which generates an electric field at an interface between said electrode and said electrolyte solution; and
an illumination source which illuminates said electrode with a predetermined light pattern to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said illumination pattern in a direction substantially orthogonal to the direction of said electric field.
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59. A sorting method for implementing the differential lateral displacement of particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps:
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providing an electrode;
providing an electrolyte solution having a substantially continuous flow which effects the displacement of said particles in a direction substantially parallel to said interface;
generating an electric field at said interface;
patterning said electrode in order to modify its electrochemical properties;
illuminating said electrode with an adjustable, predetermined light pattern; and
providing a plurality of particles located in said electrolyte solution, said particles being acted upon by a combination of forces arising from said substantially continuous electrolyte flow and from said electric field in accordance with said predetermined light pattern and said electrode electrochemical properties, said particles being displaced in accordance with variations in the physical and chemical properties which determine the mobility of said particles.
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60. An apparatus for dynamically assembling and disassembling an array of particles at an interface between an electrode and an electrolyte solution, said apparatus comprising:
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an electrode, an electrolyte solution and an interface therebetween;
a plurality of particles located in said electrolyte solution;
said electrode being patterned to include at least one area of modified electrochemical properties;
an illumination source which illuminates said electrode with a predetermined light pattern;
an electric field generator which generates an electric field at said interface to cause the assembly of an array of particles in accordance with the predetermined light pattern and the electrochemical properties of said electrode; and
an electric field removal unit which removes said electric field to cause the disassembly of said array of particles.
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61. An apparatus for forming a spatially encoded array including multiple types of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising:
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an electrode and an electrolyte solution;
multiple types of particles, each type being stored in accordance with chemically or physically distinguishable particle characteristics in one of a plurality of reservoirs, each reservoir containing a plurality of like-type particles suspended in said electrolyte solution;
said reservoirs being arranged in the form of an M×
N grid arrangement;
said electrode being patterned to define M×
N compartments corresponding to said M×
N grid of reservoirs;
M×
N droplets which are deposited from said M×
N reservoirs onto said corresponding M×
N compartments, each said droplet originating from one of said reservoirs and remaining confined to one of said M×
N compartments and each said droplet containing at least one particle;
a top electrode positioned above said droplets so as to simultaneously contact each said droplet;
an electric field generator which generates an electric field between said top electrode and said M×
N droplets;
said electric field being used to form a particle array in each of said M×
N compartments, each said particle array remaining spatially confined to one of said M×
N droplets;
an illumination source which illuminates said M×
N compartments on said patterned electrode with a predetermined light pattern to maintain the position of said particle arrays in accordance with said predetermined light pattern and the pattern of M×
N compartments; and
said top electrode being positioned closer to said electrode thereby fusing said M×
N droplets into a continuous liquid phase, while maintaining each of said M×
N particle arrays in one of the corresponding M×
N compartments.
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62. An optical lens array including particles suspended at an interface between an electrode and an electrolyte solution, said lens array comprising:
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an electrode and an electrolyte solution having an interface therebetween;
a plurality of particles located in said electrolyte solution;
said electrode being patterned to include at least one area of modified impedance; and
an electric field generator which generates an electric field at said interface to cause said particles to assemble into an ordered array within said area of modified impedance.
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63. A method for forming a diffraction grating using particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps:
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providing an electrode and an electrolyte solution having an interface therebetween;
providing a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;
patterning said electrode to include at least one area of modified impedance; and
generating an electric field at said interface to cause said large and small particles to assemble into an array, said small particles being located between said large particles to create a large particle separation distance corresponding substantially to the size of said small particles, said large particle separation distance also determining the spatial frequency characteristics of said diffraction grating, said frequency characteristics being adjustable in dependence on the size of said small particles.
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64. A method for forming an optical display using particles suspended at an interface between an electrolyte solution and an electrode, said method comprising the following steps:
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providing an electrode and an electrolyte solution having an interface therebetween;
providing a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;
patterning said electrode to include at least one area of modified impedance;
generating an electric field at said interface causing said large particles to assemble in accordance with the impedance of said patterned electrode, said electric field generator generating a time varying electric field causing said small particles to selectively move under said large particles to form an on-pixel, and also causing said small particles to selectively move away from said large particles to form an off-pixel in accordance with a selected frequency of said time varying electric field.
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65. An apparatus for performing multiple chemical and biochemical analytical procedures using at least one particle array, said apparatus comprising:
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an electrode and an electrolyte solution having an interface therebetween;
an electric field generator which generates an electric field at an interface between an electrode and an electrolyte solution;
said electrode being patterned to modify the electrochemical properties of said electrode;
an illuminating source which illuminates said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode;
means for performing a first procedure on a portion of said particles to produce a first reaction set of particles;
means for isolating said first reaction set of particles in accordance with said predetermined light pattern; and
means for performing a second procedure on said first reaction set of particles to produce a second reaction set of particles.
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66. An apparatus for manipulating nucleic acid, including DNA or RNA, said apparatus comprising:
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an electrode, an electrolyte solution and an interface therebetween;
a plurality of nucleic acid molecules in said electrolyte solution, said nucleic acid molecules being in a coiled configuration;
an electric field generator which generates an electric field at said interface to cause the movement of said particles; and
said electrode being patterned to include areas of modified electrochemical properties which in conjunction with said electric field create controlled gradients in the flow velocity across the nucleic acid, said velocity gradient causing different portions of the nucleic acid to move at different velocities such that the nucleic acid is stretched in the direction of the local velocity gradient, wherein a stagnation point of zero velocity is maintained such that the nucleic acid is substantially fixed in position.
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Specification