Manipulation of microparticles in microfluidic systems
DCFirst Claim
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1. A microfluidic device, comprising:
- a body structure having a microscale cavity disposed therein; and
an ordered array of a plurality of sets of particles disposed within the microscale cavity, wherein said sets of particles are flowable, and wherein at least one of the sets of particles is retained in position within the microscale cavity, wherein the plurality of particles sets comprises a first particle set which is retained in position abutting a second particle set, which is retained in position by contacting the first particle set.
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Abstract
Arrays of flowable or fixed particle sets are used in microfluidic systems for performing assays and modifying hydrodynamic flow. Also provided are assays utilizing flowable or fixed particle sets within a microfluidic system, as well as kits, apparatus and integrated systems comprising arrays and array members.
858 Citations
71 Claims
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1. A microfluidic device, comprising:
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a body structure having a microscale cavity disposed therein; and
an ordered array of a plurality of sets of particles disposed within the microscale cavity, wherein said sets of particles are flowable, and wherein at least one of the sets of particles is retained in position within the microscale cavity, wherein the plurality of particles sets comprises a first particle set which is retained in position abutting a second particle set, which is retained in position by contacting the first particle set. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
members of the sets of particles are beads selected from: - polymer beads, silica beads, ceramic beads, clay beads, glass beads, magnetic beads, metauic beads, inorganic beads, and organic beads; and
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wherein the shape of the beads is selected from one or more of;
spherical, helical, spheroid, irregular, rod-shaped, cone-shaped, cubic, and polyhedral.
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33. The microfluidic device of claim 1, wherein particles forming the sets of particles are about 0.1 mm to about 500 mm in at least one cross-sectional dimension.
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34. The microfluidic device of claim 33, wherein particles forming the sets of particles are about 0.5 mm to about 50 mm in at least one cross-sectional dimension.
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35. The microfluidic device of claim 34, wherein particles forming the sets of particles are about 1 mm to about 20 mm in at least one cross-sectional dimension.
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36. The microfluidic device of claim 1, wherein the sets of particles are coupled to one or more of:
- a nucleic acid synthesis reagent, a peptide synthesis reagent, a polymer synthesis reagent, a nucleic acid, a nucleic acid template, a primer, a nucleatide, a nucleotide analog, a nucleobase, a nucleoside, a nucleoside analog, a fluorescently labeled nucleotide, a peptide, an amino acid, a monomer, an intercalating dye, a cell, a biological sample, and a synthetic molecule.
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37. The microfluidic device of claim 1, wherein the sets of particles comprise one or more set of one or more of:
- blank particles, calibration particles, marker particles, sample particles, reagent particles and test particles.
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38. The microfluidic device of claim 37, wherein the marker particles or the calibration particles comprise a charged bead or a charged particle.
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39. The microfluidic device of claim 38, wherein the marker particles or the calibration particles further comprise a label moiety.
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40. The microfluidic device of claim 39, wherein the label moiety is a fluorescent dye.
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41. The microfluidic device of claim 37, wherein the marker particles or the calibration particles comprise a neutral particle.
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42. The microfluidic device of claim 41, wherein the marker particle further comprises a charged label moiety.
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43. The microfluidic device of claim 37, wherein the marker particles or the calibration particles comprise a DNA molecule or an RNA molecule.
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44. The microfluidic device of claim 43, wherein the DNA molecule or the RNA molecule comprises at least about thousand to about thousand base pairs.
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45. The microfluidic device of claim 1, wherein the array is mobile.
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46. The microfluidic device of claim 1, wherein the array is flowable.
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47. The microfluidic device of claim 1, the microscale cavity comprising an array channel comprising the array, the microfluidic device comprising a fluid transport system which directs particle movement within the array channel.
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48. The microfluidic device of claim 1, the microscale cavity comprising an array channel comprising the array, the microfluidic device comprising movement means for moving the array within the array channel.
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49. The microfluidic device of claim 48, the movement means comprising one or more of:
- a fluid pressure source for modulating fluid pressure in the array channel, an electrokinetic controller for modulating voltage or current in the array channel, a gravity flow modulator, a centrifugal field, and a magnetic control element for modulating magnetic field within the array channel.
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50. The microfluidic device of claim 1, further comprising a detector positioned to simultaneously monitor a plurality of signals from the plurality of particle sets.
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51. The microfluidic device of claim 50, wherein the detector detects one or more signal selected from:
- fluorescence, phosphorescence, radioactivity, pH, charge, absorbance, luminescence, temperature and magnetism.
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52. The microfluidic device of claim 50, wherein the plurality of signals comprises a plurality of optical signals, wherein the optical signals correspond in position to sets of particles within the array.
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53. The microfluidic device of claim 50, wherein the detector is a charge coupled device (CCD) array positioned to simultaneously monitor the plurality of sets of particles of the array.
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54. The microfluidic device of claim 50, wherein the detector is selected from:
- a plurality of photo multiplier tubes, a charge coupled device (CCD) array, and a scanning detector.
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55. The microfluidic device of claim 1, the microfluidic device further comprising a signal detector, wherein, during operation of the device, the plurality of sets of particles is flowed past the detector, wherein one or more of the sets of particles emits a detectable signal which is detected by the detector.
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56. The microfluidic device of claim 1, the microfluidic device further comprising a detector operably linked to a computer, which computer comprises software for one or more of:
- converting detector signal information into nucleic acid sequence information, converting detector signal information into reaction kinetic information, converting signal information into antibody binding data, converting signal information into cell receptor binding data and converting signal information into hybridization data.
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57. The microfluidic device of claim 1, the microscale cavity comprising a serial stream to parallel stream fluidic converter, which converter permits conversion of at least one serial stream of reagents into parallel streams of reagents for parallel delivery of reagents to a reaction site within the microscale cavity.
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58. The microfluidic device of claim 1, wherein the ordered array of a plurality of sets of particles is produced by flowing a substantially homogeneous or heterogeneous set of particles into a particle modification region and flowing a plurality of particle modification reagents across the substantially homogeneous or heterogeneous set of particles, which reagents react with the substantially homogeneous or heterogeneous set of particles to create a plurality of sets of different particles.
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59. The microfluidic device of claim 58, wherein the homogeneous or heterogeneous set of particles comprises a plurality of particles comprising a tag.
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60. The microfluidic device of claim 58, wherein the homogeneous or heterogeneous set of particles comprises a plurality of particles comprising a tag, wherein the plurality of particle modification reagents comprises an anti-tag ligand, wherein the plurality of particle modification reagents are flowed sequentially across the substantially homogeneous set of particles, thereby binding the anti-tag ligand to the tag and producing the sets of different particles, each set comprising a different bound particle modification reagent.
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61. The microfluidic device of claim 60, wherein at least one of the particle modification reagents comprise a nucleic acid.
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62. The microfluidic device of claim 60, wherein the tag or anti tag ligand comprise.one or more of streptavidin, biotin, an antibody, an antibody ligand, a nucleic acid or a nucleic acid binding molecule.
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63. The microfluidic device of claim 58, wherein the plurality of sets of particles comprise a plurality of particles having at least one linker moiety attached thereto.
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64. A system for optimizing and performing a desired chemical reaction, comprising:
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a microfluidic device which includes a microscale cavity having a particle array disposed therein, the particle array comprising a plurality of particle sets, wherein at least one of the particle sets is retained in position within the microscale device wherein the plurality of particles sets comprises a first particle set which is retained in position abutting a second particle set, which is retained in position by contacting the first particle set;
an electrokinetic, centrifugal, or pressure based fluid direction system for transporting a selected volume of a first reactant to the array, or for reconfiguring the position of the array or for reconfiguring the arrangement of array members;
a control system which instructs the fluid direction system to move members of the array into proximity with the first reactant, wherein mixing of the first reactant and at least one member of the array produces a first chemical reaction product; and
,a detection system for detecting the first chemical reaction product. - View Dependent Claims (65, 66, 67, 68, 69)
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70. A microfluidic device, comprising:
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a body structure having a microscale cavity disposed therein; and
a set of particles disposed within the microscale cavity, wherein said sets of particles is flowable, and wherein the microscale cavity comprises a first microchannel comprising at least one reagent flow region and at least one particle capture region, wherein the at least one particle capture region has an increased depth relative to the at least one reagent flow region.
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71. A microfluidic device, comprising:
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a body structure having a mcroscale cavity disposed therein; and
at least one set of particles disposed within the microscale cavity, wherein said at least one set of particles is flowable, and wherein the microscale cavity comprises a plurality of microchannels, the cavity further comprising a fluid movement region transverse to at least one of the plurality of microchannels, at least one of the plurality of microchannels comprising a deep channel region within the fluid movement region, which deep channel region has an increased depth dimension relative to the fluid movement region, thereby providing a site for collecting said at least one of particles set within the deep channel region.
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Specification