Nucleic acid amplification utilizing microfluidic devices
First Claim
1. A microfluidic device, comprising:
- (a) a substrate comprising an elastomeric material;
(b) a flow channel disposed within the substrate, the flow channel configured such that a sample introduced into the flow channel can be cycled around the flow channel; and
comprising a plurality of temperature regions at which temperature can be regulated, each temperature region located at a different location along the flow channel;
(c) an inlet in fluid communication with the flow channel via which the sample can be introduced into the flow channel; and
(d) a temperature controller operatively disposed to regulate temperature within at least one of the plurality of temperature regions.
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Accused Products
Abstract
The present invention provides microfluidic devices and methods using the same in various types of thermal cycling reactions. Certaom devices include a rotary microfluidic channel and a plurality of temperature regions at different locations along the rotary microfluidic channel at which temperature is regulated. Solution can be repeatedly passed through the temperature regions such that the solution is exposed to different temperatures. Other microfluidic devices include an array of reaction chambers formed by intersecting vertical and horizontal flow channels, with the ability to regulate temperature at the reaction chambers. The microfluidic devices can be used to conduct a number of different analyses, including various primer extension reactions and nucleic acid amplification reactions.
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Citations
99 Claims
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1. A microfluidic device, comprising:
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(a) a substrate comprising an elastomeric material;
(b) a flow channel disposed within the substrate, the flow channel configured such that a sample introduced into the flow channel can be cycled around the flow channel; and
comprising a plurality of temperature regions at which temperature can be regulated, each temperature region located at a different location along the flow channel;
(c) an inlet in fluid communication with the flow channel via which the sample can be introduced into the flow channel; and
(d) a temperature controller operatively disposed to regulate temperature within at least one of the plurality of temperature regions. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A microfluidic device, comprising
(a) a substantially circular microfabricated flow channel in fluid communication with an inlet; -
(b) a plurality of temperature regions, each region located at a different location along the substantially circular flow channel; and
(c) a temperature controller operatively disposed to regulate the temperature within at least one of the plurality of temperature regions.
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21. A method for conducting an analysis, the method comprising:
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(a) providing a microfluidic device, comprising (i) a substrate comprising an elastomeric material;
(ii) a flow channel disposed within the substrate, the flow channel configured such that a sample introduced into the flow channel can be cycled around the flow channel; and
comprising a plurality of temperature regions at which temperature can be regulated, each temperature region located at a different location along the flow channel;
(b) introducing a sample into the flow channel; and
(c) transporting the sample between the different temperature regions. - View Dependent Claims (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, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94)
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49. A microfluidic device, comprising
(a) a substrate comprising an elastomeric material; -
(b) a first plurality of flow channels formed within the substrate;
(c) a second plurality of flow channels, each formed within the substrate and in fluid communication with an inlet, the second flow channels intersecting the first flow channels to define an array of reaction chambers;
(d) isolation valves selectively actuatable to block flow between junctions along at least one of the first and second flow channels, and to regulate solution flow to the reaction chambers; and
(e) a plurality of temperature regions located along each of the second plurality of microfabricated flow channels; and
(f) a temperature controller operatively disposed to regulate temperature at one or more of the temperature regions.
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67. A method for conducting an analysis, the method comprising:
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(a) providing a microfluidic device, comprising (i) a substrate comprising an elastomeric material;
(ii) a first plurality of flow channels formed within the substrate;
(iii) a second plurality of microfabricated flow channels formed within the substrate and in fluid communication with an inlet, the second flow channels intersecting the first flow channels to define an array of reaction chambers;
(iv) isolation valves selectively actuatable to block flow between reaction chambers along at least one of the first and second flow channels, and to regulate solution flow to the reaction chambers; and
(b) introducing a sample and one or more reactants into the reaction chambers by selective actuation of one or more of the isolation valves, whereby reaction between the sample and the one or more reactants can occur; and
(c) heating regions of the microfluidic device to promote reaction between the sample and the one or more reactants within the reaction chambers.
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95. A temperature controller, comprising
(a) a plate assembly comprising a first plate and a second plate that are separated from one another by a separation material, the separation material forming a fluid-tight seal around the periphery of the plates, the space between the plates and bounded by the separation material defining a chamber; -
(b) an inlet assembly located at a first end region of the plate assembly and in fluid communication with the chamber; and
(c) an outlet assembly located at a second end region of the plate assembly opposite the first end region and in fluid communication with the chamber such that fluid in the chamber can exit therefrom via the outlet assembly, wherein a region located between the inlet and outlet assembly and adjacent or abutting a surface of the first plate is adapted to receive a microfluidic chip;
the first and second plate comprise a transparent region that permits optical detection of the microfluidic chip; and
the top plate is less than 100 microns thick. - View Dependent Claims (96)
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97. A temperature controller, comprising
(a) a plate assembly comprising (i) a hinged assembly that comprises a first plate and a second plate that are hingeably connected, such that the first plate can be moved toward or away from an upper face of the second plate; -
(ii) a third plate (iii) a separation material that separates a lower face of the second plate opposite the upper face from the third plate and forms a fluid-tight seal therebetween;
(iv) a chamber formed by the space between the lower face of the second plate and the third plate and being bounded by the separation material; and
(v) a pair of holes, one hole being located in the first plate and the other hole being located in the second plate, the holes positioned such that when the first plate is folded onto the second plate, the pair of holes are aligned;
(b) an inlet assembly located at a first end region of the plate assembly and in fluid communication with the chamber; and
(c) an outlet assembly located at a second end region of the plate assembly opposite the first end region and in fluid communication with the chamber such that fluid in the chamber can exit therefrom via the outlet assembly, wherein the hinged assembly is adapted to receive a microfluidic chip between the first and second plate. - View Dependent Claims (98)
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99. A microfluidic device, comprising
(a) a substrate comprising an elastomeric material; -
(b) a first plurality of flow channels formed within the substrate;
(c) a second plurality of flow channels, each formed within the substrate and in fluid communication with an inlet, the second flow channels intersecting the first flow channels to define an array of reaction chambers; and
(c) isolation valves selectively actuatable to block flow between junctions along at least one of the first and second flow channels, and to regulate solution flow to the reaction chambers, wherein the isolation valves comprise a first and second isolation valve that have differing activation thresholds.
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Specification