High throughput screening assay systems in microscale fluidic devices
First Claim
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1. A method of screening a plurality of test compounds for an effect on a biochemical system, comprising:
- providing a substrate having at least a first surface, and at least two intersecting channels fabricated in said first surface, at least one of said at least two intersecting channels having at least one cross-sectional dimension in a range from 0.1 to 500 μ
m;
flowing a first component of a biochemical system in a first of said at least two intersecting channels;
flowing at least a first test compound from a second channel into said first channel whereby said first test compound contacts said first component of said biochemical system; and
detecting an effect of said at least first test compound on said biochemical system.
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Abstract
The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.
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Citations
74 Claims
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1. A method of screening a plurality of test compounds for an effect on a biochemical system, comprising:
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providing a substrate having at least a first surface, and at least two intersecting channels fabricated in said first surface, at least one of said at least two intersecting channels having at least one cross-sectional dimension in a range from 0.1 to 500 μ
m;
flowing a first component of a biochemical system in a first of said at least two intersecting channels;
flowing at least a first test compound from a second channel into said first channel whereby said first test compound contacts said first component of said biochemical system; and
detecting an effect of said at least first test compound on said biochemical system. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 60, 61)
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12. A method of screening a plurality of test compounds for an effect on a biochemical system, comprising:
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providing a substrate having at least a first surface, and at least two intersecting channels fabricated in said first surface, at least one of said at least two intersecting channels having at least one cross-sectional dimension in a range from 0.1 to 500 μ
m;
continuously flowing a first component of a biochemical system in a first channel of said at least two intersecting channels;
periodically introducing a different test compound into said first channel from a second channel of said at least two intersecting channels; and
detecting an effect of said test compound on said at least first component of a biochemical system.
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24. A method of screening a plurality of different test compounds for an effect on a biochemical system, comprising:
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providing a substrate having at least a first surface, and a plurality of reaction channels fabricated in said first surface, each of said plurality of reaction channels being fluidly connected to at least two transverse channels fabricated in said surface;
introducing at least a first component of a biochemical system into said plurality of reaction channels;
flowing a plurality of different test compounds through at least one of said at least two transverse channels, each of said plurality of test compounds being introduced into said at least one transverse channels in a discrete volume;
directing each of said plurality of different test compounds into a separate one of said plurality of reaction channels; and
detecting an effect of each of said test compounds on said at least one component of said biochemical system.
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37. An apparatus for screening test compounds for an effect on a biochemical system, comprising:
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a substrate having at least one surface;
at least two intersecting channels fabricated into said surface of said substrate, at least one of said at least two intersecting channels having at least one cross-sectional dimension in the range from about 0.1 to about 500 μ
m;
a source of a plurality different test compounds fluidly connected to a first of said at least two intersecting channels;
a source of at least one component of said biochemical system fluidly connected to a second of said at least two intersecting channels;
a fluid direction system for flowing said at least one component within said second of said at least two intersecting channels and for introducing said different test compounds from said first to said second of said at least two intersecting channels;
a cover mated with said surface; and
a detection zone in said second channel for detecting an effect of said test compound on said biochemical system.
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54. An apparatus for detecting an effect of a test compound on a biochemical system, comprising:
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a substrate having at least one surface;
a plurality of reaction channels fabricated into said surface;
at least two transverse channels fabricated into said surface, each of said plurality of reaction channels being fluidly connected to a first of said at least two transverse channels at a first point in said reaction channels, and fluidly connected to a second of said at least two transverse channels at a second point in said reaction channels, said at least two transverse channels and said plurality of reaction channels each having at least one cross-sectional dimension in the range from about 0.1 to about 500 μ
m;
a source of at least one component of said biochemical system, said source of at least one component of said biochemical system being fluidly connected to each of said plurality of reaction channels;
a source of test compounds fluidly connected to said first of said at least two transverse channels;
a fluid direction system for controlling movement of said test compound and said at least one component within said at least two transverse channels and said plurality of reaction channels;
a cover mated with said surface; and
a detection system for detecting an effect of said test compound on said biochemical system. - View Dependent Claims (55, 56, 57, 58, 59, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)
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Specification