Method and apparatus based on bundled capillaries for high throughput screening
First Claim
1. A high throughput screening apparatus for ultra high throughput screening of chemical compounds for a biological target, comprising a substrate having a plurality of channels, wherein each of said channels has a first end at a first face of the apparatus and wherein each of said channels has a second end, each said first end being one of a plurality of first ends and each said second end being one of a plurality of second ends, wherein the first ends of said channels are secured to a plurality of reaction chambers such that at least one of said first ends is in fluid communication with a different reaction chamber from at least one other of said first ends.
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Abstract
Disclosed are systems and methods involved in extreme high throughput screening of compounds which have an affinity for a biological target. The system is based on a capillary bundle with two distinguishable ends wherein capillaries on one end are connected to compounds stored in discrete reservoirs and capillaries on the other end are bound and processed to form a two dimensional microarray. A capillary bundle having reaction wells for hybridization and compound reaction in one end of the capillaries is disclosed. The capillaries may be light-conducting. Also disclosed are various methods of identifying a target compound in a liquid using this capillary bundle as well as methods of fabricating the bundle.
A novel surface tension guided reaction chamber is also provided. Methods and chemistry for fabrication and use of a surface tension guided reaction chamber in binding and hybridization assays are also disclosed. Methods and systems for precise metering of fluids within the capillaries and at the reaction chambers, including the surface tension guided “virtual” reaction well is provided. Methods for performing high throughput screens using optical fiber lined capillaries of the invention are also provided. The capillary arrays are used with both liquid probes as well as probes immobilized on the walls of the capillary.
143 Citations
62 Claims
- 1. A high throughput screening apparatus for ultra high throughput screening of chemical compounds for a biological target, comprising a substrate having a plurality of channels, wherein each of said channels has a first end at a first face of the apparatus and wherein each of said channels has a second end, each said first end being one of a plurality of first ends and each said second end being one of a plurality of second ends, wherein the first ends of said channels are secured to a plurality of reaction chambers such that at least one of said first ends is in fluid communication with a different reaction chamber from at least one other of said first ends.
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39. A method of fabricating a high throughput screening apparatus comprising
(a) forming a substrate having channels that terminate in a first face; - and
(b) forming a plurality of reaction chambers at the first face such that at least one of said channels is in fluid communication with a different reaction chamber from at least one other of said channels. - View Dependent Claims (41, 42, 43, 44, 45, 46, 47, 48)
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- 50. A method of metering a volume of a liquid comprising placing a first liquid having a surface tension suitable to form a droplet of predetermined volume in a hydrophilic region and a hydrophobic region of a substrate, which hydrophobic region surrounds said hydrophilic region, and removing the first liquid from the hydrophobic region.
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55. A method for determining an affinity of a compound for a receptor, the method comprising:
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(a) immobilizing the receptor on a wall defining a channel of an array of channels;
(b) binding to the receptor a saturating amount of ligand specific for the receptor;
(c) contacting the array with an excess of said compound; and
(d) measuring a rate of displacement of bound ligand by the compound. - View Dependent Claims (56, 57, 58, 60, 61)
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59. A method for determining an affinity of a compound for a receptor, the method comprising:
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(a) immobilizing the receptor on a wall defining a channel of an array of channels;
(b) binding to the receptor a mixture of a saturating amount of a ligand specific for the receptor and a saturating amount of a compound; and
(c) measuring a ratio of bound ligand to bound compound. - View Dependent Claims (62)
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Specification