MULTIPLEXED MOLECULAR ANALYSIS SYSTEMS
First Claim
1. A device for preparing a reaction substrate for conducting multiplexed microassays to determine binding between a target analyte and a capture probe, including:
- a plurality of capillary tubes, each tube having a proximal end and a distal end;
an attachment site for holding said capillary tubes at a point spaced from the distal ends of such capillary tubes;
an array template for slidably holding each capillary tube near its distal end, and for allowing the distal end of each capillary tube to move with respect to the attachment site;
at least one manifold for positioning the proximal end of each capillary tube within a corresponding supply chamber, wherein each supply chamber is capable of supplying a liquid reagent to at least one corresponding capillary tube; and
a positioning device for precisely positioning the array template and said capillary tubes with respect to said reaction substrate and depositing liquid reagents from said capillary tubes onto said reaction substrate as biosites.
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Accused Products
Abstract
A method and apparatus for analyzing molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. The invention is also directed to a method and apparatus for constructing molecular arrays having a plurality of test sites. The invention allows for definitive high throughput analysis of multiple analytes in complex mixtures of sample substances. A combinatorial analysis process is described that results in the creation of an array of integrated chemical devices. These devices operate in parallel, each unit providing specific sets of data that, when taken as a whole, give a complete answer for a defined experiment. This approach is uniquely capable of rapidly providing a high density of information from limited amounts of sample in a cost-effective manner.
97 Citations
92 Claims
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1. A device for preparing a reaction substrate for conducting multiplexed microassays to determine binding between a target analyte and a capture probe, including:
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a plurality of capillary tubes, each tube having a proximal end and a distal end; an attachment site for holding said capillary tubes at a point spaced from the distal ends of such capillary tubes; an array template for slidably holding each capillary tube near its distal end, and for allowing the distal end of each capillary tube to move with respect to the attachment site; at least one manifold for positioning the proximal end of each capillary tube within a corresponding supply chamber, wherein each supply chamber is capable of supplying a liquid reagent to at least one corresponding capillary tube; and a positioning device for precisely positioning the array template and said capillary tubes with respect to said reaction substrate and depositing liquid reagents from said capillary tubes onto said reaction substrate as biosites. - 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)
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- 25. A reaction substrate for conducting multiplexed microassays to determine binding of a target molecule and a capture probe/target probe complex, said reaction substrate including an array of biosites, each biosite comprising a single type of capture probe bound to said substrate, each capture probe capable of binding to a corresponding target probe having a capture probe specific domain which specifically binds with a corresponding capture probe, and a target analyte specific domain which specifically binds with a target analyte.
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40. The reaction substrate of claim 40, further including a reaction vessel, wherein a plurality of reaction chambers are contained within said reaction vessel.
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55. A reaction substrate for use in conducting multiplexed microassays to determine binding between a target molecule and a capture probe, said reaction substrate having an array of parallel printed biosites, wherein each biosite comprises a single type of capture probe bound to said reaction substrate.
- 56. A method for preparing a reaction substrate for use as an assay device, comprising the step of parallel printing an array of biosites on said reaction substrate, wherein each biosite comprises a single type of capture probe bound to said reaction substrate.
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60. A method for identifying target analytes in a plurality of separate samples, each target analyze capable of binding a corresponding capture probe, including the steps of parallel printing an array of biosites on a reaction substrate, each biosite comprising a single type of capture probe bound to said substrate;
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contacting each biosite with a sample including at least one target analyze; and determining the presence or absence of binding of a target analyte at each biosite in said array. - View Dependent Claims (61, 62, 63, 64, 65, 66, 67)
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68. An apparatus for preparing a reaction substrate for use as an assay device, including:
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an attachment site for holding a plurality of flexible capillary tubes at a point spaced from the distal ends of such capillary tubes; a structure for positioning the proximal end of each capillary tube within a corresponding supply chamber, each supply chamber capable of supplying a liquid reagent to at least one corresponding capillary tube; a print head for holding said plurality of capillary tubes near their distal ends and for precisely positioning the distal ends of said capillary tubes with respect to said reaction substrate to deposit liquid reagents onto said reaction substrate as biosites. - View Dependent Claims (69)
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70. A method for detecting labeled sample molecules, comprising the steps of:
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providing a reaction substrate having a plurality of biosites, each biosite being attached to the reaction substrate, the reaction substrate having an embedded conductive maternal connected to an electrical source; contacting each biosite with a sample of labeled molecules; initiating an electrochemical event within the labeled molecules which releases electromagnetic energy; detecting the released electromagnetic energy. - View Dependent Claims (71, 72, 73, 74, 75)
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76. A method for detecting particle emissions from labeled sample molecules, comprising the steps of:
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providing a reaction substrate having a plurality of biosites, each biosite comprising a single type of capture probe bound to said substrate; providing a lensless array of particle detectors disposed in close proximity to said plurality of biosites; contacting each biosite with a sample of labeled molecules; converting, in said particle detectors, particle emissions emanating directly from said sample into corresponding electrical signals; forming an image from said electric signals representing the quantitative presence or absence of the labeled molecules on each biosite from said sample. - View Dependent Claims (77, 78, 79)
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- 80. A set of nucleic acid capture probes, each configured to be bound to a reaction substrate, each capture probe having a length sufficient to provide dissimilarity among capture probes, each capture probe having a percentage base composition in the range of about 30-40% G, 30-40% C, 10-20% A, and 10-20% T, wherein the set is selected such that the nucleic acid sequence of each capture probe in the set is substantially dissimilar from the nucleic acid sequence of all other capture probes in the set.
Specification