Arrays comprising pre-labeled biological molecules and methods for making and using these arrays
First Claim
1. An array comprising a plurality of biological molecules, wherein each biological molecule is immobilized to a discrete and known spot on a substrate surface to form an array of biological molecules, and the biological molecule comprises a detectable label.
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Abstract
The invention provides arrays comprising a plurality of biological molecules, wherein each biological molecule is immobilized to a discrete and known spot on a substrate surface to form an array of biological molecules, and each biological molecule comprises a detectable label. The invention provides a multiplexed system for performing comparative genomic hybridization (CGH) using an array of the invention. The invention also provides methods of making and using these arrays, including a method of comparing copy numbers of unique nucleic acid sequences in a sample.
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Citations
81 Claims
- 1. An array comprising a plurality of biological molecules, wherein each biological molecule is immobilized to a discrete and known spot on a substrate surface to form an array of biological molecules, and the biological molecule comprises a detectable label.
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- 57. An array comprising a plurality of bacterial artificial chromosomes (BACs), wherein each bacterial artificial chromosome is immobilized to a discrete and known spot on a substrate surface to form an array of bacterial artificial chromosomes (BACs), and each bacterial artificial chromosome comprises a detectable label.
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60. A method of making an array, wherein the array comprises a plurality of genomic nucleic acids covalently labeled with a compound comprising a fluorescent label, comprising
labeling the plurality of genomic nucleic acid segments, wherein the segments have lengths averaging between about 50 kilobases and about 500 kilobases or are fragmented or digested to have lengths averaging between about 50 kilobases and about 500 kilobases, with a fluorescent label; - and
immobilizing the labeled nucleic acids to discrete and known spots on a substrate surface to form an array of nucleic acids. - View Dependent Claims (61, 62, 63, 64, 65, 66, 67, 68, 69)
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70. A method of performing comparative genomic hybridization (CGH) using an array comprising a plurality of genomic nucleic acids covalently labeled with a compound comprising a detectable label, comprising:
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contacting an array comprising a plurality of cloned genomic nucleic acid segments, wherein each genomic nucleic acid segment is immobilized to a discrete and known spot on a substrate surface to form an array, and the genomic nucleic acid segments comprise a first detectable label, with a sample comprising a plurality of genomic nucleic acid segments, wherein the sample genomic nucleic acid segments are labeled with at least a second detectable label;
under conditions wherein the nucleic acid in the sample can specifically hybridize to the genomic nucleic acid segments andmeasuring an amount of the first and the second fluorescent label on each spot, thereby performing comparative genomic hybridization. - View Dependent Claims (71, 72, 73, 74, 75, 76)
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77. A method of comparing copy numbers of unique nucleic acid sequences in a first sample comprising nucleic acid sequences of a first cell or cell population relative to copy numbers of substantially identical sequences in at least a second sample comprising nucleic acid sequences of at least a second cell or cell population, wherein the nucleic acids of the first sample comprise a first detectable label, and the nucleic acids of the second sample comprise a second detectable label, said method comprising:
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contacting an array comprising the nucleic acid sequences of the first sample, wherein the nucleic acid sequences of the first sample are immobilized to discrete and known spots on a substrate surface to form an array, with a second sample comprising nucleic acid sequences of the second sample;
under conditions wherein the nucleic acid sequences in the second sample can specifically hybridize to the immobilized nucleic acid sequences of the first sample; and
comparing the intensities of the signals from the nucleic acids sequences of the second sample to the nucleic acid sequences of the second sample, thereby comparing copy numbers of unique nucleic acid sequences in the first sample compared to the second sample.
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78. A multiplexed system for performing comparative genomic hybridization (CGH) using an array comprising:
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the array comprising a plurality of biological molecules, wherein the biological molecule is immobilized to a discrete and known spot on a substrate surface to form the array of biological molecules, and each biological molecule comprises a first detectable label;
a device for detecting the immobilized first detectable label and at least a second detectable label, wherein the device can measure the first and the second detectable labels on the spots on the substrate surface. - View Dependent Claims (79, 80, 81)
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Specification