ANALYSIS OF RARE CELL-ENRICHED SAMPLES
First Claim
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1. A method for detecting cancer in a subject comprising:
- enriching a sample from said subject for rare cells by flowing said sample through an array of obstacles coated with antibodies that specifically bind to one or more cell populations in said sample to obtain a rare cell-enriched sample, wherein said rare cells in said sample are in a concentration of less than 1 in 100,000 cells prior to said enrichment, anddetecting the presence or absence of a rare cell nucleic acid in said rare cell-enriched sample, wherein the presence of said rare cell nucleic acid in said rare cell-enriched sample indicates the presence of said cancer in said subject.
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Abstract
The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g., epithelial cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject by analyzing a cellular sample from the subject.
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Citations
47 Claims
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1. A method for detecting cancer in a subject comprising:
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enriching a sample from said subject for rare cells by flowing said sample through an array of obstacles coated with antibodies that specifically bind to one or more cell populations in said sample to obtain a rare cell-enriched sample, wherein said rare cells in said sample are in a concentration of less than 1 in 100,000 cells prior to said enrichment, and detecting the presence or absence of a rare cell nucleic acid in said rare cell-enriched sample, wherein the presence of said rare cell nucleic acid in said rare cell-enriched sample indicates the presence of said cancer in said subject. - 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, 25)
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26. A method for detecting cancer in a subject comprising:
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(i) enriching a sample from said subject for rare cells by flowing said sample through an array of obstacles that selectively directs cells smaller than a predetermined size to a first outlet and cells equal to or larger than said predetermined size to a second outlet to obtain a first rare cell-enriched sample, wherein said rare cells in said sample are in a concentration of less than 1 in 100,000 cells; (ii) flowing said first rare cell-enriched sample through an array of obstacles coated with antibodies that specifically bind to one or more cell populations in said sample to obtain a second rare cell-enriched sample; and (iii) detecting the presence or absence of a rare cell nucleic acid in said second rare-cell enriched sample, wherein the presence of said rare cell nucleic acid in said second rare-cell enriched sample indicates the presence of said cancer in said subject. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33)
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34. A method for determining cancer treatment efficacy in a patient, comprising:
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(i) enriching, for epithelial cells, each of a plurality of blood samples from said patient by flowing each blood sample in said plurality through an array of obstacles coated with one or more antibodies that specifically bind to epithelial cells to obtain a plurality of epithelial cell-enriched blood samples, wherein said plurality of blood samples was generated by obtaining a blood sample from said patient at a series of time points during said cancer treatment, and said series of time points includes at least a first time point at the beginning of said treatment and at least two points subsequent to said first time point; (ii) quantifying in each epithelial-cell enriched sample of said plurality, the expression level of at least one gene expressed in epithelial cells and not expressed in other cells present in blood, to obtain a temporal expression profile for said at least one gene in said plurality of epithelial cell-enriched blood samples; and (iii) determining that said cancer treatment is efficacious if said temporal expression profile indicates a decreasing trend of expression levels for said at least one gene. - View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42)
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43. A kit for detecting cancer cells in a subject, comprising a device comprising an array of obstacles coated with antibodies that specifically bind to one or more cell populations and a set of reagents for detecting the expression of a gene identified in
FIG. 5 .
Specification