Devices and methods for enrichment and alteration of cells and other particles
First Claim
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1. A device for producing a sample enriched in an analyte, said device comprising:
- (a) a first channel comprising a structure that deterministically deflects particles having a hydrodynamic size above a critical size in a direction not parallel to the average direction of flow in said structure, wherein said particles are analyte particles or are a non-analyte component of said sample; and
(b) a reservoir fluidly coupled to an output of said first channel through which said analyte passes into said reservoir, wherein said reservoir comprises a reagent that alters a magnetic property of said analyte.
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Abstract
The invention features a device for the deterministic separation of analytes coupled to a reservoir containing a reagent that alters a magnetic propert of the analyte. Exemplary methods include the enrichment of a sample in a desired analyte (e.g., using deterministic separation) or the alteration of a desired analyte in the device. The devices and methods may be advantageously employed to enrich for rare cells, e.g., fetal cells or epithelial cells, present in a sample, e.g., maternal blood.
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Citations
43 Claims
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1. A device for producing a sample enriched in an analyte, said device comprising:
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(a) a first channel comprising a structure that deterministically deflects particles having a hydrodynamic size above a critical size in a direction not parallel to the average direction of flow in said structure, wherein said particles are analyte particles or are a non-analyte component of said sample; and
(b) a reservoir fluidly coupled to an output of said first channel through which said analyte passes into said reservoir, wherein said reservoir comprises a reagent that alters a magnetic property of said analyte. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A method for producing a sample enriched in a first analyte relative to a second analyte, said method comprising:
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(a) applying at least a portion of said sample to a device comprising a structure that deterministically deflects particles having a hydrodynamic size above a critical size in a direction not parallel to the average direction of flow in said structure, thereby producing a second sample enriched in said first analyte and comprising said second analyte;
(b) combining said second sample with a reagent that alters a magnetic property of said first analyte to produce an altered first analyte; and
(c) applying a magnetic field to said second sample, wherein said magnetic field generates a differential force to physically separate said altered first analyte from said second analyte, thereby producing a sample enriched in said first analyte. - View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method of producing a sample enriched in red blood cells relative to a second blood component, said method comprising:
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(a) contacting a sample comprising red blood cells with a reagent that oxidizes iron to produce oxidized hemoglobin; and
(b) applying a magnetic field to said sample, wherein said red blood cells having oxidized hemoglobin are attracted to said magnetic field to a greater extent than said second blood component, thereby producing said sample enriched in said red blood cells. - View Dependent Claims (36, 37, 38, 39, 40)
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41. A device for producing a sample enriched in red blood cells, said device comprising:
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(a) an analytical device that enriches said red blood cells based on size, shape, deformability, or affinity; and
(b) a reservoir comprising a reagent that oxidizes iron, wherein said reagent increases the magnetic responsiveness of said red blood cells. - View Dependent Claims (42, 43)
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Specification