Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems
First Claim
1. A device for detecting the presence of an analyte in a fluid sample, the device comprising:
- a solid substrate microfabricated to define;
a sample inlet port, said port being dimensioned for connection to a pump means; and
a mesoscale flow system comprising;
a sample flow channel extending from said inlet port; and
an analyte binding region in fluid communication with said flow channel comprising a binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds to analyte in said fluid sample, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and
a binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting binding of said analyte to said binding moiety.
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Abstract
Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.
1312 Citations
44 Claims
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1. A device for detecting the presence of an analyte in a fluid sample, the device comprising:
a solid substrate microfabricated to define; a sample inlet port, said port being dimensioned for connection to a pump means; and a mesoscale flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds to analyte in said fluid sample, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting binding of said analyte to said binding moiety. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A device for detecting the presence of an analyte in a fluid sample, the device comprising:
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a solid substrate microfabricated to define; a sample inlet port; and a mesoscale flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety immobilized on a surface of said analyte binding region, wherein said binding moiety specifically binds to analyte in said sample, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; a pump means for delivering to said analyte binding region a labelled substance which binds analyte bound to said binding moiety to produce an optically detectable signal indicative of the presence of said analyte; and a binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting said optically detectable signal, thereby to determine the presence of the analyte. - View Dependent Claims (16, 17, 18)
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19. A device for detecting the presence of multiple analytes in a fluid sample, the device comprising:
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a solid substrate microfabricated to define; a sample inlet port; and a first and at least a second mesoscale flow system, each said flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds to analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a binding means associated with each analyte binding region or in fluid communication with each analyte binding region for detecting the binding of analyte to the binding moiety in each analyte binding region, thereby to determine the presence of said analyte; and wherein the analyte binding regions of said flow systems comprise different immobilized binding moieties capable of binding different analytes.
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20. A device for detecting the presence of an analyte in a fluid sample, the device comprising:
a solid substrate microfabricated to define; a sample inlet port; and a mesoscale flow system comprising; a tortuous sample flow channel extending from said inlet port, wherein said tortuous flow channel is microfabricated with a length which allows timed mixing of reagents and sample fluid; and an analyte binding region in fluid communication with said tortuous flow channel comprising a binding moiety immobilized on a surface in said analyte binding region, said binding moiety specifically binds to said analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting the binding of analyte to the binding moiety thereby to determine the presence of the analyte.
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21. A method for detecting the presence of an analyte in a fluid sample, the method comprising the steps of:
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(i) providing a device comprising; a solid substrate microfabricated to define; a sample inlet port, said port being dimensioned for connection to a pump means; and a mesoscale flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds to said analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting binding of said analyte to said binding moiety, thereby to determine the presence of said analyte; (ii) delivering a sample to said inlet port and, by a pump means, through said flow system to said analyte binding region to permit binding of said analyte to said binding moiety; and (iii) detecting the binding of analyte to said binding moiety with said binding means, thereby to determine the presence of the analyte. - View Dependent Claims (22, 23, 24, 25, 26, 27)
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28. The method for detecting the presence of a cell population in a sample, the method comprising the steps of:
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(i) providing a device comprising; a sample inlet port, said port being dimensioned for connection to a pump means; and a mesoscale flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds a surface molecule on members of said cell population, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a window disposed over said analyte binding region on said substrate; (ii) delivering a sample to said inlet port and, by a pump means, through said flow system to said binding region, to permit said binding moiety to bind to a surface molecule on members of said cell population to induce agglutination of said cell population on the surface of said binding region; and (iii) detecting said agglutination optically in said binding region through said window, thereby to determine the presence of the cell population in the sample.
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29. A method for detecting the presence of one or more analytes in a fluid sample, the method comprising the steps of:
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(i) providing a device comprising; a solid substrate microfabricated to define; a sample inlet port; and a first and at least a second mesoscale flow system, each said flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising binding moiety immobilized on a surface in said analyte binding region, wherein said binding moiety specifically binds to analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; and a detection means associated with each analyte binding region or in fluid communication with each analyte binding region for detecting binding of analyte to the binding moiety in each analyte binding region, thereby to determine the presence of said analyte; (ii) delivering a sample to said inlet port and, by pump means, through said flow system to a said analyte binding regions; and (iii) detecting the binding of an analyte to the binding moiety in each of the analyte binding regions in said first and at least second system with said binding means, thereby to determine the presence of the analytes.
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30. In combination, a device for determining an analyte in a fluid sample, said device comprising a solid substrate having at least one surface and being microfabricated to define:
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a sample inlet port; and a flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety which specifically binds to said analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; detection means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting binding of said analyte to said binding moiety; and an appliance for use with said device, said appliance comprising a holder for said device, a fluid sample input conduit interfitting with said inlet port of said device and a pump for passing fluid sample through said flow system. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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41. A method for determining the presence or amount of an intercellular component in a cell-containing biological fluid sample, said method comprising the steps of:
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(i) providing a device comprising a solid substrate microfabricated to define; a sample inlet port; and a flow system comprising; a sample flow channel extending from said inlet port; and an analyte binding region in fluid communication with said flow channel comprising a binding moiety which specifically binds said analyte, at least one of said sample flow channel or said analyte binding region having mesoscale cross-sectional dimensions; cell lysing means in said mesoscale flow system, and upstream of said analyte binding region, in fluid communication with said flow channel; binding means associated with said analyte binding region or in fluid communication with said analyte binding region for detecting binding of said analyte to said binding moiety; (ii) delivering said sample to said inlet port; (iii) lysing said cells within said device to release said intercellular component; (iv) delivering said intercellular component to said analyte binding region; and (v) detecting binding of said intercellular component to said binding moiety as determinative of the presence or amount of said intercellular component in said sample. - View Dependent Claims (42, 43, 44)
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Specification