Method and device for detecting analytes in fluids
First Claim
1. A method for detecting and quantifying at least one analyte in a fluid sample suspected of containing the analyte by employing a liquid reactant that reacts with the analyte to form a detectable reaction product, by relating the analyte to the detectable reaction product of analyte and liquid reactant comprising:
- providing a fluid transport material that absorbs a liquid and supports capillary flow of the liquid, the fluid transport material having a first zone for the application of the fluid sample suspected of containing the analyte, and a second zone for the application of the liquid reactant;
adding the fluid sample to the first zone, and the liquid reactant to the second zone, wherein the fluid sample thereafter flows in a first direction from a fluid sample edge toward the second zone, and the liquid reactant flows in a second direction opposite to that of the first direction and toward the first zone from a liquid reactant edge;
whereby when the flowing fluid sample and the flowing liquid reactant meet, flow stops and the detectable reaction product is formed by a reaction between the liquid reactant and the analyte, and a stable reaction interface is formed at a juncture between and visually distinct from the fluid sample and the liquid reactant; and
detecting the detectable reaction product.
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Abstract
A disposable, dry chemistry analytical system is disclosed which is broadly useful for the detection of a variety of analytes present in biological fluids such as whole blood, serum, plasma, urine and cerebral spinal fluid. The invention discloses the use of the reaction interface that forms between two liquids converging from opposite directions within a bibulous material. The discovery comprises a significant improvement over prior art disposable, analytical reagent systems in that the detectable reactant zone is visually distinct and separate from the unreacted reagents allowing for the use of reaction indicators exhibiting only minor changes as well as extremely high concentrations of reactants. In addition, staged, multiple reagents can be incorporated. Whole blood can be used as a sample without the need for separate cell separating materials. Finally, the invention is useful for the detection of analytes in a broad variety of materials such as milk, environmental samples, and other samples containing target analytes.
217 Citations
57 Claims
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1. A method for detecting and quantifying at least one analyte in a fluid sample suspected of containing the analyte by employing a liquid reactant that reacts with the analyte to form a detectable reaction product, by relating the analyte to the detectable reaction product of analyte and liquid reactant comprising:
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providing a fluid transport material that absorbs a liquid and supports capillary flow of the liquid, the fluid transport material having a first zone for the application of the fluid sample suspected of containing the analyte, and a second zone for the application of the liquid reactant;
adding the fluid sample to the first zone, and the liquid reactant to the second zone, wherein the fluid sample thereafter flows in a first direction from a fluid sample edge toward the second zone, and the liquid reactant flows in a second direction opposite to that of the first direction and toward the first zone from a liquid reactant edge;
whereby when the flowing fluid sample and the flowing liquid reactant meet, flow stops and the detectable reaction product is formed by a reaction between the liquid reactant and the analyte, and a stable reaction interface is formed at a juncture between and visually distinct from the fluid sample and the liquid reactant; and
detecting the detectable reaction product. - 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, 26, 27, 28)
whereby the flowing analyte in the amount of the analyte and the flowing liquid reactant meet, flow stops and a detectable calibration product is formed by a reaction between the analyte in the amount of the analyte and the liquid reactant, and a stable calibration reaction interface is formed at a juncture between and visually distinct from the analyte in the amount of the analyte and the liquid reactant; and
detecting the detectable reaction product.
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23. The method of claim 22, wherein the amount of the analyte added to the calibration zone is in excess of the amount of the analyte in the fluid sample, such that the amount of the analyte added to the calibration zone is sufficient to form an amount of the calibration product that enables determination of an amount of the liquid reactant.
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24. The method of claim 22, wherein the detectable calibration product is formed at a rate that is proportional to a concentration of the analyte.
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25. The method of claim 24, wherein the rate is calculated as a change over time of a peak intensity of reflectance or absorption of the detectable calibration product.
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26. The method of claim 25, wherein the peak intensity of reflectance or absorption is measured across a line substantially perpendicular to the calibration interface.
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27. The method of claim 25, wherein the peak intensity of reflectance or absorption is measured within a polygonal region encompassing all or a portion of the calibration interface.
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28. The method of claim 22, wherein the detectable reaction product is formed in an amount greater than or equal to a predetermined threshold intensity of reflectance or absorption indicative of the presence of the analyte.
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29. A method for detecting and quantifying at least one analyte in a fluid sample suspected of containing the analyte by employing a liquid reactant that reacts with the analyte to form a detectable reaction product, by relating the analyte to the detectable reaction product of analyte and liquid reactant comprising:
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providing a fluid transport material that absorbs a liquid and supports capillary flow of the liquid, the fluid transport material having a first zone for the application of the fluid sample suspected of containing the analyte, and a second zone for the application of a liquid to a pad containing a reconstitutable reagent, wherein when the fluid sample is added to the first zone, and the liquid is added to the second zone, the fluid sample flows in a first direction from a fluid sample edge toward the second zone, the reagent is reconstituted and the reagent and the liquid form a liquid reagent containing a liquid reactant that reacts with the analyte to form a detectable reaction product, and the liquid reactant flows in a second direction opposite to that of the first direction and toward the first zone from a liquid reactant edge;
whereby when the flowing fluid sample and the flowing liquid reactant meet, flow stops and the detectable reaction product is formed by a reaction between the liquid reactant and the analyte, and a stable reaction interface is formed at a juncture between and visually distinct from the fluid sample and the liquid reactant; and
detecting the detectable reaction product. - View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
whereby the flowing analyte in the amount of the analyte and the flowing liquid reactant meet, flow stops and a detectable calibration product is formed by a reaction between the analyte in the amount of the analyte and the liquid reactant, and a stable calibration reaction interface is formed at a juncture between and visually distinct from the analyte in the amount of the analyte and the liquid reactant, the calibration interface further being adjacent to the reaction interface; and
measuring the calibration product at the same at least one desired wavelength of reflectance or absorbance as the reaction product.
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52. The method of claim 51, wherein the amount of the analyte added to the calibration zone is in excess of the amount of the analyte in the fluid sample, such that the amount of the analyte added to the calibration zone is sufficient to form an amount of the calibration product that enables determination of an amount of the liquid reactant.
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53. The method of claim 51, wherein the detectable calibration product is formed at a rate that is proportional to the concentration of the analyte.
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54. The method of claim 53, wherein the rate is calculated as a change over time of a peak intensity of reflectance or absorption of the detectable calibration product.
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55. The method of claim 54, wherein the peak intensity of reflectance or absorption is measured across a line substantially perpendicular to the reaction interface.
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56. The method of claim 54, wherein the peak intensity of reflectance or absorption is measured within a polygonal region encompassing all or a portion of the reaction interface.
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57. The method of claim 51, wherein the detectable reaction product is formed in an amount greater than or equal to a predetermined threshold intensity of reflectance or absorption indicative of the presence of the analyte.
Specification