Lateral flow assays using two dimensional features

• US 9,851,366 B2
• Filed: 04/12/2013
• Issued: 12/26/2017
• Est. Priority Date: 01/18/2011
• Status: Active Grant

• Current Assignee: Symbolics, LLC
• Original Assignee: Symbolics, LLC
• Inventors: O'Farrell, Brendan, Tisone, Thomas C.
• Primary Examiner(s): Chin, Chris L
• Application Number:
  US13/862,301
• Publication Number:
  US 20130225448A1
• Time in Patent Office: 1,719 Days
• Field of Search: None
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 33/76 Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors

Abstract

The present invention relates to novel lateral flow devices using two dimensional features, preferably, uniform two dimensional test and control features, and the methods for detecting an analyte using the lateral flow devices, and processes for making the lateral flow devices.

Claims

1. A test device for detecting an analyte in a liquid sample, which device comprises a plurality of reagent dots on a matrix, wherein said plurality of reagent dots do not overlap and are sufficiently spaced apart from each other so that when said liquid sample flows laterally along said matrix, flow of said liquid sample to, through and/or around one of said plurality of reagent dots does not substantially affect flow of said liquid sample to, through and/or around said other reagent dots, said plurality of reagent dots do not form a reagent line across the entire width of said matrix in a direction perpendicular to the direction of said liquid sample flow or a complete circle of a reagent line, and after a liquid sample flows laterally along said test device and passes said plurality of reagent dots, said plurality of reagent dots form a predetermined pattern to indicate presence, absence and/or amount of said analyte in said liquid sample,

wherein said plurality of reagent dots comprise different binding reagents that are capable of binding to different analytes or other binding reagents that are capable of binding to the analytes, said plurality of reagent dots form a line that is substantially parallel to the liquid sample flow direction, as the liquid sample flows laterally along the test device, the analytes, if present in the liquid sample, become bound to the binding reagents at each of said plurality of reagent dots, the binding of the analytes to said reagent dots generates detectable signals at said reagent dots, and the presence and/or intensity of the detectable signals at said reagent dots indicates the presence and/or amount of the analytes in the liquid sample, and

wherein at least a quarter, a third, half or all of said reagent dots do not overlap and are sufficiently spaced apart from each other so that when the liquid sample flows laterally along the matrix, flow of the liquid sample to, through and/or around one of the reagent dots does not substantially affect flow of the liquid sample to, through and/or around the other reagent dots.

2. The test device of claim 1, wherein the plurality of reagent dots comprise different groups of binding reagents, each group of the binding reagents is capable of binding to the same analyte or another binding reagent that is capable of binding to the same analyte, and the binding reagents in different groups are capable of binding to different analytes or other binding reagents that are capable of binding to different analytes,

each group of the reagent dots forms a line that is substantially parallel to the liquid sample flow direction, and the different lines formed by the different groups of the reagent dots are substantially parallel to each other,

as the liquid sample flows laterally alone the test device, the analytes, if present in the liquid sample, become sequentially bound to the binding reagents at each of the reagent dots in each group of the reagent dots until the analytes are depleted by binding to the upstream reagent dots, the binding of the analytes to the reagent dots generates detectable signals at the reagent dots, and the intensity and/or the number of the detectable signals at the reagent dots provides a quantitation or a semi- quantitation of the different analytes in the liquid sample.

3. The test device of claim 1, wherein the plurality of reagent dots comprise at least 10, 50, 100, 500, 1,000, 5,000, 10,000 or more reagent dots.

4. The test device of claim 1, wherein at least a quarter, a third, half or all of the reagent dots have a diameter of about 0.1-1 um, 1-10 um, 10-50 um, 51-100 um, 101-200 um, 201-300 um, 301-400 um, 401-500 um or 501-1000 um, or at least a quarter, a third, half or all of the reagent dots have a diameter or surface area that is about 10%, 5%, 1%, 0.5%, 0.1%, 0.05%, 0.01%, 0.001% or smaller diameter or surface area of the length, width or surface of the matrix.

5. The test device of claim 1, wherein the distance between edges of the reagent dots is about 1-10 um, 10-50 um, 51-100 um, 101-200 um, 201-300 um, 301-400, 401-500, or 501-600 um.

6. The test device of claim 1, wherein at least a quarter, a third, half or all of the reagent dots comprise a reagent that is capable of specifically binding to an analyte or another binding reagent that is capable of binding to an analyte.

7. The test device of claim 1, which is a competitive test wherein a labeled reagent comprising an analyte or an analyte analog linked to a detectable label is used.

8. The test device of claim 1, wherein the predetermined pattern is selected from the group consisting of a line, multiple lines, a symbol, a geometric shape and an alpha-numeric shape.

9. The test device of claim 8, wherein the alpha-numeric shape is a letter, a word, a number or a combination thereof.

10. The test device of claim 8, wherein the line is substantially parallel to the liquid sample flow direction.

11. The test device of claim 8, wherein the line is substantially perpendicular to the liquid sample flow direction.

12. The test device of claim 1, wherein at least a quarter, a third, half or all of the reagent dots have substantially the same size or diameter.

13. The test device of claim 1, wherein at least one of the reagent dots has a shape selected from the group consisting of a line, a circle, a rod, a square, a triangle, a rectangle and an irregular shape.

14. The test device of claim 13, wherein at least a quarter, a third, half or all of the reagent dots have a shape selected from the group consisting of a line, a circle, a rod, a square, a triangle, a rectangle and an irregular shape.

15. The test device of claim 1, wherein at least a quarter, a third, half or all of the reagent dots have the same shape.

16. The test device of claim 1, wherein the distance between at least a quarter, a third, half or all of the reagent dots is substantially the same.

17. The test device of claim 1, which comprises multiple layers of the plurality of reagent dots.

18. The test device of claim 17, which comprises at least a layer of the plurality of reagent dots on both sides of the matrix.

19. The test device of claim 1, wherein the matrix has a porous structure.

20. The test device of claim 19, wherein the matrix comprises nitrocellulose, glass fiber, polypropylene, polyethylene, polyvinylidene flouride, ethylene vinylacetate, acrylonitrile, polytetrafluoro-ethylene, or a combination thereof.

21. The test device of claim 1, wherein the matrix has a non-porous structure.

22. The test device of claim 1, wherein the matrix comprises a plastic material, a film of a matrix having a hydrophilic surface, or a material with a controlled contact angle with the sample liquid.