Lateral flow assays using two dimensional features

• US 9,874,576 B2
• Filed: 04/12/2013
• Issued: 01/23/2018
• 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:
  US13/862,313
• Publication Number:
  US 20130225449A1
• Time in Patent Office: 1,747 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 at least two of said 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 two reagent dots does not substantially affect flow of said liquid sample to, through and/or around said other reagent dot, 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 at least two reagent dots, said at least two reagent dots form a predetermined pattern to indicate presence, absence and/or amount of said analyte in said liquid sample,

wherein the plurality of reagent dots comprises two different groups of binding reagents, one group of the reagent dots forms a line that is at a first angle relative to the liquid sample flow direction, and the other group of the reagent dots forms a line that is at a second, different angle relative to the liquid sample flow direction,

after the liquid sample flows laterally along the test device, the reagent dots in one of the lines generate a signal indicating the presence and/or amount of an analyte in the liquid sample, and the reagent dots in the other line generate a control signal indicating the test is properly conducted, and

when the liquid sample comprises the analyte and the test is properly conducted, the two lines of the reagent dots generate a positive symbol, indicating the presence and/or amount of the analyte in the liquid sample, and when the liquid sample does not comprise the analyte and the test is properly conducted, only one line of the reagent dots generates a negative symbol, indicating the absence of the analyte in the liquid sample, and

wherein at least a quarter, a third, half or all 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 one group of the reagent dots forms a line that is substantially parallel to the liquid sample flow direction, and the other group of the reagent dots forms a line that is substantially perpendicular to the liquid sample flow direction, and

when the liquid sample comprises the analyte and the test is properly conducted, the two lines of the reagent dots generate a “

+”

symbol, indicating the presence and/or amount of the analyte in the liquid sample, and when the liquid sample does not comprise the analyte and the test is properly conducted, only one line of the reagent dots generates a “

−

”

symbol, indicating the absence of the analyte in the liquid sample.

3. The test device of claim 1, wherein the plurality of reagent dots comprises 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 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 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 at least two 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 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, or the test device is configured for a competitive test.

7. 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.

8. The test device of claim 7, wherein the alpha-numeric shape is a letter, a word, a number or a combination thereof.

9. The test device of claim 7, wherein the line is substantially parallel to the liquid sample flow direction.

10. The test device of claim 7, wherein the line is substantially perpendicular to the liquid sample flow direction.

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

12. 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.

13. The test device of claim 12, wherein at least a quarter, a third, half or all 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.

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

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

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

17. The test device of claim 16, which comprises at least a layer of the plurality of reagent dots on both sides of the matrix.

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

19. The test device of claim 18, wherein the matrix comprises nitrocellulose, glass fiber, polypropylene, polyethylene, polyvinylidene flouride, ethylene vinylacetate, acrylonitrile polytetrafluoro-ethylene, or a combination thereof.

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

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

22. 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.