Lateral flow assays using two dimensional features

• US 9,874,556 B2
• Filed: 03/13/2013
• Issued: 01/23/2018
• Est. Priority Date: 07/18/2012
• 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:
  US13/802,036
• Publication Number:
  US 20140024016A1
• Time in Patent Office: 1,777 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/148 Specific details about calibrations
• CPC Class Codes: B01L 2300/028 Graduation
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• 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

Abstract

The present invention relates to novel lateral flow devices using two dimensional features, preferably, uniform two dimensional test and control features, to provide flow control information, to function as an internal control and/or to provide internal calibration information for the test device. The present invention also relates to methods for using the lateral flow devices to provide flow control information, to function as an internal control and/or to provide internal calibration information for the test device.

Claims

1. A test device, 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 a liquid flows laterally along said matrix, flow of said liquid 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, each of said two reagent dots is neither a reagent line across the entire width of said matrix in a direction perpendicular to the direction of said liquid flow nor a complete circle of a reagent line circulating the center or sample or liquid application site of said test device, and after a liquid flows laterally along said test device and passes said at least two reagent dots, detectable signals are formed at said at least two reagent dots to provide for flow control information, and:

1) to function as an internal control;

or

2) to provide for internal calibration information for said test device;

or

3) to function as an internal control and to provide for internal calibration information for said test device, and

wherein

said internal calibration information is for quantification of an analyte,

said flow control information allows internal calibration within said test device for perturbation in test results caused by variability in flow rate or flow pattern laterally across the surface and/or along the length of a flow field, and

at least a quarter, a third, half of or all said reagent dots have a diameter of about 0.1-1 μ

m, 1-10 μ

m, 10-50 μ

m, 51-100 μ

m, 101-200 μ

m, 201-300 μ

m, or 301-400 μ

m.

2. The test device of claim 1, which test device further comprises a detection site to indicate presence, absence and/or amount of an analyte in a liquid sample.

3. The test device of claim 1, wherein the at least two reagent dots form a line that is substantially parallel to the liquid flow direction, a line that is substantially perpendicular to the liquid flow direction and/or a line that is at a predetermined angle relative to the liquid flow direction.

4. The test device of claim 1, wherein the detectable signal is formed at one or more of the at least two reagent dots to function as an internal control for the test device.

5. The test device of claim 4, wherein the detectable signal is formed at a single reagent dot to function as an internal control for the test device.

6. The test device of claim 4, wherein the detectable signals are formed at a plurality of reagent dots to function as an internal control for the test device.

7. The test device of claim 4, wherein the internal control is an internal control for cross reactivity or an interfering substance, an internal positive control, and/or an internal negative control.

8. The test device of claim 1, wherein the detectable signals are formed at the at least two reagent dots to provide internal calibration information for the test device.

9. The test device of claim 8, wherein the formation of the detectable signals at the at least two reagent dots is independent from the presence, absence and/or amount of the analyte in a liquid sample.

10. The test device of claim 8, wherein each of the at least two reagent dots comprises a reagent that binds to a labeled binding reagent for the analyte.

11. The test device of claim 8, wherein the detectable signals are formed at the at least two reagent dots to provide for internal calibration information for the desired analyte testing range.

12. The test device of claim 8, wherein the at least two reagent dots form a line that is substantially parallel to the liquid flow direction, a line that is substantially perpendicular to the liquid flow direction and/or a line that is at a predetermined angle relative to the liquid flow direction.

13. The test device of claim 8, wherein the test device does not comprise a detection site to indicate presence, absence and/or amount of an analyte in a liquid sample and the detectable signals are formed at the at least two reagent dots to provide for internal calibration information for the test device.

14. The test device of claim 1, wherein the test device does not comprise a detection site to indicate presence, absence and/or amount of an analyte in a liquid sample and the at least two reagent dots comprise a binding reagent that generates signals of specific signal strengths relative to one another or absolute signal strengths of differing levels.

15. The test device of claim 1, wherein the detectable signals are formed to provide for flow control information, to function as an internal control and to provide for internal calibration information for the test device.

16. The test device of claim 1, wherein a portion of the matrix, upstream from the at least two of the reagent dots, comprises a dried, labeled reagent, the labeled reagent being capable of being moved by a liquid or liquid sample to the at least two of the reagent dots and/or a test site to generate a detectable signal.

17. The test device of claim 1, wherein the distance between edges of at least two of the reagent dots is about 1-10 μ

m, 10-50 μ

m, 51-100 μ

m, 101-200 μ

m, 201-300 μ

m, or 301-400, μ

m.

18. A method for providing for flow control information, internal control or internal calibration information for a test device, which method comprises:

a) contacting a liquid with the test device of claim 1, wherein the liquid is applied to a site of said test device upstream of said at least two reagent dots;

b) transporting a labeled reagent to said at least two reagent dots; and

c) assessing the presence, absence, amount and/or pattern of signal(s) generated by said labeled reagent at said at least two reagent dots to provide for flow control information, and;

1) to function as an internal control or;

2) to provide for internal calibration information for said test device;

or

3) to function as an internal control and to provide for internal calibration information for said test device, and

wherein

said internal calibration information is for quantification of an analyte,

said flow control information allows internal calibration within said test device for perturbation in test results caused by variability in flow rate or flow pattern laterally across the surface and/or along the length of a flow field, and

at least a quarter, a third, half of or all said reagent dots have a diameter of about 0.1-1 μ

m, 1-10 μ

m, 10-50 μ

m, 51-100 μ

m, 101-200 μ

m, 201-300 μ

m, or 301-400 μ

m.

19. The method of claim 18, wherein the liquid and the labeled reagent are premixed to form a mixture and the mixture is applied to the test device.

20. The method of claim 18, wherein the test device comprises a dried labeled reagent before use and the dried labeled reagent is solubilized or resuspended, and transported to the at least two reagent dots by the liquid.

21. The method of claim 18, wherein the detectable signals are formed at the at least two reagent dots to:

a) to provide for flow control information;

b) to function as an internal control; and

c) to provide for internal calibration information for the test device.

22. The method of claim 18, which further comprises detecting an analyte in a liquid sample.