Lateral flow assay systems and methods

• US 9,243,997 B2
• Filed: 09/05/2013
• Issued: 01/26/2016
• Est. Priority Date: 04/01/2004
• Status: Active Grant

• Current Assignee: Alverix, Inc. (Becton, Dickinson & Co)
• Original Assignee: Alverix, Inc. (Becton, Dickinson & Co)
• Inventors: Petruno, Patrick T., Petrilla, John F., Brosnan, Michael J., Zhou, Rong, Roitman, Daniel B.
• Primary Examiner(s): SIEFKE, SAMUEL P
• Application Number:
  US14/019,166
• Publication Number:
  US 20140004624A1
• Time in Patent Office: 873 Days
• US Class Current: 1/1
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/17 Systems in which incident light is modified in accordance with the properties of the material investigated where the material investigated is optically excited causing a change in wavelength of the incident light G01N21/63
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 2201/062 LED's
• CPC Class Codes: G01N 2201/067 Electro-optic, magneto-optic, acousto-optic elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 435/823 Acetobacter
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick
• CPC Class Codes: Y10S 436/823 Immunogenic carrier or carrier per se
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials

Abstract

In one aspect, a diagnostic test system includes a housing, a reader, and a data analyzer. The housing includes a port for receiving a test strip. The reader obtains separable light intensity measurements from localized regions of an area of the detection zone exposed for optical inspection, wherein each of the localized regions is characterized by at least one surface dimension smaller than the first dimension. The data analyzer identifies ones of the light intensity measurements obtained from the at least one test region and computes at least one parameter from the identified ones of the light intensity measurements. In another aspect, the reader obtains a respective set of light intensity measurements from each of multiple corresponding regions of the exposed surface area of the detection zone, and the data analyzer computes at least one parameter from at least one of the sets of light intensity measurements.

Claims

1. A diagnostic test system, comprising:

a test strip comprising a detection zone containing an immobilized substance that binds a target analyte, wherein the detection zone comprises one or more test regions and one or more control regions;

a reader that obtains separable light intensity measurements from multiple localized regions of the one or more test regions and the one or more control regions, wherein the reader comprises;

a light source that illuminates the multiple localized regions of the one or more test regions and the one or more control regions; and

a light detector array that comprises individual light detectors, wherein the individual light detectors each obtain a separable light intensity measurement from one of the multiple localized regions of the one or more test regions and the one or more control regions; and

a data analyzer comprising software that identifies one or more of the separable light intensity measurements obtained from the one or more test regions and the one or more control regions and computes at least one parameter from the identified one or more separable light intensity measurements.

2. The diagnostic test system of claim 1, wherein the test strip supports lateral flow of a fluid along a lateral flow direction, and wherein the one or more test regions and one or more control regions include an area that is exposed for optical inspection and is characterized by a first dimension transverse to the lateral flow direction and a second dimension parallel to the lateral flow direction.

3. The system of claim 2, wherein each of the localized regions of the one or more test regions and the one or more control regions illuminated by the light beam has at least one dimension at most as large as a narrowest surface dimension of the test region.

4. The system of claim 2, wherein the light source is operable to scan the light beam across the exposed area of the one or more test regions and the one or more control regions in a direction substantially parallel to the lateral flow direction.

5. The system of claim 2, wherein the light source is operable to scan the light beam along a circuitous path across the exposed area of the one or more test regions and the one or more control regions.

6. The system of claim 2, wherein the reader is operable to modulate the illuminating light and to synchronize the obtaining of the light intensity measurements with the modulation of the illuminating light.

7. The system of claim 1, wherein the reader comprises an aperture through which the one or more separable light intensity measurements are obtained, wherein the aperture is positioned over at least one test region when the test strip is loaded in the port.

8. The system of claim 2, wherein the data analyzer is operable to identify the one or more separable light intensity measurements obtained from the test region based on intensity measurements obtained from at least one position marker on the test strip.

9. The system of claim 2, wherein the reader is operable to obtain a respective set of light intensity measurements from each of multiple corresponding regions of the exposed area of the one or more test regions and the one or more control regions.

10. The system of claim 9, wherein:

the reader is operable to illuminate each of the corresponding regions of the one or more test regions and the one or more control regions with light and to obtain the respective sets of light intensity measurements after the corresponding regions of the one or more test regions and the one or more control regions have been illuminated with the light; and

the data analyzer is operable to determine respective decay time parameters from the respective sets of light intensity measurements and to identify the one or more separable light intensity measurements obtained from the at least one test region based on the determined decay time parameters.

11. The system of claim 10, wherein the data analyzer is operable to compute peak intensity parameter values for each of the corresponding regions of the one or more test regions and the one or more control regions based at least in part on the determined decay time parameters.

12. The system of claim 11, wherein the data analyzer is operable to identify the one or more separable light intensity measurements obtained from a second test region in the one or more test regions and the one or more control regions based on the determined decay time parameters.

13. The system of claim 12, wherein the data analyzer is operable to compute a parameter value from respective one or more of the peak intensity parameter values corresponding to the first and second test regions.

14. The system of claim 9, wherein the reader is operable to illuminate each of the corresponding regions of the one or more test regions and the one or more control regions with light having different wavelength profiles and to obtain one or more multiple light intensity measurements in each set under different wavelength profiles of light illuminating the corresponding regions.

15. The system of claim 14, wherein the data analyzer is operable to determine wavelength response profiles across the exposed area of the one or more test regions and the one or more control regions from the respective sets of light intensity measurements and to identify the one or more separable light intensity measurements obtained from the at least one test region based on the determined wavelength response profiles.

16. The system of claim 15, wherein the reader is operable to illuminate each of the corresponding regions of the one or more test regions and the one or more control regions with light of different respective polarizations and to obtain one or more of the multiple light intensity measurements in each set under different polarizations of light illuminating the corresponding regions.

17. The system of claim 16, wherein the data analyzer is operable to determine polarization response profiles across the exposed area of the one or more test regions and the one or more control regions from the respective sets of light intensity measurements and to identify the one or more separable light intensity measurements obtained from the at least one test region based on the determined polarization response profiles.

18. A diagnostic test method, comprising:

binding a target analyte to an immobilized substance on a test strip comprising a detection zone, wherein the detection zone comprises the immobilized substance, and wherein the detection zone comprises one or more test regions and the one or more control regions;

obtaining separable light intensity measurements from multiple localized regions of the one or more test regions and the one or more control regions with a reader, wherein the reader comprises;

a light source that illuminates the multiple localized regions of the one or more test regions and the one or more control regions; and

a light detector array that comprises individual light detectors, wherein the individual light detectors each obtain a separable light intensity measurement from one of the multiple localized regions of the one or more test regions and the one or more control regions; and

identifying one or more separable light intensity measurements obtained from the one or more test regions and the one or more control regions and computing at least one parameter from the identified one or more separable light intensity measurements.

19. The diagnostic test method of claim 18, wherein the test strip supports lateral flow of a fluid along a lateral flow direction, and wherein the one or more test regions and the one or more control regions include an area that is exposed for optical inspection and is characterized by a first dimension transverse to the lateral flow direction and a second dimension parallel to the lateral flow direction.

20. The diagnostic test method of claim 19, wherein each of the localized regions illuminated by the light beam has at least one dimension at most as large as a narrowest surface dimension of the test region.

21. The diagnostic test method of claim 19, wherein the light beam is scanned across the exposed area of the one or more test regions and the one or more control regions in a direction substantially parallel to the lateral flow direction.

22. The diagnostic test method of claim 19, wherein the light beam is scanned along a circuitous path across the exposed area of the one or more test regions and the one or more control regions.

23. The diagnostic test method of claim 22, wherein the steps of scanning a light beam to illuminate each of multiple localized regions of the exposed area of the one or more test regions and the one or more control regions;

and obtaining separable light intensity measurements from each of multiple localized regions of the exposed area of the detection zone are synchronized.

24. The diagnostic test method of claim 18, wherein the illumination by the light beam is synchronized with the obtaining of the one or more separable light intensity measurements.

25. The diagnostic test method of claim 18, wherein the at least one parameter is decay time.

26. The diagnostic test method of claim 18, wherein the at least one parameter is peak intensity.

27. The diagnostic test method of claim 19, wherein the light beam illuminates each of the corresponding regions of the exposed surface area of the one or more test regions and the one or more control regions with light having different wavelength profiles.

28. The diagnostic test method of claim 19, wherein the light beam illuminates each of the corresponding regions of the exposed surface area of the one or more test regions and the one or more control regions with light of different respective polarizations.