Lateral flow assay systems and methods

• US 9,989,527 B2
• Filed: 01/25/2016
• Issued: 06/05/2018
• 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:
  US15/005,776
• Publication Number:
  US 20160313254A1
• Time in Patent Office: 862 Days
• 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 one or more test regions and one or more control regions, the one or more test regions comprising multiple localized regions containing an immobilized substance configured to bind a target analyte;

a reader programed to obtain light intensity measurements from the multiple localized regions of the one or more test regions, the reader comprising

one or more light sources configured to illuminate the multiple localized regions of the one or more test regions, and

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

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

2. The diagnostic test system of claim 1, wherein the at least one parameter comprises a peak intensity value or an aggregative intensity value.

3. The diagnostic test system of claim 1, wherein the test strip supports lateral flow of a fluid along a lateral flow direction, and wherein at least one test region includes 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.

4. The system of claim 3, wherein each of the localized regions of the one or more test regions is characterized by at least one dimension that is the same size or smaller than the second dimension of the at least one test region.

5. The system of claim 1, further comprising a mechanism for imparting relative motion between the test strip and the reader.

6. The system of claim 5, wherein the mechanism comprises a motorized carriage that moves the test strip relative to the reader.

7. The system of claim 5, wherein the test strip supports lateral flow of a fluid along a lateral flow direction and wherein the mechanism is configured to move the reader relative to the test strip in the lateral flow direction.

8. The system of claim 7, wherein the light detector array comprises a linear light detector array oriented in a direction transverse to the direction of motion of the reader.

9. The system of claim 1, wherein the data analyzer is configured to identify the separable light intensity measurements obtained from the test region based at least in part on intensity measurements obtained from at least one position marker on the test strip.

10. A diagnostic test system, comprising:

a reader programed to measure an intensity of a light signal arising from a measurement zone of a lateral flow assay test strip as a result of the presence of a labeled target analyte complex immobilized in the measurement zone, the reader further configured to measure an intensity of a light signal arising from a control zone of the lateral flow assay test strip as a result of the presence of a labeling substance immobilized in the control zone, the lateral flow assay test strip comprising multiple localized regions, the reader comprising

a light source configured to illuminate the lateral flow assay test strip, and

a plurality of light detectors, each light detector configured to detect intensity of light signals arising from one of the multiple localized regions and generate a light intensity measurement; and

a data analyzer programed to individually analyze each light intensity measurement and isolate light intensity measurements arising from the measurement zone and the control zone from light intensity measurements that do not arise from the measurement zone or the control zone, the data analyzer further configured to compute at least one parameter from the isolated light intensity measurements arising from the measurement zone and the control zone.

11. The system of claim 10, wherein the measurement zone comprises immobilized compounds configured to bind the labeled target analyte complexes and retain the labeled target analyte complexes in the measurement zone.

12. The system of claim 10, wherein the control zone comprises a compound configured to bind the labeling substance and retain the labeling substance in the control zone.

13. The system of claim 10, wherein the data analyzer is further configured to determine the presence of a labeled target analyte complex immobilized in the measurement zone based on isolated light intensity measurements arising from the measurement zone.

14. The system of claim 10, wherein the data analyzer is further configured to determine when sufficient quantity of the labeling substance has accumulated in the control zone based on isolated light intensity measurements arising from the control zone.

15. The system of claim 10, further comprising a test result indicator configured to indicate the presence of a labeled target analyte complex immobilized in the measurement zone.

16. The system of claim 15, wherein the test result indicator comprises one or more lights or an alphanumeric display.

17. The system of claim 15, wherein the test result indicator is further configured to indicate completion of an assay test when sufficient quantity of the labeling substance has accumulated in the control region.

18. The system of claim 10, wherein the reader is configured to communicate light intensity measurements to the data analyzer over a wireless connection.