System and method for spatiotemporally analyzed rapid assays

• US 10,067,125 B2
• Filed: 09/04/2013
• Issued: 09/04/2018
• Est. Priority Date: 09/04/2012
• Status: Active Grant

• Current Assignee: Edward L. Mamenta
• Original Assignee: Edward L. Mamenta
• Inventors: Mamenta, Edward L
• Primary Examiner(s): Crawford, Erik B
• Application Number:
  US14/018,397
• Publication Number:
  US 20140065647A1
• Time in Patent Office: 1,826 Days
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: G01N 2021/8494 Measuring or storing parameters of the band
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• 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 21/85 Investigating moving fluids or granular solids
• CPC Class Codes: G01N 33/54306 Solid-phase reaction mechanisms
• 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 invention relates to methods of reliably and quantitatively determining the amount of an analyte of interest in a fluid sample using a flow-induced assay, such as an immunochromatographic assay, in which spatiotemporal measurements are recorded during the course of the assay reaction, generating a spatiotemporal dataset, and subsequently analyzed. The invention also relates to a system incorporating instruments for recording spatiotemporal datasets (spatiotemporal data recorders), devices comprised of flow-induced assays configured for analysis on a spatiotemporal recorder, and programs for analyzing the recorded spatiotemporal datasets.

Claims

1. A method for determining the amount of target analyte in a fluid sample, comprising:

a) providing the fluid sample;

b) providing a set of fluid calibrator samples containing the target analyte at defined levels;

c) providing a plurality of assay devices, each assay device comprising a particle region incorporating test particles coated with a target analyte binding reagent and a test area incorporating a capture zone coated with the target analyte binding reagent, each assay device capable of forming, in response to an application of the fluid sample, a collection of measurable assay device compositions comprising an analyte-independent movement of the test particles through the test area and an analyte-dependent immobilization of the test particles in the capture zone, wherein the analyte-independent movement of the test particles correlates with assay parameters that define device-specific assay conditions;

d) providing an imaging instrument operatively connected to the plurality of assay devices, wherein the imaging instrument is configured for collecting and recording each collection of measurable assay device compositions as a set of numerical spatiotemporal data points;

e) providing a computing device operatively connected to the imaging instrument, wherein the computing device comprises an executable software program configured for analyzing each set of numerical spatiotemporal data points from the imaging instrument so as to calculate the amount of target analyte present in the fluid sample, the program using calibration processes that incorporate correlations between the assay parameters and the immobilization of the test particles in the capture zone;

f) applying one of the set of fluid calibrator samples to one of the plurality of assay devices so as to induce the formation of one collection of measurable assay device compositions;

g) collecting and recording the one collection of measurable assay device compositions of step f) on the imaging instrument to generate one set of numerical spatiotemporal data points for analysis;

h) repeating steps f) and g) for each of the set of fluid calibrator samples to induce the formation of additional collections of measureable assay device compositions, and collecting and recording the additional collections of measurable assay device compositions on the imaging instrument to create a plurality of sets of numerical spatiotemporal data points for the set of fluid calibrator samples;

i) repeating steps f), g), and h) for each of the plurality of assay devices;

j) using the software program to create a database of the plurality of sets of numerical spatiotemporal data points generated for the set of fluid calibrator samples for each of the plurality of assay devices;

k) applying the fluid sample to each of the plurality of assay devices so as to induce the formation of a plurality collection of fluid sample measurable assay device compositions;

l) collecting and recording the plurality of collection of fluid sample measurable assay device compositions of step k) on the imaging instrument to generate the fluid sample set of numerical spatiotemporal data points for analysis;

m) analyzing the fluid sample set of numerical spatiotemporal data points from step l) with the software program and the database so as to determine the amount of target analyte in the fluid sample, wherein the amount of target analyte is determined based on the amount of test particles coated with the target analyte binding reagent immobilized in the capture zone coated with the target analyte binding reagent together with the assay parameters determined from the analyte-independent movement of the particles in the test area, the assay parameters used to generate device-specific calibration.

2. The method of claim 1, wherein each assay device is an immunochromatographic assay device comprising a sample application region, the particle region containing test particles coated with the target analyte binding reagent, and the test area containing the capture zone coated with the target analyte binding reagent.

3. The method of claim 1, wherein the assay parameters that define device-specific assay conditions are selected from a group consisting of:

a parameter defining the amount of test particles coated with the target analyte binding reagent that move from the particle region to the test area, a parameter defining the time required for the test particles to move from the particle region to the capture zone coated with the target analyte binding reagent, a parameter defining the time required for the test particles to traverse the capture zone, a parameter defining the total amount of test particles that traverse the capture zone at a first defined time point, and a parameter defining the instantaneous concentration of test particles in the capture zone at defined time points.

4. The method of claim 1, wherein the spatiotemporal data points are organized into a spatiotemporal table.

5. The method of claim 1, wherein the software program comprises a plurality of machine learning algorithms that use the database of the plurality of sets of numerical spatiotemporal data points as training examples to establish device-specific calibration processes.

6. The method of claim 1, wherein the the imaging instrument comprises a digital camera that records the plurality of sets of numerical spatiotemporal data points as a set of gray scale values derived from a succession of digital images of the test area captured over time.