Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1998-06-05
2001-07-10
Chin, Christopher L. (Department: 1641)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C422S051000, C422S051000, C422S051000, C422S067000, C435S007900, C435S007910, C435S007920, C435S007930, C435S007940, C435S287100, C435S287200, C435S287700, C435S287800, C435S287900, C435S805000, C435S810000, C435S970000, C435S973000, C436S169000, C436S172000, C436S514000, C436S518000, C436S524000, C436S525000, C436S805000, C436S810000
Reexamination Certificate
active
06258548
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to a diagnostic device and more specifically to a lateral flow assay device (“LFD”) that provides quantitative or semi-quantitative results.
2. Background Information
Assays are needed and used for detecting the presence of analytes in liquid test samples in fields such as clinical and forensic medicine, environmental testing, food contaminant testing, and drug use testing. In particular demand are single step assays that are based on reactions between specifically reactive substances that can be conducted outside of the laboratory setting and in remote sites.
At present, there are a number of over-the-counter home testing and health care professional diagnostic devices that act to both collect human body fluids and perform a diagnostic assay. Some of these devices are used for midstream urine collection, while other devices involve dipstick collection of a fluid biological sample placed in a receptacle. Both types of diagnostic devices can employ a lateral flow technology with common features, including an absorbent wick, matrix and reaction zones.
Using such a device involves applying a biological or aqueous test sample to the matrix. The matrix usually is a porous carrier material. When the matrix does not have sufficient absorbent capacity, a wick is used to transfer the sample to the matrix. The test sample is applied to the wick or one end of the matrix strip and moves by capillary action in one direction along the matrix to a reaction zone.
The reaction zone contains a first reactant. The first reactant is usually diffusible conjugate formed from an antibody, or other ligand, and a marker substance. The first reactant is specifically selected to react with a component of interest in the test sample. The sample enters the reaction zone and the component of interest binds with the first reactant to form complexes.
The reactant complexes, any unreacted sample, and conjugate move by capillary action out of the reactant zone and into a single test capture zone. Within the test capture zone is a second reactant that is immobilized to the matrix. The reactant complexes that contain test capture zone binding sites are retained at the test capture site through the formation of a sandwich reaction product. Those reactant complexes that do not contain test capture binding sites move by capillary action out of the test capture zone, into a control capture zone where they are bound or continue to move along the matrix and out of the capture zones. The control capture zone usually contains an antibody that has a specificity for binding the conjugate.
LFD formats require a control indicator to insure that the test was performed properly. This indicator is a validity test, i.e., it shows whether enough sample has migrated past the test capture binding site and, therefore, that the test procedure is performing properly.
Two formats exist for test and control zones on LFDs. In the format used in the overwhelming majority of LFDs, each zone forms a line across the matrix strip. The first line (i.e., the line first touched by the sample's fluid front after moving through the reaction zone) is the test line. Parallel and adjacent to the test line is the control line. The second format, a +/− indicator system, is present in a few formats (see U.S. Pat. Nos. 4,916,056, 5,008,080 and 5,075,078). Several other indicator configurations, including dots, curved lines and triangles, are possible but have not received wide commercial use.
Using existing lateral flow devices, test results are based on the visual detection of a threshold using a single color for the test result indicator. The test results are determined in one of two methods. In one method, the test results are determined from the total number of discrete lines or bands containing the indicator color (see e.g., U.S. Pat. Nos. 4,425,438, 5,073,484, 5,229,073 and 5,451,504). In the alternative method, the test results are determined from the migration distance of a continuous color front (see e.g., U.S. Pat. No. 5,416,000). Discriminating the last line or band or where the color front ends is difficult in these methods and results in uncertainty. The uncertainty in determining the last line/band or the end of the color front is due to the lack of competition for unbound immobilized binding sites and lot-to-lot manufacturing variability in the number of immobilized binding sites present on the device. Thus, a need exits for a lateral flow device that provides accurate, reproducible, semi-quantitative results with a single line or region independent of the number of binding sites present. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF THE INVENTION
The present invention provides a sandwich format LFD with a single test line that is compatible with semi-quantitative detection of large molecule analytes (molecular weight is greater than 3,000 daltons) at low concentrations. Marker competition for binding sites at the single test line within an analyte test zone (ATZ) will indicate zero, low or high concentrations of the analyte of interest.
In accordance with one embodiment of the present invention, a sandwich format LFD with multiple test lines within the ATZ allows for titration of the analyte concentration and semi-quantitative detection.
In another aspect of the present invention, an analyte capture zone referred to as an analyte modulating zone (AMZ) is included in a location reached by the sample prior to reaching the ATZ. The AMZ alters performance by removing a fraction of the analyte and, thereby, increases the detectable range of analyte concentration.
In another aspect of the present invention, an LFD is provided in which a differential amount of immobilized binding ligand in a specified gradient among the multiple test lines is used to modulate the range of concentrations of analyte competing for the limited number of binding sites on the test line. This modulation allows the LFD to accommodate a particular range of concentrations according to the specification of the test.
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A-Fem Medical Corporation
Chin Christopher L.
Klarquist Sparkman Campbell & Leigh & Whinston, LLP
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