Immunoassay controls

Details Immunoassay controls Immunoassay controls

2000-04-19

2003-09-30

Chin, Christopher L. (Department: 1641)

Chemistry: analytical and immunological testing

Involving diffusion or migration of antigen or antibody

C422S051000, C422S051000, C422S051000, C435S007100, C435S007200, C435S007210, C435S007320, C435S007920, C435S287100, C435S287200, C435S087000, C435S287900, C435S805000, C435S810000, C435S970000, C436S169000, C436S518000, C436S530000, C436S810000

Reexamination Certificate

active

06627459

ABSTRACT:

FIELD OF THE INVENTION
The invention is directed generally to controls used with point of care immunological tests.
BACKGROUND OF THE INVENTION
Many types of qualitative and/or quantitative assays that were once performed only by trained technical personnel are now routinely performed by individuals having either no training or less than optimal training in specific laboratory procedures and techniques. As one example, medical professionals such as nursing staff frequently perform point of care patient tests, yet frequently lack familiarity with the nuances of these analytical procedures. Such a lack of familiarity can lead to inaccurate test performance because of oversight, technical errors, unfamiliarity with the test procedure, etc. As another example, many types of rapid assay test kits are available for over the counter purchase and home use. In these instances, testing is performed by individuals having no laboratory training whatsoever.
For the above reasons, many point of care tests incorporate the use of an analyte or chemical that will yield a pre-determined result if the assay is performed correctly, known simply as a control specimen or a control. In laboratory analysis, a control is defined as a substance whose composition is qualitatively and/or quantitatively known and that is subject to the same assay procedure as the sample to be tested. A detectable result is displayed, indicative of proper test function and performance, and, hence, a valid assay result. One or more controls may be assayed along with a particular test to determine different concentration ranges of an analyte (e.g., high, low and normal control levels for a particular analyte), or to provide additional assurance of test accuracy and user competence. When medical laboratories perform such tests, assay of a control is a mandatory part of the normal daily routine to ensure accurate results, and incorporation of a control is a component of virtually all state and national quality assurance programs.
One type of control is a sample known to contain a detectable level of an analyte of interest. This control is termed a positive control for the particular analyte because it is known to contain the analyte and thus will yield a positive result if a functional assay is properly performed. Assay of a positive control verifies accuracy of a procedure. However, for a point of care test where one or several tests are performed, an external positive control doubles both the cost and the time required to perform a single patient assay, since a control sample must be tested using one device and a patient sample must be tested using a second device. Additionally, the control must be purchased and stored separately, which imposes added cost and inconvenience. To overcome these drawbacks, some manufacturers have incorporated a positive control directly into the assay device, a so-called “built-in” positive control.
One general type of built-in positive control in a sandwich immunoassay may utilize a protein that is a member of a specific binding pair, such as IgG or other types of antibodies, or antigens. The protein is labeled through binding to any of various types of labels or markers (e.g., enzymes, chromophores, fluorophores, metal sols, etc.) to render it detectable, either directly or indirectly. The labeled protein is captured on a defined zone (“positive control zone”) of a test device by an immobilized protein that is its specific binding partner.
One example of a test incorporating a positive control for a sandwich immunoassay is the ICON® II HCG ImmunoConcentratione™ Assay (Hybritech Inc., San Diego, Calif.) for the determination of human chorionic gonadotropin (hCG) in a sample of serum or urine. In the ICON® assay, the analyte serving as a positive control is an antibody against IgG (anti-IgG) which is immobilized at a positive control site in the test device. The immobilized anti-IgG antibody binds to IgG, present as mouse monoclonal IgG (anti-hCG) that is conjugated or labeled with alkaline phosphatase enzyme (IgG-Enz). The anti-IgG immobilizes the IgG-Enz conjugate and, when the substrate for the enzyme is added, a color forms at the positive control site. Thus, the positive control in the ICON® test is a two component complex of one antigen (IgG) and one antibody (anti-IgG), and a positive result is indicated by the presence of color at the positive control site.
Similarly, and as an example of a test incorporating a control for a competitive immunoassay, the Triage® Drugs of Abuse Panel plus Tricyclic Antidepressants (Biosite Diagnostics, San Diego, Calif.) test for urine drug detection forms a two component complex in the positive control zone. In the Triage® test, which is a competitive binding immunoassay, a labeled antigen (drug) provided as a reagent competes with drug which may be present in the patient urine sample for antibody binding sites. Labeled antigen, displaced from antibody binding sites by drug that was present in the patient sample, binds to a zone of antibody that is immobilized on the test membrane. While the composition of the positive control in the Triage® test is not disclosed by the manufacturer, it is likely a two component complex of one antigen and one antibody and a positive result is indicated by the presence of color at the positive control site. As in the ICON® test, the immunological reaction for a positive control is different from the reaction for a test sample.
Both the ICON® and the Triage® tests use the presence of a color at the positive control site as an internal assay control to indicate correct reagent addition and test performance. In competitive assays, one can assay either the labeled antigen that has bound to the antibody by measuring the amount of label in the antigen-antibody complex (bound fraction), or one can assay the labeled antigen that has not bound to the antibody by measuring the amount of label in the supernatant (free fraction). In rapid immunoassays involving a test strip or membrane, it is the bound fraction that is routinely monitored, since the test strip or membrane itself contains the bound fraction.
If analyte is absent from the sample, there will be no competition and the labeled antigen will occupy all of the limited number of antibody binding sites. If analyte is present in a sample, there will be competition and less labeled antigen will be present in the bound fraction. Thus, when analyzing the bound fraction in competitive assays, presence of analyte is indicated by the absence of color in the test site. What is needed, therefore, and what is not provided in the assays presently available, is a test incorporating a built-in positive control that generates a positive result as an absence of color, as occurs in competitive assays.
A positive control should preferably test for the presence of the same or a related analyte as that being assayed, using the same device as is used for detecting the analyte, and using the same chemistry and the same type of immunological reaction as is used for detecting the analyte. However, in competitive reactions, the presence of analyte is indicated by the absence of color formation on the test strip. Thus, a need exists for an improved positive control for point of care testing of one or more analytes in a sample which reflects the use of the same chemistry and the same type of immunological reaction as occurs for the analyte of interest.
SUMMARY
The invention is directed to a device and method of using the device in which a test strip incorporates a positive control that is identical or closely related to at least one biological analyte, and that uses same device and the same immunological reaction as is used for detecting the analyte. Such a device and method provide a more reliable indicator that the assay was functional and was correctly performed, and that an accurate result was achieved. This is particularly useful for tests performed by lay operators, for example, tests sold over-the-counter for at home use.
The invention is also directed to a test strip for immunoassay of at least

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