Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals
Reexamination Certificate
1999-02-11
2001-10-02
Chin, Christopher L. (Department: 1641)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
C422S051000, C422S051000, C422S051000, C422S051000, C422S067000, C435S287100, C435S287200, C435S287900, C435S287700, C435S287800, C435S805000, C435S810000, C435S970000, C436S169000, C436S170000, C436S514000, C436S805000, C436S810000
Reexamination Certificate
active
06297060
ABSTRACT:
FIELD OF THE INVENTION
This invention is in the field of assay devices, including devices for ligand-receptor methods which are used for the detection of selected analytes in a fluid sample. More particularly, this invention relates to devices for performing solid-phase assays requiring a separation of bound from unbound labeled reagents. The inventive devices described herein may be used in the performance of assays to obtain qualitative, semi-quantitative or quantitative determinations of one or more analytes within a single test format.
BACKGROUND OF THE INVENTION
As used herein, the term “ligand-receptor” assay refers to an assay for an analyte which may be detected by the formation of a complex between a ligand and another substance capable of specific interaction with that ligand, i.e., ligand receptor. The ligand may be the analyte itself or a substance which, if detected, can be used to infer the presence of the analyte in a sample. In the context of the present invention, the term “ligand”, includes haptens, hormones, antigens, antibodies, deoxyribonucleic acid (DNA), ribonucleic acids (RNA), metabolites of the aforementioned materials and other substances of either natural or synthetic origin which may be of diagnostic interest and have a specific binding partner therefor, i.e., the ligand receptor in the ligand-receptor assay. The term “ligand receptor” includes materials for which there is a specific binding partner, i.e., the ligand of the ligand-receptor assay. Those skilled in the art will appreciate that the analyte of interest, a member of a specific binding pair, may be either ligand or ligand receptor depending upon assay design.
Ligand-receptor assays are generally useful for the in-vitro determination of the presence and/or concentration of ligands in body fluids, food products, and environmental samples. For example, the determination of specific hormones, proteins, therapeutic drugs, and toxins in human body fluids has significantly improved the ability of medical practice to diagnose and minister to the human condition. There is a continuing need for simple, rapid, non-instrumental assays for the qualitative and semi-quantitative determination of such ligands in a sample. This need for simple, rapid methods entails a concomitant requirement for assay devices to complement such assay methods. Furthermore, in many situations, such assays methods need to be simple enough to be performed and interpreted by non-technical users without the requirement of costly and complex apparatus suitable for use only in a laboratory setting by highly skilled personnel.
Ligand-receptor assays rely on the binding of ligands by receptors to determine the concentration of ligands in a sample. Ligand-receptor assays can be characterized as either competitive or non-competitive. Non-competitive assays generally utilize receptors in substantial excess over the amount of ligand to be determined. Sandwich assays, in which the ligand is detected by binding to two receptors, one receptor labeled to permit detection and a second receptor typically bound to a solid phase to facilitate separation of bound from unbound reagents, such as unbound labeled first receptor, are examples of noncompetitive ligand-receptor assays. Proteins, hormones and deoxyribonucleic acid (DNA) are examples of ligands commonly detected using non-competitive assays. Competitive assays generally involve ligand from the sample, a ligand analogue labeled to permit detection, and the competition of these species for a limited number of ligand receptor binding sites. Examples of ligands which are commonly measured by competitive ligand-receptor assays include haptens, hormones and proteins. Antibodies that can bind these classes of ligands are frequently used in both non-competitive and competitive assays as the ligand receptors.
Ligand-receptor assays can be further described as being either homogeneous or heterogeneous. In homogeneous assays, all of the reactants participating in the reaction are admixed and the quantity of ligand is determined by its effect on the binding events involving the labeled species. The signal observed is modulated by the extent of this binding and can be related to the amount of ligand in the sample. U.S. Pat. No. 3,817,837 describes such a homogeneous, competitive immunoassay in which the labeled ligand analogue is a ligand-enzyme conjugate and the ligand receptor is an antibody capable of binding to either the ligand or the ligand analogue. The binding of the antibody to the ligand-enzyme conjugate decreases the activity of the enzyme relative to the activity observed when the ligand-enzyme conjugate is in the unbound state. Due to competition between unbound ligand and ligand-enzyme conjugate for antibody binding sites, as the ligand concentration increases the amount of free ligand-enzyme conjugate increases and thereby increases the observed signal. The product of the enzyme reaction may then be measured kinetically using a spectrophotometer.
Heterogeneous ligand-receptor assays require a separation of bound labeled ligand receptor or labeled ligand analogue from the free labeled ligand receptor or labeled ligand analogue and a subsequent measurement of either the bound or the free fraction. Methods for performing such heterogeneous, competitive assays are described in U.S. Pat. Nos. 3,654,090, 4,298,685, and 4,506,009; such a non-competitive assay is described in U.S. Pat. No. 4,376,110.
The need for ligand-receptor assays that can be performed without the use of instrumentation has led to the development of assay devices that can be visually interpreted. U.S. Pat. Nos. 4,125,372, 4,200,690, 4,246,339, 4,366,241, 4,446,232, 4,477,576, 4,496,654, 4,632,901, 4,727,019, and 4,740,468 describe devices and methods for heterogeneous, ligand-receptor assays that can develop colored responses to permit visual interpretation of the results.
Among the first devices developed for ligand-receptor assays were simple dipstick type devices designed for contacting a porous material such as a membrane with both the sample and labeled reagents via immersion allowing appropriate reagent incubations to occur and then separating the free from the bound label using a wash step. Such devices are described in U.S. Pat. Nos. 3,715,192, 4,200,690, and 4,168,146 and EPO Appl. Nos. 0 032 286 and 0 063 810. A common distinguishing feature of devices constructed in a dipstick format is the absence of a fluid receiving zone within the device for containing the sample, liquid reagents and wash solutions after the performance of the sample and reagent incubations and the separation of free from bound label. The lack of such a fluid receiving zone precludes characterization of such a dipstick device as self-contained, given that some external fluid receptor must be provided to capture used sample, unbound labeled reagents and spent wash fluid.
A class of devices which constitute an improvement over the simple dipstick construct is the immunochromatographic test strip device. This class of device generally exhibits improved sensitivity in ligand detection relative to that of simple dipstick devices by virtue of the ligand concentrating effect achieved by the flow of sample containing the ligand past an immobilized ligand receptor zone. Such devices also provide a limited fluid receiving zone for fluids used in the performance of the assay. A fluid receiving zone is created by increasing the length of the porous member to provide a suitable amount of total void volume capacity. Such devices are described in U.S. Pat. Nos. 4,094,647, 4,235,601, 4,361,537, 4,366,241, 4,435,504, 4,624,929, 4,740,468, 4,756,828, and 4,757,004; EPO. Appl. Nos. 0 267 006, 0 271 204, and 0 299 428; and PCT Appl. No. US86/0668. Even though such immunochromatographic devices do include a limited fluid receiving zone, they do not enable an efficient free/bound label separation, since the rate of separation is slow and limited by the rate at which fluid travels along the length of the porous member. Some immunochromatographic devices are so
Anderson Richard R.
Buechler Kenneth F.
Nowakowski Mark R.
Valkirs Gunars E.
Biosite Diagnostics, Inc.
Chin Christopher L.
Foley & Lardner
LandOfFree
Assay devices comprising a porous capture membrane in... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Assay devices comprising a porous capture membrane in..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Assay devices comprising a porous capture membrane in... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2611441