Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving oxidoreductase
Reexamination Certificate
1999-10-04
2001-06-05
Leary, Louise N. (Department: 1623)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving oxidoreductase
C435S028000, C435S014000, C435S808000, C435S814000, C435S970000, C564S305000, C564S250000, C562S089000, C562S493000, C544S049000
Reexamination Certificate
active
06242207
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to dye compositions used for colorimetric determination of a chemical or biochemical component (analyte) in an aqueous fluid, such as blood. In particular, the present invention relates to the field of dry reagent matrix compositions for use on test strips adapted to receive a liquid sample of body fluid whereby a dye indicator composition wetted by the fluid reacts with an analyte in the body fluid and provides a visual or color indication of the presence or concentration of the analyte.
2. State of the Art
Indicator compositions for use in devices for color indication of various analytes in liquid samples, such as body fluids, are well known in the art and are embodied in numerous commercial products, such as dry reagent test strips. In such test strips, a dye or dye couple composition is typically formulated in a solution which is applied to a test strip matrix and then dried to form a dry chemistry reagent system on the test strip. The dry chemistry reagent system commonly involves an oxidizable dye or dye couple composition in combination with a oxidase or peroxidase specific for the analyte to be tested. When the dry chemistry reagent system is contacted with a liquid sample containing the analyte, the analyte reacts with its corresponding oxidase or peroxidase producing hydrogen peroxide which in turn oxidizes the dye or dye couple to produce the desired color change thereby indicating the presence or concentration of the analyte.
Example of such dry chemistry reagent systems are disclosed by Phillips et al. in U.S. Pat. Nos. 4,734,360; 5,059,394 and 5,304,468; by Yu in U.S. Pat. No. 5,453,360; Hoenes in U.S. Pat. No. 5,334,508 and by Hochstrasser in U.S. Pat. Nos. 3,964,871 and 4,059,407. The disclosures of these patents are incorporated herein by reference in their entirety.
A number of dry chemistry reagent systems have been incorporated into various commercial products. While such products generally provide acceptable indication and testing under some conditions, certain problems exist with prior dry chemistry systems. For example, in some dry chemistry reagent systems, the dye components tend to sublime over time from the test strip so that when the test strip is used by the consumer it may not provide an accurate indication. This problem limits the shelf life of the test strips.
Additionally, in some dry chemistry reagent systems, the color change provided by the dye or dye couple components continues to change over time rather than reaching a stable end point. When such dye systems are employed, the color indication must be accurately read at specific time intervals in order to obtain an accurate indication of the presence or concentration of an analyte.
Moreover, some dry chemistry reagent systems require a low pH to provide the necessary stability for the dye or dye couple system. However, the pH of such systems is often below the desired pH level for stability of the enzyme used in the dry chemistry system. Therefore, the amount of enzyme employed in the formulation must be increased to compensate for the enzyme's instability, thus increasing the cost of the dry chemistry reagent system. Additionally, when the enzyme is used under non-optimal pH conditions, the enzyme may give undesired or false indications of the presence or concentration of the analyte.
Finally, in some dye or dye couple systems, the optimum wavelength for determining the presence or concentration of an analyte is often obscured or interfered with by components of the body fluid being analyzed, such as hemoglobin.
In view of the above, it is an object of this invention to provide a dry chemistry reagent system having improved stability regarding sublimation of the dye or dye couple system from the dry chemistry test strips.
It is also an object of this invention to provide a dry chemistry reagent system which rapidly produces a stable end point in a short period of time thus eliminating the time dependent measurements or determinations by the user.
It is a further object of this invention to provide a dry chemistry reagent system which can be formulated and used at a pH range more closely approximating physiological pH thus providing a more stable system for the enzyme or enzymes employed in the manufacture and use of the dry chemistry system.
It is a still further object of this invention to provide a dry chemistry reagent system which permits an accurate determination of the presence or concentration of an analyte in a body fluid without significant spectral interference by components of the body fluid being tested.
The above objects as well as others are achieved by the compositions, devices and methods of this invention as disclosed herein.
SUMMARY OF THE INVENTION
The present invention provides dry chemistry reagent matrix composition comprising a matrix material and a reagent composition comprising 3-methyl-6-(sulfonate salts)-benzothiazolinone-(2)-hydrazone (MBTH-S), N-ethyl-N-(3sulfopropyl)aniline (ALPS), and an oxidase and/or a peroxidase enzyme, wherein the reagent composition has been imbibed and dried into or onto the matrix material. This invention is also directed to devices containing such dry chemistry reagent matrix compositions and to methods for determining the presence or concentration of analytes in a fluid sample, such as blood, using the compositions and devices described herein.
Among other factors, the present invention is based on the surprising and unexpected discovery that a dry chemistry reagent system comprising MBTH-S, ALPS and an oxidase enzyme and/or peroxidase enzyme permits the determination of the presence or concentration of an analyte in blood without spectral interference from hemoglobin, i.e., it has improved hematocrit performance. Additionally, this dry chemistry reagent system has a stable end point and may be formulated at a pH range of about 6. Moreover, in another embodiment of this invention, it has been discovered that a dry chemistry reagent system comprising MBTH-S, ALPS, N-(3-sulfopropyl)aniline (HALPS) and an oxidase enzyme and/or peroxidase enzyme has improved dry chemistry stability compared to a dry chemistry system comprising MBTH-S, HALPS and an oxidase enzyme and/or peroxidase enzyme.
Accordingly, in one of its composition aspects, the present invention is directed to a dry chemistry reagent matrix composition comprising a matrix material and a reagent composition comprising 3-methyl-6(M sulfonate)-benzothiazolinone-(2)-hydrazone (MBTH-S) where M is a positive ion providing a stable sulfonate salt; N-ethyl-N-(3-sulfopropyl)aniline or a salt thereof; and an oxidase enzyme or a peroxidase enzyme or mixture thereof, wherein the reagent composition has been imbibed and dried into or onto the matrix material.
Optionally, the reagent composition further comprises a third dye component selected from the group consisting of 3,3-dimethylaminobenzoic acid, 3,5-dichloro-2-hydroxybenzenesulfonic acid, 8-anilino-1-naphthelenesulfonate, N-(3-sulfopropyl)aniline or salts thereof. Preferably, the third dye component is N-(3-sulfopropyl)aniline (HALPS) or a salt thereof.
The dry chemistry reagent composition may further comprise conventional binders, chelating agents, buffers and the like. Such components are well known in the art. The dry chemistry reagent composition is imbibed and dried into or onto a matrix material (i.e., a filter material), such as Gelman Sciences polyethersulfone membrane. The matrix material provides a carrier system for the reagent composition.
The MBTH-S is used in the composition in form of a stable sulfonate salt, of which the sodium salt is preferred, but the potassium, ammonium or other ionic form of the sulfonate salt may be used. In this invention, the MBTH-S is used with ALPS to form a dye couple having improved indication properties. Preferably, the dye composition is used at a physiological pH, more preferably at a pH in the range of about 6 to 8, still more preferably at a pH of about 6.
In another of its composition aspects,
Douglas Joel S.
Drexler Karen R.
Gleisner John M.
Priest John H.
Amira Medical
Burns Doane Swecker & Mathis L.L.P.
Leary Louise N.
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