Diagnostic assay for a sample of biological fluid

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...

Reexamination Certificate

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C435S283100

Reexamination Certificate

active

06312888

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the field of monitoring the amount of an analyte, e. g., glucose, cholesterol, in body fluid. More particularly, this invention provides an article and method that monitors the amount of analyte in body fluid by means of a reagent that reacts with the analyte in the body fluid.
2. Discussion of the Art
The prevalence of diabetes has been increasing markedly in the world. At this time, diagnosed diabetics represented about 3% of the population of the United States. It is believed that the total actual number of diabetics in the United States is over 16,000,000. Diabetes can lead to numerous complications, such as, for example, retinopathy, nephropathy, and neuropathy.
The most important factor for reducing diabetes-associated complications is the maintenance of an appropriate level of glucose in the blood stream. The maintenance of the appropriate level of glucose in the blood stream may prevent and even reverse many of the effects of diabetes.
Glucose monitoring devices of the prior art have operated on the principle of first taking a sample of blood from an individual by any of a variety of methods, such as by needle or lancet. The individual then inserts a strip carrying reagents into a blood glucose meter in which glucose concentration is determined by a change in reflectance. The individual then applies the sample of blood to the strip. The blood reacts with the reagents and causes a change in reflectance of the strip, thereby indicating the concentration of glucose in the sample of blood. There are numerous devices currently available for diabetics to monitor the concentration of glucose in blood.
One of these devices is the “LIFESCAN” glucose meter. This glucose meter is sold under the tradenames “ONE TOUCH PROFILE” and “ONE TOUCH BASIC.” This glucose meter and products associated therewith are described in U.S. Pat. Nos. 4,935,346; 5,304,468; 5,426,032; 5,563,042; 5,049,487; 5,059,394; 5,179,005, all of which are incorporated herein by reference. This glucose meter uses optical detection technology and a mixture of reagents comprising glucose oxidase, horse radish peroxidase, and color-generating materials known as chromogens. The reagents are located on “ONE TOUCH” reagent-carrying test strips. These devices suffer from the shortcoming of interference from serum components, which adversely affect the accuracy of glucose readings. The glucose oxidase reagent system suffers interference from such materials as bilirubin and ascorbic acid, both of which are always present in the blood in substantial amounts. Another shortcoming of these devices is that the blood applied to the “ONE TOUCH” test strip often migrates to the bottom surface of the “ONE TOUCH” test strip. The blood then transfers onto the glucose meter, and, as a result, users are required to clean the glucose meter after each use. Otherwise, residual blood remaining on the glucose meter will have a detrimental effect on the performance of the glucose meter or on the optical measuring component thereof.
In view of the aforementioned shortcomings, it would be desirable to provide a test strip having a reagent system that resists the effects of such blood components as bilirubin and ascorbic acid. It would also be desirable to provide a test strip that would minimize the migration of blood from the test strip to the glucose meter.
SUMMARY OF THE INVENTION
This invention provides an article and a method for monitoring the concentration of an analyte, e. g., glucose, in blood. In one aspect, the invention involves an article comprising an element having a plurality of layers, i. e., a multiple-layer element. In one embodiment, the article comprises:
a multiple-layer element comprising:
(a) a base layer
(b) a cover layer, the cover layer having a first opening for venting the multiple-layer element and a second opening for receiving a biological sample; and
(c) a core layer having a first major surface and a second major surface, the core layer disposed between the base layer and the cover layer, the core layer comprising a sample introduction chamber and a optical reading chamber, the first major surface of the core layer in face-to-face contact with the base layer, the second major surface of the core layer in face-to-face contact with the cover layer.
The opening for receiving the biological sample communicates with the sample introduction chamber. The opening for venting communicates with a vent channel, which, in turn, communicates with the optical reading chamber. The optical reading chamber and the sample introduction chamber can be adjacent to one another or the optical reading chamber and the sample introduction chamber can be separated from one another but connected by means of a flow channel. Alternatively, the optical reading chamber and the sample introduction chamber can be combined, so long as the size of the combined chambers is sufficiently great that the sample is not introduced directly into the optical reading chamber.
Reagents that are capable of reacting with the analyte to form a reaction product that can be read by an optical instrument to provide the value of concentration of the analyte in the sample are located in the optical reading chamber. When the analyte is glucose, the reagents preferably comprise at least one enzyme and at least one dye. The device is capable of providing a determination of concentration of analyte in a meter designed for colorimetric measurements, such as, for example, the “LIFESCAN” “ONE TOUCH” devices, in about 45 seconds.
The multiple-layer element of this invention allows the use of samples of blood or other biological fluids, such as interstitial fluid, to provide extremely sensitive assay results. The device has been shown to provide accurate and reproducible results with samples having volumes ranging from about 5 &mgr;L to about 20 &mgr;L.
In another embodiment, the article comprises a multiple-layer element comprising:
(a) a cover layer, the cover layer having a first opening for venting the multiple-layer element and a second opening for receiving a sample of biological fluid;
(b) a base layer having a major surface in contact with the cover layer; and
(c) a sample introduction chamber and an optical reading chamber formed in either the cover layer, the base layer, or both the cover layer and the base layer.
The opening for receiving the biological sample communicates with the sample introduction chamber. The opening for venting communicates with a vent channel, which, in turn, communicates with the optical reading chamber. The sample introduction chamber and the optical reading chamber can be adjacent to one another or the sample introduction chamber and the optical reading chamber can separated from one another but connected by means of a flow channel. Alternatively, the optical reading chamber and the sample introduction chamber can be combined, so long as the size of the combined chambers is sufficiently great that the sample is not introduced directly into the optical reading chamber.
The invention also provides means for determining when the optical reading chamber contains a sufficient volume of sample for allowing an accurate reading of an enzymatic reaction. One means involves a colorant that is introduced into the optical reading chamber from the sample introduction chamber or some other location in the element upstream of the optical reading chamber. The colorant would be dissolved or dispersed by the sample as the sample flows through the element. The sample containing the colorant would then be transported to the optical reading chamber where a reading would indicate a change in the optical property of the optical path of the optical reading chamber to indicate that the optical reading chamber contains the sample. The reading from the optical reading chamber can also be used to indicate when a sufficient volume of sample is present for a determination of concentration of an analyte. Another means involves a highly reflective coating overlying and aligned with the

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