Chemistry: analytical and immunological testing – Heterocyclic carbon compound – Hetero-o
Reexamination Certificate
1997-05-12
2002-05-21
Snay, Jeffrey (Department: 1743)
Chemistry: analytical and immunological testing
Heterocyclic carbon compound
Hetero-o
C436S151000, C422S082020
Reexamination Certificate
active
06391645
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a biosensor, and, more particularly, to a new and improved method and apparatus for correcting ambient temperature effect in biosensors.
DESCRIPTION OF THE PRIOR ART
The quantitative determination of analytes in body fluids is of great importance in the diagnoses and maintenance of certain physiological abnormalities. For example lactate, cholesterol and bilirubin should be monitored in certain individuals. In particular, the determination of glucose in body fluids is of great importance to diabetic individuals who must frequently check the level of glucose in their body fluids as a means of regulating the glucose intake in their diets. While the remainder of the disclosure herein will be directed towards the determination of glucose, it is to be understood that the procedure and apparatus of this invention can be used for the determination of other analytes upon selection of the appropriate enzyme. The ideal diagnostic device for the detection of glucose in fluids must be simple, so as not to require a high degree of technical skill on the part of the technician administering the test. In many cases, these tests are administered by the patient which lends further emphasis to the need for a test which is easy to carry out. Additionally, such a device should be based upon elements which are sufficiently stable to meet situations of prolonged storage.
Methods for determining analyte concentration in fluids can be based on the electrochemical reaction between an enzyme and the analyte specific to the enzyme and a mediator which maintains the enzyme in its initial oxidation state. Suitable redox enzymes include oxidases, dehydrogenases, catalase and peroxidase. For example, in the case where glucose is the analyte, the reaction with glucose oxidase and oxygen is represented by equation (A).
glucose
+
O
2
glucose
oxidase
(
GO
)
_
>
gluconolactone
+
H
2
O
2
(
A
)
In a calorimetric assay, the released hydrogen peroxide, in the presence of a peroxidase, causes a color change in a redox indicator which color change is proportional to the level of glucose in the test fluid. While calorimetric tests can be made semi-quantitative by the use of color charts for comparison of the color change of the redox indicator with the color change obtained using test fluids of known glucose concentration, and can be rendered more highly quantitative by reading the result with a spectrophotometric instrument, the results are generally not as accurate nor are they obtained as quickly as those obtained using an electrochemical biosensor. As used herein, the term biosensor is intended to refer to an analytical device that responds selectively to analytes in an appropriate sample and converts their concentration into an electrical signal via a combination of a biological recognition signal and a physico-chemical transducer. Aside from its greater accuracy, a biosensor is an instrument which generates an electrical signal directly thereby facilitating a simplified design. Furthermore, a biosensor offers the advantage of low material cost since a thin layer of chemicals is deposited on the electrodes and little material is wasted.
H
2
O
2
→O
2
+2H
30
2e
−
(B)
The electron flow is then converted to the electrical signal which directly correlates to the glucose concentration.
In the initial step of the reaction represented by equation (A), glucose present in the test sample converts the oxidized flavin adenine dinucleotide (FAD) center of the enzyme into its reduced form, (FADH
2
).
Because these redox centers are essentially electrically insulated within the enzyme molecule, direct electron transfer to the surface of a conventional electrode does not occur to any measurable degree in the absence of an unacceptably high overvoltage. An improvement to this system involves the use of a nonphysiological redox coupling between the electrode and the enzyme to shuttle electrons between the (FADH
2
) and the electrode. This is represented by the following scheme in which the redox coupler, typically referred to as a mediator, is represented by M:
Glucose+GO(FAD)→gluconolactone+GO(FADH
2
)
GO(FADH
2
)+2M
OX
→GO(FAD)+2M
red
+2H
2M
red
→2M
OX
+2e
−
(at the electrode)
In this scheme, GO(FAD) represents the oxidized form of glucose oxidase and GO(FADH
2
) indicates its reduced form. The mediating species M
red
shuttles electrons from the reduced enzyme to the electrode thereby oxidizing the enzyme causing its regeneration in situ which, of course, is desirable for reasons of economy. The main purpose for using a mediator is to reduce the working potential of the sensor. An ideal mediator would be re-oxidized at the electrode at a low potential under which impurity in the chemical layer and interfering substances in the sample would not be oxidized thereby minimizing interference.
Many compounds are useful as mediators due to their ability to accept electrons from the reduced enzyme and transfer them to the electrode. Among the mediators known to be useful as electron transfer agents in analytical determinations are the substituted benzo and naphthoquinones disclosed in U.S. Pat. No. 4,746,607; the N-oxides, nitroso compounds, hydroxylamines and oxines specifically disclosed in EP 0 354 441; the flavins, phenazines, phenothiazines, indophenols, substituted 1,4-benzoquinones and indamins disclosed in EP 0 330 517 and the phenazinium/phenoxazinium salts described in U.S. Pat. No. 3,791,988. A comprehensive review of electrochemical mediators of biological redox systems can be found in
Analytica Clinica Acta
. 140 (1982), Pp 1-18.
Among the more venerable mediators is hexacyanoferrate, also known as ferricyanide, which is discussed by Schläpfer et al in
Clinica Chimica Acta
., 57 (1974), Pp. 283-289. In U.S. Pat. No. 4,929,545 there is disclosed the use of a soluble ferricyanide compound in combination with a soluble ferric compound in a composition for enzymatically determining an analyte in sample. Substituting the iron salt of ferricyanide for oxygen in equation (A) provides:
since the ferricyanide is reduced to ferrocyanide by its acceptance of electrons from the glucose oxidase enzyme.
Another way of expressing this reaction is by use of the following equation (C):
Glucose+GO(FAD)→Gluconolactone+GO(FADH
2
)
GO(FADH
2
)+2FE(CN
3
)
3−
6
→GO(FAD)+2FE(CN)
6
4−
+2H
+
2FE(CN)
6
4−
→2FE(CN)
6
3−
+2e
−
(at the electrode) (C)
The electrons released are directly proportional to the amount of glucose in the test fluid and can be related thereto by measurement of the current which is produced upon the application of a potential thereto. Oxidation of the ferrocyanide at the anode renews the cycle.
SUMMARY OF THE INVENTION
Important objects of the present invention are to provide a new and improved method and apparatus for correcting ambient temperature effect in biosensors; to provide such method and apparatus that eliminates or minimizes the ambient temperature effect in analyte concentration value identified by a biosensor; and to provide such method and apparatus that overcome many of the disadvantages of prior art arrangements.
In brief, a method and apparatus are provided for correcting ambient temperature effect in biosensors. An ambient temperature value is measured. A sample is applied to the biosensors, then a current generated in the test sample is measured. An observed analyte concentration value is calculated from the current through a standard response curve. The observed analyte concentration is then modified utilizing the measured ambient temperature value to thereby increase the accuracy of the analyte determination.
In accordance with a feature of the invention, the analyte concentration value is calculated by solving the following equation:
G
2
=
G
1
-
(
T
2
2
-
24
2
)
*
I2
-
(
T
2
-
24
)
*
I1
(
T
2
2
-
24
2
)
*
S2
+
(
T
2
-
24
)
*
S1
+
1
where
Huang Dijia
Tudor Brenda L.
Yip Kin-Fai
Bayer Corporation
Jeffers Jerome L.
Snay Jeffrey
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