Electrolysis: processes – compositions used therein – and methods – Electrolytic analysis or testing – Involving enzyme or micro-organism
Reexamination Certificate
2001-01-29
2003-06-10
Warden, Sr., Robert J. (Department: 1744)
Electrolysis: processes, compositions used therein, and methods
Electrolytic analysis or testing
Involving enzyme or micro-organism
C204S400000, C204S403010, C204S403110, C204S408000
Reexamination Certificate
active
06576117
ABSTRACT:
TECHNICAL FIELD
This invention relates to a method for electrochemically measuring a concentration of an analyte in a sample. More specifically, this invention relates to a method for electrochemical measurement to obtain a concentration of analyte in a sample by correcting errors caused by sample physical properties and sensor sensitivity.
BACKGROUND ART
Recently in the fields of biochemistry, clinical medicine or the like, electrochemical measurement has been used to measure a concentration of an analyte in a sample in a rapid and simple manner. An electrochemical measurement is a method to measure an analyte in a sample by using an electric signal such as a current that is obtained from a chemical reaction or an enzymatic reaction.
For example, the concentration of glucose in a blood is measured in the following process. Glucose as an analyte in a blood sample reacts with glucoseoxidase (GOD) to generate a GOD·H2 complex, from which electrons are liberated by an electron carrier such as potassium ferricyanide. The free electrons are captured in an electrode to calculate a current value, and thus, a glucose concentration is obtained by calculation from a calibration curve, a calibration formula or the like that is produced previously.
In an electrochemical measurement, a disposable device called a biosensor is commonly used. A biosensor has a reaction layer and an electrode system.
A reaction layer comprises a reaction reagent, an enzyme or a matrix to react specifically with an analyte in a sample, and provides a reaction site.
An electrode system comprises a working electrode and a counter electrode, and by applying voltage to perform an oxidation-reduction reaction, the electrode system captures electrons that are generated by the chemical reaction occurring in the reaction layer, where the electrons are electric signals of a current from an electron carrier to the electrode.
A biosensor is used in a combination with a measurement apparatus having various functions such as providing a certain voltage in a predetermined period, measuring electric signals transferred from the biosensor, and converting the electric signals into a concentration of the analyte. Such a system is called a biosensor system.
Among various methods to apply voltage to an electrode system, a method to apply voltage like a rectangular wave with respect to time is called a potential step method. In a typical biosensor system, sample feeding to the biosensor is detected and subsequently, an open circuit or a voltage with substantially no current flow is provided to promote a chemical reaction. After a predetermined period of time, a fixed voltage is applied to deliver electrons between the electron carrier and the electrode, i.e., to perform an oxidation-reduction reaction. A state where the biosensor is provided with a voltage to perform a desired oxidation-reduction reaction is called an excitation state. In general, a current value at an arbitrarily-predetermined point of time during the excitation state is measured, and the current value is converted into a concentration of the analyte, using a calibration curve and a calibration formula that are produced previously.
Methods in which plural excitations and plural current measurements are performed are disclosed, for example, in JP-2651278, JP-A-8-304340, and JP-A-10-10130.
JP-2651278 provides a method to determine whether a current flowing in a reaction site changes in accordance with a relationship with a certain Cottrell current.
JP-A-8-304340 suggests reduction of measurement errors caused by a reduction type intermediate product that is generated during a storage of the sensor.
JP-A-10-10130 provides a method for discriminating a whole blood sample and an aqueous solution as a control in a biosensor system.
Measurement results obtainable by using the biosensor can include errors due to various factors. One of the factors causing such errors is a sample physical property.
For example, when the sample is whole blood and the analyte is glucose in the blood, the hematocrit value (Hct) as a volume ratio of erythrocyte to the whole blood is found to cause errors in the measurement result, and differences between individuals are great. The reason appears to be a rising viscosity of the sample.
Concentrations of neutral fat and protein in the blood also affect the measurement result. In a measurement of an analyte in a blood, sample physical properties, such as blood cells, lipid and protein, will cause measurement errors.
Generally in a conventional method to avoid any influences by such errors, the composition of a chemical reaction layer or of an electrode system in a biosensor is improved. For example, JP-A-62-64940 discloses a biosensor in which an enzyme to detoxify a measurement-interfering substance is immobilized on an enzyme-immobilizing membrane. JP-A-61-3048 discloses a biosensor comprising not only a biocatalytic electrode but an electrode to detect the quantity of measurement-interfering substances. JP-A-60-211350 discloses a biosensor comprising two electrode systems including an electrode system containing an enzyme and a pigment and also an electrode system provided with a porous material containing a pigment only. However, these biosensors with complicated structures require complicated manufacturing processes, and the manufacturing cost is also raised.
Sensor sensitivity can be another factor causing measurement errors. In many cases, sensor sensitivity varies from one manufacturing lot of biosensors to another. Manufactures make sensor sensitivity correction tips for the respective lots, and ship the tips with their biosensors.
When a lot for a biosensor is changed, a user should correct sensitivity by using a correction tip corresponding to the changed lot before he performs an ordinary measurement (JP-A-4-357452).
However, such an operation will impose extra work on the user. Moreover, since the range corrected with such a correction tip is determined based on the sensitivity during manufacture of the sensor, changes of the sensor sensitivity over time, which occur after shipping, will not be corrected.
Since an electrochemical measurement includes a chemical reaction, it is affected also by an environmental temperature and a sample temperature. Namely, an environmental temperature and sample temperature also can be factors of measurement errors. JP-2748196 provides a method of correcting nonlinear temperature dependency of a chemical sensor.
Therefore, the purpose of the present invention is to provide an electrochemical measurement method that can decrease work for users and manufacturers without requiring any complicated structure or process of manufacturing a biosensor and a measurement apparatus. Such a method can provide highly accurate results by correcting errors of concentration of an analyte in a sample.
DISCLOSURE OF THE INVENTION
To achieve the purpose, the present invention provides an electrochemical measurement to measure a concentration of an analyte in a sample by using a biosensor having an electrode system and a chemical reaction layer. The measurement comprises calculation to obtain as parameters a current value obtained as a result of application of a fixed voltage to the sensor after feeding the sample and the ratio of the current value, and calculation of the concentration of the analyte by using a statistical technique. The parameters are set adequately for each error factor affecting the measurement results, and error factors can be corrected directly by selecting parameters that will be affected greatly by the sample physical properties, or by selecting current values that will be affected greatly by the sensor sensitivity.
For the above-mentioned parameters, for example, the following parameters P
1
and P
2
are preferably used, and the parameters are obtained by applying a predetermined voltage twice to a biosensor after feeding a sample in order to promote an electrochemical reaction.
P
1
: a ratio (If/Ib), where (If) is the value of maximum current or a current occurring after the maximum in a first
Hamamoto Katsumi
Iketaki Kazuo
Inoue Yoichi
Arkray
Merchant & Gould P.C.
Olsen Kaj K.
Warden, Sr. Robert J.
LandOfFree
Method and apparatus for electrochemical measurement using... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method and apparatus for electrochemical measurement using..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and apparatus for electrochemical measurement using... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3109695