Patent Application
20050194265
The present invention relates to a method for reducing measuring bias in amperometric biosensors, characterized in that at the same time an analyte is applied to a sensor whose electrode system has been applied a predetermined potential, the background current resulted from the major interferences at the initial stage of the reaction of the biosensor is eliminated in the manner of gradually lowering the level of the predetermined potential.
Methods for measuring certain analytes in liquid test samples with amperometric biosensors are often used in monitoring of clinical physiological abnormalities, such as enzymatic amperometric blood sugar and lactate measuring methods, and non-enzymatic uric acid and hemoglobin measuring methods. Regardless of enzymatic or non-enzymatic system, an electric mediator is used as a transmitting mediator for electric signals of the redox reaction of the analyte.
As indicated in
During the storage period before being applied, the electric mediator or other components of the amperometric biosensor (for example, enzyme stabilizers or surfactants having oxidizing or reducing equivalents) may undergo oxidation or reduction reactions due to environmental influence (such as luminous energy, thermal energy or humidity). If the sensor containing reacted components is used to measure an analyte in a test sample, the reacted components will become background interference, and affect the current measuring value of the electrode system of the sensor, namely forming the bias value. Therefore, when using an amperometric biosensor, interference resulted from environmental influence must be reduced or eliminated so as to accurately determine the analyte concentration in the test sample.
At present, the common method for eliminating the background noise is to switch on the circuit of the electrode system and simultaneously eliminate the background interference, when the liquid test sample is applied to the sensor whose electrode system has been applied a predetermined potential, so as to reduce the bias value.
However, while the former, which uses the power-on manner, can reduce the background current, it cannot accumulate the reaction intensity of the analyte in a short time (10 to 20 seconds) and thus reduce the signal intensity, but increases the power consumption. On the other hand, while the latter cuts off the power after using fixed potential to eliminate major background interferences so as to reduce the power consumption, it also eliminates the signal converted to the electric mediator through redox process at the initial stage after the analyte is applied to the measuring slot, and thus the signal during the earlier period of the reaction cannot be accumulated. As a result, in prior art operations, the economic efficiency and accuracy of the correlation between the current and the concentration of the analyte in the test sample remains to be improved.
The major object of this invention is to provide an improved method for reducing the measuring bias in amperometric biosensors.
The present invention provides a novel method for reducing the measuring bias in amperometric biosensors, comprising the following steps:
The method for measuring the concentration of the analyte in the test sample provided by the present invention is characterized by, at the same time when the test sample is applied to the amperometric biosensor whose electrode system has been applied a predetermined potential to switch on the electrode system circuit, gradually lowering the predetermined potential to a value unable to drive a electrochemical redox reaction.
The method according to the invention not only can eliminate the background current of the major interference at the initial stage of the reaction, but also can retain the reacted electric mediator from the analyte in the test sample at the initial stage of the redox reaction as far as possible, and thus the electric signal at the initial stage of the reaction can be accumulated. The present invention not only can eliminate the interfering noise, but also can retain a high signal value as far as possible (namely, to increase the signal/noise (S/N) ratio), and thus improve the preciseness and accuracy of the correlation between the current and the concentration. In addition, since the predetermined potential supply is gradually lowered, when interrupting the electrochemical redox to await the signal accumulation of electric mediators, power consumption can also be reduced at the same time.
Persons skilled in the art is aware of that a digital or analog converting control and current signal capturing module can be used to control the potential supplied to the electrode system of the amperometric biosensor and to capture the current generated from the electrochemical redox reaction. Thus, the operation of gradually lowering potential in the invention can be performed in a digital or analog manner, depending on the type of the used converting control and current signal capturing module.
The value of the predetermined potential applied to the electrode system of the sensor before the application of the test sample used in the method of the invention relates to the interfering degree of environmental factors, and generally ranges from about 0.1 volt to 0.9 volt, preferably from 0.3 volt to 0.7 volt, which is familiar to persons skilled in the art.
The step of gradually lowering the predetermined potential in the method according to the invention takes about 1 to 15 seconds, preferably from 4 to 10 seconds. The reaction time of the test sample and the value of the second potential used to drive the electric mediator to conduct a electrochemical redox reaction are not critical to the invention, and can be determined by persons skilled in the art according to the types of test samples and sensors actually used in the operation, wherein the second potential can be higher than, equal to, or lower than the predetermined potential.
The method according to the invention is applicable to enzymatic or non-enzymatic amperometric biosensors. The structures of enzymatic or non-enzymatic amperometric biosensors are familiar to persons skilled in the art. The method according to the invention is not limited to any particular type of amperometric biosensor. Generally, the enzymatic amperometric biosensor typically comprises an electrode system, a redox enzyme specific to particular analytes, an electric mediator for redox, a carrier and buffering agent consisted of conjugate acid and base; and the non-enzymatic amperometric biosensor typically comprises an electrode system, an electric mediator for redox and a carrier. The carrier generally includes water-soluble high polymers, and optionally includes surfactants. The electric mediator for redox is usually potassium ferricyanide.
The glucose biosensor test strip available from the implementation of ROC (Taiwan) Pat. No. 416005 is used to further show the advantages of the method according to the invention.
The glucose biosensor test strip is of the structural components and combination as shown in
The environmental interference is increased by the accelerated aging stimulation (storage environment for the test strip being at 50□, lasting for 1 week and eight weeks, respectively). A digital converting control and current signal capturing module is used to control the potential supplied to the electrode system of the amperometric glucose biosensor and to capture the current generated from the electrochemical redox reaction. Finally, the acquired current reading is converted into the glucose concentration.
The following examples are used to provide further illustration for the invention, but not intended to restrict the scope of the invention. All those skilled in the art can easily make modifications and changes without departing from the scope of the invention.
Two groups of power supply modes were set, one as the initial supply potential of 300 mV, which was reduced to 0 mV immediately after the test sample was applied to the electrode system as used in prior art (
The above-mentioned two groups of power supply setting modes and bloods with different concentration of glucose (lower, medium, and higher) were applied to the same batch of glucose biosensor test stripes being accelerated aging processed. The reaction was maintained for 16 seconds. Then, a driving potential of 300 mV was applied, and the redox current in positive correlation with the concentration of glucose was measured. The result is shown in
When applying the prior art power supply mode to the glucose biosensor test strip, the intercept of the linear equation drawn with the sensor reading (lasting one week=1W-O, and lasting 8 weeks=8W-O) and reference method (YSI electrochemistry blood sugar biochemical meter) was increased (from 3.95 to 25.75), which shows the obvious existence of background interference generated from the acceleration condition. However, when applying the power supply mode according to the conception of the invention to the glucose biosensor test strip (lasting 1 week=1W-N, and lasting 8 weeks=8W-N), the intercept of the linear equation shows no significant difference (1.51 and −0.08), which shows the apparent reduction of background interference.
Furthermore, the method according to the invention adopts the mode of gradually lowering the supplied potential to 0 mV, which interrupts the electrochemical redox reaction. Therefore, during the period awaiting the signal accumulation of electric mediator, power consumption can be reduced. In conclusion, the method according to the invention is in fact an effective method to reduce the latent bias value caused by background interference for amperometric biosensors.
| Number | Date | Country | Kind |
|---|---|---|---|
| 093105540 | Mar 2004 | CN | national |
| 094104671 | Feb 2005 | CN | national |
