CN1515682A - Biological sensor capable of correcting environmental temperature effect and its method - Google Patents

Biological sensor capable of correcting environmental temperature effect and its method Download PDF

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Publication number
CN1515682A
CN1515682A CNA031010407A CN03101040A CN1515682A CN 1515682 A CN1515682 A CN 1515682A CN A031010407 A CNA031010407 A CN A031010407A CN 03101040 A CN03101040 A CN 03101040A CN 1515682 A CN1515682 A CN 1515682A
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China
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biosensor
specific component
ambient temperature
biochip
sample
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CNA031010407A
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Chinese (zh)
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黄英俊
陈俊仁
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Transpacific IP Ltd
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Transpacific IP Ltd
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Abstract

The present invention relates to a biological sensor capable of correcting environmental temperature effect and its method. It provides a specific component discharged curve measuring method in the tested body corresponding to different environmental temperatures of biological sensor. According to Vout obtained by measurement and formula (I) Vout=(1+Rc/Rs)Vref the resistance Rc sensitive to environmental temp. in biological sensor can be obtained, according to the table of comparisons of Rc-environmental temp. the environmental temp. % can be resolved, then according to the table of comparisons of Vout of correspondent environmental temp. T and specific component discharged curve the specific component discharged curve in the tested body can be obtained, and according to the discharged curve the specific component content in the tested body can be obtained.

Description

Biosensor capable of correcting environmental temperature effect and method thereof
Technical Field
The present invention relates to a biosensor, and more particularly, to a biosensor and method for correcting the effect of ambient temperature.
Background
In recent years, various biosensors using specific enzymes to catalyze reactions have been developed for medical applications. One use of such biosensors is in the treatment of diabetes to help diabetics control their own blood glucose levels (glucose concentration in the blood) to within a normal range. For hospitalized diabetics, their own blood glucose levels can be controlled within normal ranges under the supervision of a doctor. However, for non-hospitalized diabetic patients, it becomes very important that the patients themselves control the blood sugar content themselves without direct supervision of the doctors.
Self-control of blood glucose levels can be achieved by diet, exercise, and medication. These treatment modalities are usually employed simultaneously under the supervision of a physician. When a diabetic can detect whether the blood sugar content of the diabetic is in a normal range, the diabetic can help the diabetic to control the blood sugar content of the diabetic more effectively.
FIG. 1 shows a blood glucose meter for self-testing of blood glucose levels by a patient, which includes a main test unit 10 and a biochip 12 for measuring blood glucose levels. Referring to fig. 2, the biochip 12 is shown in an exploded view, and includes a strip-shaped substrate 122 having an electrode portion 1221 at the front end thereof. The electrode 1221 is covered by a reaction layer 124, a spacer 126, and a cover plate 128. The electrode 1221 has an operating electrode 1222 and a corresponding electrode 1224 surrounding the operating electrode 1222. The operation electrode 1222 and the corresponding electrode 1224 are electrically connected to a conducting wire 1226 and a conducting wire 1228 at the end of the strip substrate 122, respectively. The reaction layer 124 covering the electrode portion 1221 contains potassium ferricyanide (potassium ferricyanide) and an oxidase (oxidase), such as glucose oxidase (glucose oxidase).
In using the above blood glucose meter, the biochip 12 is first inserted into the main test unit 10. The patient may then prick his or her skin with a lancet to exude a drop of blood, which is then dropped directly onto the end of the biochip 12 that has been inserted into the main test unit 10. The drop of blood is drawn into the reaction layer 124 over the electrode 1221, dissolving the reaction layer 124, and performing an enzyme-catalyzed reaction, as shown in the following equation:
a predetermined amount of potassium ferrocyanide (potassium ferrocyanide) is produced in response to the glucose concentration in the blood sample. After a predetermined period of time, an applied voltage VrefApplied on the biochip 12 to electrochemically react potassium ferrocyanide to release electrons, and generate a corresponding reaction current through the operation electrode 1222. The reaction current is proportional to the concentration of potassium ferrocyanide produced by the enzyme-catalyzed reaction or to the concentration of glucose in the blood sample. The glucose concentration in the blood sample can be obtained by measuring this reaction current.
FIG. 3 is a schematic diagram of a control circuit of the blood glucose meter shown in FIG. 1, in which an electrode 1221 of the biochip 12 can be regarded as a resistor RsApplication voltage VrefMay be supplied by a battery. A response current I generated by the biochip 12 is passed through a Negative Temperature Coefficient (NTC) resistor RcThe current/voltage converter 30 converts into an output voltage Vout. The output voltage VoutCan be expressed by formula (I):
Vout(1+Rc/Rs)Vref(I) output voltage VoutSupplied to an analog-to-digital converter 32. A microprocessor (microcomputer)34 reads the output signal from the ADC 32, and obtains a glucose concentration value in the blood sample according to a glucose discharge curve of the blood sample corresponding to the output signal, and displays the glucose concentration value for the patient's reference through a liquid crystal display 36.
Referring to FIG. 4, a blood sample glucose measured by the blood glucose meter of FIG. 1 is shownDischarge profile. Due to the negative temperature coefficient resistance R of the current/voltage converter 30 of the blood glucose metercWill change with the change of the environmental temperature to cause the output voltage VoutOf (3) is detected. Such existing blood glucoseThe different ambient temperatures for R are not taken into account when measuring the glucose concentration in a blood samplecAnd VoutThe influence of (c). Therefore, often the same blood sample will yield different glucose concentration measurements at different ambient temperatures, making the measurement of blood glucose levels inaccurate.
Accordingly, it is desirable to provide a biosensor capable of correcting the effect of ambient temperature and a method thereof, which can eliminate the influence of ambient temperature on the measurement accuracy of the biosensor.
Disclosure of Invention
The present invention is directed to overcoming the disadvantages and drawbacks of the prior art and providing a biosensor capable of correcting the effect of ambient temperature and a method thereof, which can correct the effect of ambient temperature on the biosensor to improve the measurement accuracy of the biosensor.
Another object of the present invention is to provide a biosensor capable of correcting the effect of ambient temperature and a method thereof, which uses a resistor R built in a microprocessor combined with the biosensorc-a table of ambient temperatures and a plurality of corresponding ambient temperatures VoutThe specific component discharge curve look-up table is used for obtaining a specific component discharge curve of the sample corresponding to different environmental temperatures so as to obtain the content of the specific component in the sample. By means of the method of the present invention, the cost can be reduced without adding additional components.
It is still another object of the present invention to provide a biosensor capable of correcting the effect of ambient temperature and a method thereof, which can measure different specific components in a biological sample depending on the enzyme components of a biochip of the biosensor.
In accordance with the above-described objects, the present invention provides a biosensor and a method thereof that can correct the effect of ambient temperature. The biosensor of the present invention includes a sensor having a resistor RsThe biochip, a voltage supply source, a resistor R changing with the change of the environmental temperaturecThe current/voltage converter, an analog-to-digital converter, a microprocessor and a display.The biochip generates a response currentcorresponding to a specific component in a sample, and the voltage supply source is applied to the sampleApplying an action voltage V to the biochip after a predetermined timerefOn the biochip, the specific component content in the corresponding sample of the biochip generates a reaction current, and the current/voltage converter is used to convert the reaction current into an output voltage Vout. A resistor R is built in the microprocessorc-an ambient temperature look-up table and a plurality of output voltages V corresponding to different ambient temperaturesout-specific composition discharge curve look-up table. The microprocessor analyzes the output voltage V via the analog-to-digital converteroutAccording to the output voltage VoutAnd formula (I):
Vout=(1+Rc/Rs)Vref(I) to obtain RcResistance value, and according to the resistance Rc-an ambient temperature look-up table for obtaining a corresponding ambient temperature T, and at the ambient temperature T, according to a corresponding output voltage Vout-specific component discharge curve look-up table to obtain output voltage VoutCorresponding to a specific component discharge curve, and obtaining a content value of the specific component in the sample by the specific component discharge curve. The display is used to display the specific component content value.
The biosensor provided by the invention utilizes the R built in the microprocessorc-an ambient temperature look-up table and a plurality of V's corresponding to different ambient temperaturesoutThe specific component discharge curve is used to obtain the discharge curve of the specific component of the sample under different environmental temperatures, and then the content of the specific component in the sample is obtained. The biosensor and the measuring method thereof according to the present invention can correct the ambient temperature effect of the biosensor to improve the measurement accuracy of the biosensor. Moreover, the biosensor capable of correcting the ambient temperature effect of the invention can achieve the purpose of reducing the cost without adding additional components.
Drawings
FIG. 1 is a schematic view of an external view of a conventional blood glucose meter;
FIG. 2 is an exploded view of a biochip component of the blood glucose meter of FIG. 1;
FIG. 3 is a schematic diagram of a control circuit of the blood glucose meter shown in FIG. 1;
FIG. 4 is a graph of the glucose discharge in a blood sample measured by the blood glucose meter shown in FIG. 1;
FIG. 5 is a flow chart of the steps of the method of the present invention for calibrating ambient temperature effects for a biosensor.
Description of the symbols in the drawings
10 main test unit
1226. 1228 conducting wire
12 biological chip
122 strip-shaped substrate
1221 electrode section
124 reaction layer
126 spacer
128 cover plate
1222 operating electrode
1224 counter electrode
Detailed Description
The invention provides a biosensor (biosensor) capable of correcting ambient temperature effect and a method for correcting ambient temperature effect. Referring again to FIG. 3, the biosensor of the present invention still includes the main components of the conventional biosensor shown in FIG. 1, i.e., includes a sensor having a resistance RsThe biochip, a voltage supply source, a resistor R changing with the change of the environmental temperaturecThe current/voltage converter, an analog-to-digital converter, a microprocessor and a display. The principle of the biosensor of the present invention for measuring the content of a specific component in a sample is the same as that of the conventional biosensor shown in FIG. 1, in which the sample is applied to a biochip having a main test unit inserted therein, and the specific component to be detected is usedThe amount of the specific component is measured as a result of the enzyme-catalyzed reaction between the fraction and the enzyme on the biochip. Therefore, the biosensor of the present invention can be used to measure different specific components in different biological samples according to the different components of enzymes contained in the biochip. For example, when a glucose oxidase (glucose oxidase) is contained in a biochip, the biosensor can be used to measure the concentration of glucose in a blood sample. When lactate oxidase (lactate oxidase) is contained on the biochip, the biosensor can be used to measure the concentration of lactic acid (lactic acid) in saliva. Taking the measurement of the glucose concentration in blood as an example, when a blood sample is dropped on the biochip of the biosensor of the present invention, glucose in the blood sample and potassium ferricyanide (potassium ferricyanide) on the biochip undergo an oxidation-reduction reaction under the catalysis of glucose oxidase to produce glucose in the blood sampleA predetermined amount of potassium ferrocyanide (potassium ferricyanide) proportional to theglucose concentration. Thus, after a predetermined time of the specimen, such as a blood sample, on the biochip, i.e. after the enzymatic reaction of the specific components of the specimen, such as glucose in the blood sample, is completed, the voltage supply source, such as a battery, applies an action voltage VrefOn the biochip, a reaction current is generated by the biochip according to the specific component content, such as the action voltage VrefA predetermined amount of potassium ferrocyanide corresponding to the glucose concentration in the blood sample is oxidized to release electrons, thereby generating a corresponding reaction current. Has a resistance R which changes with the change of the environmental temperaturecThe current/voltage converter is used to convert the response current into an output voltage Vout. A resistor R is built in the microprocessorc-an ambient temperature look-up table and a plurality of output voltages V corresponding to different ambient temperaturesout-specific composition discharge curve look-up table. The microprocessor analyzes the output voltage V via the analog-to-digital converteroutAccording to which the output voltage V isoutAnd formula (I):
Vout=(1+Rc/Rs)Vref(I) to obtain RcResistance value and according to the resistance Rc-an ambient temperature look-up table for obtaining a corresponding ambient temperature T, and for this ambient temperature T, according to a corresponding output voltage VoutA table of discharge curves of specific components, obtaining the output voltage VoutCorresponding to a specific composition discharge curve. By means of the specific component discharge curve, a content value of the specific component in the sample is obtained. The display is used to display the measured content value of the specific component.
The biosensor of the present invention utilizes a resistor R built in the microprocessorc-a table of ambient temperatures and a plurality of V's corresponding to different ambient temperaturesoutThe specific component discharge curve look-up table is used to obtain the discharge curve of a specific component of the sample corresponding to different environmental temperatures, and then the content of the specific component in the sample is calculated according to the discharge curve. Therefore, the biosensor of the present invention can not only correct the influence of the environmental temperature on the biosensor to improve the measurement accuracy of the biosensor, but also reduce the manufacturing cost without adding additional components.
In another aspect, the present invention provides a method for correcting the environmental temperature effect of a biosensor, the flow of steps of which is shown in fig. 5. First, in step 501, a sample is applied to the biochip of the biosensor of the present invention, and after a predetermined time period, an action voltage V is appliedrefOn the biochip, a specific component content in the corresponding sample of the biochip generates a reaction chargeAnd (4) streaming. Next, in step 502, the response current is converted into an output voltage V by the current/voltage converter of the biosensorout. In step 503, the microprocessor analyzes and processes the output voltage V via the ADC of the biosensor according to the present inventionoutAccording to which the output voltage V isoutAnd formula (I):
Vout=(1+Rc/Rs)Vref(I) to obtain RcA resistance value. Next, in step 504, a resistance R is determinedc-a comparison table of ambient temperatures, obtaining the corresponding resistance RcAn ambient temperature T. In step 505 of the method, the system is started,an output voltage V corresponding to the ambient temperature ToutA table of discharge curves of specific components to obtain the output voltage VoutCorresponding to a specific composition discharge curve. Then, the content of the specific component in the sample is determined according to the specific component discharge curve. The method for determining the content of the specific component in the sample according to the specific component discharge curve can determine the discharge end time t according to the specific component discharge curve. Then, the content of the specific component in the sample is calculated according to the specific component discharge curve and the discharge end time t. Another method is to obtain a peak value according to the discharge curve of the specific component, and then obtain the content of the specific component in the sample according to a peak value-specific component content comparison table built in the microprocessor of the present invention.
The above description is only an embodiment of the present invention, and is not intended to limit the scope of the present invention; other equivalent changes and modifications without departing from the spirit of the disclosure are intended to be included within the scope of the appended claims.

Claims (10)

1. A method for correcting the environmental temperature effect of a biosensor comprising a sensor having a resistor RsThe biochip and a probe having a resistance R that changes with changes in ambient temperaturecThe current/voltage converter of (a), wherein the method of correcting for the effects of ambient temperature of the biosensor comprises:
applying a sample on the biochip for sensing a specific component in the sample, and applying an action voltage V after a predetermined timerefOn the biochip, the biochip generates a reaction current corresponding to the specific component content;
converting the reaction current into an output voltage V via the current/voltage converterout
According to the output voltage VoutAnd formula (I):
Vout=(1+Rc/Rs)Vref(I),
obtaining the resistance Rc
According to a resistance Rc-a comparison table of ambient temperatures, corresponding to the resistance RcAn ambient temperature T;
an output voltage V corresponding to the ambient temperature Tout-a table of discharge curves of specific components, obtaining the output voltage VoutA corresponding discharge curve of the specific component; and
obtaining a content value of the specific component in the sample according to the specific component discharge curve.
2. The method of claim 1, wherein the resistance R is selected from the group consisting ofc-the ambient temperature look-up table is built in a microprocessor integrated with the biosensor.
3. The method of claim 1, wherein the output voltage V is a voltage level of the biosensorout-the specific component discharge curve look-up table is built in a microprocessor associated with the biosensor.
4. The method of claim 1, wherein the specific component of the sample measured by the biosensor depends on an enzyme component of the biochip.
5. A biosensor capable of correcting the effects of ambient temperature, comprising:
a resistor RsThe biochip generates a reaction current corresponding to a specific component in a sample;
a voltage supply source for applying an action voltage V after the specimen is placed on the biochip for a predetermined timerefOn the biochip, the reaction current is generated by the biochip corresponding to the specific component content;
a resistor R changing with the change of the environmental temperaturecA current/voltage converter for converting the response current into an output voltage Vout
An analog-to-digital converter;
a microprocessor with a built-in resistor Rc-an ambient temperature look-up table and a plurality of output voltages V corresponding to different ambient temperaturesout-a specific component discharge curve look-up table, the microprocessor analyzing the output voltage V via the analog-to-digital converteroutAccording to the output voltage VoutAnd formula (I):
Vout=(1+Rc/Rs)Vref(I),
obtaining the resistance RcAnd according to the resistance Rc-an ambient temperature look-up table for obtaining a corresponding ambient temperature T, and for a corresponding one of the output voltages V at the ambient temperature Tout-a table of discharge curves of specific components, obtaining the output voltage VoutAnd obtaining a content value of the specific component in the sample according to the specific component discharge curve.
6. The biosensor for calibrating the effect of ambient temperature as recited in claim 5, further comprising a display for displaying the content value of the specific component.
7. The biosensor for calibrating the effect of ambient temperature as claimed in claim 5, wherein the sample is a blood sample.
8. The biosensor of claim 5, wherein the specific component of the sample measured by the biosensor depends on an enzyme component of the biochip.
9. The biosensor for calibrating the effect of ambient temperature of claim 5, wherein the voltage supply comprises a battery.
10. The biosensor for calibrating the effect of ambient temperature as recited in claim 6, wherein the display is a liquid crystal display.
CNA031010407A 2003-01-08 2003-01-08 Biological sensor capable of correcting environmental temperature effect and its method Pending CN1515682A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101495855B (en) * 2006-07-05 2013-04-17 松下电器产业株式会社 Method and apparatus for measuring liquid sample
CN103052881A (en) * 2010-08-02 2013-04-17 西拉格国际有限责任公司 Systems and methods for improved accuracy for temperature correction of glucose results for control solution
CN101477783B (en) * 2008-01-04 2013-10-23 群创光电股份有限公司 Oled display, information device, and method for displaying image in OLED display
CN103502775A (en) * 2011-04-05 2014-01-08 萨甘安全防护公司 Method for correcting the voltage measured across the terminals of a sensor
CN114609213A (en) * 2022-03-17 2022-06-10 苏州中星医疗技术有限公司 Glucose sensor and preparation method and application thereof

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101495855B (en) * 2006-07-05 2013-04-17 松下电器产业株式会社 Method and apparatus for measuring liquid sample
CN101477783B (en) * 2008-01-04 2013-10-23 群创光电股份有限公司 Oled display, information device, and method for displaying image in OLED display
CN103052881A (en) * 2010-08-02 2013-04-17 西拉格国际有限责任公司 Systems and methods for improved accuracy for temperature correction of glucose results for control solution
CN103052881B (en) * 2010-08-02 2014-11-05 西拉格国际有限责任公司 Systems and methods for improved accuracy for temperature correction of glucose results for control solution
CN103502775A (en) * 2011-04-05 2014-01-08 萨甘安全防护公司 Method for correcting the voltage measured across the terminals of a sensor
CN103502775B (en) * 2011-04-05 2015-12-02 萨甘安全防护公司 The method of the voltage recorded on the terminal of correcting sensor
CN114609213A (en) * 2022-03-17 2022-06-10 苏州中星医疗技术有限公司 Glucose sensor and preparation method and application thereof

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