CN1246691C - Method for raising reading value resolution of biological sensor - Google Patents
Method for raising reading value resolution of biological sensor Download PDFInfo
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- CN1246691C CN1246691C CN 03100946 CN03100946A CN1246691C CN 1246691 C CN1246691 C CN 1246691C CN 03100946 CN03100946 CN 03100946 CN 03100946 A CN03100946 A CN 03100946A CN 1246691 C CN1246691 C CN 1246691C
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Abstract
The present invention relates to a method for enhancing the read-out value resolution of a biological sensor, which comprises: a detecting body is applied to a biological chip of a biological sensor; a specific ingredient in the detecting body generates a voltage-time discharge curve by biological chip sensing. A voltage V0 corresponding to time t0 in the discharge curve is a center voltage. The time t0 is selected to approach to individual voltages corresponding to different time. The average voltage of the center voltage V0 and the selected individual voltages is obtained. The average voltage is used as an output voltage corresponding to the time t0. The average voltage corresponding to each time before electric discharge terminal time in the discharge curve is obtained according to the procedures in order to be used as an individual output voltage. The output voltage corresponding to each time in the discharge curve is converted to a group of binaryzation digital signals. A read-out value of the specific ingredient concentration in the corresponding detecting body is obtained according to the binarization digital signals.
Description
(1) Field of the invention
The invention relates to a method for sampling a measured value of a biosensor; in particular, to a method for improving the resolution of the read value of a biosensor.
(2) Background of the invention
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 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 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 time, an applied voltage Vref is applied to the biochip 12 to electrochemically react the potassium ferrocyanide to release electrons, and a corresponding reaction current is generated 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. By measuring this reaction current, the glucose concentration in the blood sample can be obtained.
FIG. 3 is a schematic diagram of the control circuit of the blood glucose meter shown in FIG. 1, wherein the electrode 1221 of the biochip 12 can be regarded as a resistor Rs, and the applied voltage Vref can be supplied by a battery. A response current I generated by the biochip 12 is gradually attenuated with time to form a discharge curve corresponding to the glucose concentration in the blood sample. In addition, the response current I at each time point is converted into an output voltage Vout by a current/voltage converter 32 having an amplifying resistor Rf. Therefore, the response current I, which gradually decays with time, becomes a voltage-time discharge curve after passing through the current/voltage converter 32. A voltage corresponding to each time point in the voltage-time discharge curve is converted into a set of digital signals by an analog-to-digital converter 34. A microprocessor 36 reads the digital signals from the ADC 34, determines a glucose concentration in the blood sample according to the digital signals, and displays the glucose concentration for the patient's reference through a liquid crystal display 38.
In the voltage-time discharge curve of the glucose concentration in blood measured by the conventional blood glucose meter, each output voltage Vout can only be measured to a single digit (i.e. only an integer value can be measured), and the voltage value range is between 0 and 255mv, so that the resolution of the blood glucose reading of the conventional blood glucose meter is limited. That is, each output voltage measured by the conventional blood glucose meter cannot be accurate to a decimal point or less, so that the resolution of the blood glucose reading of the blood glucose meter cannot be improved.
Accordingly, it is desirable to provide a method for sampling a measurement of a biosensor, which can overcome the limitation of the resolution of the readings of the conventional biosensor.
(3) Summary of the invention
The invention mainly aims to provide a method for improving the resolution of a read value of a biosensor, which is a method for averaging by multiple times of sampling, so that an output signal of a measured value can be accurate to a decimal point or less, and the resolution of the read value of the biosensor is improved.
Another objective of the present invention is to provide a method for improving the resolution of the reading value of the biosensor, which can achieve the purpose of reducing the cost without adding additional components.
Another objective of the present invention is to provide a method for improving the resolution of the reading of the biosensor, which is a method for averaging the individual measurement values at different time points in the discharge curve of a specific component in the sample to reduce the noise interference of the output signal of the measurement values.
In view of the above, the present invention provides a method for improving the resolution of the reading value of a biosensor. The method of the present invention includes applying a sample to a biochip of a biosensor, wherein a specific component in the sample is sensed by the biochip to generate a voltage-time discharge curve. A voltage V0 corresponding to a time t0 in the voltage-time discharge curve is used as a central voltage, a time t0 is selected to be adjacent to a plurality of individual voltages corresponding to different times, an average voltage of the central voltage V0 and the selected individual voltages is obtained, and the average voltage is used as an output voltage corresponding to the time t 0. According to the above steps, an average voltage corresponding to each time before a discharge end time in the voltage-time discharge curve is obtained for outputting a voltage at each time. An output voltage corresponding to each time in the voltage-time discharge curve is converted into a group of binary digital signals. According to the binary digital signals, a reading value of the concentration of the specific component in the corresponding sample is obtained.
The method of the invention is to select the voltages of a plurality of adjacent different time points for a voltage-time discharge curve of a specific component in a sample to obtain a voltage average value, and the voltage average value is used as a measurement output value of a central time point between the adjacent time points, so that each measurement output value can be accurately below a decimal point, the reading value resolution of the biosensor is improved, and the noise interference of each measurement value output signal is reduced.
The objects and advantages of the present invention will become apparent from the following detailed description of specific embodiments thereof, when read in conjunction with the accompanying drawings.
(4) Description of the drawings
FIG. 1 is a schematic view of a conventional blood glucose meter;
FIG. 2 is an exploded view of a biochip component of the bloodglucose meter of FIG. 1;
FIG. 3 is a schematic diagram of a control circuit of the blood glucose machine of FIG. 1;
FIG. 4 is a graph showing the discharge of a specific component in a sample according to the present invention;
FIG. 5 is a flowchart illustrating steps of a first preferred embodiment of the present invention; and
FIG. 6 is a flowchart illustrating steps of a second preferred embodiment of the present invention.
(5) Detailed description of the preferred embodiments
The constituent members of the biosensor (biosensor) used in the present invention are the same as those of biosensors generally using a specific enzyme reaction principle. The biosensor of the present invention still includes the main components of the conventional biosensor shown in FIGS. 1 to 3, i.e., a biochip 12 having a resistor Rs, a voltage supply source 30, a current/voltage converter 32 having an amplifying resistor Rf, an analog-to-digital converter 34, a microprocessor 36 and a display 38. 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 adopted in the conventional biosensor of FIG. 1, in that the sample is applied to the biochip 12 inserted into the main testing unit 10 of the biosensor, and the content of the specific component is measured by the result of the enzyme-catalyzed reaction between the specific component to be detected and the enzyme contained in the reaction layer 124 of the biochip 12. Therefore, the biosensor of the present invention can be used to measure different specific components in different biological samples according to the enzyme components contained in the reaction layer 124 of the biochip 12. For example, when the reaction layer 124 of the biochip 12 contains glucose oxidase (glucose oxidase), the biosensor may be used to measure the concentration of glucose in a blood sample. When the reaction layer 124 of the biochip 12 contains lactate oxidase (lactate oxidase), the biosensor can be used to measure the concentration of lactate in saliva. When the reaction layer 124 of the biochip 12 contains cholesterol oxidase (cholestrol oxidase), the biosensor can be used to measure the concentration of cholesterol in a blood sample. Taking the measurement of the glucose concentration in blood as an example, when a blood sample is dropped on the biochip 12 of the biosensor of the present invention, glucose in the blood sample and potassium ferricyanide (potassium ferricyanide) on the reaction layer 124 of the biochip 12 undergo a redox reaction under the catalysis of glucose oxidase to generate a predetermined amount of potassium ferrocyanide (potassium ferrocyanide) proportional to the glucose concentration in the blood sample. Therefore, after a predetermined time, i.e. after the enzyme-catalyzed reaction of a specific component of the sample, e.g. glucose in the blood sample, is completed, the voltage supply source 30, e.g. a battery, applies an action voltage Vref to the biochip 12, so that the biochip 12 generates a reaction current I corresponding to the specific component content, e.g. the action voltage Vref causes a predetermined amount of potassium ferrocyanide corresponding to the glucose concentration in the blood sample to perform an oxidation reaction to release electrons, thereby generating the corresponding reaction current I. The response current I gradually decays with time, and the response current I at each time point is converted into an output voltage Vout by the current/voltage converter 32. Therefore, after the specific component in the sample is sensed by the biochip 12, the biosensor can measure a voltage-time discharge curve corresponding to the concentration of the specific component. An output voltage Vout corresponding to each time point in such a voltage-time discharge curve is converted into a set of binary digital signals (binary digitized data) by the adc 34. The microprocessor 36 determines a reading of the glucose concentration in the corresponding blood sample according to a discharge end time of the voltage-time discharge curve and the binarized digital signals corresponding to all time points before the discharge end time. This reading is displayed on a display 38, such as a liquid crystal display.
On the other hand, the biosensor of the present invention can select a standard specific component discharge curve corresponding to a maximum output voltage Vout generated according to a specific component in the sample sensed by the biochip 12 and an output voltage-specific component discharge curve mapping table built in the microprocessor 36. Each of the component-specific discharge curves in this map is a voltage-time discharge curve. Then, the corresponding discharge end point time is determined according to the standard specific component discharge curve. The microprocessor 36 determines the content of the specific component in the sample according to the discharge curve of the specific component of the selected standard and the discharge end time thereof.
Although the action principle of the biosensor is not different from that of the general biosensor, the invention provides a method for improving the resolution of the reading value of the biosensor, which utilizes the individual voltages of a plurality of adjacent different time points in a discharge curve of a specific component in a selected sample to obtain an average voltage for making an output voltage of a selected center time point in the adjacent different time points, thereby improving the resolution of the output voltage of the center time point. The present invention utilizes the above-mentioned method of multiple sampling and averaging to increase the resolution of the output voltage at each time point in the discharge curve of the specific component.
The method of improving the resolution of the reading value of the biosensor according to the present invention will be described in detail with reference to the following preferred embodiments and accompanying drawings.
Referring to fig. 4 and 5, fig. 4 shows a voltage-time discharge curve generated after a specific component in a sample is sensed by the biosensor of the present invention. FIG. 5 is a flowchart illustrating steps of a first preferred embodiment of the present invention. The first preferred embodiment of the present invention will be described in detail with reference to the biosensor shown in FIGS. 1 to 3. First, in step 501, a sample is applied to a biochip 12 of the biosensor of the present invention. A specific component in the sample is sensed by the biochip 12 to generate a voltage-time discharge curve, as shown in FIG. 4. Next, in step 502, a voltage V0 corresponding to a time t0 in the voltage-time discharge curve is used as a central voltage, and respective voltages V1, V2 and V3 corresponding to three different times t1, t2 and t3 adjacent to the time t0 are selected. In step 503, an average voltage of the four voltages V0, V1, V2 and V3 is obtained, and the average voltage is used as an output voltage corresponding to the time t 0. For example, with a voltage value of 101 millivolts (mv) corresponding to time t0 as a center voltage, voltage values of 103 millivolts, 100 millivolts and 99 millivolts are selected at three different time points t1, t2 and t3 adjacent to time t 0. Then, an average voltage value of the four voltage values is determined to be 100.75 mv, i.e., the average voltage value of 100.75 mv is used as an output voltage Vout corresponding to time t 0. The output voltage of 100.75 mv at time t0 is converted into a binary digital signal by the adc 34, wherein 100 mv is represented by the first eight bits (20, 21, 22, …..27) and 0.75 mv is represented by the last two bits (2-1, 2-2). Therefore, the ten-bit digital signal with the output voltage of 100.75 millivolts at time t0 is (0110010011). The biosensor can only measure the output voltage at time t0 to one digit, and the output voltage at time t0 can be analyzed to two digits below the decimal point by the method of steps 502 to 503. In addition, the number of bits of the output voltage at time t0 can be increased from eight bits to ten bits. In addition, the time sampling interval of step 502 with respect to time t0 may be milliseconds (ms) or microseconds (μ s), and the sampling method may select two voltages before and two voltages after the center voltage at time t0, two voltages before and two voltages after the center voltage at time t0, three voltages before and three voltages after the center voltage at time t0, or three voltages after the center voltage at time t 0.
Next, in step 504, according to steps 502 to 503, an average voltage corresponding to each time point before a discharge end time in the voltage-time discharge curve is obtained for use as an output voltage at each time point. In step 505, an output voltage corresponding to each time point before the discharge end point in the voltage-time discharge curve is converted into a set of binary digital signals by the adc 34. Then, in step 506, the microprocessor 36 obtains a reading value of the concentration of the specific component in the corresponding sample according to the binary digital signals, and the reading value is displayed on the display 38, such as a liquid crystal display. According to steps 502 to 504, the resolution of the output voltage at each time point in the discharge curve of the specific component in the sample can be increased to two decimal points or less, thereby increasing the resolution of the read value of the concentration of the specific component in the corresponding sample. In addition, the noise interference of the output voltage at each time point can be reduced by steps 502 to 504.
FIG. 6 is a flowchart showing the steps of a second preferred embodiment of the present invention, and the biosensor shown in the first to third figures will be described in detail as follows. First, in step 601, a sample is applied to a biochip 12 of the biosensor of the present invention, and a specific component in the sample is sensed by the biochip 12 to generate a reaction current I that gradually attenuates with time, and then converted by the current/voltage converter 32 to generate a maximum output voltage Vout. Next, in step 602, a standard specific component discharge curve corresponding to the maximum output voltage Vout is selected according to the maximum output voltage Vout measured by the biosensor and an output voltage-specific component discharge curve mapping table built in the microprocessor 36, where the standard specific component discharge curve is a voltage-time discharge curve and corresponds to a discharge end time. Next, in step 603, a voltage V0 corresponding to a time t0 in the standard specific component discharge curve is used as a center voltage, and respective voltages V1, V2 and V3 corresponding to three different times t1, t2 and t3 adjacent to the time t0 are selected. In step 604, an average voltage of the four voltages V0, V1, V2 and V3 is determined, and the average voltage is used as an output voltage corresponding to the time t 0. Step 603 of the second preferred embodiment of the present invention is the same as step 502 of the first preferred embodiment, and the time sampling interval relative to time t0 can be milliseconds (ms) or microseconds (μ s), and the sampling method can select two voltages before and two voltages after the center voltage at time t0, three voltages before and two voltages after the center voltage at time t0, three voltages before and three voltages after the center voltage at time t0, or three voltages after the center voltage at time t 0. Then, in step 605, according to steps 603 to 604, an average voltage corresponding to each time point before the discharge end time of the standard specific component discharge curve is obtained for being used as an output voltage of each time point. Next, in step 606, an output voltage corresponding to each time point before the discharge end time of the standard specific component discharge curve is converted into a set of binary digital signals through the adc 34. In step 607, the microprocessor 36 obtains a reading value of the concentration of the specific component in the corresponding sample according to the binary digital signals, and the reading value is displayed on the display 38, such as a liquid crystal display.
The method for improving the resolution of the read value of the biosensor can be executed by software, and can achieve the aim of reducing the cost without adding additional component components.
The above description is only an example of the present invention, and is not intended to limit the scope of the present invention; it is intended that all such modifications and equivalents be included within the scope of the invention as defined by the claims which follow.
Claims (10)
1. A method of improving resolution of a biosensor reading, comprising:
applying a sample on a biochip of a biosensor, wherein a specific component in the sample is sensed by the biochip to generate a voltage-time discharge curve;
taking a voltage V0 corresponding to a time t0 in the voltage-time discharge curve as a central voltage, selecting individual voltages V1, V2 and V3 corresponding to a plurality of different times adjacent to the time t0, obtaining an average voltage of the central voltage V0and the selected three voltages, and taking the average voltage as an output voltage corresponding to the time t 0;
according to the previous step, obtaining an average voltage corresponding to each time before a discharge end time in the voltage-time discharge curve so as to obtain an output voltage of each time;
converting the output voltage corresponding to each time in the voltage-time discharge curve into a group of binary digital signals; and
according to the binary digital signal, a reading value corresponding to the concentration of the specific component in the sample is obtained.
2. The method of claim 1, wherein a voltage corresponding to each time in the voltage-time discharge curve is an integer value.
3. The method of claim 1, wherein the sampling interval is milliseconds.
4. The method of claim 1, wherein the sampling interval is microseconds.
5. The method of claim 1, wherein the specific component of the sample measured by the biosensor depends on an enzyme component of the biochip.
6. A method of improving resolution of a biosensor reading, comprising:
applying a sample on a biochip of a biosensor, wherein a specific component in the sample generates a maximum output voltage through the biochip;
selecting a specific component discharge curve corresponding to the maximum output voltage according to the maximum output voltage and an output voltage-specific component discharge curve mapping table, wherein the specific component discharge curve is a voltage-time discharge curve;
selecting individual voltages corresponding to a plurality of different times adjacent to the time t0 by taking a voltage V0 corresponding to a time t0 in the specific component discharge curve as a central voltage, obtaining an average voltage of the central voltage V0 and the selected voltages, and taking the average voltage as an output voltage corresponding to the time t 0;
according to the previous step, obtaining an average voltage corresponding to each time before a discharge end time in the specific component discharge curve so as to serve as the output voltage of each time;
converting the output voltage corresponding to each time in the specific component discharge curve into a group of binary digital signals; and
according to the binary digital signal, a reading value corresponding to the concentration of the specific component in the sample is obtained.
7. The method of claim 6, wherein a voltage corresponding to each time in the discharge curve of the specific component is an integer value.
8. The method of claim 6, wherein the specific component of the sample measured by the biosensor depends on an enzyme component of the biochip.
9. The method of claim 6, wherein the sampling interval is milliseconds.
10. The method of claim 6, wherein the sampling interval is microseconds.
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| CN 03100946 CN1246691C (en) | 2003-01-07 | 2003-01-07 | Method for raising reading value resolution of biological sensor |
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| CN 03100946 CN1246691C (en) | 2003-01-07 | 2003-01-07 | Method for raising reading value resolution of biological sensor |
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| CN1246691C true CN1246691C (en) | 2006-03-22 |
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