CN1570618A - Multi time quantum offset voltage adjustment biological sensor and method thereof - Google Patents
Multi time quantum offset voltage adjustment biological sensor and method thereof Download PDFInfo
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- CN1570618A CN1570618A CN 03178774 CN03178774A CN1570618A CN 1570618 A CN1570618 A CN 1570618A CN 03178774 CN03178774 CN 03178774 CN 03178774 A CN03178774 A CN 03178774A CN 1570618 A CN1570618 A CN 1570618A
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Abstract
A biological sensor and its method for multistage bias voltage adjusting, which is first to exert a high voltage on the biological chip before providing an object to be measured above the chip and according to this high voltage to promote the particular component to quickly react with the reagent on biological chip to avoid the said reagent or particular component to react with oxygen or other impurity substance in the air. It is so to increase the accuracy of signal curve measured.
Description
Technical Field
The invention relates to a biosensor and a method thereof; more particularly, to a biosensor with multi-time bias adjustment and a method thereof.
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 (blood glucose concentrations) within normal ranges. 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 conventional blood glucose meter for self-test of blood glucose level of a patient, which includes a main test unit 10 and a biochip 12 for measuring blood glucose level. 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 overlying the electrode 1221 contains potassium ferricyanide and an oxidizing enzyme, such as glucose oxidizing enzyme.
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. By measuring this reaction current, the glucose concentration in the blood sample can be obtained.
FIG. 3 is a schematic diagram of a control circuit of the conventional 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 gradually decays with increasing time to form a time-varying signal curve corresponding to the glucose concentration in the blood sample. Furthermore, the response current I of the time-varying signal curve at each sampling time is passed through an amplifying resistor RfThe current/voltage converter 30 converts into an output voltage Vout. Thus, the time-varying signal curve becomes a voltage-time discharge curve. The output voltage V corresponding to each sampling time in the discharge curveoutThe output is sent to an analog-to-digital converter 32 for conversion into a set of digital signals. A microprocessor (microcomputer)34 continuously reads the digital signals from the analog-to-digital converter 32 over time, and determines the glucose concentration in the blood sample based on the read digital signals, and displays the glucose concentration for patient reference via a display such as a liquid crystal display 36.
FIG. 4 is a graph showing a rise time t of a glucose concentration in a corresponding blood sample in a conventional blood glucose meterrA voltage-time discharge curve of, the rise time trA peak value of the corresponding discharge curve. Usually, the discharge curves of different blood glucose concentrations have different rise times trWhich follows glucose in the bloodThe concentration increases and lengthens. However, when the applied voltage V is applied to the biochip 12refWhen too high, oxygen or other impurities in the air are easily adsorbed to the electrode portions 1221 of the biochip 12. As a result, the reagent on the biochip 12, such as potassium ferricyanide (POC), or the component in the sample, such as glucose, is liable to react with the adsorbed oxygen or other impurities, so that the discharge curve is shifted or disturbed by noise, as shown in FIG. 4, and the rise time t is elapsedrThen, the discharge curve is shifted and disturbed by noise. Thus, it is difficult to determine the glucose concentration in blood based on the measured discharge curve.
Accordingly, the conventional blood glucose meters and the measurement methods thereof need to be improved to overcome the defects.
Disclosure of Invention
The present invention provides a biosensor with multi-time bias adjustment and a method for measuring the concentration of a specific component of a sample, wherein a higher voltage is applied to a biochip before the sample is provided on the biochip, so that when the sample is provided on the biochip, a specific component in the sample and a reagent of the biochip can be rapidly reacted completely in a short time, thereby preventing the reagent or the specific component from reacting with oxygen or other impurities in the air, and further improving the measurement accuracy of the biosensor.
It is another object of the present invention to provide a multi-time bias-adjustable biosensor, which applies a higher voltage to a biochip before a sample is provided on the biochip, so that when the sample is provided on the biochip, a specific component in the sample and a reagent of the biochip can be rapidly reacted completely in a short time, thereby preventing the reagent or the specific component from reacting with oxygen or other impurities in the air and reducing noise interference.
It is still another object of the present invention to provide a multi-period bias-adjusted biosensor that can reduce the applied voltage in different periods as the detection time increases, thereby reducing the power consumption of the biosensor.
In accordance with the above-mentioned objectives, the present invention provides a multi-time bias adjustment biosensor and a method for measuring a specific component in a sample using the same. The biosensor for multi-time bias adjustment comprises a biochip, an adjustable bias generator, a current/voltage converter and a microprocessor. When an applied voltage isapplied to the biochip, the biochip generates a reaction current varying with time corresponding to a specific component in a sample provided thereon. The adjustable bias generator is used for providing the acting voltage on the biochip, and the current/voltage converter is used for converting the response current changing along with time into an output voltage changing along with time. This time-varying output voltage constitutes a discharge curve. The microprocessor is used for controlling the adjustable bias generator to provide different action voltages to the biochip at different time stages and determining a concentration value of the specific component in the sample according to the output voltage changing along with the time. Before the sample is provided on the biochip, the adjustable bias generator applies a first action voltage to the biochip, and after a signal threshold (threshold response signal) of the specific component in the corresponding sample is detected, the adjustable bias generator reduces the first action voltage to a second action voltage. Then, an output voltage curve of the specific component in the corresponding sample is obtained, and a concentration value of the specific component in the sample is determined according to the output voltage curve.
The present invention relates to a multi-time-period bias-voltage-regulated bio-sensor, and is characterized by that before the tested body is provided on the bio-chip, a higher action voltage is applied on the bio-chip, when the tested body is provided on the bio-chip, said higher action voltage can promote the quick reaction of specific component in the tested body and reagent on the bio-chip to be completely reacted in a short time so as to prevent the combination reaction of the reagent on the bio-chip or specific component in the tested body and oxygen or other impurity in the air. Thus, the noise ratio (signal to noise ratio) of the measured discharge curve and the accuracy of measuring the concentration of the specific component in the sample can be improved. Furthermore, the present invention reduces the higher applied voltage after the first period of time, thereby reducing the power consumption of the biosensor.
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.
Drawings
FIG. 1 is a schematic external view of a conventional blood glucose meter;
FIG. 2 is an exploded view of a biochip of the conventional blood glucose meter of FIG. 1;
FIG. 3 is a schematic diagram of a control circuit of the conventional blood glucose meter of FIG. 1;
FIG. 4 is a graph showing a discharge curve of glucose concentration in a corresponding blood sample measured by a conventional blood glucose meter;
FIG. 5 is a schematic diagram of a control circuit of the biosensor of the present invention;
FIG. 6 is a schematic diagram of an exemplary adjustable bias generator according to the present invention;
FIG. 7 is a flow chart of the steps of the method of the present invention;
FIG. 8 is a graph of the time dependence of the applied voltage of the present invention; and
FIG. 9 is a schematic view of a discharge curve measured by the method of the present invention.
Description of the symbols in the drawings
10 main test unit
12 biological chip
122 strip-shaped substrate
124 reaction layer
126 spacer
128 cover plate
1221 electrode section
1222 operating electrode
1224 counter electrode
1226. 1228 conducting wire
30 current/voltage converter
32A/D converter
34 microprocessor
36 liquid crystal display
50 current/voltage converter
51 Adjustable bias Generator
52 analog-to-digital converter
53 microprocessor
54 liquid crystal display
510 operational amplifier
511 bias voltage adjuster
512 current amplifier
513 ground terminal
514 node
Detailed Description
The present invention provides a biosensor with multi-time bias adjustment and a method thereof, which can apply different applied voltages on a biochip of the biosensor at different time periods. The biosensor with multi-time-interval bias adjustment of the invention applies a higher acting voltage on the biochip before providing a sample on the biochip. When the sample is provided on the biochip, the higher applied voltage can promote a specific component in the sample to react with the reagent on the biochip quickly and completely in a short time, so as to prevent the reagent or the specific component from reacting with oxygenor other impurities in the air. Furthermore, the present invention detects this in the corresponding specimenA signal threshold (signal threshold) of the specific component is set to a first action time, i.e. the reagent and the specific component in the sample are almost completely reacted, i.e. the higher action voltage is adjusted to be reduced. Therefore, the specific components and reagents which are not reacted can be further prevented from being combined with oxygen or other impurities in the air, and the power consumption of the biosensor can be reduced. The biosensor with multi-time-interval bias adjustment of the invention is provided with an adjustable bias generator which can be controlled by a microprocessor to provide different applied voltages VrefOtherwise, most of the other components are the same as those of the conventional biosensor shown in FIGS. 1 to 3. However, the principle of detecting the concentration of a specific component in a sample according to the present invention is the same as that of the conventional biosensor shown in FIGS. 1 to 3. The specific component to be detected in the present invention depends on the enzyme type of the biosensor.
FIG. 5 is a schematic diagram of a control circuit of a multi-time bias-adjusted biosensor according to the present invention, which includes a resistor RsA biochip having an operational amplifier 510 and an amplifying resistor RfA current/voltage converter 50, an adjustable bias generator 51, an analog-to-digital converter 52, a microprocessor 53 and a display, such as a liquid crystal display 54. When an action voltage V is appliedrefOn the biochip, the biochip generates a response current I varying with time according to the concentration of the specific component to be detected in the sample. This time-dependent reaction current I decays gradually with increasing time. The adjustable bias generator 51 applies different applied voltages to the biochip at different time periods under the control of the microprocessor 53. The current/voltage converter 50 converts the time-varying reaction current I into a time-varying output voltage VoutThus forming a discharge curve which changes along with time. This time-varying output voltage VoutTo an analog/digital converter 52 for conversion to digital form and then to a microprocessor 53 for further processing. The microprocessor 53 determines a concentration value of the specific component in the sample according to the time-varying discharge curve.The reading of the concentration is then displayed by the LCD 54. The adjustable bias generator 51 controlled by the microprocessor 53 applies a first applied voltage in the range of 500 millivolts to 520 millivolts to the biochip before providing the sample on the biochip. Then, after providing the sample on the biochip, a voltage threshold (V) of the specific component in the corresponding sample is detectedth) As shown in fig. 9, after a first period of time of about one second, the adjustable bias generator 51 reduces the first active voltage to a second active voltage within a range of 300 mv to 320 mv. Voltage threshold value VthA pointer representing the start of the reaction between the reagent on the biochip and the specific component in the sample. Since the first applied voltage is significantly higher than the second applied voltage, the reaction of the specific component in the specimen with the reagent on the biochip can be almost completed in a short time, i.e., the reaction of the reagent on the biochip with the specific component in the specimen is almost completed in the first applied time. A rise time t of the discharge curve corresponding to its peak valuerI.e. can be reached quickly in the first action time and after the rise time trAfter that, the discharge curve decays rapidly. The biosensor with multi-time-interval bias adjustment of the present invention can obtain a discharge curve as shown in fig. 9 after applying the first applied voltage and the second applied voltage to the biochip sequentially at different time intervals.
The biosensor with multi-time-interval bias adjustment of the invention firstly applies a higher acting voltage on the biochip before providing the sample on the biochip, and after providing the sample on the biochip, the higher acting voltage can promote the specific component in the sample to react with the reagent on the biochip quickly and completely, thereby preventing the reagent on the biochip or the specific component from reacting with the oxygen or other impurities in the air. Furthermore, the first action voltage is adjusted to the second action voltage after the first action time. The lower second applied voltage can prevent oxygen or other impurities in the air from adsorbing onto the biochip, and can further prevent the specific component and reagent unreacted on the biochip from reacting with their combination to reduce noise interference. The accuracy of the discharge curve measured by the multi-time-period bias-voltage-adjusted biosensor can be improved, and the accuracy of the measurement of the concentration value of the specific component in the sample can be improved. On the other hand, after the second action voltage is applied to the biochip for a second action time, the second action voltage can be reduced to the ground potential. The second period of action lasts about 5 to 30 seconds, depending on the concentration of the specific component in the sample. Therefore, the biosensor with multi-time bias adjustment can reduce the power consumption thereof.
FIG. 6 is a schematic circuit diagram of an exemplary adjustable bias generator 51 according to the present invention. The adjustable bias generator 51 comprises a bias adjuster 511, a first resistor R1A current amplifier 512, a second resistor R2A voltage source VDDA third resistor R3And a fourth resistor R4. The bias regulator 511 can provide different voltage outputs, the first resistor R1Is connected to the bias regulator 511 for applying a first current IBFlows through the first resistor R1. The current amplifier 512 has an input terminal, an output terminal and a ground terminal, wherein the input terminal is connected to the first resistor R1To receive the first current IBThen outputs a second current I from the output terminalC. A second resistor R2Is connected to the output terminal of the current amplifier 512 to receive the second current ICAnd a second resistor R2The other end of the voltage-controlled switch is used as a voltage output end to provide an action voltage VrefTo biochips. The current amplifier 512 may be formed by a common-emitter PNP bipolar transistor (PNP bipolar transistor) having a base connected to the first resistor R1Its emitter connected to ground and its collector connected to a second resistor R2. Third resistor R3Is connected to a voltage source VDDAnd a node 514, the node 514 being connected to the second resistor R2And a voltage output terminal. A fourth resistor R4One terminal connected to node 514 and the other terminal connected to ground 513. Voltage source VDDA third resistor R3And a fourth resistor R4The combination of (a) and (b) is designed to increase the level of the node 514. Refer to the drawingsFIG. 6 is a schematic circuit diagram of the adjustable bias generator 51, the second current ICCan be IC＝(1+β)IBTherein β is the current amplification of a common emitter PNP diode transistor, and the first current IBMay be determined by the output voltage of the bias regulator 511. Thus, the voltage V is appliedrefCan be composed of Vref＝ICR2+VDD' determined, wherein VDD′＝VDD{R3/(R3+R4)}. Therefore, the applied voltage V applied to the biochip can be controlled by the bias regulator 511refSize.
FIGS. 7 and 8 illustrate a method for measuring a specific component in a sample by a multi-time-period bias-adjusting biosensor according to the present invention. FIG. 7 is a flowchart of a step of the method of the present invention and FIG. 8 is a time-dependent graph of the applied voltage applied to the biochip of the present invention. In step 71, a first applied voltage V is applied after a biochip is inserted into the biosensor of the present inventionref，1On this biochip. First applied voltage Vref，1In the range of about 500 millivolts to 520 millivolts. At step 72, a sample is provided on the biochip. In step 73, a threshold signal V corresponding to a specific component in the sample is detectedthAfter a first period of action time t1For example, about one second, the first applied voltage Vref，1Is regulated to a second action voltage Vref，2. Second applied voltage Vref，2Can maintain a second period of action time t2E.g. about 5 to 30 seconds, and then lowered to ground potential Vref，3. Then, in step 74, a time-varying signal curve of the specific component in the corresponding sample is obtained, for example, as shown in fig. 9, a discharge curve of the concentration value of the specific component in the corresponding sample is obtained. In step 75, the concentration value of the specific component in the sample is determined based on the time-varying signal curve. The step of determining the concentration of the specific component in the sample may include determining therefromThe time-varying signal curve obtains a peak value (peak value), and determines the concentration value of the specific component according to a peak value-the specific component concentration mapping table (mapping table). The determining step of the concentration value of the specific component in the sample may include obtaining a peak value from the time-varying signal curve, obtaining a corresponding standard signal curve according to a peak value-specific component standard signal curve (prescribed curve) mapping table, and determining the concentration value of the specific component according to the standard signal curve.
The above description is only an example of the present invention, and is not intended to limit the scope of the present invention; all such modifications and variations are intended to be included herein within the scope of this disclosure and the present invention.
Claims (20)
1. A method for measuring the concentration of a specific component in a sample by a multi-time-period bias-voltage adjustment biosensor is characterized by comprising the following steps:
applying a first applied voltage to a biochip of the biosensor;
providing a sample on the biochip, the biochip generating a signal varying with time corresponding to a specific component in the sample during the first applied voltage;
detecting a signal threshold value corresponding to the specific component in the sample, and reducing the first action voltage to a second action voltage after a first action time;
obtaining a time-varying signal curve corresponding to the specific component in the sample; and
determining a concentration value of the specific component in the sample according to the time-varying signal curve.
2. The method of claim 1, further comprising reducing the second applied voltage to ground after a second period of time has elapsed since the second applied voltage is applied to the biochip.
3. The method of claim 1, wherein the first applied voltage is about 500 millivolts to 520 millivolts.
4. The method of claim 1, wherein the second applied voltage is about 300 millivolts to 350 millivolts.
5. The method of claim 1, wherein the first exposure time is about one second.
6. The method of claim 1, wherein the second exposure time is about 5 seconds to about 30 seconds.
7. The method of claim 1, wherein the step of determining the concentration of the specific component in the sample comprises obtaining a peak value from the time-varying signal curve, and determining the concentration of the specific component according to a peak-to-specific component concentration mapping table.
8. The method of claim 1, wherein the step of determining the concentration of the specific component in the sample comprises obtaining a peak value from the time-varying signal curve, and determining the concentration of the specific component according to a peak-to-specific component signal curve mapping table.
9. The method as claimed in claim 1, wherein the specific component to be detected in the sample is determined by an enzyme of the biochip.
10. The method of claim 1, wherein the time-varying signal is a time-varying response current.
11. The method of claim 10, wherein the time-varying signal curve is a time-varying discharge curve.
12. A multi-time bias-adjusted biosensor, comprising:
a biochip for generating a reaction current varying with time corresponding to a specific component in a specimen provided on the biochip when an applied voltage is applied to the biochip;
an adjustable bias generator for providing the applied voltage to the biochip;
a current/voltage converter for converting the time-varying reaction current into a time-varying output voltage; and
a microprocessor for controlling the adjustable bias generator to provide different action voltages to the biochip at different time stages and determining a concentration value of the specific component in the sample according to the time-varying output voltage;
before the sample is provided on the biochip, the adjustable bias voltage generator applies a first action voltage to the biochip, and after a first action time period elapses from the detection of a signal threshold corresponding to the specific component in the sample, the adjustable bias voltage generator reduces the first action voltage to a second action voltage.
13. The biosensor of claim 12, wherein the second applied voltage is applied to the biochip for a second period of time, and the adjustable bias generator reduces the second applied voltage to a ground potential.
14. The biosensor of claim 12, wherein the adjustable bias generator comprises:
a bias voltage regulator for providing different voltage outputs;
a first resistor, one end of which is connected to the bias regulator, so that a first current flows through the first resistor;
a current amplifier having an input terminal, an output terminal and a ground terminal, wherein the input terminal is connected to another terminal of the first resistor to receive the first current and output a second current from the output terminal; and
one end of the second resistor is connected to the output end of the current amplifier to receive the second current, so that the other end of the second resistor is used as a voltage output end to provide the acting voltage on the biochip.
15. The biosensor of claim 14, wherein the current amplifier comprises a common-emitter PNP diode transistor, wherein the common-emitter PNP diode transistor has a base connected to the first resistor, an emitter grounded, and a collector connected to the second resistor.
16. The biosensor of claim 14, further comprising:
a voltage source;
a third resistor connected between the voltage source and a node connected to the voltage output terminal of the second resistor; and
a fourth resistor, one end of which is connected to the node and the other end of which is grounded.
17. The multi-time bias-adjusted biosensor of claim 15, further comprising:
a voltage source;
a third resistor connected between the voltage source and a nodeconnected to the voltage output terminal of the second resistor; and
a fourth resistor, one end of which is connected to the node and the other end of which is grounded.
18. The biosensor of claim 12, wherein the specific component to be detected in the sample depends on an enzyme of the biochip.
19. The biosensor of claim 12, wherein the first applied voltage is about 500 millivolts to about 520 millivolts.
20. The biosensor of claim 12, wherein the second applied voltage is about 300 millivolts to 320 millivolts.
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| CN 03178774 CN1570618A (en) | 2003-07-18 | 2003-07-18 | Multi time quantum offset voltage adjustment biological sensor and method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 03178774 CN1570618A (en) | 2003-07-18 | 2003-07-18 | Multi time quantum offset voltage adjustment biological sensor and method thereof |
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| CN1570618A true CN1570618A (en) | 2005-01-26 |
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