CN100370249C - Method for reducing measurement deviation of current type biosensors - Google Patents
Method for reducing measurement deviation of current type biosensors Download PDFInfo
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- CN100370249C CN100370249C CNB200410008278XA CN200410008278A CN100370249C CN 100370249 C CN100370249 C CN 100370249C CN B200410008278X A CNB200410008278X A CN B200410008278XA CN 200410008278 A CN200410008278 A CN 200410008278A CN 100370249 C CN100370249 C CN 100370249C
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- 238000000034 method Methods 0.000 title claims abstract description 37
- 238000005259 measurement Methods 0.000 title description 4
- 238000006479 redox reaction Methods 0.000 claims abstract description 17
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 238000003487 electrochemical reaction Methods 0.000 claims abstract description 3
- -1 potassium ferricyanide Chemical compound 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 12
- 239000008103 glucose Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 9
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019846 buffering salt Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
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Abstract
The present invention provides a method for measuring the number of objects to be measured in a measured sample. The present invention comprises the steps: (a) combining a current type biosensor at least containing an electrode system and a redox electronic medium and applying persetting voltage to the electrode system; (b) inserting a measuring sample in the sensor and immediately gradually reducing the presetting voltage to a value which can not drive the electronic medium to carry out an electrochemical redox reaction; (c) resupplying second voltage which can drive the electronic medium to carry out the electrochemical redox reaction for the electrode system of the sensor after sufficient reaction time; (d) measuring the current of the electrochemical reaction of the electrode system and deciding the number of the objects to be measured in the measured sample.
Description
Technical field
The invention relates to the method for a reduction current type biology sensor measured deviation, when it is characterized in that specimen inserted preset voltage to the sensor of electrode system, progressively to lower the mode of this preset voltage, eliminate the background current of main interference early stage in the biology sensor reaction immediately.
Background technology
Utilize the current type biology sensor to measure the method for particular test in the liquid specimen, often be used in the unusual monitoring of clinical physiological, for example ferment current type blood sugar and lactic acid sensing method, and non-ferment uric acid and protoheme sensing method.No matter be ferment or non-ferment system, all use electron mediator to transmit media with electronic signal as the determinand redox reaction.
As Figure 1-1, because the determinand in the specimen carries out oxidation reaction, and the trend that makes electron mediator be reduced (promptly this electronic signal is passed to electron mediator) increases (13) gradually.When through after the enough reaction time, further on electrode system, supply with fixed voltage (12), change with the electronic signal of carrying out between electron mediator and the electrode, that is electrochemical redox reaction.So, see through Cottrell electric current and concentration relationship formula that electrochemical redox reaction produced, be the positive correlation of Cottrell electric current and testing concentration,, can know the concentration (United States Patent (USP) Re36268 number) of this determinand by inference by the electric current of surveying work electrode.
Because electron mediator or all the other compositions (the ferment stabilizing agent or the interfacial agent that for example have oxidation or reducing equivalent) of current type biology sensor, seasoning period before not being used, meeting is because of the influence of environment (as luminous energy, heat energy or moisture), and generation oxidation or reduction reaction.This moment is if contain the determinand that the sensor of reacted constituent is used for measuring specimen with this, and it will become background interference and influence the current measurement value of sensor electrical electrode systems, that is forms departure.Therefore, when using the current type biology sensor, the interference that environmental impact caused must be reduced or eliminate, the concentration of determinand in the specimen could be accurately measured.
The method of at present common this ground unrest of elimination is that the conduction electrode system circuit is also eliminated background interference simultaneously, to reduce departure when liquid specimen is inserted preset voltage to the sensor of electrode system.
Fig. 1-2 and 1-3 be the voltage-operated pattern of two kinds of prior aries of illustration respectively.Fig. 1-2 is the voltage-operated pattern of the blood glucose meter (for the current type biology sensor) of Medisense Inc. system, it is when liquid specimen is inserted preset voltage to the sensor of electrode system (10), eliminate background interference with fixed voltage (11) immediately, and measure Cottrell electric current and concentration relationship again with power-down mode not.Fig. 1-the 3rd, the voltage-operated pattern of the blood glucose meter (being the current type biology sensor) of Bayer (United States Patent (USP) the 5653863rd and No. 5620579) system, it is when liquid specimen is inserted preset voltage to the sensor of electrode system (10), eliminate background interference with fixed preset voltage 11 immediately and cut off the power supply after a period of time, determinand is through applying a driving voltage (12) again to measure Cottrell electric current and concentration relationship after the enough reaction time in specimen.
Yet the not power-down mode that the former taked reduces the background current effect though have, and can't accumulate the determinand response intensity and reduces signal intensity, also increases power consumption simultaneously; On the other hand, though the latter takes promptly to cut off the power supply to reduce the method for power consumption after the interference of fixed voltage elimination main background, eliminate determinand also and insert the initial stage behind the measuring flume, be converted to the signal of electron mediator through redox, that is the signal in early stage reaction period can't be accumulated.Thereby in the method for operating of prior art, in generation, surveyed the degree of accuracy of substrate concentration relation in Cottrell electric current and the specimen, still has to be hoisted.
Fundamental purpose of the present invention just provides a kind of method of reduction current type biology sensor measured deviation of improvement.
Summary of the invention
The invention provides a kind of novel method that reduces current type biology sensor measured deviation, its step comprises:
(a) combination one current type biology sensor, this sensor contains an electrode system and redox electron mediator at least, and applies a preset voltage in this electrode system;
(b) specimen is inserted this sensor, can't drive the value that this electron mediator carries out electrochemical redox reaction even this preset voltage of existing side by side progressively is reduced to, wherein this step that progressively lowers preset voltage is to last 1 to 15 second;
(c) after the enough reaction time, supply one again and can drive this electron mediator and carry out the electrode system of second voltage of electrochemical redox reaction at this sensor; And
(d) measure the electrochemical reaction current of this electrode system, determine the content of contained this determinand in this specimen.
The method of determinand content in the measurement specimen provided by the present invention, it is characterized in that specimen is inserted preset voltage to the current type biology sensor of electrode system with the conduction electrode system circuit time, immediately this preset voltage progressively is reduced to the value that can't drive electrochemical redox reaction.
The inventive method can not only reacted the background current of eliminating main interference in earlier stage, and preserves the electron mediator that determinand is reacted in redox reaction in earlier stage in the specimen as much as possible, so reaction electronic signal in early stage is accumulated.The not only deductible interference noise of the inventive method, and keep high signal value as far as possible, that is increase signal/noise (S/N) ratio, the degree of accuracy of Cottrell electric current and concentration relationship and accuracy are all promoted; In addition owing to progressively lower the supply of preset voltage, when interrupt this electrochemical redox reaction with the signal accumulation of waiting for electron mediator during, also can reach the effect that reduces power consumption simultaneously.
Those skilled in the art all knows, can use control of numeral or analog-converted and current signal acquisition module, is supplied to the voltage of current type biological sensor electrode system as control, with the usefulness of the acquisition Cottrell electric current that electrochemical redox reaction produced.Therefore, the progressively decreased voltage operation steps of the inventive method can numeral or analog form carry out, look closely in used conversion and control and current signal acquisition module kenel and decide.
Description of drawings
Fig. 1-1,1-2 and 1-3 are the voltage-operated pattern of three kinds of prior aries.
Fig. 2 is disclosed progressively decreased voltage operator scheme, and Fig. 2-the 1st wherein is with analog form decreased voltage progressively, and Fig. 2-the 2nd, with digital form decreased voltage progressively.
Fig. 3 shows the resolution improvement of using measured Cottrell electric current of the inventive method and blood sugar concentration relation.
Embodiment
The Reference numeral simple declaration
10 determinands are inserted preset voltage to the moment of electrode system measuring flume
11 eliminate the fixed voltage of background current
12 read the fixed voltage of Cottrell electric current
The 13 increase trend that electron mediator are reduced because of determinand oxidation reaction in the specimen
14 the voltages that fall progressively in order to the analog form of eliminating background interference
15 the voltages that fall progressively in order to the digital form of eliminating background interference
Preset voltage before 16 determinands are inserted
Fig. 2-1 and 2-2 illustrate two kinds of voltage-operated patterns of the inventive method respectively.Be that the present invention adopts the fall progressively enforcement aspect of voltage of analog form shown in Fig. 2-1, at first apply a preset voltage (16) in the electrode system of current type biology sensor, when liquid specimen is inserted sensor (10), immediately with analog form decreased voltage (14) progressively, and eliminate background interference simultaneously, wait for that determinand applies a driving voltage (12) to measure Cottrell electric current and concentration relationship again through after the enough reaction time in the specimen.
The voltage-operated pattern of Fig. 2-2 is similar to Fig. 2-1, just after sample is inserted the electrode system of sensor, changes with digital form decreased voltage (15) progressively.
The inventive method is applied to the preset voltage value of inductor electrode system before specimen is inserted relevant with the annoyance level of the environmental impact factor, its scope is that those skilled in the art is known, generally between about 0.1 volt to about 0.9 volt scope, be preferably in 0.3 volt to 0.7 volt scope.
The step that progressively lowers preset voltage of the inventive method is to last about 1 to 15 second, is preferably about 4 to 10 seconds.Reaction time of specimen and being used to drives this electron mediator, and to carry out the size of second voltage of electrochemical redox reaction unimportant to the present invention, employed specimen and inductor type decided when those skilled in the art can be according to practical operation, wherein this second voltage can be higher than, be equal to or less than this preset voltage.
The inventive method is applicable to ferment type and non-ferment type current type biology sensor.The structure of ferment type and non-ferment type current type biology sensor is apparent and easy to know to those skilled in the art, and the inventive method is not limited to the current type biology sensor of specific kenel.Generally speaking, ferment type current type biology sensor typical case is contained an electrode system, the redox ferment at particular test, redox electron mediator, carrier and is mixed the buffering agent of forming with conjugate acid and base; Non-ferment type current type biology sensor typical case is contained an electrode system, redox electron mediator and carrier.Wherein, carrier generally comprises high molecular weight water soluble polymer and selectivity contains interfacial agent, and the redox electron mediator generally is to use the potassium ferricyanide.
Implementation
Use such as the Taiwan patent of invention announce No. 416005 the glucose biological sensing test piece that forms of enforcement, with the progressive effect of further demonstration the inventive method.
This glucose biological sensing test piece has construction package and the combination as its Fig. 1 and Fig. 2, and fills a prescription after having the modification of embodiment 1 illustrated glucose response layer.This prescription comprises glucose oxidase ferment, potassium ferricyanide, interfacial agent, water soluble polymer and buffering salt etc.
By emulation accelerated deterioration (it is 50 ℃ that test pieces is preserved environment, lasts for 1 and 8 weeks) with the raising background interference; And in addition with digital conversion control and current signal acquisition module, be supplied to the voltage of current type glucose biological sensor electrode system as control, with the usefulness of the acquisition Cottrell electric current that electrochemical redox reaction produced, last, convert the electric current value of reading that is obtained to concentration of glucose.
Embodiment
Set 2 groups of powering mode states,, after sample adds electrode system, be powered down to the pattern of 0mV at once just like the initial service voltage 300mV of prior art (Fig. 1-1); Another after sample adds electrode system, progressively reduces supply voltage as the initial service voltage 300mV of notion of the present invention (Fig. 2-2) at once, makes its pattern that was reduced to 0mV after 4 seconds (electrochemical redox reaction interruption).
Powering mode with aforementioned two kinds of settings, for same batch of glucose biological sensing test piece after the accelerated deterioration, contain blood simultaneously with basic, normal, high variable concentrations glucose, react after 16 seconds, apply a driving voltage 300mV, and the redox electric current that is proportionate of measurement and concentration of glucose, its result is as shown in Figure 3.
When being used for the glucose biological sensing test piece with the powering mode of prior art, by the sensing value of reading (last for 1 week=1W-0 with last 8 the week=8W-0) with the increase (increasing to 25.75) of the linear equation intercept that is plotted with reference to method (YSI galvanochemistry blood sugar biochemical instruments) by 3.95, can find out that the background interference that acceleration environment generates obviously exists really.But when being used for the glucose biological sensing test piece with the powering mode of notion of the present invention (last for 1 week=1W-N with last 8 the week=8W-N),, can find out that background interference obviously reduces by the intercept no significant difference (1.51 and-0.08) of linear equation.
Moreover, because the inventive method is to take progressively to reduce the pattern of supply voltage to 0mV, electrochemical redox reaction is interrupted, therefore waiting for the electron mediator signal accumulation therebetween, can reach the effect that reduces power consumption simultaneously.In sum, the inventive method is one can effectively reduce the method for the potential background interference deviate of current type biology sensor really.
Following examples will the present invention is further illustrated, and only non-in order to limit the scope of the invention, modification that any those skilled in the art can reach easily and change all are covered by in protection scope of the present invention.
Claims (10)
1. method of measuring determinand content in the specimen, its step comprises:
(a) combination one current type biology sensor, this sensor contains an electrode system and redox electron mediator at least, and applies a preset voltage in this electrode system;
(b) specimen is inserted this sensor, can't drive the value that this electron mediator carries out electrochemical redox reaction even this preset voltage of existing side by side progressively is reduced to, wherein this step that progressively lowers preset voltage is to last 1 to 15 second;
(c) after the enough reaction time, supply one again and can drive this electron mediator and carry out second voltage of electrochemical redox reaction in the electrode system of this sensor; And
(d) measure the electrochemical reaction current of this electrode system, determine the content of contained this determinand in this specimen.
2. method as claimed in claim 1, wherein this step that progressively lowers preset voltage is to carry out with digital form.
3. method as claimed in claim 1, wherein this step that progressively lowers preset voltage is to carry out with analog form.
4. method as claimed in claim 1, wherein this sensor is a ferment type current type biology sensor.
5. method as claimed in claim 1, wherein this sensor is a non-ferment type current type biology sensor.
6. as each method in the claim 1 to 5, wherein this preset voltage is in 0.1 volt to 0.9 volt scope.
7. method as claimed in claim 6, wherein this preset voltage is in 0.3 volt to 0.7 volt scope.
8. method as claimed in claim 1, wherein this step that progressively lowers preset voltage is to last 4 to 10 seconds.
9. as each method in the claim 1 to 5, wherein this second voltage can be higher than, be equal to or less than this preset voltage.
10. as each method in the claim 1 to 5, wherein the redox electron mediator is the potassium ferricyanide.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200410008278XA CN100370249C (en) | 2004-03-04 | 2004-03-04 | Method for reducing measurement deviation of current type biosensors |
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| CNB200410008278XA CN100370249C (en) | 2004-03-04 | 2004-03-04 | Method for reducing measurement deviation of current type biosensors |
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| CN1664572A CN1664572A (en) | 2005-09-07 |
| CN100370249C true CN100370249C (en) | 2008-02-20 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5653863A (en) * | 1995-05-05 | 1997-08-05 | Bayer Corporation | Method for reducing bias in amperometric sensors |
| EP0800086A1 (en) * | 1996-04-01 | 1997-10-08 | Bayer Corporation | Control solution and method for testing the performance of an electrochemical device for determining the concentration of an analyte in blood |
| WO2001021827A1 (en) * | 1999-09-20 | 2001-03-29 | Roche Diagnostics Corporation | Small volume biosensor for continuous analyte monitoring |
| EP1236995A1 (en) * | 1995-11-16 | 2002-09-04 | USF Filtration and Separations Group Inc. | Repetitive potential step method for amperometric detection |
| CN1515898A (en) * | 2003-01-08 | 2004-07-28 | 力捷电脑股份有限公司 | Biological chip capable of raising measurement reliability and its method |
-
2004
- 2004-03-04 CN CNB200410008278XA patent/CN100370249C/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5653863A (en) * | 1995-05-05 | 1997-08-05 | Bayer Corporation | Method for reducing bias in amperometric sensors |
| EP1236995A1 (en) * | 1995-11-16 | 2002-09-04 | USF Filtration and Separations Group Inc. | Repetitive potential step method for amperometric detection |
| EP0800086A1 (en) * | 1996-04-01 | 1997-10-08 | Bayer Corporation | Control solution and method for testing the performance of an electrochemical device for determining the concentration of an analyte in blood |
| WO2001021827A1 (en) * | 1999-09-20 | 2001-03-29 | Roche Diagnostics Corporation | Small volume biosensor for continuous analyte monitoring |
| CN1515898A (en) * | 2003-01-08 | 2004-07-28 | 力捷电脑股份有限公司 | Biological chip capable of raising measurement reliability and its method |
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| CN1664572A (en) | 2005-09-07 |
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