CN101493466B - Method for reducing interference in electrochemical sensor using two different applied potentials - Google Patents
Method for reducing interference in electrochemical sensor using two different applied potentials Download PDFInfo
- Publication number
- CN101493466B CN101493466B CN 200910007080 CN200910007080A CN101493466B CN 101493466 B CN101493466 B CN 101493466B CN 200910007080 CN200910007080 CN 200910007080 CN 200910007080 A CN200910007080 A CN 200910007080A CN 101493466 B CN101493466 B CN 101493466B
- Authority
- CN
- China
- Prior art keywords
- current
- electric current
- electrode
- glucose
- working electrode
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Abstract
The invention relates to method of reducing influence of interfering compounds in analyte measurement, more particular, relates to method of reducing influence of interfering compounds in system, wherein testing strip (600) using two or more working electrodes (10,14). In the present invention, applying a first electric potential (E1) to a first working electrode (12), and applying a second electric potential (E2) which is bigger than the first electric potential (E1) and has the same polar, to a second working electrode (14).
Description
The application is that application number is 200480039526.5, the applying date is on October 29th, 2004, dividing an application with the topic patented claim.
Background of invention
Electrochemical glucose test strips is for example deriving from LifeScan, Inc.'s
Those electrochemical glucose test strips of using in the whole blood test kit are that design is used for measuring the concentration of glucose in diabetic's blood sample.The measurement of glucose is based on flavo-enzyme one glucose oxidase to the specific oxidation of glucose.Between this reaction period, this enzyme has been reduced.By reacting with mediator ferricyanide, this enzyme is reoxidized, and in this process or between the reaction period, self is reduced the ferricyanide.These reactions are summarized as follows.
D-Glucose+Gox
(OX)→ gluconic acid+GOx
(RED)
GOx
(RED)+2Fe(CN)
6 3-→GOx
(OX)+2Fe(CN)
6 4-
When using the current potential that applies between two electrodes to carry out above-mentioned reaction, by the electrochemical re-oxidation at the reduction amboceptor ion (ferrocyanide) of electrode surface, but generation current.Therefore the electric current that produces, due in ecotopia, is directly proportional to the amount that is placed in two sample glucose between electrode in the amount of the ferrocyanide that produces during above-mentioned chemical reaction, so will be directly proportional to the glucose content of sample.The redox mediators for example ferricyanide is at the oxidoreducing enzyme compound of exchang electron between glucose oxidase and electrode for example.When the concentration of glucose in sample increased, the amount of the reduction amboceptor of formation also increased, and therefore, had direct related between the electric current that generates and concentration of glucose by reoxidizing of reduction amboceptor.Particularly, the electronics of crossing electric interface shifts flow (the every mole of oxidized glucose of 2 moles of electronics) that causes electric current.Therefore, the electric current that causes due to the introducing of glucose is called glucose current.
Because know the concentration of glucose in blood, particularly the concentration in diabetes patient's blood may be very important, use above-mentioned principle can take a sample from the mediocrity at any time so developed, and the measuring instrument of measure glucose concentration.Monitor the glucose current of generation by measuring instrument, and use the algorithm that sets in advance to change into the reading of concentration of glucose, described algorithm connects electric current and concentration of glucose by simple mathematical formulae.Generally, measuring instrument and disposable band collaborative work, except enzyme (glucose oxidase) and amboceptor (ferricyanide), described band comprises sample room and at least two electrodes that are placed in sample room.In use, the user hold up they finger or other cause and bleed in the position easily, and blood sample is introduced sample room, begin thus above-mentioned chemical reaction.
In electrochemical terms, the function of measuring instrument is dual.At first, its provide polarizing voltage (for
Approximately 0.4V), this polarizing voltage polarizes electric interface, and allows electric current flow at the carbon working electrode surface.Secondly, the electric current that flows in the external circuit of its measurement between anode (working electrode) and negative electrode (contrast electrode).Therefore, measuring instrument can be regarded as simple electro-chemical systems, and this electro-chemical systems also can use the 3rd or even the 4th electrode with the bipolar electrode mode operation in reality, helps measure glucose and/or carry out other function in measuring instrument.
In most of the cases, the formula that the above provides is considered to the sufficient approximation to the chemical reaction that carries out on test-strips, and the reading of measuring instrument is the enough accurate expressions to the blood sample concentration of glucose.Yet in some cases and for some purposes, it is favourable improving the degree of accuracy of measuring.For example, the one part of current of measuring on electrode is because other chemical substance or the compound that exist in sample produce.When having so other chemical substance or compound, they can be described as interfering compound, and the other electric current that causes can be described as interference current.
Current potential interfering chemicals (namely for example find in blood at physiological fluid, can produce the compound of interference current under electric field exists) comprises ascorbate, urate and paracetamol (Tylenol
TMOr Paracetamol).In the electrochemical measurement instrument (for example glucose meters) of the concentration that is used for measurement physiological fluid analyte, a mechanism of generation interference current relates to the reduction by enzyme (for example glucose oxidase), the oxidation of one or more interfering compounds.In such measuring instrument, another mechanism of generation interference current relates to the reduction by amboceptor (for example ferricyanide), the oxidation of one or more interfering compounds.In such measuring instrument, another mechanism of generation interference current relates to the oxidation at one or more interfering compounds of working electrode.Therefore, the total current of measuring at working electrode is the stack of the electric current that produces because analyte is oxidized and the electric current that produces because interfering compound is oxidized.The oxidation of interfering compound can be with enzyme, the interactional result of amboceptor or can directly occur at working electrode.
Generally, the current potential interfering compound can be in the electrode surface oxidation and/or by redox mediators and oxidized.The oxidation of interfering compound in the glucose measurement system causes that measured oxidation current is both relevant with glucose also relevant with interfering compound.Therefore, if the concentration of interfering compound is significantly higher than concentration of glucose with the efficient oxidation identical with glucose and/or interfering compound concentration, it can affect the concentration of glucose of measurement.
The co-oxidation of analyte (for example glucose) and interfering compound especially is a problem in following situation: the normal potential of interfering compound (being the current potential of compound when oxidized) is similar with the normal potential of redox mediators in size, causes because the oxidized interference current that produces of interfering compound on working electrode accounts for suitable ratio.The electric current that produces due to the oxidation of interfering compound on working electrode can be called direct interference current.Therefore, reducing that direct interference current maybe minimizes this impact for the impact of analyte concentration measurement will be favourable.The method that reduced in the past or eliminated direct interference current comprises, design can prevent that interfering compound from arriving working electrode, reduces thus or eliminates the direct interference current that is produced by the compound that is eliminated.
A strategy that reduces the impact of the interfering compound that produces direct interference current is electronegative film to be placed on the top of working electrode.As an example, can be with sulfonation fluorinated polymer NAFION for example
TMBe placed on above working electrode, to repel all electronegative chemical substances.Generally, a lot of interfering compounds comprise ascorbate and urate with negative charge, and are therefore, when the surface of working electrode is covered by electronegative film, not oxidized thereby these interfering compounds are ostracised.Yet for example paracetamol is not electronegative due to some interfering compound, thereby and can pass through electronegative film, so use electronegative film can not eliminate direct interference current.Another shortcoming that covers working electrode with electronegative film is that for example the ferricyanide is electronegative for redox mediators commonly used, and can not come and the electrode exchang electron by described film.The electronegative film of use also has a shortcoming to be on working electrode, and the slowed down amboceptor of reduction of current potential is diffused on working electrode, has increased thus Measuring Time.Another shortcoming of the electronegative film of use is to have increased production complicacy and the cost of the test-strips with electronegative film on working electrode.
Another strategy that can be used for reducing direct interference current is to lay a size Selection film at the working electrode top.As an example, can with 100 dalton's size exclusion films for example acetyl cellulose film be placed on working electrode, to get rid of molecular weight greater than 100 daltonian compounds.In this embodiment, with oxidoreducing enzyme for example glucose oxidase be placed on the size exclusion film.Under glucose and oxygen existence, glucose oxidase produces hydrogen peroxide, and the amount of the hydrogen peroxide of generation is directly proportional to concentration of glucose.Should be noted that the molecular weight of glucose and most of redox mediators greater than 100 dalton, and therefore can not pass through the size Selection film.Yet the molecular weight of hydrogen peroxide is 34 dalton, therefore can pass through the size Selection film.Generally, the molecular weight of majority of compounds is greater than 100 dalton, thereby therefore can not be oxidized at electrode surface by exclusion.Because some interfering compound has less molecular weight, therefore can pass through the size Selection film, so use the size Selection film can not eliminate direct interference current.Use another shortcoming of size Selection film on working electrode, increased production complicacy and the cost of the test-strips with size Selection film.
Another strategy that can be used for reducing the impact of direct interference current is to use the redox mediators with suboxides reduction potential, for example oxidation-reduction potential be approximately-300mV extremely+redox mediators of 100mV (vs saturated calomel electrode).This makes it possible to apply lower current potential to working electrode, thereby has reduced interfering compound by the speed of working electrode oxidation.The example that has than the redox mediators of suboxides reduction potential comprises osmium bipyridine complex compound, ferrocene derivatives and quinone derivative.Yet the redox mediators that has than the suboxides reduction potential often is difficult to synthesize, and is more unstable and more insoluble.
Another strategy that can be used for reducing the impact of interfering compound is to unite and use pseudo electrode and working electrode.Then can deduct from the electric current of measuring at working electrode at the electric current that pseudo electrode is measured, with the impact of compensate for disturbances compound.If pseudo electrode is exposed (namely not covered by enzyme or amboceptor), the electric current of measuring at pseudo electrode will be directly proportional to direct interference current, and will deduct from the electric current of measuring at working electrode at the electric current that pseudo electrode is measured and will reduce or eliminate the impact of the direct oxidation of interfering compound on working electrode.If pseudo electrode covers with redox mediators, the electric current of measuring at pseudo electrode will be direct interference current and the combination of the interference current that the redox mediators reduction is caused due to interfering compound.Therefore, will deduct from the electric current of measuring at working electrode at the electric current that the pseudo electrode that covers with redox mediators is measured and to reduce or eliminate the impact of direct oxidation of interfering compound and the impact of the interference that due to interfering compound, the redox mediators reduction produced on the work electroplax.In some cases, pseudo electrode also can cover with the oxidoreducing enzyme of inert protein or inactivation, the effect to spreading with simulation redox mediators and enzyme.Thereby because preferably having little sample room, test-strips make the diabetic need not to provide large blood sample, so the sample room's volume when not coming Measurement and analysis thing (for example glucose) with additional electrode comprises that the additional electrode that makes sample room's volume increase may be disadvantageous.In addition, may be difficult to make the electric current of measuring at pseudo electrode directly related with the interference current of measuring at working electrode.At last, because can cover pseudo electrode with the material (for example redox mediators) different from the material that is used for covering working electrode (for example redox mediators and enzyme), so use pseudo electrode may increase production cost and the complicacy of test-strips as the test-strips that reduces or eliminate the method for interfering compound impact in a plurality of working electrode system.
Come the Measurement and analysis thing with a plurality of working electrodes, for example exist
Some test strip designs of the system that uses in measuring system are favourable, and this is because used two working electrodes.In such system, therefore the method for developing the impact of reduction or elimination interfering compound will be favourable.More particularly, develop in the situation that the redox mediators that does not use pseudo electrode, intermediate film or have a suboxides reduction potential reduces or the method for eliminating the impact of interfering compound will be favourable.
Summary of the invention
The present invention relates in the measurement of analyte to reduce the method for the impact of interfering compound, more particularly, relate to test-strips therein and use the method that reduces the impact of interfering compound in the system of two or more working electrodes.In one embodiment of the invention, apply first current potential for the first job electrode, apply second current potential for second working electrode, the polarity of described second current potential is identical with first current potential, but its size is larger than first current potential.For come the embodiment of Measurement and analysis substrate concentration with reduction current, the size of second current potential also may be less than first current potential.In one embodiment, first job electrode and second working electrode can cover with the specific enzyme reagent of analyte and redox mediators.Selection imposes on first current potential of first job electrode, make it be enough in the diffusion restriction mode the redox mediators oxidation that is reduced, and select second current potential to make its size (being absolute value) larger than first current potential, thereby make the higher oxidation of luminous efficiency on second working electrode.In this embodiment of the present invention, comprise analyte current and interfering compound electric current at the electric current of first job electrode measurement, and the electric current of measuring in second work unit comprises analyte overpotential current and interfering compound overpotential current.Should be noted that analyte current both refers to the electric current corresponding with analyte concentration with the analyte overpotential current, and this electric current is the oxidized result of reduction amboceptor.In one embodiment of the invention, can pass through following formula definition in electric current and the relation between the electric current of second working electrode of first job electrode,
A wherein
1The analyte current at the first job electrode, W
1The electric current at the first job electrode measurement, W
2Be the electric current of measuring at second working electrode, X is the analyte dependence voltage effects factors, and Y is the interfering compound dependence voltage effects factors.Use in the methods of the invention above-mentioned formula, can reduce the impact due to the oxidation current that exists interfering compound to bring, and the correcting current value of calculating analyte concentration in the sample that more can represent test.
in one embodiment of the invention, the concentration of glucose that is placed in the sample on test-strips can as described belowly calculate: sample is placed on test-strips, described test-strips has first job electrode and second working electrode and contrast electrode, at least first job electrode and second combined thing of working electrode (for example enzyme and redox mediators) cover, when applying current potential between first job electrode and contrast electrode and between second working electrode and contrast electrode, described compound be suitable for promoting the oxidation of glucose and electronics from the suction pressure of oxidation to the first job electrode and second working electrode on.According to the present invention, apply first current potential between first job electrode and contrast electrode, select the size of first current potential, make it possible to be enough to guarantee that the size of the electric current that the oxidation due to glucose in sample produces only is subject to the restriction of the factor (for example diffusion) except applying voltage.According to the present invention, apply second current potential between second working electrode and contrast electrode, the size of second current potential is larger than first current potential, and in one embodiment of the invention, selects second current potential to be increased in the oxidation of interfering compound on second working electrode.In another embodiment of the invention, can reduce oxidation current that the existence due to interfering compound produces for the influence of peak current that is used for calculating concentration of glucose in sample with following formula.Particularly, can use the electric current A of calculating
1GDerive concentration of glucose, wherein
A wherein
1GGlucose current, W
1The electric current of measuring on the first job electrode, W
2The electric current of measuring on second working electrode, X
GBe the dependence on the glucose voltage effects factors, and Y is the interfering compound dependence voltage effects factors.
The accompanying drawing summary
New feature of the present invention especially provides in claims.By the following detailed description that provides exemplary, can understand better the features and advantages of the present invention, wherein used principle of the present invention and accompanying drawing:
Fig. 1 is the exploded perspective illustration for test-strips embodiment of the present invention.
Fig. 2 is the diagram figure for measuring instrument of the present invention and test-strips.
Fig. 3 is the dependent hydrodynamic force voltammogram that shows between the electric current of the voltage that applies and measurement.
Detailed Description Of The Invention
Although the present invention is particularly suitable for measuring the concentration of glucose in blood, it will be apparent to one skilled in the art that the method for describing in the present invention can be suitable for improving the selectivity for other system of the electrochemical measurement of physiological fluid analyte.Can be suitable for improving the example of system optionally with the inventive method and comprise electrochemical sensor for the concentration of measuring physiological fluid lactate, alcohol, cholesterol, amino acid, choline and fructosamine.The example that can contain the physiological fluid of such analyte comprises blood, blood plasma, serum, urine and interstitial fluid.Should further understand, be to describe in the electro-chemical systems that produces by oxidation although the inventive method is measured therein electric current, and it is the system that produces by reduction that the present invention is equally applicable to wherein measured electric current.
The present invention relates to improve the optionally method of electrochemical measurement system, described method is specially adapted to blood sugar measuring system.More particularly, the present invention relates to improve by the impact of partially or completely proofreading and correct direct interference current the optionally method of blood sugar measuring system.In such system, selectivity is the ability that concentration of glucose in the physiological fluid sample is accurately measured by this system, and described physiological fluid comprises that one or more can produce the compound of interference current.Therefore, optionally raising can reduce the electric current that produces at working electrode owing to there being interfering compound (being that oxidation is to produce the compound except glucose of interference current), and makes the electric current of measurement more can represent concentration of glucose.Particularly, the electric current of measurement can be the function of the oxidation of the interfering compound usually found in physiological fluid, and described interfering compound is paracetamol (Tylenol for example
TMOr Paracetamol), ascorbic acid, cholerythrin, dopamine, gentianic acid, glutathione, levodopa, ethyldopa, tolazamide, orinase and uric acid.Such interfering compound can be oxidized by for example carrying out chemical reaction with redox mediators, and is perhaps oxidized by oxidation on electrode surface.
In system fully optionally, the oxidation current that will not produce by any interfering compound, and all oxidation current will produce by glucose oxidase.Yet, if the oxidation of interfering compound and the oxidation current that produces can not be avoided, the invention describes the method for some or all impact of eliminating interfering compound, this is to account for the ratio of whole oxidation currents by quantitatively definite oxidation current that is produced by interfering compound, and this magnitude of current is deducted to realize from whole oxidation currents.Particularly, in the methods of the invention, use comprises the test-strips of first job electrode and second working electrode, applies two different potentials, and measures the oxidation current produce and come glucose estimator and interfering compound shared oxidation current ratio separately on each working electrode.
In an embodiment of the inventive method, the test-strips of using comprises sample room, and described sample room comprises first job electrode, second working electrode and contrast electrode.First job electrode, second working electrode and contrast electrode are covered by glucose oxidase (enzyme) and the ferricyanide (redox mediators).When being placed on blood sample (physiological fluid) in sample room, glucose oxidase is produced gluconic acid by the Reduction of Glucose in blood sample.Then be reduced to ferrocyanide by the ferricyanide, gluconic acid is oxidized, has produced the redox mediators of the reduction that its concentration is directly proportional to concentration of glucose.Example applicable to the test-strips of the inventive method is by LifeScan, Inc.of Milpitas, and California sells
Test-strips.Other test-strips is described in international open WO 01/67099A1 and WO01/73124A2.
In an embodiment of the inventive method, apply first current potential for the first job electrode, apply second current potential for second working electrode.In this embodiment, select the size of first current potential, make the glucose current reaction relatively insensitive for the current potential that applies, thereby be diffused into the quantitative limitation of the redox mediators of the reduction on the first job electrode in the glucose current size on the first job electrode.Should be noted that on working electrode glucose not by direct oxidation, but by using oxidoreducing enzyme and redox mediators by indirect oxidation.In instructions of the present invention, glucose current refers to the oxidation of the redox mediators of the reduction relevant to concentration of glucose.In embodiments of the invention, when ferri/ferrocyanide is redox mediators, and carbon is when being working electrode, and first current potential can be approximately 0 millivolt-Yue 500 millivolts, more preferably approximately 385 millivolts-Yue 415 millivolts, about 395-405mV even more preferably.Apply second current potential for second working electrode, make second current potential greater than first current potential.The current potential that wherein applies is greater than the required current potential of oxidizing glucose.In one embodiment of the invention, when ferri/ferrocyanide is redox mediators, and carbon is when being working electrode, and second current potential can be approximately 50 millivolts-Yue 1000 millivolts, more preferably approximately 420 millivolts-Yue 1000 millivolts, about 395-405mV even more preferably.
Because along with the increase glucose current of current potential does not increase or only minimum degree ground increase, so the glucose current on second working electrode should equate basically with the glucose current on the first job electrode, even the current potential on second working electrode is greater than the current potential on the first job electrode.Therefore, any additional electric current of measuring on second working electrode is attributable to the oxidation of interfering compound.In other words, should cause that at the high potential on second working electrode the glucose overpotential current of measuring equals in size or is substantially equal to glucose current on the first job electrode on second working electrode, because first is that the glucose current of this scope is insensitive for the change that applies current potential in the glucose current scope of restriction with current potential and second current potential.Yet in practice, other parameter may affect the electric current of measurement, and for example, when applying higher current potential for second working electrode, as the result of IR potential drop or capacitive effect, the total current on second working electrode often can increase a little.When having IR potential drop (both uncompensated resistance) in system, higher apply the electric current that current potential causes measurement and increase.The example of IR potential drop can be the nominal resistance of the physiological fluid between first job electrode, second working electrode, contrast electrode, working electrode and contrast electrode.In addition, applying higher current potential, to cause forming larger ion double-deck, and this ion bilayer is at the electrode/liquid interface formation, is increased in ion capacitance and formed electric current on first job electrode or second working electrode.
In order to determine to develop suitable formula at the glucose current of measuring on the first job electrode and the actual relationship between the glucose current of measuring on second working electrode.Should be noted that the glucose current on second working electrode also can be called glucose overpotential current.Proportional relation between glucose current and glucose overpotential current can be described by following formula.
X
GxA
1G=A
2G(formula 1)
X wherein
GThe dependence on the glucose voltage effects factors, A
1GThe glucose current on the first job electrode, A
2GIt is the glucose current on second working electrode.
In one embodiment of the invention, when ferri/ferrocyanide is redox mediators, and carbon is when being working electrode, and for glucose, the voltage effects factor can be expected to be approximately 0.95 to approximately 1.1.In this embodiment of the present invention, higher current potential has no significant effect for the glucose oxidase electric current, because and between working electrode, redox mediators (ferrocyanide) has electron transfer kinetics and reversible electronics transfer characteristic fast.Because after a fixed point along with the increase glucose current of current potential does not increase, so can say that glucose current is saturated or in the situation of diffusion restriction.
In the embodiment of the invention described above, glucose is measured indirectly by iron protoxide prussiate on working electrode, and the ferrocyanide substrate concentration is directly proportional to concentration of glucose.For concrete galvanochemistry compound, normal potential (E °) value is the module of the ability of this compound and other compound exchang electron.In the methods of the invention, be chosen in the current potential on the first job electrode, make its normal potential greater than redox mediators (E °).Because select first current potential, make the E ° of value that is sufficiently more than redox couple, so along with the increase that applies current potential, oxidation rate does not significantly increase.Therefore, apply larger current potential and will can not be increased in second oxidation on working electrode on second working electrode, and the electric current of any increase of measuring on the electrode of high potential must be due to for example oxidation of interfering compound of other factors.
Fig. 3 is the dependent hydrodynamic force voltammogram that shows between the electric current of the voltage that applies and measurement, and wherein ferri/ferrocyanide is redox mediators, and carbon is working electrode.Each data point on this figure represents at least one experiment, and wherein electric current is measured 5 seconds after applying voltage between working electrode and contrast electrode.Fig. 3 shows, at about 400mV, electric current has formed the beginning of land regions, because this voltage that applies is sufficiently more than E ° of value of ferrocyanide.Therefore, as shown in Figure 3, when current potential reaches approximately 400mV, it is saturated that glucose current becomes, this be because the oxidation of ferrocyanide be diffusion restriction (ferrocyanide to the diffusion restriction of working electrode the size of the electric current measured, and be not subjected to the restriction of the electron transfer speed between ferrocyanide and electrode).
Usually, the electric current that oxidation by interfering compound produces can be unsaturated because executing alive increase, and compare (ferrocyanide produces by the interaction of glucose and enzyme and enzyme and ferrocyanide) with the electric current that oxidation by ferrocyanide produces, show strong a lot to applying the dependence of current potential.Interfering compound has usually than the slow electron transfer kinetics of redox mediators (being ferrocyanide).The reason of this difference is the following fact, most of interfering compound experience endosphere electron transfer, and ferrocyanide experiences ectosphere electron transfer faster.Typical endosphere electron transfer needed to occur chemical reaction before metastatic electron, for example hydride shifts.Different with it, the ectosphere electron transfer did not need chemical reaction before metastatic electron.Therefore, the endosphere electron transfer speed shifts slow usually than ectosphere electronics, because the chemical reaction step that they need to add.It is an example of endosphere oxidation that Ascorbic Acid Oxidation is become hydroascorbic acid, and it need to discharge two hydride parts.It is the example that the ectosphere electronics shifts that the ferricyanide is oxidized to ferrocyanide.Therefore, when when high potential is tested, the electric current that is produced by interfering compound can increase usually.
Can describe by following formula at the interfering compound electric current on the first job electrode and the relation between the interfering compound overpotential current on second working electrode,
YxI
1=I
2(formula 2)
Wherein Y is the interfering compound dependence voltage effects factors, I
1The interfering compound electric current, and I
2It is the interfering compound overpotential current.Because interfering compound dependence voltage effects factor Y depends on many factors, comprise the material that concrete interfering compound and working electrode are all, so for concrete system, test-strips, analyte and interfering compound, the calculating of the concrete interfering compound dependence voltage effects factor may need to test to optimize the voltage effects factor for these standards.Perhaps, under some conditions, can derive or describe the suitable voltage effects factor by mathematical method.
Ferri/ferrocyanide is redox mediators therein, and carbon is in an embodiment of the present invention of working electrode, and interfering compound dependence voltage effects factor Y can use about I
1And I
2The Tafel formula come to describe with mathematical measure,
η wherein
1=E
1-E °, η
2=E
2-E °, b ' is the constant that depends on concrete electroactive interfering compound, E
1First current potential, and E
2Second current potential.The value of E ° (normal potential of concrete interfering compound) is unessential, because it has been cancelled in the calculating of Δ η.Can be with formula 2,2a, 2b altogether, and reset, obtain following formula,
Δ η=E wherein
1-E
2Formula 2c provides the mathematical relation of the relation between description Δ η (being the difference between first current potential and second current potential) and interfering compound dependence voltage effects factor Y.In one embodiment of the invention, Y can be about 1-approximately 100, more preferably about 1-10.In one embodiment of the invention, for the combination of concrete interfering compound or interfering compound, interfering compound dependence voltage effects factor Y can be determined by experiment.Should be noted that for interfering compound, interfering compound dependence voltage effects factor Y is usually greater than the voltage effects factor X of glucose
GAs described in following chapters and sections, a) interfering compound electric current I
1With interfering compound overpotential current I
2Between mathematical relation; And b) glucose current A
1GWith glucose overpotential current A
2GBetween mathematical relation make it possible to propose the glucose algorithm, this algorithm has reduced the impact of interfering compound for glucose measurement.
In one embodiment of the invention, developing the corrected glucose current that algorithm calculates the impact of interference-free thing (is A
1GAnd A
2G).After being added to sample on test-strips, apply first current potential for the first job electrode, apply second current potential for second working electrode.At the first job electrode, measure first electric current, it can be described by following formula,
W
1=A
1G+ I
1(formula 3)
W wherein
1It is first electric current on the first job electrode.In other words, first electric current comprises glucose current A
1GWith the interfering compound electric current I
1Stack.More particularly, the interfering compound electric current can be direct interference current described above.At second working electrode, measure second electric current in second current potential or overvoltage, it can be described by following formula,
W
2=A
2G+ I
2(formula 4)
W wherein
2Second electric current on second working electrode, A
2GThe glucose overpotential current second potential measurement, I
2It is the interfering compound overpotential current second potential measurement.More particularly, the interfering compound overpotential current can be direct interference compound electric current described above.Use comprises 4 unknown quantity (A
1G, A
2G, I
1And I
2) above-described 4 formula (formula 1-4), can calculate the corrected glucose current formula of interference-free compounds affect.
As first step in deriving, can with being substituted in formula 4 from the A2G of formula 1 with from the I2 of formula 2, obtain following formula 5.
W
2=X
GA
1G+ YI
1(formula 5)
Next, formula 3 be multiply by the interfering compound dependence voltage effects factor Y of interfering compound, obtain formula 6.
YW
1=YA
1G+ YI
1(formula 6)
Formula 5 is deducted formula 6, obtain following form as shown in Equation 7
W
2-YW
1=X
GA
1G-YA
1G(formula 7)
Formula 7 is reset the corrected glucose current A that finds the solution in first potential measurement
1G, as shown in Equation 8.
Obtained corrected glucose current A by formula 8
1G, it has eliminated the impact of disturbing, and this only needs the output current (W for example of first job electrode and second working electrode
1And W
2), dependence on the glucose voltage effects factor X
GInterfering compound dependence voltage effects factor Y with interfering compound.
The glucose meters that will comprise electronic unit is electrically connected to glucose test strip with from W
1And W
2Measure electric current. in one embodiment of the invention, can be with X
GBe programmed in glucose meters with Y, so only read memory.In another embodiment of the invention, can Y be passed to measuring instrument by calibration code chip.Calibration code chip has one group specifically about X in its storer
GWith the value of Y, for a lot of concrete test-strips, can proofread and correct these values.This can explain may be at X
GAnd difference between the test-strips that occurs in Y batch.
In another embodiment of the invention, to only have when surpassing some threshold values, the corrected glucose current in formula 8 just can be used by measured instrument.For example, if W
2Compare W
1Go out greatly more than 10% or 10%, measuring instrument will be proofreaied and correct output current with formula 8.Yet, if W
2Compare W
1Go out greatly below 10% or 10%, interfering compound concentration is very low, so measuring instrument can be got W simply
1With W
2Between average current value, improve the accuracy and precision of measurement.In order to replace simply with electric current W
1And W
2On average, method can be to use W more accurately
2/ X
GCome average W
1, wherein considered dependence on the glucose voltage effects factor X
G(note, work as I
2When very low, according to formula 1 and 4, W
2/ X
GApproximate A
1G).Only in the situation that some wherein exist the interfering compound of the level of signifiance to use the strategy of formula 8 to alleviate the danger of the glucose current excessive correction of measuring in sample.Should be noted that and work as W
2Compare W
1When enough large, when (for example go out greatly approximately 100% or more), this is to have the very indication of the interfering compound of high concentration.Under these circumstances, may wish output error message rather than dextrose equivalent, because very high-caliber interfering compound can cause breaking of formula 8 accuracy.
Below chapters and sections the possible test-strips embodiment that can use together with the algorithm of the present invention shown in formula 8 proposition will be described.Fig. 1 is the exploded perspective illustration of test-strips 600, and it comprises 6 layers that are arranged on substrate 5.These 6 layers are conductive layer 50, insulation course 16, reagent layer 22, bonding coat 60, hydrophilic layer 70 and top layer 80.Test-strips 600 can be made in series of steps, and for example wherein using, the screen cloth printing method is arranged in conductive layer 50, insulation course 16, reagent layer 22, bonding coat 60 on substrate 5.Hydrophilic layer 70 and top layer 80 can take out from coiled material (roll stock) and be laminated on substrate 5.Thereby the test-strips of assembling forms and can receive the sample receiving chamber that blood sample makes blood sample to analyze fully.
Reagent layer 22 can be arranged on a part of conductive layer 50 and insulation course 16.In an embodiment of the present invention, reagent layer 22 can comprise optionally and the chemical substance of glucose response for example oxidoreducing enzyme and redox mediators.Between this reaction period, can produce the redox mediators of the reduction of certain proportion amount, can measure it with electrochemical means, thereby can calculate concentration of glucose.The example that is applicable to reagent formulation of the present invention or ink can be referring to US patent 5,708,247 and 6,046,051; The International Application No. WO 01/67099 and the WO01/73124 that publish, they all are incorporated herein by reference.
Fig. 2 is the simple diagram figure that shows the measuring instrument 500 that is connected with test-strips 600.Measuring instrument 500 has 3 electrical pickofves, and these 3 electrical pickofves form and being electrically connected to of first job electrode 12, second working electrode 14 and contrast electrode 10.Particularly, connector 101 connects voltage source 103 and first job electrode 12, and connector 102 connects voltage source 104 and second working electrode 14, and common connector 100 is connected with being connected voltage source 103 with contrast electrode 10.When testing, the voltage source 103 in measuring instrument 500 applies first current potential E between first job electrode 12 and contrast electrode 10
1, voltage source 104 applies second current potential E between second working electrode 14 and contrast electrode 10
2Apply blood sample, first job electrode 12, second working electrode 14 and contrast electrode 10 are covered by blood like this.This causes reagent layer 22 hydrations, produces the ferrocyanide that the glucose that exists in its amount and sample and/or interfering compound concentration are directly proportional.Apply 5 seconds after sample, measuring instrument 500 is measured the oxidation current of first job electrodes 12 and second working electrode 14.
In above-mentioned first and second test-strips embodiment, first job electrode 12 and second working electrode 14 have equal area.Should be noted that and the invention is not restricted to have test-strips of the same area.For the embodiment of the different above-mentioned test-strips of area wherein, the output current of each working electrode must be carried out naturalization to area.Because output current is directly proportional to area, so the term in formula 1-8 can represent with the current potential (electric current) of ampere or the ampere (being current density) in every current potential area.
Will be appreciated that, for the structure that illustrates and describe, can substitute equivalent constructions herein, and described embodiment of the present invention not the unique structure that can use in the present invention.In addition, should be appreciated that above-mentioned each structure has function, and such structure can be described as the means of implementing this function.Although to have represented and described the preferred embodiments of the invention, to have it will be apparent to one skilled in the art that the embodiment that provides such is only in order illustrating.To those skilled in the art, in the case of without departing from the present invention, can make a lot of changes, variation and substitute.The multiple replacement scheme that should be appreciated that embodiment of the present invention described herein can be used for implementing the present invention.Below claims limit scope of the present invention, and the method and structure in these claim scopes and be equal to absorption and should be included in these claim scopes.
Claims (6)
1. the method for the interference in the reduction electrochemical sensor, described method comprises:
Apply first current potential for the first job electrode;
Apply second current potential for second working electrode, wherein said second current potential is greater than the absolute value of described first current potential;
Measurement first electric current on described first job electrode, described first electric current comprises analyte current and interfering compound electric current;
Second electric current of measurement on described second working electrode, described second electric current comprises analyte overpotential current and interfering compound overpotential current, wherein said analyte overpotential current and described analyte current have first proportional relation, and wherein said interfering compound overpotential current and described interfering compound electric current have second proportional relation; With
Use formula to calculate the correcting current value that represents analyte concentration, described formula is the function of described first electric current, described second electric current, described first proportional relation and described second proportional relationship, and wherein said formula is
A wherein
1Described analyte current, W
1Described first electric current, W
2Be described second electric current, X is the analyte voltage effects factors, and Y is the interfering compound voltage effects factors;
Wherein said analyte is glucose;
Wherein for the described electrochemical sensor that comprises carbon working electrode and ferrocyanide redox mediators, described first current potential is 0 millivolt-500 millivolts, and described second current potential is 50 millivolts-1000 millivolts.
2. the process of claim 1 wherein for the described electrochemical sensor that comprises carbon working electrode and ferrocyanide redox mediators, described first current potential is 385 millivolts-415 millivolts.
3. the process of claim 1 wherein for the described electrochemical sensor that comprises carbon working electrode and ferrocyanide redox mediators, described second current potential is 420 millivolts-1000 millivolts.
4. the process of claim 1 wherein that described interfering compound electric current is because at least a oxidation that is selected from following compound produces: paracetamol, ascorbic acid, cholerythrin, dopamine, gentianic acid, glutathione, levodopa, ethyldopa, tolazamide, orinase and uric acid.
5. the process of claim 1 wherein that described first proportional relation is
X×A
1＝A
2
Wherein X is the described analyte voltage effects factor, A
1Described analyte current, and A
2It is described analyte overpotential current.
6. the process of claim 1 wherein that described second proportional relation is
Y×I
1＝I
2
Wherein Y is the described interfering compound voltage effects factor, I
1Described interfering compound electric current, and I
2It is described interfering compound overpotential current.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51625203P | 2003-10-31 | 2003-10-31 | |
| US60/516252 | 2003-10-31 | ||
| US55872804P | 2004-03-31 | 2004-03-31 | |
| US55842404P | 2004-03-31 | 2004-03-31 | |
| US60/558424 | 2004-03-31 | ||
| US60/558728 | 2004-03-31 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004800395265A Division CN100473982C (en) | 2003-10-31 | 2004-10-29 | Method for reducing interferences in an electrochemical sensor using two different applied potentials |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101493466A CN101493466A (en) | 2009-07-29 |
| CN101493466B true CN101493466B (en) | 2013-11-06 |
Family
ID=37657575
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480039544 Pending CN1902480A (en) | 2003-10-31 | 2004-10-29 | Electrochemical test strip for reducing the effect of direct interference current |
| CN 200480039546 Pending CN1902481A (en) | 2003-10-31 | 2004-10-29 | Method of reducing the effect of direct and mediated interference current in an electrochemical test strip |
| CN200480039527XA Expired - Fee Related CN101163963B (en) | 2003-10-31 | 2004-10-29 | A measurer of reducing interferences in an electrochemical sensor using two different applied potentials |
| CN 200910007080 Expired - Fee Related CN101493466B (en) | 2003-10-31 | 2004-10-29 | Method for reducing interference in electrochemical sensor using two different applied potentials |
| CNB2004800395335A Expired - Fee Related CN100473983C (en) | 2003-10-31 | 2004-10-29 | Method for reducing the effect of direct interference current in an electrochemical test strip |
| CN 200910002047 Expired - Fee Related CN101533007B (en) | 2003-10-31 | 2004-10-29 | Method of reducing the effect of direct interference current in an electrochemical test strip |
| CN 200480039541 Pending CN1902479A (en) | 2003-10-31 | 2004-10-29 | Electrochemical test strip for reducing the effect of direct and mediated interference current |
| CNB2004800395265A Expired - Fee Related CN100473982C (en) | 2003-10-31 | 2004-10-29 | Method for reducing interferences in an electrochemical sensor using two different applied potentials |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480039544 Pending CN1902480A (en) | 2003-10-31 | 2004-10-29 | Electrochemical test strip for reducing the effect of direct interference current |
| CN 200480039546 Pending CN1902481A (en) | 2003-10-31 | 2004-10-29 | Method of reducing the effect of direct and mediated interference current in an electrochemical test strip |
| CN200480039527XA Expired - Fee Related CN101163963B (en) | 2003-10-31 | 2004-10-29 | A measurer of reducing interferences in an electrochemical sensor using two different applied potentials |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004800395335A Expired - Fee Related CN100473983C (en) | 2003-10-31 | 2004-10-29 | Method for reducing the effect of direct interference current in an electrochemical test strip |
| CN 200910002047 Expired - Fee Related CN101533007B (en) | 2003-10-31 | 2004-10-29 | Method of reducing the effect of direct interference current in an electrochemical test strip |
| CN 200480039541 Pending CN1902479A (en) | 2003-10-31 | 2004-10-29 | Electrochemical test strip for reducing the effect of direct and mediated interference current |
| CNB2004800395265A Expired - Fee Related CN100473982C (en) | 2003-10-31 | 2004-10-29 | Method for reducing interferences in an electrochemical sensor using two different applied potentials |
Country Status (1)
| Country | Link |
|---|---|
| CN (8) | CN1902480A (en) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2261646B1 (en) * | 2008-03-27 | 2015-07-29 | Panasonic Healthcare Holdings Co., Ltd. | Measurement device, measurement system, and concentration measurement method |
| US20100219085A1 (en) * | 2009-02-27 | 2010-09-02 | Edwards Lifesciences Corporation | Analyte Sensor Offset Normalization |
| EP2405264B1 (en) | 2009-05-29 | 2015-09-02 | Panasonic Healthcare Holdings Co., Ltd. | Biosensor system and method for measuring concentration of analyte |
| US20110186428A1 (en) * | 2010-01-29 | 2011-08-04 | Roche Diagnostics Operations, Inc. | Electrode arrangements for biosensors |
| US8940141B2 (en) * | 2010-05-19 | 2015-01-27 | Lifescan Scotland Limited | Analytical test strip with an electrode having electrochemically active and inert areas of a predetermined size and distribution |
| GB2505694B (en) * | 2012-09-07 | 2017-03-22 | Lifescan Scotland Ltd | Electrochemical-based analytical test strip with bare interferent electrodes |
| GB2518165B (en) * | 2013-09-11 | 2016-04-27 | Cilag Gmbh Int | Electrochemical-based analytical test strip with ultra-thin discontinuous metal layer |
| CN104007150A (en) * | 2013-12-04 | 2014-08-27 | 西南大学 | Conductive polymer-based all-print biological and environmental sensor and making method thereof |
| CN105203613B (en) * | 2014-06-25 | 2018-03-02 | 达尔生技股份有限公司 | The bearing calibration of the blood glucose value of blood sample |
| CN105510391B (en) * | 2014-09-22 | 2018-08-24 | 英科新创(厦门)科技有限公司 | A kind of electric pole type blood glucose strip |
| CN104535627B (en) * | 2014-12-17 | 2017-01-04 | 浙江大学 | glucose sensing system |
| BR112017014097A2 (en) * | 2014-12-31 | 2018-03-06 | Trividia Health Inc | test strip and system and method for measuring glucose concentration in blood sample |
| CN104569102B (en) * | 2015-02-04 | 2018-04-06 | 苏州市玮琪生物科技有限公司 | Detect the bio-sensing electrode and method of Blood Trace signal |
| GB2549281A (en) * | 2016-04-11 | 2017-10-18 | Palintest Ltd | Electrochemical sensor |
| JP6778058B2 (en) * | 2016-08-31 | 2020-10-28 | シスメックス株式会社 | Sensor assembly, test substance monitoring system and test substance monitoring method |
| US20180217079A1 (en) * | 2017-01-31 | 2018-08-02 | Cilag Gmbh International | Determining an analyte concentration of a physiological fluid having an interferent |
| CN107478695B (en) * | 2017-07-13 | 2020-01-07 | 信阳师范学院 | Electrode modified based on nano copper sulfide-multiwalled carbon nanotube compound and preparation method and application thereof |
| CN108132284B (en) * | 2017-12-26 | 2019-11-29 | 三诺生物传感股份有限公司 | A kind of test method of electrochemical sensor |
| CN109164148B (en) * | 2018-09-04 | 2019-04-30 | 山东省科学院生物研究所 | The anti-interference measuring method of enzyme electrode biosensor |
| CN111387993B (en) * | 2020-04-09 | 2023-07-07 | 浙江大学 | Sensor for minimally invasive detection of levodopa and detection system thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4431004A (en) * | 1981-10-27 | 1984-02-14 | Bessman Samuel P | Implantable glucose sensor |
| WO1989002593A1 (en) * | 1987-08-28 | 1989-03-23 | Harman John N Iii | Noise reduction technique for electrochemical cells |
| US5298146A (en) * | 1991-11-08 | 1994-03-29 | Bayer Aktiengesellschaft | Device for the simultaneous detection of dissimilar gas components |
| CN1097468A (en) * | 1993-06-30 | 1995-01-18 | 中国科学院武汉病毒研究所 | Measure the double-electrode complex enzyme sensor for ditermining of dextrose plus saccharose simultaneously |
| US5830343A (en) * | 1994-07-11 | 1998-11-03 | Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V. | Electrochemical analysis process |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4655880A (en) * | 1983-08-01 | 1987-04-07 | Case Western Reserve University | Apparatus and method for sensing species, substances and substrates using oxidase |
| ZA938555B (en) * | 1992-11-23 | 1994-08-02 | Lilly Co Eli | Technique to improve the performance of electrochemical sensors |
| US6046051A (en) * | 1997-06-27 | 2000-04-04 | Hemosense, Inc. | Method and device for measuring blood coagulation or lysis by viscosity changes |
| GB2337122B (en) * | 1998-05-08 | 2002-11-13 | Medisense Inc | Test strip |
| US6287451B1 (en) * | 1999-06-02 | 2001-09-11 | Handani Winarta | Disposable sensor and method of making |
| US6258229B1 (en) * | 1999-06-02 | 2001-07-10 | Handani Winarta | Disposable sub-microliter volume sensor and method of making |
| CN1432130A (en) * | 2000-03-08 | 2003-07-23 | 糖尿病诊断公司 | Rapid response glucose sensor |
-
2004
- 2004-10-29 CN CN 200480039544 patent/CN1902480A/en active Pending
- 2004-10-29 CN CN 200480039546 patent/CN1902481A/en active Pending
- 2004-10-29 CN CN200480039527XA patent/CN101163963B/en not_active Expired - Fee Related
- 2004-10-29 CN CN 200910007080 patent/CN101493466B/en not_active Expired - Fee Related
- 2004-10-29 CN CNB2004800395335A patent/CN100473983C/en not_active Expired - Fee Related
- 2004-10-29 CN CN 200910002047 patent/CN101533007B/en not_active Expired - Fee Related
- 2004-10-29 CN CN 200480039541 patent/CN1902479A/en active Pending
- 2004-10-29 CN CNB2004800395265A patent/CN100473982C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4431004A (en) * | 1981-10-27 | 1984-02-14 | Bessman Samuel P | Implantable glucose sensor |
| WO1989002593A1 (en) * | 1987-08-28 | 1989-03-23 | Harman John N Iii | Noise reduction technique for electrochemical cells |
| US5298146A (en) * | 1991-11-08 | 1994-03-29 | Bayer Aktiengesellschaft | Device for the simultaneous detection of dissimilar gas components |
| CN1097468A (en) * | 1993-06-30 | 1995-01-18 | 中国科学院武汉病毒研究所 | Measure the double-electrode complex enzyme sensor for ditermining of dextrose plus saccharose simultaneously |
| US5830343A (en) * | 1994-07-11 | 1998-11-03 | Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V. | Electrochemical analysis process |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101533007B (en) | 2013-01-02 |
| CN100473982C (en) | 2009-04-01 |
| CN100473983C (en) | 2009-04-01 |
| CN101533007A (en) | 2009-09-16 |
| CN101163963A (en) | 2008-04-16 |
| CN1902478A (en) | 2007-01-24 |
| CN1902479A (en) | 2007-01-24 |
| CN1902481A (en) | 2007-01-24 |
| CN101493466A (en) | 2009-07-29 |
| CN101163963B (en) | 2011-05-04 |
| CN1902480A (en) | 2007-01-24 |
| CN1902477A (en) | 2007-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101493466B (en) | Method for reducing interference in electrochemical sensor using two different applied potentials | |
| KR101092350B1 (en) | A meter for use in an improved method of reducing interferences in an electrochemical sensor using two different applied potentials | |
| US7655119B2 (en) | Meter for use in an improved method of reducing interferences in an electrochemical sensor using two different applied potentials | |
| JP5044655B2 (en) | Reagent formulations using ruthenium hexamine as a transmitter for electrochemical test strips | |
| CN102778487B (en) | Oxidizable species as an internal reference in control solutions for biosensors | |
| EP2565638B1 (en) | Electrochemical analyte measurement system and method | |
| EP2080022B1 (en) | Methods for determining an analyte concentration using signal processing algorithms | |
| CA2810601C (en) | Analyte measurement method and system with hematocrit compensation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131106 Termination date: 20201029 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |