Source: https://patents.google.com/patent/US9046480B2/en
Timestamp: 2018-09-20 03:04:13
Document Index: 426343645

Matched Legal Cases: ['§371', '§119', 'Application No. 11190794', 'Application No. 1363', 'Application No. 200780044972', 'Application No. 2009', 'Application No. 07824028', 'Application No. 07824036', 'Application No. 07824045', 'Application No. 2007800449729']

US9046480B2 - Method for determining hematocrit corrected analyte concentrations - Google Patents
Method for determining hematocrit corrected analyte concentrations Download PDF
US9046480B2
US9046480B2 US13783807 US201313783807A US9046480B2 US 9046480 B2 US9046480 B2 US 9046480B2 US 13783807 US13783807 US 13783807 US 201313783807 A US201313783807 A US 201313783807A US 9046480 B2 US9046480 B2 US 9046480B2
US13783807
US20130240375A1 (en )
The method includes: providing a test strip comprising a reference electrode and a working electrode coated with a reagent layer; applying a fluid sample to the test strip for a reaction period; applying a test voltage between the reference electrode and the working electrode; measuring a test current as a function of time; measuring a steady state current value when the test current has reached an equilibrium; calculating a ratio of the test current to the steady state current value; plotting the ratio of the test current to the steady state current value as a function of the inverse square root of time; calculating an effective diffusion coefficient from the slope of the linearly regressed plot of the ratio of the test current to the steady state current value as a function of the inverse square root of time; and calculating a hematocrit-corrected concentration of analyte.
This application is a continuation application of U.S. application Ser. No. 12/305,363, filed Dec. 17, 2008, currently allowed, which is an application filed under 35 USC §371 of International Application Number PCT/GB2007/003770, filed Oct. 5, 2007, expired which claims priority under 35 U.S.C. §119 and the Paris Convention to U.S. Provisional Application Ser. No. 60/850,173 filed on Oct. 5, 2006, expired, which applications are incorporated by reference in their entirety herein.
D-Glucose+GO(ox)→Gluconic Acid+GO(red) (1)
GO(red)+2 Fe(CN)6 3−→GO(ox)+2 Fe(CN)6 4− (2)
As shown in Equation 1, glucose is oxidized to gluconic acid by the oxidized form of glucose oxidase (GO(ox)). It should be noted that GO(ox) may also be referred to as an “oxidized enzyme”. During the reaction in Equation 1, the oxidized enzyme GO(ox) is converted to its reduced state which is denoted as GO(red) (i.e., “reduced enzyme”). Next, the reduced enzyme GO(red) is re-oxidized back to GO(ox) by reaction with Fe(CN)6 3− (referred to as either the oxidized mediator or ferricyanide) as shown in Equation 2. During the regeneration of GO(red) back to its oxidized state GO(ox), Fe(CN)6 3− is reduced to Fe(CN)6 4− (referred to as either reduced mediator or ferrocyanide).
A slower dissolution rate of the reagent layer can slow down the enzymatic reaction as shown in Equations 1 and 2 because the oxidized enzyme GO(ox) must dissolve first before it can react with glucose. Similarly, ferricyanide (Fe(CN)6 3−) must dissolve first before it can react with reduced enzyme GO(red). If the undissolved oxidized enzyme GO(ox) cannot oxidize glucose, then the reduced enzyme GO(red) cannot produce the reduced mediator Fe(CN)6 4− needed to generate the test current. Further, oxidized enzyme GO(ox) will react with glucose and oxidized mediator Fe(CN)6 3− more slowly if it is in a high viscosity sample as opposed to a low viscosity sample. The slower reaction rate with high viscosity samples is ascribed to an overall decrease in mass diffusion. Both oxidized enzyme GO(ox) and glucose must collide and interact together for the reaction to occur as shown in Equation 1. The ability of oxidized enzyme GO(ox) and glucose to collide and interact together is slowed down when they are in a viscous sample. Yet further, reduced mediator Fe(CN)6 4− will diffuse to the working electrode slower when dissolved in a high viscosity sample. Because the test current is typically limited by the diffusion of reduced mediator Fe(CN)6 4− to the working electrode, a high viscosity sample will also attenuate the test current. In summary, there are several factors that cause the test current to decrease when the sample has an increased viscosity.
GO(red)+O2→GO(ox)+H2O2 (3)
As noted earlier, the reduced enzyme GO(red) can also reduce ferricyanide (Fe(CN)6 3−) to ferrocyanide (Fe(CN)6 4−) as shown in Equation 2. Thus, oxygen can compete with ferricyanide for reacting with the reduced enzyme (GO(red)). In other words, the occurrence of the reaction in Equation 3 will likely cause a decrease in the rate of the reaction in Equation 2. Because of such a competition between ferricyanide and oxygen, a higher oxygen content will cause less ferrocyanide to be produced. In turn, a decrease in ferrocyanide would cause a decrease in the magnitude of the test current. Therefore, a high oxygen content blood sample can potentially decrease the test current and affect the accuracy of the glucose measurement.
FIG. 12 illustrates a test meter 600 suitable for connecting to test strip 100. Test meter 600 includes a display 602, a housing 604, a plurality of user interface buttons 606, and a strip port connector 608. Test meter 600 further includes electronic circuitry within housing 604 such as a memory, a microprocessor, electronic components for applying a test voltage, and also for measuring a plurality of test current values. Proximal portion 4 of test strip 100 may be inserted into strip port connector 608. Display 102 may output a glucose concentration and be used to show a user interface for prompting a user on how to perform a test. The plurality of user interface buttons 606 allow a user to operate test meter 600 by navigating through the user interface software.
Method 700 includes providing a test strip 100 with a reference electrode 10, a first working electrode 12, an optional second electrode 14 and a test meter 600, as set forth by step 710. First working electrode 12includes a plurality of microelectrodes 120 (i.e., microelectrode array 110) with each disk shaped microelectrode having a diameter of about 3 microns to about 50 microns and separated by about 5 to about 10 times the diameter thereof. Reference electrode 10 includes a surface area that is at least equal to the surface area of microelectrode array 110.
I ⁡ ( t ) I SS = 1 + ( 2 ⁢ r d π ⁢ π ⁢ ⁢ Dt ) ( 4 )
rd is the radius of microelectrode 120 in centimeters;
As set forth in step 780, effective diffusion coefficient D may be used with Equation 5 below to estimate the reduced mediator concentration Cred (e.g., concentration of Fe(CN)6 4−).
C red = I SS 4 ⁢ n ⁢ ⁢ FD ⁢ ⁢ r d ( 5 )
As set forth in step 820, the fluid sample is applied to test strip 100 at t0 and is allowed to react with reagent layer 22 for a reaction period tR (see FIG. 14). The presence of sample in the reaction zone of test strip 100 is determined by measuring the current flowing through first working electrode 12. The beginning of reaction period tR is determined to begin when the current flowing through first working electrode 12 reaches a desired value, typically about 0.150 nanoamperes (not shown), at which point a test voltage of between about −50 millivolts and about +50 millivolts, typically about zero millivolts, is applied between first working electrode 12 and reference electrode 10. Reaction period tR is typically between about 2 and about 3 seconds and is more typically about 2.5 seconds. After reaction period tR, the test voltage in the exemplary method is applied to test strip 100 at t1 for a total test time tT. In an alternative method shown in FIG. 15, the reaction period tR is omitted such that the start of the test commences as soon as sufficient current is flowing through first working electrode 12.
As set forth in step 880, effective diffusion coefficient D may be used with Equation 5 above to estimate the reduced mediator concentration Cred (e.g., concentration of Fe(CN)6 4−).
D ~ = D ⁢ ⁢ exp ⁢ { θ ⁡ ( 1 T - 1 T 0 ) } ( 6 )
{tilde over (D)} is the temperature-corrected effective diffusion coefficient in centimeter2/second;
T is temperature in Kelvin of the fluid sample as measured by the test meter and generally is between about 283° K and about 317° K; and
C red = I s 4 ⁢ ⁢ n ⁢ ⁢ FD ⁢ ⁢ r d
D is the estimated diffusion coefficient in centimeter2/second; and
rd is the radius of the microelectrode in centimeters;
calculating an analyte concentration by subtracting a calibration intercept from the reduced mediator concentration and dividing with a calibration slope; and
estimating a hematocrit-corrected concentration of analyte from the calculating step.
2. The method of claim 1, wherein the calculating of the effective diffusion coefficient step utilizes an equation of the form:
I ⁡ ( t ) I SS = 1 + ( 2 ⁢ r d π ⁢ π ⁢ ⁢ D ⁢ ⁢ t )
rd is the radius of a microelectrode in centimeters; and
3. The method of claim 1, wherein the test strip further comprises an insulation portion disposed on the plurality of microelectrodes and the insulation portion has a height between about one micron and about six microns.
4. The method of claim 1, wherein the reference electrode and the working electrode are comprised of gold.
5. The method of claim 1, wherein the reagent layer comprises an enzyme, a mediator and a buffering agent wherein the mediator comprises ruthenium (III) hexamine.
6. The method of claim 1, wherein the diameter of each of the plurality of microlectrodes is between about 5 microns and about 50 microns.
7. The method of claim 1, wherein each of the plurality of micoelectrodes is spaced apart by a distance ranging from about 5 to about 10 times the diameter of a microelectrode.
8. The method of claim 1, wherein each of the plurality of microelectrodes is spaced apart by a distance ranging from about 25 microns to about 500 microns.
9. The method of claim 1, wherein the shape of each of the plurality of microelectrodes is selected from a group consisting essentially of a circle, a square, a rectangle, an oval and an ellipse and combinations thereof.
US13783807 2006-10-05 2013-03-04 Method for determining hematocrit corrected analyte concentrations Active 2027-11-20 US9046480B2 (en)
US85017306 true 2006-10-05 2006-10-05
PCT/GB2007/003770 WO2008040982A1 (en) 2006-10-05 2007-10-05 Method for determining hematocrit corrected analyte concentrations
US30536309 true 2009-12-01 2009-12-01
US13783807 US9046480B2 (en) 2006-10-05 2013-03-04 Method for determining hematocrit corrected analyte concentrations
PCT/GB2007/003770 Continuation WO2008040982A1 (en) 2006-10-05 2007-10-05 Method for determining hematocrit corrected analyte concentrations
US12305363 Continuation US8388821B2 (en) 2006-10-05 2007-10-05 Method for determining hematocrit corrected analyte concentrations
US30536309 Continuation 2009-12-01 2009-12-01
US20130240375A1 true US20130240375A1 (en) 2013-09-19
US9046480B2 true US9046480B2 (en) 2015-06-02
ID=49156635
US13783807 Active 2027-11-20 US9046480B2 (en) 2006-10-05 2013-03-04 Method for determining hematocrit corrected analyte concentrations
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US20130240375A1 (en) 2013-09-19 application
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BLYTHE, STEPHEN PATRICK;CARDOSI, MARCO F.;GILL, ANDREW;AND OTHERS;SIGNING DATES FROM 20090223 TO 20090602;REEL/FRAME:029935/0725