US007250105B1
`
`(12) United States Patent
`Davies et al.
`
`(io) Patent No.:
`(45) Date of Patent:
`
`US 7,250,105 Bl
`*Jul. 31, 2007
`
`(54) MEASUREMENT OF SUBSTANCES IN
`LIQUIDS
`
`(75) Inventors: Oliver W. H. Davies, Inverness (GB);
`Christopher P. Leach, Inverness (GB);
`Manuel Alvarez-Icaza, Inverness (GB)
`
`(73) Assignee: Lifescan Scotland Limited, Scotland
`(GB)
`
`(*) Notice: Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 369 days.
`
`This patent is subject to a terminal dis-
`claimer.
`
`(21) Appl. No.: 10/431,140
`
`(22) Filed: May 7, 2003
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 09/521,163, filed on
`Mar. 8, 2000, now Pat. No. 6,733,655.
`
`(51) Int. CI.
`G01N 27/327 (2006.01)
`G01N 27/333 (2006.01)
`(52) U.S. CI 205/777.5; 205/789
`(58) Field of Classification Search
`204/403.01^103.14, 416-418; 205/777.5,
`205/778, 792
`See application file for complete search history.
`
`(56) References Cited
`
`U.S. PATENT DOCUMENTS
`
`5,004,998 A 4/1991 Horii
`5,120,420 A * 6/1992 Nankai et al
`5,234,813 A 8/1993 McGeehan et al.
`5,582,697 A 12/1996 Ikeda et al.
`5,628,890 A 5/1997 Carter et al.
`
`204/403.11
`
`5,650,062 A 7/1997 Ikeda et al.
`5,672,256 A 9/1997 Yee
`5,786,584 A 7/1998 Button et al.
`5,791,344 A 8/1998 Schulman et al.
`5,820,551 A 10/1998 Hill et al.
`5,837,546 A 11/1998 Allen et al.
`6,004,441 A * 12/1999 Fujiwaia et al 204/403.14
`6,287,451 Bl* 9/2001 Winarta et al 205/777.5
`6,733,655 Bl * 5/2004 Davies et al 205/775
`
`FOREIGN PATENT DOCUMENTS
`
`EP 0537761 A2 4/1993
`EP 0942278 A2 9/1999
`WO WO 97/02487 Al 1/1997
`WO WO 9730344 Al 8/1997
`WO WO 9958709 Al 11/1999
`
`OTHER PUBLICATIONS
`
`V.A. Bodner "Aviation Devices", The Machine Building Publishing
`House, Moscow, Russia, 1969, p. 158.
`Official Action Issued by the Patent Office of the Russian Federa-
`tion, mailed on or about Dec. 6, 2004, re Russuan Application No.
`2002126814.
`
`* cited by examiner
`
`Primary Examiner•Alex Noguerola
`
`(57) ABSTRACT
`
`In accordance with the present invention a measuring device
`compares the current generated by two working sensor parts
`and gives an error indication if they are too dissimilar, i.e.,
`the current at one sensor part differs too greatly from what
`would be expected from considering the current at the other.
`Not only can this method detect when one of the sensor parts
`has not been properly covered with sample liquid, but it can
`also detect if there is a manufacturing defect in either sensor
`part or if either has been damaged after manufacture, since
`even with complete coverage of the working sensor parts, an
`anomalous current will be generated at the affected sensor
`part under such circumstances.
`
`3 Claims, 2 Drawing Sheets
`
`Jf
`
`,8a
`^6a
`
`4a.
`10.
`
`Case 3:14-cv-00274-RJC-DSC Document 6-2 Filed 07/21/14 Page 1 of 7
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`

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`U.S. Patent
`
`Jul. 31, 2007
`
`Sheet 1 012
`
`US 7,250,105 B1
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`4b
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`6b
`8b
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`4
`
`8a
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`6a
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`4a
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`10~/E:
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`FIG. 2
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`
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`FIG. 4
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`2
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`,
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`FIG. 1
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`
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`FIG. 3
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`
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`FIG. 5 FIG. 7
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`

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`U.S. Patent
`
`Jul. 31, 2007
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`Sheet 2 of 2
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`US 7,250,105 B1
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`VOLUME STUDY WITHOUT ERROR CHECK IN
`
`PLACE. N=8. GLUCOSE=455mg/dl
`
`" 20.00
`
`15.00
`
`10.00
`
`
`
` 5.00 STRIPCURRENT.(uA
`
`0.00
`0.6
`
`0.8
`
`1
`
`1.2
`
`1.4
`
`1.6
`
`1.8
`
`2
`
`2.2
`
`BLOOD VOLUME.(u|)
`
`FIG. 8
`
`VOLUME STUDY WITH ERROR CHECK IN PLACE.
`
`N=8. GLUCOSE=455mg/dl
`
`M O
`
`._x 0'!
`
`O
`
`.
`
`0
`
`.
`
`0
`
`0
`
`N=3 N=4 N=8 N=7 N=8 N=8
`
`01S O
`
`.0 on
`
`0.8
`
`1
`
`1.2
`
`1.4
`
`1.6
`
`1.8
`
`2
`
`2.2
`
`
`
`STRIPCURRENT.(uA)
`
`BLOOD VOLUME.(u|)
`
`FIG. 9
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`

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`US 7,250,105 B1
`
`1
`MEASUREMENT OF SUBSTANCES IN
`LIQUIDS
`
`This application is a Continuation application of Ser. No.
`09/521,163 filed Mar. 8, 2000, now U.S. Pat. No. 6,733,655,
`which is incorporated herein by reference in its entirety.
`This invention relates to apparatus for measuring the
`concentration of a substance in a liquid and particularly, but
`not exclusively, to apparatus for measuring the concentra-
`tion of glucose in blood.
`Devices for measuring blood glucose levels are invaluable
`for diabetics, especially devices that may be used by the
`sufferers themselves since they may then monitor their own
`glucose levels and take an appropriate dose of insulin.
`Correspondingly therefore the accuracy of such devices is
`very important since an inaccurate reading could lead to the
`wrong level of insulin being administered which could be
`very harmful.
`in all practical blood glucose
`It
`is also the case that
`measuring systems at least part of the device, i.e. that part
`which comes into contact with the sample blood, is dispos-
`able. This means that it is particularly important that the cost
`particularly of any disposable parts can be minimised as a
`user will generally need large numbers of them regularly.
`Known glucose measuring devices now favour an elec-
`trochemical measurement method over old colorimetric
`
`5
`
`10
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`15
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`20
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`25
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`2
`
`of measuring the concentration of a substance in a sample
`liquid comprising the steps of:
`providing a measuring device having a first working
`sensor part comprising a working layer which generates an
`electric current proportional to the concentration of said
`substance in the sample liquid, a reference sensor part and
`a second working sensor part comprising a working layer
`which also generates an electric current proportional to the
`concentration of said substance in the sample liquid;
`applying the sample liquid to said measuring device;
`comparing the electric current generated at each of the
`working sensor parts to establish a difference parameter; and
`giving an indication of an error if said difference, param-
`eter is greater than a predetermined threshold.
`Furthermore the measuring device used in this method is
`novel and inventive in its own right and thus from a second
`aspect the present invention provides a device for measuring
`the concentration of a substance in a sample liquid, said
`device comprising:
`a reference sensor part,
`a first working sensor part, comprising a working layer for
`generating an electric current proportional to the concentra-
`tion of said substance in the sample liquid; and
`a second working sensor part comprising a working layer
`also for generating an electric current proportional to the
`concentration of said substance in the sample liquid.
`Thus it will be seen that in accordance with the invention
`
`30
`
`35
`
`40
`
`methods. The general principle is that an electric current is
`measured between two sensor parts called the working and
`reference sensor parts respectively. The working sensor part
`comprises a layer of enzyme reagent,
`the current being
`generated by the transfer of electrons from the enzyme
`substrate, via the enzyme and an electron mediator com-
`pound to the surface of a conductive electrode. The current
`generated is proportional to both the area of the sensor part
`and also the concentration of glucose in the test sample.
`Since the area of the working sensor part is supposedly
`known, the electric current should be proportional to the
`glucose concentration.
`It has been recognised in the art that inaccurate results are
`obtained if the working sensor part is not fully covered with
`blood since then its effective area is reduced. Various ways
`of dealing with this problem have been proposed, two of
`which are disclosed in U.S. Pat. No. 5,628,890 and U.S. Pat.
`No. 5,582,697 Both of these methods rely on a unidirec-
`tional flow of blood across the surface of the test strip and 45
`both initiate the test measurement by detecting the presence
`of the sample liquid at an electrode or sensor part located
`downstream of the working sensor part.
`The problem of insufficient sample liquid being present
`and thus the working sensor part not being completely
`covered may of course be reduced by reducing the size of the
`working sensor part. However a small area for the working
`sensor part tends to give a greater variability in calibrated
`results.
`
`the measuring device compares the current generated by two
`working sensor parts and gives an error indication if they are
`too dissimilar—i.e. the current at one sensor part differs too
`greatly from what would be expected from considering the
`current at the other. Not only can this method detect when
`one of the sensor parts has not been properly covered with
`sample liquid, but it can also detect if there is a manufac-
`turing defect
`in either sensor part or if either has been
`damaged after manufacture, since even with complete cov-
`erage of the working sensor parts, an anomalous current will
`be generated at the affected sensor part such circumstances.
`In accordance with the invention the only type of defect
`or damage which would not necessarily be recognised is one
`which affected both of the working sensor parts to the same
`degree. However, this is logically less likely than a defect
`affecting a single working sensor part and is thus an
`improvement over the prior art. In practice such a likelihood
`is considered to be negligible. In any event the invention is
`not limited to providing just two working sensor parts and
`the skilled person could therefore choose to provide three or
`more working sensor parts to further reduce the probability
`that they are all affected by an identical defect.
`Looking at the invention another way,
`it provides an
`arrangement whereby for a given total area of working
`sensor part and thus a given minimum sample volume,
`detection of inadequate fill and of defects in the working
`sensor part provided by separating the area of the working
`The present inventors have realised that as well as incom-
`sensor part into two.
`plete coverage of the working sensor part, inaccurate results
`Some or all of the sensor parts may be provided as part of
`can also arise from occasional defects in the production of
`an integrated device. Preferably however at least the work-
`the test strips for such devices,
`in the area and/or the
`ing sensor parts are provided on a removable test member.
`thickness of the working sensor part and also from acciden-
`Thus when viewed from a further aspect the present inven-
`tal damage to the working sensor part e.g by a user. As far
`tion provides a test member for measuring the concentration
`as the inventors are aware, the only practical way to deal
`of a substance in a sample liquid comprising:
`with this problem so far has been to ensure that the printing
`a substrate; and
`process used to produce the test strips is as accurate as
`two working sensor parts provided on the substrate, each
`possible and to rely on adequate quality control.
`working sensor part comprising a working layer for gener-
`It is an object of the present invention at least partially to
`ating an electric current proportional to the concentration of
`alleviate the above-mentioned disadvantages and when
`viewed from a first aspect the invention provides a method
`said substance in the sample liquid.
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`

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`US 7,250,105 B1
`
`3
`Preferably a reference sensor part is also provided on the
`substrate.
`
`It will be appreciated by those skilled in the art that
`effectively what has been provided is a measuring device
`which is self-testing for proper use, damage and certain
`manufacturing defects. This is particularly beneficial in the
`context of a device in which the sensor parts are provided on
`a separate test member since this may typically be a mass-
`manufactured test strip, e.g. for measuring blood glucose
`levels. Since in accordance with the invention a damaged or
`defective test strip will be recognised, allowing it to be
`rejected, the accuracy of the final result and thus potentially
`the safety of a user is no longer solely dependent upon high
`manufacturing precision. Although it is of course not desir-
`able that a large number of tests is rejected,
`in many
`circumstances it is more important that inaccurate results are
`not given.
`The two working sensor parts may be dissimilar or
`different potentials may be applied to each sensor part in
`either of which cases the measuring device is preferably
`arranged to apply appropriate weights to the measurements
`returned by one or both working sensor parts to normalise
`them. The difference parameter could then for example be
`the simple arithmetic difference between the normalised
`current values. Preferably however the working layer of both
`sensor parts is of the same material and alternatively, but
`preferably additionally, both working sensor parts have the
`same area. Thus it is most preferred that the two working
`sensor parts are substantially identical. It is also preferred
`that the measuring device is arranged to apply the same
`potential to each sensor part. This allows the difference
`parameter to comprise a direct comparison between the
`respective currents at the sensor parts in order to determine
`whether a reliable measurement of the substance concentra-
`tion can be made.
`
`The two working sensor parts may be arranged as con-
`venient within the device, or in accordance with the pre-
`ferred embodiment, on the test member. The device or test
`member may be arranged to allow the sample liquid to flow
`freely over the working sensor parts. More preferably how-
`ever the sample liquid is constrained to flow substantially
`unidirectionally across the working sensor parts.
`It is presently preferred that the two working sensor parts
`are arranged one downstream of the other. This makes it
`possible to ensure that one of the sensor parts will always be
`completely covered before the other begins to be covered,
`thus avoiding the possibility, however small, that insufficient
`sample liquid is applied to cover both sensor parts and
`furthermore that each sensor part is partially covered by the
`same amount. It will be appreciated however that if the
`above-mentioned small risk is deemed acceptable, arrange-
`ments in accordance with the invention allow a much greater
`flexibility in the placement of the sensor parts than in known
`devices whilst still providing protection against an inad-
`equate volume of sample liquid being used or other incorrect
`product usage or damage.
`It
`is also preferred that both
`working sensor parts are downstream of the reference sensor
`part.
`The threshold used to determine an inaccurate measure-
`
`4
`
`example where no significant harm would be done to a
`patient relying on the results to administer insulin.
`The difference parameter may be an absolute value—e.g.
`of the difference in currents measured at each sensor part,
`but is preferably dimensionless—e.g. a percentage of one or
`other of the measured currents.
`The actual current value used to calculate the concentra-
`
`tion of the substance may just be that from one of the
`working sensor parts, but
`is preferably a combination
`thereof, e.g. the sum or mean of the two. This gives the
`advantage that
`the maximum effective working area is
`utilised which further helps to increase the precision of the
`results obtained.
`
`A particularly preferred embodiment of the invention is a
`device for measuring the concentration of glucose in blood,
`in which the two working sensor parts and the reference
`sensor part are provided on a disposable test strip.
`A preferred embodiment of the invention will now be
`described, by way of example only, with reference to the
`accompanying drawings in which:
`FIG. 1 shows a substrate for a test strip in accordance with
`the invention;
`FIG. 2 shows the layout of carbon tracks applied to the
`substrate;
`FIG. 3 shows the layer of insulation applied to the strip;
`FIG. 4 shows the enzyme reagent layer;
`FIG. 5 shows a layer of hydrophilic film;
`FIG. 6 shows the cover layer of the strip;
`FIG. 7 is a plot of the results obtained without using a
`method in accordance with the invention; and
`FIG. 8 is a plot similar to FIG. 7 obtained using a method
`in accordance with the invention.
`
`FIG. 9 is a plot similar to FIG. 8 obtained using a method
`in accordance with the invention.
`
`Turning to FIG. 1, there is shown an oblong polyester
`strip 2 which forms the substrate for a test strip for mea-
`suring the concentration of glucose in a sample of blood. The
`substrate 2 is shown in isolation although in practice an array
`of such strips is cut out from a large master sheet at the end
`of fabrication.
`
`FIG. 2 shows the pattern of carbon ink which is applied
`to the substrate by screen printing. The layer of carbon
`comprises four distinct areas which are electrically insulated
`from one another. The first track 4 forms, at the distal end
`thereof, an electrode 4b for a reference/counter sensor part.
`The track 4 extends lengthwise to form a connecting termi-
`nal 4a at its proximal end. The second and third tracks 6, 8
`form electrodes 6b, 8b at their distal ends for two working
`sensor parts and respective connecting terminals 6a, 811 at
`their proximal ends. The fourth carbon area is simply a
`connecting bridge 10 which is provided in order to close a
`circuit in a suitable measuring device in order to turr1 it on
`when the test strip has been properly inserted.
`FIG. 3 shows the next layer to be applied also by screen
`printing. This is a water insoluble insulating mask 12 which
`defines a window over the electrodes 6b, 8b and which
`therefore controls the size of the exposed carbon and hence
`where the enzyme layer 14 (FIG. 4) will come into contact
`with the carbon electrodes. The size and shape of the
`window are set so that the two electrodes 6b, 8b have a patch
`of enzyme of exactly the same area printed onto them. This
`means that for a given potential, each working sensor part
`will theoretically generate the same electric current in the
`presence of a sample of blood.
`A layer of glucose oxidase 14 (FIG. 4) is printed over the
`mask 12 and thus onto the electrodes 4b, 6b, 8b through the
`window in the mask to form the reference/counter sensor
`
`10
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`15
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`20
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`30
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`45
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`60
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`65
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`ment may be chosen as appropriate. Typically a threshold
`will be chosen empirically as a suitable value will depend on
`the inherent variability in the manufacturing process, the
`desired precision of results, etc. To some extent there is a
`trade-olf between the accuracy which may be obtained by
`setting the threshold low and the proportion of measure-
`ments which are disregarded as being too inaccurate. Thus
`the threshold might advantageously be set at a level for
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`

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`US 7,250,105 B1
`
`6
`in any liquid, not just glucose in blood. Furthermore, the
`working sensor parts need not be provided on a test strip but
`may be part of an integrated device. Also the difference
`figure of 10% used in the embodiment described above is
`5 purely exemplary and any suitable figure may be chosen.
`
`TABLE 1
`
`5
`part and the two working sensor parts respectively. A 150
`micron layer of adhesive is then printed onto the strip in the
`pattern shown in FIG. 5. This pattern has been enlarged for
`clarity as compared to the previous Figures. Three separate
`areas of adhesive 16a, 19, c together define a sample chamber
`18 between them.
`
`Two sections of hydrophilic film 20 (FIG. 6) are lami-
`nated onto the strip and are held in place by the adhesive 16.
`The first section of film has the effect of making the sample
`chamber 18 into a thin charmel which draws liquid into and
`along it by a capillary action. The final layer is shown in
`FIG. 7 and is a protective plastic cover tape 22 which has a
`transparent portion 24 at the distal end. This enables a user
`to tell instantly if a strip has been used.
`Use of the strip will now be described. The test strip is
`inserted into the meter. The bridge portion 10 completes a
`circuit in the device and thus automatically turns the device
`on. The device also has contacts to connect to the terminals
`411, 6a, 8a on the strip. The measuring device applies a
`potential of 400 mV between the counter/reference sensor
`part and each of the two working sensor parts via the
`above-mentioned terminals.
`
`A drop of blood is then placed on the distal end of the
`strip. Capillary action draws the blood along the sample
`chamber 18 and over the counter/reference sensor part and
`two working sensor parts.
`After a predetermined time the electric current generated
`by each working sensor part
`is measured and the two
`measurements are compared. If they dilfer by more than
`10% an error message is displayed on the measuring device
`and the test must be repeated. If they are within 10% of each
`other however, the two currents are added together in the
`device and are converted to a glucose level which is dis-
`played on an LCD.
`A comparative experiment was carried out using a strip
`fabricated as set out above, in order to exemplify the benefits
`achievable in accordance with the invention. In the experi-
`ment drops of blood increasing in volume from 1 to 2 micro
`liters in steps of 0.2 micro liters and with a constant glucose
`concentration, were applied to such strips, with each volume
`being repeated 8 times. The current measured at each
`working sensor part was measured and recorded. The results
`are shown in Table 1 appended to this description.
`For the first part of the test the two currents were simply
`added together to simulate a single working sensor part
`having their combined area. These results are plotted in FIG.
`8.
`
`In the second half of the test the two currents were first
`
`10
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`15
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`20
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`25
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`30
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`35
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`40
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`45
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`50
`
`55
`
`60
`
`65
`
`V0 ume Working 1: Working 2:
`3
`ILA
`ILA
`7.07
`0.00
`6.94
`5.98
`5.53
`0.01
`6.99
`7.09
`7.34
`7.02
`7.16
`6.79
`7.01
`3.47
`7.07
`5.69
`7.18
`4.54
`7.00
`6.78
`7.09
`1.79
`6.31
`0.00
`6.78
`6.79
`6.95
`6.59
`6.62
`6.28
`7.23
`3.78
`7.16
`6.90
`7.14
`6.94
`7.17
`7.02
`7.02
`6.01
`6.95
`6.91
`6.93
`6.88
`7.09
`6.92
`7.25
`7.40
`7.808
`6.59
`6.774
`6.589
`6.928
`6.904
`6.892
`6.453
`7.087
`7.314
`7.257
`6.947
`6.501
`6.306
`6.811
`6.755
`7.145
`6.536
`7.021
`6.612
`6.917
`6.828
`6.971
`6.78
`7.016
`6.941
`6.977
`7.179
`6.946
`6.794
`7.203
`7.183
`7.145
`6.536
`7.021
`6.621
`6.917
`6.828
`6.971
`6.78
`7.016
`6.941
`6.977
`7.179
`6.946
`6.794
`7.203
`7.183
`
`.2
`.2
`.2
`.2
`.2
`.2
`.2
`.2
`.4
`.4
`.4
`.4
`.4
`.4
`.4
`.4
`.6
`.6
`.6
`.6
`.6
`.6
`.6
`.6
`.8
`.8
`.8
`.8
`.8
`.8
`.8
`.8
`
`2
`2
`2
`2
`2
`2
`2
`2
`
`% Difference
`—706800
`—16.2175732
`—92050
`1.42393909
`—4.59016393
`—5.49742078
`—102.13441
`—24.2578605
`—58.2286847
`—3.35055351
`—297.032475
`—157550
`0.11788977
`—5.4029443
`—5.36795158
`—91.2721502
`—3.76811594
`—2.88184438
`—2.13675214
`—1.5918958
`—0.5788712
`—0.72674419
`—2.4566474
`2.02702703
`—18.4825493
`—2.80770982
`—0.34762457
`—6.80303735
`3.10363686
`—4.46235785
`—3.09229305
`—0.82901554
`—9.31762546
`—6.18572293
`—1.30345636
`—2.81710914
`—1.08053595
`2.81376236
`—2.23726828
`—0.27843519
`—9.31762546
`—6.18572293
`—1.30345636
`—2.81710914
`—1.08053595
`2.81376236
`—2.23726818
`—0.27843519
`
`Error
`checked
`
`4.09
`4.35
`3.94
`
`3.78
`
`3.56
`3.53
`2.89
`
`4.06
`4.08
`4.19
`3.93
`3.86
`3.81
`4.01
`4.65
`
`3.36
`3.83
`3.35
`4.40
`4.20
`2.81
`3.57
`3.68
`3.63
`3.75
`3.75
`3.96
`4.16
`3.74
`4.39
`3.68
`3.63
`3.75
`3.75
`3.96
`4.16
`3.74
`4.39
`
`No error
`check
`7.07
`2.92
`5.54
`4.09
`4.35
`3.94
`0.48
`2.77
`1.72
`3.78
`8.88
`6.31
`3.56
`3.53
`2.89
`1.01
`4.06
`4.08
`4.19
`3.93
`3.86
`3.81
`4.01
`4.65
`4.40
`3.36
`3.83
`3.35
`4.40
`4.20
`2.81
`3.57
`3.68
`3.63
`3.75
`3.75
`3.96
`4.16
`3.74
`4.39
`3.68
`3.63
`3.75
`3.75
`3.96
`4.16
`3.74
`4.39
`
`The invention claimed is:
`
`compared. Only if they dilfered by less than 10% were they
`then added together and put forward as valid results. Values
`differing by more than 10% were disregarded. The results of
`this second part of the test are plotted in FIG. 9.
`It is immediately apparent that the second set of results is
`1. Amethod of measuring the concentration of a substance
`significantly more precise, i.e. they display a much lower
`in a sample liquid comprising the steps of:
`variation. Furthermore, since in practice the two working
`providing a measuring device said device comprising:
`sensor parts will only give results consistent with one
`a first working sensor part for generating charge carri-
`another if they are both fully covered, the second set of
`ers in proportion to the concentration of said sub-
`results is also significantly more accurate than the first since
`stance in the sample liquid;
`it may be safely assumed that the results are only actually
`a second working sensor part downstream from said
`given when both working sensor parts are fully covered.
`first working sensor part also for generating charge
`Thus is will-be seen that in its preferred embodiment the
`carriers in proportion to the concentration of said
`present invention allows the detection and rejection of those
`substance in the sample liquid wherein said first and
`tests that have had insufficient sample applied to the test strip
`second working sensor parts are arranged such that,
`i.e those in which the test strip has been incorrectly used.
`in the absence of an error condition, the quantity of
`said charge carriers generated by said first working
`It will be appreciated by those skilled in the art that many
`sensors part are substantially identical to the quantity
`variations on what has been described above are possible
`of said charge carriers generated by said second
`within the scope of the invention. For example the invention
`may be used to measure the level of any suitable substance
`working sensor part; and
`Case 3:14-cv-00274-RJC-DSC Document 6-2 Filed 07/21/14 Page 6 of 7
`Case 3:14—cv—OO274—RJC—DSC Document 6-2 Filed 07/21/14 Page 6 of 7
`
`

`
`US 7,250,105 B1
`
`7
`a reference sensor part upstream from said first and
`second working sensor parts which reference sensor
`part is a common reference for both the first and
`second working sensor parts, said reference sensor
`part and said first and second working sensor parts
`being arranged such that the sample liquid is con-
`strained to flow substantially unidirectionally across
`said reference sensor part and said first and second
`working sensor parts; wherein said first and second
`working sensor parts and said reference sensor part
`are provided on a disposable test strip;
`applying the sample liquid to said measuring device;
`measuring an electric current at each working sensor part
`proportional to the concentration of said substance in
`the sample liquid;
`
`8
`comparing the electric current from each of the working
`sensor parts to establish a difference parameter; and
`giving an indication of an error if said difference param-
`eter is greater than a predetermined threshold.
`2. The method as claimed in claim 1 comprising measur-
`ing the current at each working sensor part after a prede-
`termined time following application of the sample.
`3. The method as claimed in claim 1 wherein the sub-
`
`stance to be measured is glucose, and each of the working
`sensor parts generates charge carriers in proportion to the
`concentration of glucose in the sample liquid.
`
`10
`
`Case 3:14-cv-00274-RJC-DSC Document 6-2 Filed 07/21/14 Page 7 of 7
`Case 3:14—cv—OO274—RJC—DSC Document 6-2 Filed 07/21/14 Page 7 of 7