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`US 20030094383Al
`
`(19) United States
`c12) Patent Application Publication
`Kermani
`
`c10) Pub. No.: US 2003/0094383 Al
`(43) Pub. Date:
`May 22, 2003
`
`(54) DETERMINATION OF SAMPLE VOLUME
`ADEQUACY IN BlOSENSOR DEVICES
`
`(52) U.S. Cl. .. ........................................................ 205/777.5
`
`(76)
`
`Inventor: Mahyar z. Kermani, Pleasanton, CA
`(US)
`
`(57)
`
`ABSTRACT
`
`Correspondence Address:
`Carol M. LaSalle
`Bozic.evic, Field and Francis LLP
`Suite 200
`200 Middlefield Road
`Menlo Park, CA 94025 (US)
`
`(21) Appl. No.:
`
`09/988,495
`
`(22) Filed:
`
`Nov. 20, 2001
`
`Publication Classification
`
`(51)
`
`lnt. Cl.7 .................................................. GOIN 27/327
`
`Systems and methods are provided for determining whether
`a volume of biological sample is adequate to produce an
`accurate analyte concentration measurement. Certain such
`systems and methods provide the additional function of
`compensating for a sample volume determined to be less
`
`than adequate in order to proceed with an accurate analyte
`
`concentration measurement. The present invention is
`employed with a biosensor, such as an electrochemical test
`strip to which the sample volume of biological solution is
`deposited, and a meter configured to receive such test strip
`and to measure the concentration of selected analytes within
`the biological sample.
`
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`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 1 of 14
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`

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`Patent Application Publication May 22, 2003 Sheet 1 of 3
`
`US 2003/0094383 Al
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`48---t
`
`FIG. 1
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`42
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`FIG. 2
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 2 of 14
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`

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`Patent Application Publication May 22, 2003 Sheet 2 of 3
`
`US 2003/0094383 Al
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`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 3 of 14
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`

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`Patent Application Publication May 22, 2003 Sheet 3 of 3
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`US 2003/0094383 Al
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`54 �
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`
`FIG. 6
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 4 of 14
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`US 2003/0094383 Al
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`1
`
`May 22, 2003
`
`DETERMINATION OF SAMPLE VOLUME
`ADEQUACY IN BIOSENSOR DEVICES
`
`FIELD OF THE INVENTION
`
`[0001) Tbe field of this invention is tbe electrochemical
`determination of analyte in biological fluids, particularly tbe
`electrochemical determination of the adequacy of the vol­
`ume of the biological fluid sample 10 be tested for analyle
`concentration.
`
`BACKGROUND OF THE INVENTION
`
`[0002) Analyte concentration determination in biological
`fluids, e.g., blood or blood-derived products such as plasma,
`is of ever increasing importance to today's society. Sucb
`as.says find use in a variety of applications and settings,
`including cljnical laboratory testing, home testing, etc.,
`wbere the results of such testing play a prominent role in the
`diagnosis and management of a variety of disease condi­
`tions. Common analytes of interest include glucose for
`diabetes management, cholesterol for monitoring cardiovas­
`cular conrulions, and the like. In response 10 this growing
`importance of analyte concentration detection, a variety of
`analyte detection protocols and devices for both clinical and
`home use have been developed.
`
`[0003) One type of method that is employed for analyte
`detection is an electrochemical-based method. To such meth­
`ods, an aqueous liquid sample is placed into a reaction zone
`
`in an electrochemical cell made up of at least two electrodes,
`
`i.e., a counter/reference electrode and a working electrode,
`where the electrodes have an impedance which renders them
`suitable for amperometric measmemeat. The component to
`be analyzed, e.g., an analyte, is allowed to react directly with
`an electrode, or directly or indirectly with a reclox reagent to
`form an ox:idisable (or reducible) substance in an amount
`corresponding to the concentration of the component to be
`analyzed, i.e., analyte. 'Jbe quantity of the oxidisable (or
`reducible) substance present is then estimated electrochemi­
`cally and related to the amount of analyte present in the
`initial sample.
`
`[0004) Commonly, the electrochemical cell is in the form
`of a disposable test strip on which the biological sample is
`deposited and which is receivable within a meter by which
`the electrochemical aaalyte concentration
`is made.
`Examples of as.say systems that employ these types of test
`strips, often referred to as biosensors, and meters may be
`found in U.S. Pat. Nos. 5,942,102, 6,174,420 Bl and 6,179,
`979 'Bl, the disclosures of which are herein incorporated by
`reference. With these systems, determination of the concen­
`tration of an analyte in a biological sample first involves
`obtaining a biological sample and bringing that sample into
`
`contact with a reaction area of the test strip so that the
`
`biological sample, and more particularly the analyte of
`interest or derivative thereot: may read with the chemistry,
`e.g., the testing reagent(s), associated with the reaction area.
`In order to obtain an accurate measurement of the particular
`analyte(s) of interest, a minimum sample volume must be
`applied to the reaction area. It is not uncommon for an
`inadequate amount of sample volume to be provided, often
`clue to user error or patient inexperience or misjudgment.
`Inaccurate measurements can result in a misdiagnosis or
`improper treatment, sucb as administering an inappropriate
`dosage of a drug, patient non-compliance, etc. Such can
`
`result in serious and even life-threatening consequences for
`those whose lives depend on frequent monitoring of an
`analyte in their body, for example, diabetics.
`
`(0005) Ooe approach to ensuring an adequate biological
`sample volume is to over-saturate or use a greater volume of
`sampled fluid than is necessary to fill the reaction area of the
`test strip. A disadvantage of using an unnecessarily large
`volume of sampled f:luid, a blood sample in particular, is the
`need to draw a greater volume of blood sample from the
`patient. This requires use of a blood sample volume which
`is rather large, thus necessitating use of a larger diameter
`needle and/or deeper penetration into the skin. These factors
`can increase the discomfort and pain felt by the patient, and
`may be difficult to achieve for those individuals whose
`capillary blood docs not readily express. As this sampling
`process may be repeated frequently within a single day, for
`many diabetics, for example, an increase in pain quickly
`becomes less tolerable or intolerable all together.
`
`(0006] Some analyte detection biosensors have been
`developed to provide visual confirmation of the adequacy of
`sample volume, however, this fcan1re does not exclude
`potential error by the patient in judging the adequacy of the
`sample's volume, e.g., diabetics may experience deterio­
`rated vision. Certain other analyte determination biosensors
`do provide user-independent means for determining the
`adequacy of the sample volume. Examples of such biosen­
`sors are disclosed in U.S. Pat. Nos. 5,628,890 and 5,650,062
`and PCT Patent Application Publication No. WO 99/32881
`(PCr Patent Application No. PCT/US98/27203). In particu­
`lar, the '881 publication describes an electrochemical glu­
`cose monitoring system which attempts to determine the
`adequacy of a volume of sample applied to a biosensor by
`applying a low-level AC voltage signal (witbout a DC
`voltage offset) at a known frequency lo the biosensor and
`then measming both the real component and the imaginary
`component of the resulting impedance. These impedance
`values are then compared to a look-up table in the micro­
`processor's program memory. The accuracy of this method
`may be additionally questionable considering that this sys­
`tem is dependent on blood bematocrit levels and environ­
`mental temperature variations.
`
`[0007) Another disadvantage of the technique disclosed in
`the '881 publication is that the analyte measmement test
`must be aborted if the sample volume is determined to be
`inadequate, i.e., a "go-no-go" situation. This results in the
`need to take yet another sample from the patient which, as
`mentioned above, is inconvenient and may be very painful
`to the patient, likely resulting in patient non-compliance in
`his or her medication regime. Additionally, the test must be
`repeated resulting in the waste of test strips aod increasing
`the cost of the procedure.
`
`(0008] As such, there is continued interest in the identi­
`fication of new techniques for accurately and precisely
`measuring the adequacy of the volume of the sample used
`for electrochemical analyte concentration determination. Of
`particular interest would be the development of devices and
`methods that can very accurately and expeditiously deter­
`mine the adequacy of the volume of sample. It would be
`additionally beneficial to develop such a sample volume
`adequacy determination device and technique in which a
`determination that a sample volume is inadequate does not
`require abortion of the analyte concentration measurement
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 5 of 14
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`

`

`US 2003/0094383 Al
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`2
`
`May 22, 2003
`
`test. Ideally, this device and technique would compensate for
`the Jess than optimal sample volume and provide an accurate
`measurement without having to provide a new sample or to
`conduct a new test.
`
`SUMMARY OF '11-IE INVENTION
`
`[0009] The present invention provides methods, systems
`and devices for measuring the volume of biological sample
`and determining whether such volume is adequate to pro­
`duce an accurate measurement of at least one selected
`characteristic of the biological sample, such as the concen­
`tration of an analyte contained therein. Certain such meth­
`ods, systems and devices provide the additional function of
`compensating for a sample volume determined to be less
`than adequate in order to proceed with a measurement
`procedure.
`
`[0010) The present invention is employed with a bioseo­
`sor, such as an electrochemical test strip to which the sample
`volume of biological solution is deposited, and a meter
`configured to receive such test strip and to measure the
`concentration of selected analytes within the biological
`sample. The electrochemical test strip, as will be more fully
`described below, includes an electrochemical cell comprised
`of opposing electrodes between which a reaction zone is
`defined [or receiving the biological sample, wherein the
`reaction zone has a defined thickness and volume.
`
`[0011] When sufficient voltage is applied to an electro­
`chemical cell, the cell becomes charged and an electro­
`chemical reaction will occur within the charged cell. As a
`consequence, charge flows to the electrodes of an electrical
`cell. Tbe electrode-solution interface is analogous to that of
`a capacitor. The ratio of this charge to the voltage determines
`the capacitance of the electrode-solution interface. Since the
`total charge is due to the charging of the double layer and to
`the electrochemical reaction, two distinct capacitance com­
`ponents, Cd! and Cs, respectively, contribute to the total or
`equivalent capacitance of the cell (see Bard, A J. and
`Faulkner, L. R., Electrochemical Methods, 1980).
`[0012) The inventor bas discovered that the equivalent
`capacitance of an electrochemical cell is the most relevant
`factor in precisely determining sample volume, as the
`equivalent cell capacitance is linearly proportional to the
`amount of surface area of the cell electrodes in contact with
`the sample (the "covered cell area"), and thus, is linearly
`proportional to the volume of the sample within the cell, i.e.,
`between the electrodes.
`
`[0013) The inventor has also discovered that the electro­
`chemical cell can be used as a part of an oscillator circuit
`having an oscillation period (or the inverse of the oscillation
`frequency) proportional to the cell equivalent capacitance
`produced by the electrochemical cell when a DC voltage is
`applied to the cell. Thus, a feature of the present invention
`is to provide an oscillator operatively coupled to the elec­
`trochemical cell such that an oscillation is produced having
`a period proportional to the equivalent capacitance, to mea­
`sure this period a.ad then to derive the equivalent capacitance
`from the measured period.
`
`signal from tbe charged cell and converting such voltage
`signal to an oscillating signal; means for deriving the
`capacitance of the cell from the oscillating; means for
`deriving the surface area of the cell covered by the biological
`sample from the cell capacitance; and means [or deriving the
`volume of the biological sample from the covered cell
`surface area. Certain systems further include means for
`determining whether the sample volume is adequate for
`making an accurate measurement of one or more selected
`characteristics of the biological sample, including but not
`limited to the concentration of one or more selected analytes
`within the biological sample. Certain of these systems
`further include means for compensating for an inadequate
`sample volume while the selected characteristic of the
`biological sample.
`
`[0015] Jn one embodiment, the subject system includes a
`voltage supply configured for applying a first voltage to said
`electrochemical cell; means for measuring a second voltage
`generated by said cell when said first voltage is applied lo
`said cell; means for converting said second voltage into a
`oscillating voltage; means for deriving the capacitance of
`said cell from said oscillating voltage; means for deriving
`the surface area of said cell covered by said biological
`sample from said cell capacitance; and means for deriving
`the volume of said biological sample from said surface area.
`
`[0016) The above mentioned means of tl1e subject systems
`include electronic components and/or circuitry intended to
`be used with and electronica!Jy coupled to a biosensor, e.g.,
`an electrochemical measurement cell in the form of, e.g., a
`disposable test strip, into which the sampled solution to be
`tested is deposited or is drawn by a capillary action. Most
`typically, such electronic circuitry is incorporated into a
`meter or other automated device configured to receive and
`operatively engage with such electrochemical cell, e.g., a
`disposable test strip, and to measure one or more physical or
`chemical characteristics of a biological sample held within
`the electrochemical cell. Such electronic circuitry can be
`implemented using available commercial parts or can be
`implemented as a part of an ASIC (Application Specific
`Integrated Circuit). Most typically, such characteristics
`include the concentration of one or more target analytes
`within the biological sample. Such electronic circuitry may
`comprise discrete electronic components, e.g., a voltage
`supply, and/or integrated circuits having multiple circuit
`elements and/or semiconductor devices, e.g., a micropro­
`cessor suitably programmed to execute certain steps or
`functions of the subject methods based on certain signal or
`data inputs received from the electrochemical cell.
`
`[0017] The subject circuitry may further include a display
`device or unit for displaying selected empirical or symbolic
`data, information or outputs supplied by the control device
`or microprocessor. Such data, information or outputs may
`include, but are not limited to, measured or derived values
`of selected input and output signals, impedance factors,
`sample volume size, volume adequacy/inadequacy indicator
`icons, inadequate volume compensation factors, concentra­
`tions of aoalytes of interest, biological sample versus control
`sample indicator icons, calibration results, etc.
`
`[0014) Generally described, the systems of the present
`invention may include the following components: a voltage
`supply configured for applying a voltage to the electro­
`chemical cell to charge the cell; means for receiving voltage
`
`[0018) lo certain embodiments, the systems of the present
`invention include such electronic circuitry and an automated
`measurement device or meter, wherein the electronic cir­
`cuitry is completely structurally and functionally integral
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
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`US 2003/0094383 Al
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`3
`
`May 22, 2003
`
`with the automated measurement device. For example, one
`such embodiment includes a meter for receiving an electro­
`chemical cell configured for receiving a biological sample
`and having a capacitance created by the biological sample
`when a voltage is applied to the electrochemical cell. Tbe
`system further includes a DC voltage supply configured to
`be electrically coonectable to the electrochemical cell for
`charging the electrochemical cell to create a cell capaci­
`tance, and an electronic circuit integrally configured with the
`meter and configured to be electronically connectable to the
`electrochemical cell. The circuit includes an oscillator cir­
`cuit configured to receive a voltage input signal resulting
`from the charging and discharging of the electrochemical
`cell and also configured 10 convert the voltage input signal
`to an oscillating voltage output signal, wherein the period of
`oscillating voltage output signal is proportional to the
`capacitance of the cell.
`
`[0019) Tbe present invention also includes methods for
`determining the adequacy of the volume of a biological
`sample 10 be used for determining the concentration of one
`or more selected analytes within the biological sample
`deposited or transferred to a bioseosor. The oscillator
`charges and discharges the cell capacitance and, therefore,
`its frequency or period of oscillation depends on the mag­
`nitude of the cell capacitance. The cell charge and discharge
`voltage is controlled such that a net DC voltage is applied 10
`the cell. Next, the equivalent cell capacitance of the biosen­
`sor is determined from this oscillating voltage. From the
`equivalent capacitance, the surface area of the portion of the
`biosensor in contact with the biological sample ("the cov­
`ered cell area") is then used to derive the volume of the
`biological sample within the bioscosor. Upon a determina­
`tion that the sample volume is sufficient to proceed with the
`measurement test, the targeted characteristic, e.g., analyte
`concentration, is measured. On the other band, if it is
`determined that the sample volume is inadequate, the subject
`methods may fuithcr include compensating for such inad­
`equate sample volume during the measurement process.
`Inadequate volume compensation involves determining the
`ratio of the equivalent cell capacitance of ll1e biosensor
`containing the actual sample volume to the cell capacitance
`of the biosensor when its entire available volume is filled.
`
`[0020) While the subject systems and methods may be
`used io determine the sample volume of different biological
`samples, such as urine, tears, saliva, and the like, they are
`particularly suited for use in determining the sample volume
`of blood or blood fractions and the like. Furthermore, while
`the subject systems and methods for determining the sample
`volume in preparation for measuring a variety of physical
`and chemical characteristics of the sample, they are particu­
`larly useful in preparation for measuring the concentration
`of selected analytes within the sample.
`
`[0021] Tbese and other objects, advantages, and features
`of the invention will become apparent to those persons
`skilled in the art upon reading the details of the methods and
`systems of the present invention which are more fully
`described below.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`[0022)
`I•IG. 1 is an exploded view of an exemplary
`conventional electrochemical test strip for electrochemical
`analyte concentration determination, which is usable with
`the present invention.
`
`[0023] FIG. 2 is a schematic illustration of a circuit
`representative of the equivalent cell impedance of the test
`strip of FIG. 1.
`
`[0024) FIG. 3 is a part schematic and a part block diagram
`of an electronic circuit of an embodiment of a system of the
`present invention operatively coupled to an electrochemical
`biosensor for determining ibe adequacy o[ a sample volume
`according to the present invention.
`
`[0025] FTG. 4 is a graph illustrating the input voltage (Vi)
`waveform applied to an electrochemical cell of a test strip
`and oscillator output voltage (V 0) waveform from the
`electronic circuit of FIG. 3 and in accordance with the
`present invention.
`
`[0026) FIG. 5 is a schematic diagram of another embodi­
`ment of tbe oscillator circuit o( the electronic circuit of FIG.
`3.
`
`[0027] FIG. 6 is a graph depicting the relationship of the
`change in the oscillation period (y-axis) produced by an
`electrochemical cell over time (x-axis) after blood sample
`has been applied to the cell when the cell is completely filled
`and half filled, respectively, with a sampled solution.
`
`DETAILED DESCR1P'.110N OF THE
`PREFERRED EMBODIMENTS
`
`[0028] Tbe present invention provides systems and meth­
`ods for determining the volume of a biological sample for
`purposes of measuiing a selected characteristic of the
`sample, e.g., analytc concentration, and determining
`whether sucb volume is adequate to produce an accurate
`measurement of such selected characteristic. Certain
`embodiments of the systems and methods of the present
`invention provide tbe additional function of compensating
`for a sample volume determined to be less than adequate in
`order to provide an accurate analyte concentration measure­
`ment.
`
`[0029] Before the present invention is described in further
`detail, it is lo be understood that this invention is not limited
`to the particular embodiments described, as such may, of
`course, vary. It is also to be understood that the terminology
`used herein is for the purpose of describing particular
`embodiments only, and is not intended to be limiting, since
`the scope of the present invention wiU be I imited only by the
`appended claims.
`
`[0030] Where a range of values is provided, it is under­
`stood that each intervening value, to the tenth of the unit of
`the lower limit unless the context clearly dictates otherwise,
`between the upper and lower limit of that range and any
`other stated or intervening value in that stated range is
`encompassed within the invention. The upper and lower
`limits of these smaller ranges may independently be
`included in the smaller ranges is also encompassed within
`the invention, subject to any specifically excluded limit in
`the stated range. Where the stated range includes one or both
`of tbe limits, ranges excluding either both of those included
`limits are also included in the invention.
`
`[0031) Unles.s defined otherwise, all technical and scien­
`tific terms used herein have the same meaning as commonly
`understood by one of ordinary skill in the art 10 which this
`invention belongs. Although any melllods and materials
`similar or equivalent to those described herein can also be
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
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`US 2003/0094383 Al
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`4
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`May 22, 2003
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`used in the practice or testing of the present invention, a
`limited number of the exemplary methods and materials are
`described herein.
`
`[0032) It must be noted that as used herein and in the
`appended claims, the singular forms "a", "an'', and "the"
`include plural referents unless the context clearly dictates
`otherwise.
`
`[0033] All publications mentioned herein are incorporated
`herein by reference to disclose aod describe the methods
`and/or materials in connection with which the publications
`are cited. The publications discussed herein are provided
`solely for their disclosure prior to the filing date of the
`present application. Nothing herein is to be construed as an
`admis.<;ion that the present inventio.o is .not entitled to ante­
`date such publication by virtue of prior invention. Further,
`the dates of publications provided may differ from their
`actual publication dates, which may need to be indepen­
`dently confirmed.
`
`[0034] Definitions
`
`[0035) The term "double layer" as used herein refers to the
`whole array of charged species and oriented dipoles existing
`at the interface between an electrode surface and a solution,
`e.g., a sample of a biological solution, in contact with the
`electrode surface when a voltage is applied to the electrode.
`
`[0036) The term "double layer capacitance," Cd•• as used
`herein means the capacitance contributed by the charging of
`the double layer of the electrode-solution interface.
`
`[0037) The term "Faradaic capacitance," Cs, as used
`herein refers to the pseudo-capacitance component due to
`the electrochemical reaction process that occurs on the
`electrode surface.
`
`[0038] The term "Faradic current," 11,, as used herein
`means the current or electron transfer that occurs at the
`surface of an electrode to which a voltage bas been applied.
`
`[0039) The term "equivalent cell capacitance," C, when
`used herein in reference to an electrochemical cell means the
`total equivalent capacitance across the electrochemical cell,
`which results when a voltage bas been applied to the
`electrochemical cell. The equivalent cell capacitance is
`dominated by the double layer capacitance and the Faradaic
`capacitance.
`
`[0040) The term "equivalent cell resistance," R, as used
`herein in reference to an electrochemical cell means the total
`equivalent resistance across the electrochemical cell, which
`resuJts when a voltage bas been applied to electrochemical
`cell.
`
`[0041] The "equivalent cell impedance," Z, as tt<;ed inter­
`changeably herein in reference to an electronic circuit or
`component, e.g., an electrochemical cell, means the total
`impedance of the circuit including but not necessarily lim­
`ited to the combination of the equivalent cell capacitance
`and the equivalent cell resistance, which results when a
`voltage bas been applied to the electrochemical cell.
`
`[0042] The present invention will now be described in
`detail. Io further describing the present invention, exemplary
`electrochemical bioseosors, usable with the systems and
`employable by the methods of the present invention, will be
`described first, followed by a detailed description of the
`subject systems and the subject methods, as well as a
`
`description of tbe subject kits that include the subject
`systems for use in practicing the subject methods. Io the
`following description,
`the present invention will be
`described in the context of analyte concentration measure­
`ment applications; however, such is not intended to be
`limiting and those skilled in the art will appreciate that the
`subject systems and methods are useful in measurement of
`other physical and chemical characteristics of biological
`substances such as blood coagulation time and measuring
`blood cholesterol.
`
`[0043] Electrochemical Biosenso rs
`[0044] As summarized above, the invention provides sys­
`tems and methods for measuring the volume of a sample of
`biological material used for aoalyte concentration measure­
`ment and determining whether such volume is adequate to
`produce ao accurate analyte concentration measurement.
`These methods and systems are usable with a biosensor,
`more particularly an electrochemical cell-based biosensor,
`into which the sampled biological material is deposited or
`transferred. There are varying designs of electrochemical
`cell-based bioseosors. The most common of these designs
`employed in the field of aoalyte concentration monitoring
`include test strip configurations, such as those disclosed in
`copending U.S. Pat. No. 6,193,873 and in copending U.S.
`patent application Ser. Nos. 09/497,304; 09/497,269;
`09/736,788 and 09/746,116, the disclosures of which are
`herein incorporated by reference. Such test strips are used
`with meters configured for electrochemical measurements,
`
`such as those disclosed in the above-identified patent refer­
`
`ences.
`
`[0045) Electrochemical biosensors other than test strips
`may also be suitable for use with the present invention. For
`example, the electrochemical cell may have a cylindrical
`configuration wherein a core electrode is co-axially posi­
`tioned within a second tubular electrode. Such electrochemi­
`cal cell configurations may be in the form of micro-needles
`
`and, as such, are either integral within the needle structure
`
`for in situ (e.g., typically under the skin surface) measure­
`ments or otherwise in physical or fluid communication with
`a micro-needle structure. Examples of such micro-needle are
`disclosed in co-pending U.S. patent application Ser. Nos.
`09/878,742 and 09/879,106 filed on Jun. 12, 2001, hereby
`incorporated by reference. For p11rposes of this di<;closure,
`the subject devices will be described in use with electro­
`chemical cells in test strip configurations; however, those
`skilled in the art will appreciate that the subject devices may
`be used with any suitable electrochemical cell configuration,
`including micro-needle configurations.
`
`[0046] Tbe type of electrochemical measurement that is
`made may vary depending on the particular nature of the
`assay and the meter with which the electrochemical test strip
`is employed, e.g., depending on whether the assay is cou­
`lometric, amperometric or potentiometric. The electro­
`chemical cell will measure charge in a coulometric assay,
`current in an amperometric assay and potential in a poten­
`tiometric assay. For purposes of this disclosure, the present
`invention will be described in the context of amperometric
`assays; however, the subject devices may be employed with
`any type of assay and electrochemical measurement.
`
`[0047) Generally, in any configuration, an electrochemical
`cell includes at least two electrodes spaced-apart io either a
`facing arrangement or in a side-by-side arrangement in the
`
`AGAMATRIX, INC. EXHIBIT NO. 1027
`Page 8 of 14
`
`

`

`US 2003/0094383 Al
`
`5
`
`May 22, 2003
`
`same plane. In the first arrangement, the electrodes are
`separated by a tbin spacer layer, whicb defines a reaction
`area or zooe, or chamber into wbicb a biological sample is
`deposited or traosferred for analyte concentration measure­
`ment. In the side-by-side configuration, the electrodes are in
`a chamber with a defined thickness and volume. Present in
`the reaction area or chamber, i.e., coated on one or more of
`the facing surfaces of the electrodes, are one or more redox
`reagents selected to chemically react the target analyte(s).
`Such redox reagents typically comprise an enzyme and a
`mediator.
`
`[0048] A representation of an exemplary conventional
`electrochemical test strip 2 suitable for use with the present
`invention is provided in the exploded view of FIG. l. Test
`strip 2 is made up of a two electrodes 4, 8 separated by a
`spacer layer 12 which bas a cutaway section that defines the
`reaction zone or area 14. Generally, the electrodes 4, 8 are
`configured in tbe form of elongated rectangular strips eacb
`baving a length in the range from about 2 to 6 cm, usually
`from about 3 to 4 cm, having a width in the range from about
`0.3 to 1.0 cm, usually from about 0.5 to 0.7 cm, and having
`a thickness in the range from about 0.2 to 1.2 mm, and
`usually from 0.38 to 0.64 mm.
`
`[0049] The surfaces of electrodes 4, 8 that face the reac­
`tion area in the strip is made of a conductive material,
`preferably a metal, where metals of interest include palla­
`dium, gold, platinum, silver, iridium, carbon, eloped indium
`tin oxide, stainless steel and the like. "lbe outside surfaces 6,
`10 of electrodes 4, 8 are made of an inert support or backjng
`material. Any suitable inert backing material may be used
`witb electrodes 4, 8, where typically the material is a rigid
`material that is capable of providing structural support to the
`electrode and, in turo, the electrochemical test strip as a
`
`whole. Such suitable materials include plastics, e.g., PET,
`
`PETG, polyirnide, polycarbonate, polystyrene, silicon,
`ceramic, glass, and the like. Electrodes 4, 8 aod test strip 2
`may be fabricated using any of various manufacturing
`techniques known to those skilled in the relevant art. As
`described above, a thi