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`US006837988B2
`
`(12) United States Patent
`Leong et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 6,837,988 B2
`Jan.4,2005
`
`(54) BIOLOGICAL FLUID SAMPLING AND
`ANALYTE MEASUREMENT DEVICES AND
`METHODS
`
`(75)
`
`Inventors: Koon-wah Leong, Sunnyvale, CA
`(US); Robert Shartle, Livermore, CA
`(US)
`
`(73) Assignee: LifeScan, Inc., Milpitas, CA (US)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 406 days.
`
`(21) Appl. No.: 09/879,146
`Jun. 12, 2001
`(22) Filed:
`
`6,083,196 A
`6,091,975 A
`6,162,611 A
`6,379,324 Bl
`
`7/2000 Trautman et al.
`7/2000 Daddona et al.
`12/2000 Heller et al.
`4/2002 Gartstein et al.
`
`FOREIGN PATENT DOCUMENTS
`
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`
`WO 97/00441
`WO 97/42888
`WO 98/00193
`WO 98/34541
`WO 99/13336
`WO 89/27852
`WO 99/64580
`WO 00/35530
`WO 00/45708
`WO 00/57177
`WO 00/74763
`WO 00/74765
`
`1/1977
`11/1997
`1/1998
`8/1998
`3/1999
`6/1999
`12/1999
`6/2000
`8/2000
`9/2000
`12/2000
`12/2000
`
`(65)
`
`(51)
`(52)
`
`(58)
`
`(56)
`
`Prior Publication Data
`
`* cited by examiner
`
`US 2002/0185384 Al Dec. 12, 2002
`Int. Cl.7 ......................... GOlN 27/327; A61B 5/05
`U.S. Cl. ............... 205/792; 205/777.5; 204/403.01;
`204/403.11; 600/345; 600/347
`....................... 204/403.01, 403.02,
`Field of Search
`204/403.04, 403.05, 903.11; 205/777.5,
`792; 600/345, 347, 365
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`5,161,532 A
`5,231,028 A *
`5,304,468 A
`5,529,752 A
`5,563,042 A
`5,582,184 A
`5,746,217 A
`5,820,570 A
`5,821,399 A
`5,879,310 A
`5,879,367 A
`5,942,102 A
`6,059,946 A *
`6,080,116 A
`
`11/1992
`7/1993
`4/1994
`6/1996
`10/1996
`12/1996
`5/1998
`10/1998
`* 10/1998
`3/1999
`3/1999
`8/1999
`5/2000
`6/2000
`
`Joseph
`Mullen ....................... 205/188
`Phillips et al.
`Pontis et al.
`Phillips et al.
`Erickson et al.
`Erickson et al.
`Erickson et al.
`Zelin . ... ... ... .. ... ... ... ... .. 73/1.02
`Sopp et al.
`Latterell et al.
`Hodges et al.
`Yukawa et al. ........ 204/403.14
`Erickson et al.
`
`Primary Examiner-Kaj K. Olsen
`(74) Attorney, Agent, or Firm-Carol M. LaSalle;
`Bozicevic, Field & Francis, LLP
`(57)
`
`ABSTRACT
`
`A device for sampling a biological fluid and measuring a
`target analyte within the biological fluid is provided. The
`device has at least one micro-piercing member used to
`penetrate the skin to a selected depth and access biological
`fluid, a sampling means and a measuring means. The sam­
`pling means comprises a fluid transfer medium, such as a
`hydrophilic porous material, by which sampled biological
`fluid is transferred from the micro-piercing member to the
`measuring means. The measuring means includes an elec­
`trochemical cell having at least one porous electrode and,
`typically, a reagent material, where the electrochemical cell
`is configured so as to make an electrochemical measurement
`of a target analyte in accessed biological fluid present
`therein. Methods of sampling biological fluids within the
`skin and measuring the sampled fluids are also provided, as
`well as kits comprising one or more of the inventive devices.
`
`38 Claims, 2 Drawing Sheets
`
`188
`
`'
`B
`18A
`
`13
`
`28
`
`26
`
`26
`
`30 22
`
`34
`
`10
`;-
`26 1
`27
`
`32
`
`'
`B
`
`20
`
`13
`
`AGAMATRIX, INC. EXHIBIT NO. 1022
`Page 1 of 11
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`

`

`U.S. Patent
`
`Jan.4,2005
`
`Sheet 1 of 2
`
`US 6,837,988 B2
`
`FIG. 1A
`
`28
`
`26
`
`26
`
`30
`
`22
`
`34
`
`188
`
`FIG. 18
`
`26
`
`15
`
`t
`B
`
`20
`
`._--+---27
`
`18A
`
`12
`
`12
`
`12
`
`188
`
`18A
`
`AGAMATRIX, INC. EXHIBIT NO. 1022
`Page 2 of 11
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`

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`U.S. Patent
`
`Jan.4,2005
`
`Sheet 2 of 2
`
`US 6,837,988 B2
`
`FIG. 2
`
`r- 5 0
`
`--10
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`AGAMATRIX, INC. EXHIBIT NO. 1022
`Page 3 of 11
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`

`

`US 6,837,988 B2
`
`1
`BIOLOGICAL FLUID SAMPLING AND
`ANALYTE MEASUREMENT DEVICES AND
`METHODS
`
`FIELD OF THE INVENTION
`This invention is related to percutaneous biological fluid
`sampling and analyte measurement, and more particularly to
`fluid transfer mediums to facilitate sampling of biological
`fluid.
`
`BACKGROUND
`The detection of analytes in biological fluids is of ever
`increasing importance. Analyte detection assays find use in
`a variety of applications, including clinical laboratory
`testing, home testing, etc., where the results of such testing
`play a prominent role in the diagnosis and management of a
`variety of disease conditions. Common analytes of interest
`include glucose, e.g., for diabetes management, cholesterol,
`and the like.
`A common technique for collecting a sample of blood for
`analyte determination is to pierce the skin at least into the
`subcutaneous layer to access the underlining blood vessels
`in order to produce localized bleeding on the body surface. 25
`The accessed blood is then collected into a small tube for
`delivery and analyzed by testing equipment, often in the
`form of a hand-held instrument having a reagent test strip
`onto which the blood sample is placed. The fingertip is the
`most frequently used site for this method of blood collection
`due to the large number of small blood vessels located
`therein. This method has the significant disadvantage of
`being very painful because subcutaneous tissue of the fin­
`gertip has a large concentration of nerve endings. It is not
`uncommon for patients who require frequent monitoring of 35
`an analyte, to avoid having their blood sampled. With
`diabetics, for example, the failure to frequently measure
`their glucose level on a prescribed basis results in a lack of
`information necessary to properly control the level of glu­
`cose. Uncontrolled glucose levels can be very dangerous and 40
`even life-threatening. This technique of blood sampling also
`runs the risk of infection and the transmission of disease to
`the patient, particularly when done on a high-frequency
`basis. The problems with this technique are exacerbated by
`the fact that there is a limited amount of skin surface that can 45
`be used for the frequent sampling of blood.
`To overcome the disadvantages of the above technique
`and others that are associated with a high degree of pain,
`certain analyte detection protocols and devices have been
`developed that use micro-piercing, micro-cutting elements
`or analogous structures to access the interstitial fluid within
`the skin. The micro-needles are penetrated into the skin to a
`depth less than the subcutaneous layer so as to minimize the
`pain felt by the patient. The interstitial fluid is then sampled
`and tested to determine the concentration of the target
`analyte. Some kind of mechanical or vacuum means is often
`used in conjunction with the micro-piercing elements in
`order to remove a sample of interstitial fluid from the body.
`Typically, this is accomplished by applying a pressure
`differential of approximately 6 mm Hg.
`For example, International Patent Application WO
`99/27852 discloses the use of vacuum pressure and/or heat
`to increase the availability of interstitial fluid at the area of
`skin in which the vacuum or heat is applied. The vacuum
`pressure causes the portion of skin in the vicinity of the
`vacuum to become stretched and engorged with interstitial
`fluid, facilitating the extraction of fluid upon entry into the
`
`5
`
`2
`skin. Another method is disclosed wherein a localized heat­
`ing element is positioned above the skin, causing interstitial
`fluid to flow more rapidly at that location, thereby allowing
`more interstitial fluid to be collected per given unit of time.
`Still other detection devices have been developed which
`avoid penetration of the skin altogether. Instead, the outer­
`most layer of skin, called the stratum corneum, is "dis­
`rupted" by a more passive means to provide access to or
`extraction of biological fluid within the skin. Such means
`10 includes the use of oscillation energy, the application of
`chemical reagents to the skin surface, etc. For example,
`International Patent Application WO 98/34541 discloses the
`use of an oscillation concentrator, such as a needle or wire,
`which is positioned at a distance from the skin surface and
`15 caused to vibrate by means of an electromechanical trans­
`ducer. The needle is immersed in a receptacle containing a
`liquid medium placed in contact with the skin. The mechani­
`cal vibration of the needle is transferred to the liquid,
`creating hydrodynamic stress on the skin surface sufficient
`20 to disrupt the cellular structure of the stratum corneum.
`International Patent Applications WO 97/42888 and WO
`98/00193 also disclose methods of interstitial fluid detection
`using ultrasonic vibration.
`Despite the work that has already been done in the area of
`minimally invasive analyte testing, there is a continued
`interest in the identification of new analyte detection meth­
`ods that are less expensive and eliminate the need for
`ancillary equipment (e.g., oscillation, suction and heat gen­
`erating devices). Of particular interest would be the devel-
`30 opment of a minimally invasive analyte detection system
`that is inexpensive, easy to use, is integratable into a single
`component and is safe and efficacious.
`RELEVANT LITERATURE
`U.S. Patents of interest include: U.S. Pat. Nos. 5,161,532,
`5,582,184, 5,746,217, 5,820,570, 5,879,310, 5,879,367,
`5,942,102, 6,080,116, 6,083,196, 6,091,975 and 6,162,611.
`Other patent documents and publications of interest include:
`WO 97/00441, WO 97/42888, WO 98/00193 WO 98/34541,
`WO 99/13336, WO 99/27852, WO 99/64580, WO
`00/35530, WO 00/45708, WO 00/57177, WO 00/74763 and
`WO 00/74765Al.
`SUMMARY OF THE INVENTION
`Percutaneous sensor systems and devices, as well as
`methods for using the same are provided by the subject
`invention. A feature of the subject devices is the presence of
`a fluid transfer medium that transfers biological fluid
`accessed within the skin to a measurement means for
`50 measurement of a targeted analyte within the fluid sample.
`The present invention finds use in the sampling of biological
`fluids such as blood and interstitial fluid, and in the detection
`and measurement of various analytes, e.g., glucose,
`cholesterol, electrolytes, pharmaceuticals, or illicit drugs,
`55 and the like, present in the sampled biological fluid. The
`present invention is especially well-suited for the sampling
`of interstitial fluid and the measurement of the concentration
`of glucose therein.
`In general, the subject devices include (1) at least one
`60 sampling means in the form of a fluid transfer medium and
`having a distal surface configured to pierce the skin surface
`and to provide access to biological fluid within the skin, and
`(2) a measuring means in the form of an electrochemical
`cell, a porous matrix having a signal producing system, or
`65 the like in fluid communication with the sampling means.
`The fluid transfer medium is porous, having either a
`uniform porosity or a gradient of porosity from one portion
`
`AGAMATRIX, INC. EXHIBIT NO. 1022
`Page 4 of 11
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`

`

`US 6,837,988 B2
`
`10
`
`3
`or end to another portion or end. Preferably, the fluid transfer
`medium is more porous at a proximal end than towards a
`distal end, e.g., there is a porosity gradient from the proximal
`to distal end. The change in porosity from one end to the
`other end may be gradual or sharp wherein the distal surface 5
`is the densest portion (i.e., has the fewest number of pores
`or none at all) of the fluid transfer medium to provide
`rigidity when piercing the skin. The fluid transfer medium is
`made, at least in part, of one or more hydrophilic materials
`formed in a porous structure having a plurality of pores. As
`such, the pores provide a capillary action by which the fluid
`transfer medium is able to transfer fluid.
`In certain embodiments, the skin-piercing function is
`accomplished by the distal surface of the fluid transfer
`medium. Specifically, the distal surface is formed with very 15
`sharp protrusions. In some of these embodiments, this distal
`surface is non-porous wherein the protrusions have a porous
`central core that extends through the distal surface, thereby
`defining a fluid access opening to access biological fluid.
`The fluid transfer medium extends between the access 20
`opening of the micro-piercing member to the measurement
`means of the subject invention, and functions to transfer
`biological fluid and/or its constituents present at the access
`opening to the measurement means. Still, in other
`embodiments, the entirety of the protrusions are also porous 25
`but to a much lesser extent than the proximal region. In these
`embodiments, an access opening is unnecessary since the
`porous protrusions themselves allow access of fluid into the
`sensor device.
`Other embodiments of the subject devices have skin- 30
`penetrating means discrete from the fluid transfer medium,
`such as an array of micro-needles comprised of a nonporous
`material, wherein each of the micro-needles has a distal
`access opening. The micro-needle side of the array (i.e., the
`underside of the device) may itself be formed of or coated 35
`with an insulating material. In still other embodiments, the
`micro-needles are made of or coated with a conductive
`material, such as a metal, to form a set of electro-sensors.
`The subject devices which employ an electrochemical cell
`as the measurement means preferably provide a redox 40
`reagent system or material within the electrochemical cell
`between the electrodes, often called the reaction cell or
`chamber. The target analyte of the biological fluid present
`within the reaction chamber, chemically reacts with the
`redox reagent system to produce an electrical signal mea- 45
`sured by the electrodes from which the concentration of the
`target analyte can be derived. The particular redox reagent
`material used is selected based on the analyte targeted for
`measurement. As would be apparent to one of skill in the art,
`the subject invention may also be modified for use with 50
`calorimetric or reflectance-type analyte measuring systems,
`where such reflectance systems typically comprise a porous
`matrix containing a signal producing system and a reflec­
`tance measuring apparatus which is activated upon a change
`in reflectance of the matrix when fluid penetrates the matrix. 55
`Examples of such systems may be found in U.S. Pat. Nos.
`5,563042, 5,563,031, 5,789,255 and 5,922,530, which are
`herein incorporated by reference in their entirety.
`The subject sensor devices may function as a part of an
`analyte sensing system that includes a means for controlling 60
`the sensor device. Specifically, a control unit is provided in
`which the control means is electrically coupled with the
`sensor device and functions to generate and send input
`signals to the electrochemical cell and to receive output
`signals from the cell. These functions, among others, are 65
`performed by a software algorithm programmed within the
`control unit that automatically calculates and determines the
`
`4
`concentration of the target analyte in the biological sample
`upon receipt of an output signal from the electrochemical
`cell or a matrix comprising a signal producing system.
`Also provided by the subject inventions are methods for
`using the subject devices and systems as well as kits for use
`in practicing the methods of the subject invention.
`The subject invention is useful for analyte concentration
`measurement of a variety of analytes and is particularly
`suited for use in the measurement of glucose concentration
`in interstitial fluid.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`FIG. 1 is a cross-sectional view of an exemplary biologi­
`cal fluid sensing and analyte measuring device of the present
`invention; and
`FIG. 2 is a schematic representation of an exemplary
`hand-held device for using the biological fluid sensing and
`analyte measuring devices of the present invention.
`
`DETAILED DESCRIPTION OF PREFERRED
`EMBODIMENTS
`Percutaneous biological fluid, e.g., interstitial fluid, sam­
`pling and analyte measurement sensor devices and systems,
`as well as methods for using the same, are provided.
`Before the present invention is described, it is to be
`understood that this invention is not limited to 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 will be limited only by the appended claims.
`Where a range of values is provided, it is understood 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 the limits, ranges
`excluding either both of those included limits are also
`included in the invention.
`Unless defined otherwise, all technical and scientific
`terms used herein have the same meaning as commonly
`understood by one of ordinary skill in the art to which this
`invention belongs. Although any methods and materials
`similar or equivalent to those described herein can also be
`used in the practice or testing of the present invention, the
`preferred methods and materials are now described. All
`publications mentioned herein are incorporated herein by
`reference to disclose and describe the methods and/or mate­
`rials in connection with which the publications are cited.
`It must be noted that as used herein and in the appended
`claims, the singular forms "a", "and", and "the" include
`plural referents unless the context clearly dictates otherwise.
`Thus, for example, reference to "a chamber" includes a
`plurality of such chambers and reference to "the array"
`includes reference to one or more arrays and equivalents
`thereof known to those skilled in the art, and so forth.
`The publications discussed herein are provided solely for
`their disclosure prior to the filing date of the present appli­
`cation. Nothing herein is to be construed as an admission
`that the present invention is not entitled to antedate such
`publication by virtue of prior invention. Further, the dates of
`
`AGAMATRIX, INC. EXHIBIT NO. 1022
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`US 6,837,988 B2
`
`5
`publication provided may be different from the actual pub­
`lication dates which may need to be independently con­
`firmed.
`In general, the devices of the subject invention include a
`biological fluid sampling means configured to pierce a skin
`surface and an analyte measurement means. More
`specifically, the subject devices, i.e., sensor devices, include
`at least one sampling means in the form of a fluid transfer
`medium and having a distal surface configured to pierce the
`skin surface and to provide access to biological fluid within 10
`the skin, and a measuring means in fluid communication
`with the sampling means. The measuring means of the
`present invention may comprise any suitable means, includ­
`ing an electrochemical, calorimetric or photometric means
`or the like. For purposes of this description, an electrochemi- 15
`cal cell configuration is described as an exemplary embodi­
`ment of the measuring means of the present invention.
`The fluid transfer medium is hydrophilic and is primarily
`comprised of a porous material having a plurality of pores or
`voids throughout the medium (except in those embodiments 20
`in which the fluid medium has a non-porous distal surface)
`which are sufficiently large and interconnected to permit
`passage of fluid materials there through. The pores exert a
`capillary force on the biological fluid, causing the sample
`fluid and its constituents, to be drawn or wicked into the 25
`pores.
`The more porous the transfer medium, the faster the fluid
`travels through the transfer medium, thereby reducing the
`sampling and measuring time. Additionally, a high pore 30
`density increases the volume of fluid capable of passing
`through the fluid transfer medium per unit of time. However,
`the more porous a material, the weaker it may be. Thus, in
`a preferred embodiment, the distal portion of the fluid
`transfer medium (i.e., the portion configured to pierce the 35
`skin) is less porous (i.e., contains fewer pores) than the
`proximal portion (i.e., the portion associated with the elec­
`trochemical cell, discussed below). As such, the distal por­
`tion of the fluid transfer medium provides rigidity and
`strength to ensure that the portion configured to pierce the 40
`skin, e.g., the skin piercing structure(s), does not break or
`crack upon insertion into the skin. Conversely, the porous
`proximal portion facilitates and expedites the transfer of
`sampled biological fluid into the electrochemical cell.
`In certain embodiments, at least a portion of the less
`porous distal portion is nonporous. For example, the non­
`porous portion of the distal portion may be an exterior layer
`wherein this non-porous exterior layer forms an outer coat­
`ing or shell that is strong enough to pierce the skin, i.e., the
`exterior layer functions as the skin piercing structure.
`However, a center core of the non-porous exterior remains
`porous and defines an access opening therein in order to
`allow biological fluid to be wicked into the sensor device. As
`just described, the exterior layer is made of the same
`material as the remainder of the fluid transfer medium. In 55
`other embodiments, however, this outer layer comprises a
`different material which acts more as a housing structure for
`the fluid transfer medium, as well as providing the piercing
`structures of the invention. Yet in other embodiments, the
`exterior layer of the less porous distal portion of the fluid 60
`transfer medium is not completely pore-less, having enough
`rigidity to pierce the skin without breaking or cracking yet
`able to assist in the wicking process.
`The more porous, proximal portion of the fluid transfer
`medium increases the amount and rate at which the sampled
`biological fluid enters the electrochemical cell. The proxi­
`mal portion of the fluid transfer medium generally has from
`
`6
`about 10 to 100 times, but may have more or less, as many
`pores as the distal portion. The pore density within the
`transfer medium preferably increases gradually and consis­
`tently from the end of the distal portion to the end of the
`5 proximal portion.
`As described above, the fluid transfer medium is made of
`a porous hydrophilic material. Preferably, the material is not
`water-absorbent such that the water within the biological
`fluid is not absorbed by the fluid transfer material but is
`completely passed through the medium along with the other
`components of the biological fluid. Porous hydrophilic
`materials usable as the fluid transfer medium include, but are
`not limited to, polymers, ceramics, glass and silica. Suitable
`polymers include polyacrylates, epoxies, polyesters,
`polycarbonate, polyamide-imide, polyaryletherketone,
`polyetheretherketone, polyphenylene oxide, polyphenylene
`sulfide, liquid crystalline polyesters, or their composites.
`Examples of ceramics are aluminum oxide, silicon carbide
`and zirconium oxide.
`A hydrophilic gel or the like may also be used in con­
`junction with the porous material to form the fluid transfer
`medium. Suitable gels include natural gels such as agarose,
`gelatin, mucopolysaccharide, starch and the like, and syn­
`thetic gels such as anyone of the neutral water-soluble
`polymers or polyelectrolytes, such as polyvinyl pyrrolidone,
`polyethylene glycol, polyacrylic acid, polyvinyl alcohol,
`polyacrylamide, and copolymers thereof.
`Other embodiments of the subject devices have skin­
`penetrating means on the underside of the device discrete
`from the fluid transfer medium, such as an array of micro­
`piercing structures or micro-needles comprised of a non-
`porous material. For example a non-porous material may be
`coated over the fluid transfer medium to form micro-
`piercing structures, e.g., micro-needles or the like. Each of
`the micro-piercing structures has a distal access opening to
`provide access to biological fluid. As such, certain embodi­
`ments of the subject invention have a layered configuration
`in which the proximal side of an array of micro-needles is
`covered by a layer of porous material, e.g., fluid transfer
`medium, which is then covered by a first conductive layer
`which is also porous. This layered structure provides a fluid
`transfer pathway through which biological fluid can travel.
`A second conductive layer is spaced-apart from the first
`45 conductive layer, forming a space, i.e., an electrochemical
`cell, into which biological fluid is transferred to be tested
`and measured for analyte concentration. The resulting lay­
`ered structure may also have a layer, made of insulating
`material, for example, over the second conductive layer for
`isolating the electrochemical cell and for housing the device.
`The micro-needle or under side of the device may itself be
`formed of or coated with an insulating material. In still other
`embodiments, the micro-needles may be additionally or
`alternatively coated with a conductive material, such as a
`metal, to form a set of electro-sensors. The electro-sensors
`may be employed to monitor certain physiological signals or
`events or may themselves be used as reference electrodes of
`an electrochemical cell, as is further described below.
`In all embodiments of the subject invention, the micro­
`protrusions or microneedles are configured to be mechani­
`cally stable and strong enough to penetrate the stratum
`corneum without breaking. Preferably, they are made of a
`biocompatible material so as not to cause irritation to the
`skin or an undesirable tissue response. Although the sensor
`65 devices may be disposable, for those that are intended to be
`reusable, it is preferable that the material of the m1cro­
`needles is able to withstand sterilization cycles.
`
`50
`
`AGAMATRIX, INC. EXHIBIT NO. 1022
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`US 6,837,988 B2
`
`7
`The electrochemical measurement cell of the subject
`invention comprises an electrode configuration and a reac­
`tion chamber or zone. The electrode configuration includes
`two spaced-apart electrodes positioned such that a surface of
`one electrode faces a surface of the other electrode.
`Preferably, the electrodes are substantially planar and par­
`allel to each other. This spaced apart area defines the reaction
`chamber in which the sampled biological fluid is tested for
`the concentration of a target analyte. A redox reagent system
`or material, selected according to the type of analyte being
`targeted for measurement, may be used within the electro­
`chemical cell to facilitate the measurement process.
`At least one of the electrodes of the subject electrochemi­
`cal cell is porous. More specifically, a first or distal electrode
`is porous. Accordingly, the proximal porous portion of the
`fluid transfer medium is positioned such that its proximal
`surface is flush against the outer surface of this first porous
`electrode. This electrode is made of a metalisized porous
`material, such as the type of porous material used for the
`fluid transfer medium. Similar to the function of the fluid
`transfer medium, the porous electrode exerts a capillary
`force on the sampled biological fluid within the fluid transfer
`medium causing the fluid to be drawn or wicked through the
`porous electrode into the reaction chamber, e.g., at least the
`target analyte of interest is wicked through the porous
`electrode into the reaction chamber.
`The second or proximal electrode may be entirely com­
`prised of a solid conductive material or may have a rigid
`porous structure, such as a metalized porous material, in
`which the pores run through the majority of the structure and
`are much smaller than those of the first electrode. In the
`latter configuration, i.e., wherein the second electrode has a
`porous structure, the pore sizes of the second electrode are
`sufficiently small to create a capillary force on fluid in
`contact with it thereby causing the fluid within the reaction
`zone to be drawn or wicked through the second electrode.
`This configuration facilitates the continuous wicking of the
`sampled biological fluid within the electrochemical cell
`thereby purging or displacing air within the cell. The pres­
`ence of air in the cell can interfere with the analyte mea­
`surement. Alternatively, a conventional coplanar electrode
`pair can be used instead of the top electrode. The subject
`device may further provide a layer of insulating material
`over the second electrode for isolating the electrochemical
`cell and for housing the device. With embodiments having
`a porous proximal electrode, as just described, one or more
`vent holes may be formed or made within the housing
`adjacent the electrode.
`Various types of electrochemical systems and methods
`commonly known in the art of analyte detection and mea­
`surement may be employed by the present invention, includ­
`ing systems that are amperometric (i.e., measure current),
`coulometric (i.e., measure electrical charge) or potentiomet­
`ric (i.e., measure voltage). Examples of these types of
`electrochemical measurement systems are further described
`in U.S. Pat. Nos.: 4,224,125; 4,545,382; and 5,266,179; as
`well as WO 97/18465 and WO 99/49307; the disclosures of
`which are herein incorporated by reference.
`In operation, one of the electrodes of the electrochemical
`cell is used as the reference electrode by which an input
`reference signal is provided to the sensor from a signal
`generating means. The other electrode operates as a working
`electrode which provides an output signal from the sensor to
`a signal receiving means. Preferably, the reference electrode
`is located at the bottom, i.e., the first electrode as mentioned
`above, and the working electrode at the top of the device,
`i.e., the second electrode as mentioned above. This output
`
`5
`
`8
`signal represents the concentration of the target analyte in
`the sampled fluid.
`The reference and working electrodes are in electrical
`communication with a control means that sets the input
`reference signal transmitted to the electrochemical cell,
`receives the output signal from the electrochemical cell and
`then derives the concentration level of the analyte within the
`sample from the output signal, e.g., a means for applying an
`electrical current between the two electrodes, measuring a
`10 change in the current over time and relating the observed
`change in current to the concentration of analyte present in
`the electrochemical cell. The concentration of the analyte in
`the patient's blood is then derived from the concentration
`level in the fluid sample, the numerical value of which is
`15 preferably provided as an output signal to a display means.
`Preferably, the control and display means are integrally
`housed within a handheld control unit such as that illustrated
`in FIG. 2. The control unit preferably also provides a means
`of securing or holding one or more micro-needles or an array
`20 of micro-needles in a position and arrangement suitable for
`the particular sampling and measuring application at hand.
`Before the subject invention is described further, it is to be
`understood that the invention is not limited to the particular
`embodiments of the invention described below, as variations
`25 of the particular embodiments may be made and still fall
`within the scope of the appended claims. It is also to be
`understood that the terminology employed is for the purpose
`of describing particular embodiments, and is not intended to
`be limiting. Instead, the scope of the present invention will
`30 be established by the appended claims.
`In this specification and the appended claims, singular
`references include the plural, unless the context clearly
`dictates otherwise. Unless defined otherwise, all technical
`and scientific terms used herein have the same meaning as
`35 commonly understood to one of ordinary skill in the art to
`which this invention belongs.
`Exemplary Embodiment of the Device
`The general configuration of an exemplary sensor device
`of the present invention will now be described with refer-
`40 ence to FIG. 1. There is shown a sensor device 10 having an
`array 16 of micro-needles 12 separated by skin-contact
`surfaces 20. Each micro-needle 12 has a sharp distal tip 1