111111
`
`1111111111111111111111111111111111111111111111111111111111111111111111111111
`us 20060011474Al
`
`(19) United States
`(12) Patent Application Publication
`Schulein et ai.
`
`(10) Pub. No.: US 2006/0011474 Al
`Jan. 19,2006
`(43) Pub. Date:
`
`(54) DEVICE FOR DETECTING AN ANALYTE
`
`(30)
`
`Foreign Application Priority Data
`
`(75)
`
`Inventors: Jurgen Schulein, Spardorf (DE);
`Christine Kugler, Spardorf (DE);
`Burcu Meric, Erlangen (DE); Hans
`Kosak, Bonn (DE); Jorg Hassmann,
`Erlangen (DE); Bjorn Grassl, Nurnberg
`(DE); Dirk Kuhlmeier, Nurnberg (DE)
`
`Correspondence Address:
`KANESAKA BERNER AND PARTNERS LLP
`SUITE 300,1700 DIAGONAL RD
`ALEXANDRIA, VA 22314-2848 (US)
`
`AKTIENGESELL-
`(73) Assignee: NOVEMBER
`SCHAFT, Erlangen (DE)
`
`(21) Appl. No.:
`
`10/518,498
`
`(22) PCT Filed:
`
`Jun. 27, 2003
`
`(86) PCT No.:
`
`PCT /EP03/06818
`
`Jun. 28, 2002
`
`(DE) ..................................... 102 29 210.8
`
`Publication Classification
`
`(51)
`
`Int. CI.
`(2006.01)
`COIN 27/26
`(2006.01)
`COIN 33/487
`(52) U.S. CI. ................ 204/403.01; 205/777.5; 29/592.1
`
`(57)
`ABSTRACT
`The invention relates to a device (17) for detecting an
`analyte in a liquid having a multitude of electrodes (15),
`which are insulated from one another while being arranged
`on a first side (12) of an electrically non-conductive plate
`(10) that is impermeable to the liquid. Said electrodes (15)
`have, at least in part, an analyte-specific coating or analyte(cid:173)
`specific molecules. Electrical conductors that pass through
`the plate (10) can, from a second side (14) of the plate, be
`electrically contacted and individually discharged. The coat(cid:173)
`ing or the molecules has/have a specific affinity to the
`analytes or to a substance formed due to the presence of the
`analyte. In addition, the device has no leakages.
`
`17
`
`16
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 1 of 11
`
`US 2006/0011474 Al
`
`15
`
`Fig.1a.
`
`Fig. 1b
`
`Fig.1c
`
`: : 17
`
`17
`
`5
`
`Fig.1d
`
`Fig.1e
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 2 of 11
`
`US 2006/0011474 Al
`
`17
`
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`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 3 of 11
`
`US 2006/0011474 Al
`
`15
`
`8
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`15
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`
`Fig.3b
`
`Fig.3a
`
`15
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`Fig.3c .
`
`Fig. 3d
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 4 of 11
`
`US 2006/0011474 Al
`
`Fig.4a
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`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 5 of 11
`
`US 2006/0011474 Al
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`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 6 of 11
`
`US 2006/0011474 Al
`
`12
`
`Fig.6a
`
`22
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`Fig.6c
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`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 7 of 11
`
`US 2006/0011474 Al
`
`Fig.7a
`
`Fig.7b
`
`28
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 8 of 11
`
`US 2006/0011474 Al
`
`39
`
`40
`
`41
`
`Fig.8a
`
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`
`Fig.8b
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 9 of 11
`
`US 2006/0011474 Al
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 10 of 11
`
`US 2006/0011474 Al
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`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`Patent Application Publication Jan. 19,2006 Sheet 11 of 11
`
`US 2006/0011474 Al
`
`46
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`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`US 2006/0011474 A1
`
`Jan. 19,2006
`
`1
`
`DEVICE FOR DETECTING AN ANALYTE
`[0001] The invention relates to a device for detecting an
`analyte contained in a liquid and a measuring device. The
`analyte may be present in dissolved or suspended form.
`Furthermore, the invention relates to a method for producing
`and electrically contact-connecting the device. Moreover,
`the invention relates to a use of the device for detecting an
`analyte.
`[0002] DE 197 08 529 C1 discloses a fluid sensor for
`liquid and gaseous organic compounds. The fluid sensor has
`an electrical sensor resistor that is variable in its electrical
`conductivity owing to penetrating fluid. The sensor resistor
`is applied on a nonconductive substrate. It comprises a
`non-conductor through which the relevant fluid can diffuse
`and carbon particles embedded therein. The sensor resistor
`can be contact-connected by means of electrodes which are
`contact-connected through through-holes of the substrate to
`contact areas on the rear side of the substrate. The contact
`areas produce an electrical connection between a plurality of
`the electrodes. The fluid sensor is suitable only for detecting
`organic compounds which alter the conductivity of the
`sensor resistor. It is not suitable for detecting other analytes.
`[0003] Sosnowsky et aI., (1997) Proc. Natl. Acad. Sci
`USA, 94, pages 1119 to 1123, disclose a silicon chip with an
`arrangement of electrodes for detecting a nucleic acid in a
`solution. Capture molecules which specifically bind analytes
`are immobilized on the electrodes by means of an interme(cid:173)
`diate layer. The electrodes are electrically contact-connected
`by lines on the surface of the chip. The lines are insulated by
`a silicon nitride layer. By applying a negative or positive
`potential to the electrodes, charged analytes may be attracted
`to the electrodes with the capture molecules and bind to the
`capture molecules. Unbound or unspecifically bound ana(cid:173)
`lytes can be removed again from the region of the electrodes
`by polarity reversal. The specifically bound analyte is
`detected by means of fluorescence.
`[0004] Furthermore, from the company Motorola a bio(cid:173)
`chip sold under the designation eSensor™ is known, in the
`case of which gold electrodes are arranged on the surface.
`The gold electrodes are laterally contact-connected on the
`surface of the biochip. Capture molecules are immobilized
`at the electrodes by means of an intermediate layer. An
`analyte bound to an electrode by means of the capture
`molecules is detected by means of reporter molecules which
`bind to the bound analyte and have electrochemically detect(cid:173)
`able markers. The binding of said reporter molecules is
`detected electrochemically.
`[0005] EP 0 136 362 B1 discloses a biosensor for mea(cid:173)
`suring the substrate concentration of a liquid sample. The
`biosensor comprises an insulating substrate plate provided
`with an electrode system having at least one working
`electrode and a counterelectrode. The electrode system is
`covered by a porous substrate that contains an oxidoreduc(cid:173)
`tase, can take up liquid and contains an enzyme capable of
`inducing a substrate reaction that can be detected electro(cid:173)
`chemically by means of the electrode system. The sensor
`furthermore has an electron acceptor. Both the oxidoreduc(cid:173)
`tase and the electron acceptor are soluble in the liquid
`sample. DE 36 87 646 T3 relates to a biosensor having an
`electrode system such as is known from EP 0 13.6 362 B1,
`the electrode system principally comprising carbon and the
`surface of at least the measuring electrode being covered
`with albumin or glucose oxidase by adsorption.
`
`[0006] What is disadvantageous about the biosensors
`known from EP 0 136 362 B1 and DE 36 87 646 T3 is that
`the porous substrate has to be exchanged after each mea(cid:173)
`surement and that the biosensor is not suitable for measuring
`concentrations of analytes that are not a substrate of the
`oxidoreductase. Furthermore, it is disadvantageous that the
`biosensor is not suitable for measuring many different
`analytes on a miniaturized substrate plate.
`
`[0007] DE 196 21 241 A1 relates to a membrane electrode
`for measuring the glucose concentration in liquids. Said
`membrane electrode comprises a basic membrane with at
`least one noble metal electrode arranged on one side of the
`basic membrane, a proton-selective ion membrane arranged
`on the basic membrane and the noble metal electrode and a
`double membrane arranged on the ion membrane, which
`contains glucose oxidase in a suitable medium. The mem(cid:173)
`brane electrode is suitable exclusively for measuring glucose
`concentrations and not for detecting other analytes in a
`liquid.
`
`[0008] A biosensor chip is disclosed in WO 01/75151 A2
`and DE 100 15 816 A1, on which the priority of the former
`is based. The sensor has electrodes embedded in an insulator
`layer made of insulator material. DNA probe molecules are
`immobilized on each electrode. The sensors are part of a
`silicon-based biosensor chip. Connected to the electrodes
`are electrode terminals at which the electrical potential that
`is to be applied to the electrode can be fed in. The electrode
`terminals are connected up to an integrated electrical circuit
`within the chip. What is disadvantageous in this case is that
`the production of the biosensor chip is too expensive to
`enable it to be used as only a single-use sensor chip. In the
`case of analytes that attack or alter the probe molecules, this
`may be necessary, however, for reproducible measurements.
`
`[0009] EP 0 690 134 A1 discloses a multiple-use electro(cid:173)
`chemical solid-state sensor having an electrically noncon(cid:173)
`ductive substrate, a working electrode and a semipermeable
`membrane covering the working electrode. The working
`electrode contains an electrically conductive material fixed
`to a part of the substrate. A first part of the conductive
`material is covered with an electrically insulating dielectric
`coating and a second part of the conductive material is
`covered with an active layer. The active layer comprises a
`catalytically effective quantity of an enzyme carried by
`platinized carbon powder particles distributed within the
`active layer. The electrochemical solid-state sensor is com(cid:173)
`paratively complex in its construction and therefore expen(cid:173)
`sive to produce.
`
`[0010] U.S. Pat. No. 5,363,690 discloses a gas detector
`containing an exchangeable electrochemical sensor device.
`The electrical contact between the exchangeable sensor
`device and an evaluation unit for measurement signals is
`produced by means of an elastomeric connector. The device
`is not suitable for detecting an analyte in a liquid.
`
`[0011] WO 01/13103 A1 discloses electrodes having a
`surface coating made of an oxidized phenol compound, a
`surface-active agent being integrated into the coating. Said
`agent can prevent the detection of specific detergent-sensi(cid:173)
`tive analytes. Therefore, the electrode can only be used for
`detecting specific analytes.
`
`[0012] EP 0 402 917 A2 discloses a biosensor containing
`at least two spaced-apart electrical lines on an electrically
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`US 2006/0011474 A1
`
`Jan. 19,2006
`
`2
`
`nonconductive carrier. An electrically conductive organic
`polymerized layer made of a surface-active substance is in
`electrical contact with the electrical lines and covers the
`surface between the lines. Furthermore, a sealing coating is
`fitted in order to protect the electrical contacts against
`contact with water. A layer made of organic molecules to
`which complementary molecules from an aqueous medium
`can bind is bound to the polymerized layer made of the
`surface-active substance.
`
`[0013] EP 0 987 333 A2 discloses a composition for an
`electrical thick-film conductor for use in electrochemical
`sensors, which contains conductive metal particles, graphite,
`a thermoplastic polymer and a surface-active substance. The
`compound can be used for printing working electrodes for
`electrochemical biosensors. Owing to the sensitivity of
`specific analytes with respect to surface-active substances,
`however, such sensors are only suitable for detecting spe(cid:173)
`cific analytes.
`
`[0014] The electrodes or electrode arrangements men(cid:173)
`tioned are complex to produce. Their production requires in
`part lithographic techniques. Their production is too expen(cid:173)
`sive to enable them to be used as only single-use electrodes
`or electrode arrangements. In the case of high electrode
`densities, it is necessary to provide the outgoing lines of the
`electrodes in a plurality of layers, in the so-called multilayer
`technique. Therefore, high electrode densities are only pos(cid:173)
`sible with considerable production complexity. In order to
`prevent contact of the electrical lines to the electrodes with
`a solution containing the analyte, a protective layer has to be
`applied to the lines. Furthermore, for specific applications,
`e.g. as the bottom of a microfiuid chamber, it is necessary for
`the biochip to have a smooth surface. Therefore, a compen(cid:173)
`sating layer has to be applied in order to compensate for the
`unevennesses caused by the lines.
`
`[0015]
`It is an object of the invention to avoid the disad(cid:173)
`vantages according to the prior art. In particular, the inten(cid:173)
`tion is to provide a device with electrodes for detecting an
`analyte which is simple and thus cost-effective to produce.
`
`[0016] This object is achieved by means of the features of
`claims 1, 18 to 22, 35 and 38. Expedient refinements emerge
`from the features of claims 2 to 17, 23 to 34, 36, 37 and 39
`to 51.
`
`[0017] The invention provides a device for detecting an
`analyte in a liquid having a multiplicity of electrodes that are
`insulated from one another and are arranged on a first side
`of an electrically nonconductive plate that is impermeable to
`the liquid, the electrodes, at least in part, having an analyte(cid:173)
`specific coating or analyte-specific molecules and being able
`to be electrically contact-connected and individually con(cid:173)
`ducted out from a second side of the plate by means of
`electrical conductors extending through the plate. The coat(cid:173)
`ing or the molecules is/are analyte-specific by virtue of
`having a specific affinity for the analyte or a substance, e.g.
`a decomposition product of the analyte, formed owing to the
`presence of the analyte. The device has not outgoing lines.
`The electrical conductors can be connected to the plate and
`the electrodes. The term "electrode" is understood in purely
`functional fashion. It is understood to mean the part of an
`electrical conductor through which electrical charge carriers
`can be conducted into the liquid. Consequently, the electrode
`may be the part of the electrical conductor which is situated
`on the first side of the electrically nonconductive plate.
`
`However, the electrode may also be a further electrical
`conductor connected to the electrical conductor extending
`through the plate. In this case, plate is understood to mean
`an arbitrary, in particular fiat basic body having a first and
`a second side. Here and hereinafter "in part" means that both
`a part of an individual electrode and a portion of the
`electrodes present altogether may have the respective fea(cid:173)
`ture.
`
`[0018] The device according to the invention is simple and
`thus cost-effective to produce. It is not necessary to apply a
`protective layer in order to prevent contact between the
`liquid and electrode feed lines. Furthermore, it is not nec(cid:173)
`essary to apply a compensating layer in order to produce a
`planar surface of the plate. By virtue of the lateral outgoing
`lines being obviated, it is possible in a very cost-effective
`manner to shape the device in completely plane fashion in
`the region outside the electrodes. As a result, the device can
`readily be used as the bottom of a chamber that takes up
`liquid without a liquid tight seal being problematic in this
`case. A further advantage of the device according to the
`invention is that a higher electrode density than with elec(cid:173)
`trodes that are conducted out laterally is possible because it
`is not necessary to leave space free for the lines between the
`electrodes. The higher electrode density can be provided
`without a complex multilayer technique. By means of a
`device according to the invention having a high electrode
`density and analyte-specific coatings or analyte-specific
`molecules having, at least in part, different specificity and
`electrodes that can be individually conducted out, it is
`possible to provide a device for simultaneous detection of
`many different analytes. The device according to the inven(cid:173)
`tion may be provided as an electrode array, in which the
`electrodes are in each case provided with specific molecules
`or coatings, for detecting different analytes or analyte com(cid:173)
`binations.
`
`[0019] The general trend in the development of biosensor
`chips is toward realizing ever more complex chip structures.
`However, these are complex to produce and ultimately too
`expensive for a routine sensor technology, in particular for
`different analytes. Known chips produced in silicon-based
`fashion do not have any electrical conductors that extend
`through the chip such that electrodes present on one side on
`the chip could be conducted out from the other side. Rather,
`at least a part of the silicon carrier is unperforated and
`electrodes present are ultimately conducted out laterally.
`Dispensing with any outgoing line whilst at the same time
`enabling contact-connection from the second side of the
`plate permits such a simple construction of the device
`according to the invention that this device can be produced
`cost-effectively in such a way that it is suitable for single
`use. Measurements in which the electrodes, their analyte(cid:173)
`specific coatings or the analyte-specific molecules are
`attacked can be carried out reproducibly only with a device
`for single use. The device according to the invention can be
`produced in the form of a chip for a fraction of the costs
`required for producing a silicon-based chip. The device may
`thus contribute to a breakthrough in routine sensor technol(cid:173)
`ogy. The device according to the invention can be used in an
`apparatus provided for contact-connecting the device. All
`components which are required for conducting out and
`measuring a signal and are not provided by the device
`according to the invention are provided by the apparatus in
`this case. More expensive components can thus be reused.
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`US 2006/0011474 A1
`
`Jan. 19,2006
`
`3
`
`[0020] A further advantage of the invention is that the
`contact-connection from the second side of the plate enables
`short line paths. As a result, it is possible to avoid an
`electrical noise caused by the comparatively long line paths
`in the case where the electrodes are conducted out laterally.
`The electrical noise reduces the sensitivity of the detection
`and may thereby even prevent the detection of the analyte.
`In an advantageous refinement, the electrical conductors are
`formed in one piece together with the electrodes. The
`electrodes and the conductors may comprise the same mate(cid:173)
`rial. This enables good contact-connectability from the sec(cid:173)
`ond side and very cost-effective production. It is not neces(cid:173)
`sary to produce an electrical contact between the electrodes
`and the electrical conductors of the first side of the plate.
`
`[0021] The coating or the analyte-specific molecules at the
`electrodes may in each case be different, so that different
`electrodes thereby differ from one another. As a result, the
`analyte-specific coatings or analyte-specific molecules may
`have a different specificity and enable an, in particular
`simultaneous, detection of different analytes. In this case, a
`detectable analyte is a member of a group that is prescribed
`by the specificity of the different coatings or molecules.
`
`[0022] The coating or the analyte-specific molecules may
`comprise, in particular electrochemically inert, capture mol(cid:173)
`ecules. In this case, capture molecules are molecules to
`which the analyte or a substance formed owing to the
`presence of the analyte, e.g. a decomposition product of the
`analyte, binds from the liquid. The capture molecules are
`electrochemically inert if they do not cause a signal in the
`event of an electrochemical detection of the analyte. The
`capture molecules may be, in particular single-stranded,
`nucleic acids, nucleic acid analogs, ligands, haptens, pep(cid:173)
`tides, proteins, sugars, lipids or ion exchangers. The capture
`molecules may be covalently and/or directionally bound to
`the electrodes. The advantage of the covalent bond is that the
`capture molecules cannot diffuse away from the electrodes.
`In the case of the very small distances between the elec(cid:173)
`trodes that are possible with the device according to the
`invention, even capture molecules diffusing away to a small
`extent may lead to disruption of a detection reaction. A
`directional bond is to be understood to mean that the capture
`molecules are bound to the electrodes in each case by a
`specific site of the capture molecule, e.g. by one end of the
`molecule. It can thereby be ensured that the site of the
`capture molecules which is responsible for binding the
`analyte is not influenced by the binding of said capture
`molecules to the electrodes. The capture molecules, at least
`in part, may be bound to the electrodes by means of an, in
`particular electrochemically largely inert, intermediate layer.
`Said intermediate layer may be formed from silane. The
`intermediate layer is electrochemically largely inert if it does
`not cause a signal in the event of an electrochemical detec(cid:173)
`tion of the analyte.
`
`In a preferred refinement, the coating comprises at
`[0023]
`least one semipermeable covering of the electrodes. The
`semipermeable coverings may in each case have a different
`permeability, so that the coverings of different electrodes
`may differ in their permeability. The coverings may be
`selectively permeable for molecules up to a specific size. A
`polymeric matrix with a molecular sieve action may be
`involved in this case. As a result, it is possible to permit only
`small molecules, arising e.g. from a specific decomposition
`of an analyte, to penetrate through to the electrodes, so that
`
`specifically only these molecules are detected. Such a device
`according to the invention can be used in a process control
`for tracking reactions taking place in a reactor.
`
`[0024] The electrical conductors may be arranged in per(cid:173)
`forations of the plate which taper from the second side of the
`plate, in particular conically, toward the first side. In this
`case, the electrical conductor may be arranged only at the
`tapered section of the cut-out formed by the tapering form of
`the perforation. However, it can also project freely into the
`cut-out. The tapering form of the cut-out facilitates the
`electrical contact-connection from the second side because a
`conductor led in the direction of the electrode for the
`purpose of contact-connection is led up to the electrode even
`when it initially only impinges into the cut-out.
`
`[0025] The plate may be arranged on the bottom of a
`microfluid chamber or form the bottom of a micro fluid
`chamber. The device according to the invention is well
`suited to this owing to the possibility of the particularly
`planar embodiment and the associated good sealing capa(cid:173)
`bility.
`
`[0026] The device may also be a chip. This is understood
`here to mean a small plate with electronic microstructures
`that does not necessarily comprise semiconductor material.
`In this case, the electrodes may be arranged in the form of
`an electrode array.
`
`[0027] The plate may have more than 10, preferably more
`than 20, 40, 80, 100 or 160, particularly preferably more
`than 1000, especially more than 10,000 electrodes per cm2
`.
`The electrodes, at least in part, may be formed from par(cid:173)
`ticles. The particles may be provided with analyte-specific
`coating or contain analyte-specific molecules. In this case,
`the particles may be loosely or fixedly connected among one
`another. A loose connection may be provided e.g. by the
`particles being paramagnetic and being held by magnetic
`force at the electrode or the electrical conductor.
`
`[0028] Furthermore, the electrodes, at least in part, may be
`formed from a non-metallic conductor, in particular carbon.
`Carbon-containing electrodes are particularly well suited to
`the detection of biomolecules. The electrodes, at least in
`part, may be pencil, glassy carbon, carbon fiber containing,
`carbon paste or plastic composite electrodes, preferably
`polycarbonate electrodes containing elementary carbon, in
`particular in the form of graphite or carbon black. The
`carbon black may be industrial carbon black or synthetic
`carbon black.
`
`[0029] The invention furthermore relates to a measuring
`device, comprising a device according to the invention, in
`which the electrodes comprise at least one reference elec(cid:173)
`trode and at least one counterelectrode and also a multiplic(cid:173)
`ity of working electrodes. The measuring device contains
`current/voltage converters, a potentiostat and a means for
`measuring the currents flowing through the working elec(cid:173)
`trodes. The electrodes are electrically connected to the
`potentiostat for generating a predetermined voltage profile
`between the working electrodes and the reference electrode,
`one of the current/voltage converters being connected down(cid:173)
`stream of each of the working electrodes in order to hold all
`the working electrodes at the same potential. In this case,
`only a single potentiostat is required for generating an
`identical predetermined voltage profile that is applied simul(cid:173)
`taneously to all the working electrodes. By virtue of all the
`
`Exhibit 1031
`Abbott Diabetes Care Inc. v. Dexcom Inc.
`IPR2022-00917, -00918
`
`

`

`US 2006/0011474 A1
`
`Jan. 19,2006
`
`4
`
`working electrodes being held at the same potential, it is
`possible, for example, for the currents flowing through the
`working electrodes to be measured in parallel. For this
`purpose, each of the working electrodes may be virtually
`connected to the circuit ground by means of a current
`follower for individual evaluation of the signals.
`
`[0030] The invention furthermore relates to a method for
`producing a device according to the invention having the
`following steps of:
`
`[0031] a) producing a composite of elongate electrode
`material that is essentially arranged parallel and insulating
`material surrounding the electrode material, the compos(cid:173)
`ite being produced by means of
`
`[0032] encapsulating a solid electrode material with a
`curing insulating material,
`
`[0033]
`introducing a solid electrode material into essen(cid:173)
`tially parallel cut-outs or perforations of a solid insu(cid:173)
`lating material or into a plastically deformable insulat(cid:173)
`ing material,
`
`[0034]
`filling pasty or liquid curing electrode material
`into essentially parallel cut-outs or perforations of a
`solid one-piece insulating material or of a stacked
`plate-type
`insulating material with
`congruently
`arranged perforations,
`
`[0035] connecting electrode material, having a sheath(cid:173)
`ing comprising insulating material, by melting, potting
`or adhesively bonding the sheathing, or
`
`[0036] extruding a composite made of electrode mate(cid:173)
`rial surrounded by insulating material, and
`
`[0037] b) separating the composite essentially perpendicu(cid:173)
`larly to the longitudinal direction of the electrode material
`by cutting, sawing or by means of a separating disk or by
`taking apart the stacked plate-type insulating material.
`
`[0038] The solid electrode material may be, for example,
`a plurality of pencil leads which are arranged parallel and are
`encapsulated with epoxy resin. The plastically deformable
`insulating material may adapt itself to the form of the
`electrode material in the course of introduction and/or be
`adapted thereto after introduction by pressing them together.
`A liquidtight termination is thereby ensured. Here and
`herinafter "curing" of the electrode material is understood to
`mean that the originally liquid or pasty electrode material
`solidifies over time, i.e. its hardness increases. This may be
`effected e.g. by polymerization, by drying or by cooling of
`an electrode material that is pasty at a higher temperature.
`However, the final state of the electrode material after
`solidification can still be comparatively soft.
`
`[0039] The solid one-piece insulating material may be
`produced by means of an injection molding method. When
`filling the electrode material into the stacked plate-type
`insulating material, the perforations are arranged such that
`electrode material that is filled in on one side of the stacked
`insulating material fills all perforations. The electrode mate(cid:173)
`rial can be pressed into the perforations e.g. by extrusion.
`The method used for this purpose may be a method known
`from the production of pencil leads.
`
`[0041] When producing the composite by means of
`extruding the composite made from electrode material sur(cid:173)
`rounded by insulating material, both the conductive elec(cid:173)
`trode material and the insulating material are plastically
`deformable such that both materials can be extruded jointly
`as a composite. This enables a very cost-effective produc(cid:173)
`tion.
`
`[0042] Furthermore, the invention relates to a method for
`producing a device according to the invention having the
`following steps of:
`
`[0043] a) providing an electrically nonconductive plate
`with perforations,
`
`[0044] b) applying a pasty curing electrode material to a
`first side of the plate,
`
`[0045] c) pressing the electrode material into the perfora(cid:173)
`tions, and
`[0046] d) removing the electrode material present between
`the perforations in so far as said electrode material
`electrically conductively connects the electrode material
`present in the perforations.
`[0047] The curing may be effected e.g. by polymerization,
`by drying or by cooling. Step ref. c may be carried out at the
`same time as the application in accordance with step ref. b
`or afterward. The method may be carried out in the manner
`of a screen printing method, the electrode material being
`applied instead of the ink.
`
`[0048] The invention additionally relates to a method for
`producing a device according to the invention having the
`following steps of:
`[0049] a) providing an electrically nonconductive plate
`with perforations,
`[0050] b) placing an aperture mask having holes that
`correspond to the perforations, at least in part, or a screen
`printing mask having permeable areas that correspond to
`the perforations, at least in part, onto the first side of the
`plate such that the holes or the areas are congruent, at least
`in part, with the perforations of the plate,
`[0051 ] c) applying a pasty curing electrode material to the
`aperture mask or screen printing mask,
`[0052] d) pressing the electrode material into the perfora(cid:173)
`tions by way of the holes or permeable areas, and
`[0053] e) removing the aperture mask or screen printing
`mask from the plate.
`[0054] The method has the advantage that, through step
`ref. e, the removal of excess electrode material is signifi(cid:173)
`cantly simplified and it enables a larger electrode surface
`because the electrodes are elevated on the first side of the
`plate due to the height of the aperture mask or screen
`printing mask. By virtue of the fact that, in the case o