(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2006/0183984 A1
`(43) Pub. Date:
`Aug. 17, 2006
`Dobbles et al.
`
`US 2006O183984A1
`
`ANALYTE SENSOR
`
`Inventors: J. Michael Dobbles, San Diego, CA
`(US); Mark Brister, Encinitas, CA
`(US)
`Correspondence Address:
`KNOBBE MARTENS OLSON & BEAR LLP
`2O4O MAN STREET
`FOURTEENTH FLOOR
`IRVINE, CA 92614 (US)
`Appl. No.:
`11/360,252
`
`Filed:
`
`Feb. 22, 2006
`
`(60) Provisional application No. 60/587,787, filed on Jul.
`13, 2004. Provisional application No. 60/587,800,
`filed on Jul. 13, 2004. Provisional application No.
`60/614,683, filed on Sep. 30, 2004. Provisional appli
`cation No. 60/614,764, filed on Sep. 30, 2004.
`
`Publication Classification
`
`(51) Int. Cl.
`(2006.01)
`A6IB 5/00
`(52) U.S. Cl. .............................................................. 600/316
`
`(57)
`
`ABSTRACT
`
`Related U.S. Application Data
`Continuation-in-part of application No. 11/157.746,
`filed on Jun. 21, 2005.
`
`The present invention relates generally to systems and
`methods for measuring an analyte in a host. More particu
`larly, the present invention relates to systems and methods
`for transcutaneous measurement of glucose in a host.
`
`(54)
`(76)
`
`(21)
`(22)
`
`(63)
`
`
`
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`Patent Application Publication Aug. 17, 2006 Sheet 8 of 50
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`US 2006/0183984 A1
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`Page 12 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 19 of 50
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`Page 21 of 117
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`Page 22 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 25 of 50
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`US 2006/0183984 A1
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`Page 26 of 117
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`Page 27 of 117
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`Page 28 of 117
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`Page 29 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 29 of 50
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`US 2006/0183984 A1
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`INITIAL CALIBRATION
`
`2/72
`
`RECEIVE SENSOR DATA FROM
`CONTINUOUSANALYTE SENSOR
`
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`RECEIVE REFERENCE DATA FROM
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`CONVERSION FUNCTION
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`PROVIDE OUTPUT TO USER
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`FIG. 18A
`
`Page 30 of 117
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`
`Page 31 of 117
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`Page 32 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 32 of 50
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`US 2006/0183984 A1
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`Page 33 of 117
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`Page 34 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 34 of 50
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`US 2006/0183984 A1
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`EVALUATEACCEPTABILITY OF
`REFERENCE AND SENSOR DATA
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`202
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`RECEIVE REFERENCE DATA FROM
`REFERENCE ANALYTE SOURCE
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`Page 35 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 36 of 50
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`US 2006/0183984 A1
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`RECEIVE NEW SENSOR DATA FROM
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`Page 37 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 37 of 50
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`US 2006/0183984 A1
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`SELF-DLAGNOSTIC OF SENSOR
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`Page 38 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 38 of 50
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`Patent Application Publication Aug. 17, 2006 Sheet 41 of 50
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`US 2006/0183984 A1
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`N300
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`WITH DSPOSABLE AND SINGLE-USE PARTS
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`Page 42 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 48 of 50
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`Page 49 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 49 of 50
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`US 2006/0183984 A1
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`Page 50 of 117
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`Patent Application Publication Aug. 17, 2006 Sheet 50 of 50
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`Page 51 of 117
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`US 2006/0183984 A1
`
`Aug. 17, 2006
`
`ANALYTE SENSOR
`
`RELATED APPLICATIONS
`0001. This application is a continuation-in-part of U.S.
`application Ser. No. 11/157,746 filed Jun. 21, 2005, which
`claims priority under 35 U.S.C. S 119(e) to U.S. Provisional
`Application No. 60/587,787 filed Jul. 13, 2004; U.S. Pro
`visional Application No. 60/587,800 filed Jul. 13, 2004; U.S.
`Provisional Application No. 60/614,683 filed Sep. 30, 2004;
`and U.S. Provisional Application No. 60/614,764 filed Sep.
`30, 2004, each of which is incorporated by reference herein
`in its entirety, and each of which is hereby made a part of this
`specification.
`
`FIELD OF THE INVENTION
`0002 The present invention relates generally to systems
`and methods for measuring an analyte in a host. More
`particularly, the present invention relates to Systems and
`methods for transcutaneous measurement of glucose in a
`host.
`
`BACKGROUND OF THE INVENTION
`0003 Diabetes mellitus is a disorder in which the pan
`creas cannot create Sufficient insulin (Type I or insulin
`dependent) and/or in which insulin is not effective (Type 2
`or non-insulin dependent). In the diabetic state, the victim
`Suffers from high blood Sugar, which can cause an array of
`physiological derangements associated with the deteriora
`tion of small blood vessels, for example, kidney failure, skin
`ulcers, or bleeding into the vitreous of the eye. A hypogly
`cemic reaction (low blood Sugar) can be induced by an
`inadvertent overdose of insulin, or after a normal dose of
`insulin or glucose-lowering agent accompanied by extraor
`dinary exercise or insufficient food intake.
`0004 Conventionally, a person with diabetes carries a
`self-monitoring blood glucose (SMBG) monitor, which typi
`cally requires uncomfortable finger pricking methods. Due
`to the lack of comfort and convenience, a person with
`diabetes normally only measures his or her glucose levels
`two to four times per day. Unfortunately, such time intervals
`are so far spread apart that the person with diabetes likely
`finds out too late of a hyperglycemic or hypoglycemic
`condition, sometimes incurring dangerous side effects. It is
`not only unlikely that a person with diabetes will take a
`timely SMBG value, it is also likely that he or she will not
`know if his or her blood glucose value is going up (higher)
`or down (lower) based on conventional method. This inhib
`its the ability to make educated insulin therapy decisions.
`0005) A variety of sensors are known that use an elec
`trochemical cell to provide output signals by which the
`presence or absence of an analyte, such as glucose, in a
`sample can be determined. For example, in an electrochemi
`cal cell, an analyte (or a species derived from it) that is
`electro-active generates a detectable signal at an electrode,
`and this signal can be used to detect or measure the presence
`and/or amount within a biological sample. In some conven
`tional sensors, an enzyme is provided that reacts with the
`analyte to be measured, and the byproduct of the reaction is
`qualified or quantified at the electrode. An enzyme has the
`advantage that it can be very specific to an analyte and also,
`when the analyte itself is not sufficiently electro-active, can
`be used to interact with the analyte to generate another
`
`species which is electro-active and to which the sensor can
`produce a desired output. In one conventional amperometric
`glucose oxidase-based glucose sensor, immobilized glucose
`oxidase catalyses the oxidation of glucose to form hydrogen
`peroxide, which is then quantified by amperometric mea
`Surement (for example, change in electrical current) through
`a polarized electrode.
`
`SUMMARY OF THE INVENTION
`In a first aspect, a sensor for transcutaneous mea
`0006.
`Surement of an analyte in a host is provided, the sensor
`comprising at least one electrode formed from a conductive
`material; and a membrane disposed on an electroactive
`portion of the electrode, wherein the membrane is config
`ured to control an influx of the analyte therethrough, and
`wherein the membrane comprises a Substantially non
`Smooth outer Surface.
`0007. In an embodiment of the first aspect, the substan
`tially non-Smooth Surface appears under magnification to
`resemble a Super-positioning of disc shaped objects.
`0008. In an embodiment of the first aspect, the disc
`shaped objects comprise a rounded shape.
`0009. In an embodiment of the first aspect, the disc
`shaped objects have an average diameter of from about 5
`microns to about 250 microns.
`0010. In an embodiment of the first aspect, the membrane
`further comprises an enzyme domain.
`0011. In an embodiment of the first aspect, the membrane
`further comprises an interference domain.
`0012. In an embodiment of the first aspect, the membrane
`further comprises an electrode domain.
`0013 In an embodiment of the first aspect, the membrane
`is at least partially formed by a vapor deposition coating
`process.
`0014. In an embodiment of the first aspect, the vapor
`deposition coating process comprises a physical vapor depo
`sition coating process, e.g., ultrasonic vapor deposition.
`0015. In an embodiment of the first aspect, the membrane
`substantially resists ascorbate flux therethrough.
`0016.
`In an embodiment of the first aspect, the electrode
`comprises a wire comprising a conductive material, and
`wherein the sensor is configured for Substantially continuous
`measurement of glucose in a host.
`0017. In a second aspect, a method for manufacturing a
`transcutaneous analyte sensor is provided, the method com
`prising the steps of providing at least one electrode com
`prising an electroactive portion; and applying a membrane to
`the electroactive port ion, wherein at least one layer of the
`membrane is applied by vapor deposition.
`0018. In an embodiment of the second aspect, the vapor
`deposition comprises physical vapor deposition.
`0019. In an embodiment of the second aspect, the physi
`cal vapor deposition comprises ultrasonic vapor deposition.
`0020. In an embodiment of the second aspect, the layer of
`the membrane is deposited in a vacuum chamber. The layer
`can be configured to resist flow of the analyte therethrough.
`
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`0021. In an embodiment of the second aspect, at least one
`layer of the membrane is applied using an ultrasonic nozzle.
`The layer can be configured to resist flow of the analyte
`therethrough.
`0022. In an embodiment of the second aspect, the step of
`applying a membrane comprises applying an enzyme
`domain. The enzyme domain can be applied by dip coating.
`0023. In an embodiment of the second aspect, the step of
`applying a membrane comprises applying an electrode
`domain. The electrode domain can be applied by dip coating.
`0024. In an embodiment of the second aspect, the elec
`trode comprises a wire comprising a conductive material,
`and wherein the sensor is configured for Substantially con
`tinuous measurement of glucose in a host.
`0025. In a third aspect, a method for manufacturing a
`plurality of transcutaneous analyte sensors is provided, the
`method comprising providing a plurality of electrodes, each
`electrode comprising an electroactive portion; placing the
`plurality of electrodes into a vacuum chamber, and vapor
`depositing at least one membrane layer thereon.
`0026.
`In an embodiment of the third aspect, the mem
`brane layer is configured to control influx of an analyte
`therethrough.
`0027. In an embodiment of the third aspect, wherein an in
`vitro sensitivity of the plurality of sensors deviates from a
`median in vitro sensitivity by less about 20%.
`0028. In an embodiment of the third aspect, an in vitro
`sensitivity of the plurality of sensors deviates from a median
`in vitro sensitivity by less about 16%.
`0029. In an embodiment of the third aspect, an in vitro
`sensitivity of the plurality of sensors deviates from a median
`in vitro sensitivity by less about 12%.
`0030. In an embodiment of the third aspect, the method
`further comprises curing the membrane layer. The curing
`step can include placing a plurality of electrodes, each
`comprising the membrane layer, into a vacuum oven, a
`convection oven, or a variable frequency microwave oven.
`0031. In an embodiment of the third aspect, each elec
`trode comprises a wire comprising a conductive material,
`and wherein each sensor is configured for Substantially
`continuous measurement of glucose in a host.
`0032. In a fourth aspect, a method for limiting use of an
`analyte sensor to a predetermined time period is provided,
`the method comprising providing a key associated with an
`analyte sensor, wherein the key is configured to control an
`amount of time over which information is obtained from the
`analyte sensor.
`0033. In an embodiment of the fourth aspect, the analyte
`sensor is a transcutaneous glucose sensor.
`0034. In an embodiment of the fourth aspect, the sensor
`is operatively connected to a receiver, wherein the receiver
`is configured to display sensor data.
`0035) In an embodiment of the fourth aspect, the receiver
`is configured to receive the key.
`0036). In an embodiment of the fourth aspect, the receiver
`is configured to control an amount of time over which
`information is displayed on the receiver from the sensor in
`response to the key.
`
`0037. In an embodiment of the fourth aspect, the key is
`a software key.
`0038. In an embodiment of the fourth aspect, the key is
`a unique code.
`0039. In an embodiment of the fourth aspect, the key is
`selected from the group consisting of a unique number, a
`receiver ID, a sensor duration, a number of sensor Systems,
`and combinations thereof.
`0040. In an embodiment of the fourth aspect, the key is
`configured for use with a plurality of sensors.
`0041. In an embodiment of the fourth aspect, the key is
`provided by an information tag.
`0042. In a fifth aspect, a method for distributing and
`controlling use of implantable sensor Systems comprising
`reusable and disposable parts, the method comprising pro
`viding a single-use device associated with the sensor System,
`wherein the single-use device is configured to be inserted
`into a host's tissue; providing a key associated with the
`single-use device; and providing a reusable device associ
`ated with a sensor system, wherein the reusable device is
`configured to provide sensor information responsive to
`receipt of the key.
`0043. In an embodiment of the fifth aspect, the reusable
`device comprises a receiver configured to receive sensor
`information.
`0044) In an embodiment of the fifth aspect, the reusable
`device further comprises an electronics unit configured to
`releasably mate with the single-use device.
`0045. In an embodiment of the fifth aspect, the method
`further comprises obtaining a package containing a plurality
`of single-use devices.
`0046.
`In an embodiment of the fifth aspect, the single-use
`device is a transcutaneous analyte sensor configured for
`insertion into a subcutaneous tissue of a host.
`0047. In an embodiment of the fifth aspect, the key
`comprises a written license code packaged with the single
`use device.
`0048. In an embodiment of the fifth aspect, the step of
`providing the key comprises providing a license code via at
`least one communication selected from the group consisting
`of written communication, Voice communication, and elec
`tronic communication.
`0049. In an embodiment of the fifth aspect, the reusable
`device is configured to receive the key via manual entry.
`0050. In an embodiment of the fifth aspect, the reusable
`device is configured to wirelessly receive the key.
`0051. In an embodiment of the fifth aspect, key com
`prises sensor duration information configured to enable the
`sensor system to control an amount of time over which
`information is obtained from the single-use device or is
`displayed by the reusable device.
`0052. In an embodiment of the fifth aspect, the single-use
`device comprises a transcutaneous analyte sensor configured
`for insertion in a Subcutaneous tissue of a host, and wherein
`the key comprises sensor insertion information configured to
`enable the sensor System to control a number of sensor
`insertions.
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`0053. In an embodiment of the fifth aspect, the single-use
`device comprises a transcutaneous analyte sensor configured
`for insertion in a Subcutaneous tissue of a host, and wherein
`the step of inserting the single-use device into a host
`comprises using an applicator to insert the sensor into the
`host.
`0054. In an embodiment of the fifth aspect, the step of
`obtaining sensor information from the sensor System com
`prises at least one step selected from the group consisting of
`measurement of analyte information, digitalizing of sensor
`information, transmission of sensor information, receiving
`of sensor information, storing of sensor information, pro
`cessing of sensor information, and displaying of sensor
`information.
`0055. In a sixth aspect, a method for limiting use of a
`glucose sensor system to a predetermined time period is
`provided, the method comprising inputting a key into a
`receiver, wherein the key is configured to control an amount
`of time over which information is obtained from a sensor
`system, after which time the sensor system is disabled Such
`that glucose information cannot be obtained, wherein the
`sensor system is a transcutaneous glucose sensor System
`comprising a sensor configured for insertion into a tissue of
`a host and an electronics unit operatively connected to the
`sensor and configured to provide a signal representative of
`a glucose concentration in the host, and wherein the receiver
`is configured to receive the signal representative of a glucose
`concentration in the host and to display corresponding
`glucose information; and obtaining glucose information
`from the sensor.
`0056.
`In an embodiment of the sixth aspect, the step of
`inputting the key into the receiver is performed before the
`step of obtaining glucose information from the sensor.
`0057. In a seventh aspect, a device for measuring an
`analyte in a host is provided, the device comprising a sensor
`operably connected to sensor electronics, the sensor elec
`tronics configured for measuring an analyte in a host; at least
`one electrical contact configured to connect the sensor to the
`sensor electronics; and a sealing member, wherein the
`sealing member at least partially Surrounds at least one of the
`sensor and the electrical contact, wherein the sealing mem
`ber comprises a material having a durometer hardness of
`from about 5 Shore A to about 80 Shore A.
`0.058. In an embodiment of the seventh aspect, the
`durometer hardness is from about 10 Shore A to about 50
`Shore A.
`0059. In an embodiment of the seventh aspect, the
`durometer hardness is about 20 Shore A.
`0060. In an embodiment of the seventh aspect, the
`durometer hardness is about 50 Shore A
`0061. In an embodiment of the seventh aspect, the sensor
`comprises a wire.
`0062. In an embodiment of the seventh aspect, the sensor
`comprises a planar Substrate.
`0063. In an embodiment of the seventh aspect, the sealing
`material comprises a silicone.
`0064. In an embodiment of the seventh aspect, the device
`further comprises a sealant adjacent to the sealing member.
`
`0065. In an embodiment of the seventh aspect, the sensor
`electronics are housed within an electronics unit configured
`to mate with the electrical contact.
`0066.
`In an embodiment of the seventh aspect, the elec
`tronics unit and the sealing member are configured to mate
`to provide a compression force therebetween.
`0067. In an embodiment of the seventh aspect, the device
`further comprises at least one raised portion configured to
`provide a compression force to the sealing member when the
`electrical contact is connected to the sensor electronics.
`0068 in an eighth embodiment, a device for use in
`measuring an analyte in a host is provided, the device
`comprising a sensor operably connected to sensor electron
`ics, the sensor electronics configured for measuring an
`analyte in a host; at least one electrical contact configured to
`operably connect the sensor to the sensor electronics; and a
`sealing member at least partially Surrounding at least one of
`the sensor and the electrical contact, wherein the sealing
`member is configured to seal the electrical contact from
`moisture when the sensor is operably connected to the
`sensor electronics.
`0069. In an embodiment of the eighth aspect, the sealing
`member comprises a material having a durometer hardness
`of from about 5 Shore A to about 80 Shore A.
`0070. In an embodiment of the eighth aspect, the device
`further comprises a sealant adjacent to the sealing member.
`0071. In an embodiment of the eighth aspect, the device
`further comprises a housing on which the sealing member is
`disposed, wherein the housing is configured to mechanically
`or chemically hold the sealing member thereon.
`0072. In an embodiment of the eighth aspect, the device
`further comprises an adhesive configured to hold the sealing
`member on the housing.
`0073. In an embodiment of the eighth aspect, the device
`further comprises at least one protrusion configured to
`substantially mate with at least one depression, whereby the
`sealing member is held on the housing.
`0074. In an embodiment of the eighth aspect, the sealing
`member comprises at least one gap that is maintained when
`the electrical contact is operably connected to the sensor
`electronics.
`0075. In an embodiment of the eighth aspect, the sensor
`at least partially extends through the gap.
`0076.
`In an embodiment of the eighth aspect, the gap is
`filled with a sealant.
`0077. In an embodiment of the eighth aspect, the device
`further comprises at least one channel communicating
`between a first side of the sealing member and a second side
`of the sealing member.
`0078. In an embodiment of the eighth aspect, the channel
`is filled with a sealant.
`0079. In an embodiment of the eighth aspect, substan
`tially no air gaps are adjacent to the electrical contact when
`the electrical contact is operably connected to the sensor
`electronics.
`0080. In an embodiment of the eighth aspect, the sealing
`member comprises a material selected from the group con
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`sisting of silicone, silicone/polyurethane hybrid, polyure
`thane, polysulfide, and mixtures thereof.
`0081. In an embodiment of the eighth aspect, the sealing
`member is self-lubricating.
`0082 In an embodiment of the eighth aspect, the sealing
`member comprises a sealant Sandwiched between an upper
`portion of the sealing member and a lower portion of the
`sealing member.
`0083. In an embodiment of the eighth aspect, the device
`further comprises a guide tube configured to maintain an
`opening in the sealing member prior to sensor insertion into
`the host.
`0084. In an embodiment of the eighth aspect, the device
`further comprises a lubricant between the sealing member
`and the guide tube.
`0085. In a ninth aspect, a device for use in measuring an
`analyte in a host is provided, the device comprising a sensor
`operably connected to sensor electronics, the sensor elec
`tronics configured for measuring an analyte in a host; at least
`one electrical contact configured to connect the sensor to the
`sensor electronics, wherein the electrical contact comprises
`a material having a durometer hardness of from about 5
`Shore A to about 80 Shore A; and a sealing member at least
`partially Surrounding at least one of the sensor and the
`electrical contact, wherein the sealing member comprises a
`material having a durometer hardness of from about 5 Shore
`A to about 80 Shore A.
`0086.
`In an embodiment of the ninth aspect, the durom
`eter hardness of the electrical contact is higher than the
`durometer hardness of the sealing member.
`0087. In an embodiment of the ninth aspect, the durom
`eter hardness of the electrical contact is about 50 Shore A.
`0088. In an embodiment of the ninth aspect, the durom
`eter hardness of the sealing member is higher than the
`durometer hardness of the contact.
`0089. In an embodiment of the ninth aspect, the durom
`eter hardness of the sealing member is about 50 Shore A.
`0090. In an embodiment of the ninth aspect, the sealing
`member comprises a filler material.
`0091. In an embodiment of the ninth aspect, the filler
`material is configured to stiffen the sealing member.
`0092.
`In a tenth aspect, a sensor system for measuring an
`analyte concentration in a host is provided, the system
`comprising at least one electrode configured for implanta
`tion in a host and configured to measure an analyte concen
`tration in a tissue of the host; sensor electronics operably
`connected to the electrode and configured to provide analyte
`data representative of an analyte concentration in the host;
`and an information tag comprising sensor information.
`0093. In an embodiment of the tenth aspect, the infor
`mation tag comprises a memory.
`0094. In an embodiment of the tenth aspect, the infor
`mation tag transm