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`US 20060020192Al
`
`(19) United States
`c12) Patent Application Publication
`Brister et al.
`
`(10) Pub. No.: US 2006/0020192 Al
`Jan. 26, 2006
`( 43) Pub. Date:
`
`(54) TRANSCUTANEOUS ANALYTE SENSOR
`
`Related U.S. Application Data
`
`(75)
`
`Inventors: Mark Brister, Encinitas, CA (US);
`James Brauker, San Diego, CA (US);
`Paul V. Neale, San Diego, CA (US);
`Peter C. Simpson, Del Mar, CA (US);
`Sean Saint, San Diego, CA (US)
`
`Correspondence Address:
`KNOBBE MARTENS OLSON & BEAR LLP
`2040 MAIN STREET
`IRVINE, PA 92614 (US)
`
`(73) Assignee: DexCom, Inc., San Diego, CA (US)
`
`(21) Appl. No.:
`
`11/078,230
`
`(22) Filed:
`
`Mar. 10, 2005
`
`(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(cid:173)
`cation No. 60/614,764, filed on Sep. 30, 2004.
`
`Publication Classification
`
`(51)
`
`Int. Cl.
`A61B 5/05
`(2006.01)
`(52) U.S. Cl. .............................................................. 600/345
`
`(57)
`
`ABSTRACT
`
`Abstract of the Disclosure
`
`The present invention relates generally to systems and
`methods for measuring an analyte in a host. More particu(cid:173)
`larly, the present invention relates to systems and methods
`for transcutaneous measurement of glucose in a host.
`
`DexCom Exhibit 2005
`Abbott v. DexCom
`IPR2024-00891
`
`

`

`Patent Application Publication Jan. 26, 2006 Sheet 1 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 2 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 3 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 4 of 23
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`FIG.4
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`Patent Application Publication Jan. 26, 2006 Sheet 5 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 6 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 7 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 8 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 9 of 23
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`FIG. 9A
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`Patent Application Publication Jan. 26, 2006 Sheet 10 of 23
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`FIG. lOA
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`Patent Application Publication Jan. 26, 2006 Sheet 11 of 23
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`FIG. 11A
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`Patent Application Publication Jan. 26, 2006 Sheet 12 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 16 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 17 of 23
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`lNmAL CALIBRATION
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`CONTINUOUS ANAL YTE SENSOR
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`Patent Application Publication Jan. 26, 2006 Sheet 19 of 23
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`US 2006/0020192 Al
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`EVALUATE ACCBPTABJLlTY OP
`R!PERBNCB ANO SENSOR DATA
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`

`

`Patent Application Publication Jan. 26, 2006 Sheet 20 of 23
`
`US 2006/0020192 Al
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`

`

`Patent Application Publication Jan. 26, 2006 Sheet 21 of 23
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`US 2006/0020192 Al
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`Patent Application Publication Jan. 26, 2006 Sheet 22 of 23
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`Patent Application Publication Jan. 26, 2006 Sheet 23 of 23
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`US 2006/0020192 Al
`
`Jan.26,2006
`
`1
`
`TRANSCUTANEOUSANALYTESENSOR
`
`Detailed Description of the Invention
`
`Related Applications
`[0001] This application claims the benefit of U.S. Provi(cid:173)
`sional Application No. 60/587,787 filed July 13, 2004; U.S.
`Provisional Application No. 60/587,800 filed July 13, 2004;
`U.S. Provisional Application No. 60/614,683 filed Septem(cid:173)
`ber 30, 2004; and U.S. Provisional Application No. 60/614,
`764 filed September 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 m a
`host.
`
`Background of the Invention
`
`[0003] Diabetes mellitus is a disorder in which the pan(cid:173)
`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(cid:173)
`tion of small blood vessels, for example, kidney failure, skin
`ulcers, or bleeding into the vitreous of the eye. A hypogly(cid:173)
`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(cid:173)
`dinary exercise or insufficient food intake.
`[0004] Conventionally, a person with diabetes carries a
`self-monitoring blood glucose (SMBG) monitor, which typi(cid:173)
`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(cid:173)
`its the ability to make educated insulin therapy decisions.
`
`Summary of the Invention
`
`[0005]
`In a first aspect, a transcutaneous analyte sensor is
`provided, the sensor comprising: an in vivo portion adapted
`for at least partial insertion through a skin of a host, wherein
`the in vivo portion comprises an anchoring mechanism
`adapted for maintaining the in vivo portion of the sensor in
`a stable position within the host.
`[0006]
`In an embodiment of the first aspect, the anchoring
`mechanism comprises at least one wire having a surface
`topography.
`[0007]
`In an embodiment of the first aspect, the anchoring
`mechanism comprises at least one structure extending from
`
`the in vivo portion of the sensor, wherein the structure is
`selected from the group consisting of a prong, a ridge, a
`bulbous portion, an S-bend, a spine, a barb, a wing, and a
`hook.
`[0008]
`In an embodiment of the first aspect, the anchoring
`mechanism has a variable surface topography.
`[0009]
`In an embodiment of the first aspect, a diameter of
`the anchoring mechanism changes along at least a portion of
`the in vivo portion of the sensor.
`[0010]
`In an embodiment of the first aspect, the anchoring
`mechanism comprises a porous material disposed on the in
`vivo portion of the sensor.
`[0011]
`In an embodiment of the first aspect, the porous
`material is configured to modify a response of a tissue of the
`host to the sensor.
`[0012]
`In an embodiment of the first aspect, a bioactive
`agent is incorporated in the porous material.
`[0013]
`In an embodiment of the first aspect, the porous
`material comprises an oxygen enhancing material.
`[0014]
`In an embodiment of the first aspect, a bioactive
`agent is incorporated within the in vivo portion of the sensor.
`[0015]
`In a second aspect, a transcutaneous analyte sensor
`is provided, the sensor comprising a distal portion and a
`proximal portion, wherein the distal portion is adapted to be
`inserted through a skin of a host, wherein at least a portion
`of the proximal portion is adapted to remain external to the
`host when the distal portion is inserted in the host, and
`wherein the sensor is configured to absorb movement
`between the proximal portion of the sensor and the distal
`portion of the sensor.
`[0016]
`In an embodiment of the second aspect, the sensor
`comprises a bend configured to absorb movement of an in
`vivo portion of the sensor or an ex vivo portion of the sensor.
`[0017]
`In an embodiment of the second aspect, the bend is
`configured to absorb movement by flexion.
`[0018]
`In an embodiment of the second aspect, the sensor
`comprises a member configured to expand and contract,
`whereby movement of an in vivo portion of the sensor or an
`ex vivo portion of the sensor is absorbed.
`
`[0019]
`In an embodiment of the second aspect, the mem(cid:173)
`ber configured to expand and contract is selected from the
`group consisting of a spring, an accordion, a telescoping
`device, and a bellows-type device.
`
`[0020]
`In an embodiment of the second aspect, the sensor
`further comprises a mounting unit adapted for mounting on
`the skin of the host, wherein the sensor is operably con(cid:173)
`nected to the mounting unit at the proximal portion of the
`sensor, wherein the sensor extends from the mounting unit
`at the distal portion of the sensor, wherein the distal portion
`of the sensor is adapted to be inserted into an insertion
`location under the skin of the host, wherein at least a portion
`of a length of the sensor is configured to absorb relative
`movement between the proximal portion of the sensor and
`the distal portion of the sensor without displacing the
`proximal portion of the sensor from its operable connection
`to the mounting unit and without substantially displacing the
`distal portion from the insertion location under the skin of
`the host.
`
`

`

`US 2006/0020192 Al
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`Jan.26,2006
`
`2
`
`[0021]
`In an embodiment of the second aspect, at least a
`portion of a length of the sensor has a variable stiffness.
`
`[0022]
`In an embodiment of the second aspect, the sensor
`comprises at least one wire having a helical configuration,
`and wherein the variable stiffness is provided by at least one
`of a variable pitch of the helical wire and a variable
`cross-section of the helical wire.
`
`[0023]
`In an embodiment of the second aspect, the vari(cid:173)
`able stiffness is provided by a variable hardness of the wire.
`
`[0024]
`In a third aspect, a device configured for transcu(cid:173)
`taneous insertion into a host is provided, the device com(cid:173)
`prising an in vivo portion and an ex vivo portion, wherein the
`device is configured to absorb motion, such that motion of
`the ex vivo portion does not substantially translate to the in
`vivo portion.
`
`Brief Description of the Drawings
`
`[0025] Fig. 1 is a perspective view of a transcutaneous
`analyte sensor system, including an applicator, a mounting
`unit, and an electronics unit.
`
`[0026] Fig. 2 is a perspective view of a mounting unit,
`including the electronics unit in its functional position.
`
`[0027] Fig. 3 is an exploded perspective view of a mount(cid:173)
`ing unit, showing its individual components.
`
`[0028] Fig. 4 is an exploded perspective view of a contact
`subassembly, showing its individual components.
`
`[0029] Fig. SA is an expanded cutaway view of a proximal
`portion of a sensor.
`
`[0030] Fig. 5B is an expanded cutaway view of a distal
`portion of a sensor.
`
`[0031] Fig. SC is a cross-sectional view through the
`sensor of Fig. 5B on line C-C, showing an exposed elec(cid:173)
`troactive surface of a working electrode surrounded by a
`membrane system.
`
`[0032] Fig. 6 is an exploded side view of an applicator,
`showing the components that facilitate sensor insertion and
`subsequent needle retraction.
`
`[0033] Figs. 7A to 7D are schematic side cross-sectional
`views that illustrate applicator components and their coop(cid:173)
`erating relationships.
`
`[0034] Fig. SA is a side view of an applicator matingly
`engaged to a mounting unit, prior to sensor insertion.
`
`[0035] Fig. 8B is a side view of a mounting unit and
`applicator after the plunger subassembly has been pushed,
`extending the needle and sensor from the mounting unit.
`
`[0036] Fig. SC is a side view of a mounting unit and
`applicator after the guide tube subassembly has been
`retracted, retracting the needle back into the applicator.
`
`[0037] Figs. 9A to 9C are side views of an applicator and
`mounting unit, showing stages of sensor insertion.
`
`[0038] Figs. lOA and 10B are perspective and side cross(cid:173)
`sectional views, respectively, of a sensor system showing the
`mounting unit immediately following sensor insertion and
`release of the applicator from the mounting unit.
`
`[0039] Figs. llA and 11B are perspective and side cross(cid:173)
`sectional views, respectively, of a sensor system showing the
`mounting unit after pivoting the contact subassembly to its
`functional position.
`
`[0040] Figs. 12A to 12C are perspective and side views,
`respectively, of the sensor system showing the sensor,
`mounting unit, and electronics unit in their functional posi(cid:173)
`tions.
`
`[0041] Figure 13 is a block diagram that illustrates elec(cid:173)
`tronics associated with a sensor system.
`
`[0042] Fig. 14 is a perspective view of a sensor system
`wirelessly communicating with a receiver.
`
`[0043] Fig. 15A is a block diagram that illustrates a
`configuration of a medical device including a continuous
`analyte sensor, a receiver, and an external device.
`
`[0044] Figs. 15B to 15D are illustrations of receiver liquid
`crystal displays showing embodiments of screen displays.
`
`[0045] Fig. 16A is a flow chart that illustrates the initial
`calibration and data output of sensor data.
`[0046] Fig. 16B is a graph that illustrates one example of
`using prior information for slope and baseline.
`
`[0047] Fig. 17 is a flow chart that illustrates evaluation of
`reference and/or sensor data for statistical, clinical, and/or
`physiological acceptability.
`
`[0048] Fig. 18 is a flow chart that illustrates evaluation of
`calibrated sensor data for aberrant values.
`[0049] Fig. 19 is a flow chart that illustrates self-diagnos(cid:173)
`tics of sensor data.
`
`[0050] Fig. 20A and 20B are graphical representations of
`glucose sensor data in a human obtained over approximately
`three days.
`
`Detailed Description of the Preferred Embodiment
`
`[0051] The following description and examples illustrate
`some exemplary embodiments of the disclosed invention in
`detail. Those of skill in the art will recognize that there are
`numerous variations and modifications of this invention that
`are encompassed by its scope. Accordingly, the description
`of a certain exemplary embodiment should not be deemed to
`limit the scope of the present invention.
`
`Definitions
`
`[0052]
`In order to facilitate an understanding of the pre(cid:173)
`ferred embodiments, a number of terms are defined below.
`
`[0053] The term "analyte" as used herein is a broad term
`and is used in its ordinary sense, including, without limita(cid:173)
`tion, to refer to a substance or chemical constituent in a
`biological fluid (for example, blood, interstitial fluid, cere(cid:173)
`bral spinal fluid, lymph fluid or urine) that can be analyzed.
`Analytes can include naturally occurring substances, artifi(cid:173)
`cial substances, metabolites, and/or reaction products. In
`some embodiments, the analyte for measurement by the
`sensing regions, devices, and methods is glucose. However,
`other analytes are contemplated as well, including but not
`limited to acarboxyprothrombin; acylcarnitine; adenine
`phosphoribosyl transferase; adenosine deaminase; albumin;
`alpha-fetoprotein; amino acid profiles (arginine (Krebs
`
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`cycle), histidine/urocanic acid, homocysteine, phenylala(cid:173)
`nine/tyrosine, tryptophan); andrenostenedione; antipyrine;
`arabinitol
`enantiomers;
`arginase;
`benzoylecgonine
`(cocaine); biotinidase; biopterin; c-reactive protein; car(cid:173)
`nitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic
`acid; chloroquine; cholesterol; cholinesterase; conjugated
`1-~ hydroxy-cholic acid; cortisol; creatine kinase; creatine
`kinase MM isoenzyme; cyclosporin A; d-penicillamine;
`de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA
`( acetylator polymorphism, alcohol dehydrogenase, alpha
`1-antitrypsin, cystic fibrosis, Duchenne/Becker muscular
`dystrophy, glucose-6-phosphate dehydrogenase, hemoglo(cid:173)
`bin A, hemoglobin S, hemoglobin C, hemoglobin D, hemo(cid:173)
`globin E, hemoglobin F, D-Punjab, beta-thalassemia, hepa(cid:173)
`titis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic
`neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexual
`differentiation, 21-deoxycortisol); desbutylhalofantrine;
`dihydropteridine
`reductase; diptheria/tetanus antitoxin;
`erythrocyte arginase; erythrocyte protoporphyrin; esterase
`D; fatty acids/acylglycines; free ~-human chorionic gona(cid:173)
`dotropin; free erythrocyte porphyrin; free thyroxine (FT4);
`free tri-iodothyronine (FT3); fumarylacetoacetase; galac(cid:173)
`tose/gal-1-phosphate; galactose-1-phosphate uridyltrans(cid:173)
`ferase; gentamicin; glucose-6-phosphate dehydrogenase;
`glutathione; glutathione perioxidase; glycocholic acid; gly(cid:173)
`cosylated hemoglobin; halofantrine; hemoglobin variants;
`hexosaminidase A; human erythrocyte carbonic anhydrase I;
`17-alpha-hydroxyprogesterone; hypoxanthine phosphoribo(cid:173)
`syl transferase; immunoreactive trypsin; lactate; lead; lipo(cid:173)
`proteins ((a), B/A-1, ~); lysozyme; mefloquine; netilmicin;
`phenobarbitone; phenytoin; phytanic/pristanic acid; proges(cid:173)
`terone; prolactin; prolidase; purine nucleoside phosphory(cid:173)
`lase; quinine; reverse tri-iodothyronine (rT3); selenium;
`serum pancreatic lipase; sissomicin; somatomedin C; spe(cid:173)
`cific antibodies ( adenovirus, anti-nuclear antibody, anti-zeta
`antibody, arbovirus, Aujeszky's disease virus, dengue virus,
`Dracunculus medinensis, Echinococcus granulosus, Entam(cid:173)
`oeba histolytica, enterovirus, Giardia duodenalisa, Helico(cid:173)
`bacter pylori, hepatitis B virus, herpes virus, HIV-1, IgE
`( atopic disease), influenza virus, Leishmania donovani, lep(cid:173)
`tospira, measles/mumps/rubella, Mycobacterium
`leprae,
`Mycoplasma pneumoniae, Myoglobin, Onchocerca volvu(cid:173)
`lus, parainfluenza virus, Plasmodium falciparum, poliovirus,
`Pseudomonas aeruginosa, respiratory syncytial virus, rick(cid:173)
`ettsia (scrub typhus), Schistosoma mansoni, Toxoplasma
`gondii, Trepenoma pallidium, Trypanosoma cruzi/rangeli,
`vesicular stomatis virus, Wuchereria bancrofti, yellow fever
`virus); specific antigens (hepatitis B virus, HIV-1); succiny(cid:173)
`lacetone; sulfadoxine; theophylline; thyrotropin (TSH); thy(cid:173)
`roxine (T4); thyroxine-binding globulin; trace elements;
`transferrin; UDP-galactose-4-epimerase; urea; uroporphy(cid:173)
`rinogen I synthase; vitamin A; white blood cells; and zinc
`protoporphyrin. Salts, sugar, protein, fat, vitamins and hor(cid:173)
`mones naturally occurring in blood or interstitial fluids can
`also constitute analytes in certain embodiments. The analyte
`can be naturally present in the biological fluid, for example,
`a metabolic product, a hormone, an antigen, an antibody, and
`the like. Alternatively, the analyte can be introduced into the
`body, for example, a contrast agent for imaging, a radioiso(cid:173)
`tope, a chemical agent, a fluorocarbon-based synthetic
`blood, or a drug or pharmaceutical composition, including
`but not limited to insulin; ethanol; cannabis (marijuana,
`tetrahydrocannabinol, hashish); inhalants (nitrous oxide,
`amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocar-
`
`bans); cocaine ( crack cocaine); stimulants ( amphetamines,
`methamphetamines, Ritalin, Cylert, Preludin, Didrex,
`PreState, Voranil, Sandrex, Plegine ); depressants (barbitu(cid:173)
`ates, methaqualone, tranquilizers such as Valium, Librium,
`Miltown, Serax, Equanil, Tranxene); hallucinogens (phen(cid:173)
`cyclidine, lysergic acid, mescaline, peyote, psilocybin); nar(cid:173)
`cotics (heroin, codeine, morphine, opium, meperidine, Per(cid:173)
`cocet, Percodan, Tussionex, Fentanyl, Darvon, Talwin,
`Lomotil); designer drugs (analogs of fentanyl, meperidine,
`amphetamines, methamphetamines, and phencyclidine, for
`example, Ecstasy); anabolic steroids; and nicotine. The
`metabolic products of drugs and pharmaceutical composi(cid:173)
`tions are also contemplated analytes. Analytes such as
`neurochemicals and other chemicals generated within the
`body can also be analyzed, such as, for example, ascorbic
`acid, uric acid, dopamine, noradrenaline, 3-methoxy(cid:173)
`tyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC),
`homovanillic acid (HVA), 5-hydroxytryptamine (SHT), and
`5-hydroxyindoleacetic acid (FHIAA).
`
`[0054] The term "host" as used herein is a broad term and
`is used in its ordinary sense, including, without limitation, to
`refer to mammals, particularly humans.
`
`[0055] The term "exit-site" as used herein is a broad term
`and is used in its ordinary sense, including, without limita(cid:173)
`tion, to refer to the area where a medical device (for
`example, a sensor and/or needle) exits from the host's body.
`
`[0056] The phrase "continuous ( or continual) analyte
`sensing" as used herein is a broad term and is used in its
`ordinary sense, including, without limitation, to refer to the
`period in which monitoring of analyte concentration is
`continuously, continually, and or intermittently (regularly or
`irregularly) performed, for example, about every 5 to 10
`minutes.
`
`[0057] The term "electrochemically reactive surface" as
`used herein is a broad term and is used in its ordinary sense,
`including, without limitation, to refer to the surface of an
`electrode where an electrochemical reaction takes place. For
`example, a working electrode measures hydrogen peroxide
`produced by the enzyme-catalyzed reaction of the analyte
`detected, which reacts to create an electric current. Glucose
`analyte can be detected utilizing glucose oxidase, which
`produces H 2 0 2 as a byproduct. H 2 0 2 reacts with the surface
`of the working electrode, producing two protons (2H+), two
`electrons (2e-) and one molecule of oxygen (0 2), which
`produces the electronic current being detected.
`
`[0058] The term "electronic connection" as used herein is
`a broad term and is used in its ordinary sense, including,
`without limitation, to refer to any electronic connection
`known to those in the art that can be utilized to interface the
`sensing region electrodes with the electronic circuitry of a
`device, such as mechanical (for example, pin and socket) or
`soldered electronic connections.
`
`[0059] The term "interferant" and "interferants," as used
`herein, are broad terms and are used in their ordinary sense,
`including, without limitation, to refer to species that inter(cid:173)
`fere with the measurement of an analyte of interest in a
`sensor to produce a signal that does not accurately represent
`the analyte measurement. In one example of an electro(cid:173)
`chemical sensor, interferants are compounds with oxidation
`potentials that overlap with the analyte to be measured.
`
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`[0060] The term "sensing region" as used herein is a broad
`term and is used in its ordinary sense, including, without
`limitation, to refer to the region of a monitoring device
`responsible for the detection of a particular analyte. The
`sensing region generally comprises a non-conductive body,
`a working electrode
`(anode), a
`reference electrode
`( optional), and/or a counter electrode (cathode) passing
`through and secured within the body forming electrochemi(cid:173)
`cally reactive surfaces on the body and an electronic con(cid:173)
`nective means at another location on the body, and a
`multi-domain membrane affixed to the body and covering
`the electrochemically reactive surface.
`[0061] The term "high oxygen solubility domain" as used
`herein is a broad term and is used in its ordinary sense,
`including, without limitation, to refer to a domain composed
`of a material that has higher oxygen solubility than aqueous
`media such that it concentrates oxygen from the biological
`fluid surrounding the membrane system. The domain can act
`as an oxygen reservoir during times of minimal oxygen need
`and has the capacity to provide, on demand, a higher oxygen
`gradient to facilitate oxygen transport across the membrane.
`Thus, the ability of the high oxygen solubility domain to
`supply a higher flux of oxygen to critical domains when
`needed can improve overall sensor function.
`[0062] The term "domain" as used herein is a broad term
`and is used in its ordinary sense, including, without limita(cid:173)
`tion, to refer to a region of the membrane system that can be
`a layer, a uniform or non-uniform gradient (for example, an
`anisotropic region of a membrane), or a portion of a mem(cid:173)
`brane.
`[0063] The phrase "distal to" as used herein is a broad
`term and is used in its ordinary sense, including, without
`limitation, the spatial relationship between various elements
`in comparison to a particular point of reference. In general,
`the term indicates an element is located relatively far from
`the reference point than another element.
`[0064] The term "proximal to" as used herein is a broad
`term and is used in its ordinary sense, including, without
`limitation, the spatial relationship between various elements
`in comparison to a particular point of reference. In general,
`the term indicates an element is located relatively near to the
`reference point than another element.
`[0065] The terms "in vivo portion" and "distal portion" as
`used herein are broad terms and are used in their ordinary
`sense, including, without limitation, to refer to the portion of
`the device (for example, a sensor) adapted for insertion into
`and/or existence within a living body of a host.
`
`[0066] The terms "ex vivo portion" and "proximal portion"
`as used herein are broad terms and are used in their ordinary
`sense, including, without limitation, to refer to the portion of
`the device (for example, a sensor) adapted to remain and/or
`exist outside of a living body of a host.
`
`[0067] The terms "raw data stream" and "data stream," as
`used herein, are broad terms and are used in their ordinary
`sense, including, without limitation, to refer to an analog or
`digital signal from the analyte sensor directly related to the
`measured analyte. For example, the raw data stream is
`digital data in "counts" converted by an ND converter from
`an analog signal (for example, voltage or amps) represen(cid:173)
`tative of an analyte concentration. The terms broadly encom(cid:173)
`pass a plurality of time spaced data points from a substan-
`
`tially continuous analyte sensor, each of which comprises
`individual measurements taken at time intervals ranging
`from fractions of a second up to, for example, 1, 2, or 5
`minutes or longer.
`
`[0068] The term "count," as used herein, is a broad term
`and is used in its ordinary sense, including, without limita(cid:173)
`tion, to refer to a unit of measurement of a digital signal. For
`example, a raw data stream measured in counts is directly
`related to a voltage (for example, converted by an ND
`converter), which is directly related to current from the
`working electrode.
`
`[0069] The
`term "physiologically feasible," as used
`herein, is a broad term and is used in its ordinary sense,
`including, without limitation, to refer to one or more physi(cid:173)
`ological parameters obtained from continuous studies of
`glucose data in humans and/or animals. For example, a
`maximal sustained rate of change of glucose in humans of
`about 4 to 6 mg/dL/min and a maximum acceleration of the
`rate of change of about 0.1 to 0.2 mg/dL/min/min are
`deemed physiologically feasible limits. Values outside of
`these limits are considered non-physiological and are likely
`a result of, e.g., signal error.
`
`[0070] The term "ischemia," as used herein, is a broad
`term and is used in its ordinary sense, including, without
`limitation, to refer to local and temporary deficiency of
`blood supply due to obstruction of circulation to a part (for
`example, a sensor). Ischemia can be caused, for example, by
`mechanical obstruction (for example, arterial narrowing or
`disruption) of the blood supply.
`
`[0071] The term "matched data pairs", as used herein, is a
`broad term and is used in its ordinary sense, including,
`without limitation, to refer to reference data (for example,
`one or more reference analyte data points) matched with
`substantially time corresponding sensor data (for example,
`one or more sensor data points).
`
`[0072] The term "Clarke Error Grid", as used herein, is a
`broad