U.S. patent application number 16/942528 was filed with the patent office on 2020-11-12 for transcutaneous medical device with variable stiffness.
The applicant listed for this patent is DexCom, Inc.. Invention is credited to James H. Brauker, Mark C. Brister.
Application Number | 20200352483 16/942528 |
Document ID | / |
Family ID | 1000004986634 |
Filed Date | 2020-11-12 |
United States Patent
Application |
20200352483 |
Kind Code |
A1 |
Brister; Mark C. ; et
al. |
November 12, 2020 |
TRANSCUTANEOUS MEDICAL DEVICE WITH VARIABLE STIFFNESS
Abstract
The present invention relates generally to variable stiffness
transcutaneous medical devices including a distal portion designed
to be more flexible than a proximal portion. The variable stiffness
can be provided by a variable pitch in one or more wires of the
device, a variable cross-section in one or more wires of the
device, and/or a variable hardening and/or softening in one or more
wires of the device.
Inventors: |
Brister; Mark C.; (San
Diego, CA) ; Brauker; James H.; (San Diego,
CA) |
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Applicant: |
Name |
City |
State |
Country |
Type |
DexCom, Inc. |
San Diego |
CA |
US |
|
|
Family ID: |
1000004986634 |
Appl. No.: |
16/942528 |
Filed: |
July 29, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16007725 |
Jun 13, 2018 |
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16942528 |
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14266408 |
Apr 30, 2014 |
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16007725 |
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12105227 |
Apr 17, 2008 |
8812072 |
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14266408 |
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11077759 |
Mar 10, 2005 |
7783333 |
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12105227 |
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60587800 |
Jul 13, 2004 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/6833 20130101;
A61B 5/14546 20130101; A61B 5/1411 20130101; A61B 5/14532 20130101;
A61B 5/14865 20130101; A61B 5/1468 20130101; A61B 5/150022
20130101 |
International
Class: |
A61B 5/145 20060101
A61B005/145; A61B 5/15 20060101 A61B005/15; A61B 5/00 20060101
A61B005/00; A61B 5/1486 20060101 A61B005/1486; A61B 5/1468 20060101
A61B005/1468 |
Claims
1-20. (canceled)
21. A transcutaneous analyte sensor assembly, the assembly
comprising: a sensor, wherein the sensor includes a distal portion,
adapted to be inserted through a skin of a host such that in use
the distal portion is in vivo, an intermediate portion, and a
proximal portion adapted to remain substantially external to the
host such that in use the proximal portion is ex vivo when the
distal portion is inserted in the host; wherein a stiffness of the
sensor is variable along a length of the sensor and wherein the
proximal, ex vivo, portion is stiffer than the distal, in vivo,
portion; and a housing configured for mounting on a skin of a
host.
22. The sensor assembly of claim 21, further comprising an
electronics unit configured to operably connect to the sensor.
23. The sensor assembly of claim 22, wherein the housing comprises
electrical contacts configured to operably connect the sensor to
the electronics unit.
24. The sensor assembly of claim 21, wherein the sensor is
configured to absorb a relative movement between the proximal, ex
vivo, portion and the distal, in vivo, portion.
25. The sensor assembly of claim 21, wherein the sensor comprises
at least one wire in a helical configuration, and wherein a
difference in stiffness of the distal portion and the proximal
portion is provided by varying a pitch of the helical
configuration.
26. The sensor assembly of claim 25, wherein the sensor comprises
at least one wire in a helical configuration, and wherein a
difference in flexibility of the distal portion and the proximal
portion is provided by varying a cross-section of the wire.
27. The sensor assembly of claim 21, wherein the sensor comprises
at least one wire, and wherein a difference in flexibility of the
distal portion and the proximal portion is provided by varying a
hardness of the wire.
28. The sensor assembly of claim 27, wherein a variation in
stiffness of the elongated flexible portion of the sensor is
produced by subjecting the wire to an annealing process.
29. The sensor assembly of claim 21, wherein the intermediate
portion of the sensor is more flexible than at least one of the
distal portion and the proximal portion.
30. The sensor assembly of claim 29, wherein the distal portion of
the sensor comprises a distal tip on an end of the sensor that is
stiffer than a substantial portion of the sensor.
31. The sensor assembly of claim 21, wherein the ex vivo portion of
the sensor has a preselected stiffness to maintain a stable
connection between the sensor and the electrical contacts.
32. The sensor assembly of claim 21, wherein the in vivo portion of
the sensor has a preselected flexibility to minimize mechanical
stresses caused by motion of the host.
Description
INCORPORATION BY REFERENCE TO RELATED APPLICATIONS
[0001] Any and all priority claims identified in the Application
Data Sheet, or any correction thereto, are hereby incorporated by
reference under 37 CFR 1.57. This application is a continuation of
U.S. application Ser. No. 16/007,725, filed Jun. 13, 2018, which is
a continuation of U.S. application Ser. No. 14/266,408, filed Apr.
30, 2014, now abandoned, which is a continuation of U.S.
application Ser. No. 12/105,227, filed Apr. 17, 2008, now U.S. Pat.
No. 8,812,072, which is a continuation of U.S. application Ser. No.
11/077,759, filed Mar. 10, 2005, now U.S. Pat. No. 7,783,333, which
claims the benefit of U.S. Provisional Application No. 60/587,800
filed Jul. 13, 2004. Each of the aforementioned applications is
incorporated by reference herein in its entirety, and each is
hereby expressly made a part of this specification.
FIELD OF THE INVENTION
[0002] The present invention relates generally to systems and
methods for use with partially implantable medical devices. More
particularly, the present invention relates to systems and methods
for use with transcutaneous analyte sensors.
BACKGROUND OF THE INVENTION
[0003] Transcutaneous medical devices are useful in medicine for
providing the enhanced functionality of a wholly implantable
medical device while avoiding many of the complications associated
with a wholly implantable device. For example, transcutaneous
analyte sensors are generally minimally invasive compared to wholly
implantable sensor, and are capable of measuring an analyte
concentration for a short period of time (e.g., three days) with
similar accuracy as in a wholly implantable sensor.
SUMMARY OF THE INVENTION
[0004] In a first aspect, a transcutaneous analyte sensor is
provided, the sensor comprising an elongated flexible portion,
wherein the elongated flexible portion has a variable stiffness
along at least a portion of its length.
[0005] In an embodiment of the first aspect, the sensor comprises
at least one wire in a helical configuration, and wherein the
variable stiffness is provided by a variable pitch of the helical
configuration.
[0006] In an embodiment of the first aspect, the sensor comprises
at least one wire in a helical configuration, and wherein the
variable stiffness is provided by a variable cross-section of the
wire.
[0007] In an embodiment of the first aspect, the sensor comprises
at least one wire, and wherein the variable stiffness is provided
by a variable hardness of the wire.
[0008] In an embodiment of the first aspect, the variable stiffness
of the elongated flexible portion is produced by subjecting the
wire to an annealing process.
[0009] In an embodiment of the first aspect, the sensor comprises
at least one wire, the wire having a variable diameter.
[0010] In an embodiment of the first aspect, a distal portion of
the sensor is more flexible than a proximal portion of the
sensor.
[0011] In an embodiment of the first aspect, an intermediate
portion of the sensor is more flexible than at least one of a
distal portion of the sensor and a proximal portion of the
sensor.
[0012] In an embodiment of the first aspect, a distal tip of the
sensor is stiffer than at least one of an intermediate portion of
the sensor and a proximal portion of the sensor.
[0013] In a second aspect, a transcutaneous analyte sensor is
provided, the sensor comprising a distal portion, an intermediate
portion, and a proximal portion, wherein the distal portion is
adapted to be inserted through a skin of a host, wherein the
proximal portion is adapted to remain substantially external to the
host when the distal portion is inserted in the host, and wherein a
stiffness of the sensor is variable along a length of the
sensor.
[0014] In an embodiment of the second aspect, the proximal portion
is stiffer than the distal portion.
[0015] In an embodiment of the second aspect, the sensor comprises
at least one wire in a helical configuration, and wherein a
difference in stiffness of the distal portion and the proximal
portion is provided by varying a pitch of the helical
configuration.
[0016] In an embodiment of the second aspect, the sensor comprises
at least one wire in a helical configuration, and wherein a
difference in flexibility of the distal portion and the proximal
portion is provided by a varying a cross-section of the wire.
[0017] In an embodiment of the second aspect, the sensor comprises
at least one wire, and wherein a difference in flexibility of the
distal portion and the proximal portion is provided by a varying a
hardness of the wire.
[0018] In an embodiment of the second aspect, a variation in
stiffness of the elongated flexible portion is produced by
subjecting the wire to an annealing process.
[0019] In an embodiment of the second aspect, the intermediate
portion is more flexible than at least one of the distal portion
and the proximal portion.
[0020] In an embodiment of the second aspect, the distal portion
comprises a distal tip on an end of the sensor that is stiffer a
substantial portion of the sensor.
[0021] In an embodiment of the second aspect, the intermediate
portion is more flexible than at least one of the distal portion
and the proximal portion.
[0022] In an embodiment of the second aspect, the distal portion
comprises a distal tip on an end of the sensor that is stiffer a
substantial portion of the sensor.
[0023] In a third aspect, a transcutaneous analyte sensor is
provided, the sensor comprising an in vivo portion adapted for
insertion into a host and an ex vivo portion adapted for operable
connection to a device that remains external to the host, wherein
the sensor is configured to absorb a relative movement between the
ex vivo portion of the sensor and the in vivo portion of the
sensor.
[0024] In an embodiment of the third aspect, the sensor is
configured to absorb a relative movement by a flexibility of at
least an intermediate portion located between the in vivo portion
and the ex vivo portion.
[0025] In an embodiment of the third aspect, the device comprises a
housing adapted for mounting on a skin of a host, wherein the
housing comprises electrical contacts operably connected to the
sensor.
[0026] In an embodiment of the third aspect, the ex vivo portion of
the sensor is has a preselected stiffness to maintain a stable
connection between the sensor and the electrical contacts.
[0027] In an embodiment of the third aspect, the in vivo portion of
the sensor has a preselected flexibility to minimize mechanical
stresses caused by motion of the host.
[0028] In an embodiment of the third aspect, a stiffness of the ex
vivo portion of the sensor is greater than a stiffness of the in
vivo portion of the sensor.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1A is a perspective view of a transcutaneous sensor
assembly.
[0030] FIG. 1B is a side cross-sectional view of the transcutaneous
sensor assembly of FIG. 1A.
[0031] FIG. 2 is a schematic side view of a transcutaneous medical
device.
[0032] FIG. 3A is a schematic side view of a first transcutaneous
medical device having a variable stiffness.
[0033] FIG. 3B is a schematic side view of a second transcutaneous
medical device having a variable stiffness.
[0034] FIG. 3C is a schematic side view of a third transcutaneous
medical device having a variable stiffness.
[0035] FIGS. 4A to 4D are perspective and side views of a first
variable stiffness wire for use with a transcutaneous analyte
sensor.
[0036] FIGS. 5A and 5B are perspective and cross-sectional views of
a second variable stiffness wire for use with a transcutaneous
analyte sensor.
[0037] FIGS. 6A and 6B are perspective and cross-sectional views of
a third variable stiffness wire suitable for use with a
transcutaneous analyte sensor.
[0038] FIG. 7 is an expanded view of distal and proximal portions
of a transcutaneous sensor in one example.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0039] 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
[0040] In order to facilitate an understanding of the preferred
embodiments, a number of terms are defined below.
[0041] The term "analyte" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to a substance or chemical constituent in a biological fluid (for
example, blood, interstitial fluid, cerebral spinal fluid, lymph
fluid or urine) that can be analyzed. Analytes can include
naturally occurring substances, artificial 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 cycle),
histidine/urocanic acid, homocysteine, phenylalanine/tyrosine,
tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers;
arginase; benzoylecgonine (cocaine); biotinidase; biopterin;
c-reactive protein; carnitine; carnosinase; CD4; ceruloplasmin;
chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase;
conjugated 1-.beta.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, hemoglobin A, hemoglobin S,
hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F, D-Punjab,
beta-thalassemia, hepatitis 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 .beta.-human chorionic gonadotropin; free
erythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine
(FT3); fumarylacetoacetase; galactose/gal-1-phosphate;
galactose-1-phosphate uridyltransferase; gentamicin;
glucose-6-phosphate dehydrogenase; glutathione; glutathione
perioxidase; glycocholic acid; glycosylated hemoglobin;
halofantrine; hemoglobin variants; hexosaminidase A; human
erythrocyte carbonic anhydrase I; 17-alpha-hydroxyprogesterone;
hypoxanthine phosphoribosyl transferase; immunoreactive trypsin;
lactate; lead; lipoproteins ((a), B/A-1, .beta.); lysozyme;
mefloquine; netilmicin; phenobarbitone; phenytoin;
phytanic/pristanic acid; progesterone; prolactin; prolidase; purine
nucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3);
selenium; serum pancreatic lipase; sissomicin; somatomedin C;
specific antibodies (adenovirus, anti-nuclear antibody, anti-zeta
antibody, arbovirus, Aujeszky's disease virus, dengue virus,
Dracunculus medinensis, Echinococcus granulosus, Entamoeba
histolytica, enterovirus, Giardia duodenalisa, Helicobacter pylori,
hepatitis B virus, herpes virus, HIV-1, IgE (atopic disease),
influenza virus, Leishmania donovani, leptospira,
measles/mumps/rubella, Mycobacterium leprae, Mycoplasma pneumoniae,
Myoglobin, Onchocerca volvulus, parainfluenza virus, Plasmodium
falciparum, poliovirus, Pseudomonas aeruginosa, respiratory
syncytial virus, rickettsia (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);
succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH);
thyroxine (T4); thyroxine-binding globulin; trace elements;
transferrin; UDP-galactose-4-epimerase; urea; uroporphyrinogen I
synthase; vitamin A; white blood cells; and zinc protoporphyrin.
Salts, sugar, protein, fat, vitamins and hormones 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 radioisotope, 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,
hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines,
methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState,
Voranil, Sandrex, Plegine); depressants (barbituates, methaqualone,
tranquilizers such as Valium, Librium, Miltown, Serax, Equanil,
Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline,
peyote, psilocybin); narcotics (heroin, codeine, morphine, opium,
meperidine, Percocet, 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 compositions 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-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC),
homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and
5-hydroxyindoleacetic acid (FHIAA).
[0042] The terms "operably connected" and "operably linked" as used
herein are broad terms and are used in their ordinary sense,
including, without limitation, to refer to one or more components
linked to one or more other components. The terms can refer to a
mechanical connection, an electrical connection, or a connection
that allows transmission of signals between the components. For
example, one or more electrodes can be used to detect the amount of
analyte in a sample and to convert that information into a signal;
the signal can then be transmitted to a circuit. In such an
example, the electrode is "operably linked" to the electronic
circuitry.
[0043] 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.
[0044] The term "exit-site" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to the area where a medical device (for example, a sensor arid/or
needle) exits from the host's body.
[0045] 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.
[0046] 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.sub.2O.sub.2 as a
byproduct. H.sub.2O.sub.2 reacts with the surface of the working
electrode, producing two protons (2H.sup.+), two electrons
(2e.sup.-) and one molecule of oxygen (O.sub.2), which produces the
electronic current being detected. In the case of the counter
electrode, a reducible species, for example, O.sub.2 is reduced at
the electrode surface in order to balance the current being
generated by the working electrode.
[0047] 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
electrochemically reactive surfaces on the body and an electronic
connective means at another location on the body, and a
multi-domain membrane affixed to the body and covering the
electrochemically reactive surface.
[0048] The terms "electronic connection" and "electrical
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.
[0049] The term "domain" as used herein is a broad term and is used
in its ordinary sense, including, without limitation, 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 membrane.
[0050] The term "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.
[0051] 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.
[0052] 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.
[0053] 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.
[0054] The term "intermediate portion" as used herein is a broad
term and is used in its ordinary sense, including, without
limitation, to refer to a portion of the device between a distal
portion and a proximal portion.
[0055] The terms "transdermal" and "transcutaneous" as used herein
are broad terms and is used in their ordinary sense, including,
without limitation, to refer to extending through the skin of a
host. For example, a transdermal analyte sensor is one that extends
through the skin of a host.
[0056] The term "hardening" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to an increase in hardness of a metal induced by a process such as
hammering, rolling, drawing, or the like.
[0057] The term "softening" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to an increase in softness of a metal induced by processes such as
annealing, tempering, or the like.
[0058] The term "tempering" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to the heat-treating of metal alloys, particularly steel, to reduce
brittleness and restore ductility.
[0059] The term "annealing" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to the treatment of a metal or alloy by heating to a predetermined
temperature, holding for a certain time, and then cooling to room
temperature to improve ductility and reduce brittleness.
[0060] The term "stiff" as used herein is a broad term and is used
in its ordinary sense, including, without limitation, to refer to a
material not easily bent, lacking in suppleness or responsiveness.
In the preferred embodiments, the degree of stiffness can be
relative to other portions of the device.
[0061] The term "flexible" as used herein is a broad term and is
used in its ordinary sense, including, without limitation, to refer
to a material that is bendable, pliable, or yielding to influence.
In the preferred embodiments, the degree of flexibility can be
relative to other portions of the device.
[0062] The devices of the preferred embodiments include transdermal
medical devices, such as transcutaneous sensor assemblies, with
variable stiffness configured along at least a portion of the
device. In one aspect of the preferred embodiments, a
transcutaneous sensor assembly is provided, including a sensor for
sensing an analyte linked to a housing for mounting on the skin of
the host. The housing houses an electronics unit associated with
the sensor and is adapted for secure adhesion to the host's
skin.
Transcutaneous Sensors
[0063] FIGS. 1A and 1B are perspective and side cross-sectional
views of a transcutaneous sensor assembly 10 of a preferred
embodiment. The sensor system includes a housing 12 and preferably
includes an adhesive material 14 on its backside 16 for adhesion to
a host's skin. A sensor 18 extends from the housing and is adapted
for transdermal insertion through the skin of the host. The sensor
portion can be configured for insertion into a variety of in vivo
locations, including subcutaneous, venous, or arterial locations,
for example. One or more contacts 22 are configured to provide
secure electrical contact between sensor 18 and an electronics unit
20. The housing 12 is designed to maintain the integrity of the
sensor in the host so as to reduce or eliminate translation of
motion between the housing 12, the host, and/or the sensor 18.
[0064] In general, the sensor includes at least one electrode
configured for measuring an analyte. In one embodiment, the sensor
18 includes at least two electrodes: a working electrode and at
least one additional electrode, which can function as a counter
and/or reference electrode. Preferably, the working electrode
comprises a wire formed from a conductive material, such as
platinum, palladium, graphite, gold, carbon, conductive polymer, or
the like. In some embodiments, the wire is formed from a bulk
material, or alternatively, a composite of two or more metals
and/or insulators (e.g., platinum plated steel). The working
electrode is configured to measure the concentration of an analyte.
The reference electrode, which can function as a reference
electrode alone, or as a dual reference and counter electrode, is
preferably formed from silver, silver/silver chloride, or the like.
In preferred embodiments, the reference electrode is twisted with
or around the working electrode; however other configurations for
the working electrode and the reference electrode are also
possible, for example juxtapositioned, adjacent, coaxial,
concentric, interdigitated, spiral-wound, or the like.
[0065] In some alternative embodiments, additional electrodes can
be included within the assembly. For example, a three-electrode
system (working, reference, and counter electrodes) and/or a system
including an additional working electrode (which can be used to
generate oxygen or can be configured as a baseline subtracting
electrode, for example) can be employed. Other
sensor/wire/electrode configurations (for example one, two, three,
four, or more wires and/or electrode configurations) are also
within the scope of the preferred embodiments. For example, U.S.
Pat. No. 6,613,379 to Ward et al. describes a bundle of wires
around which a counter electrode is deposed and configured for
measuring an analyte, and U.S. Pat. No. 6,329,161 to Heller et al.
describes a single wire electrode configured for measuring an
analyte. Any such configuration adapted for transcutaneous analyte
measurement can be configured with a variable stiffness in
accordance with the preferred embodiments.
[0066] In some embodiments (for example, enzymatic-based sensors),
a membrane system is disposed over some or all of the electroactive
surfaces of the sensor 18 (working and/or reference electrodes) and
provides one or more of the following functions: 1) protection of
the exposed electrode surface from the biological environment; 2)
diffusion resistance (limitation) of the analyte; 3) a catalyst for
enabling an enzymatic reaction; 4) hindering or blocking passage of
interfering species; and 5) hydrophilicity at the electrochemically
reactive surfaces of the sensor interface, such as is described in
co-pending U.S. patent application Ser. No. 11/077,715, filed on
Mar. 10, 2005 and entitled "TRANSCUTANEOUS ANALYTE SENSOR".
[0067] The electronics unit 20 can be integral with or removably
attached to the housing 12, and includes hardware, firmware and/or
software that enable measurement of levels of the analyte via the
sensor 18. For example, the electronics unit 20 comprises a
potentiostat, a power source for providing power to the sensor,
other components useful for signal processing, and preferably an RF
module for transmitting data from the electronics unit 20 to a
receiver. Electronics can be affixed to a printed circuit board
(PCB), or the like, and can take a variety of forms. For example,
the electronics can take the form of an integrated circuit (IC),
such as an application-specific integrated circuit (ASIC), a
microcontroller, or a processor. Preferably, the electronics unit
20 houses the sensor electronics, which comprise systems and
methods for processing sensor analyte data. Examples of systems and
methods for processing sensor analyte data are described in more
detail below and in co-pending U.S. application Ser. No. 10/633,367
filed Aug. 1, 2003 entitled, "SYSTEM AND METHODS FOR PROCESSING
ANALYTE SENSOR DATA."
[0068] Co-pending U.S. patent application Ser. No. 11/077,715,
filed on Mar. 10, 2005, and entitled, "TRANSCUTANEOUS ANALYTE
SENSOR," describes an embodiment of a transcutaneous analyte sensor
that benefits from variable stiffness. Variable stiffness
configurations along at least a portion of the device can be
employed with devices such as are described in U.S. Pat. No.
6,613,379 to Ward et al., U.S. Pat. No. 6,122,536 to Sun et al.,
U.S. Pat. No. 6,329,161 to Heller et al., U.S. Pat. No. 6,477,395
to Schulman, and U.S. Pat. No. 4,671,288 to Gough.
Variable Stiffness
[0069] Conventional transcutaneous devices can be subject to motion
artifact associated with host movement when the host is using the
device. For example, in the example of a transcutaneous analyte
sensor such as described above, various movements on the sensor
(for example, relative movement within and between the subcutaneous
space, dermis, skin, and external portions of the sensor) create
stresses on the device, which are known to produce artifacts on the
sensor signal.
[0070] Accordingly, the design considerations (for example, stress
considerations) vary for different sections of a transcutaneous
medical device. For example, certain portions of the device can
benefit in general from greater flexibility as the portion of the
device encounters greater mechanical stresses caused by movement of
the tissue within the patient and relative movement between the in
vivo and ex vivo portions of the sensor. Additionally or
alternatively, certain portions of the device can benefit in
general from a stiffer, more robust design to ensure structural
integrity and/or reliable electrical connections. Additionally, in
some embodiments wherein an insertion device (for example, needle
that aids in insertion) is retracted over the device, a stiffer
design can enable minimized crimping and/or easy retraction. Thus,
by designing greater flexibility into the some portions of the
device, the flexibility can compensate for movement and noise
associated therewith; and by designing greater stiffness into other
portions, column strength (for retraction of the needle over the
sensor), electrical connections, and structural integrity can be
enhanced.
[0071] FIG. 2 is a side schematic view of a transcutaneous medical
device 34, such as illustrated as the transcutaneous analyte sensor
18 of FIG. 1. In general, a transcutaneous medical device 34, can
be divided into three zones, a proximal portion 24 with a proximal
tip 26, a distal portion 28 with a distal tip 30, and an
intermediate portion 32. The preferred embodiments can employ a
variety of configurations that provide variable stiffness along at
least a portion of the device in order to overcome disadvantages of
conventional transcutaneous devices. Although the following
description is focused on an embodiment of a transcutaneous analyte
sensor, one skilled in the art can appreciate that the variable
stiffness of the preferred embodiments can be implemented with a
variety of transcutaneous medical devices.
[0072] Generally, the proximal portion 24 is adapted to remain
above the host's skin after device insertion and operably connects
to a housing ex vivo, for example. The proximal portion 24
typically provides the mechanical and/or electrical connections of
the device to housings, electronics, or the like. The proximal
portion includes a proximal tip 26 on an end thereof. It is noted
that the terms "proximal portion," "ex vivo portion," and "proximal
tip" do not necessarily imply an exact length or section, rather is
generally a section that is more proximal than distal relative to
the housing. In some embodiments, the proximal portion (or proximal
tip) is stiffer than at least one of the intermediate and distal
portions.
[0073] Generally, the distal portion 28 of the sensor is adapted
for insertion under the host's skin, and is also referred to as the
in vivo portion. The distal portion 28 typically provides the
device function in vivo, and therefore encounters stresses caused
by insertion of the device into the host's tissue and subsequent
movement of the tissue of the patient. The distal portion includes
a distal tip 30 on an end thereof. It is noted that the terms
"distal portion," "in vivo portion," and "distal tip" do not
necessarily imply an exact length or section, rather is generally a
section that is more distal than proximal relative to the housing.
In some embodiments, the distal portion is more flexible than at
least one of the intermediate and proximal portions. In some
embodiments, the distal tip is less flexible than at least one of
the remaining (non-tip) distal portion, the intermediate portion,
and the proximal portion.
[0074] Generally, the intermediate portion 32 is located between
the proximal portion 24 and the distal portion and may include
portions adapted for insertion or adapted to remain above the skin.
The intermediate portion 32 typically provides a transition between
the in vivo and ex vivo portions, and can incur stresses caused by
relative movement between the in vivo and ex vivo portions of the
sensor, for example. It is noted that the term "intermediate
portion" does not necessarily imply an exact length or section,
rather is generally a section that in-between the proximal and
distal portions. In some embodiments, the intermediate portion is
more flexible than one or both of the distal and proximal
portions.
[0075] FIG. 3A is a side schematic view of a transcutaneous medical
device 34a in one embodiment adapted for insertion through the skin
of a host. In this embodiment, the device 34a is designed with
greater flexibility generally in a distal portion 28 (relative to
intermediate and/or proximal portions), which is illustrated by
light cross-hatching in the distal portion of the device. Stated in
another way, the device is designed with a greater stiffness
generally in the proximal portion 24 than the intermediate and/or
the distal portions, which is illustrated by heavy cross-hatching
in the proximal portion 24 of the device. In some embodiments, the
intermediate portion includes a flexibility substantially similar
to that of the distal portion; in other embodiments, the
intermediate portion gradually transitions between the flexibility
of the distal portion and the stiffness of the proximal portion.
For example, in situations wherein movement of the tissue within
the patient and relative movement between the in vivo and ex vivo
portions of the device create stresses on the device, greater
flexibility in a distal portion (relative to intermediate and/or
proximal portions) can provide relief from these mechanical
stresses, protecting both the integrity of the sensor and the host
tissue. Additionally or alternatively, in situations wherein
mechanical and/or electrical connections are required for accurate
device function, greater stiffness in the proximal portion 24
(and/or the proximal tip) of the device can increase the stability
and reliability of these connections. Thus, the ex-vivo or proximal
portion 24 of the sensor is configured for stable connection to the
electronics and can additionally be configured to receive an
insertion device (such as a needle that aids in sensor insertion)
upon retraction from the skin of the host (see co-pending U.S.
patent application Ser. No. 11/077,715, filed on Mar. 10, 2005 and
entitled "TRANSCUTANEOUS ANALYTE SENSOR").
[0076] FIG. 3B is a side schematic view of a transcutaneous medical
device 34b of a preferred embodiment adapted to be inserted through
the skin of a host. In this embodiment, the device is designed with
an increased stiffness at a distal tip 30 (or a distal portion 28)
of the device (relative to intermediate and/or proximal portions)
in order to provide increased strength and/or structural integrity
to the tip, which is illustrated by heavy cross-hatching. In some
situations, the device is inserted into the host such that a tunnel
is formed therein. When the device abuts the tunnel end, increased
stress to the distal tip can occur. This increased stress can cause
the device to bend, resulting in malfunctioning of the device.
[0077] In some embodiments, this increased stiffness is designed
into the device by creating a greater hardness of the distal tip of
the device, for example, by annealing or coating the device. In one
embodiment of a transcutaneous analyte sensor as described above
with reference to FIG. 1, a higher pitch of the helically wound
reference electrode for at least a few windings at a distal end of
the reference electrode creates a relative stiffness of the distal
portion or tip of the device. It is believed that a stiffer distal
portion or tip advantageously provides increased stability, column
strength, and proper placement of the device in the host.
[0078] FIG. 3C is a side schematic view of a transcutaneous medical
device 34c in yet another embodiment adapted to be inserted through
the skin of a host. In this embodiment, the device 34c is designed
with an increased flexibility at an intermediate portion 32
thereof. Namely, the intermediate portion of the device is designed
to absorb shock between the proximal and distal portions, for
example, such that movement of the ex vivo portion of the device
does not substantially translate to the in vivo portion of the
device (and vice versa). In some aspects of this embodiment, the
distal portion is designed with a flexibility similar to that of
the intermediate portion. In some aspects of this embodiment, the
flexibility gradually changes from the distal portion to the
proximal portion, including a relatively flexible intermediate
portion 32.
[0079] In some embodiments, any combination of the above described
relatively stiff or flexible portions can be designed into a
transcutaneous medical device. In fact, a variety of additional
stiff and/or flexible portions can be incorporated into the distal
and/or proximal portions of the device without departing from the
scope of the preferred embodiments. The flexibility and/or
stiffness can be stepped, gradual, or any combination thereof.
[0080] The variable stiffness (flexibility) of the preferred
embodiments can be provided by a variable pitch of any one or more
wires of the device, a variable cross-section of any one or more
wires of the device, and/or a variable hardening and/or softening
of any one or more wires of the device, for example, as is
described in more detail below.
[0081] FIGS. 4A to 4D are perspective and side views of a variable
stiffness wire used in a transcutaneous medical device, such as an
analyte sensor. In FIG. 4A, a wire 36 is shown, which can represent
the working electrode or reference electrode of the embodiment
described with reference to FIG. 1, for example. Alternatively, the
wire 36 can represent one or more wires of a multiple wire sensor
(examples of each are described above). The variable stiffness wire
described herein can be employed in a transcutaneous medical device
to provide variable stiffness along a portion of the length of the
device, such as in an analyte sensor.
[0082] FIG. 4B is a side view of a variable stiffness wire 36b
wherein physical processing of the distal, intermediate, and/or
proximal portions of the wire provide for variability of the
stiffness of the wire. In some embodiments, some portion (for
example, the distal portion) of the wire is softened using a
process such as annealing or tempering. In some embodiments, some
portion (for example, the proximal portion) of the wire is hardened
using a process such as drawing or rolling. In some embodiments,
some combination of softening and hardening as described herein are
employed to provide variable stiffness of the wire. In the
embodiment described with reference to FIG. 1, including a working
electrode and a reference electrode, the working electrode can be
hardened and/or softened to provide for the variable stiffness of
one or more portions of the device, such as is described in more
detail elsewhere herein. Another alternative embodiment provides a
varying modulus of elasticity of the material to provide the
variable stiffness of the preferred embodiments.
[0083] FIG. 4C is a side view of an alternative variable stiffness
wire 36c, wherein the wire has a gradually increasing or decreasing
diameter along its length. The variability in diameter can be
produced by physical or chemical processes, for example, by
grinding, machining, rolling, pulling, etching, drawing, swaging,
or the like. In this way, a transcutaneous analyte sensor, or other
transcutaneous medical device, can be produced having a variable
stiffness. In the embodiment described with reference to FIG. 1,
for example, including a working electrode and a reference
electrode, the working electrode can be formed with a variable
diameter to provide for the variable stiffness of one or more
portions of the device, such as described in more detail elsewhere
herein.
[0084] FIG. 4D is a side view of another alternative variable
stiffness wire 36d, wherein the wire is step increased or decreased
to provide two (or more) different flexibilities of the wire. The
wire can be stepped by physical or chemical processes known in the
art, such as described with reference to FIG. 4C. In this way, a
transcutaneous analyte sensor, or other transcutaneous medical
device, can be produced with a variable stiffness. A noted
advantage of the smaller diameter configurations of FIGS. 4C and 4D
include reduced sizing of the in vivo portion of the device, which
is believed to be more comfortable for the patient and to induce
less invasive trauma around the device, thereby providing an
optimized device design.
[0085] FIGS. 5A and 5B are perspective and cross-sectional views of
a variable stiffness wire 38 in an alternative embodiment
representing any one or more wires associated with a transcutaneous
medical device, such as an analyte sensor. For example, the wire 38
can represent the reference electrode of the embodiment described
with reference to FIG. 1. Alternatively, the wire 38 can represent
the wire of a single or multiple wire sensor (examples of each are
described above).
[0086] In this embodiment, two distinct portions 40, 42 are shown
with first and second pitches; however, the illustration is not
meant to be limiting and the variable pitch can include any number
of gradual portions, stepped portions, or the like. Additionally,
the variable pitch and/or helical configuration can be provided on
only a portion of the wire or on the entire length of the wire, and
can include any number of pitch changes. In this embodiment, a
first portion 40 is wound to have relatively closely spaced coils,
namely, a high helix pitch, whereas a second 42 portion is not
subjected to high stress levels and can include coils wound with a
lower helix pitch. The helix pitch is defined as the number of
coils of the wire core per unit length of the device, or the
distance between the coils.
[0087] FIG. 5B is a cross-sectional view along line B-B of the
device of FIG. 5A, illustrating a first distance d.sub.1 between
the coils in the first portion 40 and a second distance d.sub.2
between the coils in the second portion 42, wherein d.sub.2 is
greater than d.sub.1. Thus, the wire has a variable stiffness
attributable to the varying helix pitch over the length of the
sensor. In this way, portions of a device having wire with a low
helix pitch are designed with greater flexibility and are more able
to handle the stresses associated with motion of the sensor while
portions of the sensor having wire with a high helix pitch are
designed with more stiffness and provide more stability for the
sensor in the housing. Any portions (proximal, intermediate, and/or
distal portions (or tips)) can be designed with a variable pitch to
impart variable stiffness.
[0088] FIGS. 6A and 6B are perspective and longitudinal views of a
variable stiffness wire 44 in yet another alternative embodiment
representing any one or more wires associated with a transcutaneous
medical device, such as an analyte sensor. For example, the wire 44
can be the reference electrode of the embodiment described with
reference to FIG. 1. Alternatively, the wire 44 can be a working
electrode, and/or one or more wires of a multiple wire sensor
(examples of each are described above).
[0089] In this embodiment, two distinct portions 46, 48 are shown
with first and second wire diameters that provide a variable
cross-section; however, the illustration is not meant to be
limiting and the variable cross-section can be gradual, stepped, or
the like. Additionally, the variable cross-section and/or helical
configuration can be provided on only a portion of the wire or on
the entire length of the wire, and can include any number of
cross-section changes. In this embodiment, the helically wound wire
is designed with a variable cross-sectional area over the length of
the sensor from a small cross-sectional area in the first portion
46 to a larger cross-sectional area in the second portion 48.
[0090] FIG. 6B is a cross-sectional view along line B-B of the
device of FIG. 6A, revealing cross-sectional information about one
or more wires that make up the coil, including a first
cross-section x, of the wire in the first portion 20 and a second
cross-section x.sub.2 of the wire in the second portion 48, wherein
x.sub.2 is greater than x.sub.1. Thus, the device of this
embodiment has a variable stiffness attributable to the varying
cross-section over the length of the sensor. In this way, first
portion 46 has a smaller cross-sectional area and is therefore more
flexible and capable of withstanding the stresses associated with
patient movement, for example; while the second portion 48 has a
larger cross-sectional area and is stiffer and provides more
stability and column strength desirable for mechanical and
electrical connections, for example.
[0091] The transcutaneous analyte sensor of FIG. 1 includes a
helical configuration. The helical surface topography of the
reference electrode surrounding the working electrode not only
provides electrochemical functionality, but can also provide
anchoring within the host tissue. The device preferably remains
substantially stationary within the tissue of the host, such that
migration or motion of the sensor with respect to the surrounding
tissue is minimized. Migration or motion can cause inflammation at
the sensor implant site due to irritation and can also cause noise
on the sensor signal due to motion-related artifact, for example.
Therefore, it can be advantageous to provide an anchoring mechanism
that provides support for the sensor in vivo portion to avoid or
minimize the above-mentioned problems. Combining advantageous
sensor geometry with advantageous anchoring minimizes additional
parts in the device, and allows for an optimally small or low
profile design of the sensor. Additionally or alternatively,
anchoring can be provided by prongs, spines, barbs, wings, hooks,
rough surface topography, gradually changing diameter, or the like,
which can be used alone or in combination with the helical surface
topography to stabilize the sensor within the subcutaneous
tissue.
EXAMPLE
[0092] FIG. 7 is an expanded view of distal and proximal portions
of a transcutaneous sensor 50 in one example. FIG. 7 illustrates a
sensor 50 broken away between its distal portion 52 and proximal
portion 54, representing any length or configuration there between.
In the illustrated embodiment, the sensor 50 includes two
electrodes: a working electrode 56 and one additional electrode,
which can function as a counter and/or reference electrode,
hereinafter referred to as the reference electrode 58. Each
electrode is formed from a fine wire with a diameter of
approximately 0.0045 inches.
[0093] The working electrode 56 comprises a platinum wire and is
configured and arranged to measure the concentration of an analyte.
In this example of an enzymatic electrochemical sensor, the working
electrode measures the hydrogen peroxide produced by an enzyme
catalyzed reaction of the analyte being detected and creates a
measurable electronic current (for example, detection of glucose
utilizing glucose oxidase produces H.sub.2O.sub.2 peroxide as a by
product, H.sub.2O.sub.2 reacts with the surface of the working
electrode producing two protons (2H.sup.+), two electrons
(2e.sup.-) and one molecule of oxygen (O.sub.2) which produces the
electronic current being detected).
[0094] The working electrode 56 is covered with an insulator 57,
e.g., Parylene, which is vapor-deposited on the working electrode.
Parylene is an advantageous conformal coating because of its
strength, lubricity, and electrical insulation properties; however,
a variety of other insulating materials can also be used, for
example, fluorinated polymers, polyethyleneterephthalate,
polyurethane, polyimide, or the like. The reference electrode 58,
which can function as a counter electrode alone, or as a dual
reference and counter electrode, is preferably silver or a
silver-containing material. In this example, the reference
electrode 58 is helically twisted around the working electrode 56.
A window 55 is formed on the insulating material to expose an
electroactive surface of the working electrode 56. Other methods
and configurations for exposing electroactive surfaces can also be
employed.
[0095] In this example, the reference electrode 58 is wound with a
variable pitch that creates a variable stiffness along the length
of the sensor 50. Namely, the sensor 50 is designed with a greater
stiffness generally in the proximal portion 54 than the
intermediate and/or the distal portions 52. However, an increased
stiffness of a section of the distal portion 52, shown adjacent to
the window 55 wherein the reference electrode 58 includes a higher
helix pitch for a few windings, provides increased strength in a
high stress location, without inhibiting the overall flexibility of
the distal portion 52. It is believed that in situations wherein
movement of the tissue within the patient and relative movement
between the in vivo and ex vivo portions of the device create
stresses on the device, greater flexibility in a distal portion
(and optionally in the intermediate portion relative to the
proximal portion) can provide relief from these mechanical
stresses, protecting both the integrity of the sensor and the host
tissue. Additionally or alternatively, in situations wherein
mechanical and/or electrical connections are employed for accurate
function, greater stiffness in the proximal portion (and/or the
proximal tip) of the device can increase the stability and
reliability of these connections. Additionally, this exemplary
configuration is advantageous for the reasons described above, and
further provides an enhanced mechanical stability by the
distribution of forces of the helical wire along the straight
wire.
[0096] Methods and devices that are suitable for use in conjunction
with aspects of the preferred embodiments are disclosed in U.S.
Pat. No. 4,994,167 issued Feb. 19, 1991 and entitled "BIOLOGICAL
FLUID MEASURING DEVICE"; U.S. Pat. No. 4,757,022 issued February
Jul. 12, 1988 and entitled "BIOLOGICAL FLUID MEASURING DEVICE";
U.S. Pat. No. 6,001,067 issued February Dec. 14, 1999 and entitled
"DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS"; U.S. Pat. No.
6,741,877 issued February May 25, 2004 and entitled "DEVICE AND
METHOD FOR DETERMINING ANALYTE LEVELS"; U.S. Pat. No. 6,702,857
issued February Mar. 9, 2004 and entitled "MEMBRANE FOR USE WITH
IMPLANTABLE DEVICES"; and U.S. Pat. No. 6,558,321 issued February
May 6, 2003 and entitled "SYSTEMS AND METHODS FOR REMOTE MONITORING
AND MODULATION OF MEDICAL DEVICES." Methods and devices that are
suitable for use in conjunction with aspects of the preferred
embodiments are disclosed in co-pending U.S. application Ser. No.
10/991,353 filed Nov. 16, 2004 and entitled "AFFINITY DOMAIN FOR
ANALYTE SENSOR"; U.S. application Ser. No. 11/055,779 filed Feb. 9,
2005 and entitled "BIOINTERFACE WITH MACRO-AND-MICRO-ARCHITECTURE";
U.S. application Ser. No. 11/004,561 filed Dec. 3, 2004 and
entitled "CALIBRATION TECHNIQUES FOR A CONTINUOUS ANALYTE SENSOR";
U.S. application Ser. No. 11/034,343 filed Jan. 11, 2005 and
entitled "COMPOSITE MATERIAL FOR IMPLANTABLE DEVICE"; U.S.
application Ser. No. 09/447,227 filed Nov. 22, 1999 and entitled
"DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS"; U.S.
application Ser. No. 11/021,046 filed Dec. 22, 2004 and entitled
"DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS"; U.S.
application Ser. No. 09/916,858 filed Jul. 27, 2001 and entitled
"DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS"; U.S.
application Ser. No. 11/039,269 filed Jan. 19, 2005 and entitled
"DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS"; U.S.
application Ser. No. 10/897,377 filed Jul. 21, 2004 and entitled
"ELECTROCHEMICAL SENSORS INCLUDING ELECTRODE SYSTEMS WITH INCREASED
OXYGEN GENERATION"; U.S. application Ser. No. 10/897,312 filed Jul.
21, 2004 and entitled "ELECTRODE SYSTEMS FOR ELECTROCHEMICAL
SENSORS"; U.S. application Ser. No. 10/838,912 filed May 3, 2004
and entitled "IMPLANTABLE ANALYTE SENSOR"; U.S. application Ser.
No. 10/838,909 filed May 3, 2004 and entitled "IMPLANTABLE ANALYTE
SENSOR"; U.S. application Ser. No. 10/838,658 filed May 3, 2004 and
entitled "IMPLANTABLE ANALYTE SENSOR"; U.S. application Ser. No.
11/034,344 filed Jan. 11, 2005 and entitled "IMPLANTABLE DEVICE
WITH IMPROVED RADIO FREQUENCY CAPABILITIES"; U.S. application Ser.
No. 10/896,772 filed Jul. 21, 2004 and entitled "INCREASING BIAS
FOR OXYGEN PRODUCTION IN AN ELECTRODE SYSTEM"; U.S. application
Ser. No. 10/789,359 filed Feb. 26, 2004 and entitled "INTEGRATED
DELIVERY DEVICE FOR CONTINUOUS GLUCOSE SENSOR"; U.S. application
Ser. No. 10/991,966 filed Nov. 17, 2004 and entitled "INTEGRATED
RECEIVER FOR CONTINUOUS ANALYTE SENSOR"; U.S. application Ser. No.
10/646,333 filed Aug. 22, 2003 and entitled "OPTIMIZED SENSOR
GEOMETRY FOR AN IMPLANTABLE GLUCOSE SENSOR"; U.S. application Ser.
No. 10/896,639 filed Jul. 21, 2004 and entitled "OXYGEN ENHANCING
MEMBRANE SYSTEMS FOR IMPLANTABLE DEVICES"; U.S. application Ser.
No. 10/647,065 filed Aug. 22, 2003 and entitled "POROUS MEMBRANES
FOR USE WITH IMPLANTABLE DEVICES"; U.S. application Ser. No.
10/896,637 filed Jul. 21, 2004 and entitled "ROLLED ELECTRODE ARRAY
AND ITS METHOD FOR MANUFACTURE"; U.S. application Ser. No.
09/916,711 filed Jul. 27, 2001 and entitled "SENSOR HEAD FOR USE
WITH IMPLANTABLE DEVICE"; U.S. application Ser. No. 11/021,162
filed Dec. 22, 2004 and entitled "SENSOR HEAD FOR USE WITH
IMPLANTABLE DEVICES"; U.S. application Ser. No. 11/007,920 filed
Dec. 8, 2004 and entitled "SIGNAL PROCESSING FOR CONTINUOUS ANALYTE
SENSOR"; U.S. application Ser. No. 10/695,636 filed Oct. 28, 2003
and entitled "SILICONE COMPOSITION FOR BIOCOMPATIBLE MEMBRANE";
U.S. application Ser. No. 11/038,340 filed Jan. 18, 2005 and
entitled "SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA";
U.S. application Ser. No. 11/007,635 filed Dec. 7, 2004 and
entitled "SYSTEMS AND METHODS FOR IMPROVING ELECTROCHEMICAL ANALYTE
SENSORS"; U.S. application Ser. No. 10/885,476 filed Jul. 6, 2004
and entitled "SYSTEMS AND METHODS FOR MANUFACTURE OF AN
ANALYTE-MEASURING DEVICE INCLUDING A MEMBRANE SYSTEM"; U.S.
application Ser. No. 10/648,849 filed Aug. 22, 2003 and entitled
"SYSTEMS AND METHODS FOR REPLACING SIGNAL ARTIFACTS IN A GLUCOSE
SENSOR DATA STREAM"; U.S. application Ser. No. 10/153,356 filed May
22, 2002 and entitled "TECHNIQUES TO IMPROVE POLYURETHANE MEMBRANES
FOR IMPLANTABLE GLUCOSE SENSORS"; U.S. application Ser. No.
10/846,150 filed May 14, 2004 and entitled "ANALYTE MEASURING
DEVICE"; U.S. application Ser. No. 10/842,716 filed May 10, 2004
and entitled "BIOINTERFACE MEMBRANES INCORPORATING BIOACTIVE
AGENTS"; U.S. application Ser. No. 10/657,843 filed Sep. 9, 2003
and entitled "DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS";
U.S. application Ser. No. 10/768,889 filed Jan. 29, 2004 and
entitled "MEMBRANE FOR USE WITH IMPLANTABLE DEVICES"; U.S.
application Ser. No. 10/633,367 filed Aug. 1, 2003 and entitled
"SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA"; U.S.
application Ser. No. 10/632,537 filed Aug. 1, 2003 and entitled
"SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA"; U.S.
application Ser. No. 10/633,404 filed Aug. 1, 2003 and entitled
"SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA"; U.S.
application Ser. No. 10/633,329 filed Aug. 1, 2003 and entitled
"SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA"; and U.S.
application Ser. No. 60/660,743, filed on Mar. 10, 2005 and
entitled "SYSTEMS AND METHODS FOR PROCESSING ANALYTE SENSOR DATA
FOR SENSOR CALIBRATION."
[0097] All references cited herein, including but not limited to
published and unpublished applications, patents, and literature
references, and also including but not limited to the references
listed in the Appendix, are incorporated herein by reference in
their entirety and are hereby made a part of this specification. To
the extent publications and patents or patent applications
incorporated by reference contradict the disclosure contained in
the specification, the specification is intended to supersede
and/or take precedence over any such contradictory material.
[0098] The term "comprising" as used herein is synonymous with
"including," "containing," or "characterized by," and is inclusive
or open-ended and does not exclude additional, unrecited elements
or method steps.
[0099] All numbers expressing quantities of ingredients, reaction
conditions, and so forth used in the specification are to be
understood as being modified in all instances by the term "about."
Accordingly, unless indicated to the contrary, the numerical
parameters set forth herein are approximations that may vary
depending upon the desired properties sought to be obtained. At the
very least, and not as an attempt to limit the application of the
doctrine of equivalents to the scope of any claims in any
application claiming priority to the present application, each
numerical parameter should be construed in light of the number of
significant digits and ordinary rounding approaches.
[0100] The above description discloses several methods and
materials of the present invention. This invention is susceptible
to modifications in the methods and materials, as well as
alterations in the fabrication methods and equipment. Such
modifications will become apparent to those skilled in the art from
a consideration of this disclosure or practice of the invention
disclosed herein. Consequently, it is not intended that this
invention be limited to the specific embodiments disclosed herein,
but that it cover all modifications and alternatives coming within
the true scope and spirit of the invention.
* * * * *