|Publication number||USRE43399 E1|
|Application number||US 12/139,305|
|Publication date||22 May 2012|
|Filing date||13 Jun 2008|
|Priority date||25 Jul 2003|
|Also published as||EP1649260A2, EP1649260A4, US7074307, US20050115832, US20120228134, US20140001042, WO2005012873A2, WO2005012873A3|
|Publication number||12139305, 139305, US RE43399 E1, US RE43399E1, US-E1-RE43399, USRE43399 E1, USRE43399E1|
|Inventors||Peter C. Simpson, James R. Petisce, Victoria E. Carr-Brendel, James H. Brauker|
|Original Assignee||Dexcom, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (103), Non-Patent Citations (338), Classifications (17), Legal Events (4)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 60/490,007, filed Jul. 25, 2003, the contents of which are hereby incorporated by reference in their entirety.
The present invention relates generally to systems and methods for improving electrochemical sensor performance.
Electrochemical sensors are useful in chemistry and medicine to determine the presence or concentration of a biological analyte. Such sensors are useful, for example, to monitor glucose in diabetic patients and lactate during critical care events.
Diabetes mellitus is a disorder in which the pancreas 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 causes an array of physiological derangements (kidney failure, skin ulcers, or bleeding into the vitreous of the eye) associated with the deterioration of small blood vessels. A hypoglycemic reaction (low blood sugar) is induced by an inadvertent overdose of insulin, or after a normal dose of insulin or glucose-lowering agent accompanied by extraordinary exercise or insufficient food intake.
Conventionally, a diabetic person carries a self-monitoring blood glucose (SMBG) monitor, which typically comprises uncomfortable finger pricking methods. Due to the lack of comfort and convenience, a diabetic will normally only measure his or her glucose level two to four times per day. Unfortunately, these time intervals are spread apart so far that the diabetic will likely find out too late, sometimes incurring dangerous side effects, of a hyperglycemic or hypoglycemic condition. It is not only unlikely that a diabetic will take a timely SMBG value, but additionally the diabetic will not know if their blood glucose value is going up (higher) or down (lower) based on conventional methods.
Consequently, a variety of transdermal and implantable electrochemical sensors are being developed for continuously detecting and/or quantifying blood glucose values. Many implantable glucose sensors suffer from complications within the body and provide only short-term or less-than-accurate working of blood glucose. Similarly, transdermal sensors have problems in accurately working and reporting back glucose values continuously over extended periods of time. Some efforts have been made to obtain blood glucose data from implantable devices and retrospectively determine blood glucose trends for analysis; however these efforts do not aid the diabetic in determining real-time blood glucose information. Some efforts have also been made to obtain blood glucose data from transdermal devices for prospective data analysis, however similar problems have occurred.
In contrast to the prior art, the sensors of preferred embodiments advantageously generate oxygen to allow the sensor to function at sufficient oxygen levels independent of the oxygen concentration in the surrounding environment. In another aspect of the preferred embodiments, systems and methods for modifying electrochemical interferants are provided.
Accordingly, in a first embodiment, an electrochemical sensor for determining a presence or a concentration of an analyte in a fluid is provided, the sensor comprising a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte; an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface.
In an aspect of the first embodiment, the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
In an aspect of the first embodiment, the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
In an aspect of the first embodiment, the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode.
In an aspect of the first embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen.
In an aspect of the first embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and permeable to interfering species.
In an aspect of the first embodiment, the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
In an aspect of the first embodiment, the polymer comprises a material that is permeable to glucose and oxygen.
In an aspect of the first embodiment, the polymer comprises a material that is permeable to glucose, oxygen, and interfering species.
In an aspect of the first embodiment, the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, glucose, urate, ascorbate, and acetaminophen.
In an aspect of the first embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
In an aspect of the first embodiment, the auxiliary electrode is configured to electrochemically modify an electrochemical interferant to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
In an aspect of the first embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
In a second embodiment, an electrochemical sensor for determining a presence or a concentration of an analyte in a fluid is provided, the sensor comprising a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte; an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferant such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode.
In an aspect of the second embodiment, the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
In an aspect of the second embodiment, the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
In an aspect of the second embodiment, the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode.
In an aspect of the second embodiment, the polymer comprises a material that is permeable to an electrochemical interferant.
In an aspect of the second embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen.
In an aspect of the second embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and interferants.
In an aspect of the second embodiment, the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
In an aspect of the second embodiment, the polymer comprises a material that is permeable to glucose and oxygen.
In an aspect of the second embodiment, the polymer comprises a material that is permeable to glucose, oxygen, and interferants.
In an aspect of the second embodiment, the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, glucose, urate, ascorbate, and acetaminophen.
In an aspect of the second embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.1V.
In an aspect of the second embodiment, the auxiliary electrode is configured to generate oxygen.
In an aspect of the second embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
In a third embodiment, an electrochemical sensor is provided comprising an electroactive surface configured to measure an analyte; and an auxiliary interferant-modifying electrode configured to modify an electrochemical interferant such that the electrochemical interferant is rendered substantially non-reactive at the electroactive surface.
In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary interferant-modifying electrode.
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.
In order to facilitate an understanding of the preferred embodiments, a number of terms are defined below.
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-β 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 β-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, β); 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 or endogenous, for example, a metabolic product, a hormone, an antigen, an antibody, and the like. Alternatively, the analyte can be introduced into the body or exogenous, 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).
The terms “operable connection,” “operably connected,” and “operably linked” as used herein are broad terms and are used in their ordinary sense, including, without limitation, one or more components linked to another component(s) in a manner 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 convert that information into a signal; the signal can then be transmitted to a circuit. In this case, the electrode is “operably linked” to the electronic circuitry.
The term “host” as used herein is a broad term and is used in its ordinary sense, including, without limitation, mammals, particularly humans.
The term “sensor,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, the portion or portions of an analyte-monitoring device that detects an analyte. In one embodiment, the sensor includes an electrochemical cell that has a working electrode, a reference electrode, and optionally a counter electrode passing through and secured within the sensor body forming an electrochemically reactive surface at one location on the body, an electronic connection at another location on the body, and a membrane system affixed to the body and covering the electrochemically reactive surface. During general operation of the sensor, a biological sample (for example, blood or interstitial fluid), or a portion thereof, contacts (directly or after passage through one or more membranes or domains) an enzyme (for example, glucose oxidase); the reaction of the biological sample (or portion thereof) results in the formation of reaction products that allow a determination of the analyte level in the biological sample.
The term “signal output,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, an analog or digital signal directly related to the measured analyte from the analyte-measuring device. The term broadly encompasses a single point, or alternatively, a plurality of time spaced data points from a substantially continuous glucose sensor, 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.
The term “electrochemical cell,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, a device in which chemical energy is converted to electrical energy. Such a cell typically consists of two or more electrodes held apart from each other and in contact with an electrolyte solution. Connection of the electrodes to a source of direct electric current renders one of them negatively charged and the other positively charged. Positive ions in the electrolyte migrate to the negative electrode (cathode) and there combine with one or more electrons, losing part or all of their charge and becoming new ions having lower charge or neutral atoms or molecules; at the same time, negative ions migrate to the positive electrode (anode) and transfer one or more electrons to it, also becoming new ions or neutral particles. The overall effect of the two processes is the transfer of electrons from the negative ions to the positive ions, a chemical reaction.
The term “potentiostat,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, an electrical system that controls the potential between the working and reference electrodes of a three-electrode cell at a preset value independent of resistance changes between the electrodes. It forces whatever current is necessary to flow between the working and counter electrodes to keep the desired potential, as long as the cell voltage and current do not exceed the compliance limits of the potentiostat.
The terms “electrochemically reactive surface” and “electroactive surface” as used herein are broad terms and are used in their ordinary sense, including, without limitation, the surface of an electrode where an electrochemical reaction takes place. In one example, a working electrode measures hydrogen peroxide produced by the enzyme catalyzed reaction of the analyte being detected reacts creating an electric current (for example, detection of glucose analyte utilizing glucose oxidase produces H2O2 as a by product, H2O2 reacts with the surface of the working electrode producing two protons (2H+), two electrons (2e−) and one molecule of oxygen (O2) which produces the electronic current being detected). In the case of the counter electrode, a reducible species, for example, O2 is reduced at the electrode surface in order to balance the current being generated by the working electrode.
The term “sensing region” as used herein is a broad term and is used in its ordinary sense, including, without limitation, 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, a reference electrode, and optionally a counter electrode 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 system affixed to the body and covering the electrochemically reactive surface.
The terms “raw data stream” and “data stream,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, an analog or digital signal directly related to the measured an analyte from an analyte sensor. In one example, the raw data stream is digital data in “counts” converted by an A/D converter from an analog signal (for example, voltage or amps) representative of a analyte concentration. The terms broadly encompass a plurality of time spaced data points from a substantially continuous analyte sensor, 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.
The term “counts,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, a unit of measurement of a digital signal. In one example, a raw data stream measured in counts is directly related to a voltage (for example, converted by an A/D converter), which is directly related to current from the working electrode. In another example, counter electrode voltage measured in counts is directly related to a voltage.
The terms “electrical potential” and “potential” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, the electrical potential difference between two points in a circuit which is the cause of the flow of a current.
The term “ischemia,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, local and temporary deficiency of blood supply due to obstruction of circulation to a part (for example, a sensor). Ischemia can be caused by mechanical obstruction (for example, arterial narrowing or disruption) of the blood supply, for example.
The term “system noise,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, unwanted electronic or diffusion-related noise which can include Gaussian, motion-related, flicker, kinetic, or other white noise, for example.
The terms “signal artifacts” and “transient non-glucose related signal artifacts that have a higher amplitude than system noise,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, signal noise that is caused by substantially non-glucose reaction rate-limiting phenomena, such as ischemia, pH changes, temperature changes, pressure, and stress, for example. Signal artifacts, as described herein, are typically transient and characterized by a higher amplitude than system noise.
The term “low noise,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, noise that substantially decreases signal amplitude.
The terms “high noise” and “high spikes,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, noise that substantially increases signal amplitude.
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. For example, some embodiments of a device include a membrane system having a cell disruptive domain and a cell impermeable domain. If the sensor is deemed to be the point of reference and the cell disruptive domain is positioned farther from the sensor, then that domain is distal to the sensor.
The phrase “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. For example, some embodiments of a device include a membrane system having a cell disruptive domain and a cell impermeable domain. If the sensor is deemed to be the point of reference and the cell impermeable domain is positioned nearer to the sensor, then that domain is proximal to the sensor.
The terms “interferants” and “interfering species,” as used herein, are broad terms and are used in their ordinary sense, including, but not limited to, effects and/or species that interfere 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 electrochemical sensor, interfering species are compounds with an oxidation potential that overlaps with the analyte to be measured.
As employed herein, the following abbreviations apply: Eq and Eqs (equivalents); mEq (milliequivalents); M (molar); mM (millimolar) μM (micromolar); N (Normal); mol (moles); mmol (millimoles); μmol (micromoles); nmol (nanomoles); g (grams); mg (milligrams); μg (micrograms); Kg (kilograms); L (liters); mL (milliliters); dL (deciliters); μL (microliters); cm (centimeters); mm (millimeters); μm (micrometers); nm (nanometers); h and hr (hours); min. (minutes); s and sec. (seconds); ° C. (degrees Centigrade).
The preferred embodiments relate to the use of an electrochemical sensor that measures a concentration of an analyte of interest or a substance indicative of the concentration or presence of the analyte in fluid. In some embodiments, the sensor is a continuous device, for example a subcutaneous, transdermal, or intravascular device. In some embodiments, the device can analyze a plurality of intermittent blood samples.
The sensor uses any known method, including invasive, minimally invasive, and non-invasive sensing techniques, to provide an output signal indicative of the concentration of the analyte of interest. The sensor is of the type that senses a product or reactant of an enzymatic reaction between an analyte and an enzyme in the presence of oxygen as a measure of the analyte in vivo or in vitro. Such a sensor typically comprises a membrane surrounding the enzyme through which a bodily fluid passes and in which an analyte within the bodily fluid reacts with an enzyme in the presence of oxygen to generate a product. The product is then measured using electrochemical methods and thus the output of an electrode system functions as a measure of the analyte. In some embodiments, the sensor can use an amperometric, coulometric, conductimetric, and/or potentiometric technique for measuring the analyte. In some embodiments, the electrode system can be used with any of a variety of known in vitro or in vivo analyte sensors or monitors.
In this embodiment, the electrode system 16 is operably connected to the sensor electronics (
In the embodiment of
The change in H2O2 can be monitored to determine glucose concentration because for each glucose molecule metabolized, there is a proportional change in the product H2O2. Oxidation of H2O2 by the working electrode is balanced by reduction of ambient oxygen, enzyme generated H2O2, or other reducible species at the counter electrode. The H2O2 produced from the glucose oxidase reaction further reacts at the surface of working electrode and produces two protons (2H+), two electrons (2e−), and one oxygen molecule (O2). In such embodiments, because the counter electrode utilizes oxygen as an electron acceptor, the most likely reducible species for this system are oxygen or enzyme generated peroxide. There are two main pathways by which oxygen can be consumed at the counter electrode. These pathways include a four-electron pathway to produce hydroxide and a two-electron pathway to produce hydrogen peroxide. In addition to the counter electrode, oxygen is further consumed by the reduced glucose oxidase within the enzyme domain. Therefore, due to the oxygen consumption by both the enzyme and the counter electrode, there is a net consumption of oxygen within the electrode system. Theoretically, in the domain of the working electrode there is significantly less net loss of oxygen than in the region of the counter electrode. In some embodiments, there is a close correlation between the ability of the counter electrode to maintain current balance and sensor function.
In general, in electrochemical sensors wherein an enzymatic reaction depends on oxygen as a co-reactant, depressed function or inaccuracy can be experienced in low oxygen environments, for example in vivo. Subcutaneously implanted devices are especially susceptible to transient ischemia that can compromise device function; for example, because of the enzymatic reaction required for an implantable amperometric glucose sensor, oxygen must be in excess over glucose in order for the sensor to effectively function as a glucose sensor. If glucose becomes in excess, the sensor turns into an oxygen sensitive device. In vivo, glucose concentration can vary from about one hundred times or more that of the oxygen concentration. Consequently, one limitation of prior art enzymatic-based electrochemical analyte sensors can be caused by oxygen deficiencies, which is described in more detail with reference to
A microprocessor 22 is the central control unit that houses EEPROM 23 and SRAM 24, and controls the processing of the sensor electronics. The alternative embodiments can utilize a computer system other than a microprocessor to process data as described herein. In some alternative embodiments, an application-specific integrated circuit (ASIC) can be used for some or all the sensor's central processing. EEPROM 23 provides semi-permanent storage of data, storing data such as sensor ID and necessary programming to process data signals (for example, programming for data smoothing such as described elsewhere herein). SRAM 24 is used for the system's cache memory, for example for temporarily storing recent sensor data.
The battery 25 is operatively connected to the microprocessor 22 and provides the necessary power for the sensor. In one embodiment, the battery is a Lithium Manganese Dioxide battery, however any appropriately sized and powered battery can be used. In some embodiments, a plurality of batteries can be used to power the system. Quartz crystal 26 is operatively connected to the microprocessor 22 and maintains system time for the computer system.
The RF Transceiver 27 is operably connected to the microprocessor 22 and transmits the sensor data from the sensor to a receiver. Although a RF transceiver is shown here, some other embodiments can include a wired rather than wireless connection to the receiver. In yet other embodiments, the sensor can be transcutaneously connected via an inductive coupling, for example. The quartz crystal 28 provides the system time for synchronizing the data transmissions from the RF transceiver. The transceiver 27 can be substituted with a transmitter in one embodiment.
In one situation, when oxygen is deficient relative to the amount of glucose, then the enzymatic reaction is limited by oxygen rather than glucose. Thus, the output signal is indicative of the oxygen concentration rather than the glucose concentration, producing erroneous signals. Additionally, when an enzymatic reaction is rate-limited by oxygen, glucose is expected to build up in the membrane because it is not completely catabolized during the oxygen deficit. When oxygen is again in excess, there is also excess glucose due to the transient oxygen deficit. The enzyme rate then speeds up for a short period until the excess glucose is catabolized, resulting in spikes of non-glucose related increased sensor output. Accordingly, because excess oxygen (relative to glucose) is necessary for proper sensor function, transient ischemia can result in a loss of signal gain in the sensor data.
In another situation, oxygen deficiency can be seen at the counter electrode when insufficient oxygen is available for reduction, which thereby affects the counter electrode in that it is unable to balance the current coming from the working electrode. When insufficient oxygen is available for the counter electrode, the counter electrode can be driven in its electrochemical search for electrons all the way to its most negative value, which could be ground or 0.0 V, which causes the reference to shift, reducing the bias voltage, such is as described in more detail below. In other words, a common result of ischemia a drop off in sensor current as a function of glucose concentration (for example, lower sensitivity). This happens because the working electrode no longer oxidizes all of the H2O2 arriving at its surface because of the reduced bias. In some extreme circumstances, an increase in glucose can produce no increase in current or even a decrease in current.
In some situations, transient ischemia can occur at high glucose levels, wherein oxygen can become limiting to the enzymatic reaction, resulting in a non-glucose dependent downward trend in the data. In some situations, certain movements or postures taken by the patient can cause transient signal artifacts as blood is squeezed out of the capillaries resulting in local ischemia and causing non-glucose dependent signal artifacts. In some situations, oxygen can also become transiently limited due to contracture of tissues around the sensor interface. This is similar to the blanching of skin that can be observed when one puts pressure on it. Under such pressure, transient ischemia can occur in both the epidermis and subcutaneous tissue. Transient ischemia is common and well tolerated by subcutaneous tissue. However, such ischemic periods can cause an oxygen deficit in implanted devices that can last for many minutes or even an hour or longer.
Although some examples of the effects of transient ischemia on a prior art glucose sensor are described above, similar effects can be seen with analyte sensors that use alternative catalysts to detect other analytes, for example, amino acids (amino acid oxidase), alcohol (alcohol oxidase), galactose (galactose oxidase), lactate (lactate oxidase), cholesterol (cholesterol oxidase), or the like.
Another problem with conventional electrochemical sensors is that they can electrochemically react not only with the analyte to be measured (or by-product of the enzymatic reaction with the analyte), but additionally can react with other electroactive species that are not intentionally being measured (for example, interfering species), which causes an increase in signal strength due to these “interfering species”. In other words, interfering species are compounds with an oxidation or reduction potential that overlaps with the analyte to be measured (or the by-product of the enzymatic reaction with the analyte). For example, in a conventional amperometric glucose oxidase-based glucose sensor wherein the sensor measures hydrogen peroxide, interfering species such as acetaminophen, ascorbate, and urate are known to produce inaccurate signal strength when they are not properly controlled.
Some conventional glucose sensors utilize a membrane system that blocks at least some interfering species, such as ascorbate and urate. In some such systems, at least one layer of the membrane system includes a porous structure that has a relatively impermeable matrix with a plurality of “micro holes” or pores of molecular dimensions, such that transfer through these materials is primarily due to passage of species through the pores (for example, the layer acts as a microporous barrier or sieve blocking interfering species of a particular size). In other such systems, at least one layer of the membrane system defines a permeability that allows selective dissolution and diffusion of species as solutes through the layer. Unfortunately, it is difficult to find membranes that are satisfactory or reliable in use, especially in vivo, which effectively block all interferants and/or interfering species in some embodiments.
Electrochemical Sensors of the Preferred Embodiments
In one aspect of the preferred embodiments, an electrochemical sensor is provided with an auxiliary electrode configured to generate oxygen in order to overcome the effects of transient ischemia. In another aspect of the preferred embodiments, an electrochemical sensor is provided with an auxiliary electrode configured to electrochemically modify (for example, oxidize or reduce) electrochemical interferants to render them substantially non-electroactively reactive at the electroactive sensing surface(s) in order to overcome the effects of interferants on the working electrode.
It is known that oxygen can be generated as a product of electrochemical reactions occurring at a positively charged electrode (for example, set at about +0.6 to about +1.2 V or more). One example of an oxygen producing reaction is the electrolysis of water, which creates oxygen at the anode (for example, the working electrode). In the exemplary electrochemical glucose sensor, glucose is converted to hydrogen peroxide by reacting with glucose oxidase and oxygen, after which the hydrogen peroxide is oxidized at the working electrode and oxygen is generated therefrom. It is noted that one challenge to generating oxygen electrochemically in this way is that while an auxiliary electrode does produce excess oxygen, the placement of the auxiliary electrode in proximity to the analyte-measuring working electrode can cause oxidation of hydrogen peroxide at the auxiliary electrode, resulting in reduced signals at the working electrode. It is also known that many electrochemical interferants can be reduced at a potential of from about +0.1V to +1.2V or more; for example, acetaminophen is reduced at a potential of about +0.4 V.
Accordingly, the sensors of preferred embodiments place an auxiliary electrode above the electrode system 16, or other electroactive sensing surface, thereby reducing or eliminating the problem of inaccurate signals as described above.
The membrane system 18 includes a plurality of domains (for example, cell impermeable domain, resistance domain, enzyme domain, and/or other domains such as are described in U.S. Published Patent Application 2003/0032874 to Rhodes et al. and copending U.S. patent 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”, the contents of which are incorporated herein by reference in their entireties) is located proximal to the external solution and finctions to transport fluids necessary for the enzymatic reaction, while protecting inner components of the sensor from harsh biohazards, for example. Although each domain is not independently shown, the enzyme 38 is shown disposed between an auxiliary electrode 36 and the working electrode 16a in the illustrated embodiment.
Preferably, the auxiliary electrode 36 is located within or adjacent to the membrane system 18, for example, between the enzyme and other domains, although the auxiliary electrode can be placed anywhere between the electroactive sensing surface and the outside fluid. The auxiliary electrode 36 is formed from known working electrode materials (for example, platinum, palladium, graphite, gold, carbon, conductive polymer, or the like) and has a voltage setting that produces oxygen (for example, from about +0.6 V to +1.2 V or more) and/or that electrochemically modifies (for example, reduces) electrochemical interferants to render them substantially non-reactive at the electroactive sensing surface(s) (for example, from about +0.1 V to +1.2 V or more). The auxiliary electrode can be a mesh, grid, plurality of spaced wires or conductive polymers, or other configurations designed to allow analytes to penetrate therethrough.
In the aspect of the preferred embodiments wherein the auxiliary electrode 36 is configured to generate oxygen, the oxygen generated from the auxiliary electrode 36 diffuses upward and/or downward to be utilized by the enzyme 38 and/or the counter electrode (depending on the placement of the auxiliary electrode). Additionally, the analyte (for example, glucose) from the outside solution (diffuses through the auxiliary electrode 36) reacts with the enzyme 38 and produces a measurable product (for example, hydrogen peroxide). Therefore, the product of the enzymatic reaction diffuses down to the working electrode 16a for accurate measurement without being eliminated by the auxiliary electrode 36.
In one alternative embodiment, the auxiliary electrode 36 can be coated with a polymeric material, which is impermeable to glucose but permeable to oxygen. By this coating, glucose will not electroactively react at the auxiliary electrode 36, which can otherwise cause at least some of the glucose to pre-oxidize as it passes through the auxiliary electrode 36 (when placed above the enzyme), which can prevent accurate glucose concentration measurements at the working electrode in some sensor configurations. In one embodiment, the polymer coating comprises silicone, however any polymer that is selectively permeable to oxygen, but not glucose, can be used. The auxiliary electrode 16 can be coated by any known process, such as dip coating or spray coating, after which is can be blown, blotted, or the like to maintain spaces within the electrode for glucose transport.
In another alternative embodiment, the auxiliary electrode 36 can be coated with a polymeric material that is permeable to glucose and oxygen and can be placed between the enzyme and the outside fluid. Consequently, the polymeric coating will cause glucose from the outside fluid to electroactively react at the auxiliary electrode 36, thereby limiting the amount of glucose that passes into the enzyme 38, and thus reducing the amount of oxygen necessary to successfully react with all available glucose in the enzyme. The polymeric material can function in place of or in combination with the resistance domain in order to limit the amount of glucose that passes through the membrane system. This embodiment assumes a stoichiometric relationship between glucose oxidation and decreased sensor signal output, which can be compensated for by calibration in some sensor configurations. Additionally, the auxiliary electrode generates oxygen, further reducing the likelihood of oxygen becoming a rate-limiting factor in the enzymatic reaction and/or at the counter electrode, for example.
In another aspect of the preferred embodiments, the auxiliary electrode 36 is configured to electrochemically modify (for example, oxidize or reduce) electrochemical interferants to render them substantially non-reactive at the electroactive sensing surface(s). In these embodiments, which can be in addition to or alternative to the above-described oxygen-generating embodiments, a polymer coating is chosen to selectively allow interferants (for example, urate, ascorbate, and/or acetaminophen such as described in U.S. Pat. No. 6,579,690 to Bonnecaze, et al.) to pass through the coating and electrochemically react with the auxiliary electrode, which effectively pre-oxidizes the interferants, rendering them substantially non-reactive at the working electrode 16a. In one exemplary embodiment, silicone materials can be synthesized to allow the transport of oxygen, acetaminophen and other interferants, but not allow the transport of glucose. In some embodiments, the polymer coating material can be chosen with a molecular weight that blocks glucose and allows the transport of oxygen, urate, ascorbate, and acetaminophen. In another exemplary embodiment, silicone materials can be synthesized to allow the transport of oxygen, glucose, acetaminophen, and other interferants. In some embodiments, the polymer coating material is chosen with a molecular weight that allows the transport of oxygen, glucose, urate, ascorbate, and acetaminophen. The voltage setting necessary to react with interfering species depends on the target electrochemical interferants, for example, from about +0.1 V to about +1.2 V. In some embodiments, wherein the auxiliary electrode is set at a potential of from about +0.6 to about +1.2 V, both oxygen-generation and electrochemical interferant modification can be achieved. In some embodiments, wherein the auxiliary electrode is set at a potential below about +0.6 V, the auxiliary electrode will function mainly to electrochemically modify interferants, for example.
Therefore, the sensors of preferred embodiments reduce or eliminate oxygen deficiency problems within electrochemical sensors by producing oxygen at an auxiliary electrode located above the enzyme within an enzyme-based electrochemical sensor. Additionally or alternatively, the sensors of preferred embodiments reduce or eliminate interfering species problems by electrochemically reacting with interferants at the auxiliary electrode rendering them substantially non-reactive at the working electrode.
Methods and devices that are suitable for use in conjunction with aspects of the preferred embodiments are disclosed in co-pending U.S. patent application Ser. No. 10/842,716, filed May 10, 2004 and entitled, “MEMBRANE SYSTEMS INCORPORATING BIOACTIVE AGENTS”; co-pending U.S. patent application Ser. No. 10/838,912 filed May 3, 2004 and entitled, “IMPLANTABLE ANALYTE SENSOR”; U.S. patent application Ser. No. 10/789,359 filed Feb. 26, 2004 and entitled, “INTEGRATED DELIVERY DEVICE FOR A CONTINUOUS GLUCOSE SENSOR”; U.S. application Ser. No. 10/685,636 filed Oct. 28, 2003 and entitled, “SILICONE COMPOSITION FOR 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. 10/646,333 filed Aug. 22, 2003 entitled, “OPTIMIZED SENSOR GEOMETRY FOR AN IMPLANTABLE GLUCOSE SENSOR”; U.S. application Ser. No. 10/647,065 filed Aug. 22, 2003 entitled, “POROUS MEMBRANES FOR USE WITH IMPLANTABLE DEVICES”; U.S. application Ser. No. 10/633,367 filed Aug. 1, 2003 entitled, “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S. Pat. No. 6,702,857 entitled “MEMBRANE FOR USE WITH IMPLANTABLE DEVICES”; 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. 09/447,227 filed Nov. 22, 1999 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; 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. 09/489,588 filed Jan. 21, 2000 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. application Ser. No. 09/636,369 filed Aug. 11, 2000 and entitled “SYSTEMS AND METHODS FOR REMOTE MONITORING AND MODULATION OF MEDICAL DEVICES”; and U.S. application Ser. No. 09/916,858 filed Jul. 27, 2001 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS,” as well as issued patents including U.S. Pat. No. 6,001,067 issued Dec. 14, 1999 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. Pat. No. 4,994,167 issued Feb. 19, 1991 and entitled “BIOLOGICAL FLUID MEASURING DEVICE”; and U.S. Pat. No. 4,757,022 filed Jul. 12, 1988 and entitled “BIOLOGICAL FLUID MEASURING DEVICE”; U.S. application Ser. No. 60/489,615 filed Jul. 23, 2003 and entitled “ROLLED ELECTRODE ARRAY AND ITS METHOD FOR MANUFACTURE”; U.S. application Ser. No. 60/490,010 filed Jul. 25, 2003 and entitled “INCREASING BIAS FOR OXYGEN PRODUCTION IN AN ELECTRODE ASSEMBLY”; U.S. application Ser. No. 60/490,009 filed Jul. 25, 2003 and entitled “OXYGEN ENHANCING ENZYME MEMBRANE FOR ELECTROCHEMICAL SENSORS”; U.S. application Ser. No. 60/490,007 filed Jul. 25, 2003 and entitled “OXYGEN-GENERATING ELECTRODE FOR USE IN ELECTROCHEMICAL SENSORS”; 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. 10/896,772 filed Jul. 21, 2004 and entitled “INCREASING BIAS FOR OXYGEN PRODUCTION IN AN ELECTRODE SYSTEM”; 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. 10/897,377 filed Jul. 21, 2004 and entitled “ELECTROCHEMICAL SENSORS INCLUDING ELECTRODE SYSTEMS WITH INCREASED OXYGEN GENERATION”. The foregoing patent applications and patents are incorporated herein by reference in their entireties.
All references cited herein are incorporated herein by reference in their entireties. 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.
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.
All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims 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 in the specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.
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 as embodied in the attached claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US1564641||10 Apr 1922||8 Dec 1925||Chicago Miniature Lamp Works||Detector for wireless systems|
|US2402306||7 Oct 1943||18 Jun 1946||Turkel Henry||Retaining guard guide for needles|
|US3210578||12 Jan 1962||5 Oct 1965||Westinghouse Electric Corp||Multispeed motor connector|
|US3381371||27 Sep 1965||7 May 1968||Sanders Associates Inc||Method of constructing lightweight antenna|
|US3775182||25 Feb 1972||27 Nov 1973||Du Pont||Tubular electrochemical cell with coiled electrodes and compressed central spindle|
|US3826244||20 Jul 1973||30 Jul 1974||Us Health Education & Welfare||Thumbtack microelectrode and method of making same|
|US3838033||31 Aug 1972||24 Sep 1974||Hoffmann La Roche||Enzyme electrode|
|US3933593||9 Aug 1972||20 Jan 1976||Beckman Instruments, Inc.||Rate sensing batch analysis method|
|US3982530||22 Apr 1975||28 Sep 1976||Egon Storch||Penial appliance|
|US4052754||14 Jul 1976||11 Oct 1977||Homsy Charles A||Implantable structure|
|US4067322||28 Jan 1976||10 Jan 1978||Johnson Joseph H||Disposable, pre-gel body electrodes|
|US4197840||29 Sep 1976||15 Apr 1980||Bbc Brown Boveri & Company, Limited||Permanent magnet device for implantation|
|US4240889||24 Jan 1979||23 Dec 1980||Toyo Boseki Kabushiki Kaisha||Enzyme electrode provided with immobilized enzyme membrane|
|US4255500||29 Mar 1979||10 Mar 1981||General Electric Company||Vibration resistant electrochemical cell having deformed casing and method of making same|
|US4324257||25 Feb 1980||13 Apr 1982||U.S. Philips Corporation||Device for the transcutaneous measurement of the partial oxygen pressure in blood|
|US4374013 *||3 Mar 1981||15 Feb 1983||Enfors Sven Olof||Oxygen stabilized enzyme electrode|
|US4378016||15 Jul 1981||29 Mar 1983||Biotek, Inc.||Artificial endocrine gland containing hormone-producing cells|
|US4388166||15 May 1982||14 Jun 1983||Tokyo Shibaura Denki Kabushiki Kaisha||Electrochemical measuring apparatus provided with an enzyme electrode|
|US4402694||16 Jul 1981||6 Sep 1983||Biotek, Inc.||Body cavity access device containing a hormone source|
|US4418148||5 Nov 1981||29 Nov 1983||Miles Laboratories, Inc.||Multilayer enzyme electrode membrane|
|US4431004||27 Oct 1981||14 Feb 1984||Bessman Samuel P||Implantable glucose sensor|
|US4431507 *||12 Jan 1982||14 Feb 1984||Matsushita Electric Industrial Co., Ltd.||Enzyme electrode|
|US4442841||30 Apr 1981||17 Apr 1984||Mitsubishi Rayon Company Limited||Electrode for living bodies|
|US4477314||20 Jul 1983||16 Oct 1984||Siemens Aktiengesellschaft||Method for determining sugar concentration|
|US4484987||19 May 1983||27 Nov 1984||The Regents Of The University Of California||Method and membrane applicable to implantable sensor|
|US4494950||19 Jan 1982||22 Jan 1985||The Johns Hopkins University||Plural module medication delivery system|
|US4545382||22 Oct 1982||8 Oct 1985||Genetics International, Inc.||Sensor for components of a liquid mixture|
|US4571292||12 Aug 1982||18 Feb 1986||Case Western Reserve University||Apparatus for electrochemical measurements|
|US4578215||12 Aug 1983||25 Mar 1986||Micro-Circuits Company||Electrical conductivity-enhancing and protecting material|
|US4650547||20 Dec 1985||17 Mar 1987||The Regents Of The University Of California||Method and membrane applicable to implantable sensor|
|US4655880||1 Aug 1983||7 Apr 1987||Case Western Reserve University||Apparatus and method for sensing species, substances and substrates using oxidase|
|US4671288||13 Jun 1985||9 Jun 1987||The Regents Of The University Of California||Electrochemical cell sensor for continuous short-term use in tissues and blood|
|US4672970||29 Jul 1985||16 Jun 1987||Mitsubishi Rayon Company, Ltd.||Electrode for living body|
|US4680268||18 Sep 1985||14 Jul 1987||Children's Hospital Medical Center||Implantable gas-containing biosensor and method for measuring an analyte such as glucose|
|US4685463||3 Apr 1986||11 Aug 1987||Williams R Bruce||Device for continuous in vivo measurement of blood glucose concentrations|
|US4703756||6 May 1986||3 Nov 1987||The Regents Of The University Of California||Complete glucose monitoring system with an implantable, telemetered sensor module|
|US4711245||7 May 1984||8 Dec 1987||Genetics International, Inc.||Sensor for components of a liquid mixture|
|US4721677||7 May 1987||26 Jan 1988||Children's Hospital Medical Center||Implantable gas-containing biosensor and method for measuring an analyte such as glucose|
|US4726381||4 Jun 1986||23 Feb 1988||Solutech, Inc.||Dialysis system and method|
|US4750496||28 Jan 1987||14 Jun 1988||Xienta, Inc.||Method and apparatus for measuring blood glucose concentration|
|US4757022||19 Nov 1987||12 Jul 1988||Markwell Medical Institute, Inc.||Biological fluid measuring device|
|US4763658||29 Jul 1987||16 Aug 1988||Solutech, Inc.||Dialysis system 2nd method|
|US4776944||1 Sep 1987||11 Oct 1988||Jiri Janata||Chemical selective sensors utilizing admittance modulated membranes|
|US4781798||8 May 1987||1 Nov 1988||The Regents Of The University Of California||Transparent multi-oxygen sensor array and method of using same|
|US4786657||2 Jul 1987||22 Nov 1988||Minnesota Mining And Manufacturing Company||Polyurethanes and polyurethane/polyureas crosslinked using 2-glyceryl acrylate or 2-glyceryl methacrylate|
|US4795542||24 Apr 1986||3 Jan 1989||St. Jude Medical, Inc.||Electrochemical concentration detector device|
|US4813424||23 Dec 1987||21 Mar 1989||University Of New Mexico||Long-life membrane electrode for non-ionic species|
|US4822336||4 Mar 1988||18 Apr 1989||Ditraglia John||Blood glucose level sensing|
|US4858615||29 Jul 1988||22 Aug 1989||Sentron V.O.F.||Catheter sensor and memory unit|
|US4861830||22 Jun 1987||29 Aug 1989||Th. Goldschmidt Ag||Polymer systems suitable for blood-contacting surfaces of a biomedical device, and methods for forming|
|US4871440||6 Jul 1988||3 Oct 1989||Daiken Industries, Ltd.||Biosensor|
|US4883057||9 Sep 1986||28 Nov 1989||Research Foundation, The City University Of New York||Cathodic electrochemical current arrangement with telemetric application|
|US4886740||28 May 1986||12 Dec 1989||Imperial Chemical Industries Plc||Enzyme-electrode sensor with organosilane treated membrane|
|US4890620||17 Feb 1988||2 Jan 1990||The Regents Of The University Of California||Two-dimensional diffusion glucose substrate sensing electrode|
|US4890621||19 Jan 1988||2 Jan 1990||Northstar Research Institute, Ltd.||Continuous glucose monitoring and a system utilized therefor|
|US4909908||27 Oct 1988||20 Mar 1990||Pepi Ross||Electrochemical cncentration detector method|
|US4919141||4 Jan 1988||24 Apr 1990||Institute fur Diabetestechnologie Gemeinnutzige Forschungs- und Entwicklungsgesellschaft mbH||Implantable electrochemical sensor|
|US4927407||19 Jun 1989||22 May 1990||Regents Of The University Of Minnesota||Cardiac assist pump with steady rate supply of fluid lubricant|
|US4953552||21 Apr 1989||4 Sep 1990||Demarzo Arthur P||Blood glucose monitoring system|
|US4955861||21 Apr 1988||11 Sep 1990||Therex Corp.||Dual access infusion and monitoring system|
|US4970145||20 Jan 1988||13 Nov 1990||Cambridge Life Sciences Plc||Immobilized enzyme electrodes|
|US4973320||2 Aug 1988||27 Nov 1990||Firma Carl Freudenberg||Tissue-compatible medical device and method for manufacturing the same|
|US4974929||28 Mar 1990||4 Dec 1990||Baxter International, Inc.||Fiber optical probe connector for physiologic measurement devices|
|US4975175||15 Jun 1989||4 Dec 1990||Isao Karube||Miniaturized oxygen electrode and miniaturized biosensor and production process thereof|
|US4992794||10 Oct 1989||12 Feb 1991||Texas Instruments Incorporated||Transponder and method for the production thereof|
|US4994167||7 Jul 1988||19 Feb 1991||Markwell Medical Institute, Inc.||Biological fluid measuring device|
|US5030333||14 Oct 1986||9 Jul 1991||Children's Hospital Medical Center||Polarographic method for measuring both analyte and oxygen with the same detecting electrode of an electroenzymatic sensor|
|US5034112||16 May 1989||23 Jul 1991||Nissan Motor Company, Ltd.||Device for measuring concentration of nitrogen oxide in combustion gas|
|US5050612||12 Sep 1989||24 Sep 1991||Matsumura Kenneth N||Device for computer-assisted monitoring of the body|
|US5063081||15 Aug 1990||5 Nov 1991||I-Stat Corporation||Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor|
|US5089112||11 Jan 1990||18 Feb 1992||Associated Universities, Inc.||Electrochemical biosensor based on immobilized enzymes and redox polymers|
|US5140985||21 Oct 1991||25 Aug 1992||Schroeder Jon M||Noninvasive blood glucose measuring device|
|US5155149||10 Oct 1991||13 Oct 1992||Boc Health Care, Inc.||Silicone polyurethane copolymers containing oxygen sensitive phosphorescent dye compounds|
|US5165407||9 Apr 1991||24 Nov 1992||The University Of Kansas||Implantable glucose sensor|
|US5171689||18 Apr 1989||15 Dec 1992||Matsushita Electric Industrial Co., Ltd.||Solid state bio-sensor|
|US5183549||26 Jan 1990||2 Feb 1993||Commtech International Management Corporation||Multi-analyte sensing electrolytic cell|
|US5190041||27 Dec 1991||2 Mar 1993||Palti Yoram Prof||System for monitoring and controlling blood glucose|
|US5198771||3 Sep 1991||30 Mar 1993||Transducer Research, Inc.||Potentiostatic apparatus and methods|
|US5200051||7 Nov 1989||6 Apr 1993||I-Stat Corporation||Wholly microfabricated biosensors and process for the manufacture and use thereof|
|US5202261||18 Nov 1991||13 Apr 1993||Miles Inc.||Conductive sensors and their use in diagnostic assays|
|US5212050||15 Aug 1990||18 May 1993||Mier Randall M||Method of forming a permselective layer|
|US5242835||21 Jul 1992||7 Sep 1993||Radiometer A/S||Method and apparatus for determining the concentration of oxygen|
|US5249576||24 Oct 1991||5 Oct 1993||Boc Health Care, Inc.||Universal pulse oximeter probe|
|US5250439||14 Dec 1992||5 Oct 1993||Miles Inc.||Use of conductive sensors in diagnostic assays|
|US5266179||19 Jul 1991||30 Nov 1993||Matsushita Electric Industrial Co., Ltd.||Quantitative analysis method and its system using a disposable sensor|
|US5281319||29 Jun 1992||25 Jan 1994||Agency Of Industrial Science And Technology||Carbon micro-sensor electrode and method for preparing it|
|US5282848||19 Apr 1993||1 Feb 1994||Meadox Medicals, Inc.||Self-supporting woven vascular graft|
|US5284140||11 Feb 1992||8 Feb 1994||Eli Lilly And Company||Acrylic copolymer membranes for biosensors|
|US5286364||29 Mar 1991||15 Feb 1994||Rutgers University||Surface-modified electochemical biosensor|
|US5298144||15 Sep 1992||29 Mar 1994||The Yellow Springs Instrument Company, Inc.||Chemically wired fructose dehydrogenase electrodes|
|US5299571||22 Jan 1993||5 Apr 1994||Eli Lilly And Company||Apparatus and method for implantation of sensors|
|US5307263||17 Nov 1992||26 Apr 1994||Raya Systems, Inc.||Modular microprocessor-based health monitoring system|
|US5310469||31 Dec 1991||10 May 1994||Abbott Laboratories||Biosensor with a membrane containing biologically active material|
|US5312361||10 Aug 1992||17 May 1994||Zadini Filiberto P||Automatic cannulation device|
|US5322063||4 Oct 1991||21 Jun 1994||Eli Lilly And Company||Hydrophilic polyurethane membranes for electrochemical glucose sensors|
|US5330634||28 Aug 1992||19 Jul 1994||Via Medical Corporation||Calibration solutions useful for analyses of biological fluids and methods employing same|
|US5337747||7 Jan 1993||16 Aug 1994||Frederic Neftel||Implantable device for estimating glucose levels|
|US5352348||3 Nov 1992||4 Oct 1994||Nova Biomedical Corporation||Method of using enzyme electrode|
|US5352351||8 Jun 1993||4 Oct 1994||Boehringer Mannheim Corporation||Biosensing meter with fail/safe procedures to prevent erroneous indications|
|US5354449||2 Jan 1992||11 Oct 1994||Band David M||pH electrode|
|US6066448 *||6 Mar 1996||23 May 2000||Meso Sclae Technologies, Llc.||Multi-array, multi-specific electrochemiluminescence testing|
|US6264825 *||23 Jun 1999||24 Jul 2001||Clinical Micro Sensors, Inc.||Binding acceleration techniques for the detection of analytes|
|USRE31916||29 Apr 1981||18 Jun 1985||Becton Dickinson & Company||Electrochemical detection cell|
|1||Aalders et al. 1991. Development of a wearable glucose sensor; studies in healthy volunteers and in diabetic patients. The International Journal of Artificial Organs 14(2):102-108.|
|2||Abe et al. 1992. Characterization of glucose microsensors for intracellular measurements. Anal. Chem. 64(18):2160-2163.|
|3||Abel et al. 1984. Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell, Biomed. Biochim. Acta 43(5):577-584.|
|4||Abel, P. U.; von Woedtke, T. Biosensors for in vivo glucose measurement: can we cross the experimental stage. Biosens Bioelectron 2002, 17, 1059-1070.|
|5||Armour, et al. Dec. 1990. Application of Chronic Intravascular Blood Glucose Sensor in Dogs. Diabetes 39:1519-1526.|
|6||Asberg et al. 2003. Hydrogels of a Conducting Conjugated Polymer as 3-D Enzyme Electrode. Biosensors Bioelectronics. pp. 199-207.|
|7||Atanasov et al. 1994. Biosensor for continuous glucose monitoring. Biotechnology and Bioengineering 43:262-266.|
|8||Atanasov et al. 1997. Implantation of a refillable glucose monitoring-telemetry device. Biosens Bioelectron 12:669-680.|
|9||Aussedat, et al. 1997. A user-friendly method for calibrating a subcutaneous glucose sensor-based hypoglycaemic alarm. Biosensors & Bioelectronics 12(11):1061-1071.|
|10||Baker et al. 1993. Dynamic concentration challenges for biosensor characterization. Biosensors & Bioelectronics, 8:433-441.|
|11||Baker, et al. 1996. Dynamic delay and maximal dynamic error in continuous biosensors. Anal Chem 68(8):1292-1297.|
|12||Bani Amer, M. M. 2002. An accurate amperometric glucose sensor based glucometer with eliminated cross-sensitivity. J Med Eng Technol 26(5):208-213.|
|13||Bard et al. 1980. Electrochemical Methods. John Wiley & Sons, pp. 173-175.|
|14||Beach et al. 1999. Subminiature implantable potentiostat and modified commercial telemetry device for remote glucose monitoring. IEEE Transactions on Instrumentation and Measurement 48(6):1239-1245.|
|15||Bellucci et al. Jan. 1986. Electrochemical behaviour of graphite-epoxy composite materials (GECM) in aqueous salt solutions, Journal of Applied Electrochemistry, 16(1):15-22.|
|16||Bessman et al., Progress toward a glucose sensor for the artificial pancreas, Proceedings of a Workshop on Ion-Selective Microelectrodes, Jun. 4-5, 1973, Boston, MA, 189-197.|
|17||Bindra et al. 1989. Pulsed amperometric detection of glucose in biological fluids at a surface-modified gold electrode. Anal Chem, 61:2566-2570.|
|18||Bindra et al. 1991. Design and in Vitro Studies of a Needle-Type Glucose Senso for Subcutaneous Monitoring. Anal. Chem 63:1692-96.|
|19||Bisenberger et al. 1995. A triple-step potential waveform at enzyme multisensors with thick-film gold electrodes for detection of glucose and sucrose. Sensors and Actuators, B 28:181-189.|
|20||Bode, B. W. 2000. Clinical utility of the continuous glucose monitoring system. Diabetes Technol Ther, 2(Suppl 1):S35-41.|
|21||Bott, A. 1998. Electrochemical methods for the determination of glucose. Current Separations, 17(1)25-31.|
|22||Bott, A. W. 1997. A comparison of cyclic voltammetry and cyclic staircase voltammetry. Current Separations, 16(1):23-26.|
|23||*||Bott, A.W. 1997. A Comparison of cyclic voltammetry and staircase voltammetry. Current Separations, 16(1):23-26.|
|24||Bowman,et al. 1986. The packaging of implantable integrated sensors. IEEE Trans Biomed Eng BME33(2):248-255.|
|25||Brooks, et al. "Development of an on-line glucose sensor for fermentation monitoring," Biosensors, 3:45-56 (1987/88).|
|26||CAI et al. 2004. A wireless, remote query glucose biosensor based on a pH-sensitive polymer. Anal Chem 76(4):4038-4043.|
|27||Campanella et al. 1993. Biosensor for direct determination of glucose and lactate in undiluted biological fluids. Biosensors & Bioelectronics 8:307-314.|
|28||Cass et al. "Ferrocene-mediated enzyme electrodes for amperometric determination of glucose," Anal. Chem., 36:667-71 (1984).|
|29||Cassidy et al., Apr. 1993. Novel electrochemical device for the detection of cholesterol or glucose, Analyst, 118:415-418.|
|30||Chen et al. 2006. A noninterference polypyrrole glucose biosensor. Biosensors and Bioelectronics 22:639-643.|
|31||Chia et al. 2004. Glucose sensors: toward closed loop insulin delivery. Endocrinol Metab Clin North Am 33:175-95.|
|32||Choleau et al. 2002. Calibration of a subcutaneo amperometric glucose sensor. Part 1. Effect of measurement uncertainties on the determination of sensor sensitivity and background current. Biosensors and Bioelectronics, 17:641-646.|
|33||Choleau, et al. 2002. Calibration of a subcutaneous amperometric glucose sensor implanted for 7 days in diabetic patients. Part 2. Superiority of the one-point calibration method. Biosensors and Bioelectronics 17:647-654.|
|34||Claremont et al. Jul. 1986. Potentially-implantable, ferrocene-mediated glucose sensor. J. Biomed. Eng. 8:272-274.|
|35||Clark et al. 1981. One-minute electrochemical enzymic assay for cholesterol in biological materials, Clin. Chem. 27(12):1978-1982.|
|36||Clark et al. 1987. Configurational cyclic voltammetry: increasing the specificity and reliablity of implanted electrodes, IEEE/Ninth Annual Conference of the Engineering in Medicine and Biology Society, pp. 0782-0783.|
|37||Clark et al. 1988. Long-term stability of electroenzymatic glucose sensors implanted in mice. Trans Am Soc Artif Intern Organs 34:259-265.|
|38||CLSI. Performance metrics for continuous interstitial glucose monitoring; approved guideline, CLSI document POCT05-A. Wayne, PA: Clinical and Laboratory Standards Institute: 2008 28(33), 72 pp.|
|39||Csoregi et al., 1994. Design, characterization, and one-point in vivo calibration of a subcutaneously implanted glucose electrode. Anal Chem. 66(19):3131-3138.|
|40||Danielsson et al. 1988. Enzyme thermistors, Methods in Enzymology, 137:181-197.|
|41||Davies, et al. 1992. Polymer membranes in clinical sensor applications. I. An overview of membrane function, Biomaterials, 13(14):971-978.|
|42||Davis et al. 1983. Bioelectrochemical fuel cell and sensor based on a quinoprotein, alcohol dehydrogenase. Enzyme Microb. Technol., vol. 5, September, 383-388.|
|43||Dixon et al. 2002. Characterization in vitro and in vivo of the oxygen dependence of an enzyme/polymer biosensor for monitoring brain glucose. Journal of Neuroscience Methods, 119:135-142.|
|44||Durliat et al. 1976. Spectrophotometric and electrochemical determinations of L(+)-lactate in blood by use of lactate dehydrogenase from yeast, Clin. Chem. 22(11):1802-1805.|
|45||El Deheigy et al. 1986. Optimization of an implantable coated wire glucose sensor. J. Biomed Eng. 8: 121-129.|
|46||Fare et al. 1998. Functional characterization of a conducting polymer-based immunoassay system. Biosensors & Bioelectronics 13(3-4):459-470.|
|47||Feldman et al. 2003. A continuous glucose sensor based on wired enzyme technology—results from a 3-day trial in patients with type 1 diabetes. Diabetes Technol Ther 5(5):769-779.|
|48||Fischer et al. 1989. Oxygen Tension at the Subcutaneous Implantation Site of Glucose Sensors. Biomed. Biochem 11/12:965-972.|
|49||Fischer et al. 1995. Hypoglycaemia-warning by means of subcutaneous electrochemical glucose sensors: an animal study, Horm. Metab. Rese. 27:53.|
|50||Frohnauer, et al. 2001. Graphical human insulin time-activity profiles using standardized definitions. Diabetes Technology & Therapeutics 3(3):419-429.|
|51||Frost, et al. 2002. Implantable chemical sensors for real-time clinical monitoring: Progress and challenges. Current Opinion in Chemical Biology 6:633-641.|
|52||Ganesh et al., Evaluation of the VIAŽ blood chemistry monitor for glucose in healthy and diabetic volunteers, Journal of Diabetese Science and Technology, 2(2):182-193, Mar. 2008.|
|53||Gilligan et al. Feasibility of continuous long-term glucose monitoring from a subcutaneous glucose sensor in humans. Diabetes Technol. Ther. 2004, 6, 378-386.|
|54||Gilligan, B. C.; Shults, M.; Rhodes, R. K.; Jacobs, P. G.; Brauker, J. H.; Pintar, T. J.; Updike, S. J. Feasibility of continuo long-term glucose monitoring from a subcutaneous glucose sensor in humans. Diabetes Technol. Ther. 2004, 6, 378-386.|
|55||Godsland, et al. 2001. Maximizing the Success Rate of Minimal Model Insulin Sensitivity Measurement in Humans: The Importance of Basal Glucose Levels. The Biochemical Society and the Medical Research Society, 1-9.|
|56||Hall et al. 1998. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part 1. An adsorption-controlled mechanism. Electrochimica Acta, 43(5-6):579-588.|
|57||Hall et al. 1998. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part II: Effect of potential. Electrochimica Acta; 43(14-15):2015-2024.|
|58||Hall et al. 1999. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part III: Effect of temperature. Electrochimica Acta, 44:2455-2462.|
|59||Hall et al. 1999. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part IV: Phosphate buffer dependence. Electrochimica Acta, 44:4573-4582.|
|60||Hall et al. 2000. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part V: Inhibition by chloride. Electrochimica Acta, 45:3573-3579.|
|61||Hashiguchi et al. (1994). "Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method: Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients," Diabetes Care, 17(5): 387-396.|
|62||Heller, "Electrical wiring of redox enzymes," Acc. Chem. Res., 23:128-134 (1990).|
|63||Heller, A. 1992. Electrical Connection of Enzyme Redox Centers to Electrodes. J. Phys. Chem. 96:3579-3587.|
|64||Heller, A. 2003. Plugging metal connectors into enzymes. Nat Biotechnol 21:631-2.|
|65||Heller, A. Implanted electrochemical glucose sensors for the management of diabetes. Annu Rev Biomed Eng 1999, 1, 153-175.|
|66||Hicks, 1985. In Situ Monitoring, Clinical Chemistry, 31(12):1931-1935.|
|67||Hitchman, M. L. 1978. "Measurement of Dissolved Oxygen." In Elving et al. (Eds.). Chemical Analysis, vol. 49, Chap. 3, pp. 34-49, 59-123. New York: John Wiley & Sons.|
|68||Hu, et al. 1993. A needle-type enzyme-based lactate sensor for in vivo monitoring, Analytica Chimica Acta, 281:503-511.|
|69||Huang et al. Electrochemical Generation of Oxygen. 1: The Effects of Anions and Cations on Hydrogen Chemisorption and Aniodic Oxide Film Formation on Platinum Electrode. 2: The Effects of Anions and Cations on Oxygen Generation on Platinum Electrode, pp. 1-116, Aug. 1975.|
|70||IPRP for PCT/US04/024178 filed Jul. 21, 2004.|
|71||ISR and WO for PCT/US04/024178 filed Jul. 21, 2004.|
|72||Jablecki et al. 2000. Simulations of the frequency response of Implantable glucose sensors. Analytical Chemistry, 72:1853-1859.|
|73||Jaremko et al. 1998. Advances toward the implantable artificial pancreas for treatment of diabetes. Diabetes Care, 21(3):444-450.|
|74||Jensen et al. 1997. Fast wave forms for pulsed electrochemical detection of glucose by incorporation of reductive desorption of oxidation products. Analytical Chemistry, 69(9):1776-1781.|
|75||Johnson (1991). "Reproducible electrodeposition of biomolecules for the fabrication of miniature electroenzymatic biosensors," Sensors and Actuators B, 5:85-89.|
|76||Johnson et al. 1992. In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue. Biosensors & Bioelectronics, 7:709-714.|
|77||Kacaniklic, May-Jun. 1994. Electroanalysis, 6(5-6):381-390.|
|78||Kang et al. In vitro and short-term in vivo characteristics of a Kel-F thin film modified glucose sensor. Anal Sci 2003, 19, 1481-1486.|
|79||Kang, S. K.; Jeong, R.A.; Park, S.; Chung, T. D.; Park, S.; Kim, H.C. In vitro and short-term in vivo characteristics of a Kel-F thin film modified glucose sensor. Anal Sci 2003, 19, 1481-1486.|
|80||Karube et al. 1993. Microbiosensors for acetylcholine and glucose. Biosensors & Bioelectronics 8:219-228.|
|81||Kawagoe et al. 1991. Enzyme-modified organic conducting salt microelectrode, Anal. Chem. 63:2961-2965.|
|82||Keedy et al. 1991. Determination of urate in undiluted whole blood by enzyme electrode. Biosensors & Bioelectronics, 6: 491-499.|
|83||Kerner et al. 1988. A potentially implantable enzyme electrode for amperometric measurement of glucose, Horm Metab Res Suppl. 20:8-13.|
|84||Kerner, et al. "The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma," Biosensors & Bioelectronics, 8:473-482 (1993).|
|85||Ko, Wen H. 1985. Implantable Sensors for Closed-Loop Prosthetic Systems, Futura Pub. Co., Inc., Mt. Kisco, NY, Chapter 15:197-210.|
|86||Kondo et al. 1982. A miniature glucose sensor, implantable in the blood stream. Diabetes Care. 5(3):218-221.|
|87||Koschinsky, et al. 1998. New approach to technical and clinical evaluation of devices for self-monitoring of blood glucose. Diabetes Care 11(8): 619-619.|
|88||Koudelka et al. 1989. In vivo response of microfabricated glucose sensors to glycemia changes in normal rats. Biomed Biochim Acta 48(11-12):953-956.|
|89||Koudelka et al. 1991. In-vivo behaviour of hypodermically implanted microfabricated glucose sensors. Biosensors & Bioelectronics 6:31-36.|
|90||Kraver et al. A mixed-signal sensor interface microinstrument. Sensors and Actuators A: Physical 2001, 91, 266-277.|
|91||Kraver, K.; Gutha, M. R.; Strong, T.; Bird, P.; Cha, G.; Hoeld, W., Brown, R. A mixed-signal sensor interface microinstrument. Sensors and Actuators A: Physical 2001, 91, 266-277.|
|92||LaCourse et al. 1993. Optimization of waveforms for pulsed amperometric detection of carbohydrates based on pulsed voltammetry. Analytical Chemistry, 65:50-52.|
|93||Lerner et al. 1984. An implantable electrochemical glucose sensor. Ann. N. Y. Acad. Sci., 428:263-278.|
|94||Leypoldt et al. 1984. Model of a two-substrate enzyme electrode for glucose. Anal. Chem., 56:2896-2904.|
|95||Linke et al. 1994. Amperometric biosensor for in vivo glucose sensing based on glucose oxidase immobilized in a redox hydrogel. Biosensors & Bioelectronics 9:151-158.|
|96||Lowe, 1984. Biosensors, Trends in Biotechnology, 2(3):59-65.|
|97||Luong et al. 2004. Solubilization of Multiwall Carbon Nanotubes by 3-Aminopropyltriethoxysilane Towards the Fabrication of Electrochemical Biosensors with Promoted Electron Transfer. Electronanalysis 16(1-2):132-139.|
|98||Maidan et al. 1992. Elimination of Electrooxidizable Interferent-Produced Currents in Amperometric Biosensors, Analytical Chemistry, 64:2889-2896.|
|99||Makale et al. 2003. Tissue window chamber system for validation of implanted oxygen sensors. Am. J. Physiol. Heart Circ. Physiol. 284:H2288-2294.|
|100||Mascini et al. 1989. Glucose electrochemical probe with extended linearity for whole blood. J Pharm Biomed Anal 7(12): 1507-1512.|
|101||Mastrototaro, et al. "An electroenzymatic glucose sensor fabricated on a flexible substrate," Sensors and Actuators B, 5:139-44 (1991).|
|102||Matthews et al. 1988. An amperometric needle-type glucose sensor testing in rats and man. Diabetic Medicine 5:248-252.|
|103||McGrath et al. The use of differential measurements with a glucose biosensor for interference compensation during glucose determinations by flow injection analysis. Biosens Bioelectron 1995, 10, 937-943.|
|104||McGrath, M. J.; Iwuoha, E. I.; Diamond, D.; Smyth, M. R. The use of differential measurements with a glucose biosensor for interference compensation during glucose determinations by flow injection analysis. Biosens Bioelectron 1995, 10, 937-943.|
|105||McKean, et al. Jul. 7, 1988. A Telemetry Instrumentation System for Chronically Implanted Glucose and Oxygen Sensors. Transactions on Biomedical Engineering 35:526-532.|
|106||Memoli et al. A comparison between different immobilised glucoseoxidase-based electrodes. J Pharm Biomed Anal 2002, 29, 1045-1052.|
|107||Moatti-Sirat et al., Reduction of acetaminophen interference in glucose sensors by a composite Nafion membrane: demonstration in rats and man, Diabetologia 37(6):610-616, Jun. 1994.|
|108||Moatti-Sirat, D, et al. 1992. Evaluating in vitro and in vivo the interference of ascorbate and acetaminophen on glucose detection by a needle-type glucose sensor. Biosensors and Bioelectronics 7:345-352.|
|109||Morff et al. 1990. Microfabrication of reproducible, economical, electroenzymatic glucose sensors, Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 12(2):0483-0484.|
|110||Mosbach et al. 1975. Determination of heat changes in the proximity of immobilized enzymes with an enzyme termistor and its use for the assay of metobolites, Biochim. Biophys. Acta. (Enzymology), 403:256-265.|
|111||Motonaka et al. 1993. Determination of cholesteral and cholesteral ester with novel enzyme microsensors, Anal. Chem. 65:3258-3261.|
|112||Mowery et al. 2000. Preparation and characterization of hydrophobic polymeric films that are thromboresistant via nitric oxide release. Biomaterials 21:9-21.|
|113||Murphy, et al. 1992. Polymer membranes in clinical sensor applications. II. The design and fabrication of permselective hydrogels for electrochemical devices, Biomaterials, 13(14):979-990.|
|114||Myler et al. 2002. Ultra-thin-polysiloxane-film-composite membranes for the optimisation of amperometric oxidase enzyme electrodes. Biosens Bioelectron 17:35-43.|
|115||Neuburger et al. 1987. Pulsed amperometric detection of carbohydrates at gold electrodes with a two-step potential waveform. Anal. Chem., 59:150-154.|
|116||Office Action dated Apr. 10, 2007 in U.S. Appl. 11/077,714.|
|117||Office Action dated Apr. 10, 2007 in U.S. Appl. No. 11/077,715.|
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|229||Office Action dated Sep. 5, 2006 in U.S. Appl. No. 09/916,711.|
|230||Office Action dated Sep. 5, 2008 in U.S. Appl. No. 11/078,230.|
|231||Office Action mailed Dec. 12, 2007 in U.S. Appl. No. 11/543,539.|
|232||Office Action mailed Dec. 12, 2007 in U.S. Appl. No. 11/543,683.|
|233||Office Action mailed Dec. 17, 2007 in U.S. Appl. No. 11/543,734.|
|234||Office Action mailed Jun. 5, 2007 in U.S. Appl. No. 11/543,734.|
|235||Office Action mailed Jun. 5, 2008 in U.S. Appl. No. 10/838,909.|
|236||Office Action mailed Mar. 16, 2009 in U.S. Appl. No. 10/838,909.|
|237||Office Action mailed May 18, 2007 in U.S. Appl. No. 11/543,683.|
|238||Office Action mailed May 18, 2007 in U.S. Appl. No. 11/543,707.|
|239||Office Action mailed May 23, 2007 in U.S. Appl. No. 11/543,539.|
|240||Ohara et al. 1994. "Wired" enzyme electrodes for amperometric determination of glucose or lactate in the presence of interfering substances. Anal Chem 66:2451-2457.|
|241||Okuda et al. 1971. Mutarotase effect on micro determinations of D-glucose and its anomers with β-D-glucose oxidase. Anal Biochem 43:312-315.|
|242||Patel et al. 2003. Amperometric glucose sensors based on ferrocene containing polymeric electron transfer systems-a preliminary report. Biosens Bioelectron 18:1073-6.|
|243||Pfeiffer, E.F. 1990. The glucose sensor: the missing link in diabetes therapy, Horm Metab Res Suppl. 24:154-164.|
|244||Pickup et al. 1988. Progress towards in vivo glucose sensing with a ferrocene-mediated amperometric enzyme electrode. 34-36.|
|245||Pickup et al. 1989. Potentially-implantable, amperometric glucose sensors with mediated electron transfer: improving the operating stability. Biosensors 4:109-119.|
|246||Pickup et al. 1993. Developing glucose sensors for in vivo use. Elsevier Science Publishers Ltd (UK), TIBTECH vol. 11: 285-291.|
|247||Pickup, et al. "Implantable glucose sensors: choosing the appropriate sensor strategy," Biosensors, 3:335-346 (1987/88).|
|248||Pickup, et al. "In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer," Diabetologia, 32:213-217 (1989).|
|249||Pishko, et al. "Amperometric glucose microelectrodes prepared through immobilization of glucose oxidase in redox hydrogels," Anal. Chem., 63:2268-72 (1991).|
|250||Poitout, et al. 1991. In Vitro and In Vivo Evaluation in Dogs of a Miniaturized Glucose Sensor, ASAIO Transactions, 37:M298-M300.|
|251||Poitout, et al. 1993. A glucose monitoring system for on line estimation in man of blood glucose concentration using a miniaturized glucose sensor implanted in the subcutaneous tissue and a wearable control unit. Diabetologia 36:658-663.|
|252||Postlethwaite et al. 1996. Interdigitated array electrode as an alternative to the rotated ring-disk electrode for determination of the reaction products of dioxygen reduction. Analytical Chemistry, 68:2951-2958.|
|253||Prabhu et al. 1981. Electrochemical studies of hydrogen peroxide at a platinum disc electrode, Electrochimica Acta 26(6):725-729.|
|254||Quinn et al. 1997. Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. Biomaterials 18:1665-1670.|
|255||Rabah et al., 1991. Electrochemical wear of graphite anodes during electrolysis of brine, Carbon, 29(2):165-171.|
|256||Rebrin et al. 1992. Subcutaenous glucose monitoring by means of electrochemical sensors: fiction or reality? J. Biomed. Eng. 14:33-40.|
|257||Rebrin, et al. "Automated feedback control of subcutaneous glucose concentration in diabetic dogs," Diabetologia, 32:573-76 (1989).|
|258||Rhodes et al. 1994. Prediction of pocket-portable and implantable glucose enzyme electrode performance from combined species permeability and digital simulation analysis. Analytical Chemistry, 66(9):1520-1529.|
|259||Rhodes, et al. 1994 Prediction of pocket-portable and implantable glucose enzyme electrode performance from combined species permeability and digital simulation analysis. Analytical Chemistry, 66(9):1520-1529.|
|260||Sakakida et al. 1992. Development of Ferrocene-Mediated Needle-Type Glucose Sensor as a Measure of True Subcutaneous Tissue Glucose Concentrations. Artif. Organs Today 2(2):145-158.|
|261||Sansen et al. 1985. "Glucose sensor with telemetry system." in Ko, W. H. (Ed.). Implantable Sensors for Closed Loop Prosthetic Systems. Chap. 12, pp. 167-175, Mount Kisco, NY: Futura Publishing Co.|
|262||Sansen et al. 1990. A smart sensor for the voltammetric measurement of oxygen or glucose concentrations. Sensors and Actuators, B 1:298-302.|
|263||Sansen, et al. 1990. A smart sensor for the voltammetric measurement of oxygen or glucose concentrations. Sensors and Actuators, B 1:298-302.|
|264||Schmidt et al. 1993. Glucose concentration in subcutaneous extracellular space. Diabetes Care 16(5):695-700.|
|265||Schmidtke et al., Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin. Proc Natl Aced Sci U S A 1998, 95, 294-299.|
|266||Schoemaker et al. 2003. The SCGM1 system: Subcutaneous continuous glucose monitoring based on microdialysis technique. Diabetes Technology & Therapeutics 5(4):599-608.|
|267||Schoonen et al. 1990 Development of a potentially wearable glucose sensor for patients with diabetes mellitus: design and in-vitro evaluation. Biosensors & Bioelectronics 5:37-46.|
|268||Schuler et al. 1999. Modified gas-permeable silicone rubber membranes for covalent immobilisation of enzymes and their use in biosensor development. Analyst 124:1181-1184.|
|269||Selam, J. L. 1997. Management of diabetes with glucose sensors and implantable insulin pumps. From the dream of the 60s to the realities of the 90s. ASAIO J, 43:137-142.|
|270||Shaw, et al. "In vitro testing of a simply constructed, highly stable glucose sensor suitable for implantation in diabetic patients," Biosensors & Bioelectronics, 6:401-406 (1991).|
|271||Shichiri et al. 1982. Wearable artificial endocrine pancrease with needle-type glucose sensor. Lancet 2:1129-1131.|
|272||Shichiri et al. 1985. Needle-type Glucose Sensor for Wearable Artificial Endocrine Pancreas in Implantable Sensors 197-210.|
|273||Shichiri, et al. 1983. Glycaemic Control in Pancreatectomized Dogs with a Wearable Artificial Endocrine Pancreas. Diabetologia 24:179-184.|
|274||Shichiri, et al. 1986. Telemetry Glucose Monitoring Device with Needle-Type Glucose Sensor: A Useful Tool for Blood Glucose Monitoring in Diabetic Individuals. Diabetes Care, Inc. 9(3):298-301.|
|275||Shults, et al. 1994. A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors. IEEE Transactions on Biomedical Engineering 41(10):937-942.|
|276||Sokol et al. 1980, Immobilized-enzyme rate-determination method for glucose analysis, Clin. Chem. 26(1):89-92.|
|277||Stern et al., 1957. Electrochemical polarization: 1. A theoretical analysis of the shape of polarization curves, Journal of the Electrochemical Society, 104(1):56-63.|
|278||Sternberg et al. 1988. Covalent enzyme coupling on cellulose acetate membranes for glucose sensor development. Anal. Chem. 69:2781-2786.|
|279||Stokes. 1988. Polyether Polyurethanes: Biostable or Not? J. Biomat. Appl. 3:228-259.|
|280||Thome et al. 1995. Can the decrease in subcutaneous glucose concentration precede the decrease in blood glucose level? Proposition for a push-pull kinetics hypothesis, Horm. Metab. Res. 27:53.|
|281||Thomé-Duret et al. 1996. Modification of the sensitivity of glucose sensor implanted into subcutaneous tissue. Diabetes Metabolism, 22:174-178.|
|282||Thome-Duret et al. 1996. Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood, Anal. Chem. 68:3822-3826.|
|283||Thompson, et al., In Vivo Probes: Problems and Perspectives, Department of Chemistry, University of Toronto, Canada, pp. 255-261, 1986.|
|284||Tierney et al. 2000. Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer. Diabetes Technol Ther 2:199-207.|
|285||Torjman et al., Glucose monitoring in acute care: technologies on the horizon, Journal of Deabetes Science and Technology, 2(2):178-181, Mar. 2008.|
|286||Tse et al. 1987. Time-Dependent Inactivation of Immobilized Glucose Oxidase and Catalase. Biotechnol. Bioeng. 29:705-713.|
|287||Turner and Pickup, "Diabetes mellitus: biosensors for research and management," Biosensors, 1:85-115 (1985).|
|288||Turner, A.P.F. 1988. Amperometric biosensor based on mediator-modified electrodes. Methods in Enzymology 137:90-103.|
|289||TURNERet al. 1984. Carbon Monoxide: Acceptor Oxidoreductase from Pseudomonas Thermocarboxydovorans Strain C2 and its use in a Carbon Monoxide Sensor. Analytica Chimica Acta, 163: 161-174.|
|290||U.S. Appl. No. 09/447,227, filed Nov. 22, 2999.|
|291||U.S. Appl. No. 10/838,658, filed May 3, 2004.|
|292||U.S. Appl. No. 10/838,909, filed May 3, 2004.|
|293||U.S. Appl. No. 10/838,912, filed May 3, 2004.|
|294||U.S. Appl. No. 10/885,476, filed Jul. 6, 2004.|
|295||U.S. Appl. No. 10/897,377, filed Jul. 21, 2004.|
|296||Updike et al. 1967. The enzyme electrode. Nature, 214:986-988.|
|297||Updike et al. 1988. Laboratory Evaluation of New Reusable Blood Glucose Sensor. Diabetes Care, 11:801-807.|
|298||Updike et al. 2000. A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration. Diabetes Care 23(2):208-214.|
|299||Updike, et al. 1979. Continuous glucose monitor based on an immobilized enzyme electrode detector. J Lab Clin Med, 93(4):518-527.|
|300||Updike, et al. 1994 Enzymatic glucose sensor: Improved long-term performance in vitro and in vivo. ASAIO Journal, 40(2):157-163.|
|301||Updike, et al. 1997. Principles of long-term fully impleated sensors with emphasis on radiotelemetric monitoring of blood glucose form inside a subcutaneous foreign body capsule (FBC). In Fraser, ed., Biosensors in the Body. New York. John Wiley & Sons, pp. 117-137.|
|302||Vadgama, P. Nov. 1981. Enzyme electrodes as practical biosensors. Journal of Medical Engineering & Technology 5(6):293-298.|
|303||Vadgama. 1988. Diffusion limited enzyme electrodes. NATO ASI Series: Series C, Math and Phys. Sci. 226:359-377.|
|304||Velho et al. 1989. Strategies for calibrating a subcutaneous glucose sensor. Biomed Biochim Acta 48(11/12):957-964.|
|305||Wagner, et al. 1998. Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode. Proc. Natl. Acad. Sci. A, 95:6379-6382.|
|306||Wang et al. 1994. Highly Selective Membrane-Free, Mediator-Free Glucose Biosensor. Anal. Chem. 66:3600-3603.|
|307||Wang et al. Improved ruggedness for membrane-based amperometric sensors using a pulsed amperometric method. Anal Chem 1997, 69, 4482-4489.|
|308||Wang, X.; Pardue, H. L. Improved ruggedness for membrane-based amperometric sensors using a pulsed amperometric method. Anal Chem 1997, 69, 4482-4489.|
|309||Ward et al. 2000. Rise in background current over time in a subcutaneous glucose sensor in the rabbit: Relevance to calibration and accuracy. Biosensors & Bioelectronics, 15:53-61.|
|310||Ward et al. 2002. A new amperometric glucose microsensor: In vitro and short-term in vivo evaluation. Biosensors & Bioelectronics, 17:181-189.|
|311||Ward et al. Understanding Spontaneous Output Fluctuations of an Amperometric Glucose Sensor: Effect of Inhalation Anesthesia and e of a Nonenzyme Containing Electrode. ASAIO Journal 2000, 540-546.|
|312||Ward, et al. 1999. Assessment of chronically implanted subcutaneous glucose sensors in dogs: The effect of surrounding fluid masses. ASAIO Journal, 45:555-561.|
|313||Ward, et al. 2000. Rise in background current over time in a subcutaneous glucose sensor in the rabbit: Relevance to calibration and accuracy. Biosensors & Bioelectronics, 15:53-61.|
|314||Ward, et al. 2002. A new amperometric glucose microsensor: In vitro and short-term in vivo evaluation, Biosensors & Bioelectronics, 17:181-189.|
|315||Ward, W. K.; Wood, M. D.; Troupe, J. E. Understanding Spontaneous Output Fluctuations of an Amperometric Glucose Sensor: Effect of Inhalation Anesthesia and e of a Nonenzyme Containing Electrode. ASAIO Journal 2000, 540-546.|
|316||Wientjes, K. J. C. Development of a glucose sensor for diabetic patients. 2000.|
|317||Wilkins et al. 1988. The coated wire electrode glucose sensor, Horm Metab Res Suppl., 20:50-55.|
|318||Wilkins et al. 1995. Integrated implantable device for long-term glucose monitoring. Biosens. Bioelectron 10:485-494.|
|319||Wilkins et al. Glucose monitoring: state of the art and future possibilities. Med Eng Phys 1995, 18, 273-288.|
|320||Wilkins, et al. 1995. Integrated implantable device for long-term glucose monitoring. Biosens. Bioelectron., 10:485-494.|
|321||Wilson et al. 1992. Progress toward the development of an implantable sensor for glucose. Clin. Chem., 38(9):1613-1617.|
|322||*||Wilson, et al. 1992. Progress toward the development of an implantable sensor for glucose. Clin. Chem., 38(9):1613-1617.|
|323||Wilson, et al. 2000. Enzyme-based biosensors for in vivo measurements. Chem. Rev., 100:2693-2704.|
|324||Worsley et al., Measurement of glucose in blood with a phenylboronic acid optical sensor, Journal of Diabetes Science and Technology, 2(2):213-220, Mar. 2008.|
|325||Wright et al., Bioelectrochemical dehalogenations via direct electrochemistry of poly(ethylene oxide)- modified myoglobin, Electrochemistry Communications 1 (1999) 603-611.|
|326||Wu et al. 1999. In situ electrochemical oxygen generation with an immunoisolation device. Ann. N.Y. Acad. Sci., 875:105-125.|
|327||Yamasaki, Yoshimitsu. Sep. 1984. The development of a needle-type glucose sensor for wearable artificial endocrine pancreas. Medical Journal of Osaka University 35(1-2):25-34.|
|328||Yamasakiet al. 1989. Direct measurement of whole blood glucose by a needle-type sensor. Clinica Chimica Acta. 93:93-98.|
|329||Yang et al (1996). "A glucose biosensor based on an oxygen electrode: In-vitro performances in a model buffer solution and in blood plasma," Biomedical Instrumentation & Technology, 30:55-61.|
|330||Yang, et al. 2004. A Comparison of Physical Properties and Fuel Cell Performance of Nafion and Zirconium Phosphate/Nafion Composite Membranes. Journal Of Membrane Science 237:145-161.|
|331||Yanget al. 1998. Development of needle-type glucose sensor with high selectivity. Science and Actuators B 46:249-256.|
|332||Zamzow et al. 1990. Development and evaluation of a wearable blood glucose monitor, ASAIO Transactions; 36(3): pp. M588-M591.|
|333||Zhang et al (1993). Electrochemical oxidation of H202 on Pt and Pt + Ir electrodes in physiological buffer and its applicability to H202-based biosensors. J. Electroanal. Chem., 345:253-271.|
|334||Zhang et al. 1993. In vitro and in vivo evaluation of oxygen effects on a glucose oxidase based implantable glucose sensor. Analytica Chimica Acta, 281:513-520.|
|335||Zhang et al. 1994. Elimination of the acetaminophen interference in an implantable glucose sensor. Analytical Chemistry 66(7):1183-1188.|
|336||Zhang et al. 1994. Elimination of the acetaminophen interference in an implantable glucose sensor. Analytical Chemistry, 66(7):1183-1188.|
|337||Zhu et al. (1994). "Fabrication and characterization of glucose sensors based on a microarray H202 electrode." Biosensors & Bioelectronics, 9: 295-300.|
|338||Zhu et al. 2002. Planar amperometric glucose sensor based on glucose oxidase immobilized by chitosan film on prussian blue layer. Sensors, 2:127-136.|
|U.S. Classification||204/403.05, 204/403.11, 600/347, 600/345|
|International Classification||A61B5/05, G01N27/327, G01N27/26, G01N27/416, G01N|
|Cooperative Classification||A61B5/14865, A61B5/14532, C12Q1/001, G01N27/3274|
|European Classification||G01N27/416, A61B5/1486B, A61B5/145G, C12Q1/00B|
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|15 Jul 2010||AS||Assignment|
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