Source: http://www.google.fr/patents/US4919767
Timestamp: 2017-12-16 20:55:01
Document Index: 524754608

Matched Legal Cases: ['Application No. 216577', 'application No. 216577', 'Application No. 216577', 'Application No. 216577', 'Application No. 225094', 'Application No. 204468']

Brevet US4919767 - Sensor and method for analyte determination - Google Brevets
A sensor of the enzyme-electrode type comprising an electrode and a membrane permeable to liquids and solutes which is positioned between the electrode and a specimen containing the analyte to be determined, is characterized by the fact that a layer of a porous material, positioned in the membrane between...http://www.google.fr/patents/US4919767?utm_source=gb-gplus-shareBrevet US4919767 - Sensor and method for analyte determination
Numéro de publication US4919767 A
Numéro de demande US 07/228,153
Date de publication 24 avr. 1990
Date de dépôt 4 août 1988
Date de priorité 4 août 1987
Autre référence de publication CA1290015C, DE3853029D1, DE3853029T2, EP0302661A1, EP0302661B1
Numéro de publication 07228153, 228153, US 4919767 A, US 4919767A, US-A-4919767, US4919767 A, US4919767A
Inventeurs Pankaj M. Vadgama, Lian X. Tang
Cessionnaire d'origine Imperial Chemical Industries Plc
Citations de brevets (4), Citations hors brevets (2), Référencé par (294), Classifications (15), Événements juridiques (7)
Sensor and method for analyte determination
US 4919767 A
A sensor of the enzyme-electrode type comprising an electrode and a membrane permeable to liquids and solutes which is positioned between the electrode and a specimen containing the analyte to be determined, is characterized by the fact that a layer of a porous material, positioned in the membrane between the enzyme-containing layer and the specimen, has been treated to at least partially fill the pores with a liquid of limited volatility which is not significantly soluble in water and is to some degree a solvent for the analyte.
1. A sensor of the enzyme-electrode type for the determination of an analyte in a sample, which analyte is convertible in the presence of an enzyme into a species which is detectable by the sensor, which sensor comprises an electrode and a membrane permeable to liquids and solutes which is positioned between the electrode and a specimen containing the analyte, which membrane comprises a first layer containing at least one enzyme and a second layer positioned between the enzyme-containing layer and the specimen, wherein said second layer contains an area through which analyte can pass, in the form of a liquid membrane formed from a porous material of which the pores have been at least partially filled with a liquid having the ability to pass the analyte while rejecting other species in the sample.
2. A sensor according to claim 1, wherein said membrane further comprises a third layer of material disposed between the enzyme-containing layer and the electrode.
3. A sensor according to claim 2, wherein said third layer is formed from a material selected from the group consisting of polymethylmethacrylate, polyurethane and cellulose acetate.
4. A sensor according to claim 1, wherein the porous material is selected from the group consisting of polycarbonates, polyurethanes and modified celluloses.
5. A sensor according to claim 1, wherein the porous material has a porosity within the range from 0.05 to 20 percent.
6. A sensor of the enzyme-electrode type for the determination of an analyte in a specimen containing said analyte, said analyte being convertible in the presence of an enzyme into a species detectable by the sensor, which sensor comprises an electrode and a membrane permeable to liquids and solutes which is positioned between the electrode and the specimen, said membrane comprising an enzyme-containing layer, a layer of material disposed between said enzyme-containing layer and said electrode and a layer disposed between said enzyme-containing layer and said specimen and having an area of a porous material of average pore diameter less than 5 μm, said pores being at least partially filled with a non-aqueous liquid having the ability to pass the analyte while rejecting other species in the specimen.
7. A sensor according to claim 6, wherein the liquid comprises a lipid.
8. A sensor according to claim 7, wherein said lipid is selected from the group consisting of isopropyl myristate and lecithin.
9. A sensor according to claim 6, wherein the liquid comprises an ester of a fatty acid.
10. A sensor according to claim 9, wherein the fatty acid ester is selected from the group consisting of methyl oleate and methyl linoleate.
11. A sensor according to claim 6, wherein the membrane contains a layer formed from a polymeric material selected from the group consisting of polyarylsulphones and polyarylketones.
12. An enzyme-electrode sensor for determining an analyte in a specimen, which analyte is convertible in the presence of an enzyme into a species detectable by the sensor, which sensor comprises an electrode, a first layer of a material selected from polymethylmethacrylate, polyurethane and cellulose acetate, disposed between the electrode and the specimen, an enzyme-containing second layer overlying said first layer, and a porous third layer overlying said second layer, which porous layer comprises a material selected from polycarbonates, polyurethanes and modified celluloses, has an average pore diameter less than 5 μm and has said pores at least partially filled with a liquid comprising a lipid or a fatty acid ester.
13. A method for determining an analyte in a specimen which comprises contacting the specimen with the outer layer of a membrane, permeable to liquids and solutes and comprising one or more enzymes, in the presence of which the analyte is convertible into a species detectable by a sensor which incorporates the membrane, and one or more layers of material, and measuring the response of the sensor to the species, characterized in that a layer in the membrane between the enzyme and the specimen contains an area through which analyte can pass formed from a porous material which has been treated to fill its pores wholly or partially with a liquid which has the ability to pass the analyte while rejecting other species in the specimen.
This invention relates to a sensor of the enzyme electrode type comprising an improved membrane and to an analytical method using the sensor.
Enzyme electrodes are increasingly used in medical and other laboratories particularly for the determination of materials such as glucose and urea in specimens of blood and other physiological fluids. Such electrodes are described in many publications notably an article by Clark and Lyons (Anals of the New York Acadamy of Science, 102, 29-45, 1962) and U.S. Pat. Nos. 3,539,455 and 3,979,274 to Clark and Newman respectively. Enzyme electrodes are generally used to determine materials which themselves are not electrochemically active but which in the presence of suitable enzymes take part in reactions which produce species which can be readily detected by the electrodes. In enzyme electrodes the enzymes are frequently located within polymeric materials in close proximity to the underlying electrode.
A considerable amount of research has been carried out in order to improve the properties of membranes for use in enzyme electrodes and many membranes for this purpose have been disclosed. An example of a type of membrane which is often used is the laminated membrane disclosed by Newman in U.S. Pat. No. 3,979,274. This membrane comprises a first or inner layer of an essentially homogeneous material, for example cellulose acetate, which can prevent the passage of materials of low molecular weight likely to interfere with the enzymic signal, a close adherent layer of the enzyme itself (with or without such other materials that may be blended with it), and a second layer (in this instance an outer layer) of a porous support film which can prevent the passage of cellular and colloidal elements.
The determination of glucose can be taken as an example of the determination of a material by an enzyme electrode. In the presence of the enzyme glucose oxidase the following reaction occurs: ##STR1## The hydrogen peroxide produced in this reaction passes through the first layer of a membrane such as that of U.S. Pat. No. 3,979,274 and can be determined using the electrode. Since the hydrogen peroxide produced is dependent upon the glucose present in a specimen, the glucose concentration can be determined using a suitably calibrated sensor.
To date a number of difficulties have limited the utility of enzyme electrodes and restricted the scale of their use in routine analysis of, e.g. blood samples. Significant among these difficulties is the limited linearity of the response of electrodes to analytes such as glucose or lactate which are substrates for the enzyme catalysed reactions. The response is linear only over a limited range of low concentrations of the analytes and hence the concentrations of the materials to be determined must be low and generally diluted samples must be used in specimens for analysis using enzyme electrodes. It is not always practicable to make diluted samples for routine analysis outside the laboratory and it would be impossible for invasive monitoring.
In our published European Patent Application No. 216577 we describe and claim a sensor for the determination of an analyte having a membrane between its electrode and a specimen of the analyte to be tested. Preferably the membrane is a membrane such as that of U.S. Pat. No. 3,979,274. However, in the membrane of the sensor of European application No. 216577 there is a restricted permeability layer of material between the enzyme-containing layer and the specimen which restricted permeability layer contains an area through which analyte can pass formed from a porous material of restricted permeability having a porosity which is not greater than 5%.
According to the present invention we provide a sensor of the enzyme-electrode type for the determination of an analyte, said analyte being convertible in the presence of an enzyme into a species which can be detected by the sensor, which comprises an electrode and a membrane permeable to liquids and solutes positioned between the electrode and a specimen containing the analyte, said membrane comprising a layer containing one or more enzymes and a layer of material positioned between the enzyme-containing layer and the specimen characterised in that said layer of material contains an area through which analyte can pass formed from a porous material which has been treated to fill its pores wholly or partially with a liquid thereby forming a supported liquid membrane.
Further according to the invention we provide a method for determining an analyte in a specimen which comprises contacting the specimen with the outer layer of a membrane, permeable to liquids and solutes and comprising one or more enzymes, in the presence of which the analyte is convertible into a species detectable by a sensor which incorporates the membrane, and one or more layers of material, and measuring the response of the sensor to the species, characterised in that a layer in the membrane between the enzyme and the specimen contains an area through which analyte can pass formed from a porous material which has been treated to fill its pores wholly or partially with a liquid thereby forming a supported liquid membrane.
The liquid is of limited volatility and is not significantly soluble in water so that loss of the liquid from the membrane via evaporation and/or dissolution is reduced and hence the stability of the liquid membrane enhanced. The liquid is to some degree a solvent for the analyte so that the analyte may pass through the liquid in the liquid membrane to reach the enzyme.
The phrase "liquid of limited volatility" includes systems in which a volatile liquid is held below another liquid having limited volatility, although such systems have limited utility in the sensors of the invention. Preferably the liquid of limited volatility is either not a solvent for interfering species such as ascorbic acid which will give rise to signals interfering with those from the analyte or is a solvent for such interfering species only to a limited extent.
The liquid may be in the form of a solution. The liquid may comprise a lipid or a fatty acid ester. The liquid treated layer can be formed by dipping a membrane in a suitable liquid, particularly lipid solutions, e.g. in n-butanol or n-decane or mixtures as solvents. Preferred lipids for liquid treatments are isopropyl myristate (IPM) and lecithin. These lipids when used in concentrations of approximately 0.5 mM will allow catechol and glucose to pass through them but are substantially impermeable to interfering species such as ascorbic acid, uric acid, hydrogen peroxide and paracetamol.
A suitable technique for forming the treated layer is to dip the membrane into the liquid, e.g. a lipid solution for a short time, e.g. 2 to 4 minutes. After this time the membrane is removed using a tissue before the membrane is fitted to the electrode. It has been found that the liquid treated membrane is quite stable with time.
The sensor of the invention is selective with regard to analytes and gives a response which is linear over a range similar to that of our published European Patent Application No. 216577. It enables this similar degree of linearity to be achieved using membranes with layers of restricted permeability which have larger pores and/or greater porosities than those of the membranes of European Application No. 216577.
The treated area causes the layer containing it to have restricted permeability. Preferably all or a major proportion of the effective area of this layer has been treated.
In its most simple form the membrane in the sensor of the invention consists of the enzyme-containing layer and the treated layer. The treated layer is the outer layer in this simple form of membrane and is contacted directly by the specimen in the method of the invention for determining an analyte.
However, it is possible for the membrane to be a laminated membrane of the type of which that disclosed in U.S. Pat. No. 3,979,274 is an example. Such a membrane comprises a first or inner layer of material positioned between the enzyme-containing layer and the electrode, the enzyme-containing layer and a second layer of material on the other side of the enzyme-containing layer which second layer is the treated layer.
Hereafter in this specification the sensor of the invention which is described will contain a laminated membrane of the type of which the membrane described in U.S. Pat. No. 3,979,274 is an example having first and second layers the treated layer being the second layer.
It should be understood that the membranes in the sensor of the invention can contain more than two layers of material in addition to the enzyme-containing layer. For instance the second layer, i.e. the treated layer is not necessarily the outermost layer of the membrane. There may be a further layer or layers of material, i.e. third, fourth etc layers, between the second layer or treated layer and the specimen. Often however the second layer will be the outer layer and its outer face will be contacted by the specimen.
Generally the porous material of the treated layer will be a polymeric material but other suitable materials may be used. Thus the treated layer may be formed from porous glass, a metal, e.g. a sintered metal, having pores cut by lasers or porous etched and sintered ceramics such as aluminas.
Suitably the treated layer of material is formed from material having a porosity in the range 0.05 to 20%.
The pore size is selected so that the liquid of limited volatility fills the pore wholly or partially to form a supported liquid membrane. The mean diameters of the pores may be less than 5 μm, and are preferably equal to or less than 3 μm. For example the mean diameters of the pores may be in the range 3 μm to 0.05 μm, particularly for the case where the liquid comprises isopropyl myristate and the layer is formed from a polycarbonate.
The sensor of the invention may have a detachable membrane or it may be a disposable sensor with an adherent membrane. Materials used in the formation of suitable electrodes for the sensors include inert metals and/or carbon.
When the sensor incorporates a laminated membrane of the type disclosed in U.S. Pat. No. 3,979,274 the first layer which is to be located between the enzyme layer and the electrode is suitably formed from polymethyl-methacrylate, polyurethane, cellulose acetate or another porous material which will restrict or prevent passage of electroactive interfering compounds such as ascorbic acid and tyrosine. Suitably the first layer has a thickness in the range 0.1 microns to 1.0 microns. Preferably the membrane contains a layer formed from a polyarylsulphone or a polyarylketone as described in our published European Application No. 225094.
Suitable porous materials for the second layer include porous polycarbonates, polyurethanes, and modified cellulose particularly cellulose nitrate, cellulose acetate and regenerated cellulose.
The enzyme present in the sensor of the invention may be located in the membrane in any suitable manner. Preferably in a laminated membrane it is present between the first and second layers of material and forms the bond between them. In this situation, and also generally, the enzyme is preferably immobilised in a gel. A very suitable material for this purpose is glutaraldehyde; proteins such as albumin and other materials may also be included. In order to facilitate the obtaining of rapid stable readings from the sensor it is preferred that the enzyme-containing layer is thin, i.e. not greater than 5 microns thick.
The enzyme to be used in the sensor of the invention will depend upon the analyte whose concentration is to be determined. If the analyte is glucose then the enzyme will be for example glucose oxidase. Other enzymes which may be present include uricase and lactate oxidase for determination of uric acid and lactic acid respectively. Enzyme systems comprising two or more enzymes may also be present.
A laminated membrane for use in the sensor of the invention for the determination of glucose may be prepared by a method including the following steps:
1. A porous polycarbonate film having a porosity of less than 20% and pores of diameter less than 10 μm and preferably less than 5 μm is dipped in isopropyl myristate in n-butanol for 3 minutes to treat it. When removed from the solution, excess liquid is removed from the film using a tissue;
2. 1 mg glucose oxidase is dissolved in 50 μl of (100 mg/ml) albumin;
3. 3 μl of 12.5% glutaraldehyde solution is mixed with 3 μl of enzyme/albumin mixture on a glass microscope slide;
4.1 μl of the mixture produced in the previous step is applied to one face of the 1 cm2 polycarbonate produced in step 1;
5. The other surface of the enzyme layer is covered immediately with a thin cellulose acetate film and the resulting laminated membrane is clamped for 3 minutes between glass slides;
6. The membrane is applied to a platinum electrode to form the sensor of the invention, the cellulose acetate film being nearest to the electrode and forming the first layer.
Use of the method of the invention gives the advantage of an increase in the concentration range over which a graph of concentration against sensor response is linear. With conventional methods linearity was generally extended only up to approximately a concentration of 3 m mol per liter for glucose. Using the method of the invention linearity is increased and the range extends to glucose concentrations of 50 m mol per liter and even higher. This is achieved through restriction of substrate entry into the enzyme layer and therefore with some loss of sensitivity. Thus the range covers the concentrations of glucose which can be anticipated in blood samples thereby enabling blood glucose levels to be determined more readily. This is a considerable advantage in situations where large numbers of determinations must be made regularly and with minimal sample preparation. Linearity is also extended by applying to the second layer of the membrane a medium comprising an organo-silane having reactive groups as described in our published European Patent Application No. 204468. This treatment may be applied to the second layer of the membrane in the sensor of the present invention to produce a combined effect and further improved linearity.
These and other objects of the present invention will be described in detail herewith with respect to the accompanying drawings, in which:
FIG. 1 shows a diagram of the sensor used according the present invention;
FIG. 2 shows the response obtained with a treated membranes in contrast with the untreated membrane;
FIG. 3 shows a response obtained with an untreated membrane of 2 μm as compared with a treated membrane;
FIG. 4 shows a response for untreated versus treated membrane 2 μm;
FIG. 5 shows the linearity of response as compared with concentration of glucose for an untreated membrane of 0.05 μm;
FIG. 6 shows the same linearlity for a treated membrane;
FIG. 7 shows a response with pore size of 0.8 μm for an untreated membrane, and shows the linearity of response;
FIG. 8 shows the same linearlity for a treated membrane.
FIGS. 9 and 10 show response for a pore size of 0.015 μm for untreated and treated membranes, respectively.
The invention is illustrated by FIG. 1 of the accompanying drawings.
In FIG. 1, reference numeral 1 is the second layer of the membrane formed from a polycarbonate film treated with a 30% solution of isopropyl myristate (IPM), 2 is a layer of glucose oxidase enzyme dissolved in albumin and mixed with glutaraldehyde, 3 is the first layer formed from cellulose acetate, 4 is the platinum working electrode and 5 is the silver reference electrode. 1, 2 and 3 together form a laminated membrane. Platinum working electrode 4 acts as an anode whilst silver reference electrode 5 acts as a cathode. The membrane is held in place on the electrode by a perspex ring pressing down on outer layer 1 towards its outer edges at 6.
The use of the sensor shown in FIG. 1 is illustrated in the following example:
Experiments were carried out using sensors having membranes prepared as described above. The second or outer layers of the membranes used were formed from polycarbonate film treated by dipping in lipid solutions in n-butanol, n-decane and mixture of these solvents. Lipids used were lecithin and isopropyl myristate. These treated membranes were found to be readily permeable to catechol but only permeable with difficulty to species such as hydrogen peroxide, ascorbic acid, paracetamol and phiroglucinol (concentrations of the species used were 0.5 mM). This is illustrated in the following table which shows the reduction in signal size observed for each of the interferring species when polycarbonate membranes with pore sizes 0.8 μm and 0.2 μm are treated with IPM.
______________________________________      Reduction in Signal size (%)SPECIES      0.8 μm pore size                      0.2 μm pore size______________________________________Hydrogen Peroxide        86.3          98.5Ascorbic acid        94.65         100Uric Acid    91.31Paracetamol  56            82Phiroglucinol        66.6          95______________________________________
The treated membranes were permeable to glucose although the magnitude of the response registered by the sensor was reduced. It was found that the range of linearity of the response obtained in a series of experiments with different glucose concentrations was increased in treated membranes.
This is illustrated by the graphs shown in FIGS. 2 to 10 of the drawings in which response magnitude is plotted against glucose concentration (mM). The treated membranes referred to are polycarbonate membranes treated with IPM.
As shown in FIG. 2, the response (in arbitrary units) obtained with membranes treated with IPM (plot A) is linear up to at least 50 mM, in contrast to the response (plot B) obtained with the untreated membrane.
FIGS. 3 to 10 further illustrate the result shown in FIG. 2 and also show the effect of pore size on linearity of response. In FIG. 3, Plot B is the response obtained with an untreated membrane having a pore size of 2 μm, and Plot A is the response obtained with a membrane treated with IPM. Linearity is thus increased for the treated membrane.
FIG. 4 shows the response obtained with membrane having a pore size of 0.2 μm. The untreated membrane gives a linear response only up to a concentration of just over 2 mM glucose (see Plot B); whereas the treated membrane (Plot A) gives a linear response at least up to a concentration of 10 mM.
As shown in FIGS. 5 and 6 the response obtained with an untreated membrane having a pore size of 0.05 μm is linear up to about a concentration of 4 mM glucose (FIG. 5); whereas the treated membrane gives a linear response up to at least 60 mM glucose (FIG. 6).
The response obtained with membranes having a pore size of 0.8 μm is shown in FIGS. 7 and 8. As shown in FIG. 7, the untreated membrane gives a linear response only up to a concentration of 2 mM glucose (Plot B). However, a membrane treated with 1PM gives a linear response up to a concentration of about 20 mM glucose (see Plot A FIG. 7, and FIG. 8).
Similarly, an increase in linearity of response was observed with a pore size of 0.015 μm when treated with 1PM--see FIG. 9 (untreated membrane) and FIG. 10 (treated membrane).
The experiments referred to above illustrate that the range of linearity is increased with treated membranes. It was also observed that the upper concentration limit of the range may vary with concentration of the liquid. For example an untreated polycarbonate membrane (pore size 0.2 μm) gave a linear response up to just over 2 mM glucose; whereas a membrane treated with 100% IPM was linear up to 30 mM glucose and a membrane treated with 90% 1PM/10% n-decanol was linear up to at least 60 mM glucose.
Experiments also showed that membranes treated with the fatty acid esters methyl oleate and methyl linoleate increased lineaty of response in a similar way to IPM. Membranes treated with lecithin also behaved in a similar fashion to these treated with IPM.
US3979274 * 24 sept. 1975 7 sept. 1976 The Yellow Springs Instrument Company, Inc. Membrane for enzyme electrodes
US4388166 * 15 mai 1982 14 juin 1983 Tokyo Shibaura Denki Kabushiki Kaisha Electrochemical measuring apparatus provided with an enzyme electrode
US4661235 * 3 août 1984 28 avr. 1987 Krull Ulrich J Chemo-receptive lipid based membrane transducers
US4759828 * 9 avr. 1987 26 juil. 1988 Nova Biomedical Corporation Glucose electrode and method of determining glucose
1 "The Structure and Electrochemical Properties of a Polymer-Supported Lipid Biosensor", by Thompson et al., Analytica Chimica Acta, vol. 117, 1980, pp. 133-145.
2 * The Structure and Electrochemical Properties of a Polymer Supported Lipid Biosensor , by Thompson et al., Analytica Chimica Acta, vol. 117, 1980, pp. 133 145.
US5262305 * 3 sept. 1991 16 nov. 1993 E. Heller & Company Interferant eliminating biosensors
US5264106 * 18 mars 1993 23 nov. 1993 Medisense, Inc. Enhanced amperometric sensor
US5356786 * 2 déc. 1993 18 oct. 1994 E. Heller & Company Interferant eliminating biosensor
US5437973 * 7 mai 1993 1 août 1995 The Victoria University Of Manchester Enzyme-electrode sensor
US5755231 * 17 mai 1995 26 mai 1998 Plus Bio, Inc. Test strip including integral specimen flow retarding structure
US5840171 * 21 déc. 1993 24 nov. 1998 Unilever Patent Holdings Bv Electrochemical reactions
US6039861 * 16 nov. 1998 21 mars 2000 Unilever Patent Holdings Bv Electrochemical reactions
US6103033 4 mars 1998 15 août 2000 Therasense, Inc. Process for producing an electrochemical biosensor
US6120676 4 juin 1999 19 sept. 2000 Therasense, Inc. Method of using a small volume in vitro analyte sensor
US6134461 4 mars 1998 17 oct. 2000 E. Heller & Company Electrochemical analyte
US6143164 16 déc. 1998 7 nov. 2000 E. Heller & Company Small volume in vitro analyte sensor
US6162611 3 janv. 2000 19 déc. 2000 E. Heller & Company Subcutaneous glucose electrode
US6175752 30 avr. 1998 16 janv. 2001 Therasense, Inc. Analyte monitoring device and methods of use
US6251260 24 août 1998 26 juin 2001 Therasense, Inc. Potentiometric sensors for analytic determination
US6284478 4 déc. 1996 4 sept. 2001 E. Heller & Company Subcutaneous glucose electrode
US6299757 6 oct. 1999 9 oct. 2001 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6329161 22 sept. 2000 11 déc. 2001 Therasense, Inc. Subcutaneous glucose electrode
US6338790 21 avr. 1999 15 janv. 2002 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6461496 27 oct. 1999 8 oct. 2002 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6484046 10 juil. 2000 19 nov. 2002 Therasense, Inc. Electrochemical analyte sensor
US6514718 29 nov. 2001 4 févr. 2003 Therasense, Inc. Subcutaneous glucose electrode
US6551494 6 avr. 2000 22 avr. 2003 Therasense, Inc. Small volume in vitro analyte sensor
US6565509 21 sept. 2000 20 mai 2003 Therasense, Inc. Analyte monitoring device and methods of use
US6576101 6 oct. 1999 10 juin 2003 Therasense, Inc. Small volume in vitro analyte sensor
US6591125 27 juin 2000 8 juil. 2003 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6592745 17 mai 2000 15 juil. 2003 Therasense, Inc. Method of using a small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6618934 15 juin 2000 16 sept. 2003 Therasense, Inc. Method of manufacturing small volume in vitro analyte sensor
US6654625 16 juin 2000 25 nov. 2003 Therasense, Inc. Mass transport limited in vivo analyte sensor
US6706532 * 7 nov. 1996 16 mars 2004 The Victoria University Of Manchester Membrane for chemical and biosensors
US7195697 21 nov. 2002 27 mars 2007 Radiometer Medical A/S Sensor membrane, a method for the preparation thereof, a sensor and a layered membrane structure for such sensor
US7288174 * 12 févr. 2004 30 oct. 2007 I-Sens, Inc. Electrochemical biosensor
US7341830 * 16 mai 2003 11 mars 2008 Roche Diagnostics Operations, Inc. Method and reagent system having a non-regenerative enzyme-coenzyme complex
US7721412 16 août 2005 25 mai 2010 Abbott Diabetes Care Inc. Method of making an electrochemical sensor
US7766829 4 nov. 2005 3 août 2010 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US7811231 26 déc. 2003 12 oct. 2010 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US7861397 30 oct. 2007 4 janv. 2011 Abbott Diabetes Care Inc. Method of making an electrochemical sensor
US7879213 30 oct. 2007 1 févr. 2011 Abbott Diabetes Care Inc. Sensor for in vitro determination of glucose
US7906009 30 juil. 2008 15 mars 2011 Abbott Diabetes Care Inc. Small volume in vitro analyte sensor
US7909984 7 févr. 2008 22 mars 2011 Abbott Diabetes Care Inc. Small volume in vitro analyte sensor
US7928850 8 mai 2008 19 avr. 2011 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US7951581 10 janv. 2008 31 mai 2011 Roche Diagnostics Operations, Inc. Method and reagent system with non-regenerable enzyme-coenzyme complex
US7976778 22 juin 2005 12 juil. 2011 Abbott Diabetes Care Inc. Blood glucose tracking apparatus
US7988845 28 janv. 2008 2 août 2011 Abbott Diabetes Care Inc. Integrated lancing and measurement device and analyte measuring methods
US7996054 20 févr. 2006 9 août 2011 Abbott Diabetes Care Inc. Electrochemical analyte sensor
US8029442 6 sept. 2007 4 oct. 2011 Abbott Diabetes Care Inc. Sensor inserter assembly
US8066639 4 juin 2004 29 nov. 2011 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US8103456 29 janv. 2009 24 janv. 2012 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8112240 29 avr. 2005 7 févr. 2012 Abbott Diabetes Care Inc. Method and apparatus for providing leak detection in data monitoring and management systems
US8117734 30 oct. 2007 21 févr. 2012 Abbott Diabetes Care Inc. Method of making an electrochemical sensor
US8123686 1 mars 2007 28 févr. 2012 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US8136220 30 oct. 2007 20 mars 2012 Abbott Diabetes Care Inc. Method of making an electrochemical sensor
US8149117 29 août 2009 3 avr. 2012 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8168051 30 oct. 2007 1 mai 2012 Abbott Diabetes Care Inc. Sensor for determination of glucose
US8187183 11 oct. 2010 29 mai 2012 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US8226891 31 mars 2006 24 juil. 2012 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US8236242 12 févr. 2010 7 août 2012 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US8268243 28 déc. 2009 18 sept. 2012 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US8273227 30 oct. 2007 25 sept. 2012 Abbott Diabetes Care Inc. Sensor for in vitro determination of glucose
US8333714 10 sept. 2006 18 déc. 2012 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US8362904 18 avr. 2011 29 janv. 2013 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8414749 12 nov. 2008 9 avr. 2013 Abbott Diabetes Care Inc. Subcutaneous glucose electrode
US8456301 8 mai 2008 4 juin 2013 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8461985 8 mai 2008 11 juin 2013 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8463351 6 août 2010 11 juin 2013 Abbott Diabetes Care Inc. Electrochemical analyte sensor
US8473220 23 janv. 2012 25 juin 2013 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8512239 20 avr. 2009 20 août 2013 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US8512243 30 sept. 2005 20 août 2013 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US8532731 8 mai 2009 10 sept. 2013 Abbott Diabetes Care Inc. Methods of determining analyte concentration
US8545403 28 déc. 2006 1 oct. 2013 Abbott Diabetes Care Inc. Medical device insertion
US8571624 29 déc. 2004 29 oct. 2013 Abbott Diabetes Care Inc. Method and apparatus for mounting a data transmission device in a communication system
US8585591 10 juil. 2010 19 nov. 2013 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US8588881 2 mars 2007 19 nov. 2013 Abbott Diabetes Care Inc. Subcutaneous glucose electrode
US8593109 3 nov. 2009 26 nov. 2013 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US8593287 20 juil. 2012 26 nov. 2013 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8597575 23 juil. 2012 3 déc. 2013 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US8602991 7 juin 2010 10 déc. 2013 Abbott Diabetes Care Inc. Analyte sensor introducer and methods of use
US8613703 29 mai 2008 24 déc. 2013 Abbott Diabetes Care Inc. Insertion devices and methods
US8622903 25 mai 2012 7 janv. 2014 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US8647269 20 avr. 2009 11 févr. 2014 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US8665091 30 juin 2009 4 mars 2014 Abbott Diabetes Care Inc. Method and device for determining elapsed sensor life
US8676513 21 juin 2013 18 mars 2014 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8706180 10 juin 2013 22 avr. 2014 Abbott Diabetes Care Inc. Electrochemical analyte sensor
US8732188 15 févr. 2008 20 mai 2014 Abbott Diabetes Care Inc. Method and system for providing contextual based medication dosage determination
US8741590 3 avr. 2007 3 juin 2014 Abbott Diabetes Care Inc. Subcutaneous glucose electrode
US8764657 30 mars 2012 1 juil. 2014 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8765059 27 oct. 2010 1 juil. 2014 Abbott Diabetes Care Inc. Blood glucose tracking apparatus
US8771183 16 févr. 2005 8 juil. 2014 Abbott Diabetes Care Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US8795176 30 juil. 2007 5 août 2014 Abbott Diabetes Care Inc. Integrated sample acquisition and analyte measurement device
US8852101 30 sept. 2009 7 oct. 2014 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US8862198 17 déc. 2012 14 oct. 2014 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US8930203 3 févr. 2010 6 janv. 2015 Abbott Diabetes Care Inc. Multi-function analyte test device and methods therefor
US8933664 25 nov. 2013 13 janv. 2015 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US8993331 31 août 2010 31 mars 2015 Abbott Diabetes Care Inc. Analyte monitoring system and methods for managing power and noise
US9000929 22 nov. 2013 7 avr. 2015 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US9017259 5 août 2014 28 avr. 2015 Abbott Diabetes Care Inc. Integrated sample acquisition and analyte measurement device
US9035767 30 mai 2013 19 mai 2015 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US9039975 2 déc. 2013 26 mai 2015 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US9042953 2 mars 2007 26 mai 2015 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066709 17 mars 2014 30 juin 2015 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US9095290 27 févr. 2012 4 août 2015 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US9177456 10 juin 2013 3 nov. 2015 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US9186098 24 mars 2011 17 nov. 2015 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9215992 24 mars 2011 22 déc. 2015 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9226701 28 avr. 2010 5 janv. 2016 Abbott Diabetes Care Inc. Error detection in critical repeating data in a wireless sensor system
US9259175 23 oct. 2006 16 févr. 2016 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US9265453 24 mars 2011 23 févr. 2016 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9271669 27 avr. 2015 1 mars 2016 Abbott Diabetes Care Inc. Method for integrated sample acquisition and analyte measurement device
US9314195 31 août 2010 19 avr. 2016 Abbott Diabetes Care Inc. Analyte signal processing device and methods
US9314198 3 avr. 2015 19 avr. 2016 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US9320461 29 sept. 2010 26 avr. 2016 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9323898 15 nov. 2013 26 avr. 2016 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US9332933 29 sept. 2014 10 mai 2016 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9351669 30 sept. 2010 31 mai 2016 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US9380971 5 déc. 2014 5 juil. 2016 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US9398882 10 sept. 2006 26 juil. 2016 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9402544 1 févr. 2010 2 août 2016 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9402570 11 déc. 2012 2 août 2016 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9477811 23 juin 2005 25 oct. 2016 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US9480421 19 août 2013 1 nov. 2016 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US9521968 30 sept. 2005 20 déc. 2016 Abbott Diabetes Care Inc. Analyte sensor retention mechanism and methods of use
US9572534 28 juin 2011 21 févr. 2017 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US9574914 3 mars 2014 21 févr. 2017 Abbott Diabetes Care Inc. Method and device for determining elapsed sensor life
US9625413 19 mai 2015 18 avr. 2017 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US9636068 24 juin 2016 2 mai 2017 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9649057 11 mai 2015 16 mai 2017 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US9662057 17 févr. 2016 30 mai 2017 Abbott Diabetes Care Inc. Integrated sample acquisition and analyte measurement method
US9668684 4 mars 2010 6 juin 2017 Abbott Diabetes Care Inc. Self-powered analyte sensor
US9669162 16 mars 2016 6 juin 2017 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US9687183 30 mars 2012 27 juin 2017 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US9693713 27 juin 2016 4 juil. 2017 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9730584 10 févr. 2014 15 août 2017 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US9743862 29 mars 2012 29 août 2017 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US9743863 1 juin 2016 29 août 2017 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US9750439 8 avr. 2016 5 sept. 2017 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9750444 27 avr. 2016 5 sept. 2017 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US9775563 21 sept. 2016 3 oct. 2017 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US9788771 23 oct. 2006 17 oct. 2017 Abbott Diabetes Care Inc. Variable speed sensor insertion devices and methods of use
US9795331 28 avr. 2016 24 oct. 2017 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9801545 30 juil. 2015 31 oct. 2017 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US9808186 26 sept. 2014 7 nov. 2017 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US20020053523 * 28 déc. 2001 9 mai 2002 Therasense, Inc. Small volume in vitro analyte sensor and methods
US20020084196 * 28 déc. 2001 4 juil. 2002 Therasense, Inc. Small volume in vitro analyte sensor and methods
US20020148739 * 28 déc. 2001 17 oct. 2002 Therasense, Inc. Small Volume in Vitro Analyte Sensor and Methods
US20020157948 * 28 déc. 2001 31 oct. 2002 Therasense, Inc. Small Volume in Vitro Analyte Sensor and Methods
US20030088166 * 11 nov. 2002 8 mai 2003 Therasense, Inc. Electrochemical analyte sensor
US20030134347 * 28 janv. 2003 17 juil. 2003 Therasense, Inc. Subcutaneous glucose electrode
US20030199744 * 17 avr. 2003 23 oct. 2003 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US20030201194 * 9 juin 2003 30 oct. 2003 Therasense, Inc. Small volume in vitro analyte sensor
US20040054267 * 15 sept. 2003 18 mars 2004 Therasense, Inc. Small volume in vitro analyte sensor
US20040060818 * 12 sept. 2003 1 avr. 2004 Therasense, Inc. Small volume in vitro analyte sensor and methods of making
US20040225230 * 12 juin 2004 11 nov. 2004 Therasense, Inc. Small volume in vitro analyte sensor and methods
US20050000808 * 12 févr. 2004 6 janv. 2005 I-Sens, Inc. Electrochemical biosensor
US20050058873 * 12 sept. 2003 17 mars 2005 Arthur Alan R. Integral fuel cartridge and filter
US20050121322 * 24 janv. 2005 9 juin 2005 Therasense, Inc. Analyte monitoring device and methods of use
US20050214891 * 16 mai 2003 29 sept. 2005 Carina Horn Method and reagent system having a non-regenerative enzyme-coenzyme complex
US20050278945 * 12 sept. 2003 22 déc. 2005 Therasense, Inc. Small volume in vitro analyte sensor
US20060003398 * 15 juil. 2005 5 janv. 2006 Therasense, Inc. Subcutaneous glucose electrode
US20060042080 * 16 août 2005 2 mars 2006 Therasense, Inc. Method of making an electrochemical sensor
US20060091006 * 17 nov. 2005 4 mai 2006 Yi Wang Analyte sensor with insertion monitor, and methods
US20070000776 * 15 avr. 2004 4 janv. 2007 National Institute Of Advanced Industrial Science Biosensor and production method therefor
US20070151869 * 2 mars 2007 5 juil. 2007 Abbott Diabetes Care, Inc. Subcutaneous Glucose Electrode
US20070215491 * 3 avr. 2007 20 sept. 2007 Abbott Diabetes Care, Inc. Subcutaneous Glucose Electrode
US20080004512 * 6 sept. 2007 3 janv. 2008 Funderburk Jeffery V Sensor inserter assembly
US20080027302 * 30 juil. 2007 31 janv. 2008 Therasense, Inc. Integrated Sample Acquisition and Analyte Measurement Device
US20080041506 * 17 août 2007 21 févr. 2008 Aijun Huang Alloy and method of treating titanium aluminide
US20080064941 * 6 sept. 2007 13 mars 2008 Funderburk Jeffery V Sensor inserter methods of use
US20080139798 * 20 sept. 2007 12 juin 2008 Dharmacon, Inc. siRNA targeting myeloid cell leukemia sequence 1
US20080182324 * 10 janv. 2008 31 juil. 2008 Carina Horn Method and reagent system with non-regenerable enzyme-coenzyme complex
US20080275423 * 30 oct. 2007 6 nov. 2008 Therasense, Inc. Method of making an electrochemical sensor
US20080276455 * 30 oct. 2007 13 nov. 2008 Therasense, Inc. method of making an electrochemical sensor
US20080277292 * 7 févr. 2008 13 nov. 2008 Therasense, Inc. Small Volume In Vitro Analyte Sensor
US20080281175 * 30 oct. 2007 13 nov. 2008 Therasense, Inc. Method of making an electrochemical sensor
US20080281176 * 30 oct. 2007 13 nov. 2008 Therasense, Inc. Method of making an electrochemical sensor
US20080281177 * 30 oct. 2007 13 nov. 2008 Therasense, Inc. method of making an electrochemical sensor
US20090014328 * 31 oct. 2007 15 janv. 2009 Abbott Diabetes Care Inc. Small Volume in vitro Analyte Sensor and Methods of Making
US20090171182 * 29 déc. 2004 2 juil. 2009 Abbott Diabetes Care Inc. Method and apparatus for mounting a data transmission device in a communication system
US20090270764 * 8 mai 2009 29 oct. 2009 Abbott Diabetes Care Inc. Methods of determining concentration of ketone bodies
US20100076287 * 29 sept. 2009 25 mars 2010 Feldman Benjamin J Small Volume In Vitro Analyte Sensor and Methods of Making
US20100213082 * 4 mars 2010 26 août 2010 Benjamin Feldman Self-Powered Analyte Sensor
US20110060196 * 31 août 2010 10 mars 2011 Abbott Diabetes Care Inc. Flexible Mounting Unit and Cover for a Medical Device
US20140058223 * 19 août 2013 27 févr. 2014 Glumetrics, Inc. Sensor for percutaneous intravascular deployment without an indwelling cannula
WO2006122554A2 16 mai 2006 23 nov. 2006 Radiometer Medical Aps Enzyme sensor with a cover membrane layer covered by a hydrophilic polymer
Classification aux États-Unis 205/778, 204/403.08, 204/403.11, 204/403.09, 435/287.9, 435/817, 435/287.1, 435/4
Classification internationale C12Q1/00, G01N27/327
Classification coopérative Y10S435/817, C12Q1/001, C12Q1/002
Classification européenne C12Q1/00B, C12Q1/00B2
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