Biomedix, Inc.

Other

Ricoh Company, Ltd.

Paul Shieh

Dingli Guo

Shek-Hong Lau

Shu-Hui Chen

Esfir Goldberg

Shaw-Ping Chang

A method of determining the concentration of glycoproteins and glycosylated hemoglobin in whole blood and whole blood components by means of an amperometric biosensor and an amperometric biosensor for this determination are provided. In one embodiment, whole blood is introduced into a version of an amperometric sensor having a component that removes erythrocytes. Redox mediators are used to obtain a current flow based on the oxidation of fructosamine derivatives that can be correlated with the concentration of glycosylated proteins in the fraction of the blood from which erythrocytes have been excluded. To obtain the concentration of glycosylated hemoglobin, whole blood is introduced into a version of the sensor which includes a component that produces lysis of the erythrocytes yielding a current flow proportional to the total quality of glycosylated proteins including glycosylated hemoglobin. The glycosyltaed hemoglobin concentration is obtained by subtracting the glycoprotein concentration in the absence of erythrocytes from the glycoprotein concentration of the lysed whole blood. The sensor generally comprises a sensing electrode having a first redox mediator dispersed in an electrically conductive medium such as an electrically conductive graphite formulation; a reference electrode such as a standard silver-silver chloride electrode; a reagent strip containing a pH buffer and a second redox mediator system in a gel medium; and a whole blood treatment component consisting of either a membrane or other means to filter erythrocytes from whole blood or a means to lyse erythrocytes. In a preferred form, that has high sensitivity, the sensing electrode and the reference electrode may be formed as coatings on separate non-conductive strips such as polyester film with these strips arranged so that they form 'the bread' of a sandwich in which the electrode coatings are face-to-face and the reagent strip and the filtration or lysing component form the 'filling' of the sandwich. The filtration or cell lysing component covers an opening in the reference electrode through which samples are introduced, and is superimposed on the reagent strip.

Determination of glycoprotein and glycosylated hemoglobin in blood

A highly sensitive sensor for the amperometric assay of glucose in aqueous media having a face-to-face sandwich configuration is provided which comprises a sensing electrode strip containing a first redox mediator in an electrically conductive coating and a reference electrode strip in simultaneous contact with a reagent strip containing a second redox mediator which is sandwiched between the active electrode surfaces. An opening is provided in the reference electrode for the introduction of samples. In one embodiment, a whole blood separation membrane is interposed between the reference electrode and the reagent strip to filter red blood cells and other particles from whole blood to enable direct assay of glucose without sample preparation. The sensing electrode comprises a non-conductive support member having an electrically conductive layer containing the first redox mediator. The reference electrode is typically a Ag/AgCl electrode formed by coating an ink containing Ag/AgCl dispersed in a resin on a non-conductive base. The reagent strip is a porous or fibrous carrier, typically a paper, impregnated with a mixture containing the second redox mediator, glucose oxidase, horseradish peroxidase, at least one surfactant and at least one stabilizer comprising an aqueous thickening agent. In one version of the sensor, the sensing electrode comprises a support member of polyester film coated with an electrically conductive graphite composition containing dimethylferrocene as the first redox mediator and the second redox mediator comprises potassium ferrocyanide.

Highly sensitive amperometric bi-mediator-based glucose biosensor

An amperometric glucose biosensor having high sensitivity and accuracy over a wide range of glucose concentrations and a method for the rapid detection of glucose in urine are provided. The biosensor strip comprises an electrically conductive carbon layer, having a first redox mediator, a reagent strip containing an enzyme system for the oxidation of glucose and a second redox mediator, and a silver/silver chloride reference electrode. In a preferred form of the sensor that has high sensitivity, a sensing electrode and a reference electrode are arranged so that the electrically conductive layers of the electrodes are face-to-face and sandwich the reagent strip between them. Screening for glucose is achieved by contacting the sensor with a drop of the patient's urine and comparing the current read-out with a standard calibration curve or by automatically converting the current flow generated by the test sample to units of glucose concentration. The sensor can measure urine glucose concentrations below 3 mg/dl. Measurement of urine glucose concentration with the sensor provides a non-invasive probe of a patient's blood glucose level since a linear relationship exists between blood glucose concentration and urine glucose concentration, approximately in the range between 0 to 400 mg/dl.

Non-invasive glucose biosensor: determination of glucose in urine

A self contained glucose sensor is provided that generally comprises a strip type glucose sensing electrode having an active surface comprising an organic conducting redox salt dispersed in a polymeric membrane, with the membrane coating a conductive strip and a strip type Ag/AgCl reference electrode having its active surface separated from physical contact with the strip type glucose sensor and a carrier strip of water absorbent paper or film containing an enzyme system and an oxidizable dye. The water absorbent carrier strip is in simultaneous contact with both the active surface of the strip type glucose electrode and the active surface of the strip type reference electrode. When an aqueous solution containing glucose is brought in contact with the carrier strip containing the enzyme system an electrical potential, proportional to the concentration of glucose in the solution, is created which can be detected by an electrometer or other suitable device.

Dry chemistry glucose sensor

A sensor for the amperometric assay of cholesterol is provided which comprises a sensing electrode containing a first redox mediator and a reference electrode in simultaneous contact with a reagent strip containing a second redox mediator. The presence of the second redox mediator greatly amplifies the current flow produced by the presence of cholesterol and produces linear correlation of current flow with concentration over an extended range. The sensing electrode comprises a non-conductive support member having an electrically conductive layer containing the first redox mediator. The reference electrode is typically a Ag/AgCl electrode formed by coating an ink containing Ag/AgCl dispersed in a resin on a non-conductive base. The reagent strip is a porous or fibrous carrier, typically a paper, impregnated with a mixture containing the second redox mediator, cholesterol esterase, cholesterol oxidase, horseradish peroxidase, at least one surfactant and at least one stabilizer comprising an aqueous thickening agent. In one version of the sensor, the sensing electrode comprises a support member of polyester film coated with an electrically conductive graphite composition containing dimethylferrocene as the first redox mediator and the second redox mediator comprises 3,3',5,5'-tetramethylbenzidine. The sensor may be constructed in several physical forms. In one form, the sensing and reference electrodes are in the form of strips and the reagent strip is sandwiched between the electrically conductive layers of the electrodes with the reference electrode having a hole, through which the reagent strip is exposed, for the introduction of sample.

Amperometric cholesterol biosensor

A redox electrode for the rapid detection of glucose in aqueous media and a method for its use are provided. The redox electrode comprises an electrically conductive member such as copper, and a redox membrane in direct contact with said electrically conductive member. The redox membrane comprises a polymer matrix such as PVC containing a plasticizer, and a complex of 7,7,8,8-tetracyanoquinodimethane and tetrathiafulvalene with the complex having a burgundy-red coloration and characterized by a broad absorption from about 340 nm to about 550 nm and weaker absorption between about 650 nm to about 800 nm having about six small peaks with an absorption maximum at about 750 nm. Glucose is rapidly assayed by bringing the redox electrode and a reference electrode into simultaneous contact with an aqueous medium containing KCl, phosphate buffer, glucose oxidase, peroxidase, and 3,3',5,5'-tetramethylbenzidine dihydrochloride. The potential of the redox membrane is then monitored until it is stable. A sample containing glucose is added to the aqueous medium, and the change of potential of the redox electrode, which is related to glucose concentration, is then observed. In a variant of this method, the redox electrode is treated with ascorbic acid before a glucose oxidation to magnify the potential difference generated, and after oxidation to rapidly collapse the potential and prepare the electrode for another analysis.

Glucose sensor and assay method

A redox electrode for the rapid detection of glucose in aqueous media and a method for its use are provided. The redox electrode comprises an electrically conductive member such as copper, and a redox membrane in direct contact with said electrically conductive member. The redox membrane comprises a polymer matrix such as PVC containing a plasticizer, and a complex of 7,7,8,8 -tetracyanoquinodimethane and tetrathiafulvalene with the complex having a burgundy-red coloration and characterized by a broad absorption from about 340 nm to about 550 nm and weaker absorption between about 650 nm to about 800 nm having about six small peaks with an absorption maximum at about 750nm. Glucose is rapidly assayed by bringing the redox electrode and a reference electrode into simultaneous contact with an aqueous medium containing KCl, phosphate buffer, glucose oxidase, peroxidase, and 3,3',5,5'-tetramethylbenzidine dihydrochloride. The potential of the redox membrane is then monitored until it is stable. A sample containing glucose is added to the aqueous medium, and the change of potential of the redox electrode, which is related to glucose concentration, is then observed. In a variant of this method, the redox electrode is treated with ascorbic acid before a glucose oxidation to magnify the potential difference generated, and after oxidation to rapidly collapse the potential and prepare the electrode for another analysis.

Glucose sensor

An ion-selective electrode having an ion-selective membrane in direct contact with an electrical conductor is provided in which the membrane coats an uninsulated zone surrounded by insulation on the surface of a conductor which is coated with a layer of electrical insulation. The membrane overlays the insulation surrounding the insulation free zone and comprises a polymer which is generally of sufficiently similar composition to that comprising the electrical insulation layer so that it adheres to the insulation forming a membrane with increased structural strength. Embodiments of the electrode containing phosphatidylcholine in the ion-selective membrane have increased sensitivity.

Ion-selective sensor with polymeric membrane having phospholipid

A novel toner composition with improved thermal and rheological properties, improved surface energy, and better frangibility is provided. The toner comprises a thermoplastic polymeric blend and a coloring agent. The polymeric blend is comprised of propoxylated bisphenol-A fumarate and a polyester resin with a chemically bound halogen. A preferred polyester resin with a chemically bound halogen is tetrabromo-bisphenol fumarate polyester. An improved electrophotographic imaging process using the toner particles of the present invention is also provided.

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Fremont, CA, United States of America

Paul Shieh