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US20080064937A1 - Analyte monitoring system and method - Google Patents

Analyte monitoring system and method Download PDF

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US20080064937A1
US20080064937A1 US11759923 US75992307A US2008064937A1 US 20080064937 A1 US20080064937 A1 US 20080064937A1 US 11759923 US11759923 US 11759923 US 75992307 A US75992307 A US 75992307A US 2008064937 A1 US2008064937 A1 US 2008064937A1
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glucose
sensor
analyte
error
data
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Abandoned
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US11759923
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Geoffrey McGarraugh
Benjamin Feldman
Thomas Peyser
John Mazza
Timothy Goodnow
Kerstin Rebrin
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Abbott Diabetes Care Inc
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Abbott Diabetes Care Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/07Endoradiosondes
    • A61B5/076Permanent implantations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1495Calibrating or testing of in-vivo probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271Specific aspects of physiological measurement analysis
    • A61B5/7282Event detection, e.g. detecting unique waveforms indicative of a medical condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient ; user input means
    • A61B5/746Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/005Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006Enzyme electrodes involving specific analytes or enzymes for glucose
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/48785Electrical and electronic details of measuring devices for physical analysis of liquid biological material not specific to a particular test method, e.g. user interface or power supply
    • G01N33/48792Data management, e.g. communication with processing unit
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
    • A61M2005/1726Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure the body parameters being measured at, or proximate to, the infusion site

Abstract

Devices and methods for monitoring an analyte are provided. Embodiments include continuous analyte sensors having a high degree of accuracy.

Description

    RELATED APPLICATIONS
  • [0001]
    This application claims priority under 35 USC § 119 to Provisional Application No. 60/804,170 filed Jun. 7, 2006 entitled “Analyte Monitoring”, and to Provisional Application No. 60/804,169 filed Jun. 7, 2006 entitled “Analyte Monitoring System” the disclosure of each of which are incorporated in their entirety by reference for all purposes
  • BACKGROUND OF THE INVENTION
  • [0002]
    The association of chronic hyperglycemia and the devastating long-term complications of diabetes was clearly established by the Diabetes Control and Complication Trial (DCCT) (The Diabetes Control and Complications Trial Research Group. “The effect of intensive treatment of diabetes on the development and progression of long-term complications of insulin-dependent diabetes mellitus” N Engl J Med 329: 978-986, 1993; Santiago J V “Lessons from the Diabetes Control and Complications Trial” Diabetes 1993, 42: 1549-1554).
  • [0003]
    The DCCT found that in patients receiving intensive insulin therapy, there was a reduced risk of 76% for diabetic retinopathy, 50% for diabetic nephropathy and 60% for diabetic neuropathy. The long-term benefits of tight glycemic control have been further substantiated by the Epidemiology of Diabetes Interventions and Complications study which found over a 50% reduced risk of macrovascular disease as a result of intensive insulin therapy (The Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complication (DCCT/EDIC) Study Group, “Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes”, 353, 2643-2653, 2005).
  • [0004]
    However, the DCCT found that patients receiving intensive insulin therapy were at a threefold increased risk of severe hypoglycemia. Patients adhering to intensive insulin therapy regimens were found to have lowered thresholds for activation of neurogenic warning systems and consequently were at increased risk for more severe hypoglycemic events. (Amiel S A, Tamborlane W V, Simonson D C, Sherwin R S., “Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus.” N Engl J. Med. 1987 28; 316(22):1376-83).
  • [0005]
    The increased risk of hypoglycemia and the fear associated with patients' perception of that risk has been cited as the leading obstacle for patients to achieve the targeted glycemic levels (Cryer P E. “Hypoglycaemia: The limiting factor in the glycemic management of type I and type II diabetes” Diabetologia, 2002, 45: 937-948). In addition to the problem of chronic hyperglycemia contributing to long-term complications and the problem of acute iatrogenic hypoglycemia contributing to short-term complications, recent research suggests that transient episodes of hyperglycemia can lead to a wide range of serious medical problems besides previously identified microvascular complications as well as macrovascular complications such as increased risk for heart disease. (Haffner S “The importance of postprandial hyperglycemia in development of cardiovascular disease in people with diabetes” International Journal of Clinical Practice, 2001, Supplement 123: 24-26; Hanefeld M: “Postprandial hyperglycemia: noxious effects on the vessel wall” International Journal of Clinical Practice, 2002, Supplement 129: 45-50).
  • [0006]
    Additional research has found that glycemic variation and the associated oxidative stress may be implicated in the pathogenesis of diabetic complications (Hirsh I B, Brownlee M “Should minimal blood glucose variability become the gold standard of glycemic control?” J of Diabetes and Its Complications, 2005, 19: 178-181; Monnier, L., Mas, E., Ginet, C., Michel, F., Villon L, Cristol J-P, and Collette C, “Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes”. JAMA 2006, 295, 1681-1687). Glycemic variation has also been identified as a possible explanation for the increased prevalence of depression in both type 1 and type 2 diabetes (Van der Does F E. De Neeling J N, Snoek F J, Kostense P J, Grootenhuis P A, Bouter L M, and R J Heine: Symptoms and well-being in relation to glycemic control in type II diabetes Diabetes Care, 1996, 19: 204-210; De Sonnaville J J. Snoek F J. Colly L P. Deville W. Wijkel D. Heine R J: “Well-being and symptoms in relation to insulin therapy in type 2 diabetes” Diabetes Care, 1998, 21: 919-24; Cox D J, Gonder-Frederick L A, McCall A, et al. “The effects of glucose fluctuation on cognitive function and QOL: the functional costs of hypoglycaemia and hyperglycaemia among adults with type 1 or type 2 diabetes” International Journal of Clinical Practice, 2002, Supplement 129: 20-26).
  • [0007]
    The potential benefits of continuous glucose monitoring have been recognized by numerous researchers in the field (Skyler J S “The economic burden of diabetes and the benefits of improved glycemic control: the potential role of a continuous glucose monitoring system” Diabetes Technol Ther 2 (Suppl 1): S7-S12, 2000; Tansey M J, Beck R W, Buckingham B A, Mauras N, Fiallo-Scharer R, Xing D, Kollman C, Tamborlane W V, Ruedy K J, “Accuracy of the modified Continuous Glucose Monitoring System (CGMS) sensor in an outpatient setting: results from a diabetes research in children network (DirecNet) study.” Diab. Tech. Ther. 7(1):109-14, 2005; Klonoff, D C: “Continuous glucose monitoring: Roadmap for 21st century diabetes therapy” Diabetes Care, 2005, 28: 1231:1239). Accurate and reliable real-time continuous glucose monitoring devices have the ability to alert patients of high or low blood sugars that might otherwise be undetected by episodic capillary blood glucose measurements.
  • [0008]
    Continuous glucose monitors have the potential to permit more successful adherence to intensive insulin therapy regimens and also to enable patients to reduce the frequency and extent of glycemic fluctuations. However, the development of this technology has proceeded more slowly than anticipated. For example, two recent comprehensive reviews of decades of research in the field cited the lack of accuracy and reliability as the major factor limiting the acceptance of this new technology as well as the development of an artificial pancreas (Chia, C. W. and Saudek, C. D., “Glucose sensors: toward closed loop insulin delivery” Endocrinol. Metab. Clin. N. Am., 33, 174-195, 2004; Hovorka, R. “Continuous glucose monitoring and closed-loop systems” Diabet. Med. 23, 1-12, 2006).
  • [0009]
    As continuous analyte monitoring becomes more prevalent, of use are continuous analyte sensors and systems that are accurate to such a high degree that confirmatory analyte measurement are not needed to verify the continuous sensing measurements, e.g., prior to a user relying on the continuous measurements. Also of interest are such sensors that work in concert with a drug delivery device.
  • SUMMARY OF THE INVENTION
  • [0010]
    Generally, the present disclosure relates to methods and devices for monitoring of the level of an analyte using a continuous and/or automatic in vivo monitoring analyte sensor. Embodiments include sensors in which at least a portion of the sensor is adapted to be positioned beneath the skin of a user and which are adapted for providing clinically accurate analyte data, i.e., data with accuracy sufficient so that a user may confidently rely on the sensor results, e.g., to manage a disease condition and/or make a healthcare decision based thereon. Accordingly, sensors capable of providing clinically accurate (i.e., clinically relevant) analyte information to a user are provided.
  • [0011]
    Embodiments include continuous analyte monitoring systems that do not require additional analyte information obtained by a second system and/or sensor to confirm the results reported by the continuous sensing system.
  • [0012]
    Embodiments also include high accuracy continuous analyte sensors and systems with drug delivery systems e.g., insulin pumps, or the like. A communication link (e.g., by cable or wirelessly such as by infrared (IR) or RF link or the like) may be provided for transfer of data from the sensor to the drug delivery device. The drug delivery device may include a processor to determine the amount of drug to be delivered using sensor data, and may deliver such drug automatically or after user direction to do so.
  • [0013]
    Also provided are methods of analyte monitoring using highly accurate continuous analyte sensors.
  • [0014]
    These and other objects, features and advantages of the present disclosure will become more fully apparent from the following detailed description of the embodiments, the appended claims and the accompanying drawings.
  • BRIEF DESCRIPTIONS OF THE DRAWINGS
  • [0015]
    The figures shown herein are not necessarily drawn to scale, with some components and features being exaggerated for clarity. Each of the figures diagrammatically illustrates aspects of the present disclosure. Of these:
  • [0016]
    FIG. 1 is a block diagram of one embodiment of a highly accurate continuous glucose monitoring system such as Freestyle Navigator® system using a subcutaneously implantable analyte sensor, according to one embodiment of the present disclosure;
  • [0017]
    FIG. 2 shows five day accuracy data for the monitoring system of FIG. 1 (arm and abdomen) and 50 hours of YSI venous sampling in one embodiment;
  • [0018]
    FIG. 3 shows a Clarke error grid for the continuous monitoring system of FIG. 1 in one embodiment;
  • [0019]
    FIG. 4A shows a view (four hour duration) of profile plot centered glucose challenge, and FIG. 4B shows a view (four hour duration) of profile plot centered insulin challenge;
  • [0020]
    FIG. 5 shows rate of change histogram showing underlying rate of change at high resolution (in units of 0.25 mg/dL/min) and in units of the continuous monitoring system of FIG. 1 receiver trend arrows (1.0 mg/dL/min);
  • [0021]
    FIG. 6 shows a Clarke error grid for YSI rates of change between −1 to 1 mg/dL/min;
  • [0022]
    FIG. 7 shows the Clarke error grid from a high accurate continuous glucose monitoring system user study; and
  • [0023]
    FIG. 8 illustrates the time spent in hypoglycemic, euglycemic, and hyperglycemic ranges for type 1 and 2 subjects in the blinded and unblinded phases of the study described in conjunction with FIG. 7.
  • DETAILED DESCRIPTION
  • [0024]
    Before the various embodiments of the present disclosure is described, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.
  • [0025]
    Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the present disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the present disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the present disclosure.
  • [0026]
    Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this present disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of various embodiments of the present disclosure, exemplary methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
  • [0027]
    It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise.
  • [0028]
    The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
  • [0029]
    As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure.
  • [0030]
    The present disclosure is applicable to analyte monitoring systems using a sensor—at least a portion of which is positioned beneath the skin of the user, for the in vivo determination of a concentration of an analyte, such as glucose, lactate, and the like, in a body fluid. The sensor may be, for example, subcutaneously positioned in a patient for the continuous or periodic monitoring an analyte in a patient's interstitial fluid. This may be used to infer the glucose level in the patient's bloodstream. The sensors of the subject disclosure also include in vivo analyte sensors for insertion into a vein, artery, or other portion of the body containing fluid. A sensor of the subject disclosure may be configured for monitoring the level of the analyte over a time period which may range from hours, days, weeks, or longer, as described in greater detail below.
  • [0031]
    More specifically, FIG. 1 illustrates a data monitoring and management system such as, for example, analyte (e.g., glucose) monitoring system 100, in accordance with one embodiment of the present disclosure. The subject disclosure is further described primarily with respect to a glucose monitoring system for convenience and such description is in no way intended to limit the scope of the present disclosure. It is to be understood that the analyte monitoring system may be configured to monitor a variety of analytes. Analytes that may be monitored include, for example, acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growth hormones, hormones, ketones, lactate, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid stimulating hormone, and troponin, and the like. The concentration of drugs, such as, for example, antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs of abuse, theophylline, and warfarin, and the like, may also be monitored.
  • [0032]
    The analyte monitoring system 100 includes a highly accurate sensor 101, a transmitter unit 102 coupled to the sensor 101, and a receiver unit 104 which is configured to communicate with the transmitter unit 102 via a communication link 103. The receiver unit 104 may be further configured to transmit data to a data processing terminal 105 for evaluating the data received by the receiver unit 104. Moreover, the data processing terminal in one embodiment may be configured to receive data directly from the transmitter unit 102 via a communication link 106 which may optionally be configured for bi-directional communication. Some or all of the various components may be separate components, or some or all may be integrated into a single unit.
  • [0033]
    Only one sensor 101, transmitter unit 102, receiver unit 104, communication link 103, and data processing terminal 105 are shown in the embodiment of the analyte monitoring system 100 illustrated in FIG. 1. However, it will be appreciated by one of ordinary skill in the art that the analyte monitoring system 100 may include one or more sensor 101, transmitter unit 102, receiver unit 104, communication link 103, and data processing terminal 105. Moreover, within the scope of the present disclosure, the analyte monitoring system 100 may be a continuous monitoring system, or semi-continuous, or a discrete monitoring system. In a multi-component environment, each device is configured to be uniquely identified by each of the other devices in the system so that communication conflict is readily resolved between the various components within the analyte monitoring system 100.
  • [0034]
    In one embodiment of the present disclosure, the sensor 101 is physically positioned in or on the body of a user whose analyte level is being monitored. The sensor 101 may be configured to continuously sample the analyte level of the user and convert the sampled analyte level into a corresponding data signal for transmission by the transmitter unit 102. In one embodiment, the transmitter unit 102 is coupled to, e.g., mounted on, the sensor 101 so that both devices are positioned on the user's body. The transmitter unit 102 performs data processing such as filtering and encoding on data signals, each of which corresponds to a sampled analyte level of the user, for transmission to the receiver unit 104 via the communication link 103.
  • [0035]
    In one embodiment, the analyte monitoring system 100 is configured as a one-way RF communication path from the transmitter unit 102 to the receiver unit 104. In such embodiment, the transmitter unit 102 transmits the sampled data signals received from the sensor 101 without acknowledgement from the receiver unit 104 that the transmitted sampled data signals have been received. For example, the transmitter unit 102 may be configured to transmit the encoded sampled data signals at a fixed rate (e.g., at one minute intervals) after the completion of the initial power on procedure. Likewise, the receiver unit 104 may be configured to detect such transmitted encoded sampled data signals at predetermined time intervals. Alternatively, the analyte monitoring system 100 may be configured with a bi-directional RF (or otherwise) communication between the transmitter unit 102 and the receiver unit 104.
  • [0036]
    Additionally, in one aspect, the receiver unit 104 may include two sections. The first section is an analog interface section that is configured to communicate with the transmitter unit 102 via the communication link 103. In one embodiment, the analog interface section may include an RF receiver and an antenna for receiving and amplifying the data signals from the transmitter unit 102, which are thereafter, demodulated with a local oscillator and filtered through a band-pass filter. The second section of the receiver unit 104 is a data processing section which is configured to process the data signals received from the transmitter unit 102 such as by performing data decoding, error detection and correction, data clock generation, and data bit recovery.
  • [0037]
    In certain embodiments, in operation, the receiver unit 104 is configured to detect the presence of the transmitter unit 102 within its range based on, for example, the strength of the detected data signals received from the transmitter unit 102 or a predetermined transmitter identification information. Upon successful synchronization with the corresponding transmitter unit 102, the receiver unit 104 is configured to begin receiving from the transmitter unit 102 data signals corresponding to the user's detected analyte level. More specifically, the receiver unit 104 in one embodiment is configured to perform synchronized time hopping with the corresponding synchronized transmitter unit 102 via the communication link 103 to obtain the user's detected analyte level.
  • [0038]
    Referring again to FIG. 1, the data processing terminal 105 may include a personal computer, a portable computer such as a laptop or a handheld device (e.g., personal digital assistants (PDAs)), and the like, each of which may be configured for data communication with the receiver via a wired or a wireless connection. Additionally, the data processing terminal 105 may further be connected to a data network (not shown) for storing, retrieving and updating data corresponding to the detected analyte level of the user.
  • [0039]
    Within the scope of the present disclosure, the data processing terminal 105 may include an infusion device such as an insulin infusion pump or the like, which may be configured to administer insulin to patients, and which may be configured to communicate with the receiver unit 104 for receiving, among others, the measured analyte level. Alternatively, the receiver unit 104 may be configured to integrate an infusion device therein so that the receiver unit 104 is configured to administer insulin therapy to patients, for example, for administering and modifying basal profiles, as well as for determining appropriate boluses for administration based on, among others, the detected analyte levels received from the transmitter unit 102.
  • [0040]
    Additionally, the transmitter unit 102, the receiver unit 104 and the data processing terminal 105 may each be configured for bi-directional wireless communication such that each of the transmitter unit 102, the receiver unit 104 and the data processing terminal 105 may be configured to communicate (that is, transmit data to and receive data from) with each other via the wireless communication link 103. More specifically, the data processing terminal 105 may in one embodiment be configured to receive data directly from the transmitter unit 102 via the communication link 106, where the communication link 106, as described above, may be configured for bi-directional communication.
  • [0041]
    In this embodiment, the data processing terminal 105 which may include an insulin pump, may be configured to receive the analyte signals from the transmitter unit 102, and thus, incorporate the functions of the receiver 103 including data processing for managing the patient's insulin therapy and analyte monitoring. In one embodiment, the communication link 103 may include one or more of an RF communication protocol, an infrared communication protocol, a Bluetooth enabled communication protocol, an 802.11x wireless communication protocol, or an equivalent wireless communication protocol which would allow secure, wireless communication of several units (for example, per HIPPA requirements) while avoiding potential data collision and interference.
  • [0042]
    Continuous Glucose Monitoring Sensors and Systems
  • [0043]
    As described above, the various embodiments of the present disclosure relate to continuous analyte sensors and systems having a high degree of accuracy, e.g., as demonstrated by a Clark Error Grid, Parks Error Grid, Continuous Glucose Error Grid, MARD analysis, and the like. The high degree of accuracy permits a user to rely on the results of the sensor without the need to confirm sensor results. In certain embodiments, the sensors have at least about 80% of its paired data points within zone A of one or more of the Clark Error Grid, the Consensus Error Grid, or the Continuous Glucose Error Grid Analysis, e.g., at least about 85% of its paired data points within zone A of one or more of the Clark Error Grid, the Consensus Error Grid, or the Continuous Glucose Error Grid Analysis, e.g., at least about 90% of its paired data points within zone A of one or more of the Clark Error Grid, the Consensus Error Grid, or the Continuous Glucose Error Grid Analysis, e.g., at least about 95% of its paired data points within zone A of one or more of the Clark Error Grid, the Consensus Error Grid, or the Continuous Glucose Error Grid Analysis.
  • [0044]
    In certain embodiments, a sensor may have about 80% or greater, e.g., 85% or greater, e.g., 90% or greater of its paired data points within zone A of the Clark Error Grid, and 80% or greater, e.g., 85% or greater, e.g., 90% or greater, of its paired data points within zone A of the Consensus Error Grid.
  • [0045]
    The sensors are continuous analyte monitoring sensors. The sensors are adapted to continuously or periodically monitor analyte levels for a period of time, e.g., usually at least about 24 hours, e.g., about 1 day to about 30 days, e.g., about 3 days to about 7 days, e.g., a 5 day sensor or 7 day sensor.
  • [0046]
    Embodiments of the clinically accurate continuous glucose monitoring systems of the present disclosure include four components: a small, miniaturized analyte sensor element (which may be an electrochemical or optical sensor) for placement in the subcutaneous adipose tissue in the arm or abdomen (or elsewhere); a disposable sensor delivery unit containing a spring-loaded sharp for mechanical insertion of the sensor into the tissue and a sensor support mount; a transmitter (e.g., wireless transmitter) which connects to the sensor support mount on the skin surface and to the inserted electrochemical sensor; and a hand-held receiver device for communication (e.g., wireless) with the transmitter and for the communication (e.g., audio and/or visual display) of the continuous glucose values to the user. The system may also include a data management system in which information from the receiver (and/or transmitter) is forwarded (e.g., wirelessly or otherwise) to a data management system such as a personal computer (“PC”), personal digital assistant (“PDA”), telephone, facsimile machine, drug delivery device (e.g., internal or external insulin pump) or the like.
  • [0047]
    Embodiments of the sensors of the present disclosure vary, but in all embodiments have a high degree of accuracy. In other words, the sensors' accuracy enables a user of the system to solely and confidently rely on the sensors' results that are reportable to the user, e.g., to manage a disease state such as diabetes or the like, make healthcare decisions (e.g., insulin delivery, meals, exercise, etc.). In this manner, adjunctive measurements are not required to confirm the readings of the highly accurate sensors of the present disclosure, thereby eliminating burdensome and painful fingersticks required for testing analyte using conventional blood analyte monitoring systems such as blood glucose test strips and the like, used for such confirmations.
  • [0048]
    In certain embodiments a sensor is adapted to be wholly or partially positioned beneath the skin surface of a user. A sensor may be a transcutaneous sensor in which a portion of the sensor is configured to be positioned beneath a skin surface and portion is configured to be positioned above the skin surface. In many embodiments at least a portion of the sensor is configured to be inserted into the subcutaneous adipose tissue. Sensors may vary in size, where in certain embodiments a sensor may be about 5.5 mm long, about 600 microns wide and about 250 microns thick. Sensors having different lengths and/or widths and/or thicknesses are also encompassed by the present disclosure. The sensors are configured to accurately measure an analyte, e.g., glucose concentration in the interstitial fluid, which has correlates with blood glucose. The sensor is typically provided to a user as a sterile, single-use disposable element.
  • [0049]
    The sensors may be configured to continuously monitor analyte levels of a user for a period of time. In certain embodiments, the period of time ranges from about 1 day to about 30 days, e.g., from about 3 days to about 7 days, where in certain embodiments a sensor may configured for up to about five days of continuous use. A system may include two or more sensors, which may be temporally overlapped for a certain period of usage time, thereby extending the amount of time of continuous sensing and/or doing away with any time gaps that may result from removing a first sensor and inserting a second. Furthermore, a sensor may be calibrated from a previous sensor in certain embodiments.
  • [0050]
    The glucose measurement is made using sensing chemistry. Sensing chemistry may include an enzyme and may include a mediator. In certain embodiments, the sensing chemistry is a modified glucose oxidase polymeric matrix with an osmium dopant in the supporting polymer matrix. The sensing chemistry (also referred to as the “transduction chemistry”) used in the sensors of the present disclosure permits detection of signal, e.g., a nanoampere electrical current from the reaction with an applied potential, such as of only about 40 mV.
  • [0051]
    More specifically, in one embodiment, the sensor includes at least one working electrode formed on a substrate. The sensor may also include at least one counter electrode (or counter/reference electrode) and/or at least one reference electrode. The counter electrode and/or reference electrode may be formed on the substrate or may be separate units. For example, the counter electrode and/or reference electrode may be formed on a second substrate which is also implanted in the patient or, for some embodiments of the implantable sensors, the counter electrode and/or reference electrode may be placed on the skin of the patient with the working electrode or electrodes being implanted into the patient.
  • [0052]
    The working electrode or electrodes are formed using conductive traces disposed on the substrate. The counter electrode and/or reference electrode, as well as other optional portions of the sensor, such as a temperature probe, may also be formed using conductive traces disposed on the substrate. These conductive traces may be formed over a smooth surface of the substrate or within channels formed by, for example, embossing, indenting or otherwise creating a depression in the substrate.
  • [0053]
    A sensing layer is often formed proximate to or on at least one of the working electrodes to facilitate the electrochemical detection of the analyte and the determination of its level in the sample fluid, particularly if the analyte can not be electrolyzed at a desired rate and/or with a desired specificity on a bare electrode. The sensing layer may include an electron transfer agent to transfer electrons directly or indirectly between the analyte and the working electrode. The sensing layer may also contain a catalyst to catalyze a reaction of the analyte. The components of the sensing layer may be in a fluid or gel that is proximate to or in contact with the working electrode. Alternatively, the components of the sensing layer may be disposed in a polymeric or sol-gel matrix that is proximate to or on the working electrode. In one aspect, the components of the sensing layer are non-leachably disposed within the sensor. Further, the components of the sensor are immobilized within the sensor.
  • [0054]
    In addition to the electrodes and the sensing layer, the sensor may also include a temperature probe, a mass transport limiting layer, a biocompatible layer, and/or other optional components, as described below. Each of these items enhances the functioning of and/or results from the sensor, as discussed below.
  • [0000]
    The Substrate
  • [0055]
    The substrate may be formed using a variety of non-conducting materials, including, for example, polymeric or plastic materials and ceramic materials. Suitable materials for a particular sensor may be determined, at least in part, based on the desired use of the sensor and properties of the materials.
  • [0056]
    In some embodiments, the substrate is flexible. In other embodiments, the sensors are made using a relatively rigid substrate to, for example, provide structural support against bending or breaking.
  • [0000]
    Conductive Traces
  • [0057]
    At least one conductive trace is formed on the substrate for use in constructing a working electrode. In addition, other conductive traces may be formed on the substrate for use as electrodes (e.g., additional working electrodes, as well as counter, counter/reference, and/or reference electrodes) and other components, such as a temperature probe. The conductive traces may be formed on the substrate by a variety of techniques, including, for example, photolithography, screen printing, or other impact or non-impact printing techniques. The conductive traces may also be formed by carbonizing conductive traces in an organic (e.g., polymeric or plastic) substrate using a laser.
  • [0058]
    The conductive traces are typically formed using a conductive material 56 such as carbon (e.g., graphite), a conductive polymer, a metal or alloy (e.g., gold or gold alloy), or a metallic compound (e.g., ruthenium dioxide or titanium dioxide). The formation of films of carbon, conductive polymer, metal, alloy, or metallic compound are well-known and include, for example, chemical vapor deposition (CVD), physical vapor deposition, sputtering, reactive sputtering, printing, coating, and painting.
  • [0059]
    In addition to the particles of carbon, metal, alloy, or metallic compound, the conductive ink may also contain a binder. The binder may optionally be cured to further bind the conductive material within the channel and/or on the substrate.
  • [0060]
    Suitable redox couples for binding to the conductive material of the reference electrode include, for example, redox polymers (e.g., polymers having multiple redox centers.). In one aspect, the reference electrode surface may be non-corroding so that an erroneous potential is not measured. Examples of conductive materials include less corrosive metals, such as gold and palladium, and may include non-corrosive materials including non-metallic conductors, such as carbon and conducting polymers. A redox polymer can be adsorbed on or covalently bound to the conductive material of the reference electrode, such as a carbon surface of a conductive trace. Non-polymeric redox couples can be similarly bound to carbon or gold surfaces.
  • [0061]
    A variety of methods may be used to immobilize a redox polymer on an electrode surface. One method is adsorptive immobilization. This method is particularly useful for redox polymers with relatively high molecular weights. The molecular weight of a polymer may be increased, for example, by cross-linking.
  • [0062]
    Another method for immobilizing the redox polymer includes the functionalization of the electrode surface and then the chemical bonding, often covalently, of the redox polymer to the functional groups on the electrode surface.
  • [0000]
    Sensing Layer
  • [0063]
    Some analytes, such as oxygen, can be directly electrooxidized or electroreduced on the working electrode. Other analytes, such as glucose and lactate, require the presence of at least one electron transfer agent and/or at least one catalyst to facilitate the electrooxidation or electroreduction of the analyte. Catalysts may also be used for those analyte, such as oxygen, that can be directly electrooxidized or electroreduced on the working electrode. For these analytes, each working electrode has a sensing layer formed proximate to or on a working surface of the working electrode. Typically, the sensing layer is formed near or on only a small portion of the working electrode, often near a tip of the sensor. This limits the amount of material needed to form the sensor and places the sensing layer 64 in the best position for contact with the analyte-containing fluid (e.g., a body fluid, sample fluid, or carrier fluid).
  • [0000]
    Electron Transfer Agent
  • [0064]
    In many embodiments, the sensing layer contains one or more electron transfer agents in contact with the conductive material of the working electrode. In some embodiments of the present disclosure, there is little or no leaching of the electron transfer agent away from the working electrode during the period in which the sensor is implanted in the patient. A diffusing or leachable (i.e., releasable) electron transfer agent often diffuses into the analyte-containing fluid, thereby reducing the effectiveness of the electrode by reducing the sensitivity of the sensor over time.
  • [0065]
    In some embodiments of the present disclosure, to prevent leaching, the electron transfer agents are bound or otherwise immobilized on the working electrode or between or within one or more membranes or films disposed over the working electrode. The electron transfer agent may be immobilized on the working electrode using, for example, a polymeric or sol-gel immobilization technique. Alternatively, the electron transfer agent may be chemically (e.g., ionically, covalently, or coordinatively) bound to the working electrode, either directly or indirectly through another molecule, such as a polymer, that is in turn bound to the working electrode.
  • [0066]
    In general, electron transfer agents may be electroreducible and electrooxidizable ions or molecules having redox potentials that are a few hundred millivolts above or below the redox potential of the standard calomel electrode (SCE). Further, the electron transfer agents are not more reducing than about −150 mV and not more oxidizing than about +400 mV versus SCE.
  • [0000]
    Catalyst
  • [0067]
    The sensing layer may also include a catalyst which is capable of catalyzing a reaction of the analyte. The catalyst may also, in some embodiments, act as an electron transfer agent. One example of a suitable catalyst is an enzyme which catalyzes a reaction of the analyte. In one aspect, the catalyst is non-leachably disposed on the sensor, whether the catalyst is part of a solid sensing layer in the sensor or solvated in a fluid within the sensing layer. In a further aspect, the catalyst is immobilized within the sensor (e.g., on the electrode and/or within or between a membrane or film) to prevent unwanted leaching of the catalyst away from the working electrode and into the patient. This may be accomplished, for example, by attaching the catalyst to a polymer, cross linking the catalyst with another electron transfer agent (which can be polymeric), and/or providing one or more barrier membranes or films with pore sizes smaller than the catalyst.
  • [0000]
    Biocompatible Layer
  • [0068]
    An optional film layer is formed over at least that portion of the sensor which is subcutaneously inserted into the patient. This optional film layer may serve one or more functions. The film layer prevents the penetration of large biomolecules into the electrodes. This is accomplished by using a film layer having a pore size that is smaller than the biomolecules that are to be excluded. Such biomolecules may foul the electrodes and/or the sensing layer thereby reducing the effectiveness of the sensor and altering the expected signal amplitude for a given analyte concentration. The fouling of the working electrodes may also decrease the effective life of the sensor. The biocompatible layer may also prevent protein adhesion to the sensor, formation of blood clots, and other undesirable interactions between the sensor and body.
  • [0000]
    Interferent-Eliminating Layer
  • [0069]
    An interferent-eliminating layer may be included in the sensor. The interferent-eliminating layer may be incorporated in the biocompatible layer or in the mass transport limiting layer (described below) or may be a separate layer. Interferents are molecules or other species that are electroreduced or electrooxidized at the electrode, either directly or via an electron transfer agent, to produce a false signal. In one embodiment, a film or membrane prevents the penetration of one or more interferents into the region around the working electrodes. In one aspect, this type of interferent-eliminating layer is much less permeable to one or more of the interferents than to the analyte.
  • [0000]
    Mass Transport Limiting Layer
  • [0070]
    A mass transport limiting layer may be included with the sensor to act as a diffusion-limiting barrier to reduce the rate of mass transport of the analyte, for example, glucose or lactate, into the region around the working electrodes. By limiting the diffusion of the analyte, the steady state concentration of the analyte in the proximity of the working electrode (which is proportional to the concentration of the analyte in the body or sample fluid) can be reduced. This extends the upper range of analyte concentrations that can still be accurately measured and may also expand the range in which the current increases approximately linearly with the level of the analyte. Particularly useful materials for the film layer are membranes that do not swell in the analyte-containing fluid that the sensor tests.
  • [0071]
    Suitable membranes include 3 to 20,000 nm diameter pores. Membranes having 5 to 500 nm diameter pores with well-defined, uniform pore sizes and high aspect ratios may be used. In one embodiment, the aspect ratio of the pores may be two or greater, or in one aspect five or greater.
  • [0072]
    Embodiments of the system include a receiver that includes both the signal processing algorithms and the user interface system for operation of the system and display of the results—although one or both may be incorporated wholly or partially into the transmitter of the system. In operation, the glucose display on the main screen of the receiver is updated during a predetermined time period, e.g., about once a minute or the like, and gives the instantaneous continuous glucose value. Also provided may be the direction and/or rate of change averaged over a predetermined period of time, e.g., the preceding fifteen minutes, or the like. The direction may be communicated using any suitable audio and/or visual indicator(s). For example, direction may be displayed with trend arrows that give quantitative ranges of the rate of change in units of about 1 mg/dL/min from about −2 mg/dL/min to about +2 mg/dL/min. The receiver may also include threshold and/or projected warnings—audible and/or visual warnings. These may be settable at the factory and/or by the user to different glucose levels to provide warnings of actual and impending hypo- or hyperglycemia. Other warnings may also be included, e.g., battery level, and the like. Time-to-calibrate indicators may also be included.
  • [0073]
    The system may also include a blood glucose (“BG”) meter for use with glucose test strips which may be used for calibration of the continuous glucose sensor, but as noted above, is not needed to confirm the continuous sensor results. The BG meter may be a separate, though connectable component, or may be integrated into the receiver as a single unitary device. For example, the receiver may include a test strip port and a processor to process a reading from the test strip. The built-in blood glucose meter eliminates the possibility of transcription errors during sensor calibration and also provides the user with a backup glucose meter system.
  • [0074]
    The continuous glucose systems of the present disclosure may be calibrated according to a predetermined calibration schedule. In certain embodiments, this schedule may be limited to factory-only calibration. However in certain embodiments, the calibration schedule may include calibrations by the user. For example, over the period of use of the system, it may be calibrated from about 0 to about 10 times, e.g., from about 1 to about 5 times, e.g., about 4 times. An exemplary calibration schedule may include calibration 4 times over a 5 day period, e.g., at 10, 12, 24 and 72 hours after sensor insertion. In certain embodiments, the system may be configured for single point calibration, e.g., as described in U.S. Pat. No. 6,121,009 and elsewhere. In other embodiments, exemplary calibration schedule may include calibration 1-2 times over a 5-7 day period. The system may be configured to accept calibration values that fall within a certain range or are at least meet a threshold value. For example, calibration values may be accepted for blood glucose input between about 60 and about 300 mg/dL and when the absolute rate of change of glucose is estimated to be less than about 2 mg/dL/min. These constraints on the acceptance of calibration input values are designed to limit the potential adverse effects of the intrinsic physiological lag between interstitial fluid glucose and blood glucose.
  • [0075]
    In the embodiments in which at least one calibration by the user is required, the system may be configured so that it does not display (i.e., does not report to the user) real-time glucose values from the continuous monitor until the first calibration, e.g., at about ten hours after sensor insertion in certain instances. This delay after insertion is designed so that the initial system calibration is performed after the sensor has reached a stable equilibrium with the surrounding tissue.
  • [0076]
    Moreover, in one embodiment, the use of fingerstick calibration in response to the Freestyle Navigator® system hypoglycemic alarm may increase the overall system accuracy.
  • [0077]
    An exemplary, analyte sensor and sensing system having the high accuracy described herein is the Freestyle Navigator® continuous glucose monitoring system from Abbott Diabetes Care, Inc., of Alameda, Calif.
  • [0078]
    Kits
  • [0079]
    Finally, kits are also provided. Embodiments of the subject kits may include one or more highly accurate sensors as described herein. Embodiments may also include a sensor insertion device and/or transmitter and/or receiver. Embodiments may also include a drug delivery device such as an insulin pump.
  • [0080]
    In certain embodiments, a kit may include a blood glucose meter to be used with the continuous sensing system, e.g., for calibration. The meter may be a separate component from continuous sensing components (in which case a communication link for transferring data from the meter to the sensing system (such as to the receiver) may be included) or may be integrated therein, e.g., the receiver may include a blood glucose meter.
  • [0081]
    The subject kits may also include written instructions for using a sensor. The instructions may be printed on a substrate, such as paper or plastic, etc. As such, the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or sub-packaging) etc. In other embodiments, the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g., CD-ROM, diskette, etc. In yet other embodiments, the actual instructions are not present in the kit, but means for obtaining the instructions from a remote source, e.g. via the Internet, are provided. An example of this embodiment is a kit that includes a web address where the instructions can be viewed and/or from which the instructions can be downloaded. As with the instructions, this means for obtaining the instructions is recorded on a suitable substrate.
  • [0082]
    In many embodiments of the subject kits, the components of the kit are packaged in a kit containment element to make a single, easily handled unit, where the kit containment element, e.g., box or analogous structure, may or may not be an airtight container, e.g., to further preserve the one or more sensors and additional reagents (e.g., control solutions), if present, until use.
  • EXPERIMENTAL
  • [0083]
    The accuracy of a highly accurate continuous monitoring system such as the Freestyle Navigator® continuous glucose monitoring system measuring glucose in the interstitial fluid is studied, in comparison with a laboratory reference method over five days of sensor wear.
  • [0000]
    Study Design and Methods
  • [0084]
    Fifty-eight subjects with Type 1 diabetes ranging in age from 18-64 were enrolled in a multi-center, prospective, single-arm study. Each subject wore two sensors simultaneously—one on the arm and the other on the abdomen. All the FreeStyle Navigator® devices were calibrated with separate capillary fingerstick measurements at 10, 12, 24 and 72 hours after sensor insertion. Data from the continuous glucose monitor was collected at one-minute intervals for the entire study. Measurements from the FreeStyle Navigator® system were compared with reference venous sample measurements taken in an in-patient clinical research center once every fifteen minutes over a fifty hour time period covering a distribution over the entire 120 hour wear period for the Freestyle Navigator® sensor.
  • [0085]
    The subjects were admitted to a healthcare facility either in the evening or in the morning for sensor insertion. The sensors were inserted by a health care professional on both the lateral or posterior upper arm and the right or left lower abdominal quadrant using the disposable sensor delivery unit. The subjects returned to the clinic approximately nine hours later for the placement of the venous access line and for the calibration of the sensor using the built-in FreeStyle® blood glucose meter. Calibration of the FreeStyle Navigator® device in this study was deliberately scheduled to occur at different times of day as well as both pre- and post-prandially. During two separate periods in which the subjects were in the clinic and venous samples were being taken, each subject was administered intravenous insulin or a 75 gram fast-acting glucose drink, such as Glucola, in order to obtain data for evaluation of the sensor performance during deliberately-induced periods of rapidly-falling and rapidly-rising glucose. Data from the sensor and transmitter were stored in the receiver with a one minute frequency, but were not displayed to the subjects or the clinic staff. Throughout the study, all the subjects continued with their previously established diabetes management regimen. The high frequency and volume of the venous blood samples, 2.5 mL once every fifteen minutes, required a limitation of 50 hours of intensive testing in order to maintain the total volume of blood drawn from each subject within accepted safety limits. Subjects were assigned to different study schedules so as to provide an optimal distribution of the fifty hours of laboratory reference data over the total five day duration of the sensor life.
  • [0086]
    FIG. 2 illustrates five-day data from the Freestyle Navigator® continuous glucose monitor (arm and abdomen) and 50 hours of YSI venous sampling taken two separate in-patient admissions from one subject. The timing of the glucose and insulin challenges is also shown. The shaded blocks are night time. The black solid line is the Freestyle Navigator® sensor in the arm, the dashed line is the sensor in the abdomen. YSI measurements are shown in white triangles. The plus and cross symbols are the Freestyle Navigator® system blood glucose calibrations for the arm and abdominal sensors, respectively.
  • [0087]
    Referring to FIG. 2, a typical profile plot for the five-days of the study with one-minute data from the arm and abdominal sensors as well as the fifteen minute venous samples taken over three separate periods during the five days. The glucose concentration from the venous sample was measured using a YSI 2300 STAT Plus™ Glucose & Lactate Analyzer YSI analyzer (YSI Life Sciences, Yellow Springs, Ohio). All YSI measurements were made in duplicate from a single blood sample. YSI measurements were multiplied by 1.12 to obtain plasma equivalent value.
  • [0000]
    Results
  • [0088]
    A number of separate metrics were used to evaluate the accuracy and performance of the FreeStyle Navigator® system compared with the venous blood samples measured with the laboratory reference method. These metrics included the Clarke error grid, the Consensus error grid, the mean and median absolute relative difference as well as cross-correlation statistics for comparison of abdominal and upper arm sensors. The sensor performance was evaluated for the entire five days, for each day individually as well as diurnally and nocturnally. Characteristic physiological lag times were derived from analysis of the data. The data was also analyzed using the Continuous Glucose Error Grid Analysis (CG-EGA) (Kovatchev, 2004). Finally, the accuracy of the FreeStyle Navigator® system compared to the venous reference samples was analyzed as a function of the measured rates of change in the underlying blood glucose.
  • [0089]
    Comparison of the FreeStyle Navigator® continuous glucose measurements with the laboratory reference method (n=20,362) gave a mean absolute relative difference of 12.8% and a median absolute relative difference of 9.3%. The percentage in the clinically-accurate Clarke Error Grid zone A was 81.7% and 16.7% in the clinically-acceptable B zone. This included periods of high rates of change of blood glucose during intravenous glucose and insulin challenges. The precision of the matched Freestyle Navigator® sensors worn on the arm and abdomen had a coefficient of variation of 10% (n=312,953). The accuracy remained unchanged over the five days with the percent of data in the Clarke Error Grid Zone A equal to 82.5% on the first day and 80.9% on the fifth day.
  • [0090]
    Clinical Accuracy Overall
  • [0091]
    FIG. 3 shows the Clarke error grid for the study reported herein. More specifically, FIG. 3 illustrates an overall Clarke error grid showing 81.7% in the clinically-accurate A zone, 16.7% of the paired points in the clinically-acceptable or benign error zone B and only 1.7% outside of the A and B zones
  • [0092]
    The Clarke error grid was developed to assess the clinical implications of new glucose monitoring technology relative to accepted reference methods (Cox D J, Clarke W L, Gonder-Frederick L A, Pohl S, Hoover C, Snyder A, “Accuracy of perceiving blood glucose in IDDM”, Diabetes Care, 8(6):529-36, 1985; Clarke W L, Cox D, Gonder-Frederick L A, Carter W and Pohl S L. “Evaluating clinical accuracy of systems for self-monitoring of blood glucose” Diabetes Care, 10, 622-628, 1987). There were a total of 20,362 paired points for all 58 subjects with YSI venous measurements and Freestyle Navigator® system interstitial fluid glucose measurements. 81.7% of the paired points fell in the Clarke error grid zone A indicating a high level of clinical accuracy. There were 16.7% of the paired points in the clinically-acceptable (benign error) zone “B”, 0.1% in the overtreatment error zone “C”, 1.9% in the failure to detect error zone “D” and 0.01% in the clinically inaccurate and dangerous error zone “E”.
  • [0093]
    The Consensus error grid has been proposed as an alternative to the original error grid zone demarcations, specifically to eliminate the physical proximity of the clinically-unacceptable D zone with the clinically-accurate A zone in the lower left portion of the grid. The results of the Clarke error grid and the Consensus error grid are summarized in the Table (1) below. The Consensus error grid was also defined with five distinct risk levels, but the definitions were specified in terms of effect on clinical action by the patient. Zone A has no effect. Zone B has little or no effect. Zone C has altered clinical action. Zone D has altered clinical action with significant medical risk. Zone E has altered clinical action with potentially dangerous consequences.
  • [0094]
    On the Clarke error grid, there were 316 individual points in the D zone. Ninety-five percent of these points were in the lower left quadrant of the error grid.
    TABLE (1)
    Summary statistics of Clarke and Consensus Error Grid
    Clarke Consensus
    Error Error
    Grid Grid
    Zone % N = 20362 % N = 20362
    A 81.7 16627 85.5 17419
    B 16.7 3398 13.6 2776
    C 0.1 19 0.8 161
    D 1.6 316 0.03 6
    E 0.0 2 0.0 0
  • [0095]
    On the Consensus error grid, by contrast, the number of points in the significant medical risk D zone is reduced to 6. In addition to the reduction in D zone points, the Consensus error grid shows a higher percentage in the clinically-accurate A zone, a slightly lower percentage in the clinically-acceptable B zone, a slightly higher percentage in the altered clinical action C zone and no points in the dangerous consequence E zone.
  • [0096]
    The performance of the Freestyle Navigator® system was also assessed using the mean and median absolute relative difference between the sensor interstitial glucose measurements and the YSI venous sample measurements. The mean absolute relative difference was 12.8% and the median absolute relative difference was 9.3%. A comparison of accuracy and performance by day shows that the system's performance on the fifth day is equivalent to the performance of the first or second day. Table (2) contains data with the error grid statistics as well as the mean and median absolute relative difference from the study separated by day.
    TABLE (2)
    Clarke Error Grid, mean and median absolute relative difference by day
    Day 1 Day 2 Day 3 Day 4 Day 5
    Zone N % N % N % N % N %
    A 4354 82.5 3215 82.4 2903 79.4 1688 84.0 4467 80.9
    B 865 16.4 646 16.6 668 18.3 285 14.2 934 16.9
    C 12 0.2 4 0.1 1 0.0 0 0.0 2 0.0
    D 47 0.9 34 0.9 82 2.2 37 1.8 116 2.1
    E 0 0.0 2 0.1 0 0.0 0 0.0 0 0.0
    Mean ARD 12.6 12.3 14.1 11.9 13.0
    Median ARD 9.4 9.3 9.9 7.8 9.5
    Total 5278 100.0 3901 100.0 3654 100.0 2010 100.0 5519 100.0
  • [0097]
    Additional analysis was done comparing the accuracy and performance of the Freestyle Navigator® system nocturnally and diurnally. The percentage of points in the Clarke error grid A zone was 87.1% at night and 80.6% during the day. The difference in accuracy during the day may be associated with the higher rates of change during the daytime, when all of the glucose and insulin challenges were conducted.
  • [0098]
    The data from the present study has also been analyzed using the Continuous Glucose Error Grid Analysis (CG-EGA), designed to incorporate the extra temporal dimension of data provided by continuous glucose monitoring systems (Kovatchev et al.). The rate analysis using the CG-EGA gave a 81.1% in the rate error grid A zone, 14.4% in the rate error grid B zone, 1.5% in the rate error grid C zone, 2.3% in the rate error grid D zone, and 0.7% in the rate error grid E zone. The point analysis using the CG-EGA gave a 83.6% in point error grid A zone, 15.0% in point error grid B zone, 0.1% in point error grid C zone, 1.3% in point error grid D zone, and 0% in point error grid E zone. The CG-EGA analysis combining rate and point information revealed that accuracy, measured as a percentage of accurate readings plus benign errors, was 97.5% (94.2% accurate, 3.4% benign). The CG-EGA accuracy stratified by glycemic state gave 60.4% in hypoglycemia (53.1% accurate, 7.3% benign), 99.3% in euglycemia (95.7% accurate, 3.6% benign) and 98.2% in hyperglycemia (95.4% accurate, 2.8% benign). The difference in accuracy between the hypoglycemic, euglycemic, and hyperglycemic ranges may be related to the high rate of change often associated with the descent into hypoglycemia. Standard egression analysis and Deming regression analysis both gave small, but significant offsets 24.9 and 14.3 mg/dL) that could contribute to the slight decrease in accuracy in hypoglycemia.
  • [0099]
    FIGS. 4A and 4B give an expanded view of the data from FIG. 2 on a four-hour time axis and centered about the glucose challenge and the insulin challenge, respectively. More specifically, FIG. 4A illustrates a zoomed in view (four hour duration) of Freestyle Navigator®™ sensor data and YSI measurements during the glucose challenge. Referring to FIG. 4A, the continuous glucose sensor data in one minute intervals are shown in the two solid curves (solid from the arm, dashed from the abdomen). The 15 minute YSI venous sample data are shown in the triangles. The time between the nadir of the YSI data and the Freestyle Navigator® system is approximately 24 minutes. The time between the peak of the YSI data and the Freestyle Navigator® system data is approximately 19 minutes.
  • [0100]
    Additionally, FIG. 4B shows data from two Freestyle Navigator® sensors, compared with fifteen minutes venous samples measured with the YSI from the insulin challenge in one patient in the study. Referring to FIG. 4B, the Freestyle Navigator® projected alarm, would have alerted the subject to an impending hypoglycemic event 26 minutes before the blood sugar crossed the 70 mg/dL hypoglycemic threshold. At the time of the alarm, the Freestyle Navigator® system glucose was approximately 175 mg/dL and the YSI reading was approximately 90 mg/dL and the rate of change was −3.5 mg/dL/min.
  • [0101]
    Both FIGS. 4A and 4B show the temporal tracking of the FreeStyle Navigator® system compared against the venous reference samples. The expanded temporal axis used in FIGS. 4A and 4B also permits more direct visualization of the time lag between the Freestyle Navigator® system interstitial fluid glucose measurement and the venous reference sample measurements. The temporal offset between the FreeStyle® Navigator system and the venous reference measurements was also analyzed by applying a time shift in order to minimize the mean absolute relative difference.
  • [0102]
    After correction for the calibration bias, this resulted in an average 12.8 minute lag between the glucose values measured in the interstitial fluid and in the venous samples. This is consistent with previously published studies on the physiological lag between interstitial fluid glucose and blood glucose (see for example: Rebrin K, Steil G M, van Antwerp W P, Mastrotoraro J J, “Subcutaneous glucose predicts plasma glucose independent of insulin: implications for continuous monitoring”, Am J Physiol., 277 (3 Pt 1):E561-71, 1999; Steil G M, Rebrin K, Mastrototaro J, Bernaba B, Saad M F, “Determination of plasma glucose during rapid glucose excursions with a subcutaneous glucose sensor”, Diab. Tech. Ther, 5:27-31, 2003; Thennadil S N, Rennert J L, Wenzel B J, Hazen K H, Ruchti T L, Block MB, “Comparison of glucose concentration in interstitial fluid, and capillary and venous blood during rapid changes in blood glucose levels”, Diab. Tech. Ther., 3(3):357-65, 2001).
  • [0103]
    The performance of the arm and abdominal sensors was comparable with equivalent Clarke error grid statistics and mean absolute relative difference. The precision of the matched Freestyle Navigator® sensors worn on the arm and abdomen had a coefficient of variation of 10% (n=312, 953). There was no difference in performance of the sensor as a function of age, gender or ethnicity. However, there were small but measurable differences in the accuracy of the sensor depending on the subject's BMI and also on the years since diagnosis. Subjects with BMI less than 25.0 had 78.8% in the Clarke error grid A zone (N=4844), whereas subjects with BMI between 25.0 and 30.0 had 82.2% in the Clarke error grid A zone (N=7855) and subjects with BMI greater than 30.0 had 84.4% in the Clarke error grid A zone (N=3928). Similarly, there were small but measurable differences in accuracy depending on the years since diagnosis of type 1 diabetes. The highest accuracy, 88.5% in the Clarke error grid A zone, was found in subjects who had been diagnosed with diabetes for five years or less (N=2066) and 81.3% for subjects diagnosed between 5 and 25 years (N=9133). Subjects diagnosed with type 1 diabetes for over 25 years had 79.9% in the Clarke error grid A zone (N=5448).
  • [0000]
    Clinical Accuracy Under Special Circumstances
  • [0104]
    The evaluation of the overall accuracy and performance of the FreeStyle Navigator® continuous glucose monitor included periods of deliberately-induced rapidly rising and rapidly falling blood glucose, i.e. in response to the glucose and insulin challenges. There were significant differences in the accuracy compared with the laboratory reference measurements depending on the different rates of change of the underlying blood glucose. Table (3) gives the Clarke error grid statistics and the median absolute relative difference percentage as a function of the rate of change of blood glucose as determined by the YSI measurements. The effect of the physiological lag on the accuracy of the sensor values compared to venous reference samples is more pronounced at the high rates of change, particularly during when the absolute rate of change exceeds 2 mg/dL/min.
    TABLE (3)
    Rate of change and Clarke error grid statistics and median ARD
    Rate of
    Change Clarke Error Grid Region Median
    (mg/dL/min) N A B C D E ARD %
    <−2 601 54.6 42.3 1.3 1.8 0.0 17.4
    −2 to −1 1728 71.7 26.2 0.3 1.8 0.0 11.8
    −1 to 1   14653 84.9 13.5 0.0 1.5 0.0 8.5
    1 to 2 1954 79.8 18.9 0.0 1.3 0.0 11.0
      >2 691 63.5 34.7 0.0 1.7 0.0 16.9
  • [0105]
    FIG. 5 illustrates the rate of change histogram showing underlying rate of change at high resolution (in units of 0.25 mg/dL/min) and in units of the Navigator receiver trend arrows (1.0 mg/dL/min). The rate of change of glucose as measured by the sensor was between −1 and +1 mg/dL/min 74.6% of the time. Referring to FIG. 5, there is a slight difference in the measured occurrence of absolute rates of change less than 1 mg/dL/min due to the different sampling frequency and temporal extent of the Freestyle Navigator® system and YSI measurements.
  • [0106]
    The Freestyle Navigator® trend arrows would have been in the horizontal position indicating an absolute rate of change less than 1 mg/dL/min 74.1% of the time for which the YSI data revealed 71.9% of all readings in this range. Both values are consistent with previously reported results (see for example: Dunn T C, Eastman R C, Tamada J A, “Rates of glucose change measured by blood glucose meter and the GlucoWatch Biographer during day, night, and around mealtimes”, Diabetes Care 27: 2161-2165, 2004; Kovatchev, B. P., Clarke, W. L., Breton, M., Brayman, K. and McCall, A. “Quantifying Temporal Glucose Variability in Diabetes via Continuous Glucose Monitoring: Mathematical Methods and Clinical Application” Diab. Technol. Thera., 7, 849-862, 2005).
  • [0107]
    FIG. 6 illustrates Clarke error grid for YSI rates of change between −1 to 1 mg/dL/min showing increase in accuracy during modest rates of change. Referring to FIG. 6, whereas the overall percentage of paired points in the Clarke error grid A zone was 81.7%, the percentage in the A zone for rates of change between −1 mg/dL/min and +1 mg/dL/min was significantly higher at 84.9%. Similarly, the mean and median absolute relative differences at these times were 11.4% and 8.5% respectively.
  • [0108]
    The accuracy of the Freestyle Navigator® continuous glucose monitor was evaluated in comparison to a standard laboratory reference method using venous blood samples. The overall mean and median absolute relative difference of the sensor in the current study of 12.8% and 9.3% represent a significantly higher level of accuracy than previously published results from other continuous glucose monitoring systems (see for example, Diabetes Research in Children Network (DirecNet) Study Group: “The Accuracy of the CGMS in Children with Type 1 Diabetes: Results of the Diabetes Research in Children Network (DirecNet) Accuracy Study”. Diabetes Technol Ther 5(5):781-789, 2003; Diabetes Research in Children Network (DirecNet) Study Group: “The Accuracy of the GlucoWatch G2 Biographer in Children with Type 1 Diabetes: Results of the Diabetes Research in Children Network (DirecNet) Accuracy Study”. Diabetes Technol Ther 5(5):791-800, 2003; Tansey M J, Beck R W, Buckingham B A, Mauras N, Fiallo-Scharer R, Xing D, Kollman C, Tamborlane W V, Ruedy K J, “Accuracy of the modified Continuous Glucose Monitoring System (CGMS) sensor in an outpatient setting: results from a diabetes research in children network (DirecNet) study.” Diab. Tech. Ther. 7(1):109-14, 2005; Garg S., Zisser H., Schwartz S., Bailey T., Kaplan R., Ellis S. and Jovanovic L, “Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor”, Diabetes Care, 29, 44-50, 2006).
  • [0109]
    The high accuracy of the system as measured by the percentage in the Clarke error grid A zone and the mean and median absolute relative differences remained high over the entire five days. There was a small, but measurable improvement in the Clarke error grid statistics and the absolute relative difference values on the fourth day. This is due principally to the fact that there were no glucose challenges administered on the fourth day of the study resulting in fewer rates of change on that day less than 2 mg/dL/min than on other days. In addition, there may be a small increase in accuracy on the fourth day associated with the final system calibration at 72 hours after sensor insertion. Similarly, the slight decrease in accuracy observed on the third and fifth days of the sensor wear may be associated with the fact that these days had a greater number of glucose and insulin challenges than other days in the study, resulting in more absolute rates of change on those days in excess of 2 mg/dL/min.
  • [0110]
    A significant portion of the apparent discrepant points between the Freestyle Navigator® and the venous reference samples are likely due to the physiological lag alone. An example of the effect of physiological lag on accuracy is the point at the nadir of the curves in FIG. 4B, which is categorized in the Clarke error grid analysis as a clinically unacceptable D zone point. In this case, although the point-wise comparison of the Freestyle Navigator® sensor value and the venous reference sample value suggests a failure to detect a hypoglycemic event, it is clear from the data that the Freestyle Navigator® system is correctly tracking the fall of the subject's glucose level.
  • [0111]
    In the case shown in FIG. 4B, with the projected alarm capability enabled and the detection threshold set at 70 mg/dL, the device would have alerted the user to a predicted change in clinical state from euglycemia to hypoglycemia when the Freestyle Navigator® glucose value was approximately 175 mg/dL and the measured rate of glucose decrease was in excess of −3.5 mg/dL/min. At that moment, the trend arrow was in the downward vertical direction, indicating a rate of glucose decrease of greater than 2 mg/dL/min, and the device's alarm would have used predictive algorithm to identify that the subject would be hypoglycemic in thirty minutes.
  • [0112]
    At the time when the projected alarm would have alerted the subject to an impending hypoglycemic event, the YSI reading was approximately 90 mg/dL. An interpolation of the YSI data indicates that the subject's blood sugar crossed the 70 mg/dL threshold for hypoglycemia approximately twenty-six minutes later. Although the paired YSI and Freestyle Navigator® system points at the nadir of the curve result in a D zone point on the Clarke error grid, it is clear from a detailed analysis that the projected alarm would have alerted the subject to an impending hypoglycemic event in a timely manner.
  • [0113]
    Another important measure of the clinical accuracy, and ultimately the clinical utility, of the Freestyle Navigator® system is the percentage of points in the clinically-accurate Clarke error grid A zone. A recent numerical simulation study evaluated the effect of sensor inaccuracy on the statistics associated with glucose monitoring error grid analysis using data from a clinical trial of a continuous glucose monitoring system in type 1 children and adolescents (Kollman et al., 2005). In the numerical study, paired points from the actual continuous glucose monitoring system and a laboratory reference method were randomly “shuffled” to simulate a high degree of sensor inaccuracy. The study found that 78% of the randomly shuffled paired points were still in the combined A and B zones of the Clarke error grid. A more useful measure of the clinical accuracy and utility of new glucose monitoring technology may be the percentage of points in the clinically-accurate Clarke error grid A zone alone. (Kollman C, Wilson D M, Wysocki T, Tamborlane W V, Beck R W, “Limitations of the Statistical measures of Error in Assessing the Accuracy of continuous Glucose Sensors”, Diab. Tech. Ther., 7(5):665-672, 2005). An alternative to the more commonly-used metric of combined A and B zone percentage is to rely instead on the total percentage in the A zone alone. The results of the present study showing the Freestyle Navigator® system achieving 81.7% in the A zone alone represent a new level of performance for continuous glucose monitoring systems.
  • [0114]
    The high accuracy and performance of the Freestyle Navigator® system at night is also in contrast with previous reports of continuous glucose monitoring systems that exhibited sustained periods of anomalous nocturnal hypoglycemia (see for example: MTcGowan K. Thomas W, Moraii A. “Spurious reporting of nocturnal J hypoglycemia by CGMS in patients with tightly controlled type I diabetes” Diabetes Care 2002; 25: 1499-1503; Metzger M, Leibowitz G, Wainstein J, Glaser B, Raz I. “Reproducibility of glucose measurements using the glucose sensor” Diabetes Care 2002; 25: 1185-1191; Mauras N, Beck R W, Ruedy K J, Koliman C, Tamborlane W V, Chase H P “Lack of accuracy of continuous glucose sensors in healthy nondiabetic children: results of the Diabetes Research in (Children Network (DirecNet) accuracy study” J Pediatr 2004; 144:770-775).
  • [0115]
    The difference in accuracy as a function of BMI may be related to the length of the Freestyle Navigator® sensor and the thickness of the subcutaneous adipose tissue layer in subjects with BMI less than 25. Anthropometric data strongly suggests that the insertion of the Freestyle Navigator® sensor in the upper arm or abdomen will result in the sensor being placed as intended in the subcutaneous adipose tissue layer in most individuals (Horejsi, R., Moller, R., Pieber, T R, Wallner, S., Sudi, K, Reibnegger, G. and Tafeit “Differences of subcutaneous adipose tissue topography between type 2 diabetic men and healthy controls” Exp. Biol. Med., 227, 794-798, 2002). However, in some individuals with low BMI, the data indicate that the subcutaneous adipose tissue layer thickness on the posterior arm upper arm or even the lower abdominal quadrant may be only slightly greater than the required 6 mm thickness needed to properly accommodate the sensor. Although the overall sensor performance in subjects with BMI less than 25 is still excellent (78.8% in the clinically-accurate Clarke error grid A zone), there is a small but measurable difference when compared with subjects with BMI greater than 30 (84.4% in the clinically-accurate Clarke error grid A zone). In the low BMI subjects with reduced subcutaneous adipose tissue layer thickness, the proximity of skeletal muscle tissue to the sensor in the adipose tissue could increase the effect reported by Moberg et al. in which tissue glucose nadirs were not only delayed relative to plasma, but also reduced especially during insulin-induced hypoglycemia (Moberg E, Hagstrom-Toft E, Amer P. and Bolinder J. “Protracted glucose fall in subcutaneous adipose tissue and skeletal muscle compared with blood during insulin-induced hypoglycaemia” Diabetologia 40, 1320-1326, 1997).
  • [0116]
    In the present study, the apparent difference in accuracy as a function of years since diagnosis is most likely also a result of the weak dependence of accuracy on BMI. The 6 subjects with a diagnosis of diabetes less than five years, for whom there was the highest percentage in the Clarke error grid A zone and the lowest median absolute relative difference, also by chance had the highest mean BMI (29.8). Similarly, the 18 subjects with lowest BMI (<24.9) in the study happened to also have the highest mean years since diagnosis of diabetes (30.1 years).
  • [0117]
    Insulin adjustment Procedure—Clinical Decision Analyses
  • [0000]
    Insulin Adjustment Analysis
  • [0118]
    The Insulin Adjustment Analysis evaluates the difference between insulin dosing based on Freestyle Navigator® Continuous Glucose Monitoring System (CM) readings and that based on reference readings. The interpretation of the analysis is best understood considering a hypothetical patient with a glucose target level of 90-120 mg/dL and an insulin sensitivity of 30 mg/dL/unit. The glucose target level represents aggressive therapy where the therapeutic goal is to keep glucose squarely in the normal range. The analysis is targeted to meet the requirements of intensive insulin therapy. The choice of insulin sensitivity was made to simplify interpretation—the treatment differences between Navigator CM and YSI are calculated in whole number differences in the units of insulin. This seemingly arbitrary choice of the hypothetical patient has no influence on the results of the Insulin Adjustment Analysis—the choice was based on the goals of intensive insulin therapy and the ease of interpretation of the results.
  • [0119]
    The Insulin Adjustment Analysis data is reported as differences in units of insulin. (see Table 4). This is an intermediate result that allows a more detailed characterization of the data than the final summary (see Table 5). Decisions with Navigator CM were rated Correct 89.3% (1180/1322) of the time and Acceptable 7.6% (100/1322) of the time. Since the Acceptable rating translates to a glucose adjustment to within the normal glucose range, accurate adjustments are the sum of Correct and Acceptable categories, 96.8% (1280/1322).
    TABLE 4
    Treatment Difference for the Hypothetical Patient with Insulin
    Sensitivity = 30 mg/dL/unit and Glucose Target = 90-120 mg/dL
    Navigator CM -
    YSI Treatment
    Difference Glucose < 200 mg/dL Glucose ≧ 200 mg/dL
    (Units of insulin) N % Category N % Category
    −4   0 0 Hyperglycemia 2 4 0.6 Hyperglycemia 2
    −3   1 0.1 Hyperglycemia 1 13 2.0 Hyperglycemia 1
    −2   11 1.6 Acceptable 78 12.1 Acceptable
    −1   120 17.7 Correct 215 33.4 Correct
    0 353 52.0 Correct 240 37.3 Correct
    1 173 25.5 Correct 79 12.3 Correct
    2 18 2.7 Possible Error 11 1.7 Acceptable
    3 2 0.3 Error 3 0.5 Possible Error
    4 1 0.1 Error 0 0 Error
    Total 679 100 643 100
  • [0120]
    TABLE 5
    Insulin Adjustment Analysis Summary
    Category Effect on Blood Glucose N %
    Correct Within ±30 mg/dL of target 1180 89.3
    glucose
    Acceptable Within normal glucose range 100 7.6
    Possible Error (hypo)  60 mg/dL below target glucose 21 1.6
    Error (hypo)  ≧90 mg/dl below target glucose 3 0.2
    Hyperglycemia 1  90 mg/dL above target glucose 14 1.1
    Hyperglycemia 2 ≧120 mg/dl above target glucose 4 0.3
    Total 1322 100
  • [0121]
    In summary, this analysis describes 3 occurrences of “Error (hypo)” and 4 occurrences of “hyperglycemia 2” being potentially indicated from 1322 decision points
  • [0000]
    Glucose Peak
  • [0122]
    Continuous glucose monitoring provides the ability to identify and quantify the maximum glucose excursions after meals and during the night. The quantification of glucose peaks was clinically accurate 88.1% of the time and clinically useful 97.6% of the time (see Table 6).
    TABLE 6
    Glucose Peak Analysis
    Difference Clinical Assessment N %
    ±15 mg/dL Accurate 263 41.5
    ±45 mg/dL Accurate 295 46.6
    ±75 mg/dL Useful 60 9.5
    ±105 mg/dL  Misclassification 14 2.2
    ±135 mg/dL  Misclassification 1 0.2
    Total 633 100.0

    Insulin Adjustment Analysis
  • [0123]
    The Insulin Adjustment Analysis evaluates the hypothetical difference between insulin dosing based on Navigator CM readings to that based on a blood glucose meter such as Freestyle Blood Glucose (BG) readings. The interpretation of the analysis is best understood considering a hypothetical patient with a glucose target level of 90-120 mg/dL and an insulin sensitivity of 30 mg/dL/unit. The glucose target level represents aggressive therapy where the therapeutic goal is to keep glucose squarely in the normal range. The analysis is targeted to meet the requirements of intensive insulin therapy. The choice of insulin sensitivity was made to simplify interpretation—the treatment differences between Navigator CM and Freestyle BG YSI (see Table 7) are calculated in whole number differences in the units of insulin. This seemingly arbitrary choice of the hypothetical patient has no influence on the results of the Insulin Adjustment Analysis—the choice was based the goals of intensive insulin therapy and the ease of interpretation of the results.
  • [0124]
    The Insulin Adjustment Analysis data is reported as differences in units of insulin (see Table 7). There were 6,040 paired (Navigator CM-Freestyle BG) glucose readings available at times of subject-reported insulin dosing or bedtime in the Home Use Study. The analysis is summarized in Table 8 with 86.5% (5226/6040) of the readings correct and 94.3% (5696/6040) accurate or acceptable. These results provide approximately 89.3% (1180/1322) correct and 96.8% (1280/1322) accurate or acceptable.
    TABLE 7
    Treatment Difference for the Hypothetical Patient with Insulin
    Sensitivity = 30 mg/dL/unit and Glucose
    Target = 90-120 mg/dL
    Glucose < 200 Glucose ≧ 200
    Difference in Insulin Dose mg/dL mg/dL
    (Units) N (%) N (%)
    4 0 0 1 0.0
    3 11 0.3 2 0.1
    2 84 2.1 14 0.7
    1 810 20.1 162 8.1
    0 2362 58.5 530 26.5
    −1  675 16.7 687 34.3
    −2  89 2.2 367 18.3
    −3  8 0.2 163 8.1
    −4  0 0 75 3.7
    Total 4039 2001
  • [0125]
    TABLE 8
    Insulin Adjustment Analysis Summary
    Category Effect on Blood Glucose N %
    Correct Within ±30 mg/dL of target 5226 86.5
    glucose
    Acceptable Within normal glucose range 470 7.8
    Possible Error 60 mg/dL below target glucose 86 1.4
    (hypo)
    Error (hypo) ≧90 mg/dl below target 12 0.2
    glucose
    Hyperglycemia 1 90 mg/dL above target glucose 171 2.8
    Hyperglycemia 2 ≧120 mg/dl above target 75 1.2
    glucose
    Total 6040 100
  • [0126]
    Insulin dosing or bedtime was not indicated for 5,447 of the 11,487 Freestyle BG duplicate points. The Insulin Adjustment Analysis was also conducted using the 5,447 Freestyle BG duplicate points for which there was no indication of insulin injection to determine if there was a substantive difference between the two populations. The Insulin Adjustment Analysis data is reported as differences in units of insulin (See Table 9). The results are slightly better for the points where insulin injections were not indicated (See Table 10) with 89.4% (4868/5447) correct and 95.5 (5203/5447) correct or acceptable.
    TABLE 9
    Treatment Difference for the Hypothetical Patient with
    Insulin Sensitivity = 30 mg/dL/unit and
    Glucose Target = 90-120 mg/dL - Non-insulin Injection Points
    Glucose < 200 Glucose ≧ 200
    Difference in Insulin Dose mg/dL mg/dL
    (Units) N (%) N (%)
    4 2 0.0 0 0
    3 11 0.3 1 0.1
    2 95 2.3 26 2.0
    1 876 21.2 132 10.0
    0 2473 59.9 388 29.5
    −1  588 14.2 411 31.2
    −2  81 2.0 228 17.3
    −3  5 0.1 88 6.7
    −4  0 0 42 3.2
    Total 4131 1316
  • [0127]
    TABLE 10
    Insulin Adjustment Analysis Summary
    Non-insulin Injection Points
    Category Effect on Blood Glucose N %
    Correct Within ±30 mg/dL of target 4868 89.4
    glucose
    Acceptable Within normal glucose range 335 6.2
    Possible Error  60 mg/dL below target glucose 96 1.8
    (hypo)
    Error (hypo)  ≧90 mg/dl below target glucose 13 0.2
    Hyperglycemia 1  90 mg/dL above target glucose 93 1.7
    Hyperglycemia 2 ≧120 mg/dl above target glucose 42 0.8
    Total 5447 100
  • [0128]
    When a patient adjusts an insulin dose using a blood glucose meter such as Freestyle Blood Glucose monitor, there is no indication if glucose is changing. If glucose is rising at the time of glucose dosing, there is insufficient insulin to stabilize blood glucose and the predicted insulin dose will be too small. Likewise, if glucose is descending, there is already insulin in the blood, and the predicted insulin dose will be too large. The rate of glucose change indicated by Navigator CM at the time of insulin dosing (see Table 11) indicates glucose changes >±2 mg/dL/minute 4.0% of the time, and >±1 mg/dL/minute 18.3% of the time. The agreement of static the blood glucose meter readings with static reference readings is excellent, but the interpretation of this agreement to suggest accurate insulin dosing with the blood glucose meter is not correct. When insulin is dosed with no knowledge of changing glucose levels, the dosing will be incorrect a significant fraction of the time. The determination of 94.3% Navigator CM dosing accuracy in this study and 96.8% Navigator CM dosing accuracy in a previous study provide realistic estimations when the rate of glucose change is also known.
    TABLE 11
    Navigator CM Rate Indication at the Time of Insulin Dosing
    Navigator CM Rate of Change (mg/dL/minute) N (%)
     >2.0 330 3.3
    1.0 to 2.0 897 9.0
    −1.0 to 1.0  8140 81.7
    −2.0 to −1.0 526 5.3
    <−2.0 72 0.7
  • [0129]
    The description below details a further user study results from a highly accurate continuous glucose monitoring system such as, for example, Freestyle Navigator® system. Of the 137 subjects enrolled in the investigation, 123 completed the 40-day monitoring period. The other 14 subjects withdrew from the study due to non-compliance with protocol demands (n=8) or difficulties handling the device (n=6). None of the discontinued subjects participated in the unblinded portion of the study. The glucose data available for the discontinued subjects was included in the paired point analysis.
  • [0130]
    The performance of the Freestyle Navigator® was assessed using the absolute relative difference between the sensor interstitial glucose measurements and the blood glucose measurements. Data from 961 sensors with 11,487 paired FreeStyle BG reference values were evaluated. The mean absolute relative difference was 14.4% and the median absolute relative difference was 111%. The mean absolute relative difference indicates that, on average, the CM reading was 14.4% higher or lower than the corresponding BG reading. The median absolute relative difference indicates that the CM reading was equally as likely to be within 11.1% of the BG reading, either higher or lower, as it was to be outside of that range.
  • [0131]
    The equation for the Deming regression had a slope of 0.83, an intercept of 21.8 mg/dL and correlation coefficient of 0.92. These results demonstrate a strong correlation between CM and BG readings.
  • [0132]
    FIG. 7 shows the Clarke error grid for the study. There were a total of 11,487 paired points with averaged duplicate BG reference values and interpolated CM values, from 131 subjects. No paired points were available from six subjects. Of the 11,487 paired points, 77.2% fell in the Clarke error grid zone A, indicating a high level of correspondence between the reference blood glucose measurements and the CM results. There were 19.6% of the paired points in zone B and only 3.2% outside the A and B zones. Results for all the Clarke error grid zones are shown in Table 12 below. The results of the Consensus error grid are also included in Table 12.
    TABLE 12
    Summary statistics of Clarke and Consensus Error Grid
    Clarke Error Consensus
    Grid Error Grid
    Zone N (%) N (%)
    A 8863 77.2 9180 79.9
    B 2255 19.6 2194 19.1
    C 1 0.0 109 0.9
    D 365 3.2 4 0.0
    E 3 0.0 0 0.0
    N paired points 11487 11487
  • [0133]
    On the Clarke error grid, there were 365 individual points in the D zone. On the Consensus error grid, by contrast, the number of points in the D zone is reduced to four. In addition, the Consensus error grid shows 79.9% in the A zone, 99.0% in the A and B zones, less than 1% in the C and D zones and no points in the E zone.
  • [0134]
    A comparison of accuracy and performance by day of sensor wear shows that the system's performance on the fifth day is nearly equivalent to the performance on the first or second day. Table 13 contains data with the error grid statistics as well as the mean absolute relative difference from the study separated by day.
    TABLE 13
    Clarke Error Grid, absolute relative difference by day
    Day 1 Day 2 Day 3 Day 4 Day 5
    Zone N/(%) N/(%) N/(%) N/(%) N/(%)
    Clarke A 1061 (77.8) 2182 (77.4) 2110 (77.7) 1884 (79.3) 1626 (73.5)
    Clarke B  266 (19.5)  551 (19.6)  516 (19.0)  427 (18.0)  495 (22.4)
    Clarke C  0 (0.0)  0 (0.0)  0 (0.0)  0 (0.0)  1 (0.0)
    Clarke D  36 (2.6)  84 (3.0)  91 (3.3)  63 (2.7)  91 (4.1)
    Clarke E  1 (0.1)  1 (0.0)  0 (0.0)  1 (0.0)  0 (0.0)
    N paired 1364 2818 2717 2375 2213
    points
    Consensus A
    Consensus B
    Consensus C
    Consensus D
    Consensus E
    N paired 1364 2818 2717 2375 2213
    points
    Mean 14.8 14.3 14.0 13.9 15.3
    ARD
    Median
    ARD
  • [0135]
    Table 14 shows that the CM readings are optimal when blood glucose is relatively stable (i.e., when the rate is within +/−1 mg/dL/min). As expected the bias increases somewhat as the magnitude of the rate of glucose change increases. However, the displayed rate arrow provides the necessary information to properly interpret the glucose result in these situations. The mean bias for glucose <100 mg/dL and the mean percent bias for glucose ≧100 mg/dL become increasingly positive as the rate decreases from +2 mg/dL/minute to −2 mg/dL/minute. Lag in the interstitial readings versus capillary blood glucose readings is the explanation for this result. When glucose levels were rising, the CM values were low, on average, versus BG with the difference versus BG lower for rising glucose (>1 mg/dL/minute) than for stable glucose (±1 mg/dL/minute). When glucose levels were falling CM was high, on average, versus BG with the difference versus BG higher for falling glucose (<1 mg/dL/minute) than for stable glucose (±1 mg/dL/minute).
    TABLE 14
    Difference measures vs. glucose rate of change
    Navigator CM Rate of Change
    (mg/dL per minute) Mean Median N
    Difference (mg/dL) for glucose < 100 mg/dL
     >2.0 3.7 −1.2 3
    1.0 to 2.0 4.7 5.5 33
    −1.0 to 1.0  7.6 7.1 2028
    −2.0 to −1.0 17.9 18.7 261
    <−2.0 26.5 24.4 50
    Absolute difference (mg/dL) for glucose < 100 mg/dL
     >2.0 11.0 9.8 3
    1.0 to 2.0 12.5 9.9 33
    −1.0 to 1.0  13.3 10.8 2028
    −2.0 to −1.0 21.5 19.4 261
    <−2.0 32.4 27.0 50
    Percent difference % for glucose ≧= 100 mg/dL
     >2.0 −13.7 −14.3 152
    1.0 to 2.0 −10.9 −10.7 581
    −1.0 to 1.0  −3.5 −3.7 7245
    −2.0 to −1.0 6.9 6.8 432
    <−2.0 7.5 9.1 69
    Absolute % difference % for glucose ≧= 100 mg/dL
     >2.0 17.0 16.1 152
    1.0 to 2.0 14.8 12.6 581
    −1.0 to 1.0  12.2 9.8 7274
    −2.0 to −1.0 15.9 12.6 432
    <−2.0 18.3 14.5 69
  • [0136]
    The Clarke EGA as a function of Navigator rate (Table 15) exhibits the expected behavior. When glucose is descending by at least −2 mg/dL/min, there is a higher likelihood that a reading would fall into the left Zone D than when the glucose is stable or rising. When glucose is rising, there is a higher likelihood that a reading would fall into the right Zone D. The rate arrow provides the valuable information to properly interpret the glucose result (i.e. when glucose is rapidly descending Navigator CM tends to be higher than Navigator BG and when glucose is rapidly ascending Navigator CM tends to be lower than Navigator BG).
    TABLE 15
    Clarke EGA vs. glucose rate of change
    Zone <−2.0 % −2.0 to −1.0 % −1.0 to 1.0 % 1.0 to 2.0 % >2.0 %
    A 61 51.3 425 61.3 7372 79.3 455 74.1 101 65.2
    B 45 37.8 194 28.0 1688 18.1 149 24.3 48 31.0
    C 0 0.0 1 0.1 0 0.0 0 0.0 0 0.0
    D 12 10.1 73 10.5 240 2.6 10 1.6 6 3.9
    E 1 0.8 0 0.0 2 0.0 0 0.0 0 0.0
    Total 119 692 9302 614 155

    Sensor Success Measures
  • [0137]
    The rate of successful sensor insertions was evaluated from reported results of each sensor insertion attempt, as well as the electronic records stored by the Receiver. The electronic records were used to determine whether each sensor was detected by the Receiver, and whether the user followed the steps in the labeling. The percentage of insertions that were successful, when used as directed, was similar for the blinded (96.0%) and unblinded (96.8%) phases of the study (96.4% overall). The percentage of successful insertions was similar for the arm (95.7%) and abdomen (97.4%) insertion sites. Abdomen insertions may have been more successful because it is easier to see the entire insertion process at the abdomen site when inserting a sensor on oneself.
  • [0138]
    The success rate for the initial Sensor Calibration process was evaluated from results recorded in the receiver log data for each successful sensor insertion attempt. The time required to complete the first sensor calibration was evaluated in addition to the overall success or failure. The percentage of sensors that were successfully calibrated and produced glucose results within the first 12 hours was calculated. Sensor calibration is not allowed within the first 10 hours. Sensors that could not be calibrated because conditions were out of range were excluded, e.g., if the glucose was changing too rapidly for calibration. The percentage of sensors that were successfully calibrated within 12 hours, when used as directed, was similar for the blinded (90.5%) and unblinded (92.6%) phases of the study (91.5% overall).
  • [0139]
    Sensor duration was evaluated as the time duration from sensor insertion to the last CM glucose result reported for the sensor. Some sensors were removed early by user error or discretion, or because of protocol logistics such as the end of the trial. These sensors are excluded from analysis, unless the sensor reached the nominal 5-day sensor life (>108 hours). The median sensor life was similar for the blinded (119.9 hours) and unblinded (120.0 hours) phases of the study. The percentage of sensors, used as directed, that produced glucose results for 108 hours or more was similar for the blinded (83.5%) and unblinded (83.0%) phases of the study. Sensors on the arm tended to have slightly longer duration (86.2% for >108 hours) than those on the abdomen (79.4%), because there is somewhat less flexing and folding of the skin at the posterior arm insertion site than on the abdomen, improving the effectiveness of the skin adhesive that holds the sensor in place.
  • [0000]
    Glycemic Analysis
  • [0140]
    The change in glycemic status between the blinded and unblinded phases of the study was stratified by type 1 and type 2 diabetes. During the unblinded phase when alarms were set, subjects were instructed to perform a BG test when alarms were triggered. Some important differences in controlling glucose concentration with insulin administration between the two types of diabetes are the following:
      • Subjects with type 2 diabetes are less likely to induce hypoglycemia with insulin because they are insensitive to insulin. Type 1 subjects, with normal insulin sensitivity are much more likely to induce hypoglycemia.
      • Subjects with type 2 diabetes can reduce hyperglycemia by reducing carbohydrate ingestion and allowing endogenous insulin to reduce blood glucose. Patients with type 1 diabetes produce no endogenous insulin, so a reduction of carbohydrates is not a viable strategy for controlling glucose. Controlling glucose with injected insulin is much more difficult than control with endogenous insulin.
  • [0143]
    The time spent in hypoglycemic (<70 mg/dL), euglycemic (70-180 mg/dL) and hyperglycemic ranges is illustrated in FIG. 8 for type 1 and 2 subjects in the blinded and unblinded phases of the study.
  • [0144]
    The type 1 subjects improved in the unblinded phase by reducing time in hypoglycemia. The time spent below the 70 mg/dL threshold for hypoglycemia was reduced by 42% from 1.4 hours to 0.8 hours (p<0.0001). The time spent in hyperglycemia (>180 mg/dL) did not change.
  • [0145]
    For type 2 subjects, the duration of hyperglycemia improved in the unblinded phase. The time spent in the euglycemic range increased by 12% (p=0.0027) and the time spent >180 mg/dL decreased by 18% (p=0.0057). As anticipated, the measures of hypoglycemia for type 2 subjects, which were low in the blinded phase, were largely unchanged in the unblinded phase.
  • [0146]
    Accordingly, a continuous analyte monitoring system in one embodiment includes an analyte sensor having at least about 80% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid, a transmitter capable of receiving information from the sensor, and a receiver capable of receiving information from the transmitter.
  • [0147]
    In one aspect, analyte sensor has at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  • [0148]
    In a further aspect, the analyte sensor has at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0149]
    In still a further aspect, the analyte sensor has more than approximately 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0150]
    Additionally, in another aspect, the analyte sensor has at least about 85% of its paired data points within zone A of the Consensus Error Grid, and further, where the analyte sensor has at least about 90% of its paired data points within zone A of the Continuous Glucose Error Grid Analysis.
  • [0151]
    The analyte sensor may be a glucose sensor.
  • [0152]
    In yet another aspect, the system may not require confirmation of analyte data obtained by the system.
  • [0153]
    The system may include a drug delivery device, where one or more of the transmitter and the receiver may be adapted to transmit analyte information to the drug delivery device.
  • [0154]
    In another aspect, the analyte sensor may be calibrated using single point calibration.
  • [0155]
    A continuous analyte monitoring system in accordance with another embodiment includes an analyte sensor having at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Consensus Error Grid, a transmitter capable of receiving information from the sensor, and a receiver capable of receiving information from the transmitter.
  • [0156]
    The analyte sensor may have at least about 85% of its paired data points within zone A of the Consensus Error Grid.
  • [0157]
    The analyte sensor may have at least about 90% of its paired data points within zone A of the Consensus Error Grid.
  • [0158]
    The analyte sensor may have more than approximately 90% of its paired data points within zone A of the Consensus Error Grid.
  • [0159]
    In another aspect, the system may not require confirmation of analyte data obtained by the system.
  • [0160]
    The system may include a drug delivery device, where one or more of the transmitter and the receiver may be adapted to transmit analyte information to the drug delivery device.
  • [0161]
    Also, the analyte sensor may be calibrated using single point calibration.
  • [0162]
    A method of monitoring glucose levels in accordance with still another embodiment includes determining glucose concentration using a first transcutaneously positioned analyte sensor, reporting glucose concentration to a user, where a second sensor is not used to confirm the accuracy of the first transcutaneously positioned analyte sensor.
  • [0163]
    In one aspect, determining may include over a period of time ranging from about 1 day to about 7 days.
  • [0164]
    The first transcutaneously positioned analyte sensor may have at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  • [0165]
    The first transcutaneously positioned analyte sensor may have at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0166]
    The first transcutaneously positioned analyte sensor may have more than about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0167]
    The first transcutaneously positioned analyte sensor may be a glucose sensor.
  • [0168]
    The method in a further aspect may include determining health related information based on the reported glucose concentration, where the health related information may include a bolus amount, or one or more of a food intake, medication dosage level, or activity level.
  • [0169]
    Also, the medication dosage level may include insulin dosage level.
  • [0170]
    In a further aspect, the method may include transmitting the reported glucose concentration, and where transmitting may include one or more of a wired transmission or a wireless transmission.
  • [0171]
    In still another aspect, the method may include calibrating the first transcutaneously positioned analyte sensor using single point calibration.
  • [0172]
    The first transcutaneously positioned analyte sensor may have at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid.
  • [0173]
    The first sensor may have at least about 85% of its paired data points within zone A.
  • [0174]
    A method of monitoring glucose levels in accordance with yet another embodiment includes determining glucose concentration using a first transcutaneously positioned analyte sensor, reporting glucose concentration to a user, where accuracy of the first transcutaneously positioned analyte sensor is established other than with a second sensor.
  • [0175]
    In one aspect, the first transcutaneously positioned analyte sensor has at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  • [0176]
    In another aspect, the first transcutaneously positioned analyte sensor has at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0177]
    In still another aspect, the first transcutaneously positioned analyte sensor has more than about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0178]
    The first transcutaneously positioned analyte sensor may be a glucose sensor.
  • [0179]
    A method of monitoring glucose levels using a single glucose sensor in accordance with still yet a further embodiment includes transcutaneously positioning a glucose sensor in a patient for a period of time, determining glucose concentration of the patient using the transcutaneously positioned glucose sensor, and using one or more additional devices during the period of time only to calibrate the glucose sensor but not to confirm the accuracy of the transcutaneously positioned glucose sensor.
  • [0180]
    The glucose sensor in one embodiment has at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid.
  • [0181]
    The glucose concentration may be determined over a period of time ranging from about 1 day to about 7 days.
  • [0182]
    In a further aspect, the glucose sensor has at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  • [0183]
    In yet another aspect, the glucose sensor has at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0184]
    The glucose sensor in still another aspect has more than approximately 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0185]
    In still a further aspect, the method may include determining a health related information based on the determined glucose concentration, where the health related information includes one or more of a food intake, medication dosage level, or activity level, and further, where medication dosage level includes insulin dosage level.
  • [0186]
    The method may include transmitting data associated with the determined glucose concentration, where transmitting may include one or more of a wired transmission or a wireless transmission.
  • [0187]
    Also, calibration of the glucose sensor may include performing single point calibration.
  • [0188]
    An analyte monitoring system in accordance with still yet another embodiment includes an analyte sensor configured to detect one or more analyte levels of a patient, a transmitter unit operatively coupled to the analyte sensor, the transmitter unit configured to transmit one or more signals associated with the detected one or more analyte levels, and a receiver unit configured to receive the transmitted one or more signals associated with the detected one or more analyte levels, where the accuracy of the detected one or more analyte levels relied upon to make a clinically relevant decision is established without using a blood glucose measurement.
  • [0189]
    In one aspect, the clinically relevant decision may include healthcare decision.
  • [0190]
    The clinically relevant decision may include a bolus amount determination.
  • [0191]
    The blood glucose measurement may include a confirmatory blood glucose measurement.
  • [0192]
    The detected one or more analyte level may be calibrated, for example, using single point calibration.
  • [0193]
    The transmitter unit may be configured to wirelessly transmit the one or more signals to the receiver unit.
  • [0194]
    The analyte sensor in one embodiment has at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid.
  • [0195]
    An analyte monitoring device in accordance with still yet a further embodiment includes a receiver unit for receiving one or more signals related to an analyte level detected by an electrochemical sensor, the receiver unit including a display to display an indication of the analyte level, where the electrochemical sensor has at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid.
  • [0196]
    The electrochemical sensor may have at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  • [0197]
    The electrochemical sensor may have at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0198]
    The electrochemical sensor may have more than approximately 90% of its paired data points within zone A of the Consensus Error Grid.
  • [0199]
    The receiver unit may be configured to calibrate the one or more signals related to the analyte level, and further, where the receiver unit may be configured to display the calibrated one or more signals related to the analyte level without a confirmatory blood glucose measurement.
  • [0200]
    In another aspect, the receiver unit may be configured to calibrate the one or more signals related to the analyte level using single point calibration.
  • [0201]
    The receiver unit may be configured to display the one or more signals related to the analyte level without a confirmatory blood glucose measurement.
  • [0202]
    The receiver unit in one embodiment may include one of an rf receiver or an rf transceiver.
  • [0203]
    The receiver unit in still a further aspect may be configured to calibrate the one or more signals related to the analyte level using a calibration value of less that about one microliter of body fluid, where the body fluid includes blood.
  • [0204]
    The receiver unit may include an alarm configured to indicate when the analyte level is at or near a threshold level.
  • [0205]
    The threshold level may include one of hypoglycemia, impending hypoglycemia, hyperglycemia, or impending hyperglycemia.
  • [0206]
    The alarm may include one or more of an audible signal, a visual display, or a vibratory signal.
  • [0207]
    The alarm may be configured to automatically deactivate after a predetermined time period.
  • [0208]
    The receiver unit in one aspect may be a portable handheld unit.
  • [0209]
    The receiver unit may be configured for wearing on or under an article of clothing.
  • [0210]
    The receiver unit may include an rf transceiver configured to receive or transmit the one or more signals related to an analyte level.
  • [0211]
    In still another aspect, the display may be configured to display one or more of analyte level trend information, rate of change information associated with the analyte level, basal profile information, bolus amount information, or therapy related information.
  • [0212]
    In a further aspect, the receiver may include a blood glucose meter.
  • [0213]
    The display may be configured to display the indication of the analyte level at least one or more of once per minute, once per five minutes, once per ten minutes, or over a predetermined time period, where the predetermined time period may include one or more of less than 24 hour period, one day, three days, seven days, fourteen days, twenty one days, twenty eight days, less than thirty days, or greater than thirty days.
  • [0214]
    A monitoring device in a further embodiment includes a portable housing, an rf receiver coupled to the portable housing, the rf receiver configured to wirelessly receive one or more signals related to an analyte level of a patient detected by an electrochemical sensor, a processing unit coupled to the portable housing and to the rf receiver, the processing unit configured to process the one or more signal received by the rf receiver, and a display unit coupled to the portable housing and the processing unit, the display unit configured to display an indication associated with the one or more signals related to the analyte level of the patient, where the electrochemical sensor has at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Consensus Error Grid.
  • [0215]
    The electrochemical sensor may have at least about 85% of its paired data points within zone A of the Consensus Error Grid.
  • [0216]
    The electrochemical sensor may have at least about 90% of its paired data points within zone A of the Consensus Error Grid.
  • [0217]
    An analyte monitoring device in accordance with still another embodiment includes a receiver unit for receiving one or more signals related to an analyte level detected by an electrochemical sensor, the receiver unit including a display to display an indication of the analyte level, and the receiver unit further configured to process one or more signals related to analyte related therapy for communication with a drug administration system, where the electrochemical sensor has at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid.
  • [0218]
    In one aspect, the electrochemical sensor has at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  • [0219]
    Various other modifications and alterations in the structure and method of operation of this disclosure will be apparent to those skilled in the art without departing from the scope and spirit of the present disclosure. Although the present disclosure has been described in connection with specific embodiments, it should be understood that the embodiments of the present disclosure as claimed should not be unduly limited to such specific embodiments. It is intended that the following claims define the scope of the present disclosure and that structures and methods within the scope of these claims and their equivalents be covered thereby.

Claims (20)

  1. 1. A continuous analyte monitoring system, comprising:
    an analyte sensor having at least about 80% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Clarke Error Grid;
    a transmitter capable of receiving information from the sensor; and
    a receiver capable of receiving information from the transmitter.
  2. 2. The system of claim 1, wherein the analyte sensor has at least about 85% of its paired data points within zone A of the Clarke Error Grid.
  3. 3. The system of claim 1, wherein the analyte sensor has at least about 90% of its paired data points within zone A of the Clarke Error Grid.
  4. 4. The system of claim 1 wherein the analyte sensor has more than approximately 90% of its paired data points within zone A of the Clarke Error Grid.
  5. 5. The system of claim 1, wherein the analyte sensor has at least about 85% of its paired data points within zone A of the Consensus Error Grid.
  6. 6. The system of claim 5, wherein the analyte sensor has at least about 90% of its paired data points within zone A of the Continuous Glucose Error Grid Analysis.
  7. 7. The system of claim 1, wherein the analyte sensor is a glucose sensor.
  8. 8. The system of claim 1, wherein the system does not require confirmation of analyte data obtained by the system.
  9. 9. The system of claim 1, further comprising a drug delivery device.
  10. 10. The system of claim 9, wherein one or more of the transmitter and the receiver is adapted to transmit analyte information to the drug delivery device.
  11. 11. The system of claim 1 wherein the analyte sensor is calibrated using single point calibration.
  12. 12. A continuous analyte monitoring system, comprising:
    an analyte sensor having at least about 85% of its paired data points within zone A and at least about 95% of its paired data points within zone A and zone B of the Consensus Error Grid;
    a transmitter capable of receiving information from the sensor; and
    a receiver capable of receiving information from the transmitter.
  13. 13. The system of claim 12, wherein the analyte sensor has at least about 85% of its paired data points within zone A of the Consensus Error Grid.
  14. 14. The system of claim 12, wherein the analyte sensor has at least about 90% of its paired data points within zone A of the Consensus Error Grid.
  15. 15. The system of claim 12, wherein the analyte sensor has more than approximately 90% of its paired data points within zone A of the Consensus Error Grid.
  16. 16. The system of claim 12, wherein the analyte sensor is a glucose sensor.
  17. 17. The system of claim 12, wherein the system does not require confirmation of analyte data obtained by the system.
  18. 18. The system of claim 12, further comprising a drug delivery device.
  19. 19. The system of claim 18, wherein one or more of the transmitter and the receiver is adapted to transmit analyte information to the drug delivery device.
  20. 20. The system of claim 12 wherein the analyte sensor is calibrated using single point calibration.
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Cited By (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070078322A1 (en) * 2005-09-30 2007-04-05 Abbott Diabetes Care, Inc. Integrated introducer and transmitter assembly and methods of use
US20080300476A1 (en) * 2007-05-31 2008-12-04 Abbott Diabetes Care, Inc. Insertion devices and methods
US20090105570A1 (en) * 2006-03-31 2009-04-23 Abbott Diabetes Care, Inc. Analyte monitoring devices and methods therefor
US20090171269A1 (en) * 2006-06-29 2009-07-02 Abbott Diabetes Care, Inc. Infusion Device and Methods Therefor
US20090247855A1 (en) * 2008-03-28 2009-10-01 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US20100094110A1 (en) * 1998-04-30 2010-04-15 Abbott Diabetes Care Inc. Analyte Monitoring Device and Methods of Use
US7768387B2 (en) 2007-04-14 2010-08-03 Abbott Diabetes Care Inc. Method and apparatus for providing dynamic multi-stage signal amplification in a medical device
US7768386B2 (en) 2007-07-31 2010-08-03 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US20100204557A1 (en) * 2007-02-18 2010-08-12 Abbott Diabetes Care Inc. Multi-Function Analyte Test Device and Methods Therefor
US20100274107A1 (en) * 2008-03-28 2010-10-28 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US7826382B2 (en) 2008-05-30 2010-11-02 Abbott Diabetes Care Inc. Close proximity communication device and methods
US20100280341A1 (en) * 2008-03-28 2010-11-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US7885698B2 (en) 2006-02-28 2011-02-08 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US20110054275A1 (en) * 2009-08-31 2011-03-03 Abbott Diabetes Care Inc. Mounting Unit Having a Sensor and Associated Circuitry
US7928850B2 (en) 2007-05-08 2011-04-19 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US7996158B2 (en) 2007-05-14 2011-08-09 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
WO2011119896A1 (en) 2010-03-24 2011-09-29 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8029441B2 (en) 2006-02-28 2011-10-04 Abbott Diabetes Care Inc. Analyte sensor transmitter unit configuration for a data monitoring and management system
US8066639B2 (en) 2003-06-10 2011-11-29 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US8103471B2 (en) 2007-05-14 2012-01-24 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8112240B2 (en) 2005-04-29 2012-02-07 Abbott Diabetes Care Inc. Method and apparatus for providing leak detection in data monitoring and management systems
US8116840B2 (en) 2003-10-31 2012-02-14 Abbott Diabetes Care Inc. Method of calibrating of an analyte-measurement device, and associated methods, devices and systems
US8121857B2 (en) 2007-02-15 2012-02-21 Abbott Diabetes Care Inc. Device and method for automatic data acquisition and/or detection
US8135548B2 (en) 2006-10-26 2012-03-13 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US8140312B2 (en) 2007-05-14 2012-03-20 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US8140142B2 (en) 2007-04-14 2012-03-20 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US8149117B2 (en) 2007-05-08 2012-04-03 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US20120108929A1 (en) * 1998-04-30 2012-05-03 Abbott Diabetes Care Inc. Analyte Monitoring Device and Methods of Use
US8185181B2 (en) 2009-10-30 2012-05-22 Abbott Diabetes Care Inc. Method and apparatus for detecting false hypoglycemic conditions
US8211016B2 (en) 2006-10-25 2012-07-03 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US8216138B1 (en) 2007-10-23 2012-07-10 Abbott Diabetes Care Inc. Correlation of alternative site blood and interstitial fluid glucose concentrations to venous glucose concentration
US8219173B2 (en) 2008-09-30 2012-07-10 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US8224415B2 (en) 2009-01-29 2012-07-17 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US8239166B2 (en) 2007-05-14 2012-08-07 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8260558B2 (en) 2007-05-14 2012-09-04 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8346335B2 (en) 2008-03-28 2013-01-01 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8368556B2 (en) 2009-04-29 2013-02-05 Abbott Diabetes Care Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US8374668B1 (en) 2007-10-23 2013-02-12 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
US8377031B2 (en) 2007-10-23 2013-02-19 Abbott Diabetes Care Inc. Closed loop control system with safety parameters and methods
US8376945B2 (en) 2006-08-09 2013-02-19 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US8409093B2 (en) 2007-10-23 2013-04-02 Abbott Diabetes Care Inc. Assessing measures of glycemic variability
US8444560B2 (en) 2007-05-14 2013-05-21 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8456301B2 (en) 2007-05-08 2013-06-04 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8473022B2 (en) 2008-01-31 2013-06-25 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US8478557B2 (en) 2009-07-31 2013-07-02 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
US8483967B2 (en) 2009-04-29 2013-07-09 Abbott Diabetes Care Inc. Method and system for providing real time analyte sensor calibration with retrospective backfill
US8497777B2 (en) 2009-04-15 2013-07-30 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
US8514086B2 (en) 2009-08-31 2013-08-20 Abbott Diabetes Care Inc. Displays for a medical device
US8515517B2 (en) 2006-10-02 2013-08-20 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US8545403B2 (en) 2005-12-28 2013-10-01 Abbott Diabetes Care Inc. Medical device insertion
US8560038B2 (en) 2007-05-14 2013-10-15 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8583205B2 (en) 2008-03-28 2013-11-12 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8593109B2 (en) 2006-03-31 2013-11-26 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US8600681B2 (en) 2007-05-14 2013-12-03 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8597188B2 (en) 2007-06-21 2013-12-03 Abbott Diabetes Care Inc. Health management devices and methods
US8617069B2 (en) 2007-06-21 2013-12-31 Abbott Diabetes Care Inc. Health monitor
US8622988B2 (en) 2008-08-31 2014-01-07 Abbott Diabetes Care Inc. Variable rate closed loop control and methods
US8635046B2 (en) 2010-06-23 2014-01-21 Abbott Diabetes Care Inc. Method and system for evaluating analyte sensor response characteristics
US8641618B2 (en) 2007-06-27 2014-02-04 Abbott Diabetes Care Inc. Method and structure for securing a monitoring device element
US8665091B2 (en) 2007-05-08 2014-03-04 Abbott Diabetes Care Inc. Method and device for determining elapsed sensor life
US8676513B2 (en) 2009-01-29 2014-03-18 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US8710993B2 (en) 2011-11-23 2014-04-29 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US8727982B2 (en) 2006-08-07 2014-05-20 Abbott Diabetes Care Inc. Method and system for providing integrated analyte monitoring and infusion system therapy management
US8734422B2 (en) 2008-08-31 2014-05-27 Abbott Diabetes Care Inc. Closed loop control with improved alarm functions
US8771183B2 (en) 2004-02-17 2014-07-08 Abbott Diabetes Care Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US8795252B2 (en) 2008-08-31 2014-08-05 Abbott Diabetes Care Inc. Robust closed loop control and methods
US8834366B2 (en) 2007-07-31 2014-09-16 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor calibration
US8862198B2 (en) 2006-09-10 2014-10-14 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US8920319B2 (en) 2005-11-01 2014-12-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8932216B2 (en) 2006-08-07 2015-01-13 Abbott Diabetes Care Inc. Method and system for providing data management in integrated analyte monitoring and infusion system
US8986208B2 (en) 2008-09-30 2015-03-24 Abbott Diabetes Care Inc. Analyte sensor sensitivity attenuation mitigation
US8993331B2 (en) 2009-08-31 2015-03-31 Abbott Diabetes Care Inc. Analyte monitoring system and methods for managing power and noise
US9008743B2 (en) 2007-04-14 2015-04-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9069536B2 (en) 2011-10-31 2015-06-30 Abbott Diabetes Care Inc. Electronic devices having integrated reset systems and methods thereof
US9078607B2 (en) 2005-11-01 2015-07-14 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9095290B2 (en) 2007-03-01 2015-08-04 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US9125548B2 (en) 2007-05-14 2015-09-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9204827B2 (en) 2007-04-14 2015-12-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9226701B2 (en) 2009-04-28 2016-01-05 Abbott Diabetes Care Inc. Error detection in critical repeating data in a wireless sensor system
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US9317656B2 (en) 2011-11-23 2016-04-19 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
US9314195B2 (en) 2009-08-31 2016-04-19 Abbott Diabetes Care Inc. Analyte signal processing device and methods
US9320461B2 (en) 2009-09-29 2016-04-26 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
US9326709B2 (en) 2010-03-10 2016-05-03 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US9326707B2 (en) 2008-11-10 2016-05-03 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
US9339217B2 (en) 2011-11-25 2016-05-17 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US9351669B2 (en) 2009-09-30 2016-05-31 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
CN105651850A (en) * 2015-11-13 2016-06-08 南京农业大学 Method for detecting residual kanamycin
US9392969B2 (en) 2008-08-31 2016-07-19 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US9398882B2 (en) 2005-09-30 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9402570B2 (en) 2011-12-11 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9402544B2 (en) 2009-02-03 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9474475B1 (en) 2013-03-15 2016-10-25 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
US9501272B2 (en) 2010-05-24 2016-11-22 Abbott Diabetes Care Inc. Systems and methods for updating a medical device
US9521968B2 (en) 2005-09-30 2016-12-20 Abbott Diabetes Care Inc. Analyte sensor retention mechanism and methods of use
US9532737B2 (en) 2011-02-28 2017-01-03 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US9572534B2 (en) 2010-06-29 2017-02-21 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US9615780B2 (en) 2007-04-14 2017-04-11 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9622691B2 (en) 2011-10-31 2017-04-18 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
US9675290B2 (en) 2012-10-30 2017-06-13 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US9743862B2 (en) 2011-03-31 2017-08-29 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US9782076B2 (en) 2006-02-28 2017-10-10 Abbott Diabetes Care Inc. Smart messages and alerts for an infusion delivery and management system
US9788771B2 (en) 2006-10-23 2017-10-17 Abbott Diabetes Care Inc. Variable speed sensor insertion devices and methods of use
US9795331B2 (en) 2005-12-28 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9795326B2 (en) 2009-07-23 2017-10-24 Abbott Diabetes Care Inc. Continuous analyte measurement systems and systems and methods for implanting them
US9907492B2 (en) 2012-09-26 2018-03-06 Abbott Diabetes Care Inc. Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US9931066B2 (en) 2017-05-31 2018-04-03 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods

Families Citing this family (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9282925B2 (en) 2002-02-12 2016-03-15 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US8423113B2 (en) * 2003-07-25 2013-04-16 Dexcom, Inc. Systems and methods for processing sensor data
US8260393B2 (en) 2003-07-25 2012-09-04 Dexcom, Inc. Systems and methods for replacing signal data artifacts in a glucose sensor data stream
US7778680B2 (en) 2003-08-01 2010-08-17 Dexcom, Inc. System and methods for processing analyte sensor data
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
US8369919B2 (en) 2003-08-01 2013-02-05 Dexcom, Inc. Systems and methods for processing sensor data
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US20100168542A1 (en) 2003-08-01 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US8886272B2 (en) * 2004-07-13 2014-11-11 Dexcom, Inc. Analyte sensor
US8761856B2 (en) 2003-08-01 2014-06-24 Dexcom, Inc. System and methods for processing analyte sensor data
US20070208245A1 (en) * 2003-08-01 2007-09-06 Brauker James H Transcutaneous analyte sensor
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US8626257B2 (en) 2003-08-01 2014-01-07 Dexcom, Inc. Analyte sensor
US7933639B2 (en) 2003-08-01 2011-04-26 Dexcom, Inc. System and methods for processing analyte sensor data
US8233959B2 (en) 2003-08-22 2012-07-31 Dexcom, Inc. Systems and methods for processing analyte sensor data
US8010174B2 (en) 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US7519408B2 (en) 2003-11-19 2009-04-14 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US8425417B2 (en) 2003-12-05 2013-04-23 Dexcom, Inc. Integrated device for continuous in vivo analyte detection and simultaneous control of an infusion device
EP2239567B1 (en) 2003-12-05 2015-09-02 DexCom, Inc. Calibration techniques for a continuous analyte sensor
EP1711791B1 (en) 2003-12-09 2014-10-15 DexCom, Inc. Signal processing for continuous analyte sensor
US8452368B2 (en) 2004-07-13 2013-05-28 Dexcom, Inc. Transcutaneous analyte sensor
US7783333B2 (en) 2004-07-13 2010-08-24 Dexcom, Inc. Transcutaneous medical device with variable stiffness
US8251907B2 (en) * 2005-02-14 2012-08-28 Optiscan Biomedical Corporation System and method for determining a treatment dose for a patient
US8880138B2 (en) 2005-09-30 2014-11-04 Abbott Diabetes Care Inc. Device for channeling fluid and methods of use
US7785258B2 (en) 2005-10-06 2010-08-31 Optiscan Biomedical Corporation System and method for determining a treatment dose for a patient
US7766829B2 (en) 2005-11-04 2010-08-03 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US7826879B2 (en) 2006-02-28 2010-11-02 Abbott Diabetes Care Inc. Analyte sensors and methods of use
US20080071157A1 (en) 2006-06-07 2008-03-20 Abbott Diabetes Care, Inc. Analyte monitoring system and method
US20100056993A1 (en) * 2006-07-21 2010-03-04 The Regents Of The University Of Colorado Medical Systems and Methods of Use
US8478377B2 (en) 2006-10-04 2013-07-02 Dexcom, Inc. Analyte sensor
US8275438B2 (en) 2006-10-04 2012-09-25 Dexcom, Inc. Analyte sensor
US8298142B2 (en) 2006-10-04 2012-10-30 Dexcom, Inc. Analyte sensor
US8449464B2 (en) 2006-10-04 2013-05-28 Dexcom, Inc. Analyte sensor
US8364231B2 (en) 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
US8425416B2 (en) * 2006-10-04 2013-04-23 Dexcom, Inc. Analyte sensor
US8364230B2 (en) * 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
US8532730B2 (en) 2006-10-04 2013-09-10 Dexcom, Inc. Analyte sensor
US8562528B2 (en) 2006-10-04 2013-10-22 Dexcom, Inc. Analyte sensor
US8447376B2 (en) 2006-10-04 2013-05-21 Dexcom, Inc. Analyte sensor
US9636450B2 (en) 2007-02-19 2017-05-02 Udo Hoss Pump system modular components for delivering medication and analyte sensing at seperate insertion sites
US20080228056A1 (en) * 2007-03-13 2008-09-18 Michael Blomquist Basal rate testing using frequent blood glucose input
US20080316048A1 (en) * 2007-03-28 2008-12-25 Vmonitor, Inc. System and method for monitoring a well
US20080240105A1 (en) * 2007-03-28 2008-10-02 Vmonitor, Inc. System and method for extending a serial protocol to create a network in a well monitoring environment
US8221345B2 (en) 2007-05-30 2012-07-17 Smiths Medical Asd, Inc. Insulin pump based expert system
EP2152350A4 (en) 2007-06-08 2013-03-27 Dexcom Inc Integrated medicament delivery device for use with continuous analyte sensor
US7972296B2 (en) 2007-10-10 2011-07-05 Optiscan Biomedical Corporation Fluid component analysis system and method for glucose monitoring and control
US8417312B2 (en) 2007-10-25 2013-04-09 Dexcom, Inc. Systems and methods for processing sensor data
US9135402B2 (en) 2007-12-17 2015-09-15 Dexcom, Inc. Systems and methods for processing sensor data
US9839395B2 (en) 2007-12-17 2017-12-12 Dexcom, Inc. Systems and methods for processing sensor data
US20090299155A1 (en) * 2008-01-30 2009-12-03 Dexcom, Inc. Continuous cardiac marker sensor system
WO2009105337A3 (en) * 2008-02-20 2010-12-16 Dexcom, Inc. Continuous medicament sensor system for in vivo use
CA2715628A1 (en) 2008-02-21 2009-08-27 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
US8396528B2 (en) 2008-03-25 2013-03-12 Dexcom, Inc. Analyte sensor
US8924159B2 (en) 2008-05-30 2014-12-30 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US8591410B2 (en) 2008-05-30 2013-11-26 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
WO2010009172A1 (en) 2008-07-14 2010-01-21 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US9161714B2 (en) * 2008-08-21 2015-10-20 Palo Alto Research Center Incorporated Specificity of analyte detection in etalons
US8417311B2 (en) * 2008-09-12 2013-04-09 Optiscan Biomedical Corporation Fluid component analysis system and method for glucose monitoring and control
CA2954728A1 (en) * 2008-09-15 2010-03-18 Deka Products Limited Partnership Systems and methods for fluid delivery
WO2010114929A1 (en) * 2009-03-31 2010-10-07 Abbott Diabetes Care Inc. Overnight closed-loop insulin delivery with model predictive control and glucose measurement error model
WO2010135638A3 (en) * 2009-05-22 2011-06-23 Abbott Diabetes Care Inc. Method and system for reducing false hypoglycemia alarm occurrence
US8641671B2 (en) 2009-07-30 2014-02-04 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
EP2537032A1 (en) * 2010-02-19 2012-12-26 Lightship Medical Limited Subcutaneous glucose sensor
EP2624745A2 (en) * 2010-10-07 2013-08-14 Abbott Diabetes Care, Inc. Analyte monitoring devices and methods
US20130046153A1 (en) 2011-08-16 2013-02-21 Elwha LLC, a limited liability company of the State of Delaware Systematic distillation of status data relating to regimen compliance
US9320465B2 (en) 2012-06-25 2016-04-26 International Business Machines Corporation Bio-chips and nano-biochips
US9119529B2 (en) 2012-10-30 2015-09-01 Dexcom, Inc. Systems and methods for dynamically and intelligently monitoring a host's glycemic condition after an alert is triggered
US9351670B2 (en) 2012-12-31 2016-05-31 Abbott Diabetes Care Inc. Glycemic risk determination based on variability of glucose levels
US9227014B2 (en) 2013-02-07 2016-01-05 The Board Of Trustees Of The Laland Stanford Junior University Kalman filter based on-off switch for insulin pump
US9486171B2 (en) 2013-03-15 2016-11-08 Tandem Diabetes Care, Inc. Predictive calibration
US9492608B2 (en) 2013-03-15 2016-11-15 Tandem Diabetes Care, Inc. Method and device utilizing insulin delivery protocols
CA2945063A1 (en) 2014-04-17 2015-10-22 Z-Integrated Digital Technologies, Inc. Electronic test device data communication
US9669160B2 (en) 2014-07-30 2017-06-06 Tandem Diabetes Care, Inc. Temporary suspension for closed-loop medicament therapy
US20160283343A1 (en) * 2015-03-27 2016-09-29 Ca, Inc. Monitoring environmental parameters associated with computer equipment
WO2016205558A1 (en) 2015-06-18 2016-12-22 Ultradian Diagnostics Llc Methods and devices for determining metabolic states

Citations (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6168568A (en) *
US3635926A (en) * 1969-10-27 1972-01-18 Du Pont Aqueous process for making improved tetrafluoroethylene / fluoroalkyl perfluorovinyl ether copolymers
US3785939A (en) * 1970-10-22 1974-01-15 Conversion Chem Corp Tin/lead plating bath and method
US3930889A (en) * 1974-07-22 1976-01-06 Bell & Howell Company Multiple source battery-powered apparatus
US3933593A (en) * 1971-02-22 1976-01-20 Beckman Instruments, Inc. Rate sensing batch analysis method
US4245634A (en) * 1975-01-22 1981-01-20 Hospital For Sick Children Artificial beta cell
US4247297A (en) * 1979-02-23 1981-01-27 Miles Laboratories, Inc. Test means and method for interference resistant determination of oxidizing substances
US4424125A (en) * 1981-12-14 1984-01-03 Axis Products Limited Separator apparatus
US4425920A (en) * 1980-10-24 1984-01-17 Purdue Research Foundation Apparatus and method for measurement and control of blood pressure
US4427004A (en) * 1981-03-16 1984-01-24 Viridan Inc. Annular flow entrainment nebulizer
US4427770A (en) * 1982-06-14 1984-01-24 Miles Laboratories, Inc. High glucose-determining analytical element
US4494950A (en) * 1982-01-19 1985-01-22 The Johns Hopkins University Plural module medication delivery system
US4633878A (en) * 1983-04-18 1987-01-06 Guiseppe Bombardieri Device for the automatic insulin or glucose infusion in diabetic subjects, based on the continuous monitoring of the patient's glucose, obtained without blood withdrawal
US4633881A (en) * 1982-07-01 1987-01-06 The General Hospital Corporation Ambulatory ventricular function monitor
US4637403A (en) * 1985-04-08 1987-01-20 Garid, Inc. Glucose medical monitoring system
US4717673A (en) * 1984-11-23 1988-01-05 Massachusetts Institute Of Technology Microelectrochemical devices
US4718893A (en) * 1986-02-03 1988-01-12 University Of Minnesota Pressure regulated implantable infusion pump
US4721677A (en) * 1985-09-18 1988-01-26 Children's Hospital Medical Center Implantable gas-containing biosensor and method for measuring an analyte such as glucose
US4721601A (en) * 1984-11-23 1988-01-26 Massachusetts Institute Of Technology Molecule-based microelectronic devices
US4795707A (en) * 1984-11-27 1989-01-03 Hitachi, Ltd. Electrochemical sensor having three layer membrane containing immobilized enzymes
US4796634A (en) * 1985-08-09 1989-01-10 Lawrence Medical Systems, Inc. Methods and apparatus for monitoring cardiac output
US4890620A (en) * 1985-09-20 1990-01-02 The Regents Of The University Of California Two-dimensional diffusion glucose substrate sensing electrode
US4986271A (en) * 1989-07-19 1991-01-22 The University Of New Mexico Vivo refillable glucose sensor
US5082550A (en) * 1989-12-11 1992-01-21 The United States Of America As Represented By The Department Of Energy Enzyme electrochemical sensor electrode and method of making it
US5279294A (en) * 1985-04-08 1994-01-18 Cascade Medical, Inc. Medical diagnostic system
US5379238A (en) * 1989-03-03 1995-01-03 Stark; Edward W. Signal processing method and apparatus
US5593852A (en) * 1993-12-02 1997-01-14 Heller; Adam Subcutaneous glucose electrode
US5711001A (en) * 1992-05-08 1998-01-20 Motorola, Inc. Method and circuit for acquisition by a radio receiver
US5711861A (en) * 1995-11-22 1998-01-27 Ward; W. Kenneth Device for monitoring changes in analyte concentration
US5857967A (en) * 1997-07-09 1999-01-12 Hewlett-Packard Company Universally accessible healthcare devices with on the fly generation of HTML files
US5857983A (en) * 1996-05-17 1999-01-12 Mercury Diagnostics, Inc. Methods and apparatus for sampling body fluid
US5860917A (en) * 1997-01-15 1999-01-19 Chiron Corporation Method and apparatus for predicting therapeutic outcomes
US5861009A (en) * 1997-10-21 1999-01-19 Sulzer Intermedics, Inc. Implantable cardiac stimulator with rate-adaptive T-wave detection
US5861019A (en) * 1997-07-25 1999-01-19 Medtronic Inc. Implantable medical device microstrip telemetry antenna
US5862803A (en) * 1993-09-04 1999-01-26 Besson; Marcus Wireless medical diagnosis and monitoring equipment
US6011984A (en) * 1995-11-22 2000-01-04 Minimed Inc. Detection of biological molecules using chemical amplification and optical sensors
US6013113A (en) * 1998-03-06 2000-01-11 Wilson Greatbatch Ltd. Slotted insulator for unsealed electrode edges in electrochemical cells
US6014577A (en) * 1995-12-19 2000-01-11 Abbot Laboratories Device for the detection of analyte and administration of a therapeutic substance
US6015390A (en) * 1998-06-12 2000-01-18 D. Krag Llc System and method for stabilizing and removing tissue
US6016448A (en) * 1998-10-27 2000-01-18 Medtronic, Inc. Multilevel ERI for implantable medical devices
US6018678A (en) * 1993-11-15 2000-01-25 Massachusetts Institute Of Technology Transdermal protein delivery or measurement using low-frequency sonophoresis
US6017435A (en) * 1995-05-10 2000-01-25 Imperial College Of Science, Technology And Medicine Molecular imaging
US6167614B1 (en) * 1997-10-20 2001-01-02 Micron Technology, Inc. Method of manufacturing and testing an electronic device, and an electronic device
US6168563B1 (en) * 1992-11-17 2001-01-02 Health Hero Network, Inc. Remote health monitoring and maintenance system
US6168568B1 (en) * 1996-10-04 2001-01-02 Karmel Medical Acoustic Technologies Ltd. Phonopneumograph system
US6170318B1 (en) * 1995-03-27 2001-01-09 California Institute Of Technology Methods of use for sensor based fluid detection devices
US6175752B1 (en) * 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US6180416B1 (en) * 1998-09-30 2001-01-30 Cygnus, Inc. Method and device for predicting physiological values
US6275717B1 (en) * 1997-06-16 2001-08-14 Elan Corporation, Plc Device and method of calibrating and testing a sensor for in vivo measurement of an analyte
US6334778B1 (en) * 1994-04-26 2002-01-01 Health Hero Network, Inc. Remote psychological diagnosis and monitoring system
US20020002328A1 (en) * 1994-06-24 2002-01-03 Cygnus, Inc. Device and method for sampling of substances using alternating polarity
US20020002326A1 (en) * 1998-08-18 2002-01-03 Causey James D. Handheld personal data assistant (PDA) with a medical device and method of using the same
US6336900B1 (en) * 1999-04-12 2002-01-08 Agilent Technologies, Inc. Home hub for reporting patient health parameters
US20020004640A1 (en) * 1998-05-13 2002-01-10 Cygnus, Inc. Collection assemblies, laminates, and autosensor assemblies for use in transdermal sampling systems
US6338790B1 (en) * 1998-10-08 2002-01-15 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6340588B1 (en) * 1995-04-25 2002-01-22 Discovery Partners International, Inc. Matrices with memories
US6340421B1 (en) * 2000-05-16 2002-01-22 Minimed Inc. Microelectrogravimetric method for plating a biosensor
US20020010414A1 (en) * 1999-08-25 2002-01-24 Coston Anthony F. Tissue electroperforation for enhanced drug delivery and diagnostic sampling
US20020009810A1 (en) * 1997-06-12 2002-01-24 O'connor Stephen D. Electronics methods for the detection of analytes
US6343225B1 (en) * 1999-09-14 2002-01-29 Implanted Biosystems, Inc. Implantable glucose sensor
US20030004457A1 (en) * 2001-06-26 2003-01-02 Andersson Stig O. Hypodermic implant device
US6505059B1 (en) * 1998-04-06 2003-01-07 The General Hospital Corporation Non-invasive tissue glucose level monitoring
US20030006669A1 (en) * 2001-05-22 2003-01-09 Sri International Rolled electroactive polymers
US6510329B2 (en) * 2001-01-24 2003-01-21 Datex-Ohmeda, Inc. Detection of sensor off conditions in a pulse oximeter
US6512939B1 (en) * 1997-10-20 2003-01-28 Medtronic Minimed, Inc. Implantable enzyme-based monitoring systems adapted for long term use
US20030023182A1 (en) * 2001-07-26 2003-01-30 Mault James R. Respiratory connector for respiratory gas analysis
US20030023317A1 (en) * 2001-07-27 2003-01-30 Dexcom, Inc. Membrane for use with implantable devices
US20030023461A1 (en) * 2001-03-14 2003-01-30 Dan Quintanilla Internet based therapy management system
US20030023171A1 (en) * 2000-02-03 2003-01-30 Katsuhiko Sato Noninvasion biological optical measuring instrument, measured portion holding device, and method for manufacturing the same
US6673625B2 (en) * 1999-09-15 2004-01-06 The Regents Of The University Of California Saccharide sensing molecules having enhanced fluorescent properties
US6673596B1 (en) * 1997-11-25 2004-01-06 Ut-Battelle, Llc In vivo biosensor apparatus and method of use
US20040010207A1 (en) * 2002-07-15 2004-01-15 Flaherty J. Christopher Self-contained, automatic transcutaneous physiologic sensing system
US20040015134A1 (en) * 1998-11-13 2004-01-22 Elan Pharma International, Ltd. Drug delivery systems and methods
US20040015063A1 (en) * 2001-12-21 2004-01-22 Denuzzio John D. Minimally-invasive system and method for monitoring analyte levels
US20040011671A1 (en) * 1997-03-04 2004-01-22 Dexcom, Inc. Device and method for determining analyte levels
US6683040B2 (en) * 1999-12-23 2004-01-27 Ecolab Gmbh & Co. Ohg Peracids with good adhesion to surfaces
US6683535B1 (en) * 2000-08-09 2004-01-27 Alderon Industries, Llc Water detection system and method
US6682938B1 (en) * 1999-09-15 2004-01-27 The Regents Of The University Of California Glucose sensing molecules having selected fluorescent properties
US20040018486A1 (en) * 1998-09-30 2004-01-29 Cygnus, Inc. Method and device for predicting physiological values
USRE38681E1 (en) * 1997-03-25 2005-01-04 Cygnus, Inc. Electrode with improved signal to noise ratio
US6837858B2 (en) * 1996-12-06 2005-01-04 Abbott Laboratories Method and apparatus for obtaining blood for diagnostic tests
US20050004494A1 (en) * 2001-01-22 2005-01-06 Perez Edward P. Lancet device having capillary action
US20050003470A1 (en) * 2003-06-10 2005-01-06 Therasense, Inc. Glucose measuring device for use in personal area network
US6840912B2 (en) * 2001-12-07 2005-01-11 Micronix, Inc Consolidated body fluid testing device and method
US20050010087A1 (en) * 2003-01-07 2005-01-13 Triage Data Networks Wireless, internet-based medical-diagnostic system
US20050010269A1 (en) * 2000-01-21 2005-01-13 Medical Research Group, Inc. Microprocessor controlled ambulatory medical apparatus with hand held communication device
US6844023B2 (en) * 1996-12-20 2005-01-18 Medtronic Minimed, Inc. Alumina insulation for coating implantable components and other microminiature devices
US20060001538A1 (en) * 2004-06-30 2006-01-05 Ulrich Kraft Methods of monitoring the concentration of an analyte
US20060004271A1 (en) * 2004-07-01 2006-01-05 Peyser Thomas A Devices, methods, and kits for non-invasive glucose measurement
US20060001551A1 (en) * 2004-06-30 2006-01-05 Ulrich Kraft Analyte monitoring system with wireless alarm
US20060001550A1 (en) * 1998-10-08 2006-01-05 Mann Alfred E Telemetered characteristic monitor system and method of using the same
US20060010098A1 (en) * 2004-06-04 2006-01-12 Goodnow Timothy T Diabetes care host-client architecture and data management system
US20060015024A1 (en) * 2004-07-13 2006-01-19 Mark Brister Transcutaneous medical device with variable stiffness
US20060015020A1 (en) * 2004-07-06 2006-01-19 Dexcom, Inc. Systems and methods for manufacture of an analyte-measuring device including a membrane system
US20060016700A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060019327A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor

Family Cites Families (1462)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6241704B1 (en) 1901-11-22 2001-06-05 Sims Deltec, Inc. Drug pump systems and methods
US2402306A (en) 1943-10-07 1946-06-18 Turkel Henry Retaining guard guide for needles
US3132123A (en) 1960-11-25 1964-05-05 Du Pont Polymers of perfluoroalkoxy perfluorovinyl ethers
US3210578A (en) 1962-01-12 1965-10-05 Westinghouse Electric Corp Multispeed motor connector
US3260656A (en) 1962-09-27 1966-07-12 Corning Glass Works Method and apparatus for electrolytically determining a species in a fluid
BE629985A (en) 1962-11-29
US3304413A (en) 1963-03-26 1967-02-14 Hewlett Packard Co Cardiac output computer
US3310606A (en) 1963-08-28 1967-03-21 Du Pont Thermosetting perfluorinated divinyl ether resins
US3282875A (en) 1964-07-22 1966-11-01 Du Pont Fluorocarbon vinyl ether polymers
US3397191A (en) 1965-06-02 1968-08-13 Du Pont Fluorocarbon ethers
US3381371A (en) 1965-09-27 1968-05-07 Sanders Associates Inc Method of constructing lightweight antenna
GB1191363A (en) 1968-02-19 1970-05-13 Pavelle Ltd Improvements in or relating to Electronic Thermostats.
US3653841A (en) 1969-12-19 1972-04-04 Hoffmann La Roche Methods and compositions for determining glucose in blood
US3651318A (en) 1970-01-26 1972-03-21 Jan A Czekajewski Cardiac output computer
US3776832A (en) 1970-11-10 1973-12-04 Energetics Science Electrochemical detection cell
USRE31916E (en) 1970-11-10 1985-06-18 Becton Dickinson & Company Electrochemical detection cell
US3719564A (en) 1971-05-10 1973-03-06 Philip Morris Inc Method of determining a reducible gas concentration and sensor therefor
US3698386A (en) 1971-07-16 1972-10-17 Robert Fried Cardiac rhythm computer device
GB1412983A (en) 1971-11-30 1975-11-05 Debell & Richardson Method of producing porous plastic materials
US3943918A (en) 1971-12-02 1976-03-16 Tel-Pac, Inc. Disposable physiological telemetric device
US3768014A (en) 1972-01-28 1973-10-23 Gen Electric Cardiac pacemaker rate/interval computer system
US3837339A (en) 1972-02-03 1974-09-24 Whittaker Corp Blood glucose level monitoring-alarm system and method therefor
US3775182A (en) 1972-02-25 1973-11-27 Du Pont Tubular electrochemical cell with coiled electrodes and compressed central spindle
DE2247608B2 (en) 1972-09-28 1976-07-08 Means and method for the enzymatic determination of glucose
US3949388A (en) 1972-11-13 1976-04-06 Monitron Industries, Inc. Physiological sensor and transmitter
US3908657A (en) 1973-01-15 1975-09-30 Univ Johns Hopkins System for continuous withdrawal of blood
US3929971A (en) 1973-03-30 1975-12-30 Research Corp Porous biomaterials and method of making same
US3826244A (en) 1973-07-20 1974-07-30 Us Health Education & Welfare Thumbtack microelectrode and method of making same
US3851018A (en) 1973-07-31 1974-11-26 Du Pont Crosslinked fluoroelastomer and composition containing same
US4100048A (en) 1973-09-20 1978-07-11 U.S. Philips Corporation Polarographic cell
US3926760A (en) 1973-09-28 1975-12-16 Du Pont Process for electrophoretic deposition of polymer
US4032729A (en) 1973-12-21 1977-06-28 Rockwell International Corporation Low profile keyboard switch having panel hinged actuators and cantilevered beam snap acting contacts
US3898984A (en) 1974-02-04 1975-08-12 Us Navy Ambulatory patient monitoring system
US4146029A (en) 1974-04-23 1979-03-27 Ellinwood Jr Everett H Self-powered implanted programmable medication system and method
US3919051A (en) 1974-07-11 1975-11-11 Honeywell Inc Biological analyzer and method
US3972320A (en) 1974-08-12 1976-08-03 Gabor Ujhelyi Kalman Patient monitoring system
US3966580A (en) 1974-09-16 1976-06-29 The University Of Utah Novel protein-immobilizing hydrophobic polymeric membrane, process for producing same and apparatus employing same
US3957613A (en) 1974-11-01 1976-05-18 General Electric Company Miniature probe having multifunctional electrodes for sensing ions and gases
US4036749A (en) 1975-04-30 1977-07-19 Anderson Donald R Purification of saline water
US4052754A (en) 1975-08-14 1977-10-11 Homsy Charles A Implantable structure
US3979274A (en) 1975-09-24 1976-09-07 The Yellow Springs Instrument Company, Inc. Membrane for enzyme electrodes
DE2645048A1 (en) 1975-10-08 1977-04-21 Gen Electric Einpflanzbarer electrochemical sensor
DE7537747U (en) 1975-11-06 1977-08-11 Bbc Ag Brown, Boveri & Cie, Baden (Schweiz)
FR2334107B1 (en) 1975-12-05 1978-09-22 Pasteur Institut
US4016866A (en) 1975-12-18 1977-04-12 General Electric Company Implantable electrochemical sensor
US4040908A (en) 1976-03-12 1977-08-09 Children's Hospital Medical Center Polarographic analysis of cholesterol and other macromolecular substances
US4055175A (en) 1976-05-07 1977-10-25 Miles Laboratories, Inc. Blood glucose control apparatus
DE2625834C3 (en) 1976-06-09 1989-11-23 Boehringer Mannheim Gmbh, 6800 Mannheim, De
US4024312A (en) 1976-06-23 1977-05-17 Johnson & Johnson Pressure-sensitive adhesive tape having extensible and elastic backing composed of a block copolymer
US4059406A (en) 1976-07-12 1977-11-22 E D T Supplies Limited Electrochemical detector system
US4059708A (en) 1976-07-30 1977-11-22 Bell Telephone Laboratories, Incorporated Method for selective encapsulation
US4076596A (en) 1976-10-07 1978-02-28 Leeds & Northrup Company Apparatus for electrolytically determining a species in a fluid and method of use
US4129128A (en) 1977-02-23 1978-12-12 Mcfarlane Richard H Securing device for catheter placement assembly
FR2387659B1 (en) 1977-04-21 1984-03-09 Armines
US4098574A (en) 1977-08-01 1978-07-04 Eastman Kodak Company Glucose detection system free from fluoride-ion interference
US4178916A (en) 1977-09-26 1979-12-18 Mcnamara Elger W Diabetic insulin alarm system
JPS5912135B2 (en) 1977-09-28 1984-03-21 Matsushita Electric Ind Co Ltd
US4154231A (en) 1977-11-23 1979-05-15 Russell Robert B System for non-invasive cardiac diagnosis
US4151845A (en) 1977-11-25 1979-05-01 Miles Laboratories, Inc. Blood glucose control apparatus
DE2758467C2 (en) 1977-12-28 1985-04-04 Siemens Ag, 1000 Berlin Und 8000 Muenchen, De
JPS5921500B2 (en) 1978-01-28 1984-05-21 Toyo Boseki
DK151000C (en) 1978-02-17 1988-06-13 Radiometer As Method and apparatus for determining a patient's in vivo plasma pH
NL7801867A (en) 1978-02-20 1979-08-22 Philips Nv A device for transcutaneously measuring the partieele pressure of oxygen in blood.
FR2420331B1 (en) 1978-03-23 1982-05-14 Claude Bernard
US4172770A (en) 1978-03-27 1979-10-30 Technicon Instruments Corporation Flow-through electrochemical system analytical method
DE2817363C2 (en) 1978-04-20 1984-01-26 Siemens Ag, 1000 Berlin Und 8000 Muenchen, De
US4259540A (en) 1978-05-30 1981-03-31 Bell Telephone Laboratories, Incorporated Filled cables
DE2827918A1 (en) 1978-06-26 1980-01-10 Vdo Schindling Means for adjusting an electric clock
US4958632A (en) 1978-07-20 1990-09-25 Medtronic, Inc. Adaptable, digital computer controlled cardiac pacemaker
US4344438A (en) 1978-08-02 1982-08-17 The United States Of America As Represented By The Department Of Health, Education And Welfare Optical sensor of plasma constituents
WO1980000453A1 (en) 1978-08-15 1980-03-20 Nat Res Dev Enzymatic processes
US4215703A (en) 1978-08-29 1980-08-05 Willson James K V Variable stiffness guide wire
DE2926647A1 (en) 1978-09-08 1980-03-20 Radelkis Electrokemiai Industrial molekuelselektiver sensor and method of manufacturing the same
EP0010375B1 (en) 1978-10-02 1983-07-20 Xerox Corporation Electrostatographic processing system
US4240438A (en) 1978-10-02 1980-12-23 Wisconsin Alumni Research Foundation Method for monitoring blood glucose levels and elements
JPS584982B2 (en) 1978-10-31 1983-01-28 Matsushita Electric Ind Co Ltd
CA1146607A (en) 1978-12-07 1983-05-17 Robert B. Phillips Target apparatus
US4360019A (en) 1979-02-28 1982-11-23 Andros Incorporated Implantable infusion device
US4275225A (en) 1979-03-14 1981-06-23 E. I. Du Pont De Nemours And Company Polyfluoroallyloxy compounds, their preparation and copolymers therefrom
US4255500A (en) 1979-03-29 1981-03-10 General Electric Company Vibration resistant electrochemical cell having deformed casing and method of making same
US4271449A (en) 1979-04-04 1981-06-02 Rockwell International Corporation Method and apparatus for protecting alternating current circuits
US4253469A (en) 1979-04-20 1981-03-03 The Narda Microwave Corporation Implantable temperature probe
US4731051A (en) 1979-04-27 1988-03-15 The Johns Hopkins University Programmable control means for providing safe and controlled medication infusion
US4573994A (en) 1979-04-27 1986-03-04 The Johns Hopkins University Refillable medication infusion apparatus
USRE32361E (en) 1979-05-14 1987-02-24 Medtronic, Inc. Implantable telemetry transmission system for analog and digital data
US4365637A (en) 1979-07-05 1982-12-28 Dia-Med, Inc. Perspiration indicating alarm for diabetics
US4467811A (en) 1979-08-02 1984-08-28 Children's Hospital Medical Center Method of polarographic analysis of lactic acid and lactate
US4458686A (en) 1979-08-02 1984-07-10 Children's Hospital Medical Center Cutaneous methods of measuring body substances
US4401122A (en) 1979-08-02 1983-08-30 Children's Hospital Medical Center Cutaneous methods of measuring body substances
JPS6129667B2 (en) 1979-08-14 1986-07-08 Tokyo Shibaura Electric Co
US4357282A (en) 1979-08-31 1982-11-02 E. I. Du Pont De Nemours And Company Preparation of fluorocarbonyl compounds
US4293396A (en) 1979-09-27 1981-10-06 Prototech Company Thin carbon-cloth-based electrocatalytic gas diffusion electrodes, and electrochemical cells comprising the same
US4403984A (en) 1979-12-28 1983-09-13 Biotek, Inc. System for demand-based adminstration of insulin
US4345603A (en) 1980-02-19 1982-08-24 Pacesetter Systems, Inc. Implantable battery monitoring means and method
EP0035480B1 (en) 1980-03-05 1984-07-25 Sven-Olof Enfors Enzyme electrode using electrolytic oxygen
NL8001420A (en) 1980-03-10 1981-10-01 Cordis Europ For an electrochemical measurement usable electrode assembly comprising, in particular one as an ISFET carried out assembly, and method of manufacturing the assembly.
US4335255A (en) 1980-04-03 1982-06-15 E. I. Du Pont De Nemours And Company Alkyl perfluoro (2-methyl-5-oxo-3-oxahexanoate)
US4450842A (en) 1980-04-25 1984-05-29 Cordis Corporation Solid state reference electrode
US4340458A (en) 1980-06-02 1982-07-20 Joslin Diabetes Center, Inc. Glucose sensor
US4331869A (en) 1980-06-23 1982-05-25 Capintec, Inc. Dynamic cardiac quality assurance phantom system and method
US4356074A (en) 1980-08-25 1982-10-26 The Yellow Springs Instrument Company, Inc. Substrate specific galactose oxidase enzyme electrodes
US4404066A (en) 1980-08-25 1983-09-13 The Yellow Springs Instrument Company Method for quantitatively determining a particular substrate catalyzed by a multisubstrate enzyme
CA1174284A (en) 1980-09-02 1984-09-11 Medtronic, Inc. Body implantable lead
US4352960A (en) 1980-09-30 1982-10-05 Baptist Medical Center Of Oklahoma, Inc. Magnetic transcutaneous mount for external device of an associated implant
USRE32947E (en) 1980-09-30 1989-06-13 Baptist Medical Center Of Oklahoma, Inc. Magnetic transcutaneous mount for external device of an associated implant
US4444892A (en) 1980-10-20 1984-04-24 Malmros Mark K Analytical device having semiconductive organic polymeric element associated with analyte-binding substance
US4407959A (en) 1980-10-29 1983-10-04 Fuji Electric Co., Ltd. Blood sugar analyzing apparatus
US4420564A (en) 1980-11-21 1983-12-13 Fuji Electric Company, Ltd. Blood sugar analyzer having fixed enzyme membrane sensor
US4327725A (en) 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4483924A (en) 1980-12-09 1984-11-20 Fuji Electric Company, Ltd. System for controlling a printer in a blood sugar analyzer
US4390621A (en) 1980-12-15 1983-06-28 Miles Laboratories, Inc. Method and device for detecting glucose concentration
US4353888A (en) 1980-12-23 1982-10-12 Sefton Michael V Encapsulation of live animal cells
JPH0136063B2 (en) 1981-01-14 1989-07-28 Matsushita Electric Ind Co Ltd
US4407288B1 (en) 1981-02-18 2000-09-19 Mieczyslaw Mirowski Implantable heart stimulator and stimulation method
US4436094A (en) 1981-03-09 1984-03-13 Evreka, Inc. Monitor for continuous in vivo measurement of glucose concentration
US4512348A (en) 1981-04-24 1985-04-23 Kabushiki Kaisha Kyoto Daiichi Kagaku Device for automatically and continuously measuring the constituent parts of blood
US4442841A (en) 1981-04-30 1984-04-17 Mitsubishi Rayon Company Limited Electrode for living bodies
DE3272121D1 (en) 1981-05-07 1986-08-28 Ottosensors Corp Mecidal trial
FR2508305B1 (en) 1981-06-25 1986-04-11 Slama Gerard Device to cause a small bite to collect a drop of blood
US4440175A (en) 1981-08-10 1984-04-03 University Patents, Inc. Membrane electrode for non-ionic species
DE3138194A1 (en) 1981-09-25 1983-04-14 Basf Ag Water-insoluble porous material protein whose production and use
DE3278334D1 (en) 1981-10-23 1988-05-19 Genetics Int Inc Sensor for components of a liquid mixture
US4431004A (en) 1981-10-27 1984-02-14 Bessman Samuel P Implantable glucose sensor
US4418148A (en) 1981-11-05 1983-11-29 Miles Laboratories, Inc. Multilayer enzyme electrode membrane
US4415666A (en) 1981-11-05 1983-11-15 Miles Laboratories, Inc. Enzyme electrode membrane
JPH0147152B2 (en) 1981-11-12 1989-10-12 Wako Pure Chem Ind Ltd
JPS58153154A (en) 1982-03-09 1983-09-12 Ajinomoto Co Inc Qualified electrode
US4417588A (en) 1982-03-22 1983-11-29 Critikon, Inc. Apparatus and method for initiating cardiac output computations
US4581336A (en) 1982-04-26 1986-04-08 Uop Inc. Surface-modified electrodes
FI831399L (en) 1982-04-29 1983-10-30 Agripat Sa Kontaktlinsen of haerdad polyvinylalkohol
JPS6236045B2 (en) 1982-04-30 1987-08-05 Daikin Kogyo Co Ltd
DE3221339A1 (en) 1982-06-05 1983-12-08 Basf Ag A process for the electrochemical hydrogenation of nicotinamide adenine dinucleotide
EP0098592A3 (en) 1982-07-06 1985-08-21 Fujisawa Pharmaceutical Co., Ltd. Portable artificial pancreas
US4509531A (en) 1982-07-28 1985-04-09 Teledyne Industries, Inc. Personal physiological monitor
DE3228551A1 (en) 1982-07-30 1984-02-02 Siemens Ag Method for determining the glucose concentration
US4534356A (en) 1982-07-30 1985-08-13 Diamond Shamrock Chemicals Company Solid state transcutaneous blood gas sensors
US4571292A (en) 1982-08-12 1986-02-18 Case Western Reserve University Apparatus for electrochemical measurements
US4443218A (en) 1982-09-09 1984-04-17 Infusaid Corporation Programmable implantable infusate pump
WO1984001715A1 (en) 1982-10-25 1984-05-10 Hellgren Lars G I Enzyme composition for therapeutical and/or non-therapeutical cleaning, the use thereof and preparation of the composition
US4595479A (en) 1982-11-09 1986-06-17 Ajinomoto Co., Inc. Modified electrode
US4552840A (en) 1982-12-02 1985-11-12 California And Hawaiian Sugar Company Enzyme electrode and method for dextran analysis
US4527240A (en) 1982-12-29 1985-07-02 Kvitash Vadim I Balascopy method for detecting and rapidly evaluating multiple imbalances within multi-parametric systems
CA1231016A (en) 1983-01-23 1988-01-05 Amir Porat Syringe
US4461691A (en) 1983-02-10 1984-07-24 The United States Of America As Represented By The United States Department Of Energy Organic conductive films for semiconductor electrodes
US5059654A (en) 1983-02-14 1991-10-22 Cuno Inc. Affinity matrices of modified polysaccharide supports
US4679562A (en) 1983-02-16 1987-07-14 Cardiac Pacemakers, Inc. Glucose sensor
US4561443A (en) 1983-03-08 1985-12-31 The Johns Hopkins University Coherent inductive communications link for biomedical applications
WO1984003562A1 (en) 1983-03-11 1984-09-13 Matsushita Electric Ind Co Ltd Biosensor
US4506680A (en) 1983-03-17 1985-03-26 Medtronic, Inc. Drug dispensing body implantable lead
US4476003A (en) 1983-04-07 1984-10-09 The United States Of America As Represented By The United States Department Of Energy Chemical anchoring of organic conducting polymers to semiconducting surfaces
FR2544525A1 (en) 1983-04-12 1984-10-19 Simatec Sarl portable input device and related information processing to the health of a person
US5682884A (en) 1983-05-05 1997-11-04 Medisense, Inc. Strip electrode with screen printing
CA1218704A (en) 1983-05-05 1987-03-03 Graham Davis Assay systems using more than one enzyme
CA1220818A (en) 1983-05-05 1987-04-21 Hugh A.O. Hill Assay techniques utilising specific binding agents
CA1226036A (en) 1983-05-05 1987-08-25 Irving J. Higgins Analytical equipment and sensor electrodes therefor
CA1219040A (en) 1983-05-05 1987-03-10 Elliot V. Plotkin Measurement of enzyme-catalysed reactions
US4484987A (en) 1983-05-19 1984-11-27 The Regents Of The University Of California Method and membrane applicable to implantable sensor
US4650547A (en) 1983-05-19 1987-03-17 The Regents Of The University Of California Method and membrane applicable to implantable sensor
US4569589A (en) 1983-05-25 1986-02-11 University Of Pennsylvania Lung water computer system
US5509410A (en) 1983-06-06 1996-04-23 Medisense, Inc. Strip electrode including screen printing of a single layer
US4530696A (en) 1983-06-13 1985-07-23 Institute Of Critical Care Medicine Monitor for intravenous injection system for detecting occlusion and/or infiltration
WO1985000463A1 (en) 1983-07-05 1985-01-31 Matsushita Electric Industrial Co., Ltd. Aluminum electrolytic capacitor and method of manufacture thereof
US4524114A (en) 1983-07-05 1985-06-18 Allied Corporation Bifunctional air electrode
US4538616A (en) 1983-07-25 1985-09-03 Robert Rogoff Blood sugar level sensing and monitoring transducer
US4655880A (en) 1983-08-01 1987-04-07 Case Western Reserve University Apparatus and method for sensing species, substances and substrates using oxidase
US4543955A (en) 1983-08-01 1985-10-01 Cordis Corporation System for controlling body implantable action device
US4554927A (en) 1983-08-30 1985-11-26 Thermometrics Inc. Pressure and temperature sensor
US4544869A (en) 1983-10-05 1985-10-01 Unisen, Inc. Electronic control circuit for bi-directional motion
DE3475834D1 (en) 1983-10-18 1989-02-02 Leo Ab cuvette
US4560534A (en) 1983-11-02 1985-12-24 Miles Laboratories, Inc. Polymer catalyst transducers
US4522690A (en) 1983-12-01 1985-06-11 Honeywell Inc. Electrochemical sensing of carbon monoxide
US4840893A (en) 1983-12-16 1989-06-20 Medisense, Inc. Electrochemical assay for nucleic acids and nucleic acid probes
US4826810A (en) 1983-12-16 1989-05-02 Aoki Thomas T System and method for treating animal body tissues to improve the dietary fuel processing capabilities thereof
US4526948A (en) 1983-12-27 1985-07-02 E. I. Du Pont De Nemours And Company Fluorinated vinyl ethers, copolymers thereof, and precursors thereto
JPS61502402A (en) 1984-04-30 1986-10-23
US4753652A (en) 1984-05-04 1988-06-28 Children's Medical Center Corporation Biomaterial implants which resist calcification
US4883057A (en) 1984-05-09 1989-11-28 Research Foundation, The City University Of New York Cathodic electrochemical current arrangement with telemetric application
NL8401536A (en) 1984-05-11 1985-12-02 Medscan B V I O Blood Sampler.
CA1231136A (en) 1984-06-13 1988-01-05 Ian A. Shanks Capillary action chemical test device
US5141868A (en) 1984-06-13 1992-08-25 Internationale Octrooi Maatschappij "Octropa" Bv Device for use in chemical test procedures
GB8417301D0 (en) 1984-07-06 1984-08-08 Serono Diagnostics Ltd Assay
DK8601218A (en) 1984-07-18 1986-03-17
DE3429596A1 (en) 1984-08-10 1986-02-20 Siemens Ag Device for the physiological frequency control of a stimulation electrode provided with a pacemaker
US4820399A (en) 1984-08-31 1989-04-11 Shimadzu Corporation Enzyme electrodes
US5030333A (en) 1984-09-13 1991-07-09 Children's Hospital Medical Center Polarographic method for measuring both analyte and oxygen with the same detecting electrode of an electroenzymatic sensor
CA1254091A (en) 1984-09-28 1989-05-16 Vladimir Feingold Implantable medication infusion system
JPH0134911Y2 (en) 1984-10-11 1989-10-24
US5171689A (en) 1984-11-08 1992-12-15 Matsushita Electric Industrial Co., Ltd. Solid state bio-sensor
GB8428599D0 (en) 1984-11-13 1984-12-19 Genetics Int Inc Bioelectrochemical assay
US4936956A (en) 1984-11-23 1990-06-26 Massachusetts Institute Of Technology Microelectrochemical devices based on inorganic redox active material and method for sensing
US5034192A (en) 1984-11-23 1991-07-23 Massachusetts Institute Of Technology Molecule-based microelectronic devices
DE3585915D1 (en) 1984-12-28 1992-10-15 Terumo Corp Ion sensor.
US4963595A (en) 1985-01-04 1990-10-16 Thoratec Laboratories Corporation Polysiloxane-polylactone block copolymers
US5235003A (en) 1985-01-04 1993-08-10 Thoratec Laboratories Corporation Polysiloxane-polylactone block copolymers
GB8500729D0 (en) 1985-01-11 1985-02-13 Hill H A O Surface-modified electrode
US5088981A (en) 1985-01-18 1992-02-18 Howson David C Safety enhanced device and method for effecting application of a therapeutic agent
US4577642A (en) 1985-02-27 1986-03-25 Medtronic, Inc. Drug dispensing body implantable lead employing molecular sieves and methods of fabrication
EP0200321A3 (en) 1985-03-20 1987-03-11 Erwin S. Hochmair Transcutaneous signal transmission system
US4681111A (en) 1985-04-05 1987-07-21 Siemens-Pacesetter, Inc. Analog and digital telemetry system for an implantable device
US4787398A (en) 1985-04-08 1988-11-29 Garid, Inc. Glucose medical monitoring system
US4674652A (en) 1985-04-11 1987-06-23 Aten Edward M Controlled dispensing device
US4781798A (en) 1985-04-19 1988-11-01 The Regents Of The University Of California Transparent multi-oxygen sensor array and method of using same
US4671288A (en) 1985-06-13 1987-06-09 The Regents Of The University Of California Electrochemical cell sensor for continuous short-term use in tissues and blood
EP0230472B2 (en) 1985-06-21 2000-12-13 Matsushita Electric Industrial Co., Ltd. Biosensor and method of manufacturing same
US5185256A (en) 1985-06-21 1993-02-09 Matsushita Electric Industrial Co., Ltd. Method for making a biosensor
US4938860A (en) 1985-06-28 1990-07-03 Miles Inc. Electrode for electrochemical sensors
US4835372A (en) 1985-07-19 1989-05-30 Clincom Incorporated Patient care system
US4653513A (en) 1985-08-09 1987-03-31 Dombrowski Mitchell P Blood sampler
US4805624A (en) 1985-09-09 1989-02-21 The Montefiore Hospital Association Of Western Pa Low-potential electrochemical redox sensors
GB8522834D0 (en) 1985-09-16 1985-10-23 Ici Plc Sensor
US4614760A (en) 1985-09-27 1986-09-30 Dow Corning Corporation Low consistency, one-part silicone elastomers
US5111818A (en) 1985-10-08 1992-05-12 Capintec, Inc. Ambulatory physiological evaluation system including cardiac monitoring
US5140393A (en) 1985-10-08 1992-08-18 Sharp Kabushiki Kaisha Sensor device
US5007427A (en) 1987-05-07 1991-04-16 Capintec, Inc. Ambulatory physiological evaluation system including cardiac monitoring
US4920969A (en) 1985-10-08 1990-05-01 Capintec, Inc. Ambulatory physiological evaluation system including cardiac monitoring
US4627908A (en) 1985-10-24 1986-12-09 Chevron Research Company Process for stabilizing lube base stocks derived from bright stock
US4830959A (en) 1985-11-11 1989-05-16 Medisense, Inc. Electrochemical enzymic assay procedures
GB8529300D0 (en) 1985-11-28 1986-01-02 Ici Plc Membrane
EP0226570A3 (en) 1985-12-09 1989-03-15 OttoSensors Corporation Measuring device and tube connection with method of producing the same
US4714462A (en) 1986-02-03 1987-12-22 Intermedics Infusaid, Inc. Positive pressure programmable infusion pump
US4857713A (en) 1986-02-14 1989-08-15 Brown Jack D Hospital error avoidance system
US4755173A (en) 1986-02-25 1988-07-05 Pacesetter Infusion, Ltd. Soft cannula subcutaneous injection set
US4776944A (en) 1986-03-20 1988-10-11 Jiri Janata Chemical selective sensors utilizing admittance modulated membranes
US5137827A (en) 1986-03-25 1992-08-11 Midwest Research Technologies, Inc. Diagnostic element for electrical detection of a binding reaction
JPH0521923B2 (en) 1986-03-26 1993-03-26 Shinetsu Chem Ind Co
US4685463A (en) 1986-04-03 1987-08-11 Williams R Bruce Device for continuous in vivo measurement of blood glucose concentrations
GB8608700D0 (en) 1986-04-10 1986-05-14 Genetics Int Inc Measurement of electroactive species in solution
US4726378A (en) 1986-04-11 1988-02-23 Minnesota Mining And Manufacturing Company Adjustable magnetic supercutaneous device and transcutaneous coupling apparatus
US4994167A (en) 1986-04-15 1991-02-19 Markwell Medical Institute, Inc. Biological fluid measuring device
US4757022A (en) 1986-04-15 1988-07-12 Markwell Medical Institute, Inc. Biological fluid measuring device
US4909908A (en) 1986-04-24 1990-03-20 Pepi Ross Electrochemical cncentration detector method
DE3614821A1 (en) 1986-05-02 1987-11-05 Siemens Ag Implantable, can be calibrated measuring device for a koerpersubstanz and calibration procedures
US4703756A (en) 1986-05-06 1987-11-03 The Regents Of The University Of California Complete glucose monitoring system with an implantable, telemetered sensor module
US4731726A (en) * 1986-05-19 1988-03-15 Healthware Corporation Patient-operated glucose monitor and diabetes management system
GB8612861D0 (en) 1986-05-27 1986-07-02 Cambridge Life Sciences Immobilised enzyme biosensors
US4837049A (en) 1986-06-17 1989-06-06 Alfred E. Mann Foundation For Scientific Research Method of making an electrode array
US4969468A (en) 1986-06-17 1990-11-13 Alfred E. Mann Foundation For Scientific Research Electrode array for use in connection with a living body and method of manufacture
CA1283447C (en) 1986-06-20 1991-04-23 John W. Parce Zero volume electrochemical cell
US5001054A (en) 1986-06-26 1991-03-19 Becton, Dickinson And Company Method for monitoring glucose
JPH0419503B2 (en) 1986-06-27 1992-03-30 Terumo Corp
US4803625A (en) 1986-06-30 1989-02-07 Buddy Systems, Inc. Personal health monitor
US4764416A (en) 1986-07-01 1988-08-16 Mitsubishi Denki Kabushiki Kaisha Electric element circuit using oxidation-reduction substances
US4917800A (en) 1986-07-07 1990-04-17 Bend Research, Inc. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers
US4784736A (en) 1986-07-07 1988-11-15 Bend Research, Inc. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers
US4726716A (en) 1986-07-21 1988-02-23 Mcguire Thomas V Fastener for catheter
GB8618022D0 (en) 1986-07-23 1986-08-28 Unilever Plc Electrochemical measurements
US4698582A (en) 1986-07-23 1987-10-06 Motorola, Inc. Power driver having short circuit protection
US5049487A (en) 1986-08-13 1991-09-17 Lifescan, Inc. Automated initiation of timing of reflectance readings
US4935346A (en) 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
GB8621061D0 (en) 1986-09-01 1986-10-08 Hewlett Packard Ltd User interface simulation
US5002572A (en) 1986-09-11 1991-03-26 Picha George J Biological implant with textured surface
US4894137A (en) * 1986-09-12 1990-01-16 Omron Tateisi Electronics Co. Enzyme electrode
US5055171A (en) 1986-10-06 1991-10-08 T And G Corporation Ionic semiconductor materials and applications thereof
US4889744B1 (en) 1986-11-04 1993-03-09 Method for making open-cell,silicone-elastomer medical implant
US5007929B1 (en) 1986-11-04 1994-08-30 Medical Products Dev Open-cell silicone-elastomer medical implant
US4897162A (en) * 1986-11-14 1990-01-30 The Cleveland Clinic Foundation Pulse voltammetry
JPH0431544B2 (en) 1986-11-20 1992-05-26
US4747828A (en) 1986-12-09 1988-05-31 Fisher Scientific Group IV fluid line occlusion detector
WO1988004456A1 (en) 1986-12-12 1988-06-16 Metrologic Instruments, Inc. Bar code reader with digitizer and sequencer
US4803726A (en) 1986-12-31 1989-02-07 Motorola, Inc. Bit synchronization method for a digital radio telephone system
DE3700119A1 (en) 1987-01-03 1988-07-14 Inst Diabetestechnologie Gemei Implantable electrochemical sensor
EP0274683B1 (en) * 1987-01-08 1991-07-17 Julius Blum Gesellschaft m.b.H. Connecting piece to connect a drawer rail
US4750496A (en) 1987-01-28 1988-06-14 Xienta, Inc. Method and apparatus for measuring blood glucose concentration
US4934369A (en) 1987-01-30 1990-06-19 Minnesota Mining And Manufacturing Company Intravascular blood parameter measurement system
WO1988005643A1 (en) 1987-02-02 1988-08-11 Avl Ag Process and device for determining parameters of interest in living organisms
EP0278647A3 (en) 1987-02-09 1989-09-20 AT&amp;T Corp. Electronchemical processes involving enzymes
GB2201248B (en) 1987-02-24 1991-04-17 Ici Plc Enzyme electrode sensors
US5002054A (en) * 1987-02-25 1991-03-26 Ash Medical Systems, Inc. Interstitial filtration and collection device and method for long-term monitoring of physiological constituents of the body
US4777953A (en) 1987-02-25 1988-10-18 Ash Medical Systems, Inc. Capillary filtration and collection method for long-term monitoring of blood constituents
US4854322A (en) 1987-02-25 1989-08-08 Ash Medical Systems, Inc. Capillary filtration and collection device for long-term monitoring of blood constituents
US4848351A (en) 1987-03-04 1989-07-18 Sentry Medical Products, Inc. Medical electrode assembly
US4923586A (en) 1987-03-31 1990-05-08 Daikin Industries, Ltd. Enzyme electrode unit
US4935345A (en) 1987-04-07 1990-06-19 Arizona Board Of Regents Implantable microelectronic biochemical sensor incorporating thin film thermopile
US4832034A (en) 1987-04-09 1989-05-23 Pizziconi Vincent B Method and apparatus for withdrawing, collecting and biosensing chemical constituents from complex fluids
US4759828A (en) 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
US5352348A (en) 1987-04-09 1994-10-04 Nova Biomedical Corporation Method of using enzyme electrode
US4749985A (en) 1987-04-13 1988-06-07 United States Of America As Represented By The United States Department Of Energy Functional relationship-based alarm processing
US4896142A (en) * 1987-04-16 1990-01-23 Aycox Dale G Moisture detection system for carpet cleaning apparatus
EP0290683A3 (en) 1987-05-01 1988-12-14 Diva Medical Systems B.V. Diabetes management system and apparatus
US5216597A (en) 1987-05-01 1993-06-01 Diva Medical Systems Bv Diabetes therapy management system, apparatus and method
US5074977A (en) 1987-05-05 1991-12-24 The Washington Technology Center Digital biosensors and method of using same
US5198192A (en) 1988-05-18 1993-03-30 Inax Corporation Apparatus for detecting ingredient in urine, a toilet stool equipped with a urine detecting device and a room for urine detecting facility
US5286364A (en) 1987-06-08 1994-02-15 Rutgers University Surface-modified electochemical biosensor
US5540828A (en) 1987-06-08 1996-07-30 Yacynych; Alexander Method for making electrochemical sensors and biosensors having a polymer modified surface
US4810470A (en) 1987-06-19 1989-03-07 Miles Inc. Volume independent diagnostic device
US4822337A (en) 1987-06-22 1989-04-18 Stanley Newhouse Insulin delivery method and apparatus
DE3721237A1 (en) 1987-06-27 1989-01-05 Boehringer Mannheim Gmbh Diagnostic testtraeger and process for its manufacture
JPH07122624B2 (en) 1987-07-06 1995-12-25 ダイキン工業株式会社 Biosensor
US4805625A (en) 1987-07-08 1989-02-21 Ad-Tech Medical Instrument Corporation Sphenoidal electrode and insertion method
US4874500A (en) 1987-07-15 1989-10-17 Sri International Microelectrochemical sensor and sensor array
JPS6423155A (en) 1987-07-17 1989-01-25 Daikin Ind Ltd Electrode refreshing device for biosensor
GB8718430D0 (en) 1987-08-04 1987-09-09 Ici Plc Sensor
WO1989001310A1 (en) 1987-08-11 1989-02-23 Terumo Kabushiki Kaisha Automatic sphygmomanometer
US4897457A (en) * 1987-08-14 1990-01-30 Asahi Glass Company Ltd. Novel fluorine-containing cyclic polymer
US5037527A (en) 1987-08-28 1991-08-06 Kanzaki Paper Mfg. Co., Ltd. Reference electrode and a measuring apparatus using the same
US4858617A (en) 1987-09-10 1989-08-22 Ith, Inc. Cardiac probe enabling use of personal computer for monitoring heart activity or the like
US4974929A (en) 1987-09-22 1990-12-04 Baxter International, Inc. Fiber optical probe connector for physiologic measurement devices
NL8702370A (en) 1987-10-05 1989-05-01 Groningen Science Park A method and system for determination of glucose and therefor useful meetcelsamenstel.
US4845035A (en) 1987-10-06 1989-07-04 The United States Of America As Represented By The Secretary Of Agriculture Enzyme immobilization with a hydrolyzed polysaccharide graft copolymer
US4815469A (en) 1987-10-08 1989-03-28 Siemens-Pacesetter, Inc. Implantable blood oxygen sensor and method of use
GB8725936D0 (en) 1987-11-05 1987-12-09 Genetics Int Inc Sensing system
JPH01140054A (en) * 1987-11-26 1989-06-01 Nec Corp Glucose sensor
US4856340A (en) 1987-12-01 1989-08-15 Minimed Technologies Pressure diaphragm for a medication infusion system
US4852573A (en) 1987-12-04 1989-08-01 Kennedy Philip R Implantable neural electrode
US4838887A (en) 1987-12-15 1989-06-13 Shiley Infusaid Inc. Programmable valve pump
US4813424A (en) 1987-12-23 1989-03-21 University Of New Mexico Long-life membrane electrode for non-ionic species
US5073500A (en) 1988-01-08 1991-12-17 Inax Corporation Method and apparatus for detecting urinary constituents
US4890621A (en) * 1988-01-19 1990-01-02 Northstar Research Institute, Ltd. Continuous glucose monitoring and a system utilized therefor
DE68924026D1 (en) 1988-03-31 1995-10-05 Matsushita Electric Ind Co Ltd Biosensor and its production.
US5034112A (en) 1988-05-19 1991-07-23 Nissan Motor Company, Ltd. Device for measuring concentration of nitrogen oxide in combustion gas
US5126247A (en) 1988-02-26 1992-06-30 Enzymatics, Inc. Method, system and devices for the assay and detection of biochemical molecules
US5108564A (en) 1988-03-15 1992-04-28 Tall Oak Ventures Method and apparatus for amperometric diagnostic analysis
US4957115A (en) 1988-03-25 1990-09-18 New England Medical Center Hosp. Device for determining the probability of death of cardiac patients
US4955861A (en) 1988-04-21 1990-09-11 Therex Corp. Dual access infusion and monitoring system
US4942127A (en) 1988-05-06 1990-07-17 Molecular Devices Corporation Polyredox couples in analyte determinations
US5206145A (en) 1988-05-19 1993-04-27 Thorn Emi Plc Method of measuring the concentration of a substance in a sample solution
US4874499A (en) 1988-05-23 1989-10-17 Massachusetts Institute Of Technology Electrochemical microsensors and method of making such sensors
US4849458A (en) 1988-06-17 1989-07-18 Matrix Medica, Inc. Segmented polyether polyurethane
US5094951A (en) 1988-06-21 1992-03-10 Chiron Corporation Production of glucose oxidase in recombinant systems
US5208147A (en) 1988-07-21 1993-05-04 Radiometer A/S Means for measuring a characteristic in a sample fluid
GB8817421D0 (en) 1988-07-21 1988-08-24 Medisense Inc Bioelectrochemical electrodes
US4925268A (en) 1988-07-25 1990-05-15 Abbott Laboratories Fiber-optic physiological probes
US4954129A (en) 1988-07-25 1990-09-04 Abbott Laboratories Hydrodynamic clot flushing
EP0353328A1 (en) * 1988-08-03 1990-02-07 Dräger Nederland B.V. A polarographic-amperometric three-electrode sensor
US5340722A (en) 1988-08-24 1994-08-23 Avl Medical Instruments Ag Method for the determination of the concentration of an enzyme substrate and a sensor for carrying out the method
US4844076A (en) 1988-08-26 1989-07-04 The Johns Hopkins University Ingestible size continuously transmitting temperature monitoring pill
US5438984A (en) 1988-09-08 1995-08-08 Sudor Partners Apparatus and method for the collection of analytes on a dermal patch
US5264106A (en) 1988-10-07 1993-11-23 Medisense, Inc. Enhanced amperometric sensor
NL8802481A (en) 1988-10-10 1990-05-01 Texas Instruments Holland Transponder as well as method for the manufacture thereof.
US4995402A (en) 1988-10-12 1991-02-26 Thorne, Smith, Astill Technologies, Inc. Medical droplet whole blood and like monitoring
US4920977A (en) 1988-10-25 1990-05-01 Becton, Dickinson And Company Blood collection assembly with lancet and microcollection tube
GB8825800D0 (en) 1988-11-04 1988-12-07 Baker J Cardiac device
JPH02128152A (en) 1988-11-08 1990-05-16 Nec Corp Immobilization of enzyme and biosensor
US5054300A (en) 1988-11-09 1991-10-08 Ohi Seisakusho Co., Ltd. Vehicle door lock system
US5063081A (en) 1988-11-14 1991-11-05 I-Stat Corporation Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
US5200051A (en) 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5360404A (en) 1988-12-14 1994-11-01 Inviro Medical Devices Ltd. Needle guard and needle assembly for syringe
DE3842700A1 (en) 1988-12-19 1990-06-21 Boehringer Mannheim Gmbh A method for protein immobilization on a solid phase, thus produced protein-carrying solid phase, and their use
FI99250C (en) 1989-01-10 1997-12-29 Nintendo Co Ltd The system for preventing unauthorized use of the external memory,
US5068536A (en) 1989-01-19 1991-11-26 Futrex, Inc. Method for providing custom calibration for near infrared instruments for measurement of blood glucose
US5077476A (en) 1990-06-27 1991-12-31 Futrex, Inc. Instrument for non-invasive measurement of blood glucose
EP0385964B1 (en) 1989-01-27 1993-08-11 AVL Medical Instruments AG Biosensor array
US5153827A (en) 1989-01-30 1992-10-06 Omni-Flow, Inc. An infusion management and pumping system having an alarm handling system
US5016201A (en) 1989-02-06 1991-05-14 Bryan Avron I System for calibrating, monitoring and reporting the status of a pH sensor
EP0384504A1 (en) 1989-02-24 1990-08-29 Duphar International Research B.V Detection strip for detecting and identifying chemical air contaminants, and portable detection kit comprising said strips
US5205920A (en) 1989-03-03 1993-04-27 Noboru Oyama Enzyme sensor and method of manufacturing the same
US5269891A (en) 1989-03-09 1993-12-14 Novo Nordisk A/S Method and apparatus for determination of a constituent in a fluid
JPH02298855A (en) 1989-03-20 1990-12-11 Assoc Univ Inc Electrochemical biosensor using immobilized enzyme and redox polymer
US5089112A (en) * 1989-03-20 1992-02-18 Associated Universities, Inc. Electrochemical biosensor based on immobilized enzymes and redox polymers
US4986671A (en) * 1989-04-12 1991-01-22 Luxtron Corporation Three-parameter optical fiber sensor and system
US4953552A (en) 1989-04-21 1990-09-04 Demarzo Arthur P Blood glucose monitoring system
JPH061151Y2 (en) * 1989-04-28 1994-01-12 シャープ株式会社 Tube pressure display device in the infusion pump
EP0396788A1 (en) 1989-05-08 1990-11-14 Dräger Nederland B.V. Process and sensor for measuring the glucose content of glucosecontaining fluids
US5096560A (en) 1989-05-30 1992-03-17 Mitsubishi Petrochemical Co., Ltd. Electrode for electrochemical detectors
US5236567A (en) 1989-05-31 1993-08-17 Nakano Vinegar Co., Ltd. Enzyme sensor
US5139023A (en) 1989-06-02 1992-08-18 Theratech Inc. Apparatus and method for noninvasive blood glucose monitoring
US5198367A (en) 1989-06-09 1993-03-30 Masuo Aizawa Homogeneous amperometric immunoassay
US4899839A (en) 1989-06-14 1990-02-13 Dessertine Albert L Compliance and patient status monitoring system and method
US5016172A (en) 1989-06-14 1991-05-14 Ramp Comsystems, Inc. Patient compliance and status monitoring system
FR2648353B1 (en) 1989-06-16 1992-03-27 Europhor Sa Microdialysis probe
US4927407A (en) 1989-06-19 1990-05-22 Regents Of The University Of Minnesota Cardiac assist pump with steady rate supply of fluid lubricant
DE59005357D1 (en) 1989-07-07 1994-05-19 Disetronic Holding Ag Burgdorf Glucose meter.
US5272060A (en) 1989-07-13 1993-12-21 Kyoto Daiichi Kagaku Co., Ltd. Method for determination of glucose concentration in whole blood
JPH0737991B2 (en) 1989-07-13 1995-04-26 株式会社京都第一科学 Method of measuring the glucose concentration
US5431160A (en) 1989-07-19 1995-07-11 University Of New Mexico Miniature implantable refillable glucose sensor and material therefor
US4979509A (en) 1989-07-19 1990-12-25 Northstar Research Institute, Ltd. Continuous glucose monitoring and a system utilized therefor
US5264104A (en) 1989-08-02 1993-11-23 Gregg Brian A Enzyme electrodes
US5262035A (en) 1989-08-02 1993-11-16 E. Heller And Company Enzyme electrodes
US5264105A (en) 1989-08-02 1993-11-23 Gregg Brian A Enzyme electrodes
US5320725A (en) 1989-08-02 1994-06-14 E. Heller & Company Electrode and method for the detection of hydrogen peroxide
US4944299A (en) 1989-08-08 1990-07-31 Siemens-Pacesetter, Inc. High speed digital telemetry system for implantable device
US4931795A (en) 1989-08-09 1990-06-05 Alfred E. Mann Foundation Digital to analog signal converter
US5101814A (en) 1989-08-11 1992-04-07 Palti Yoram Prof System for monitoring and controlling blood glucose
US5190041A (en) * 1989-08-11 1993-03-02 Palti Yoram Prof System for monitoring and controlling blood glucose
CA2049589A1 (en) 1990-08-24 1992-02-25 Naoki Tsukamura Stool-type apparatus for sampling and assay of urine with swingable carriage
DK0415288T3 (en) 1989-08-25 1996-07-22 Toto Ltd Toilet unit with facilities for inspecting health conditions
US5095904A (en) 1989-09-08 1992-03-17 Cochlear Pty. Ltd. Multi-peak speech procession
US5050612A (en) 1989-09-12 1991-09-24 Matsumura Kenneth N Device for computer-assisted monitoring of the body
US5522865A (en) 1989-09-22 1996-06-04 Alfred E. Mann Foundation For Scientific Research Voltage/current control system for a human tissue stimulator
US4991582A (en) 1989-09-22 1991-02-12 Alfred E. Mann Foundation For Scientific Research Hermetically sealed ceramic and metal package for electronic devices implantable in living bodies
US5084828A (en) * 1989-09-29 1992-01-28 Healthtech Services Corp. Interactive medication delivery system
FR2652736A1 (en) 1989-10-06 1991-04-12 Neftel Frederic Device implantable evaluation of glucose levels.
JPH0414980B2 (en) 1989-10-18 1992-03-16 Nishitomo Kk
EP0429076B1 (en) 1989-11-24 1996-01-31 Matsushita Electric Industrial Co., Ltd. Preparation of biosensor
US5036860A (en) 1989-11-24 1991-08-06 Medical Device Technologies, Inc. Disposable soft tissue biopsy apparatus
US4994068A (en) 1989-11-24 1991-02-19 Unidex, Inc. Combination sterile pad support and lancet containing lancet disposal element
US5067491A (en) 1989-12-08 1991-11-26 Becton, Dickinson And Company Barrier coating on blood contacting devices
US5140985A (en) 1989-12-11 1992-08-25 Schroeder Jon M Noninvasive blood glucose measuring device
US5985129A (en) 1989-12-14 1999-11-16 The Regents Of The University Of California Method for increasing the service life of an implantable sensor
US5342789A (en) 1989-12-14 1994-08-30 Sensor Technologies, Inc. Method and device for detecting and quantifying glucose in body fluids
US6040194A (en) 1989-12-14 2000-03-21 Sensor Technologies, Inc. Methods and device for detecting and quantifying substances in body fluids
US5508171A (en) 1989-12-15 1996-04-16 Boehringer Mannheim Corporation Assay method with enzyme electrode system
KR0171222B1 (en) 1989-12-15 1999-02-18 스티브 올드함 Redox mediator reagent and biosensor
US4990845A (en) 1989-12-18 1991-02-05 Alfred E. Mann Foundation For Scientific Research Floating current source
US5036861A (en) 1990-01-11 1991-08-06 Sembrowich Walter L Method and apparatus for non-invasively monitoring plasma glucose levels
US5127404A (en) 1990-01-22 1992-07-07 Medtronic, Inc. Telemetry format for implanted medical device
US5354319A (en) 1990-01-22 1994-10-11 Medtronic, Inc. Telemetry system for an implantable medical device
US5078854A (en) * 1990-01-22 1992-01-07 Mallinckrodt Sensor Systems, Inc. Polarographic chemical sensor with external reference electrode
US5286362A (en) 1990-02-03 1994-02-15 Boehringer Mannheim Gmbh Method and sensor electrode system for the electrochemical determination of an analyte or an oxidoreductase as well as the use of suitable compounds therefor
US5109850A (en) 1990-02-09 1992-05-05 Massachusetts Institute Of Technology Automatic blood monitoring for medication delivery method and apparatus
US6515593B1 (en) 1995-02-15 2003-02-04 Izex Technologies, Inc. Communication system for an instrumented orthopedic restraining device and method therefor
US5031618A (en) 1990-03-07 1991-07-16 Medtronic, Inc. Position-responsive neuro stimulator
US5131441A (en) 1990-03-20 1992-07-21 Saber Equipment Corporation Fluid dispensing system
US5114678A (en) 1990-03-21 1992-05-19 Miles Inc. Device for wiping a reagent strip
US5016631A (en) 1990-03-23 1991-05-21 The Johns Hopkins University Minimum interface biomedical monitoring system
US5501956A (en) 1990-03-23 1996-03-26 Molecular Devices Corporation Polyredox couples in analyte determinations
US5316008A (en) 1990-04-06 1994-05-31 Casio Computer Co., Ltd. Measurement of electrocardiographic wave and sphygmus
US5165407A (en) 1990-04-19 1992-11-24 The University Of Kansas Implantable glucose sensor
US5161532A (en) 1990-04-19 1992-11-10 Teknekron Sensor Development Corporation Integral interstitial fluid sensor
US5059158A (en) 1990-05-08 1991-10-22 E.B.T., Inc. Electronic transmission control system for a bicycle
US5331555A (en) 1990-05-11 1994-07-19 Sharp Kabushiki Kaisha Electronic apparatus
DK0462426T3 (en) 1990-06-01 1998-02-23 Fidia Spa Biocompatible perforated membranes and their uses as artificial skin
US5265888A (en) 1990-06-22 1993-11-30 Nintendo Co., Ltd. Game apparatus and memory cartridge used therefor
US5147725A (en) 1990-07-03 1992-09-15 Corvita Corporation Method for bonding silicone rubber and polyurethane materials and articles manufactured thereby
US5202261A (en) 1990-07-19 1993-04-13 Miles Inc. Conductive sensors and their use in diagnostic assays
US5250439A (en) 1990-07-19 1993-10-05 Miles Inc. Use of conductive sensors in diagnostic assays
JPH0820412B2 (en) 1990-07-20 1996-03-04 松下電器産業株式会社 Quantitative analysis method using the disposable sensor, and a device
US5182707A (en) * 1990-07-23 1993-01-26 Healthdyne, Inc. Apparatus for recording reagent test strip data by comparison to color lights on a reference panel
US5082796A (en) * 1990-07-24 1992-01-21 National Semiconductor Corporation Use of polysilicon layer for local interconnect in a CMOS or BiCMOS technology incorporating sidewall spacers
US5176662A (en) * 1990-08-23 1993-01-05 Minimed Technologies, Ltd. Subcutaneous injection set with improved cannula mounting arrangement
DE69114505T2 (en) 1990-08-28 1996-04-18 Meadox Medicals Inc Self-supporting woven vascular graft.
US5120421A (en) 1990-08-31 1992-06-09 The United States Of America As Represented By The United States Department Of Energy Electrochemical sensor/detector system and method
GB9019126D0 (en) 1990-09-01 1990-10-17 Cranfield Biotech Ltd Electrochemical biosensor stability
US5217442A (en) 1990-09-28 1993-06-08 Minimed Technologies Aspiration and refill kit for a medication infusion pump
US5431921A (en) 1990-09-28 1995-07-11 Pfizer Inc Dispensing device containing a hydrophobic medium
US5380536A (en) * 1990-10-15 1995-01-10 The Board Of Regents, The University Of Texas System Biocompatible microcapsules
US5251126A (en) 1990-10-29 1993-10-05 Miles Inc. Diabetes data analysis and interpretation method
US5733336A (en) 1990-10-31 1998-03-31 Baxter International, Inc. Ported tissue implant systems and methods of using same
CA2070816A1 (en) 1990-10-31 1992-05-01 James H. Brauker Close vascularization implant material
US5713888A (en) 1990-10-31 1998-02-03 Baxter International, Inc. Tissue implant systems
US5058592A (en) 1990-11-02 1991-10-22 Whisler G Douglas Adjustable mountable doppler ultrasound transducer device
EP0512122A4 (en) 1990-11-22 1993-04-28 Toray Industries, Inc. Implant material
US5176644A (en) * 1990-11-29 1993-01-05 Minimed Technologies, Ltd. Medication infusion pump with improved liquid-vapor pressure reservoir
US5197322A (en) 1990-11-29 1993-03-30 Minimed Technologies, Ltd. Pressure reservoir filling process for an implantable medication infusion pump
JP2646848B2 (en) 1990-11-30 1997-08-27 日本電気株式会社 Method of measuring the glucose sensor
WO1992010133A1 (en) 1990-12-12 1992-06-25 Intelligent Medical Systems, Inc. Infrared thermometer utilizing calibration mapping
NL9002764A (en) 1990-12-14 1992-07-01 Tno Electrode, provided with a polymer coating having a redox enzyme bound thereto.
US5243983A (en) 1990-12-14 1993-09-14 Georgia Tech Research Corporation Non-invasive blood glucose measurement system and method using stimulated raman spectroscopy
US5354449A (en) 1991-01-10 1994-10-11 Band David M pH electrode
US5348788A (en) 1991-01-30 1994-09-20 Interpore Orthopaedics, Inc. Mesh sheet with microscopic projections and holes
FR2673289B1 (en) * 1991-02-21 1994-06-17 Asulab Sa sensor for measuring the quantity of a solution component.
FR2673183B1 (en) 1991-02-21 1996-09-27 Asulab Sa Complex mono, bis or tris (2,2'-bipyridine substituted) of a metal selected from iron, ruthenium, osmium or vanadium and their methods of preparation.
US5232668A (en) 1991-02-27 1993-08-03 Boehringer Mannheim Corporation Test strip holding and reading mechanism for a meter
US5262305A (en) 1991-03-04 1993-11-16 E. Heller & Company Interferant eliminating biosensors
US5192415A (en) 1991-03-04 1993-03-09 Matsushita Electric Industrial Co., Ltd. Biosensor utilizing enzyme and a method for producing the same
CA2050057A1 (en) 1991-03-04 1992-09-05 Adam Heller Interferant eliminating biosensors
US5632272A (en) 1991-03-07 1997-05-27 Masimo Corporation Signal processing apparatus
US5469855A (en) 1991-03-08 1995-11-28 Exergen Corporation Continuous temperature monitor
DE4138702A1 (en) * 1991-03-22 1992-09-24 Madaus Medizin Elektronik Process and apparatus for diagnosis and quantitative analysis of apnea, and for simultaneous determination of other diseases
CA2106378A1 (en) 1991-04-05 1992-10-06 Tom D. Bennett Subcutaneous multi-electrode sensing system
US5208154A (en) 1991-04-08 1993-05-04 The United States Of America As Represented By The Department Of Energy Reversibly immobilized biological materials in monolayer films on electrodes
US5192416A (en) * 1991-04-09 1993-03-09 New Mexico State University Technology Transfer Corporation Method and apparatus for batch injection analysis
US5293546A (en) 1991-04-17 1994-03-08 Martin Marietta Corporation Oxide coated metal grid electrode structure in display devices
US5122925A (en) 1991-04-22 1992-06-16 Control Products, Inc. Package for electronic components
US5397848A (en) 1991-04-25 1995-03-14 Allergan, Inc. Enhancing the hydrophilicity of silicone polymers
EP0585368B1 (en) 1991-04-25 1997-08-06 Brown University Research Foundation Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products
US5271736A (en) 1991-05-13 1993-12-21 Applied Medical Research Collagen disruptive morphology for implants
JP3118015B2 (en) 1991-05-17 2000-12-18 アークレイ株式会社 Biosensors and separation quantification method using the same
US5209229A (en) 1991-05-20 1993-05-11 Telectronics Pacing Systems, Inc. Apparatus and method employing plural electrode configurations for cardioversion of atrial fibrillation in an arrhythmia control system
FI88223C (en) 1991-05-22 1993-04-13 Polar Electro Oy Telemetrisk saendarenhet
US5328460A (en) 1991-06-21 1994-07-12 Pacesetter Infusion, Ltd. Implantable medication infusion pump including self-contained acoustic fault detection apparatus
US5284570A (en) 1991-06-26 1994-02-08 Ppg Industries, Inc. Fluid sample analyte collector and calibration assembly
JP2816262B2 (en) 1991-07-09 1998-10-27 三菱鉛筆株式会社 Carbon microelectrode sensor electrodes and a manufacturing method thereof
DE4123348A1 (en) 1991-07-15 1993-01-21 Boehringer Mannheim Gmbh Electrochemical analysis system
JP2740587B2 (en) * 1991-07-18 1998-04-15 三菱鉛筆株式会社 Fine composite electrode and a manufacturing method thereof
US5453278A (en) 1991-07-24 1995-09-26 Baxter International Inc. Laminated barriers for tissue implants
US5314471A (en) 1991-07-24 1994-05-24 Baxter International Inc. Tissue inplant systems and methods for sustaining viable high cell densities within a host
US5344454A (en) 1991-07-24 1994-09-06 Baxter International Inc. Closed porous chambers for implanting tissue in a host
US5231988A (en) 1991-08-09 1993-08-03 Cyberonics, Inc. Treatment of endocrine disorders by nerve stimulation
US5429129A (en) 1991-08-22 1995-07-04 Sensor Devices, Inc. Apparatus for determining spectral absorption by a specific substance in a fluid
US5284156A (en) 1991-08-30 1994-02-08 M3 Systems, Inc. Automatic tissue sampling apparatus
US5198771A (en) 1991-09-03 1993-03-30 Transducer Research, Inc. Potentiostatic apparatus and methods
DE69210832T2 (en) * 1991-09-13 1996-12-19 Rodney Arthur Stafford An electronic identification system for animals
US5312361A (en) 1991-09-13 1994-05-17 Zadini Filiberto P Automatic cannulation device
GB9120144D0 (en) 1991-09-20 1991-11-06 Imperial College A dialysis electrode device
US5322063A (en) 1991-10-04 1994-06-21 Eli Lilly And Company Hydrophilic polyurethane membranes for electrochemical glucose sensors
US5605162A (en) 1991-10-15 1997-02-25 Advanced Cardiovascular Systems, Inc. Method for using a variable stiffness guidewire
US5264103A (en) 1991-10-18 1993-11-23 Matsushita Electric Industrial Co., Ltd. Biosensor and a method for measuring a concentration of a substrate in a sample
US5249576A (en) 1991-10-24 1993-10-05 Boc Health Care, Inc. Universal pulse oximeter probe
US5217595A (en) 1991-10-25 1993-06-08 The Yellow Springs Instrument Company, Inc. Electrochemical gas sensor
EP0539625A1 (en) 1991-10-28 1993-05-05 Dräger Medical Electronics B.V. Electrochemical sensor for measuring the glucose content of glucose containing fluids
US5866217A (en) 1991-11-04 1999-02-02 Possis Medical, Inc. Silicone composite vascular graft
US5415164A (en) 1991-11-04 1995-05-16 Biofield Corp. Apparatus and method for screening and diagnosing trauma or disease in body tissues
DE4139122C1 (en) 1991-11-28 1993-04-08 Fenzlein, Paul-Gerhard, 8500 Nuernberg, De
US5358514A (en) 1991-12-18 1994-10-25 Alfred E. Mann Foundation For Scientific Research Implantable microdevice with self-attaching electrodes
US5193540A (en) 1991-12-18 1993-03-16 Alfred E. Mann Foundation For Scientific Research Structure and method of manufacture of an implantable microstimulator
US5193539A (en) 1991-12-18 1993-03-16 Alfred E. Mann Foundation For Scientific Research Implantable microstimulator
US5372427A (en) 1991-12-19 1994-12-13 Texas Instruments Incorporated Temperature sensor
US5271815A (en) 1991-12-26 1993-12-21 Via Medical Corporation Method for measuring glucose
US5310469A (en) 1991-12-31 1994-05-10 Abbott Laboratories Biosensor with a membrane containing biologically active material
WO1993013408A1 (en) 1991-12-31 1993-07-08 Abbott Laboratories Composite membrane
US5544651A (en) 1992-09-08 1996-08-13 Wilk; Peter J. Medical system and associated method for automatic treatment
US5285792A (en) 1992-01-10 1994-02-15 Physio-Control Corporation System for producing prioritized alarm messages in a medical instrument
US5246867A (en) 1992-01-17 1993-09-21 University Of Maryland At Baltimore Determination and quantification of saccharides by luminescence lifetimes and energy transfer
DE69215204D1 (en) 1992-01-29 1996-12-19 Hewlett Packard Gmbh A method and system for monitoring vital functions
JPH07508183A (en) 1992-02-01 1995-09-14
NL9200207A (en) 1992-02-05 1993-09-01 Nedap Nv Implantable biomedical sensor device, in particular for measurement of the glucose concentration.
US5284140A (en) 1992-02-11 1994-02-08 Eli Lilly And Company Acrylic copolymer membranes for biosensors
JP3144030B2 (en) 1992-02-24 2001-03-07 東陶機器株式会社 Health management network system
US5431691A (en) 1992-03-02 1995-07-11 Siemens Pacesetter, Inc. Method and system for recording and displaying a sequential series of pacing events
US5309919A (en) 1992-03-02 1994-05-10 Siemens Pacesetter, Inc. Method and system for recording, reporting, and displaying the distribution of pacing events over time and for using same to optimize programming
US5328927A (en) 1992-03-03 1994-07-12 Merck Sharpe & Dohme, Ltd. Hetercyclic compounds, processes for their preparation and pharmaceutical compositions containing them
US5372719A (en) 1992-03-30 1994-12-13 Perseptive Biosystems, Inc. Molecular imaging
JPH05277185A (en) 1992-04-03 1993-10-26 Baxter Internatl Inc Infusion device
US5589563A (en) 1992-04-24 1996-12-31 The Polymer Technology Group Surface-modifying endgroups for biomedical polymers
WO1993022360A1 (en) 1992-04-24 1993-11-11 The Polymer Technology Group, Inc. Copolymers and non-porous, semi-permeable membrane thereof and its use for permeating molecules of predetermined molecular weight range
EP0569618B1 (en) 1992-05-12 1997-01-02 Siemens Aktiengesellschaft Dosing device for the controlled release of a liquid
US5227042A (en) 1992-05-15 1993-07-13 The United States Of America As Represented By The United States Department Of Energy Catalyzed enzyme electrodes
US5580527A (en) 1992-05-18 1996-12-03 Moltech Corporation Polymeric luminophores for sensing of oxygen
US5269212A (en) 1992-05-26 1993-12-14 The Fletcher-Terry Company Mat cutter
GB9211402D0 (en) 1992-05-29 1992-07-15 Univ Manchester Sensor devices
US5330521A (en) 1992-06-29 1994-07-19 Cohen Donald M Low resistance implantable electrical leads
US5337258A (en) 1992-07-10 1994-08-09 Microsoft Corporation Cost metrics
JP2541081B2 (en) * 1992-08-28 1996-10-09 日本電気株式会社 METHOD manufacture and use of biosensors and biosensor
US5330634A (en) 1992-08-28 1994-07-19 Via Medical Corporation Calibration solutions useful for analyses of biological fluids and methods employing same
US5278079A (en) * 1992-09-02 1994-01-11 Enzymatics, Inc. Sealing device and method for inhibition of flow in capillary measuring devices
US6283761B1 (en) 1992-09-08 2001-09-04 Raymond Anthony Joao Apparatus and method for processing and/or for providing healthcare information and/or healthcare-related information
US5452173A (en) 1992-09-08 1995-09-19 Challenge Technologies, Inc. Diagnostic circuit protection device
US5935099A (en) 1992-09-09 1999-08-10 Sims Deltec, Inc. Drug pump systems and methods
CA2079192C (en) 1992-09-25 1995-12-26 Bernard Strong Combined lancet and multi-function cap and lancet injector for use therewith
US5898025A (en) 1992-09-25 1999-04-27 Henkel Kommanditgesellschaft Auf Aktien Mildly alkaline dishwashing detergents
US5259769A (en) 1992-09-29 1993-11-09 Molex Incorporated Electrical connector with preloaded spring-like terminal with improved wiping action
US5376070A (en) 1992-09-29 1994-12-27 Minimed Inc. Data transfer system for an infusion pump
GB9221099D0 (en) 1992-10-07 1992-11-18 Ecossensors Ltd Improvements in and relating to gas permeable membranes for amperometric gas electrodes
US5400782A (en) 1992-10-07 1995-03-28 Graphic Controls Corporation Integral medical electrode including a fusible conductive substrate
US5421816A (en) 1992-10-14 1995-06-06 Endodermic Medical Technologies Company Ultrasonic transdermal drug delivery system
US5750029A (en) 1992-10-16 1998-05-12 Suprex Corporation Method and apparatus for determination of analyte concentration
US5387327A (en) 1992-10-19 1995-02-07 Duquesne University Of The Holy Ghost Implantable non-enzymatic electrochemical glucose sensor
US5320098A (en) 1992-10-20 1994-06-14 Sun Microsystems, Inc. Optical transdermal link
WO1994010553A1 (en) 1992-10-23 1994-05-11 Optex Biomedical, Inc. Fibre-optic probe for the measurement of fluid parameters
US5368224A (en) 1992-10-23 1994-11-29 Nellcor Incorporated Method for reducing ambient noise effects in electronic monitoring instruments
ES2170090T3 (en) 1992-11-09 2002-08-01 Ilife Systems Inc Apparatus and method for remote monitoring of physiological parameters.
US7970620B2 (en) 1992-11-17 2011-06-28 Health Hero Network, Inc. Multi-user remote health monitoring system with biometrics support
US5960403A (en) 1992-11-17 1999-09-28 Health Hero Network Health management process control system
US5899855A (en) 1992-11-17 1999-05-04 Health Hero Network, Inc. Modular microprocessor-based health monitoring system
US5307263A (en) 1992-11-17 1994-04-26 Raya Systems, Inc. Modular microprocessor-based health monitoring system
US20010011224A1 (en) 1995-06-07 2001-08-02 Stephen James Brown Modular microprocessor-based health monitoring system
US5371687A (en) * 1992-11-20 1994-12-06 Boehringer Mannheim Corporation Glucose test data acquisition and management system
US6256522B1 (en) 1992-11-23 2001-07-03 University Of Pittsburgh Of The Commonwealth System Of Higher Education Sensors for continuous monitoring of biochemicals and related method
CA2103325C (en) 1992-11-23 2004-07-20 Kirk W. Johnson Techniques to improve the performance of electrochemical sensors
US5285513A (en) 1992-11-30 1994-02-08 At&T Bell Laboratories Optical fiber cable provided with stabilized waterblocking material
DK148592D0 (en) 1992-12-10 1992-12-10 Novo Nordisk As Apparatus
US5375604A (en) 1992-12-11 1994-12-27 Siemens Medical Electronics, Inc. Transportable modular patient monitor
US5350407A (en) 1992-12-30 1994-09-27 Telectronics Pacing Systems, Inc. Implantable stimulator having quiescent and active modes of operation
US5587273A (en) 1993-01-21 1996-12-24 Advanced Microbotics Corporation Molecularly imprinted materials, method for their preparation and devices employing such materials
US5299571A (en) 1993-01-22 1994-04-05 Eli Lilly And Company Apparatus and method for implantation of sensors
US5371734A (en) 1993-01-29 1994-12-06 Digital Ocean, Inc. Medium access control protocol for wireless network
FR2701117B1 (en) 1993-02-04 1995-03-10 Asulab Sa System of electrochemical measurement multizone sensor, and its application to glucose analysis.
JPH0816669B2 (en) 1993-02-18 1996-02-21 日本電気株式会社 Manufacturing method of the glucose sensor
US5257971A (en) 1993-03-16 1993-11-02 Minimed Technologies, Ltd. Recondition process for a medication infusion pump
US5433710A (en) 1993-03-16 1995-07-18 Minimed, Inc. Medication infusion pump with fluoropolymer valve seat
US5394879A (en) 1993-03-19 1995-03-07 Gorman; Peter G. Biomedical response monitor-exercise equipment and technique using error correction
US5411866A (en) 1993-03-30 1995-05-02 National Research Council Of Canada Method and system for determining bioactive substances
US5257980A (en) 1993-04-05 1993-11-02 Minimed Technologies, Ltd. Subcutaneous injection set with crimp-free soft cannula
EP0622626B1 (en) * 1993-04-23 2002-03-06 Boehringer Mannheim Gmbh System for analysing the components of fluid samples
US5364797A (en) 1993-05-20 1994-11-15 Mobil Oil Corp. Sensor device containing mesoporous crystalline material
EP0700520B1 (en) 1993-05-29 1997-07-30 Cambridge Life Sciences Plc Sensors based on polymer transformation
US5411536A (en) 1993-06-03 1995-05-02 Intermedics, Inc. Method and apparatus for communicating data between medical devices to improve detectability of errors
DE4318519C2 (en) 1993-06-03 1996-11-28 Fraunhofer Ges Forschung An electrochemical sensor
US5366609A (en) 1993-06-08 1994-11-22 Boehringer Mannheim Corporation Biosensing meter with pluggable memory key
US5352351A (en) 1993-06-08 1994-10-04 Boehringer Mannheim Corporation Biosensing meter with fail/safe procedures to prevent erroneous indications
DE4320463A1 (en) 1993-06-21 1994-12-22 Boehringer Mannheim Gmbh Blood lancet device for withdrawing blood for diagnostic purposes
US5642365A (en) 1993-07-05 1997-06-24 Mitsubishi Denki Kabushiki Kaisha Transmitter for encoding error correction codes and a receiver for decoding error correction codes on a transmission frame
WO1995002426A1 (en) 1993-07-13 1995-01-26 Sims Deltec, Inc. Medical pump and method of programming
US5477855A (en) 1993-07-16 1995-12-26 Alfred E. Mann Foundation For Scientific Research Shield for conductors of an implantable device
US6007845A (en) 1994-07-22 1999-12-28 Massachusetts Institute Of Technology Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers
US5413690A (en) 1993-07-23 1995-05-09 Boehringer Mannheim Corporation Potentiometric biosensor and the method of its use
US5410474A (en) 1993-07-27 1995-04-25 Miles Inc. Buttonless memory system for an electronic measurement device
US5368562A (en) 1993-07-30 1994-11-29 Pharmacia Deltec, Inc. Systems and methods for operating ambulatory medical devices such as drug delivery devices
DE4427363A1 (en) 1993-08-03 1995-03-09 A & D Co Ltd A disposable chemical sensor
US5837546A (en) 1993-08-24 1998-11-17 Metrika, Inc. Electronic assay device and method
WO1995006240A1 (en) 1993-08-24 1995-03-02 Metrika Laboratories, Inc. Novel disposable electronic assay device
US5377258A (en) * 1993-08-30 1994-12-27 National Medical Research Council Method and apparatus for an automated and interactive behavioral guidance system
US5456692A (en) 1993-09-03 1995-10-10 Pacesetter, Inc. System and method for noninvasively altering the function of an implanted pacemaker
FR2710413B1 (en) 1993-09-21 1995-11-03 Asulab Sa Measuring device for removable sensors.
EP0644266A1 (en) 1993-09-22 1995-03-22 Siemens Aktiengesellschaft Working electrode for electrochemical-enzymatical sensor systems
EP0670738A1 (en) 1993-09-24 1995-09-13 Baxter International Inc. Methods for enhancing vascularization of implant devices
FR2710537B1 (en) 1993-09-30 1995-12-01 Becton Dickinson Co Method and occlusion detection device in an infusion line.
US5582184A (en) 1993-10-13 1996-12-10 Integ Incorporated Interstitial fluid collection and constituent measurement
DE69322968D1 (en) 1993-10-22 1999-02-18 Siemens Elema Ab Method and device for continuous monitoring of a Anolytpegels
US5781455A (en) 1993-11-02 1998-07-14 Kyoto Daiichi Kagaku Co., Ltd. Article of manufacture comprising computer usable medium for a portable blood sugar value measuring apparatus
JPH07128338A (en) 1993-11-02 1995-05-19 Kyoto Daiichi Kagaku:Kk Convenient blood sugar meter and data managing method therefor
KR970010981B1 (en) 1993-11-04 1997-07-05 구자홍 Alcohol concentration measuring bio-sensor, manufacturing method and related apparatus
US5545220A (en) 1993-11-04 1996-08-13 Lipomatrix Incorporated Implantable prosthesis with open cell textured surface and method for forming same
US5399823A (en) 1993-11-10 1995-03-21 Minimed Inc. Membrane dome switch with tactile feel regulator shim
US5885211A (en) 1993-11-15 1999-03-23 Spectrix, Inc. Microporation of human skin for monitoring the concentration of an analyte
US5458140A (en) 1993-11-15 1995-10-17 Non-Invasive Monitoring Company (Nimco) Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers
US5791344A (en) 1993-11-19 1998-08-11 Alfred E. Mann Foundation For Scientific Research Patient monitoring system
US5497772A (en) 1993-11-19 1996-03-12 Alfred E. Mann Foundation For Scientific Research Glucose monitoring system
US5553616A (en) 1993-11-30 1996-09-10 Florida Institute Of Technology Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator
US5445611A (en) 1993-12-08 1995-08-29 Non-Invasive Monitoring Company (Nimco) Enhancement of transdermal delivery with ultrasound and chemical enhancers
WO1995016970A1 (en) 1993-12-14 1995-06-22 Mochida Pharmaceutical Co., Ltd. Medical measuring apparatus
US5443080A (en) 1993-12-22 1995-08-22 Americate Transtech, Inc. Integrated system for biological fluid constituent analysis
US5437824A (en) 1993-12-23 1995-08-01 Moghan Medical Corp. Method of forming a molded silicone foam implant having open-celled interstices
US5724968A (en) * 1993-12-29 1998-03-10 First Opinion Corporation Computerized medical diagnostic system including meta function
US5589326A (en) 1993-12-30 1996-12-31 Boehringer Mannheim Corporation Osmium-containing redox mediator
US5549675A (en) 1994-01-11 1996-08-27 Baxter International, Inc. Method for implanting tissue in a host
DE4401400A1 (en) 1994-01-19 1995-07-20 Ernst Prof Dr Pfeiffer Method and apparatus for continuously monitoring the concentration of a metabolite
FR2715566B1 (en) 1994-02-03 1996-03-08 Synthelabo A concentrated aqueous solution of argatroban.
WO1995022051A1 (en) 1994-02-09 1995-08-17 Abbott Laboratories Diagnostic flow cell device
FI95574C (en) 1994-02-16 1996-02-26 Valtion Teknillinen The electron-conducting molecular preparation
US5437999A (en) 1994-02-22 1995-08-01 Boehringer Mannheim Corporation Electrochemical sensor
US5536249A (en) 1994-03-09 1996-07-16 Visionary Medical Products, Inc. Pen-type injector with a microprocessor and blood characteristic monitor
US5531679A (en) 1994-03-14 1996-07-02 Schulman; Joseph H. Fluidic infusion system for catheter or probe
US5391250A (en) * 1994-03-15 1995-02-21 Minimed Inc. Method of fabricating thin film sensors
US5390671A (en) * 1994-03-15 1995-02-21 Minimed Inc. Transcutaneous sensor insertion set
DE4408718A1 (en) 1994-03-15 1995-09-21 Henkel Kgaa Breakage and storage stable, polyfunctional cleaning tablets, processes for their preparation and their use
EP0672427A1 (en) 1994-03-17 1995-09-20 Siemens Elema AB System for infusion of medicine into the body of a patient
US5456940A (en) 1994-03-28 1995-10-10 Minimed Inc. System for lubricating a syringe barrel
US5527307A (en) 1994-04-01 1996-06-18 Minimed Inc. Implantable medication infusion pump with discharge side port
US5505713A (en) 1994-04-01 1996-04-09 Minimed Inc. Indwelling catheter with stable enzyme coating
US5609575A (en) * 1994-04-11 1997-03-11 Graseby Medical Limited Infusion pump and method with dose-rate calculation
US5451260A (en) 1994-04-15 1995-09-19 Cornell Research Foundation, Inc. Method and apparatus for CVD using liquid delivery system with an ultrasonic nozzle
US5569186A (en) 1994-04-25 1996-10-29 Minimed Inc. Closed loop infusion pump system with removable glucose sensor
JP3061351B2 (en) 1994-04-25 2000-07-10 松下電器産業株式会社 Determination and its apparatus of the specific compound
EP0760138A4 (en) 1994-04-26 1998-04-01 Raya Systems Inc Modular microprocessor-based diagnostic measurement system for psychological conditions
US5940801A (en) 1994-04-26 1999-08-17 Health Hero Network, Inc. Modular microprocessor-based diagnostic measurement apparatus and method for psychological conditions
US5370622A (en) 1994-04-28 1994-12-06 Minimed Inc. Proctective case for a medication infusion pump
US5584876A (en) 1994-04-29 1996-12-17 W. L. Gore & Associates, Inc. Cell excluding sheath for vascular grafts
US5476460A (en) 1994-04-29 1995-12-19 Minimed Inc. Implantable infusion port with reduced internal volume
CA2189542A1 (en) 1994-05-03 1995-11-09 Karen M. Oxenbýll Alkaline glucose oxidase
DE4415896A1 (en) 1994-05-05 1995-11-09 Boehringer Mannheim Gmbh Analysis system for monitoring the concentration of an analyte in the blood of a patient
US5710630A (en) * 1994-05-05 1998-01-20 Boehringer Mannheim Gmbh Method and apparatus for determining glucose concentration in a biological sample
US5545191A (en) 1994-05-06 1996-08-13 Alfred E. Mann Foundation For Scientific Research Method for optimally positioning and securing the external unit of a transcutaneous transducer of the skin of a living body
US5484404A (en) * 1994-05-06 1996-01-16 Alfred E. Mann Foundation For Scientific Research Replaceable catheter system for physiological sensors, tissue stimulating electrodes and/or implantable fluid delivery systems
US5651767A (en) 1994-05-06 1997-07-29 Alfred F. Mann Foundation For Scientific Research Replaceable catheter system for physiological sensors, stimulating electrodes and/or implantable fluid delivery systems
US5482473A (en) * 1994-05-09 1996-01-09 Minimed Inc. Flex circuit connector
US6330426B2 (en) 1994-05-23 2001-12-11 Stephen J. Brown System and method for remote education using a memory card
US5678571A (en) 1994-05-23 1997-10-21 Raya Systems, Inc. Method for treating medical conditions using a microprocessor-based video game
US5913310A (en) 1994-05-23 1999-06-22 Health Hero Network, Inc. Method for diagnosis and treatment of psychological and emotional disorders using a microprocessor-based video game
US6186145B1 (en) 1994-05-23 2001-02-13 Health Hero Network, Inc. Method for diagnosis and treatment of psychological and emotional conditions using a microprocessor-based virtual reality simulator
US5918603A (en) 1994-05-23 1999-07-06 Health Hero Network, Inc. Method for treating medical conditions using a microprocessor-based video game
JP3027306B2 (en) 1994-06-02 2000-04-04 松下電器産業株式会社 Biosensor and a method of manufacturing the same
US6932084B2 (en) 1994-06-03 2005-08-23 Ric Investments, Inc. Method and apparatus for providing positive airway pressure to a patient
DE59509994D1 (en) 1994-06-03 2002-02-21 Metrohm Ag Herisau Apparatus for voltammetry, indicator electrode assembly for such a device, in particular as part of a tape cartridge, and series analysis method for voltammetry
US5472317A (en) 1994-06-03 1995-12-05 Minimed Inc. Mounting clip for a medication infusion pump
US5462525A (en) 1994-06-14 1995-10-31 Minimed, Inc., A Delaware Corporation Flow sensor for an infusion pump
US5514103A (en) 1994-06-14 1996-05-07 Minimed Inc. Medication infusion pump with improved pressure reservoir
US5460618A (en) 1994-06-20 1995-10-24 Minimed Inc. Side slit catheter
DE4422068A1 (en) * 1994-06-23 1996-01-04 Siemens Ag Electro-catalytic glucose sensor in catheter form
US5474552A (en) 1994-06-27 1995-12-12 Cb-Carmel Biotechnology Ltd. Implantable drug delivery pump
US5494562A (en) 1994-06-27 1996-02-27 Ciba Corning Diagnostics Corp. Electrochemical sensors
EP0715779B1 (en) 1994-06-28 1998-09-30 Philips Electronics N.V. Circuit arrangement
US5514253A (en) 1994-07-13 1996-05-07 I-Stat Corporation Method of measuring gas concentrations and microfabricated sensing device for practicing same
US5605152A (en) 1994-07-18 1997-02-25 Minimed Inc. Optical glucose sensor
US5582593A (en) 1994-07-21 1996-12-10 Hultman; Barry W. Ambulatory medication delivery system
US5720733A (en) 1994-07-22 1998-02-24 Raya Systems, Inc. Apparatus for determining and recording injection doses in syringes using electrical capacitance measurements
US5792117A (en) 1994-07-22 1998-08-11 Raya Systems, Inc. Apparatus for optically determining and electronically recording injection doses in syringes
US6110148A (en) 1994-07-22 2000-08-29 Health Hero Network, Inc. Capacitance-based dose measurements in syringes
US5782814A (en) 1994-07-22 1998-07-21 Raya Systems, Inc. Apparatus for determining and recording injection doses in syringes using electrical inductance
US5569212A (en) 1994-07-22 1996-10-29 Raya Systems, Inc. Apparatus for electrically determining injection doses in syringes
US6068615A (en) 1994-07-22 2000-05-30 Health Hero Network, Inc. Inductance-based dose measurement in syringes
US5695473A (en) 1994-07-27 1997-12-09 Sims Deltec, Inc. Occlusion detection system for an infusion pump
US5629981A (en) 1994-07-29 1997-05-13 Texas Instruments Incorporated Information management and security system
US5518006A (en) 1994-08-09 1996-05-21 International Technidyne Corp. Blood sampling device
US5513636A (en) 1994-08-12 1996-05-07 Cb-Carmel Biotechnology Ltd. Implantable sensor chip
DE4430023A1 (en) 1994-08-24 1996-02-29 Boehringer Mannheim Gmbh An electrochemical sensor
US5462051A (en) 1994-08-31 1995-10-31 Colin Corporation Medical communication system
US5837276A (en) 1994-09-02 1998-11-17 Delab Apparatus for the delivery of elongate solid drug compositions
US5526120A (en) 1994-09-08 1996-06-11 Lifescan, Inc. Test strip with an asymmetrical end insuring correct insertion for measuring
US5505709A (en) 1994-09-15 1996-04-09 Minimed, Inc., A Delaware Corporation Mated infusion pump and syringe
US5624537A (en) 1994-09-20 1997-04-29 The University Of British Columbia - University-Industry Liaison Office Biosensor and interface membrane
US5549115A (en) 1994-09-28 1996-08-27 Heartstream, Inc. Method and apparatus for gathering event data using a removable data storage medium and clock
US5807406A (en) 1994-10-07 1998-09-15 Baxter International Inc. Porous microfabricated polymer membrane structures
US5667983A (en) 1994-10-24 1997-09-16 Chiron Diagnostics Corporation Reagents with enhanced performance in clinical diagnostic systems
US5545152A (en) 1994-10-28 1996-08-13 Minimed Inc. Quick-connect coupling for a medication infusion system
CA2159052C (en) 1994-10-28 2007-03-06 Rainer Alex Injection device
US5551953A (en) 1994-10-31 1996-09-03 Alza Corporation Electrotransport system with remote telemetry link
JPH10508518A (en) 1994-11-04 1998-08-25 イーラン・メディカル・テクノロジーズ・リミテッド Liquid is regulated by analyte dispensing device and analyte monitoring
US5601435A (en) * 1994-11-04 1997-02-11 Intercare Method and apparatus for interactively monitoring a physiological condition and for interactively providing health related information
US5487751A (en) * 1994-11-04 1996-01-30 Physio-Control Corporation Mechanical connector for securing compatible medical instruments together
US5573506A (en) 1994-11-25 1996-11-12 Block Medical, Inc. Remotely programmable infusion system
EP0718010B1 (en) 1994-12-15 2003-02-19 St. Jude Medical AB Magnetic field detector unit
US5571682A (en) 1994-12-22 1996-11-05 Johnson & Johnson Clinical Diagnostics, Inc. Calibrating and testing immunoassays to minimize interferences
EP0722691A1 (en) 1994-12-24 1996-07-24 Boehringer Mannheim Gmbh System for determining properties of tissue
US5637095A (en) 1995-01-13 1997-06-10 Minimed Inc. Medication infusion pump with flexible drive plunger
US5590651A (en) * 1995-01-17 1997-01-07 Temple University - Of The Commonwealth System Of Higher Education Breathable liquid elimination analysis
US5562713A (en) 1995-01-18 1996-10-08 Pacesetter, Inc. Bidirectional telemetry apparatus and method for implantable device
US5697366A (en) 1995-01-27 1997-12-16 Optical Sensors Incorporated In situ calibration system for sensors located in a physiologic line
US5837728A (en) 1995-01-27 1998-11-17 Molecular Design International 9-cis retinoic acid esters and amides and uses thereof
US5676820A (en) 1995-02-03 1997-10-14 New Mexico State University Technology Transfer Corp. Remote electrochemical sensor
US6153069A (en) 1995-02-09 2000-11-28 Tall Oak Ventures Apparatus for amperometric Diagnostic analysis
US5551427A (en) 1995-02-13 1996-09-03 Altman; Peter A. Implantable device for the effective elimination of cardiac arrhythmogenic sites
US5568806A (en) 1995-02-16 1996-10-29 Minimed Inc. Transcutaneous sensor insertion set
US5586553A (en) 1995-02-16 1996-12-24 Minimed Inc. Transcutaneous sensor insertion set
US5651869A (en) 1995-02-28 1997-07-29 Matsushita Electric Industrial Co., Ltd. Biosensor
US5647853A (en) 1995-03-03 1997-07-15 Minimed Inc. Rapid response occlusion detector for a medication infusion pump
US5596150A (en) * 1995-03-08 1997-01-21 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Capacitance probe for fluid flow and volume measurements
CA2213854C (en) 1995-03-10 2010-08-10 Meso Scale Technologies, Llc Multi-array, multi-specific electrochemiluminescence testing
JPH08247987A (en) * 1995-03-15 1996-09-27 Omron Corp Portable measuring instrument
US5582697A (en) 1995-03-17 1996-12-10 Matsushita Electric Industrial Co., Ltd. Biosensor, and a method and a device for quantifying a substrate in a sample liquid using the same
US5650062A (en) 1995-03-17 1997-07-22 Matsushita Electric Industrial Co., Ltd. Biosensor, and a method and a device for quantifying a substrate in a sample liquid using the same
US5882494A (en) 1995-03-27 1999-03-16 Minimed, Inc. Polyurethane/polyurea compositions containing silicone for biosensor membranes
US5607565A (en) 1995-03-27 1997-03-04 Coulter Corporation Apparatus for measuring analytes in a fluid sample
JP3498105B2 (en) 1995-04-07 2004-02-16 アークレイ株式会社 Sensors, measuring methods of using the manufacturing method and sensor
US5695949A (en) 1995-04-07 1997-12-09 Lxn Corp. Combined assay for current glucose level and intermediate or long-term glycemic control
FR2733104B1 (en) 1995-04-12 1997-06-06 Droz Francois Answering small size and method of manufacture of such answering machines
DE19515524C2 (en) 1995-04-27 1999-09-09 Private Uni Witten Herdecke Gm Method and apparatus for the continuous detection of at least one substance in a gaseous or liquid mixture by means of a sensor electrode
US5620579A (en) 1995-05-05 1997-04-15 Bayer Corporation Apparatus for reduction of bias in amperometric sensors
US5752512A (en) 1995-05-10 1998-05-19 Massachusetts Institute Of Technology Apparatus and method for non-invasive blood analyte measurement
US5876484A (en) 1995-05-17 1999-03-02 Phytotech, Inc. Method for removing soluble metals from an aqueous phase
US5628310A (en) 1995-05-19 1997-05-13 Joseph R. Lakowicz Method and apparatus to perform trans-cutaneous analyte monitoring
US5640764A (en) 1995-05-22 1997-06-24 Alfred E. Mann Foundation For Scientific Research Method of forming a tubular feed-through hermetic seal for an implantable medical device
US6035237A (en) 1995-05-23 2000-03-07 Alfred E. Mann Foundation Implantable stimulator that prevents DC current flow without the use of discrete output coupling capacitors
US5665065A (en) 1995-05-26 1997-09-09 Minimed Inc. Medication infusion device with blood glucose data input
US5806517A (en) 1995-05-26 1998-09-15 The Regents Of The University Of Colorado In vivo electrochemistry computer system and method
WO1996037527A1 (en) 1995-05-26 1996-11-28 Igen, Inc. Molecularly imprinted beaded polymers and stabilized suspension polymerization of the same in perfluorocarbon liquids
US5623925A (en) 1995-06-05 1997-04-29 Cmed, Inc. Virtual medical instrument for performing medical diagnostic testing on patients
US5567302A (en) 1995-06-07 1996-10-22 Molecular Devices Corporation Electrochemical system for rapid detection of biochemical agents that catalyze a redox potential change
US5626561A (en) 1995-06-07 1997-05-06 Gore Hybrid Technologies, Inc. Implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein
US5721783A (en) 1995-06-07 1998-02-24 Anderson; James C. Hearing aid with wireless remote processor
US5743262A (en) 1995-06-07 1998-04-28 Masimo Corporation Blood glucose monitoring system
US5584813A (en) 1995-06-07 1996-12-17 Minimed Inc. Subcutaneous injection set
DE69630266D1 (en) 1995-06-07 2003-11-13 Gore Hybrid Technologies Inc Implantable cradle for a therapeutic device
US5653735A (en) 1995-06-28 1997-08-05 Pacesetter, Inc. Implantable cardiac stimulation device having an improved backup mode of operation and method thereof
US5840148A (en) 1995-06-30 1998-11-24 Bio Medic Data Systems, Inc. Method of assembly of implantable transponder
US5995860A (en) 1995-07-06 1999-11-30 Thomas Jefferson University Implantable sensor and system for measurement and control of blood constituent levels
CA2259254C (en) 1996-07-08 2008-02-19 Animas Corporation Implantable sensor and system for in vivo measurement and control of fluid constituent levels
US5611900A (en) 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
US6002961A (en) 1995-07-25 1999-12-14 Massachusetts Institute Of Technology Transdermal protein delivery using low-frequency sonophoresis
US6001471A (en) 1995-08-11 1999-12-14 3M Innovative Properties Company Removable adhesive tape with controlled sequential release
US5750926A (en) 1995-08-16 1998-05-12 Alfred E. Mann Foundation For Scientific Research Hermetically sealed electrical feedthrough for use with implantable electronic devices
DE19530376C2 (en) 1995-08-18 1999-09-02 Fresenius Ag biosensor
US6034622A (en) 1995-08-18 2000-03-07 Robert A. Levine Location monitoring via implanted radio transmitter
US5786584A (en) 1995-09-06 1998-07-28 Eli Lilly And Company Vial and cartridge reading device providing audio feedback for a blood glucose monitoring system
US5682233A (en) 1995-09-08 1997-10-28 Integ, Inc. Interstitial fluid sampler
US5989409A (en) 1995-09-11 1999-11-23 Cygnus, Inc. Method for glucose sensing
US5735273A (en) 1995-09-12 1998-04-07 Cygnus, Inc. Chemical signal-impermeable mask
US5628890A (en) 1995-09-27 1997-05-13 Medisense, Inc. Electrochemical sensor
US6689265B2 (en) 1995-10-11 2004-02-10 Therasense, Inc. Electrochemical analyte sensors using thermostable soybean peroxidase
US5665222A (en) 1995-10-11 1997-09-09 E. Heller & Company Soybean peroxidase electrochemical sensor
US5741211A (en) 1995-10-26 1998-04-21 Medtronic, Inc. System and method for continuous monitoring of diabetes-related blood constituents
JP3592416B2 (en) 1995-10-31 2004-11-24 晃敏 吉田 Apparatus for measuring intraocular substance
US5701894A (en) 1995-11-09 1997-12-30 Del Mar Avionics Modular physiological computer-recorder
JP4307550B2 (en) 1995-11-13 2009-08-05 メドトロニック ミニメッド、 インコーポレイティド Methods and compositions for delivery of monomeric protein
US5748103A (en) 1995-11-13 1998-05-05 Vitalcom, Inc. Two-way TDMA telemetry system with power conservation features
DE19543020A1 (en) 1995-11-18 1997-05-22 Boehringer Mannheim Gmbh Method and apparatus for determining analytical data concerning the inside of a scattering matrix
US6766183B2 (en) 1995-11-22 2004-07-20 Medtronic Minimed, Inc. Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers
WO1998022820A1 (en) 1996-11-21 1998-05-28 Lawrence Livermore National Laboratory Detection of biological molecules using boronate-based chemical amplification and optical sensors
US6002954A (en) 1995-11-22 1999-12-14 The Regents Of The University Of California Detection of biological molecules using boronate-based chemical amplification and optical sensors
US5981294A (en) 1995-11-29 1999-11-09 Metrika, Inc. Device for blood separation in a diagnostic device
US6063637A (en) 1995-12-13 2000-05-16 California Institute Of Technology Sensors for sugars and other metal binding analytes
US5730654A (en) 1995-12-18 1998-03-24 Raya Systems, Inc. Multi-player video game for health education
US5947921A (en) 1995-12-18 1999-09-07 Massachusetts Institute Of Technology Chemical and physical enhancers and ultrasound for transdermal drug delivery
US6041253A (en) 1995-12-18 2000-03-21 Massachusetts Institute Of Technology Effect of electric field and ultrasound for transdermal drug delivery
WO1997024059A1 (en) 1995-12-28 1997-07-10 Cygnus, Inc. Continuous monitoring of physiological analyte
US5827184A (en) 1995-12-29 1998-10-27 Minnesota Mining And Manufacturing Company Self-packaging bioelectrodes
JP3365184B2 (en) 1996-01-10 2003-01-08 松下電器産業株式会社 Biosensor
US6309526B1 (en) 1997-07-10 2001-10-30 Matsushita Electric Industrial Co., Ltd. Biosensor
US5957958A (en) 1997-01-15 1999-09-28 Advanced Bionics Corporation Implantable electrode arrays
US5830341A (en) 1996-01-23 1998-11-03 Gilmartin; Markas A. T. Electrodes and metallo isoindole ringed compounds
US5628309A (en) 1996-01-25 1997-05-13 Raya Systems, Inc. Meter for electrically measuring and recording injection syringe doses
US5704922A (en) * 1996-01-25 1998-01-06 Raya Systems, Inc. Syringe having electrical contact points for metering doses
US6219565B1 (en) 1996-02-05 2001-04-17 Diasense, Inc. Methods and apparatus for non-invasive glucose sensing: non-invasive probe
FI960636A (en) 1996-02-12 1997-08-13 Nokia Mobile Phones Ltd A method for monitoring the patient's state of health
FI118509B (en) 1996-02-12 2007-12-14 Nokia Oyj A method and apparatus for predicting a patient's blood glucose concentration
US5708247A (en) 1996-02-14 1998-01-13 Selfcare, Inc. Disposable glucose test strips, and methods and compositions for making same
US6241862B1 (en) 1996-02-14 2001-06-05 Inverness Medical Technology, Inc. Disposable test strips with integrated reagent/blood separation layer
US20010044588A1 (en) 1996-02-22 2001-11-22 Mault James R. Monitoring system
US5948512A (en) 1996-02-22 1999-09-07 Seiko Epson Corporation Ink jet recording ink and recording method
US5833603A (en) 1996-03-13 1998-11-10 Lipomatrix, Inc. Implantable biosensing transponder
US5728296A (en) 1996-03-20 1998-03-17 Bio-Rad Laboratories, Inc. Selective recognition of solutes in chromatographic media by artificially created affinity
US5753452A (en) 1996-04-04 1998-05-19 Lifescan, Inc. Reagent test strip for blood glucose determination
US5713353A (en) 1996-04-19 1998-02-03 Castano; Jaime A. Optical method and device for determining blood glucose levels
US6113537A (en) 1996-04-19 2000-09-05 Castano; Jaime A. Optical method and device for determining blood glucose levels
DE19618597B4 (en) 1996-05-09 2005-07-21 Institut für Diabetestechnologie Gemeinnützige Forschungs- und Entwicklungsgesellschaft mbH an der Universität Ulm A method for determining the concentration of tissue glucose
US5968839A (en) 1996-05-13 1999-10-19 Metrika, Inc. Method and device producing a predetermined distribution of detectable change in assays
US6048691A (en) 1996-05-13 2000-04-11 Motorola, Inc. Method and system for performing a binding assay
US5725559A (en) 1996-05-16 1998-03-10 Intermedics Inc. Programmably upgradable implantable medical device
US5879311A (en) 1996-05-17 1999-03-09 Mercury Diagnostics, Inc. Body fluid sampling device and methods of use
US5951492A (en) 1996-05-17 1999-09-14 Mercury Diagnostics, Inc. Methods and apparatus for sampling and analyzing body fluid
ES2121565T6 (en) 1996-05-17 1998-11-16 Mercury Diagnostics Inc A disposable device for use in a sampling of body fluids.
US5954685A (en) 1996-05-24 1999-09-21 Cygnus, Inc. Electrochemical sensor with dual purpose electrode
US5735285A (en) 1996-06-04 1998-04-07 Data Critical Corp. Method and hand-held apparatus for demodulating and viewing frequency modulated biomedical signals
FR2749462B1 (en) 1996-06-04 1998-07-24 Ela Medical Sa autonomous device, in particular an active implantable medical device and the external programmer a synchronous transmission
DE19781229T1 (en) 1996-06-17 1999-01-28 Mercury Diagnostics Inc The electrochemical test device and related method
JP4012252B2 (en) 1996-06-18 2007-11-21 アルザ コーポレイション Apparatus for enhancing the transdermal delivery or sampling of an agent
US5879163A (en) 1996-06-24 1999-03-09 Health Hero Network, Inc. On-line health education and feedback system using motivational driver profile coding and automated content fulfillment
US6032199A (en) 1996-06-26 2000-02-29 Sun Microsystems, Inc. Transport independent invocation and servant interfaces that permit both typecode interpreted and compiled marshaling
US5947749A (en) 1996-07-02 1999-09-07 Johnstech International Corporation Electrical interconnect contact system
JP2943700B2 (en) 1996-07-10 1999-08-30 日本電気株式会社 Biosensor
EP0944414B1 (en) 1996-07-11 2005-11-09 Medtronic, Inc. Minimally invasive implantable device for monitoring physiologic events
US5707502A (en) * 1996-07-12 1998-01-13 Chiron Diagnostics Corporation Sensors for measuring analyte concentrations and methods of making same
US6054142A (en) 1996-08-01 2000-04-25 Cyto Therapeutics, Inc. Biocompatible devices with foam scaffolds
US5885245A (en) 1996-08-02 1999-03-23 Sabratek Corporation Medical apparatus with remote virtual input device
US6689091B2 (en) 1996-08-02 2004-02-10 Tuan Bui Medical apparatus with remote control
US6741163B1 (en) 1996-08-13 2004-05-25 Corinna A. Roberts Decorative motion detector
US5804048A (en) 1996-08-15 1998-09-08 Via Medical Corporation Electrode assembly for assaying glucose
US5895371A (en) 1996-08-27 1999-04-20 Sabratek Corporation Medical treatment apparatus and method
US5945345A (en) 1996-08-27 1999-08-31 Metrika, Inc. Device for preventing assay interference using silver or lead to remove the interferant
FI112029B (en) 1996-09-02 2003-10-31 Nokia Corp The device, such as receiving and analyzing blood samples in liquid samples
US6544193B2 (en) 1996-09-04 2003-04-08 Marcio Marc Abreu Noninvasive measurement of chemical substances
US5869963A (en) 1996-09-12 1999-02-09 Alps Electric Co., Ltd. Magnetoresistive sensor and head
US5836887A (en) 1996-09-19 1998-11-17 Colin Corporation Physical information monitor system having means for determining reference range for abnormality determination, based on moving average of previously obtained values
JP2001500915A (en) 1996-09-24 2001-01-23 ヘンケル―エコラープ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング・ウント・コンパニー・オッフェネ・ハンデルスゲゼルシャフト Compact detergents containing a surfactant
US6148094A (en) 1996-09-30 2000-11-14 David J. Kinsella Pointing device with biometric sensor
US5714123A (en) 1996-09-30 1998-02-03 Lifescan, Inc. Protective shield for a blood glucose strip
US5872820A (en) 1996-09-30 1999-02-16 Intel Corporation Synchronization in TDMA systems in a non-realtime fashion
US5718234A (en) 1996-09-30 1998-02-17 Northrop Grumman Corporation Physiological data communication system
US5800387A (en) 1996-10-04 1998-09-01 Alaris Medical Systems, Inc. Safety monitoring apparatus for a patient care system
US5963132A (en) 1996-10-11 1999-10-05 Avid Indentification Systems, Inc. Encapsulated implantable transponder
DE19642453C2 (en) 1996-10-15 1998-07-23 Bosch Gmbh Robert Arrangement for gas sensor electrodes
US5977476A (en) 1996-10-16 1999-11-02 United Solar Systems Corporation High efficiency photovoltaic device
US5832448A (en) 1996-10-16 1998-11-03 Health Hero Network Multiple patient monitoring system for proactive health management
US6001068A (en) 1996-10-22 1999-12-14 Terumo Kabushiki Kaisha Guide wire having tubular connector with helical slits
US5786439A (en) 1996-10-24 1998-07-28 Minimed Inc. Hydrophilic, swellable coatings for biosensors
ES2384705T3 (en) 1996-10-30 2012-07-11 F. Hoffmann-La Roche Ag synchronized analyte test system
US6443942B2 (en) 1996-11-01 2002-09-03 Minimed, Inc. Medication device with protein stabilizing surface coating
US5854078A (en) 1996-11-06 1998-12-29 University Of Pittsburgh Polymerized crystalline colloidal array sensor methods
WO1998020960A1 (en) 1996-11-12 1998-05-22 Whatman, Inc. Hydrophilic polymeric phase inversion membrane
US5771001A (en) 1996-11-18 1998-06-23 Cobb; Marlon J. Personal alarm system
US5811487A (en) 1996-12-16 1998-09-22 Dow Corning Corporation Thickening silicones with elastomeric silicone polyethers
US5964993A (en) 1996-12-19 1999-10-12 Implanted Biosystems Inc. Glucose sensor
US6151586A (en) 1996-12-23 2000-11-21 Health Hero Network, Inc. Computerized reward system for encouraging participation in a health management program
US5933136A (en) 1996-12-23 1999-08-03 Health Hero Network, Inc. Network media access control system for encouraging patient compliance with a treatment plan
US5836989A (en) 1996-12-26 1998-11-17 Medtronic, Inc. Method and apparatus for controlling an implanted medical device in a time-dependent manner
US5914026A (en) 1997-01-06 1999-06-22 Implanted Biosystems Inc. Implantable sensor employing an auxiliary electrode
US5956501A (en) 1997-01-10 1999-09-21 Health Hero Network, Inc. Disease simulation system and method
US5887133A (en) 1997-01-15 1999-03-23 Health Hero Network System and method for modifying documents sent over a communications network
DE69807042T2 (en) 1997-01-17 2003-02-06 Metracor Technologies Inc A method of calibrating of sensors in diagnostic testing methods
ES2124186B1 (en) 1997-01-20 1999-08-01 Carpe Diem Salud S L Section and telematic control system of physiological parameters of patients.
US6122351A (en) 1997-01-21 2000-09-19 Med Graph, Inc. Method and system aiding medical diagnosis and treatment
US5974124A (en) 1997-01-21 1999-10-26 Med Graph Method and system aiding medical diagnosis and treatment
US7329239B2 (en) 1997-02-05 2008-02-12 Medtronic Minimed, Inc. Insertion device for an insertion set and method of using the same
CA2575064C (en) 1997-12-31 2010-02-02 Medtronic Minimed, Inc. Insertion device for an insertion set and method of using the same
US5851197A (en) 1997-02-05 1998-12-22 Minimed Inc. Injector for a subcutaneous infusion set
US6093172A (en) 1997-02-05 2000-07-25 Minimed Inc. Injector for a subcutaneous insertion set
US6607509B2 (en) 1997-12-31 2003-08-19 Medtronic Minimed, Inc. Insertion device for an insertion set and method of using the same
JP3394262B2 (en) 1997-02-06 2003-04-07 イー.ヘラー アンド カンパニー Small volume in vitro analyte sensor
US5749907A (en) 1997-02-18 1998-05-12 Pacesetter, Inc. System and method for identifying and displaying medical data which violate programmable alarm conditions
US5785681A (en) 1997-02-25 1998-07-28 Minimed Inc. Flow rate controller for a medication infusion pump
US6208894B1 (en) 1997-02-26 2001-03-27 Alfred E. Mann Foundation For Scientific Research And Advanced Bionics System of implantable devices for monitoring and/or affecting body parameters
US6309884B1 (en) 1997-02-26 2001-10-30 Diasense, Inc. Individual calibration of blood glucose for supporting noninvasive self-monitoring blood glucose
US5827179A (en) 1997-02-28 1998-10-27 Qrs Diagnostic, Llc Personal computer card for collection for real-time biological data
US6159147A (en) 1997-02-28 2000-12-12 Qrs Diagnostics, Llc Personal computer card for collection of real-time biological data
US5950632A (en) 1997-03-03 1999-09-14 Motorola, Inc. Medical communication apparatus, system, and method
US6558321B1 (en) 1997-03-04 2003-05-06 Dexcom, Inc. Systems and methods for remote monitoring and modulation of medical devices
US6741877B1 (en) 1997-03-04 2004-05-25 Dexcom, Inc. Device and method for determining analyte levels
US20050033132A1 (en) 1997-03-04 2005-02-10 Shults Mark C. Analyte measuring device
US7899511B2 (en) 1997-03-04 2011-03-01 Dexcom, Inc. Low oxygen in vivo analyte sensor
US6001067A (en) 1997-03-04 1999-12-14 Shults; Mark C. Device and method for determining analyte levels
US5951300A (en) 1997-03-10 1999-09-14 Health Hero Network Online system and method for providing composite entertainment and health information
US6968375B1 (en) 1997-03-28 2005-11-22 Health Hero Network, Inc. Networked system for interactive communication and remote monitoring of individuals
US5997476A (en) 1997-03-28 1999-12-07 Health Hero Network, Inc. Networked system for interactive communication and remote monitoring of individuals
US5897493A (en) 1997-03-28 1999-04-27 Health Hero Network, Inc. Monitoring system for remotely querying individuals
US6101478A (en) 1997-04-30 2000-08-08 Health Hero Network Multi-user remote health monitoring system
US6248065B1 (en) 1997-04-30 2001-06-19 Health Hero Network, Inc. Monitoring system for remotely querying individuals
US5961451A (en) 1997-04-07 1999-10-05 Motorola, Inc. Noninvasive apparatus having a retaining member to retain a removable biosensor
US5942979A (en) 1997-04-07 1999-08-24 Luppino; Richard On guard vehicle safety warning system
US5987353A (en) 1997-04-10 1999-11-16 Khatchatrian; Robert G. Diagnostic complex for measurement of the condition of biological tissues and liquids
US6059946A (en) 1997-04-14 2000-05-09 Matsushita Electric Industrial Co., Ltd. Biosensor
US5944661A (en) 1997-04-16 1999-08-31 Giner, Inc. Potential and diffusion controlled solid electrolyte sensor for continuous measurement of very low levels of transdermal alcohol
US6214185B1 (en) 1997-04-17 2001-04-10 Avl Medical Instruments Sensor with PVC cover membrane
US5935785A (en) 1997-04-30 1999-08-10 Motorola, Inc. Binding assay methods
US6115634A (en) 1997-04-30 2000-09-05 Medtronic, Inc. Implantable medical device and method of manufacture
US5779665A (en) 1997-05-08 1998-07-14 Minimed Inc. Transdermal introducer assembly
EP0880936A3 (en) 1997-05-29 1999-03-24 Koji Akai Monitoring physical condition of a patient by telemetry
US6274686B1 (en) 1997-05-30 2001-08-14 Klaus Mosbach Amide containing molecular imprinted polymers
DE69839149D1 (en) 1997-06-04 2008-04-03 Sensor Technologies Inc Method and apparatus for detecting or quantifying of carbohydrates containing compounds
US5957890A (en) 1997-06-09 1999-09-28 Minimed Inc. Constant flow medication infusion pump
US5954643A (en) 1997-06-09 1999-09-21 Minimid Inc. Insertion set for a transcutaneous sensor
JP5264026B2 (en) 1997-06-10 2013-08-14 エルパス・インコーポレイテッドLpath, Inc. A method for the early detection of heart disease
US6093167A (en) 1997-06-16 2000-07-25 Medtronic, Inc. System for pancreatic stimulation and glucose measurement
US6013711A (en) 1997-06-18 2000-01-11 Ck Witco Corporation Hydrophilic polysiloxane compositions
DE69838389D1 (en) 1997-07-09 2007-10-18 Senzime Point Of Care Ab Regeneration of biosensors
DE69817704D1 (en) 1997-07-17 2003-10-09 Siemens Elema Ab The method for flushing and calibrating a sensor system for analyzing a bodily fluid
US6063459A (en) 1997-07-21 2000-05-16 Velte; Stephen K. Antenna ornament
US6066243A (en) 1997-07-22 2000-05-23 Diametrics Medical, Inc. Portable immediate response medical analyzer having multiple testing modules
US5871514A (en) 1997-08-01 1999-02-16 Medtronic, Inc. Attachment apparatus for an implantable medical device employing ultrasonic energy
DE69840306D1 (en) 1997-08-01 2009-01-15 Mann Alfred E Found Scient Res The implantable device having an improved arrangement for charging the battery and for supplying energy
WO1999007277A1 (en) 1997-08-09 1999-02-18 Roche Diagnostics Gmbh Analytical device for in vivo analysis in the body of a patient
US5997475A (en) 1997-08-18 1999-12-07 Solefound, Inc. Device for diabetes management
US6071391A (en) 1997-09-12 2000-06-06 Nok Corporation Enzyme electrode structure
GB9717906D0 (en) 1997-08-23 1997-10-29 Univ Manchester Sensor Devices And Analytical Methods
KR100241052B1 (en) 1997-08-27 2000-02-01 박찬구 Process for preparation of block copolymer
US6731976B2 (en) 1997-09-03 2004-05-04 Medtronic, Inc. Device and method to measure and communicate body parameters
US6051372A (en) 1997-09-09 2000-04-18 Nimbus Biotechnologie Gmbh Template induced patterning of surfaces and their reversible stabilization using phase transitions of the patterned material
US5917346A (en) 1997-09-12 1999-06-29 Alfred E. Mann Foundation Low power current to frequency converter circuit for use in implantable sensors
US6259937B1 (en) 1997-09-12 2001-07-10 Alfred E. Mann Foundation Implantable substrate sensor
US5999849A (en) 1997-09-12 1999-12-07 Alfred E. Mann Foundation Low power rectifier circuit for implantable medical device
US5999848A (en) 1997-09-12 1999-12-07 Alfred E. Mann Foundation Daisy chainable sensors and stimulators for implantation in living tissue
US6117290A (en) 1997-09-26 2000-09-12 Pepex Biomedical, Llc System and method for measuring a bioanalyte such as lactate
US6858403B2 (en) 1999-05-11 2005-02-22 M-Biotech, Inc. Polymer matrix containing catalase co-immobilized with analytic enzyme that generates hydrogen peroxide
WO1999017095A1 (en) 1997-09-30 1999-04-08 M-Biotech, Inc. Biosensor
US6835553B2 (en) 1999-05-11 2004-12-28 M-Biotech, Inc. Photometric glucose measurement system using glucose-sensitive hydrogel
US6475750B1 (en) 1999-05-11 2002-11-05 M-Biotech, Inc. Glucose biosensor
US5904671A (en) * 1997-10-03 1999-05-18 Navot; Nir Tampon wetness detection system
US7115884B1 (en) 1997-10-06 2006-10-03 Trustees Of Tufts College Self-encoding fiber optic sensor
US20010032278A1 (en) 1997-10-07 2001-10-18 Brown Stephen J. Remote generation and distribution of command programs for programmable devices
US6585763B1 (en) 1997-10-14 2003-07-01 Vascusense, Inc. Implantable therapeutic device and method
US6097831A (en) 1997-10-14 2000-08-01 Chiron Corporation Non-contract method for assay reagent volume dispense verification
EP0910023A2 (en) 1997-10-17 1999-04-21 Siemens Aktiengesellschaft Method and device for the neuronal modelling of a dynamic system with non-linear stochastic behavior
US6088608A (en) 1997-10-20 2000-07-11 Alfred E. Mann Foundation Electrochemical sensor and integrity tests therefor
US6119028A (en) 1997-10-20 2000-09-12 Alfred E. Mann Foundation Implantable enzyme-based monitoring systems having improved longevity due to improved exterior surfaces
FI107080B (en) 1997-10-27 2001-05-31 Nokia Mobile Phones Ltd Measuring Instruments
JP2001521804A (en) 1997-10-31 2001-11-13 アミラ メディカル Acquisition and communication system of analyte concentration information
US6144922A (en) 1997-10-31 2000-11-07 Mercury Diagnostics, Incorporated Analyte concentration information collection and communication system
US5931791A (en) 1997-11-05 1999-08-03 Instromedix, Inc. Medical patient vital signs-monitoring apparatus
JPH11141577A (en) 1997-11-05 1999-05-25 Nsk Warner Kk One-way clutch
US6319566B1 (en) 1997-11-12 2001-11-20 John C. Polanyi Method of molecular-scale pattern imprinting at surfaces
ES2281143T3 (en) 1997-11-12 2007-09-16 Lightouch Medical, Inc. Method for non-invasive measurement of an analyte.
DE19824036A1 (en) 1997-11-28 1999-06-02 Roche Diagnostics Gmbh Analytical instrument with lancing
US5990684A (en) 1997-12-02 1999-11-23 Merrill; John H. Method and apparatus for continuously monitoring an aqueous flow to detect and quantify ions
US5971941A (en) 1997-12-04 1999-10-26 Hewlett-Packard Company Integrated system and method for sampling blood and analysis
US6635167B1 (en) 1997-12-04 2003-10-21 Roche Diagnostics Corporation Apparatus and method for determining the concentration of a component of a sample
US6071294A (en) 1997-12-04 2000-06-06 Agilent Technologies, Inc. Lancet cartridge for sampling blood
US6036924A (en) 1997-12-04 2000-03-14 Hewlett-Packard Company Cassette of lancet cartridges for sampling blood
US6579690B1 (en) 1997-12-05 2003-06-17 Therasense, Inc. Blood analyte monitoring through subcutaneous measurement