Advanced analyte sensor calibration and error detection

ABSTRACT

Systems and methods for processing sensor data and self-calibration are provided. In some embodiments, systems and methods are provided which are capable of calibrating a continuous analyte sensor based on an initial sensitivity, and then continuously performing self-calibration without using, or with reduced use of, reference measurements. In certain embodiments, a sensitivity of the analyte sensor is determined by applying an estimative algorithm that is a function of certain parameters. Also described herein are systems and methods for determining a property of an analyte sensor using a stimulus signal. The sensor property can be used to compensate sensor data for sensitivity drift, or determine another property associated with the sensor, such as temperature, sensor membrane damage, moisture ingress in sensor electronics, and scaling factors.
INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 15/994,905, filed May 31, 2018, which is a continuation of U.S.application Ser. No. 14/860,392, filed Sep. 21, 2015, now U.S. Pat. No.10,004,442, which is a continuation of U.S. application Ser. No.13/446,977, filed Apr. 13, 2012, now U.S. Pat. No. 9,149,220, which is acontinuation of U.S. application Ser. No. 13/446,848, filed Apr. 13,2012, now U.S. Pat. No. 9,801,575, which claims the benefit of U.S.Provisional Application No. 61/476,145, filed Apr. 15, 2011. Each of theaforementioned applications is incorporated by reference herein in itsentirety, and each is hereby expressly made a part of thisspecification.
TECHNICAL FIELD

The embodiments described herein relate generally to systems and methodsfor processing sensor data from continuous analyte sensors and forself-calibration.
 BACKGROUND

Diabetes mellitus is a chronic disease, which occurs when the pancreasdoes not produce enough insulin (Type I), or when the body cannoteffectively use the insulin it produces (Type II). This conditiontypically leads to an increased concentration of glucose in the blood(hyperglycemia), which can cause an array of physiological derangements(e.g., kidney failure, skin ulcers, or bleeding into the vitreous of theeye) associated with the deterioration of small blood vessels.Sometimes, a hypoglycemic reaction (low blood sugar) is induced by aninadvertent overdose of insulin, or after a normal dose of insulin orglucose-lowering agent accompanied by extraordinary exercise orinsufficient food intake.
A variety of sensor devices have been developed for continuouslymeasuring blood glucose concentrations. Conventionally, a diabeticperson carries a self-monitoring blood glucose (SMBG) monitor, whichtypically involves uncomfortable finger pricking methods. Due to a lackof comfort and convenience, a diabetic will often only measure his orher glucose levels two to four times per day. Unfortunately, thesemeasurements can be spread far apart, such that a diabetic may sometimeslearn too late of a hypoglycemic or hyperglycemic event, therebypotentially incurring dangerous side effects. In fact, not only is itunlikely that a diabetic will take a timely SMBG measurement, but evenif the diabetic is able to obtain a timely SMBG value, the diabetic maynot know whether his or her blood glucose value is increasing ordecreasing, based on the SMBG alone.
 Heretofore, a variety of glucose sensors have been developed forcontinuously measuring glucose values. Many implantable glucose sensorssuffer from complications within the body and provide only short-termand less-than-accurate sensing of blood glucose. Similarly, transdermalsensors have run into problems in accurately sensing and reporting backglucose values continuously over extended periods of time. Some effortshave been made to obtain blood glucose data from implantable devices andretrospectively determine blood glucose trends for analysis; howeverthese efforts do not aid the diabetic in determining real-time bloodglucose information. Some efforts have also been made to obtain bloodglucose data from transdermal devices for prospective data analysis,however similar problems have occurred.
SUMMARY OF THE INVENTION

In a first aspect, a method is provided for calibrating sensor datagenerated by a continuous analyte sensor, comprising: generating sensordata using a continuous analyte sensor; iteratively determining, with anelectronic device, a sensitivity value of the continuous analyte sensoras a function of time by applying a priori information comprising sensorsensitivity information; and calibrating the sensor data based at leastin part on the determined sensitivity value.
In an embodiment of the first aspect or any other embodiment thereof,calibrating the sensor data is performed iteratively throughout asubstantially entire sensor session.
In an embodiment of the first aspect or any other embodiment thereof,iteratively determining a sensitivity value is performed at regularintervals or performed at irregular intervals, as determined by the apriori information.
In an embodiment of the first aspect or any other embodiment thereof,iteratively determining a sensitivity value is performed throughout asubstantially entire sensor session.
In an embodiment of the first aspect or any other embodiment thereof,determining a sensitivity value is performed in substantially real time.
 In an embodiment of the first aspect or any other embodiment thereof,the a priori information is associated with at least one predeterminedsensitivity value that is associated with a predetermined time afterstart of a sensor session.
In an embodiment of the first aspect or any other embodiment thereof, atleast one predetermined sensitivity value is associated with acorrelation between a sensitivity determined from in vitro analyteconcentration measurements and a sensitivity determined from in vivoanalyte concentration measurements at the predetermined time.
In an embodiment of the first aspect or any other embodiment thereof,the a priori information is associated with a predetermined sensitivityfunction that uses time as input.
In an embodiment of the first aspect or any other embodiment thereof,time corresponds to time after start of a sensor session.
In an embodiment of the first aspect or any other embodiment thereof,time corresponds to at least one of time of manufacture or time sincemanufacture.
In an embodiment of the first aspect or any other embodiment thereof,the sensitivity value of the continuous analyte sensor is also afunction of at least one other parameter.
In an embodiment of the first aspect or any other embodiment thereof,the at least one other parameter is selected from the group consistingof: temperature, pH, level or duration of hydration, curing condition,an analyte concentration of a fluid surrounding the continuous analytesensor during startup of the sensor, and combinations thereof.
In an embodiment of the first aspect or any other embodiment thereof,calibrating the sensor data is performed without using reference bloodglucose data.
 In an embodiment of the first aspect or any other embodiment thereof,the electronic device is configured to provide a level of accuracycorresponding to a mean absolute relative difference of no more thanabout 10% over a sensor session of at least about 3 days, and whereinreference measurements associated with calculation of the mean absoluterelative difference are determined by analysis of blood.
In an embodiment of the first aspect or any other embodiment thereof,the sensor session is at least about 4 days.
In an embodiment of the first aspect or any other embodiment thereof,the sensor session is at least about 5 days.
In an embodiment of the first aspect or any other embodiment thereof,the sensor session is at least about 6 days.
In an embodiment of the first aspect or any other embodiment thereof,the sensor session is at least about 7 days.
In an embodiment of the first aspect or any other embodiment thereof,the sensor session is at least about 10 days.
In an embodiment of the first aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 7% over thesensor session.
In an embodiment of the first aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 5% over thesensor session.
In an embodiment of the first aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 3% over thesensor session.
In an embodiment of the first aspect or any other embodiment thereof,the a priori information is associated with a calibration code.
In an embodiment of the first aspect or any other embodiment thereof,the a priori sensitivity information is stored in the sensor electronicsprior to use of the sensor.
 In a second aspect, a system is provided for implementing the method ofthe first aspect or any embodiments thereof.
In a third aspect, a method is provided for calibrating sensor datagenerated by a continuous analyte sensor, the method comprising:generating sensor data using a continuous analyte sensor; determining,with an electronic device, a plurality of different sensitivity valuesof the continuous analyte sensor as a function of time and ofsensitivity information associated with a priori information; andcalibrating the sensor data based at least in part on at least one ofthe plurality of different sensitivity values.
In an embodiment of the third aspect or any other embodiment thereof,calibrating the continuous analyte sensor is performed iterativelythroughout a substantially entire sensor session.
In an embodiment of the third aspect or any other embodiment thereof,the plurality of different sensitivity values are stored in a lookuptable in computer memory.
In an embodiment of the third aspect or any other embodiment thereof,determining a plurality of different sensitivity values is performedonce throughout a substantially entire sensor session.
In an embodiment of the third aspect or any other embodiment thereof,the a priori information is associated with at least one predeterminedsensitivity value that is associated with a predetermined time afterstart of a sensor session.
In an embodiment of the third aspect or any other embodiment thereof,the at least one predetermined sensitivity value is associated with acorrelation between a sensitivity determined from in vitro analyteconcentration measurements and a sensitivity determined from in vivoanalyte concentration measurements at the predetermined time.
In an embodiment of the third aspect or any other embodiment thereof,the a priori information is associated with a predetermined sensitivityfunction that uses time as input.
In an embodiment of the third aspect or any other embodiment thereof,time corresponds to time after start of a sensor session.
 In an embodiment of the third aspect or any other embodiment thereof,time corresponds to time of manufacture or time since manufacture.
In an embodiment of the third aspect or any other embodiment thereof,the plurality of sensitivity values are also a function of at least oneparameter other than time.
In an embodiment of the third aspect or any other embodiment thereof,the at least one other parameter is selected from the group consistingof: temperature, pH, level or duration of hydration, curing condition,an analyte concentration of a fluid surrounding the continuous analytesensor during startup of the sensor, and combinations thereof.
In an embodiment of the third aspect or any other embodiment thereof,calibrating the continuous analyte sensor is performed without usingreference blood glucose data.
In an embodiment of the third aspect or any other embodiment thereof,the electronic device is configured to provide a level of accuracycorresponding to a mean absolute relative difference of no more thanabout 10% over a sensor session of at least about 3 days; and whereinreference measurements associated with calculation of the mean absoluterelative difference are determined by analysis of blood.
In an embodiment of the third aspect or any other embodiment thereof,the sensor session is at least about 4 days.
In an embodiment of the third aspect or any other embodiment thereof,the sensor session is at least about 5 days.
In an embodiment of the third aspect or any other embodiment thereof,the sensor session is at least about 6 days.
In an embodiment of the third aspect or any other embodiment thereof,the sensor session is at least about 7 days.
In an embodiment of the third aspect or any other embodiment thereof,the sensor session is at least about 10 days.
 In an embodiment of the third aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 7% over thesensor session.
In an embodiment of the third aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 5% over thesensor session.
In an embodiment of the third aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 3% over thesensor session.
In an embodiment of the third aspect or any other embodiment thereof,the a priori information is associated with a calibration code.
In a fourth aspect, a system is provided for implementing the method ofthe third aspect or any embodiments thereof.
In a fifth aspect, a method is provided for processing data from acontinuous analyte sensor, the method comprising: receiving, with anelectronic device, sensor data from a continuous analyte sensor, thesensor data comprising at least one sensor data point; iterativelydetermining a sensitivity value of the continuous analyte sensor as afunction of time and of an at least one predetermined sensitivity valueassociated with a predetermined time after start of a sensor session;forming a conversion function based at least in part on the sensitivityvalue; and determining an analyte output value by applying theconversion function to the at least one sensor data point.
In an embodiment of the fifth aspect or any other embodiment thereof,the iteratively determining a sensitivity of the continuous analytesensor is performed continuously.
In an embodiment of the fifth aspect or any other embodiment thereof,iteratively determining a sensitivity is performed in substantially realtime.
In an embodiment of the fifth aspect or any other embodiment thereof,the method further comprises determining a baseline of the continuousanalyte sensor, and wherein the conversion function is based at least inpart on the baseline.
 In an embodiment of the fifth aspect or any other embodiment thereof,determining a baseline of the continuous analyte sensor is performedcontinuously.
In an embodiment of the fifth aspect or any other embodiment thereof,determining a sensitivity of the continuous analyte sensor anddetermining a baseline of the analyte sensor are performed atsubstantially the same time.
In an embodiment of the fifth aspect or any other embodiment thereof,the at least one predetermined sensitivity value is set at amanufacturing facility for the continuous analyte sensor.
In an embodiment of the fifth aspect or any other embodiment thereof,the method further comprises receiving at least one calibration code;and applying the at least one calibration code to the electronic deviceat a predetermined time after start of the sensor session.
In an embodiment of the fifth aspect or any other embodiment thereof,iteratively determining a sensitivity is performed at regular intervalsor performed at irregular intervals, as determined by the at least onecalibration code.
In an embodiment of the fifth aspect or any other embodiment thereof,the at least one calibration code is associated with the at least onepredetermined sensitivity.
In an embodiment of the fifth aspect or any other embodiment thereof,the at least one calibration code is associated with a predeterminedsensitivity function that uses time of the function of time as input.
In an embodiment of the fifth aspect or any other embodiment thereof,time corresponds to time after start of the sensor session.
In an embodiment of the fifth aspect or any other embodiment thereof,time corresponds to time of manufacture or time since manufacture.
In an embodiment of the fifth aspect or any other embodiment thereof,the sensitivity value of the continuous analyte sensor is also afunction of at least one other parameter.
 In an embodiment of the fifth aspect or any other embodiment thereof,the at least one other parameter is selected from the group consistingof: temperature, pH, level or duration of hydration, curing condition,an analyte concentration of a fluid surrounding the continuous analytesensor during startup of the sensor, and combinations thereof.
In a sixth aspect, a system is provided for implementing the method ofthe fifth aspect or any embodiments thereof.
In a seventh aspect, a method is provided for calibrating a continuousanalyte sensor, the method comprising: receiving sensor data from acontinuous analyte sensor; forming or receiving a predeterminedsensitivity profile corresponding to a change in sensor sensitivity toan analyte over a substantially entire sensor session, wherein thepredetermined sensitivity profile is a function of at least onepredetermined sensitivity value associated with a predetermined timeafter start of the sensor session; and applying, with an electronicdevice, the sensitivity profile in real-time calibrations.
In an embodiment of the seventh aspect or any other embodiment thereof,the at least one predetermined sensitivity value, the predeterminedsensitivity profile, or both are set at a manufacturing facility for thecontinuous analyte sensor.
In an embodiment of the seventh aspect or any other embodiment thereof,the method further comprises receiving at least one calibration code;and applying the at least one calibration code to the electronic deviceat a predetermined time after start of the sensor session.
In an embodiment of the seventh aspect or any other embodiment thereof,the at least one calibration code is associated with the at least onepredetermined sensitivity.
In an embodiment of the seventh aspect or any other embodiment thereof,the at least one calibration code is associated with a predeterminedsensitivity function that uses time as input.
In an embodiment of the seventh aspect or any other embodiment thereof,the sensitivity profile is a function of time.
 In an embodiment of the seventh aspect or any other embodiment thereof,time corresponds to time after start of the sensor session.
In an embodiment of the seventh aspect or any other embodiment thereof,time corresponds to time of manufacture or time since manufacture.
In an embodiment of the seventh aspect or any other embodiment thereof,the sensitivity value is a function of time, the predeterminedsensitivity value, and at least one parameter selected from the groupconsisting of: temperature, pH, level or duration of hydration, curingcondition, an analyte concentration of a fluid surrounding thecontinuous analyte sensor during startup of the sensor, and combinationsthereof.
In an eighth aspect, a system is provided for implementing the method ofthe seventh aspect or any embodiments thereof.
In a ninth aspect, a method is provided for processing data from acontinuous analyte sensor, the method comprising: receiving, with anelectronic device, sensor data from a continuous analyte sensor, thesensor data comprising at least one sensor data point; receiving orforming a sensitivity profile corresponding to a change in sensorsensitivity over a substantially entire sensor session; forming aconversion function based at least in part on the sensitivity profile;and determining an analyte output value by applying the conversionfunction to the at least one sensor data point.
In an embodiment of the ninth aspect or any other embodiment thereof,the sensitivity profile is set at a manufacturing facility for thecontinuous analyte sensor.
In an embodiment of the ninth aspect or any other embodiment thereof,the method comprises receiving at least one calibration code; andapplying the at least one calibration code to the electronic device at apredetermined time after start of the sensor session.
In an embodiment of the ninth aspect or any other embodiment thereof,the at least one calibration code is associated with the at least onepredetermined sensitivity.
 In an embodiment of the ninth aspect or any other embodiment thereof,the at least one calibration code is associated with the sensitivityprofile.
In an embodiment of the ninth aspect or any other embodiment thereof,the sensitivity profile is a function of time.
In an embodiment of the ninth aspect or any other embodiment thereof,time corresponds to time after start of the sensor session.
In an embodiment of the ninth aspect or any other embodiment thereof,time corresponds to time of manufacture or time since manufacture.
In an embodiment of the ninth aspect or any other embodiment thereof,the sensitivity is a function of time and at least one parameter isselected from the group consisting of: temperature, pH, level orduration of hydration, curing condition, an analyte concentration of afluid surrounding the continuous analyte sensor during startup of thesensor, and combinations thereof.
In a tenth aspect, a system is provided for implementing the method ofthe ninth aspect or any embodiments thereof.
In an eleventh aspect, a system is provided for monitoring analyteconcentration in a host, the system comprising: a continuous analytesensor configured to measure analyte concentration in a host and toprovide factory-calibrated sensor data, the factory-calibrated sensordata being calibrated without reference blood glucose data; wherein thesystem is configured to provide a level of accuracy corresponding to amean absolute relative difference of no more than about 10% over asensor session of at least about 3 days, wherein reference measurementsassociated with calculation of the mean absolute relative difference aredetermined by analysis of blood.
In an embodiment of the eleventh aspect or any other embodiment thereof,the sensor session is at least about 4 days.
In an embodiment of the eleventh aspect or any other embodiment thereof,the sensor session is at least about 5 days.
 In an embodiment of the eleventh aspect or any other embodiment thereof,the sensor session is at least about 6 days.
In an embodiment of the eleventh aspect or any other embodiment thereof,the sensor session is at least about 7 days.
In an embodiment of the eleventh aspect or any other embodiment thereof,the sensor session is at least about 10 days.
In an embodiment of the eleventh aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 7% over thesensor session.
In an embodiment of the eleventh aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 5% over thesensor session.
In an embodiment of the eleventh aspect or any other embodiment thereof,the mean absolute relative difference is no more than about 3% over thesensor session.
In a twelfth aspect, a method for determining a property of a continuousanalyte sensor, the method comprising: applying a bias voltage to ananalyte sensor; applying a voltage step above the bias voltage to theanalyte sensor; measuring, using sensor electronics, a signal responseof the voltage step; determining, using the sensor electronics, a peakcurrent of the signal response; determining, using the sensorelectronics, a property of the sensor by correlating the peak current toa predetermined relationship.
In an embodiment of the twelfth aspect or any other embodiment thereof,correlating the peak current to the predetermined relationship comprisescalculating an impedance of the sensor based on the peak current andcorrelating the sensor impedance to the predetermined relationship.
In an embodiment of the twelfth aspect or any other embodiment thereof,the property of the sensor is a sensitivity of the sensor or atemperature of the sensor.
 In an embodiment of the twelfth aspect or any other embodiment thereof,the peak current is a difference between a magnitude of the responseprior to the voltage step and a magnitude of the largest measuredresponse resulting from the voltage step.
In an embodiment of the twelfth aspect or any other embodiment thereof,the predetermined relationship is an impedance-to-sensor sensitivityrelationship, and wherein the property of the sensor is a sensitivity ofthe sensor.
In an embodiment of the twelfth aspect or any other embodiment thereof,the method further comprises compensating sensor data using thedetermined property of the sensor.
In an embodiment of the twelfth aspect or any other embodiment thereof,the compensating comprises correlating a predetermined relationship ofthe peak current to sensor sensitivity or change in sensor sensitivityand modifying a value or values of the sensor data responsive to thecorrelated sensor sensitivity or change in sensor sensitivity.
In an embodiment of the twelfth aspect or any other embodiment thereof,predetermined relationship is a linear relationship over time of use ofthe analyte sensor.
In an embodiment of the twelfth aspect or any other embodiment thereof,the predetermined relationship is a non-linear relationship over time ofuse of the analyte sensor.
In an embodiment of the twelfth aspect or any other embodiment thereof,wherein the predetermined relationship is determined by prior testing ofsensors similar to the analyte sensor.
In an embodiment of the thirteenth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or more processorof the sensor system, cause the sensor system to implement the method ofthe twelfth aspect or any embodiment thereof.
 In a fourteenth aspect, a method is provided for calibrating an analytesensor, the method comprising: applying a time-varying signal to theanalyte sensor; measuring a signal response to the applied signal;determining, using sensor electronics, a sensitivity of the analytesensor, the determining comprising correlating at least one property ofthe signal response to a predetermined sensor sensitivity profile; andgenerating, using sensor electronics, estimated analyte concentrationvalues using the determined sensitivity and sensor data generated by theanalyte sensor.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the sensitivity profile comprises varying sensitivity valuesover time since implantation of the sensor.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the predetermined sensitivity profile comprises a plurality ofsensitivity values.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the predetermined sensitivity profile is based on sensorsensitivity data generated from studying sensitivity changes of analytesensors similar to the analyte sensor.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises applying a bias voltage to thesensor, wherein the time-varying signal comprises a step voltage abovethe bias voltage or a sine wave overlaying a voltage bias voltage.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the determining further comprises calculating an impedancevalue based on the measured signal response and correlating theimpedance value to a sensitivity value of the predetermined sensitivityprofile.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises applying a DC bias voltage to thesensor to generate sensor data, wherein the estimating analyteconcentration values includes generating corrected sensor data using thedetermined sensitivity.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises applying a conversion function tothe corrected sensor data to generate the estimated analyteconcentration values.
 In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises forming a conversion functionbased at least in part of the determined sensitivity, and wherein theconversion function is applied to the sensor data to generate theestimated analyte concentration values.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the property is a peak current value of the signal response.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the determining further comprises using at least one ofperforming a Fast Fourier Transform on the signal response data,integrating at least a portion of a curve of the signal response, anddetermining a peak current of the signal response.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the determining further comprises selecting the predeterminedsensitivity profile based on the determined sensor property from aplurality of different predetermined sensitivity profiles.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the selecting includes performing a data association analysisto determine a correlation between the determined sensor property andeach of the plurality of different predetermined sensitivity profilesand wherein the selected predetermined sensitivity profile has thehighest correlation.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises generating estimated analyteconcentration values using the selected sensitivity profile.
In an embodiment of the fourteenth aspect or any other embodimentthereof, the method further comprises determining a second sensitivityvalue using the selected sensitivity profile, wherein a first set ofestimated analyte concentration values is generated using the determinedsensitivity value and sensor data associated with a first time period,and wherein a second set of concentration values is generated using thesecond sensitivity value and sensor data associated with a second timeperiod.
 In a fifteenth aspect, a sensor system is provided for implementing themethod of the fourteenth aspect or any embodiments thereof.
In an embodiment of the fifteenth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the fourteenth aspect or any embodiment thereof

In a sixteenth aspect, a method is provided for determining whether ananalyte sensor system is functioning properly, the method comprising:applying a stimulus signal to the analyte sensor; measuring a responseto the stimulus signal; estimating a value of a sensor property based onthe signal response; correlating the sensor property value with apredetermined relationship of the sensor property and a predeterminedsensor sensitivity profile; and initiating an error routine if thecorrelation does not exceed a predetermined correlation threshold.
In an embodiment of the sixteenth aspect or any other embodimentthereof, correlating includes performing a data association analysis.
In an embodiment of the sixteenth aspect or any other embodimentthereof, the error routine comprises displaying a message to a userindicating that the analyte sensor is not functioning properly.
In an embodiment of the sixteenth aspect or any other embodimentthereof, the sensor property is an impedance of the sensor membrane.
In a seventeenth aspect, a sensor system is provided configured toimplement the method of the sixteenth aspect or any embodiment thereof.
In an embodiment of the seventeenth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the sixteenth aspect or any embodiment thereof.
 In an eighteenth aspect, a method is provided for determining atemperature associated with an analyte sensor, the method comprising:applying a stimulus signal to the analyte sensor; measuring a signalresponse of the signal; and determining a temperature associated with ofthe analyte sensor, the determining comprising correlating at least oneproperty of the signal response to a predetermined relationship of thesensor property to temperature.
In an embodiment of the eighteenth aspect or any other embodimentthereof, the method further comprises generating estimated analyteconcentration values using the determined temperature and sensor datagenerated from the analyst sensor.
In an embodiment of the eighteenth aspect or any other embodimentthereof, the generating includes compensating the sensor data using thedetermined temperature and converting the compensated sensor data to thegenerated estimated analyte values using a conversion function.
In an embodiment of the eighteenth aspect or any other embodimentthereof, the generating includes forming or modifying a conversionfunction using the determined temperature and converting the sensor datato the generated estimated analyte values using the formed or modifiedconversion function.
In an embodiment of the eighteenth aspect or any other embodimentthereof, the method further comprises measuring a temperature using asecond sensor, wherein the determining further comprises using themeasured temperature to determine the temperature associated with theanalyte sensor.
In an embodiment of the eighteenth aspect or any other embodimentthereof, the second sensor is a thermistor.
In a nineteenth aspect, a sensor system is provided configured toimplement the methods of the eighteenth aspect or any embodimentthereof.
In an embodiment of the nineteenth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the eighteenth aspect or any embodiment thereof.
 In a twentieth aspect, a method is provided for determining moistureingress in an electronic sensor system, comprising: applying a stimulussignal having a particular frequency or a signal comprising a spectrumof frequencies to an analyte sensor; measuring a response to thestimulus signal; calculating, using sensor electronics, an impedancebased on the measured signal response; determining, using sensorelectronics, whether the impedance falls within a predefined levelcorresponding to moisture ingress; initiating, using sensor electronics,an error routine if the impedance exceeds one or both of the respectivepredefined levels

In an embodiment of the twentieth aspect or any other embodimentthereof, the method further comprises the error routine includes one ormore of triggering an audible alarm and a visual alarm on a displayscreen to alert a user that the sensor system may not be functioningproperly.
In an embodiment of the twentieth aspect or any other embodimentthereof, the stimulus signal has a predetermined frequency.
In an embodiment of the twentieth aspect or any other embodimentthereof, the stimulus signal comprises a spectrum of frequencies.
In an embodiment of the twentieth aspect or any other embodimentthereof, the calculated impedance comprises a magnitude value and aphase value, and wherein the determination comprises comparing theimpedance magnitude value to a predefined impedance magnitude thresholdand the phase value to a predefined phase threshold.
In an embodiment of the twentieth aspect or any other embodimentthereof, the calculated impedance is a complex impedance value.
In a twenty-first aspect, a sensor system is provided configured toimplement the methods of the twentieth aspect or any embodiment thereof.
In an embodiment of the twenty-first aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twentieth aspect or any embodiment thereof.
 In an twenty-second aspect, a method is provided for determiningmembrane damage of an analyte sensor using a sensor system, comprising:applying a stimulus signal to an analyte sensor; measuring a response tothe stimulus signal; calculating, using sensor electronics, an impedancebased on the signal response; determining, using the sensor electronics,whether the impedance falls within a predefined level corresponding tomembrane damage; and initiating, using the sensor electronics, an errorroutine if the impedance exceeds the predefined level.
In an embodiment of the twenty-second aspect or any other embodimentthereof, the error routine includes triggering one or more of an audiblealarm and a visual alarm on a display screen.
In an embodiment of the twenty-second aspect or any other embodimentthereof, the stimulus signal has a predetermined frequency.
In an embodiment of the twenty-second aspect or any other embodimentthereof, the stimulus signal comprises a spectrum of frequencies.
In an embodiment of the twenty-second aspect or any other embodimentthereof, the calculated impedance comprises a magnitude value and aphase value, and wherein the determination comprises comparing theimpedance magnitude value to a predefined impedance magnitude thresholdand the phase value to a predefined phase threshold.
In an embodiment of the twenty-second aspect or any other embodimentthereof, the calculated impedance is a complex impedance value.
In a twenty-third aspect, a sensor system is provided configured toimplement the methods of the twenty-second aspect or any embodimentthereof.
In an embodiment of the twenty-third aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twenty-second aspect or any embodiment thereof.
 In a twenty-fourth aspect, a method for determining reuse of an analytesensor, comprising, applying a stimulus signal to an analyte sensor;measuring a response of the stimulus signal; calculating an impedanceresponse based on the response; comparing the calculated impedance to apredetermined threshold; initiating a sensor reuse routine if it isdetermined that the impedance exceeds the threshold.
In an embodiment of the twenty-fourth aspect or any other embodimentthereof, the sensor reuse routine includes triggering an audible and/orvisual alarm notifying the user of improper sensor reuse.
In an embodiment of the twenty-fourth aspect or any other embodimentthereof, the sensor reuse routing includes causing a sensor system tofully or partially shut down and/or cease display of sensor data on auser interface of the sensor system.
In a twenty-fifth aspect, a sensor system is provided configured toimplement the methods of the twenty-fourth aspect or any embodimentsthereof.
In an embodiment of the twenty-fifth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twenty-fourth aspect or any embodiments thereof.
In a twenty-sixth aspect, a system is provided for determining reuse ofan analyte sensor, comprising, applying a stimulus signal to an analytesensor; measuring a response of the stimulus signal; calculating animpedance based on the response; using a data association function todetermine a correlation of the calculated impedance to one or morerecorded impedance values; and initiating a sensor reuse routine if itis determined that the correlation is above a predetermined threshold.
In an embodiment of the twenty-sixth aspect or any other embodimentthereof, the sensor reuse routine includes triggering an audible and/orvisual alarm notifying the user of improper sensor reuse.
 In an embodiment of the twenty-sixth aspect or any other embodimentthereof, the sensor reuse routing includes causing a sensor system tofully or partially shut down and/or cease display of sensor data on auser interface of the sensor system.
In an embodiment of the twenty-sixth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twenty-fifth aspect.
In a twenty-seventh aspect, a method is provided for applying anoverpotential to an analyte sensor, comprising, applying a stimulussignal to an analyte sensor; measuring a response of the stimulussignal; determining a sensor sensitivity or change in sensor sensitivitybased on the response; and applying an over potential to the sensorbased on the determined sensitivity or sensitivity change.
In an embodiment of the twenty-seventh aspect or any other embodimentthereof, the determining further comprises calculating an impedancebased on the response and determining the sensitivity or sensitivitychange based on the impedance.
In an embodiment of the twenty-seventh aspect or any other embodimentthereof, the determining the sensitivity or sensitivity change furthercomprises correlating the impedance to a predetermined impedance tosensitivity relationship.
In an embodiment of the twenty-seventh aspect or any other embodimentthereof, the applying comprises determining or modifying a length oftime the over potential is applied to the sensor.
In an embodiment of the twenty-seventh aspect or any other embodimentthereof, the applying comprises determining or modifying a magnitude ofthe over potential applied to the sensor.
In a twenty-eighth aspect, a sensor system is provided configured toimplement the methods of the twenty-seventh aspect or any embodimentsthereof.
 In an embodiment of the twenty-eighth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twenty-seventh aspect or any embodiment thereof.
In a twenty-ninth aspect, a method is provided for determining aproperty of a continuous analyte sensor, the method comprising: applyinga stimulus signal to a first analyte sensor having a first workingelectrode and a first reference electrode; measuring a signal responseof the stimulus signal using a second analyte sensor having a secondworking electrode and a second reference electrode; and determining aproperty of the first sensor by correlating the response to apredetermined relationship.
In an embodiment of the twenty-ninth aspect or any other embodimentthereof, the method further comprises generating sensor data by applyinga bias voltage to the first working electrode and measuring a responseto the bias voltage.
In an embodiment of the twenty-ninth aspect or any other embodimentthereof, the method further comprises calibrating the sensor data usingthe determined property.
In an embodiment of the twenty-ninth aspect or any other embodimentthereof, the determined property is one of an impedance and atemperature.
In an embodiment of the twenty-ninth aspect or any other embodimentthereof, the method further comprises determining sensor membrane damageusing the determined property.
In an embodiment of the twenty-ninth aspect or any other embodimentthereof, the method further comprises determining moisture ingress in asensor system encompassing the first and second analyte sensors usingthe determined property.
In a thirtieth aspect, a sensor system is provided configured toimplement the methods of one of the twenty-ninth aspect or anyembodiments thereof.
 In an embodiment of the thirtieth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the twenty-ninth aspect or any embodiments thereof.
In a thirty-first aspect, a method is provided for determining a scalingused in a continuous analyte sensor system, the method comprising:applying a first stimulus signal to a first working electrode of ananalyte sensor; measuring a response to the first stimulus signal;applying a second stimulus signal to a second working electrode of theanalyte sensor; measuring a response to the first stimulus signal;determining, using sensor electronics, a scaling factor based on themeasured responses to the first and second stimulus signals; and usingthe scaling factor to generate estimated analyte values based on sensordata generated by the analyte sensor.
In an embodiment of the thirty-first aspect or any other embodimentthereof, the method further comprises the method is performedperiodically.
In an embodiment of the thirty-first aspect or any other embodimentthereof, the determining comprises calculating a first impedance usingthe response to the first stimulus signal and calculating a secondimpedance using the response to the second stimulus signal, and whereinthe scaling factor is a ratio of the first impedance and the secondimpedance.
In an embodiment of the thirty-first aspect or any other embodimentthereof, the first working electrode has a membrane comprising an enzymeconfigured to react with the analyte and the second working electrodehas a membrane does not have the enzyme.
In an embodiment of the thirty-first aspect or any other embodimentthereof, determining the scaling factor comprises updating a previousscaling factor based on the measured responses to the first and secondstimulus signals.
 In an embodiment of the thirty-first aspect or any other embodimentthereof, scaling factor is an acetaminophen scaling factor, wherein themethod further comprises updating a further scaling factor based on theacetaminophen scaling factor, and wherein the further scaling factorapplied to the sensor data to generate the estimated analyte values.
In a thirty-second aspect, a sensor system is provided configured toimplement the methods of the thirty-first aspect or any embodimentsthereof.
In an embodiment of the thirty-second aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the thirty-first aspect or any embodiment thereof

In a thirty-third aspect, a method is provided for calibrating ananalyte sensor, the method comprising: applying a predetermined signalto an analyte sensor; measuring a response to the applied signal;determining, using sensor electronics, a change in impedance associatedwith a membrane of the analyte sensor based on the measured response;calculating a sensitivity change of the analyte sensor based on thedetermined impedance; calculating a corrected sensitivity based on thecalculated sensitivity change and a previously used sensitivity of theanalyte sensor; and generating estimated analyte values using thecorrected sensitivity.
In an embodiment of the thirty-third aspect or any other embodimentthereof, calculating the sensitivity change comprises applying anon-linear compensation function.
In an embodiment of the thirty-third aspect or any other embodimentthereof, the non-linear compensation function is expressed as theequation ΔS=(a*log(t)+b)*ΔI, where ΔS is the change in sensitivity, t isa time since calibration of the analyte sensor, ΔI is the determinedchange in impedance, and a and b are a predetermined coefficients.
In an embodiment of the thirty-third aspect or any other embodimentthereof, a and b are determined by prior testing of similar analytesensors.
 In a thirty-fourth aspect, a sensor system is provided configured toimplement the methods of the thirty-third aspect or any embodimentsthereof.
In an embodiment of the thirty-fourth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the thirty-third aspect or any embodiments thereof.
In a thirty-fifth aspect, a method is provided for calibrating ananalyte sensor, comprising: generating sensor data using a subcutaneousanalyte sensor; forming or modifying a conversion function, whereinpre-implant information, internal diagnostic information, and/orexternal reference information are used as inputs to form or modify theconversion function; and calibrating the sensor data using theconversion function.
In an embodiment of the thirty-fifth aspect or any other embodimentthereof, the pre-implant information comprises information selected fromthe group consisting of: a predetermined sensitivity profile associatedwith the analyte sensor, a previously determined relationship between ameasured sensor property and sensor sensitivity, one or more previouslydetermined relationships between a measured sensor property and sensortemperature; sensor data obtained from previously used analyte sensors,a calibration code associated with the analyte sensor, patient specificrelationships between the analyte sensor and one or more of sensitivity,baseline, drift and impedance, information indicative of a site ofsensor implantation; time since manufacture of the analyte sensor, andinformation indicative of the analyte being exposed to temperature orhumidity.
 In an embodiment of the thirty-fifth aspect or any other embodimentthereof, the internal diagnostic information comprises informationselected from the group consisting of: stimulus signal output; sensordata indicative of an analyte concentration measured by the sensor;temperature measurements using the sensor or a separate sensor; sensordata generated by a redundant sensor, where the redundant sensor isdesigned to be substantially the same as analyte sensor; sensor datagenerated by an auxiliary sensors, where the auxiliary sensor is havinga different modality as the analyte sensor; a time since the sensor wasimplanted or connected to sensor electronics coupled to the sensor; datarepresentative of a pressure on the sensor or sensor system generated bya pressure sensor; data generated by an accelerometer; a measure ofmoisture ingress; and a measure of noise in an analyte concentrationsignal.
In an embodiment of the thirty-fifth aspect or any other embodimentthereof, the reference information comprises information selected fromthe group consisting of: real-time and/or prior analyte concentrationinformation obtained from a reference monitor, information relating to atype/brand of reference monitor used to provide reference data;information relating to an amount of carbohydrate consumed by a user;information received from a medicament delivery device, glucagonsensitivity information, and information gathered from population baseddata.
In a thirty-sixth aspect, a sensor system is provided configured toimplement the methods of the thirty-fifth aspect or any embodimentsthereof.
In an embodiment of the thirty-sixth aspect or any other embodimentthereof, the sensor system comprises instructions stored in computermemory, wherein the instructions, when executed by one or moreprocessors of the sensor system, cause the sensor system to implementthe method of the thirty-fifth aspect or any embodiment thereof.
 BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages will be appreciated, as theybecome better understood by reference to the following detaileddescription when considered in connection with the accompanyingdrawings, wherein:

FIG. 1A illustrates a schematic diagram of sensor sensitivity as afunction of time during a sensor session, in accordance with oneembodiment; FIG. 1B illustrates schematic diagrams of conversionfunctions at different time periods of a sensor session, in accordancewith the embodiment of FIG. 1A.
FIGS. 2A-2B and FIGS. 2C-2D collectively illustrate differentembodiments of processes for generating a sensor sensitivity profile.
FIG. 3A is a Bland-Altman plot illustrating differences between YSIreference measurements and certain in vivo continuous analyte sensorsthat were factory calibrated, in accordance with one embodiment; FIG. 3Bis a Clarke error grid associated with data from the continuous analytesensors associated with FIG. 3A.
FIG. 4 illustrates data from one study that examined the accuracy levelof continuous analyte sensors that accepted one reference measurementabout one hour after insertion into patients, in accordance with oneembodiment.
FIG. 5 illustrates a diagram showing different types of information thatcan be input into the sensor system to define the sensor sensitivityprofile over time

FIG. 6 illustrates a schematic diagram of sensor sensitivity as afunction of time between completion of sensor fabrication and the startof the sensor session, in accordance with one embodiment.
FIG. 7A is a schematic diagram depicting distribution curves of sensorsensitivity corresponding to the Bayesian learning process, inaccordance with one embodiment; FIG. 7B is a schematic diagram depictingconfidence levels, associated with the sensor sensitivity profile, thatcorrespond with the distribution curves shown in FIG. 7A.
FIG. 8 illustrates a graph that provides a comparison between anestimated glucose equivalent baseline and detected glucose equivalentbaseline, in accordance with one study.
FIG. 9 is a schematic of a model sensor circuit in accordance with oneembodiment.
 FIG. 10 is a Bode plot of an analyte sensor in accordance with oneembodiment.
FIG. 11 is a flowchart describing a process for determining an impedanceof a sensor in accordance with one embodiment.
FIG. 12 is a flowchart describing a process for determining an impedanceof a sensor based on a derivative response in accordance with oneembodiment.
FIG. 13 is a flowchart describing a process for determining an impedanceof a sensor based on a peak current response in accordance with oneembodiment.
FIG. 14A illustrates a step voltage applied to a sensor and FIG. 14Billustrates a response to the step voltage in accordance with oneembodiment.
FIG. 15 is a flowchart describing a process for estimating analyteconcentration values using a corrected signal based on an impedancemeasurement in accordance with one embodiment.
FIG. 16 is a flowchart describing a process for estimating analyteconcentration values using a predetermined sensitivity profile selectedbased on an impedance measurement in accordance with one embodiment.
FIG. 17 is a flowchart describing a process for determining an errorbased whether a sensitivity determined using an impedance measurementsufficiently corresponds to a predetermined sensitivity in accordancewith one embodiment.
FIG. 18 is a flowchart describing a process for determining atemperature associated with a sensor by correlating an impedancemeasurement to a predetermined temperature-to-impedance relationship inaccordance with one embodiment.
FIG. 19 is a flowchart describing a process for determining moistureegress in sensor electronics associates with an analyte sensoraccordance with one embodiment.
FIG. 20 is a flowchart describing a process for determining membranedamage associated with an analyte sensor in accordance with oneembodiment.
FIG. 21 is a flowchart describing a first process for determining sensorreuse associated in accordance with one embodiment.
FIG. 22 is a flowchart describing a second process for determiningsensor reuse associated in accordance with one embodiment.
 FIG. 23 is a schematic of a dual-electrode configuration used todetermine sensor properties in accordance with one embodiment.
FIG. 24 is a diagram of a calibration process that uses various inputsto form a conversion function in accordance with one embodiment.
FIGS. 25-49 collectively illustrate results of studies using stimulussignals to determine sensor properties.
FIG. 50 is a flowchart describing a process for generating estimatedanalyte values using a compensation algorithm based on a measured changein impedance in accordance with one embodiment.
FIGS. 51-53 are graphs of studies comparing use of compensationalgorithms based on measured changes in impedance.
DETAILED DESCRIPTION Definitions

In order to facilitate an understanding of the embodiments describedherein, a number of terms are defined below.
