CN101557754A - Method and apparatus for background current arrangements for a biosensor - Google Patents

Abstract

Embodiments of the present invention provide for raising a background current setting for a biosensor above the actual (measured) background current present (i.e., overestimating the background current), particularly in the hypoglycemic range, to improve sensor accuracy and decrease the chance of glucose value overestimation by the sensor.

Description

The method and apparatus that is used for the background current setting of biosensor

Quoting of related application

The application requires to be called the U.S. Patent application of submitting on November 14th, 2,006 11/559 of " Method and Apparatus for Background CurrentArrangements for a Biosensor ", No. 521 priority, and the provisional application 60/739 of the submission in 22 days November in 2005 of requirement " Method and Apparatus for VariableBackground Current Arrangements for a Biosensor " by name, No. 147 priority is incorporated their full content by reference into.

Technical field

Embodiments of the present invention relate to field of medical devices, and relate to the background current setting of biosensor particularly.

Background technology

In the current mode enzyme sensor, even background current is meant the small quantity electric current that tested analyte also exists when not existing.This current value special make up without enzyme, can be measured in thus can not be the pick off that produces response such as glucose or Lactated analyte.When the implanted animal or human's body of this type of pick off (no enzyme), between normally about 0.5nA of exemplary background current and the 2nA (receive ampere).

In addition, from clinical angle, the accuracy of the glucose biological sensor in the hypoglycemia scope is very important.For example, if real capillary blood glucose value is 65mg/dl (lower) and the pick off valuation is 80mg/dl, this will be a gross mistake, and promptly because pick off is crossed estimation, real hypoglycemia is left in the basket.Hypoglycemic error diagnosis will cause stupor, cerebral hemorrhage, vehicle accident etc.

Description of drawings

By hereinafter in conjunction with the detailed description of appended accompanying drawing, with the easy to understand embodiments of the present invention.

Embodiments of the present invention illustrate by the mode of example, and are not subjected to the restriction of appended accompanying drawing.

Fig. 1 is a table, shows the result who utilizes different background current value according to the pick off that works in glucose range 40-400mg/dl of each embodiment of the present invention, and the right corresponding percentage ratio of data in each Clarke errors table case analysis zone;

Fig. 2 is a table, show the result who utilizes different background current value according to the pick off that works in hypoglycemia glucose range (70mg/dl and lower) of each embodiment of the present invention, and the right corresponding percentage ratio of data in each Clarke errors table case analysis zone;

Fig. 3 is that the pick off to working in 75mg/dl and lower glucose range according to each embodiment of the present invention adopts the 1.5nA background current and adopts the errors table trrellis diagram of the data that the 0.8nA background current produces to working in pick off above the dextrose equivalent of 75mg/dl;

Fig. 4 is a table, illustrate and utilize variable background current method (left plate), 0.8nA fixed background current method (intermediate plate), and the fixedly background current (right plate) of 1.5nA, Clarke errors table case analysis regional peace is the result of absolute relative mistake (MARD) data all;

Fig. 5 shows the pick off output of pick off background current of 2.0nA with respect to the exemplary diagram of dextrose equivalent, the actual glucose value of 70mg/dl is shown and the dextrose equivalent of the 68mg/dl that estimates;

Fig. 6 illustrates the figure of data on Clarke error form of Fig. 5;

Fig. 7 illustrates the pick off of the pick off background current of 0.0nA and exports with respect to dextrose equivalent exemplary data figure, and the actual glucose value of 70mg/dl and the dextrose equivalent that estimates of 80mg/dl are shown; And

Fig. 8 shows the figure of data on Clarke error form of Fig. 7.

The specific embodiment

In the following detailed description, the appended accompanying drawing with reference to constituting a description part wherein shows and can realize exemplary embodiment of the present invention.Should be appreciated that under the situation that does not deviate from scope of the present invention, can utilize other embodiments and can carry out structure or logical changes.Therefore, detailed description subsequently is not to be intended to restriction, and scope is according to the embodiment of the present invention limited by claims and equivalent thereof.

Various operations can be described as a plurality of successively discrete operations by the mode of being convenient to understand embodiments of the present invention; Yet, should not think that the order of describing has hinted that these operations depend on order.

Described description can be used the description based on direction, for example goes up/descend back/preceding, and top/bottom.This class description only is to be used for the auxiliary application of discussing rather than being intended to show embodiments of the present invention.For purpose of the present invention, the phrase of " A/B " form is meant " A or B ", and for the present invention, the phrase of " A and/or B " form is meant " (A), (B), or (A and B) ".For the present invention, the phrase of " at least one between A, B and the C " form is meant " (A), (B), (C), (A and B), (A and C), (B and C) or (A, B and C) ".For the present invention, the phrase of the form of " (A) B " is meant " (B) or (AB) ", that is, A is optional key element.

This description can be used the phrase of " in one embodiment ", or " in embodiment ", and wherein each all is meant the embodiment that one or more is identical or different.In addition, the phrase such as " comprising ", " comprising ", " having " that is used for corresponding to embodiments of the present invention is a synonym.

In embodiments of the present invention, particularly, in hypoglycemic, by the background current setting being brought up to (promptly greater than existing reality (measuring) background current, background current is over-evaluated), with the chance that improves sensor accuracy and reduce to over-evaluate by the blood glucose value that described pick off causes.

Method according to the embodiment of the present invention will cause underestimating of dextrose equivalent, and this will be welcome clinically, particularly in hypoglycemic.Particularly, this can reduce the generation of over-evaluating to the dextrose equivalent of reality in hypoglycemic.Thus, in embodiment, can reduce the quantity of false negative (inaccurate hypoglycemia) value.In hypoglycemic, described difference can be important and be relevant clinically, even the intensity of variation of background current hour, also is like this.

In embodiments of the present invention, a kind of algorithm of real time operation can use different background current value to different glucose range.

In exemplary embodiment, for example the background current of about 1.3-1.7nA is applicable to hypoglycemic (90mg/dl and lower for example, or 70mg/ and lower), and for example the value of about 0.6-1.0nA is applicable to all the other scopes (greater than 70mg/dl, or greater than 90mg/dl).In embodiment, also can use other threshold values.

Although above-mentioned background current value can be in one or more concrete pick off works fine, may need to use different value for other different sensors.In other words, in embodiments of the present invention, for allowing more interference preparations to arrive the pick off of working electrode, background current can be higher for all glucose levels, but embodiments of the present invention still can be used.That is,, use higher background current to cause clinical improvement for lower dextrose equivalent by reducing the probability of high valuation in LG scope more.

Thus, in embodiment, provide a kind of method, described method comprises the initial background current value of determining analyte sensor; Utilize the initial analysis thing sensor output value of the definite analyte sensor that is using of described initial background current value; Use based on the described initial background current value of the parameter adjustment of determined initial analysis thing sensor output value, to form background current value through adjusting; And utilize the described analyte sensor output valve of background current value formation through adjusting through adjusting.

In embodiments of the present invention, parameter can be: the multiplication parameter, and for example less than 3, or less than 2 parameter; Definitely/digital value increases or (for example ,-3mg/dl) reduces; Maybe can or reduce by the increase of predetermined ratio value.

In embodiment, can be scheduled to a series of background current value, for example 0,0.8,1.5,2.2,3.0nA etc.When determine to measure/during the background current that exists, according to the embodiment of the present invention, be used for finally determining that the background current of the dextrose equivalent that estimates can be the highest background current value of the next one of predetermined tabulation.In the embodiment of alternative, only the dextrose equivalent that goes out when described initial estimation less than such as the predetermined threshold of 70mg/dl or 90mg/dl the time, the value of just utilizing the described next one the highest (or second height or the like) as required background current value replacement to measure.

In embodiment, when the dextrose equivalent that estimates was in preset range or is lower than predetermined value, according to the dextrose equivalent that concrete initial estimation goes out, the background current of measuring can be adjusted specific percentage point of number or the specific amperage of receiving.In embodiment, the adjustment of background current can be inversely proportional to the Mean Speed that glucose level descends in the given time.For example, if the dextrose equivalent of the individuality that estimates in the past 10 minutes descended with 1mg/dl/ minute, background current can be conditioned the per minute 0.1nA that for example measures so.Thus, in having 1mg/dl/ minute 10 minutes of glucose decline Mean Speed, the background current that can revise the 1.0nA that measures is to form the background current of the 2.0nA through regulating.This only is the embodiment of this notion, and according to the embodiment of the present invention instruction can be regulated or be provided with concrete speed, threshold value and/or revise according to expectation thus.

In embodiment, can use fixed background current, and determined initial glucose value as a result can be regulated (for example reducing parameter) by parameter through simplifying.This parameter can be percentage ratio or the fixed amount that initial glucose value increases or reduce initial value.In another embodiment, described parameter can change according to initial glucose value.For example, if initial glucose value is lower than 90mg/dl, for example 5%-10% that then can be by reducing this value or regulate this value less than about 15% or 10%, or regulate this value by the fixed amount that for example reduces 5mg/dl.In addition, in embodiment, if initial glucose value greater than 90mg/dl, can not regulated this value.For example 5% reduction parameter is meant that dextrose equivalent is reduced 5%, so that the initial glucose value of 80mg/dl will provide the dextrose equivalent through regulating of 76mg/dl after having used this parameter.This embodiment guarantees to be positioned at or to be regulated to the hypoglycemia reading to attempt guaranteeing not ignore real hypoglycemia situation near the value of hypoglycemia.The result that embodiments of the present invention can cause is the increase to the quantity of the minimizing of the sensitivity of hypoglycemia and/or false alarm; Yet this advantage comparison sensitivity potential lost and/or the increase of false alarm is more important to guarantee not to be left in the basket real hypoglycemia situation.

Therefore, in embodiment, provide a kind of method of utilizing analyte sensor to obtain the analyte value of sample, described method comprises: the fixed background current value of determining to be used for described analyte sensor; Described analyte sensor is contacted with described sample to form initial analysis thing sensor electrical flow valuve; From described initial analysis thing sensor electrical flow valuve, deduct described fixed background current value to form clean analyte sensor current value; Sensitirity va1ue with described analyte sensor removes described clean analyte sensor current value to form the glucose estimator value; And if described glucose estimator value is higher than predetermined threshold, show described glucose estimator value, and if described glucose estimator value be equal to or less than predetermined threshold then use the reduction parameter to form dextrose equivalent and then to show described dextrose equivalent through adjusting through adjusting.

In the embodiment that uses single-point calibration, can from pick off output, deduct background current (is unit with nA).The capillary blood sugar level that income value (clean pick off output) obtains in the time of can then being calibrated removes, and produces Sensitirity va1ue.In embodiment, in order to calculate (estimation) concentration of glucose according to sensor reading, can descend column count: deduct background current from total pick off output, income value then removes with sensitivity, produces the glucose estimator value.Thus, it is influential to the sensitivity of the pick off set up significantly to regulate background current, and influential to the dextrose equivalent that estimates thus.

In embodiments of the present invention, can use the multipoint system of calibration and not use the single-point mode.In multipoint system, can use current one point sensing device value (dextrose equivalent that estimates) and capillary blood glucose, and in addition, the previous sensor values of up time weighting and the series of capillary blood glucose value.For example, in multipoint system, can 80% weight be provided and provide 20% total weight (time value farthest has minimum weight) to currency to whole previous values.In this way, can in the multiple spot calibrating mode, use some or all of previous calibration value (within a few days).

Thus, in embodiment, provide a kind of method, described method comprises: first background current value that deducts analyte sensor from the first analyte sensor output valve is to form the first clean analyte sensor output valve; Obtain individual capillary blood glucose value; Remove the described first clean analyte sensor output valve to form Sensitirity va1ue with described capillary blood glucose value; Determine second background current value of described analyte sensor; Utilize described second background current value to determine the second analyte sensor output valve of described analyte sensor; Use based on described second background current value of the parameter adjustment of the second analyte sensor output valve of being determined, to form the 3rd background current value; From the described second analyte sensor output valve, deduct the 3rd background current value to form the second clean analyte sensor output valve; And remove the described second clean analyte sensor output valve with described Sensitirity va1ue and estimate blood glucose value to form.

In addition, embodiments of the present invention can be used various processing and/or method and the calculating of accountant to expect.In addition, estimate that the data that each embodiment of the present invention obtains can be presented on the various devices, and can send by variety of way.Thus, in embodiment, a kind of device is provided, described device comprises: storage medium, store in the described storage medium and design a plurality of programmed instruction that are used for starting described device, after having carried out described programmed instruction, determine the initial background current value of analyte sensor, utilize the initial analysis thing sensor output value of the definite analyte sensor that is using of described initial background current value, use based on the described initial background current value of parameter adjustment of described definite initial analysis thing sensor output value producing background current value, and utilize described background current value to form analyte sensor output valve through adjusting through adjusting through adjusting; And processor, described processor is connected to described storage medium to carry out described a plurality of programmed instruction.

Other data algorithms of support maximum likelihood according to the embodiment of the present invention comprise biological filters.Particularly, the understanding for general physiology shows that the speed that increases or reduce of the concentration of glucose in the human body is conditional.The factor that the control glucose increases speed comprise intestinal to the absorption rate of carbohydrate and in the fasting period liver glycogen can be converted into the speed of glucose.The rate dependent that glucose descends in muscle cell and adipose cell to the absorption of glucose, main insulin concentration, insulin sensitivity and fatigue degree.Can calculate, wherein also artefact (for example because motion) can be separated from the true skew of concentration of glucose thus these biological factor modelings.

Another data analysis algorithm according to the embodiment of the present invention is to remove detection (dislodgement detection).Particularly, because the improper contact strength of module adhesive and skin, wired sensor can become and partly or wholly remove.The technology of discerning the typical module that removes or partly remove has been arranged.If kinematic error is very small, the demonstration of data can temporarily be interrupted.If error continues, may require the patient to insert a new pick off.

In exemplary embodiment of the present invention, used from 15 patient's data, wherein subcutaneous implantation current formula wired sensor among continuous 5 days of each patient with type 1 diabetes.Except implanting subcutaneous sensor, these patients assess the accuracy of these pick offs by 17 measurements every day finger tip capillary blood glucose.In this exemplary embodiment, utilize following background current value assessment accuracy: 0,0.8,1.5, the 2.2nA (see figure 1).Some tests are (its data are not illustrated) of carrying out under the background current of 2.2nA being higher than, but these results cause exceeding the higher average absolute relative mistake (MARD) of normal range.

According to the embodiment of the present invention, in Fig. 1, shown tabular summary (for the glucose range of 40-400mg/dl) of the result who utilizes different background current value, the right percentage ratio of data of each Clarke error network analysis (EGA) has been shown.Please note that the D range percentage has improvement (reduction) along with background current raises, this demonstrates progress.Yet when using the background current of 2.2nA, MARD some rising that becomes surpasses 20%, but the D range percentage still has and reduces.

In addition, according to the embodiment of the present invention, specifically use identical background current value with test sensors data accuracy in hypoglycemic.Fig. 2 shows these accuracy data.Please note that along with background current value is elevated to 1.5nA from 0.8nA the accuracy of error grid data and MARD data increases substantially.The percentage ratio that please notes the D value obviously descends, and 26.1% during from 0.0nA is reduced to background current 1.5% when being 2.2nA.And please note that MARD improves along with background current is elevated to 1.5nA from 0.0, then along with background current continues to raise and raise once more from 2.2nA.

In embodiments of the present invention, in hypoglycemic, spendable suitable background current value is the value of about 1.5nA.This value causes outstanding error network analysis and outstanding MARD.

Above-mentioned data illustrate utilizes the background current of about 1.5nA good in hypoglycemic work.Yet, in embodiments of the present invention, the check of overall glucose range is demonstrated when using different background currents 0.8nA for example, MARD best (minimum).Thus, embodiments of the present invention are provided at and use different background current value in the different glucose range.

In embodiments of the present invention, for 75mg/dl and lower glucose range, utilize 1.5nA data to be reanalysed, and utilize 0.8nA for other four corners as exemplary background current.The error grid chart of Fig. 3 is provided with generation with this.

In the zone of the glucose range that is lower than 75mg/dl, have only the D scope of several values on, and these values are near the border of D zone and a-quadrant.

According to the embodiment of the present invention, Fig. 4 provides the error net region of method (right plate) of fixedly background current of (intermediate plate) of the fixedly background current method of utilizing variable background current method (left plate), 0.8nA and 1.5nA and the result of MARD data.

In embodiment of the present invention shown in Figure 4, variable background current method produces maximum overall accuracy.For example, the method can comprise the approximate or estimation of setting up dextrose equivalent, utilizes the fixed background current between operable two other background currents of selecting, for example, among the embodiment in Fig. 4, use (0.8 and 1.5nA between) background current of 1nA, to reach estimation.Then, for example, in embodiment, in the embodiment that 75mg/dl or lower initial glucose are estimated, for example background current of 1.5nA can be used, in the embodiment that the initial glucose that surpasses 75mg/dl is estimated, for example background current of 0.8nA can be used.In embodiment, can use new background current value to recomputate each estimated value, but and accuracy of measurement.

Utilize variable background current method, the percentage ratio of A+B is the highest (97.8%), and the percentage ratio of D value is minimum (1.0%), and MARD is minimum (17.26%).In hypoglycemic, the data of variable background current method are better than the data that background current is fixed in 0.8nA.

For different background current value is applied to different glucose range, even, can utilize interim background current amplitude (for example 1nA) to estimate (the user not being illustrated) to reach interim initial glucose in real time down.For example, this initial estimation can be 200mg/dl for example.This will identify scope, and at this point, algorithm will calculate the final estimation of background current, for example 0.8nA.If the interim value (for example being arranged under the threshold value in 65-80mg/dl scope somewhere) of estimating to produce hypoglycemic, so alternative use for example the background current value of 1.5nA to calculate the described final estimation that shows to the user.

In embodiments of the present invention, improve background current and can cause the too high estimation (estimation is higher than reportable dextrose equivalent) that reduces in the hypoglycemic.Following accompanying drawing shows exemplary results.

In embodiments of the present invention shown in Figure 5, (actual glucose=70mg/dl, the glucose that estimates=68mg/dl), in the error grid chart as shown in Figure 6, these data are to falling into error net region A.

In embodiments of the present invention shown in Figure 7, show the calibration program when background current is 0.0nA.Data are sinked into more top D zone now to (actual glucose 70mg/dl, glucose estimator 80mg/dl).Error grid chart shown in Figure 8 illustrates the dextrose equivalent that estimates and falls into the D zone.

Although in order to describe the purpose of preferred implementation, illustrate and described specific implementations, it will be understood by those skilled in the art that under the situation that does not deviate from scope of the present invention, at embodiment shown and that describe, can carry out multiple replacement and/or equivalent embodiments or embodiment to reach identical purpose.The person skilled in the art will easily understand according to the embodiment of the present invention and can implement in several ways.This understanding will cover any distortion or the change to embodiment discussed herein.Therefore, significantly, according to the embodiment of the present invention only by claim and equivalent restriction thereof.

Claims (23)

1, a kind of method, described method comprises:

Determine the initial background current value of analyte sensor;

Utilize described initial background current value to determine the initial analysis thing sensor output value of employed analyte sensor;

Use based on the described initial background current value of the parameter adjustment of determined initial analysis thing sensor output value, to form background current value through adjusting; And

Utilize the described analyte sensor output valve of background current value formation through adjusting through adjusting.

2, method according to claim 1, wherein, described parameter is the multiplication parameter that is applied to described initial background current value.

3, method according to claim 2, wherein, described multiplication parameter is less than 3.

4, method according to claim 1, wherein, described parameter comprises recruitment or the decrease of described initial background current value to the background current value of selecting through adjusting from the predetermined tabulation of a plurality of acceptable background current value through adjusting.

5, method according to claim 4, wherein, the predetermined tabulation of described acceptable background current value through adjusting comprises 0nA, 0.8nA, 1.5nA, 2.2nA and 3.0nA.

6, according to the described method of claim 1, wherein, described background current value through adjusting is greater than described initial background current value.

7, method according to claim 1, wherein, determine whether that described initial analysis thing sensor output value falls into preset range described comprising based on initial analysis thing sensor values.

8, method according to claim 7, wherein, described preset range is 70mg/dl and lower.

9, method according to claim 8, wherein, described background current value about 1.3 to 1.7nA through adjusting.

10, method according to claim 7, wherein, described preset range is greater than 70mg/dl.

11, method according to claim 10, wherein, the described about 0.6nA of background current value through adjusting is to 1.0nA.

12, method according to claim 1, wherein, described definite initial background current value comprises any background current level of about 0.5nA to the 2.0nA scope that be provided at.

13, method according to claim 1, wherein, described analyte sensor output valve through adjusting is shown in the related display device.

14, method according to claim 1, wherein, along with the analyte sensor output valve through adjusting changes, described background current value through adjusting is further adjusted in real time.

15, method according to claim 1, wherein, the initial background current value of described utilization comprises and deducts described initial background current value forming described initial analysis thing sensor output value from first the analyte sensor output valve through measuring, and the background current value of described utilization through adjusting comprises from second the analyte sensor output valve through measuring and deduct described background current value through adjusting to form described analyte sensor output valve through adjusting.

16, a kind of device, described device comprises:

Storage medium, store in the described storage medium and design a plurality of programmed instruction that are used for starting described device, after having carried out described programmed instruction, determine the initial background current value of analyte sensor, utilize the initial analysis thing sensor output value of the definite analyte sensor that is using of described initial background current value, use based on the described initial background current value of parameter adjustment of described definite initial analysis thing sensor output value producing background current value, and utilize described background current value to form analyte sensor output valve through adjusting through adjusting through adjusting; And

Processor, described processor are connected to described storage medium to carry out described a plurality of programmed instruction.

17, a kind of method, described method comprises:

First background current value that deducts analyte sensor from the first analyte sensor output valve is to form the first clean analyte sensor output valve;

Obtain individual capillary blood glucose value;

Remove the described first clean analyte sensor output valve to form Sensitirity va1ue with described capillary blood glucose value;

Determine second background current value of described analyte sensor;

Utilize described second background current value to determine the second analyte sensor output valve of described analyte sensor;

Use based on described second background current value of the parameter adjustment of the second analyte sensor output valve of being determined, to form the 3rd background current value;

Deduct the 3rd background current value to form the second clean analyte sensor output valve from the described second analyte sensor output valve; And

Remove the described second clean analyte sensor output valve with described Sensitirity va1ue and estimate blood glucose value to form.

18, method according to claim 17, wherein said Sensitirity va1ue are to form according to time-weighted a series of previous clean analyte sensor output valves and previous capillary blood glucose value.

19, a kind of method of utilizing analyte sensor to obtain the analyte value of sample, described method comprises:

Determine to be used for the fixed background current value of described analyte sensor;

Described analyte sensor is contacted with described sample to form initial analysis thing sensor electrical flow valuve;

From described initial analysis thing sensor electrical flow valuve, deduct described fixed background current value to form clean analyte sensor current value;

Sensitirity va1ue with described analyte sensor removes described clean analyte sensor current value to form the estimation blood glucose value; And

If described estimation blood glucose value is higher than predetermined threshold, show described estimation blood glucose value, and if described estimation blood glucose value be equal to or less than predetermined threshold then use the reduction parameter to form blood glucose value and then to show described blood glucose value through adjusting through adjusting.

20, method according to claim 19, wherein, described fixed background current value is from 0.0nA to 10nA.

21, according to the described method of claim 19, wherein, described Sensitirity va1ue is to determine by removing described clean analyte sensor current value with the capillary blood glucose value of measuring.

22, method according to claim 19, wherein, described predetermined threshold is 90mg/dl.

23, method according to claim 19, wherein, described application reduction parameter comprises described estimation blood glucose value used and is about 15% or still less reduction parameter.

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