CN110208352A - The factory calibration method of glucose sensor - Google Patents
The factory calibration method of glucose sensor Download PDFInfo
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- CN110208352A CN110208352A CN201910551646.1A CN201910551646A CN110208352A CN 110208352 A CN110208352 A CN 110208352A CN 201910551646 A CN201910551646 A CN 201910551646A CN 110208352 A CN110208352 A CN 110208352A
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- glucose
- sensor
- enzyme layer
- calibration method
- factory calibration
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/4163—Systems checking the operation of, or calibrating, the measuring apparatus
Abstract
Present disclose provides a kind of factory calibration methods of glucose sensor comprising: obtain multiple glucose sensors of technological parameter with uniformity；At least one glucose sensor is chosen as sample sensor from multiple glucose sensors, analysis test is carried out to sample sensor, obtains the electric current of sample sensor with the change curve of concentration of glucose and the attenuation curve of sensitivity；The compensation model of sample sensor is generated based on change curve and attenuation curve；And compensation model is embedded into multiple glucose sensors to realize the automatic calibration to multiple glucose sensors.In the factory calibration method of the glucose sensor involved in the disclosure, compensation model can be generated based on change curve and attenuation curve, glucose sensor can constantly correct itself by the compensation model of insertion, and thereby, it is possible to realize the automatic calibration of sensor.
Description
Technical field
This disclosure relates to glucose sensor field, in particular to the factory calibration method of a kind of glucose sensor.
Background technique
Diabetes are a series of metabolic disorder syndromes such as sugar, protein, fat, water and electrolyte, by inherent cause,
The various virulence factors such as immunologic function disorder, microorganism infection and its toxin, which act on body, leads to hypoinsulinism, pancreas islet
Element resist etc. and cause.If diabetes do not obtain good control, it is likely that some complication, such as ketosis can be caused
Acid poisoning, lactic acidosis, chronic renal failure and retinopathy.With the continuous raising of the disease incidence of diabetes, glycosuria
Disease has become worldwide public health problem.
Currently, blood sugar monitoring is a ring important in diabetes management, can be significantly reduced by the blood glucose of managing patient
Diabetic complication risk.Existing blood sugar monitoring mode is mainly glycosylated hemoglobin and refers to blood blood sugar monitoring.However, saccharification
What hemoglobin reflected is 2~3 months average blood glucose levels, can not realize blood glucose by observing short-term blood sugar concentration
Control in time.In addition, refer to that blood blood sugar monitoring can only obtain single point blood glucose value, can not obtain in short term than more comprehensive blood glucose numerical value,
It is difficult to realize comprehensive control of blood glucose, and operating process is complicated in blood collection procedure and needs repeatedly invasive acquisition, to trouble
Person brings undesirable user experience, and the compliance for causing patient periodically to carry out blood sugar monitoring is poor.In view of the above problems, even
Continuous blood sugar monitoring is that diabetic carries out the more promising developing direction of blood sugar monitoring.It is monitored by continuous blood sugar, it can
Reflection current blood glucose concentration in real time, and continuous and comprehensive blood glucose value is obtained, it can facilitate patient or help is instructed to cure in this way
It is raw that patient is instructed to carry out glycemic control.
However, traditional continuous blood sugar monitoring since consistency can not be controlled well, need daily 1~2 time even more
Multiple frequent finger blood blood sugar monitoring is calibrated, and applicable range is also mainly for type-1 diabetes mellitus patient
Just need market.
Summary of the invention
The disclosure in view of the above-mentioned prior art situation and complete, its purpose is to provide a kind of glucose sensors
Factory calibration method.
For this purpose, the disclosure provides a kind of factory calibration method of glucose sensor characterized by comprising obtain tool
There are multiple glucose sensors of consistency technological parameter；At least one glucose is chosen from the multiple glucose sensor to pass
Sensor carries out analysis test as sample sensor, to the sample sensor, obtains the electric current of the sample sensor with Portugal
The change curve of grape sugar concentration variation and the attenuation curve of sensitivity；It is generated based on the change curve and the attenuation curve
The compensation model of the sample sensor；And the compensation model is embedded into the multiple glucose sensor to realize pair
The automatic calibration of the multiple glucose sensor.
It, can be bent based on change curve and decaying in the factory calibration method of the glucose sensor involved in the disclosure
Line generates compensation model, and glucose sensor can constantly correct itself by the compensation model of insertion, as a result, can
Enough realize the automatic calibration of sensor.
In addition, optionally, the glucose sensor includes successively layer in the factory calibration method involved in the disclosure
The semi-permeable membrane of the quantity of folded substrate, the glucose enzyme layer and control glucose that can react with glucose, it is described consistent
Property technological parameter include the quality of the glucose enzyme layer, the volume of the glucose enzyme layer, the glucose enzyme layer thickness,
At least one of the film thickness of active, the described semi-permeable membrane of the glucose enzyme layer, diffusion coefficient of the semi-permeable membrane.This
In the case of, by controlling the quality of glucose enzyme layer, the volume of glucose enzyme layer, the thickness of glucose enzyme layer, glucose enzyme layer
Activity, the parameters such as diffusion coefficient of the film thickness of semi-permeable membrane, semi-permeable membrane, enable to glucose sensor technique with uniformity
Parameter.
In addition, in the factory calibration method involved in the disclosure, optionally, the attenuation curve and the sensor sample
The quality of the glucose enzyme layer in product, the volume of the glucose enzyme layer, the thickness of the glucose enzyme layer, the grape
At least one of the diffusion coefficient correlation of the film thickness of active, the described semi-permeable membrane of carbohydrase layer, the semi-permeable membrane.In such case
Under, it can be by controlling the quality of glucose enzyme layer, the volume of glucose enzyme layer, the thickness of glucose enzyme layer, glucose enzyme layer
Activity, the film thickness of semi-permeable membrane, semi-permeable membrane diffusion coefficient to control the trend of attenuation curve.
In addition, in the factory calibration method involved in the disclosure, optionally, by the matter for controlling the glucose enzyme layer
Active, the described semi-permeable membrane of amount, the volume of the glucose enzyme layer, the thickness of the glucose enzyme layer, the glucose enzyme layer
Film thickness, the semi-permeable membrane at least one of diffusion coefficient improve the attenuation curve.It is optimal thereby, it is possible to obtain
Attenuation curve.
In addition, in the factory calibration method involved in the disclosure, optionally, by reducing the multiple glucose sensing
The operating voltage of device reduces the background current of the glucose sensor to improve the consistency technological parameter.As a result, can
Enough so that the background current of glucose sensor has preferable consistency.
In addition, optionally, the attenuation curve reflects the sensor in the factory calibration method involved in the disclosure
Sensitivity in sample changes with time.Thereby, it is possible to the variation of sensitivity is observed by attenuation curve.
In addition, optionally, obtaining the biography according to the attenuation curve in the factory calibration method involved in the disclosure
The initial sensitivity and attenuation coefficient of sensor sample, to calculate compensation rate.Thereby, it is possible to easily obtain to glucose sensor
Required compensation rate.
In addition, further including by spin coating, Best-Effort request, drop optionally in the factory calibration method involved in the disclosure
It applies at least one of spraying process technique and realizes the consistency technological parameter.Thereby, it is possible to improve glucose sensing
The consistency of device.
In addition, in the factory calibration method involved in the disclosure, optionally, in the automatic calibration, by described
The compensation rate that compensation model calculates calibrates concentration of glucose.Thereby, it is possible to improve the reliability of the concentration of glucose measured.
In addition, in the factory calibration method involved in the disclosure, optionally, in analysis test, by the biography
Sensor sample is placed in the glucose solution with defined concentration of glucose, and acquires the sample sensor institute at any time
The concentration of glucose measured, to obtain the change curve and the attenuation curve of the sample sensor.Thereby, it is possible to
By the test to sample sensor to obtain the electrochemical parameter with a batch of glucose sensor.
According to the disclosure, it is capable of providing a kind of factory calibration method of glucose sensor.
Detailed description of the invention
Fig. 1 is to show the flow chart of the factory calibration method of glucose sensor involved in the disclosure.
Fig. 2 is to show the factory calibration method testing flow diagram of glucose sensor involved in the disclosure.
Fig. 3 is to show the factory calibration method testing status diagram of glucose sensor involved in the disclosure.
Fig. 4 is to show the structural schematic diagram of the working electrode of glucose sensor involved in the disclosure.
Fig. 5 is to show the system schematic of the factory calibration method of glucose sensor involved in the disclosure.
Fig. 6 is that the electric current that shows involved in the disclosure with a batch of glucose sensor is dense with glucose solution
The change curve of degree.
Fig. 7 is the sensitivity attenuation curve of the sensitivity for showing glucose sensor involved in the disclosure and time.
Specific embodiment
In the following, illustrating the disclosure in further detail in conjunction with the drawings and specific embodiments.In the accompanying drawings, identical portion
Part or component with the same function use identical sign flag, omit the repeated explanation to it.
Fig. 1 is to show the flow chart of the factory calibration method of glucose sensor 1 involved in the disclosure.Fig. 2 is to show
The factory calibration method testing flow diagram of glucose sensor involved in the disclosure is gone out.Fig. 3 is to show this public affairs
The factory calibration method testing status diagram of glucose sensor 1 involved in opening.
In the present embodiment, as shown in Figure 1, glucose sensor involved in the disclosure (also referred to as " passes sometimes below
Sensor ") 1 factory calibration method the step of include: obtain technological parameter with uniformity multiple glucose sensors 1 (step
Rapid S100)；At least one sample sensor 10 is chosen from multiple glucose sensors 1, analysis survey is carried out to sample sensor 10
Examination obtains the electric current change curve (being described later on) changed with concentration of glucose of sample sensor 10 and the decaying of sensitivity
Curve (is described later on) (step S200)；Compensation model (the step of sample sensor 10 is generated based on change curve and attenuation curve
Rapid S300)；And compensation model is embedded into multiple glucose sensors 1 to realize to the automatic of multiple glucose sensors 1
It calibrates (step S400).
In the factory calibration method of the glucose sensor 1 involved in the disclosure, change curve and decaying can be based on
Curve generates compensation model, and glucose sensor 1 can constantly correct itself by the compensation model of insertion, by
This, can be realized the automatic calibration of sensor 1.
By using the glucose blood sugar monitoring continuous blood sugar after the check and correction of factory calibration method involved in present embodiment
Detection device once after painless piercing can long term monitoring blood sugar concentration, do not need to refer to that blood blood sugar monitoring frequently carries out referring to that blood is adopted
Collection, the user experience is improved well, and many type-II diabetes people other than a diabetes mellitus type just needs is allowed also to be ready out
Begin to carry out comprehensive diabetes management using continuous blood sugar monitoring.
In the step s 100, multiple glucose sensors 1 of technological parameter with uniformity are obtained.Here, glucose passes
The consistency of sensor 1 includes glucose sensor 1 under concentration of glucose response sensitivity consistency and low-work voltage
The consistency of background current.Wherein, background current refers under certain voltage, electric current existing for glucose sensor 1 itself.
In addition, in the present embodiment, the glucose sensor of technological parameter with uniformity refers to same in production
The glucose sensor of batch factory, the glucose sensor that usually same batch products are prepared under identical technique.
In some instances, referring to the Fig. 4 being described later on, consistency technological parameter may include glucose enzyme layer 112
Quality, the volume of glucose enzyme layer 112, the thickness of glucose enzyme layer 112, the activity of glucose enzyme layer 112, semi-permeable membrane 113
At least one of film thickness, diffusion coefficient of semi-permeable membrane 113.In this case, pass through the matter of control glucose enzyme layer 112
The film of amount, the volume of glucose enzyme layer 112, the thickness of glucose enzyme layer 112, the activity of glucose enzyme layer 112, semi-permeable membrane 113
The parameters such as thick, semi-permeable membrane 113 diffusion coefficient, can make glucose sensor 1 have preferable consistency technological parameter.
In some instances, further include by least one of spin coating, Best-Effort request, drop coating and spraying process technique come
Realize consistency technological parameter.Thereby, it is possible to improve the consistency of glucose sensor 1.In some instances, for glucose
For the film thickness of enzyme layer 112, semi-permeable membrane 113 etc., can by spin speed and in terms of control.
In some instances, glucose sensor 1 can also be reduced by reducing the operating voltage of glucose sensor 1
Background current.Thereby, it is possible to make the background current of glucose sensor 1 have preferable consistency.
In the present embodiment, as described above, choosing at least one sample sensor 10 from multiple glucose sensors 1,
Analysis test carried out to sample sensor 10, obtain the electric current of sample sensor 10 with the change curve that concentration of glucose changes with
And the attenuation curve of sensitivity.
As shown in Fig. 2, being selected to be measured in No. 1 to No. n-th sensor in the sensor 1 of same batch factory
The sample sensor 10 of examination, then carries out analysis test to sample sensor 10.
In some instances, analysis test, which can be by the way that sample sensor 10 is placed in glucose solution 20, carries out,
And obtain the electrochemical parameter of sample sensor 10.In some instances, specifically, being placed in the sensing in glucose solution 20
Glucolase (the specifically glucolase of the working electrode 11 of sample sensor 10, referring to Fig. 3) normal concentration of device sample 10
Glucose solution 20 generate redox reaction, and generate electronics, electric current formed in sample sensor 10, so as to root
It is converted into concentration of glucose according to electric current, and then glucose sensor 1 is obtained according to the relationship between concentration of glucose and electric current
Electric current with concentration of glucose change curve, then, persistently to concentration of glucose variation and response current be monitored, thus
Obtain the attenuation curve of 1 sensitivity of glucose sensor.
In the present embodiment, the concentration of glucose of glucose solution 20 is not particularly limited, but from suitable for human body
From the point of view of continuous blood sugar detection, the concentration of glucose of glucose solution 20 can be equal or close to the concentration of blood sugar for human body.
In the present embodiment, the glucose sensor 1 with preferable consistency is produced by consistency technique, thus
It is capable of the electrochemical parameter of sensor 1 a small amount of by measurement or partial amt to obtain with a batch of other sensors 1
Electrochemical parameter.
In some instances, glucolase can be one of glucose oxidase or glucose dehydrogenase or a variety of.
In other words, glucolase can be glucose oxidase or glucose dehydrogenase, can also have simultaneously glucose oxidase and
Glucose dehydrogenase.
As described above, the analysis test of the electrode of glucose sensor 1 can be by the way that sample sensor 10 is put into Portugal
To measure its electrochemical parameter in grape sugar juice 20.In some instances, multiple sample sensors 10 can be divided simultaneously
Analysis test.
In addition, in some instances, glucose sensor 1 can have unique physical address (MAC), the physical address
It can store in electronic system 2 (referring to Fig. 5).In such a case, it is possible to obtain corresponding sensor sample according to physical address
The electrochemical parameter of product 10 improves testing efficiency thereby, it is possible to measure the electrochemical parameter of multiple sample sensors 10 simultaneously.
In some instances, glucose sensor 1 can be that by the glucose sensor of continuous blood sugar monitoring.Cause
This, glucose sensor 1 is referred to as continuous blood sugar monitoring sensor sometimes.
Fig. 4 is to show the structural schematic diagram of the working electrode of glucose sensor involved in the disclosure.Fig. 5 is to show
The system schematic of the factory calibration method of glucose sensor involved in the disclosure.
In the present embodiment, glucose sensor 1 can also be including working electrode 11, reference electrode 12 and to electrode
13。
In some instances, the glucose sensor 1 after being pierced into skin can pass through the glucolase in working electrode 11
Redox reaction is carried out with the glucose in tissue fluid or blood, and is believed with being formed into a loop to electrode 13 to generate electric current
Number.Wherein, reference electrode 12 provides reference voltage.
In some instances, glucose sensor 1 can generate electronics by working electrode 11 and glucose response, then pass through
It crosses sensor 1 and generates electric current, electric current is converted into glucose concentration signal by electronic system 2.It is obtained by electronic system
Glucose concentration signal can be carried out being received and displayed on the display screen 3a for reading equipment 3 by reading equipment 3 (referring to Fig. 5).
In some instances, electronic system 2 can also record the relevant parameters such as time of measuring, the number of sensor 1.
In addition, electronic system 2 mode such as bluetooth, wifi etc. can launch by wireless communication.External reading
Equipment 3 can receive the glucose concentration signal of the sending of electronic system 2, and show glucose concentration value.In addition, due to this reality
Applying glucose sensor 1 involved in mode may be implemented to continue to monitor, therefore can be realized for a long time (such as 1 day to 24 days)
Continue to monitor the purpose of human glucose concentration value.
In addition, in some instances, reading equipment 3 can be reader or cell phone application.It can be read by reading equipment 3
The Portugal for taking the information being stored in from sensor 1 in electronic system 2 and showing continuous time (such as 1 day) on display screen 3a
Grape sugar concentration signal.
In some instances, the working electrode 11 of glucose sensor 1 may include the substrate 111 stacked gradually, can
The semi-permeable membrane 113 of the quantity of the glucose enzyme layer 112 and control glucose that react with glucose (referring to as shown in Figure 4).
In some instances, the substrate 111 of glucose sensor 1 can be flexible.Thereby, it is possible to reduce glucose to pass
Sensor 1 is implanted into bring sense of discomfort after human body.
In some instances, substrate 111 can be flexible substrates.Wherein, substrate 111 can substantially by polyethylene (PE),
Polypropylene (PP), polystyrene (PS), polyethylene terephthalate (PET), gathers to naphthalenedicarboxylic acid second polyimides (PI)
At least one of diol ester (PEN) is made.In addition, in other examples, substrate 111 can also substantially by metal foil,
Ultra-thin glass, single-layer inorganic film, multilayer organic film or multilayer inorganic thin film etc. are made.
In some instances, substrate 111 is also possible to non-flexible substrates 111.Non-flexible substrates 111 can be generallyd include and be led
Electrically weaker ceramics, aluminium oxide or silica etc..In this case, with the glucose sensing of non-flexible substrates 111
Device 1 can have cusp or sharp edge simultaneously, so as in the case where not needing auxiliary implanted device (not shown)
Glucose sensor 1 is implanted into skin (for example, skin shallow-layer etc.).
In some instances, the thickness of glucose enzyme layer 112 may be about 0.1 μm~100 μm, preferably about 2 μm~10 μ
M, in one example, the thickness of glucose enzyme layer 112 can be 10 μm.In this case, by the thickness control of glucolase
System to a certain extent, so as to avoid glucolase it is excessive caused by adhesive force decline, cause material to fall off in vivo,
Avoid glucolase it is very few caused by the problems such as reacting insufficient, normal concentration of glucose information out can not be fed back.
In some instances, semi-permeable membrane 113 can also include diffusion-controlled layer and be layered in anti-dry on diffusion-controlled layer
Disturb layer.In some instances, diffusion-controlled layer can be set outside anti-interference layer.In semi-permeable membrane 113, diffusion-controlled layer can be with
The diffusion of glucose molecule is controlled, anti-interference layer can prevent the diffusion of non-glucose substance.Thus, it is possible to first reduce by half
The tissue fluid or blood constituent of permeable membrane 113, then chaff interferent is blocked in outside semi-permeable membrane 113 by anti-interference layer.Common interference
Object may include generally existing in vivo uric acid, ascorbic acid, acetaminophen etc..
In some instances, semi-permeable membrane 113 can control the percent of pass of glucose molecule, i.e. semi-permeable membrane 113 can limit
The quantity of the glucose molecule of glucose enzyme layer 112 is reached in tissue fluid or blood.Specifically, the diffusion control of semi-permeable membrane 113
Preparative layer can effectively reduce the quantity for diffusing to the glucose of glucose enzyme layer 112 according to a certain percentage.
In other examples, glucose sensor 1 can also include bio-compatible film.In some instances, semi-permeable membrane
113 can also have biocompatibility.Thereby, it is possible to avoid reducing the production cost using bio-compatible film.
In other examples, reference electrode 12 can form known and fixed potential difference with tissue fluid or blood.?
In this case, working electrode 11 and tissue fluid can be measured by the potential difference that reference electrode 12 and working electrode 11 are formed
Or the potential difference between blood, to accurately grasp voltage caused by working electrode 11.Thus, it is possible to according to preset electricity
Pressure value automatically adjusts and maintains the stabilization of voltage at working electrode 11, to guarantee that the current signal of measurement can accurately reflect Portugal
Grape sugar concentration value.
In addition, in some instances, electrode 13 can be made of platinum, silver, silver chlorate, palladium, titanium or iridium.Thus, it is possible to
The electrochemical reaction at working electrode 11 is not influenced with satisfactory electrical conductivity.But present embodiment is without being limited thereto,
In other examples, to electrode 13 can also by gold, vitreous carbon, graphite, silver, silver chlorate, palladium, titanium or iridium at least
One kind is made.Thus, it is possible to reduce the influence to working electrode 11 with satisfactory electrical conductivity.
Hereinafter, in order to further illustrate the disclosure, using GOX (FAD) as glucose oxidase for illustrate working
The reaction that the glucose enzyme layer 112 of electrode 11 occurs.
In glucose enzyme layer 112, work as GOX(FAD) when encountering the glucose in tissue, it may occur that following reaction:
Glucose+GOX(FAD) → gluconolactone+GOX(FADH2) ... reaction formula (I)
GOX(FADH2)+O2→GOX(FAD)+H2O2... reaction formula (II)
Oxygen (the O in above-mentioned reaction process as can be seen that in chemical reaction2) be consumed, O2Deficiency makes to react formula (II)
O is limited to formula (I) reaction speed is reacted2Amount, can slow down with reacting for tissue glucose, and glucose sensor 1 is caused to fail.
In addition, reacting in formula (II) in above-mentioned reaction process and having H2O2Product, H2O2Collection party make in glucose enzyme layer 112
Enzyme activity decline, also result in glucose sensor 1 failure.Therefore, in some instances, can by 111 layers of substrate with
Catalyst such as nano particle is added between glucose enzyme layer 112 can make H under the effect of the catalyst2O2It decomposes anti-
It answers, specific reaction is as follows:
H2O2→2H++O2+ 2e- ... reacts formula (III)
By above-mentioned reaction formula (I) to formula (III) is reacted, can make persistently to carry out with reacting for tissue glucose.In addition,
The catalytic action that decomposing hydrogen dioxide solution reaction is played by using nano particle, thus, it is possible to accelerate the progress of reaction (III) and drop
The voltage applied required for during low reaction, to be conducive to the sensitivity for improving glucose sensor 1, extension glucose passes
Sensor 1 uses the time, and obtains low-work voltage.
Fig. 6 is to show the related electric current with a batch of glucose sensor of the disclosure with glucose concentration
Change curve.Fig. 7 is that the sensitivity decaying for the sensitivity and time for showing glucose sensor involved in the disclosure is bent
Line.
In step S300, the compensation model of sample sensor 10 is generated based on change curve and attenuation curve.
In some instances, the quality of the glucose enzyme layer 112 in attenuation curve L shown in Fig. 7 and sample sensor 10,
The volume of glucose enzyme layer 112, the thickness of glucose enzyme layer 112, the activity of glucose enzyme layer 112, semi-permeable membrane 113 film thickness,
The diffusion coefficient of semi-permeable membrane 113 is related.It in some instances, can be by controlling the quality of glucose enzyme layer 112, glucolase
The volume of layer 112, the thickness of glucose enzyme layer 112, the activity of glucose enzyme layer 112, the film thickness of semi-permeable membrane 113, semi-permeable membrane 113
Diffusion coefficient improve attenuation curve, for example, inhibiting the trend of control attenuation curve decaying.
In some instances, the consistency with higher of glucose sensor 1 of same batch factory, for example, can limit
The fixed sensitivity error with a batch of glucose sensor 1 can be no more than 6%.In some instances, same batch production
No. 1 to No. n-th sensor 1, wherein with higher sensitivity sensor 1 (such as No. n-th) and the lower sensor of sensitivity
The error of 1 (such as No. 2) can be no more than 6%.It is preferable consistent thereby, it is possible to guarantee to have with a batch of sensor 1
Property or consistency technological parameter.
It in some instances, can be by controlling the quality of glucose enzyme layer 112, the volume of glucose enzyme layer 112, grape
The thickness of carbohydrase layer 112, the activity of glucose enzyme layer 112, the film thickness of semi-permeable membrane 113, semi-permeable membrane 113 diffusion coefficient in one
Kind or a variety of improve attenuation curve.Suitable attenuation curve is obtained as a result,.
Fig. 6 shows the electric current of glucose sensor (sample sensor) a, sensor b, sensor c and sensor d with Portugal
The change curve of grape sugar concentration variation.By Fig. 6 it can be concluded that, sensor a, sensor b, sensor c and sensor d electric current with
The change curve consistency of concentration of glucose is preferably (initial value and slope are closer to).It can be with based on above-mentioned corresponding each curve
Obtain the relational expression of the response current y and concentration of glucose x of the glucose sensor 1 of batch factory:
Y=Ax+B ... (IV)
In formula (IV), A indicates the sensitivity of sensor, and B indicates the background current of sensor, example shown in Fig. 6
In, A is taken as 1.5, B and is taken as 0.2.
In the relational expression of response current and concentration of glucose shown in Fig. 6, y=Ax+B has reflected glucose sensor
1 change of sensitivity curve transforms into the electric current measured thus, it is possible to pass through the relationship of response current and concentration of glucose
Glucose concentration value.
In some instances, the value of A can the sensitivity attenuation curve based on sample sensor 10 and change.Thereby, it is possible to
Realize the automatic calibration function to glucose sensor 1.
In the present embodiment, initial sensitivity can be calculated according to attenuation curve L (referring to the Fig. 7 being described later on) and declined
Subtract coefficient, calculates compensation rate Δ L (t) (wherein, t is the time, similarly hereinafter).In use, it will be surveyed by glucose sensor 1
To initial sensitivity and attenuation coefficient be for example stored in electronic system 2, thereby, it is possible to utilize initial sensitivity and attenuation coefficient
It calculates compensation rate Δ L (t), to obtain compensation model appropriate.In the example in figure 7, compensation rate is Δ L (t)=L (t)-L0
(t)。
In some instances, the sensitivity of sensor 1 can change with the variation of environment.For example, in a certain range,
The sensitivity of the more high then sensor 1 of temperature is higher.
In some instances, in the case where stringent for required precision, user, which still can be used, refers to that blood examination is surveyed to grape
Sugared sensor 1 carries out assisted calibration.Thereby, it is possible to improve the accuracy of glucose detection.
In step S400, as set forth above, it is possible to which compensation model is embedded into multiple glucose sensors 1 to realize to more
The automatic calibration of a glucose sensor 1.
In some instances, the sensitivity of glucose sensor 1 can decay with the time, form the attenuation curve of sensitivity
L (referring to Fig. 7).It in this case, can be according to the stability for using the time to judge the glucose sensor 1.Show some
In example, attenuation amplitude can be 0.01%/h to 0.1%/h.In this case, even if having passed through several days, the change of sensitivity
Changing will not be too big, even if also can accurately calculate the concentration of glucose in the case where not changing sensitivity coefficient as a result,.
By sensitivity attenuation curve L, it can be concluded that, compensation model can be based on the difference DELTA L (t) of reduced sensitivity
Numerical value measured by glucose sensor 1 is compensated.
In some instances, compensation model can be embedded into electronic system 2 in the form of software.Here, glucose sensing
Device 1, electronic system 2 and reading equipment 3 may be constructed continuous blood sugar monitor.In the continuous blood sugar monitor, electronic system 2
It is electrically connected with glucose sensor 1, electronic system 2 can store the concentration signal of the glucose obtained by glucose sensor 1.
The concentration signal of the glucose, which can be wirelessly transmitted to, reads equipment 3, and thus, it is possible to know that the concentration of glucose is believed
Number.In addition, in some instances, the concentration signal of glucose can also be directly displayed on the display screen 3a for reading equipment 3.
In the present embodiment, compensation model can be embedded into multiple glucose sensors 1 to realize to multiple grapes
The automatic calibration of sugared sensor 1.
In some instances, the sensitivity that attenuation curve can reflect in sample sensor 10 changes with time.As a result,
The variation of sensitivity can be observed by attenuation curve.
In some instances, compensation model is based on change curve and attenuation curve calculates, to compensate by glucose sensor 1
The measured concentration of glucose decayed at any time.Thereby, it is possible to improve the accuracy of the measurement of glucose sensor 1.It is specific and
Speech, the compensation rate that compensation model is calculated can be the changing value of sensitivity.In other examples, what compensation model was calculated
Compensation rate can also be the changing value of concentration of glucose.
In some instances, in automatic calibration, the compensation rate that can be calculated by compensation model is dense to calibrate glucose
Degree.Thereby, it is possible to improve the reliability of the concentration of glucose measured.
In some instances, the concentration of glucose in the available tissue fluid of glucose sensor 1 or blood.But this implementation
Mode is without being limited thereto, for example, can also be used as biosensor by changing the glucose enzyme layer 112 on glucose sensor 1
Other body fluid components data in addition to glucose are obtained, it is red that body fluid components here for example can be acetylcholine, amylase, gallbladder
Element, cholesterol, human chorionic gonadtropin, creatine kinase, creatine, kreatinin, DNA, fructosamine, glucose, glutamine, life
Long hormone, hormone, ketoboidies, lactate, oxygen, peroxide, prostate-specific antigen, factor, RNA, thyroid swash
Element and troponin etc..
In other examples, the concentration of drug in body fluid can also be monitored, for example, antibiotic (for example, gentamicin,
Vancomycin etc.), foxalin, digoxin, theophylline and warfarin (warfarin) etc..
Although being illustrated in conjunction with the accompanying drawings and embodiments to the disclosure above, it will be appreciated that above description
The disclosure is not limited in any form.Those skilled in the art can without departing from the connotation and range of the disclosure
To be deformed and be changed to the disclosure as needed, these deformations and variation are each fallen in the scope of the present disclosure.
Claims (10)
1. a kind of factory calibration method of glucose sensor, which is characterized in that
Include:
Obtain multiple glucose sensors of technological parameter with uniformity；
At least one glucose sensor is chosen as sample sensor, to the sensor from the multiple glucose sensor
Sample carries out analysis test, obtains change curve and sensitivity that the electric current of the sample sensor changes with concentration of glucose
Attenuation curve；
The compensation model of the sample sensor is generated based on the change curve and the attenuation curve；And
The compensation model is embedded into the multiple glucose sensor with realize to the multiple glucose sensor from
Dynamic calibration.
2. factory calibration method as described in claim 1, which is characterized in that
The glucose sensor includes the substrate stacked gradually, the glucose enzyme layer and control that can react with glucose
The semi-permeable membrane of the quantity of glucose,
The consistency technological parameter includes the quality of the glucose enzyme layer, the volume of the glucose enzyme layer, the grape
The thickness of carbohydrase layer, the film thickness of active, the described semi-permeable membrane of the glucose enzyme layer, in the diffusion coefficient of the semi-permeable membrane extremely
Few one kind.
3. factory calibration method as described in claim 1, which is characterized in that
The attenuation curve and the quality of the glucose enzyme layer in the sample sensor, the body of the glucose enzyme layer
The thickness of long-pending, the described glucose enzyme layer, the glucose enzyme layer active, the described semi-permeable membrane film thickness, the semi-permeable membrane expansion
Dissipate at least one of coefficient correlation.
4. factory calibration method as claimed in claim 3, which is characterized in that
By the quality, the volume of the glucose enzyme layer, the thickness of the glucose enzyme layer, institute that control the glucose enzyme layer
At least one of the film thickness of active, the described semi-permeable membrane of glucose enzyme layer, diffusion coefficient of the semi-permeable membrane are stated to improve
State attenuation curve.
5. factory calibration method as described in claim 1, which is characterized in that
Reduced by reducing the operating voltage of the multiple glucose sensor the background current of the glucose sensor with
Improve the consistency technological parameter.
6. factory calibration method as described in claim 1, which is characterized in that
The attenuation curve reflects that the sensitivity in the sample sensor changes with time.
7. factory calibration method as described in claim 1 or 6, which is characterized in that
The initial sensitivity and attenuation coefficient of the sample sensor are obtained, according to the attenuation curve to calculate compensation rate.
8. factory calibration method as described in claim 1, which is characterized in that
It further include that the consistency work is realized by least one of spin coating, Best-Effort request, drop coating and spraying process technique
Skill parameter.
9. factory calibration method as described in claim 1, which is characterized in that
In the automatic calibration, concentration of glucose is calibrated by compensation rate that the compensation model calculates.
10. factory calibration method as described in claim 1, which is characterized in that
In analysis test, the sample sensor is placed in the glucose solution with defined concentration of glucose,
And concentration of glucose measured by the sample sensor is acquired at any time, to obtain the change of the sample sensor
Change curve and the attenuation curve.
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