A kind of wireless and passive flexible sensing device and method for sweat glucose detectionTechnical field
The present invention relates to a kind of electrochemical measuring techniques of wireless and passive, more particularly to one kind to be used for sweat glucose detectionWireless and passive flexible sensing device and method.
Background technique
Sweat is the common liquid of body surface secretion, is a more complicated liquid environment, contains such as glucoseDeng substance relevant to human body physiological characteristics.These substances include physiologic information abundant, by these objects in sweatThe analysis of matter, so that it may realize the non-invasive monitoring to human motion state and health status.Concentration of glucose and blood in sweatConcentration of glucose in liquid there are certain correlations can be to a certain extent by the concentration of glucose in detection sweatCorresponding blood sugar concentration is gone, realizes the non-invasive monitoring of blood glucose.
At present about wearable sweat glucose detection, there are some relevant researchs both at home and abroad.But it reportsThe wearable sweat glucose sensing device in road is powered using battery, carries out data biography with Bluetooth Communication TechnologyDefeated, these devices can not be accomplished further to minimize due to the limitation of battery, flexibility and integrated, can not be noninductive to peopleAnd comfortable lagging formula wearing experience.
Summary of the invention
It is an object of the invention to above-mentioned equipment there are aiming at the problem that, provide a kind of for sweat glucose detectionWireless and passive flexible sensing device and method.
The purpose of the present invention is achieved through the following technical solutions: a kind of wireless nothing for sweat glucose detectionSource flexible sensing device, including reusable circuit and replaceable two parts of electrode, wherein reusable electricityRoad part include the first substrate and processing in the first substrate and be sequentially connected NFC antenna, NFC chip and its peripheral circuit,Single-chip minimum system, AFE chip and its peripheral circuit, connector；Replaceable electrode section is glucose electrode；GlucoseElectrode is installed on connector, Portugal when which is placed on body surface skin, in body surface skin sweatGrape glycan molecule on glucose electrode by catalysis oxidation, react the response current of generation by connector pass to AFE chip and itsPeripheral circuit is converted to voltage signal after signal condition, is sent into single-chip minimum system and carries out analog-to-digital conversion, after conversionData are transmitted to NFC chip and its peripheral circuit；Mobile terminal with NFC module by inductive coupling between antenna withWireless data interaction and energy transmission occur for NFC antenna and NFC chip and its peripheral circuit, read comprising concentration of glucoseThe voltage change data of information.
Further, by the mobile terminal with NFC module close to NFC antenna within 2cm, NFC chip and its peripheryCircuit can obtain electric energy by the inductive coupling between antenna, to single-chip minimum system and AFE chip and its periphery electricityThe voltage of road offer highest 3.3V.
Further, the glucose electrode is printed with using printed electronic technique to electrode, reference electricity in the second substratePole and working electrode.
Further, multiple modification has been carried out on the working electrode, has been successively Prussian blue layer, sensing from below to upLayer and separation layer.
Further, the Prussian blue layer is deposited by electrochemical method.
Further, the sensing layer the production method is as follows:
The chitosan of 1wt% is dissolved in the acetum that mass fraction is 2%, adds 2mg/mL singleIt is ultrasonically treated after pipe, obtains aaerosol solution；10mg/mL glucose oxidase solution and aaerosol solution are mixed by 1:2 volume ratioAfter uniformly, it is added drop-wise to Prussian blue layer surface, forms sensing layer after dry.
Further, it also added single-walled carbon nanotube in the mixed solution.
Further, the separation layer uses perfluorinated sulfonic acid separation layer.
It is soft using the above-mentioned wireless and passive for body surface sweat glucose detection that it is a further object of the present invention to provide a kind ofProperty sensing device carry out sweat examination of glucose concentration method, include the following steps:
(1) with the Glucose standards sample solution of sensing device detection various concentration:
Configure the Glucose standards sample solution of various concentration；By the mobile terminal with NFC module close to NFC antenna,Sensing device is set to work；The Glucose standards sample solution of the various concentration of preparation number is successively added dropwise on glucose electrode surface,Mobile terminal persistently receives the current signal that sensing device measures, the value after record current signal is steady under each concentration, asCurrent-responsive under the concentration rinses glucose electrode surface and drying after having surveyed each concentration；
(2) standard curve of Glucose standards sample solution concentration and current signal is established:
It uses at least three pieces glucose electrode instead, repeats the measurement process in step (1), obtain every glucose electrode notWith the current-responsive under the Glucose standards sample solution of concentration；Obtain Glucose standards sample solution concentration and sensor currentRelation curve between response, current value of the relation curve for by measuring are dense to calculate the glucose in true sweatDegree；
(3) concentration of glucose in body test sweat:
Glucose electrode to be measured is inserted into connector, one layer of mandruka, is used in the surface cushion of glucose electrodeOf short duration absorption and storage sweat；And one layer of medical silicon is sticked on the surface of wireless and passive flexible sensing device and skin contactGel exposes the sensitive zones of glucose electrode, cleans target skin area with alcohol swab, and wireless and passive flexible sensing is filledIt sets and is attached at skin surface；After fixing wireless and passive flexible sensing device, user starts to perform physical exercises, and works as body surfaceWhen starting to secrete sweat, glucose electrode surface is absorbed into the sweat from skin surface by mandruka, the Portugal in sweatGrape sugar, by catalysis oxidation, generates current signal on glucose electrode；By the mobile terminal with NFC module close to NFC antenna,The current signal data that sensing device measures will be transferred to mobile terminal by NFC antenna, the grape obtained using step (2)Relation curve between Standard for Sugars sample solution concentration and sensor current response, mobile terminal calculate Portugal in user's solutionThe concentration information of grape sugar, and real-time display concentration value on mobile terminals, draw corresponding concentration curve.
The present invention has the advantages that scheme is given up completely relative to existing wearable sweat glucose sensing deviceBattery power supply has been abandoned, energy transmission and data interaction have been carried out by the way of NFC, compared to traditional sensing device, this hairThe bright structure design for enormously simplifying hardware, allows system to accomplish further lightening, integration and miniaturization.DeviceHardware circuit part using polyimides material flexible as substrate, entire circuit part can repeatedly use；ElectricityPole part uses the dimethyl silicone polymer of flexible extensible as substrate, so that whole system has accomplished complete flexibility,Cooperation is flexible and has the Silica hydrogel of bioaffinity, can ideally be bonded with skin, the almost noninductive and comfortable patch to peopleThe wearing experience of skin formula, carries out the detection of real-time sweat concentration of glucose.Simultaneously as smart phone is popularized out at presentCome, and is all integrated with NFC module in most smart phone, therefore the device can be with the intelligent hand with NFC moduleMachine is used cooperatively, and realizes that wireless energy and data transmission, the data for being transferred to mobile phone terminal can be analyzed further, handled, protectedIt deposits and uploads.According to the above advantage, the present invention can be widely applied to noninvasive health monitoring based on sweat glucose sensing andMedical diagnosis on disease is with a wide range of applications.
Detailed description of the invention
Fig. 1 is the overall structure frame in the present invention for the wireless and passive flexible sensing device of body surface sweat glucose detectionFigure；
Fig. 2 is glucose electrode structure chart in the present invention；
Fig. 3 is smart phone surface chart in the present invention；
Fig. 4 is the workflow in the present invention for the wireless and passive flexible sensing device of body surface sweat glucose detectionFigure；
Fig. 5 is the result figure that different glucose standard solution is tested in the present invention；
Fig. 6 is the linear graph of the glucose standards solution concentration and current-responsive tested in the present invention；
Fig. 7 is that the glucose solution tested in the present invention repeats linearity curve；
Fig. 8 is the glucose solution stability curve tested in the present invention；
Fig. 9 is the special linearity curve of glucose solution tested in the present invention；
Figure 10 is done in the present invention in body glucose detection result.
In figure: detection circuit NFC antenna 1, NFC chip and its peripheral circuit 2, single-chip minimum system 3, AFE chip andIts peripheral circuit 4, connector 5, glucose electrode 6, the first substrate 7, the second substrate 61, to electrode 62, reference electrode 63, workElectrode 64, Prussian blue layer 65, sensing layer 66, separation layer 67.
Specific embodiment
Below in conjunction with drawings and concrete examples, the present invention is described in detail, but is not the limitation present invention.
As shown in Figure 1, the present invention provides a kind of wireless and passive flexible sensing device for sweat glucose detection, includingReusable circuit and replaceable two parts of electrode, wherein reusable circuit part includes the first substrate 7With processing in the first substrate 7 and be sequentially connected NFC (i.e. Near Field Communication, near-field communication) antenna 1,NFC chip and its peripheral circuit 2, single-chip minimum system 3, AFE (Analog Front End, AFE(analog front end)) chip and its outerEnclose circuit 4, connector 5；Replaceable electrode section is glucose electrode 6, and glucose electrode 6 is installed on connector 5；SweatIn glucose molecule on glucose electrode 6 by catalysis oxidation, the response current for reacting generation passes to AFE by connector 5Chip and its peripheral circuit 4 are converted to voltage signal after signal condition, are sent into single-chip minimum system 3 and carry out modulus turnIt changes, the data after conversion are transmitted to NFC chip and its peripheral circuit 2；Mobile terminal with NFC module passes through between antennaInductive coupling and NFC antenna 1 and NFC chip and its peripheral circuit 2 occur wireless data and interact and energy transmission, read packetThe voltage change data of the information containing concentration of glucose.
Further, by the mobile terminal with NFC module close to NFC antenna 1 within 2cm, NFC chip and its peripheryCircuit 2 can obtain electric energy by the inductive coupling between antenna, to single-chip minimum system 3 and AFE chip and its peripheryThe voltage of circuit (4) offer highest 3.3V
Further, as shown in Fig. 2, the glucose electrode 6 is printed on the second substrate 61 brush using printed electronic techniqueHave to electrode 62, reference electrode 63 and working electrode 64.Multiple modification is carried out on the working electrode 64, from below to up successivelyIt is Prussian blue layer 65, sensing layer 66 and separation layer 67.The Prussian blue layer 65 is deposited by electrochemical method.InstituteState sensing layer 66 the production method is as follows: by the chitosan of 1wt% be dissolved in mass fraction be 2% acetum in, then plusIt is ultrasonically treated after entering 2mg/mL single-walled carbon nanotube, obtains aaerosol solution；By 10mg/mL glucose oxidase solution and suspend moltenLiquid after mixing, is added drop-wise to Prussian blue 65 surface of layer, forms sensing layer 66 after dry by 1:2 volume ratio.The separation layer67 use perfluorinated sulfonic acid separation layer.
It is soft using the above-mentioned wireless and passive for body surface sweat glucose detection that it is a further object of the present invention to provide a kind ofProperty sensing device carry out sweat examination of glucose concentration method, include the following steps:
(1) with the Glucose standards sample solution of sensing device detection various concentration:
Prepare the Glucose standards sample solution of various concentration；By the mobile terminal with NFC module close to NFC antenna 1,Sensing device is set to work；The Glucose standards sample solution of the various concentration of preparation number is successively added dropwise on 6 surface of glucose electrode,Mobile terminal persistently receives the current signal that sensing device measures, the value after record current signal is steady under each concentration, asCurrent-responsive under the concentration rinses 6 surface of glucose electrode and drying after having surveyed each concentration；
(2) standard curve of Glucose standards sample solution concentration and current signal is established:
It uses at least three pieces glucose electrode 6 instead, repeats the measurement process in step (1), obtain every glucose electrode 6 and existCurrent-responsive under the Glucose standards sample solution of various concentration；Obtain Glucose standards sample solution concentration and sensor electricityRelation curve between stream response, current value of the relation curve for by measuring are dense to calculate the glucose in true sweatDegree；
(3) concentration of glucose in body test sweat:
It is inserted into connector 5 in glucose electrode 6 to be measured, one layer of mandruka in the surface cushion of glucose electrode 6 is usedIn of short duration absorption and storage sweat；And the surface of wireless and passive flexible sensing device and skin contact stick one layer it is medicalSilica hydrogel exposes the sensitive zones of glucose electrode 6, cleans target skin area with alcohol swab, and wireless and passive flexibility is passedInduction device is attached at skin surface；After fixing wireless and passive flexible sensing device, user starts to perform physical exercises, whenWhen body surface starts to secrete sweat, 6 surface of glucose electrode is absorbed into the sweat from skin surface by mandruka, in sweatGlucose on glucose electrode 6 by catalysis oxidation, generate current signal；By the mobile terminal with NFC module close to NFCAntenna 1, the current signal data that sensing device measures will be transferred to mobile terminal by NFC antenna 1, be obtained using step (2)Relation curve between the Glucose standards sample solution concentration arrived and sensor current response, mobile terminal calculate userThe concentration information of glucose in sweat, and real-time display concentration value on mobile terminals, draw corresponding concentration curve.
Fig. 3 is the interface schematic diagram with the mobile terminal of NFC module, and the NFC module of mobile terminal is filled close to sensingThe NFC antenna 1 set, is coupled by coil, between mobile terminal and wireless and passive flexible sensing device occur energy transmission andData interaction can show the glucose concentration data read in real time from sensing device on mobile terminal, and will test fructufyWhen be shown on interface of mobile terminal.
Below by embodiment further the present invention is described in detail.
Embodiment:
The analysis that concentration of glucose in sweat is carried out using the flexible sensing device of the wireless and passive, is included the following steps:
(1) biochemical modification of working electrode 64:
One layer of Prussian blue layer 65 is deposited by cyclic voltammetry (Cyclic Voltammetry, hereinafter referred to as CV), it is moltenIt include 2.5mM ferric trichloride, 100mM potassium chloride, the 2.5mM potassium ferricyanide and 100mM hydrochloric acid in liquid, the scanning range of CV is0-0.5V, scanning speed 0.02V/s；The chitosan of 1wt% is dissolved in the acetum of 2% mass fraction, is addedIt is ultrasonically treated 30min after 2mg/mL single-walled carbon nanotube, obtains aaerosol solution, by 10mg/mL glucose oxidase solution and is hangedFloating solution after mixing according to 1:2 volume ratio takes 3 μ L to be added drop-wise to Prussian blue 65 surface of layer, is dried at room temperature for forming biographyFeel layer 66；0.5% perfluorinated sulfonic acid is added dropwise on 66 surface of sensing layer, one layer of more firm film can be formed after its drying,Substance in the step of front two can be fixed on working electrode surface and be unlikely to fall off easily；
(2) design of circuit:
The resonant frequency of the NFC antenna 1 of wireless and passive flexible sensing device for body surface sweat glucose detection is13.56MHz, NFC chip use the NT3H2111 at grace intelligence Pu, energy can be coupled by antenna, and pass through internal energy source capsuleReason module is modulated into the voltage output of 3.3V, single-chip microcontroller and AFE(analog front end) power supply to rear end.What single-chip microcontroller was selected is TI companySuper low-power consumption MSP430FR5959, for electrochemical sensing AFE chip select is TI company super low-power consumptionLMP91002.In actual use, what the mobile terminal with NFC module was selected is the Galaxy S5 mobile phone of Samsung；
The workflow of entire sensing device is as shown in Figure 4.Energy transmission passes through from the NFC module of smart phoneThe mutual inductance of antenna is transferred to the NFC antenna 1 of sensing device, and the NFC chip connecting with NFC antenna obtains energy from NFC antenna 1Amount, and energy is managed into circuit by internal electric source and continues rear end circuit transmission, what the single-chip microcontroller of rear end was provided in NFC chipIt works under energy, sends control instruction to AFE chip.Glucose electrode is catalyzed Portugal in the presence of having glucose moleculeGrape are glycoxidative, generate response current signal and are transferred to AFE chip, AFE passes through internal conditioning circuit for response current signalVoltage signal is converted to, and the signal is sent to modulus conversion port in the piece of single-chip microcontroller, single-chip microcontroller is performing voltage signalChange data is transmitted to the internal storage space of NFC chip, the application software (Smart of smart phone after conversion operationPhone Application, hereinafter referred to as APP) by calling internal NFC to drive relevant application programming interfaces(Abbreviation for Application Programming Interface, hereinafter referred to as API) reads NFC chipStorage inside data, and the results are shown on smart phone interface；
(3) sensitivity test of sensor:
Compound concentration is 100 μM, 200 μM, 300 μM, 400 μM, 500 μM of Glucose standards sample solution.It will be to be measuredGlucose electrode 6, which is inserted into connector 5, works normally sensing device by Samsung S5 close to NFC antenna 1.Electrode surface successivelyPrepared 100 μM to 500 μM of concentration of glucose standard sample solution is added dropwise, then is successively added dropwise prepared 400 μM to 100μM concentration of glucose standard sample solution, mobile terminal persistently receives the current signal that sensing device measures, under each concentrationThe detection data for recording 100s takes the data of rear 30s as the current-responsive under the concentration, has surveyed each concentration need to spend fromSub- water rinses electrode surface and with being dried with nitrogen, and the result of obtained sensitivity test is as shown in Figure 5, it can be seen that all concentrationThe test result of glucose solution show good gradient, sensitivity is 0.714nA/ μM；
(6) the linear and reperformance test of sensor:
Compound concentration is 100 μM, 200 μM, 300 μM, 400 μM, 500 μM of Glucose standards sample solution.It will be to be measuredGlucose electrode 6, which is inserted into connector 5, works normally sensing device by Samsung S5 close to NFC antenna 1.Electrode surface successivelyPrepared 100 μM to 500 μM of concentration of glucose standard sample solution is added dropwise, mobile phone terminal persistently receives what sensing device measuredCurrent signal records the detection data of 40s under each concentration, takes the data of 40s as the current-responsive under the concentration, surveyedEach concentration needs to be rinsed electrode surface with deionized water and with being dried with nitrogen.With 5 different glucose electrodes 6, repeat withUpper measurement process obtains current-responsive of each glucose electrode 6 under 5 kinds of different concentration of glucose.Obtain Glucose standardsLinear relationship curve (Fig. 6) between sample solution concentration and sensor current response, it can be seen that five groups of test result fittingsIt is fine, slope be -0.716nA/ μM, R2It is 0.99, which calculates true sweat for the current value by measuringConcentration of glucose in liquid.In addition, also obtaining the repetition linearity curve (Fig. 7) of 5 glucose sensors 6, repeat to draw in linearity curveThe response results for having made multiple groups glucose solution are compareed, it can be seen that the testing result of multiple groups glucose solution is kissed substantiallyIt closes, has good repeatability；
(7) stability test of sensor:
Glucose electrode 6 to be measured is inserted into connector 5 by the Glucose standards sample solution that compound concentration is 300 μM, willSamsung S5 works normally sensing device close to NFC antenna 1.The glucose of prepared 300 μM of concentration is added dropwise in electrode surfaceStandard sample solution, smart phone persistently receive the current signal that sensing device measures, the inspection of 180min are recorded under each concentrationMeasured data takes the data of rear 120min as the current-responsive under the concentration, has surveyed each concentration and needed to be rinsed with deionized waterElectrode surface and with being dried with nitrogen, the result of obtained stability test is as shown in figure 8, as can be seen from the figure glucose electricityThe fluctuation of pole response current is 16.69 μ A/h, with good stability；
(8) specific test of sensor:
Respectively prepare phosphate-buffered to, 10mM lactic acid solution, 10mM sodium chloride solution, 10mM Klorvess Liquid, 1mM chlorineChange calcium solution, 10 μM of ascorbic acid solutions, the Mcllvaine buffer of pH=6 and 100 μM of glucose solution and carries out specificityGlucose electrode 6 to be measured insertion connector 5 works normally sensing device by Samsung S5 close to NFC antenna 1 by test.Solution to be measured is successively added dropwise in electrode surface, smart phone persistently receives the current signal that sensing device measures, every kind of solution noteThe detection data for recording 120s, takes the data of rear 60s as the current-responsive under the concentration, has surveyed each concentration and needed to use deionizationWater rinses electrode surface and with being dried with nitrogen, obtained specific test result as shown in figure 9, it can be seen from the figure thatIt is added to after other solution, is not much affected using the obtained glucose responding result of sensing device, it was demonstrated thatThe electrode has good specificity to glucose；
(9) it is tested in the sweat glucose of body:
Glucose electrode 6 to be measured is inserted into connector 5, one layer of mandruka in the surface cushion of glucose electrode 6 is usedIn of short duration absorption and storage sweat.And one layer of medical Silica hydrogel is sticked in the bottom of entire sensing device, expose glucoseThe sensitive zones of electrode 6, the target skin area of subject is cleaned with alcohol swab, and sensing device is attached at skin surface(upper arm).It is completed in the sweat glucose test of body in gymnasium, after fixing sensing device, subject starts to carry out stepping on listVehicle movement, motion continuation 35 minutes, first 20 minutes were high-intensity exercise, were moved for low-intensity within intermediate 10 minutes, last 5 minutes stopOnly move.When body surface starts to secrete sweat, glucose electrode surface is absorbed into the sweat from skin surface by mandrukaLiquid, the glucose in sweat, by catalysis oxidation, generate current signal on glucose electrode 6.When starting per minute, subject is beatenCorresponding APP on Samsung S5 is opened, by mobile phone close to the NFC antenna 1 of sensing device, the current signal data that sensing device measures are justIt can be transferred to mobile terminal by NFC antenna 1, Glucose standards sample solution concentration and the sensor electricity obtained using step 6Relation curve between stream response, mobile terminal can calculate the concentration of glucose in this minute sweat of subject, and softReal-time display concentration value on part interface, draws corresponding concentration curve.In our actual tests, test per minute continues40s, and take the concentration of glucose of 40s as this minute concentration of glucose result.After test, subject removes sensingDevice removes mandruka and glucose electrode 6, the sweat stain on sensing device surface is cleaned out in case next time uses.?The mandruka and glucose electrode 6 used needs to abandon.The resulting 35 minutes glucose concentration curves in body test are as schemedShown in 10, it can be seen that with being incremented by for subject motion's time, the sweat concentration of glucose detected shows decline and becomesGesture, this is consistent with the result that special instrument is tested.