CN113433193A - Noninvasive blood glucose detector and blood glucose detection method thereof - Google Patents
Noninvasive blood glucose detector and blood glucose detection method thereof Download PDFInfo
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 title claims abstract description 150
- 239000008103 glucose Substances 0.000 title claims abstract description 128
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- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
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Abstract
The invention discloses a noninvasive blood glucose detector and a blood glucose detection method thereof, the noninvasive blood glucose detector comprises an electrochemical detection sensor, an excitation circuit, a constant potential circuit, a transimpedance amplifier circuit, an FIFO memory and a central processing unit, the electrochemical detection sensor is connected with the transimpedance amplifier circuit, the electrochemical detection sensor is respectively connected with the input end of the constant potential circuit and the input end of the excitation circuit, the output end of the constant potential circuit is connected with the input end of the FIFO memory through a first AD converter, the transimpedance amplifier circuit is connected with the FIFO memory through a second AD converter, the FIFO memory is connected with the central processing unit, the feedback output end of the central processing unit is connected with the excitation circuit through a DA converter, the excitation circuit is connected with the electrochemical detection sensor end, the noninvasive blood glucose detection is realized by measuring the glucose content in saliva to convert the glucose content in blood glucose, the detection error is small, the circuit performance is stable, and the threshold and the risk of blood sugar detection can be effectively reduced.
Description
Technical Field
The invention belongs to the technical field of biomedical detection, and particularly relates to a noninvasive blood glucose detector and a blood glucose detection method thereof.
Background
At present, the number of people suffering from diabetes in China exceeds more than 1 hundred million, and the number of people dying due to diabetes is as high as millions every year. Because the current medical level cannot completely cure diabetes, how to detect the blood sugar concentration to remind patients of using hypoglycemic drugs becomes a main means. Along with the continuous development of the technology, most problems of blood sugar measurement can be solved by the novel electronic blood sugar detector, a traditional blood sugar detector needs to frequently collect blood samples, a pricking sampling process has trauma and obvious pain sense, and the traditional blood sugar detector cannot detect for a long time, easily causes complications caused by diabetes, brings great pain and affliction to diabetic patients, and is not accurate enough, easily influenced by the environment and the like. Therefore, blood glucose concentration detection cannot be separated from the base of needle insertion blood sampling, and many patients feel bored or even afraid of carrying out multiple blood glucose tests every day. Therefore, in recent years, noninvasive glucose meters become research and development hotspots of research and development departments of various countries, at present, noninvasive glucose detection in China is basically in a basic research stage, and no successful research and development product is found, so people hope to obtain an noninvasive glucose meter which can cause no pain and has enough precision so as to arrange medical treatment and medication of people.
Disclosure of Invention
The invention aims to provide a noninvasive blood glucose detector and a blood glucose detection method thereof. In order to achieve the purpose, the invention adopts the following technical effects:
according to one aspect of the present invention, there is provided a noninvasive blood glucose monitor, comprising an electrochemical detection sensor, an excitation circuit, a constant potential circuit, a transimpedance amplifier circuit, a FIFO memory, a central processing unit, and an OLED display, wherein a first acquisition output terminal of the electrochemical detection sensor is connected to an input terminal of the transimpedance amplifier circuit, a second acquisition output terminal of the electrochemical detection sensor is connected to an input terminal of the constant potential circuit and a first input terminal of the excitation circuit, respectively, an output terminal of the constant potential circuit is connected to a data input terminal of the FIFO memory through a first AD converter, an output terminal of the transimpedance amplifier circuit is connected to a data input terminal of the FIFO memory through a second AD converter, the FIFO memory is connected to the central processing unit, and a display output terminal of the central processing unit is connected to the OLED display, the feedback output end of the central processing unit is connected with the second input end of the excitation circuit through a DA converter, and the output end of the excitation circuit is connected with the excitation input end of the electrochemical detection sensor.
Preferably, in the above scheme, the excitation circuit includes a voltage amplification isolation unit and an excitation voltage unit, the second acquisition output end of the electrochemical detection sensor is connected to the first input end of the excitation voltage unit and the input end of the constant potential circuit, the feedback output end of the central processing unit is connected to the second input end of the excitation voltage unit sequentially through the DA converter and the voltage amplification isolation unit, and the output end of the excitation voltage unit is connected to the excitation input end of the electrochemical detection sensor.
Further preferably, the excitation voltage unit includes a first operational amplifier U10, a resistor R1, a resistor R2, a resistor R10, a resistor R11, a resistor R12, a resistor R13, and a capacitor C1, the second acquisition output end of the electrochemical detection sensor is respectively connected with one end of a capacitor C1, the input end of a constant potential circuit and the first input end of a first operational amplifier U10 through a resistor R1, the output end of the voltage amplification isolation unit is respectively connected with one end of a resistor R2 and one end of a resistor R11 through a resistor R13, the other end of the resistor R11 is connected with the second input end of the first operational amplifier U10, the output terminal of the first operational amplifier U10 is connected to one terminal of a capacitor C1 and one terminal of a resistor R2, the other end of the resistor R12 is connected to ground, and the other end of the resistor R2 is connected to the excitation input of the electrochemical detection sensor.
Preferably, the voltage amplification and isolation unit includes a second operational amplifier U11, a transistor T12, a resistor R14, a resistor R15, and a resistor R16, a positive input terminal of the second operational amplifier U11 is connected to one end of the resistor R16, the other end of the resistor R16 is connected to ground, a negative input terminal of the second operational amplifier U11 is respectively connected to one end of the resistor R14 and an output terminal of the DA converter, an output terminal of the second operational amplifier U11 is respectively connected to the other end of the resistor R14 and a base input terminal of the transistor T12, and an output terminal of the transistor T12 is connected to one end of the resistor R11 and one end of the resistor R12 through the resistor R13.
In the above aspect, it is further preferable that the constant potential circuit is an emitter follower circuit.
Further preferably, the transimpedance amplification circuit includes a reference voltage source, a fourth operational amplifier U30, a resistor R30, a resistor R31, a resistor R32, a resistor R33, a resistor R34, a resistor R35, and a capacitor C2; the negative input end of the fourth operational amplifier U30 is connected to one end of the resistor R30 and one end of the resistor R31, the other end of the resistor R30 is connected to a reference voltage source, the first acquisition output end of the electrochemical detection sensor is connected to the negative input end of the fourth operational amplifier U30 and one end of the resistor R32, the other end of the resistor R32 is connected to one end of the resistor R33 and one end of the resistor R34, the output end of the fourth operational amplifier U30 is connected to the other end of the resistor R33 and one end of the resistor R35, the other end of the resistor R35 is connected to one end of the capacitor C2 and the data input end of the second AD converter, and the other end of the resistor R31, the other end of the resistor R34 and the other end of the capacitor C2 are connected to ground.
According to another aspect of the present invention, there is provided a non-invasive blood glucose detecting method including the steps of:
starting a noninvasive blood glucose detector, putting a saliva solution of a sample to be detected into a reaction area of a glucose test strip, putting an electrochemical detection sensor into the reaction area, detecting an oxidation current generated when the saliva solution of the sample to be detected reacts with the glucose test strip, and respectively sending the detected oxidation current into a constant potential circuit, a collapse resistance amplifying circuit and an exciting circuit by the electrochemical detection sensor for conditioning;
respectively performing AD conversion on a first voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the resistance-collapse amplifying circuit and a second voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the constant potential circuit, and transmitting the converted voltage signals into an FIFO memory in a time-sharing manner for storage;
step three, the central processing unit respectively reads a first voltage signal and a second voltage signal stored in the FIFO memory in a time-sharing manner, the central processing unit continuously detects and calculates the read first voltage signal, saliva glucose concentration data of the glucose test strip are obtained, the glucose concentration in blood is calculated according to the saliva glucose concentration data, the glucose concentration data in the blood is sent to the OLED display to be displayed, the central processing unit carries out PID (proportion integration differentiation) regulation and calculation processing on the second voltage signal, the calculation processing result is sent to the DA converter to be converted, and a first excitation signal output to the excitation circuit is obtained;
and step four, the detected oxidation current of the electrochemical detection sensor is used as a second excitation signal, the first excitation signal and the second excitation signal are simultaneously sent to the excitation circuit for conditioning, the excitation voltage for the electrochemical detection sensor is output, the surface of the electrode of the electrochemical detection sensor is excited to generate chemical reaction, and the electrode is detected under constant potential.
The above-mentioned method is further preferably such that the step of calculating the glucose concentration in blood from the saliva glucose concentration data comprises the steps of:
step 31: processing the read voltage data through a Kalman filtering algorithm, and calculating a voltage estimation value, a voltage estimation error and a Kalman gain Kk according to the voltage data to finally obtain an optimal voltage value;
step 32: calculating the relation between the input current and the output voltage of the transimpedance amplification circuit, and then calculating the current data flowing through the working electrode and the auxiliary electrode;
step 33: storing the current data into an array until the array is full;
step 34: integrating the current data to obtain the data of the electric charge quantity flowing through the auxiliary electrode and the working electrode;
step 35: substituting the charge quantity into a chemical reaction equation to calculate the molecular weight of glucose participating in the reaction, and obtaining the concentration Glc of the saliva sugar;
step 36: the saliva glucose concentration data is substituted into a set linear correlation regression equation of the saliva glucose concentration and the blood glucose concentration, and the blood glucose concentration in blood can be calculated, wherein the linear correlation regression equation satisfies the following conditions:
Gls＝-3.7301*Glc*Glc*Glc+15.018*Glc*Glc-5.1045*Glc+2.2862；
where Gls is the blood glucose concentration in blood and Glc is the glucose concentration in saliva.
Preferably, the step of performing PID control calculation processing on the second voltage signal by the central processing unit includes the following steps:
step 41: initializing the P value, the I value and the D value of the incremental PID link;
step 42: the central processing unit continuously records a second voltage signal which is amplified, conditioned and output by the constant potential circuit to the oxidation current, takes the second voltage signal as an input comparison parameter and carries out digital filtering on the input comparison parameter;
step 43: sequentially arranging input comparison parameters acquired within the continuous recording time to obtain a voltage value deviation sequence, and comparing the continuously acquired voltage value deviation sequence with a preset voltage value to obtain a deviation value;
step 44: inputting the deviation value into a P value, an I value and a D value in an incremental PID (proportion integration differentiation) link for regulation and outputting a regulation value, so that the output regulation value approaches a preset voltage value;
step 45: and sending the regulating value to a DA converter for conversion, and acquiring a first excitation signal output to an excitation circuit.
In summary, due to the adoption of the technical scheme, the invention has the following technical effects:
(1) the invention adopts the combination of electrochemical measurement such as three-electrode measurement and the like, and converts the glucose content in blood sugar by measuring the glucose content in saliva, thereby realizing the design of a noninvasive blood sugar detector, facilitating the arrangement of the patient on the medicine taking, timely adjusting the diet and avoiding the psychological condition that the patient feels bored or even afraid of carrying out a plurality of blood sugar tests every day. Obviously, the noninvasive blood glucose detector has wide development prospect and is a great development direction of the existing electronic blood glucose detection technology
(2) The noninvasive glucose meter provided by the invention observes the voltage following stability by exciting the input and output of the follower of the voltage unit, the input and output of the constant potential circuit, the input and output of the trans-impedance amplifier and the overall measurement data of the system and comparing the output voltage value with the input voltage value, thereby reducing the actual error between the input voltage and the output voltage; therefore, the threshold and the risk of blood sugar detection can be effectively reduced, the diabetic patient can control the blood sugar more intuitively and conveniently, the healthy person can make a health management plan more effectively, and the happiness index of all people is improved.
Drawings
FIG. 1 is a system diagram of a non-invasive blood glucose monitor of the present invention;
FIG. 2 is a schematic circuit diagram of a non-invasive blood glucose monitor of the present invention;
FIG. 3 is a flow chart of a non-invasive blood glucose test of the present invention;
FIG. 4 is a flow chart of blood glucose concentration data calculation of the present invention;
FIG. 5 is a flow chart of the Kalman filtering calculation process of the present invention;
FIG. 6 is a flow chart of the PID regulation calculation of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail below with reference to the accompanying drawings by way of examples of preferred embodiments. It should be noted, however, that the numerous details set forth in the description are merely for the purpose of providing the reader with a thorough understanding of one or more aspects of the present invention, which may be practiced without these specific details.
As shown in FIG. 1 and FIG. 2, the present invention provides a non-invasive blood glucose monitor, which comprises an electrochemical detection sensor, an excitation circuit, a constant potential circuit, a transimpedance amplifier circuit, an FIFO memory, a central processing unit and an OLED display, wherein the central processing unit adopts an STM32F407 single chip, the OLED display adopts a 0.96 inch dot matrix OLED, a first collection output terminal 1(WE) of the electrochemical detection sensor T1 is connected with an input terminal of the transimpedance amplifier circuit, a second collection output terminal 2(RE) of the electrochemical detection sensor is respectively connected with an input terminal of the constant potential circuit and a first input terminal of the excitation circuit, an output terminal of the constant potential circuit is connected with a data input terminal of the FIFO memory through a first AD converter, an output terminal of the transimpedance amplifier circuit is connected with a data input terminal of the FIFO memory through a second AD converter, the FIFO memory is connected with the central processing unit, the display output end of the central processing unit is connected with the OLED display, the feedback output end of the central processing unit is connected with the second input end of the excitation circuit through the DA converter, and the output end of the excitation circuit is connected with the excitation input end 3(CE) of the electrochemical detection sensor; the excitation circuit comprises a voltage amplification isolation unit and an excitation voltage unit, a second acquisition output end of the electrochemical detection sensor is connected with a first input end of the excitation voltage unit and an input end of the constant potential circuit, a feedback output end of the central processing unit is connected with a second input end of the excitation voltage unit sequentially through the DA converter and the voltage amplification isolation unit, and an output end of the excitation voltage unit is connected with an excitation input end of the electrochemical detection sensor T1 (a three-electrode detection circuit). In the invention, the content of saliva glucose and the content of blood glucose present a certain correlation, and other substances in saliva can also react with enzyme to generate glucose, and the glucose concentration in saliva is collected and converted into the blood glucose concentration; during detection, a glucose test strip is adopted to absorb saliva, glucose in the saliva reacts with Glucose Oxidase (GOD) and ferrocene (oxidation state, Fe3+) fixed on the surface of the glucose test strip to generate oxidation current, the oxidation current is in correlation (direct proportion) with the concentration of the glucose in the saliva solution to be detected, the solution is dripped into a reaction area of the glucose test strip to start reaction detection, when the reaction area in an electrode circuit has no solution reaction conduction circuit, the current flowing through an electrode is zero, and the detection is finished; collecting oxidation current, respectively sending the oxidation current to an excitation circuit, a constant potential circuit and a transimpedance amplifier circuit for collection and processing, collecting saliva glucose solution signals by an electrochemical detection sensor T1, respectively sending the saliva glucose solution signals to the constant potential circuit and the transimpedance amplifier circuit (transimpedance amplifier), then respectively sending the saliva glucose solution signals to a first AD converter and a second AD converter for digital-to-analog conversion, obtaining current collection conversion data, storing the current data converted by the first AD converter and the second AD converter into an FIFO memory in a time-sharing manner, obtaining the relationship between input current and output voltage of the transimpedance amplifier circuit by a central processing unit from the current data read from the FIFO memory, outputting the obtained input current data, obtaining glucose molecular weight participating in reaction according to the correlation (direct ratio) to obtain glucose concentration data in the saliva solution, wherein the solution concentration data is equivalent saliva glucose concentration data (blood glucose concentration), and finally, displaying through the OLED display.
In the present invention, as shown in fig. 1 and 2, the excitation voltage unit includes a first operational amplifier U10, a resistor R1, a resistor R2, a resistor R10, a resistor R11, a resistor R12, a resistor R13, and a capacitor C1, the second acquisition output terminal 2(RE) of the electrochemical detection sensor is connected to one terminal of a capacitor C1, an input terminal of the constant potential circuit, and a first input terminal (negative input terminal) of the first operational amplifier U10 through a resistor R1, the output terminal of the voltage amplification isolation unit is connected to one terminal of a resistor R2 and one terminal of a resistor R11 through a resistor R13, the other terminal of the resistor R11 is connected to a second input terminal (positive input terminal) of the first operational amplifier U10, the output terminal of the first operational amplifier U10 is connected to one terminal of a capacitor C1 and one terminal of a resistor R2, the other terminal of the resistor R12 is connected to ground, the other terminal of the resistor R2 is connected to the CE input terminal of the electrochemical detection sensor T1, the voltage amplification isolation unit comprises a second operational amplifier U11, a triode T12, a resistor R14, a resistor R15 and a resistor R16, wherein a positive electrode input end of the second operational amplifier U11 is connected with one end of a resistor R16, the other end of the resistor R16 is connected with the ground, a negative electrode input end of the second operational amplifier U11 is respectively connected with one end of a resistor R14 and an output end of the DA converter, an output end of the second operational amplifier U11 is respectively connected with the other end of a resistor R14 and a base electrode input end of the triode T12, an output end of the triode T12 is connected with one end of the resistor R11 and one end of a resistor R12 through the resistor R13, the constant potential circuit is an emitter follower circuit which is composed of a third operational amplifier U20, a resistor R20 and a resistor R21, a second acquisition output end of the electrochemical detection sensor T1 is respectively connected with one end of a capacitor C1 through the resistor R1, One end of a resistor R20 is connected with a first input end of a first operational amplifier U10, the other end of the resistor R20 is connected with a positive input end of a third operational amplifier U20, an output end of the third operational amplifier U20 is respectively connected with one end of a resistor R21 and a positive input end of a third operational amplifier U20, and the other end of the resistor R21 is connected with an input end of a first AD converter; in the invention, an electrochemical detection sensor collects oxidation current generated by reaction of saliva liquid and a glucose test strip, the current obtained by the electrochemical detection sensor is respectively sent to an excitation circuit and a constant potential circuit through a first collection end and is sent to a trans-impedance amplification circuit through a second collection output end, the current obtained by the electrochemical detection sensor is respectively sent to a negative input end of a first operational amplifier U10 and a negative input end of a third operational amplifier U20 through a resistor R1 through the first collection end, an analog voltage signal output by a peripheral DAC (digital-to-analog converter) output device of a central processing unit (single chip microcomputer) is received by a positive input end of an excitation voltage unit consisting of the first operational amplifier U10, the analog voltage signal (first excitation signal) is amplified mainly through the second operational amplifier U11 and amplified and isolated through a triode T12, and then passes through a resistor R13, The resistor R11 is sent to the first operational amplifier U10, the analog voltage signal (the first excitation signal) and the oxidation current signal collected by the electrochemical detection sensor are fed back to the feedback input end of the electrochemical detection sensor through the excitation voltage converted and output by the first operational amplifier U10, the voltage output by the voltage follower formed by the third operational amplifier U20 is input into the AD converter for conversion, and then the voltage is sent to the central processing unit for measuring the output voltage, the output voltage is used for controlling the output voltage of the DAC converter by following the central processing unit, the size of the excitation voltage can be controlled by the electrochemical detection sensor, the output voltage value is compared with the input voltage value, the voltage following stability is observed, the actual error between the measured input voltage and the measured output voltage is reduced, and the potential difference is kept constant. In the present invention, the electrochemical detection sensor comprises three detection terminals consisting of a working electrode 1(WE), a reference electrode 2(RE) and an auxiliary electrode 3(CE), and is configured to maintain a constant voltage between the working electrode 1(WE) and the reference electrode 2(RE) when no current flows through the working electrode 1 (WE); the auxiliary electrode 3(CE) is used for outputting an oxidation current signal generated by the reaction, when the excitation voltage of the auxiliary electrode 3(CE) is stable, the stable oxidation current signal is output, along with the progress of the chemical reaction, the potential of the reference electrode 2(RE) can float, so that the potential difference between the potential of the auxiliary electrode 3(CE) and the potential of the working electrode 1(WE) changes, the measured data does not have authenticity and reference value directly, and the constant potential circuit has the function that the potential difference between the potential of the auxiliary electrode 3(CE) and the potential of the working electrode 1(WE) is constant, so that the authenticity and the reference value of the measured data are improved; the relative electrode potential between the two ends of the working electrode 1(WE) and the reference electrode 2(RE) is equal to the difference between the relative electrode potentials of the auxiliary electrode 3(CE) and the reference electrode 2(RE), the loop current formed by the working electrode 1(WE) and the auxiliary electrode 3(CE) is the actual working current, at this time, a potential difference is formed between the two ends of the working electrode 1(WE) and the reference electrode 2(RE), the current generated by the reaction is output through the reference electrode 2(RE), the chemical reaction is generated on the surface of the working electrode 1(WE) under the action of the voltage, the voltage between the working electrode 1(WE) and the reference electrode 2(RE) is changed and can not be kept constant along with the change of the reaction current, the auxiliary electrode 3(CE) is added to keep the voltages of the working electrode 1(WE) and the reference electrode 2(RE) constant through the feedback action, to ensure that no current flows through the reference electrode, for this reason, if accurate measurement is required, that is, the measured value conforms to the theoretical calculated value, it is required that the current flowing through the loop formed between the working electrode 1(WE) and the reference electrode 2(RE) is as small as possible (tends to 0), the solution resistance between the working electrode 1(WE) and the reference electrode 2(RE) is as small as possible (tends to 0), and the excitation voltage has the characteristic that the potential difference relative to the potential of the working electrode is a fixed value, so that the chemical reaction can be effectively promoted, free electrons generated in the chemical reaction move from the working electrode 1(WE) to the reference electrode 2(RE) to form a complete current loop, and thus, the current flowing from the auxiliary electrode 3(CE) to the working electrode 1(WE) is generated. Therefore, by analyzing, a voltage reference value can be generated by using the DA converter, and then the voltage amplification isolation unit, the excitation voltage unit and the voltage follower are used for improving the loading capacity of the reference voltage to generate an excitation voltage; the constant potential circuit formed by the voltage follower outputs a signal which is the excitation voltage through the central processing unit and the DA converter, the excitation voltage is connected to the auxiliary electrode 3(CE) in the three-electrode working circuit through the voltage amplification isolation unit and the excitation voltage unit, and the magnitude of the excitation voltage can be controlled by changing the output voltage of the DA converter.
In the invention, as shown in fig. 1 and fig. 2, the transimpedance amplification circuit includes a reference voltage source (or current source), a fourth operational amplifier U30, a resistor R30, a resistor R31, a resistor R32, a resistor R33, a resistor R34, a resistor R35 and a capacitor C2; the negative input end of the fourth operational amplifier U30 is connected to one end of the resistor R30 and one end of the resistor R31, the other end of the resistor R30 is connected to a reference voltage source, the first acquisition output end of the electrochemical detection sensor is connected to the negative input end of the fourth operational amplifier U30 and one end of the resistor R32, the other end of the resistor R32 is connected to one end of the resistor R33 and one end of the resistor R34, the output end of the fourth operational amplifier U30 is connected to the other end of the resistor R33 and one end of the resistor R35, the other end of the resistor R35 is connected to one end of the capacitor C2 and the data input end of the second AD converter, and the other end of the resistor R31, the other end of the resistor R34 and the other end of the capacitor C2 are connected to ground.
The voltage of the reference voltage source Vcc (or current source) can be divided by a resistor by adopting a 5V power supply to be used as a positive phase input voltage UbasFurther, a bias voltage of 1/2Vcc, which is a half of the power supply (reference voltage source Vcc (or current source)) voltage of 2.5V, may be used. Therefore, the voltage output formula of the transimpedance amplification circuit is calculated as follows: u shapeout＝Ubas–IsX R; when inputting current IsVery small, approximately 0, output voltage UoutApproximately equal to the bias voltage UbasI.e. output voltage is U out1/2Vcc 2.5V; while the input current IsThe larger the inverted input voltage is, the larger the output voltage U isoutThe smaller, the output voltage U is caused by the fourth operational amplifier U30 chip negative supply VEE to groundoutFails to output negative voltage, resulting in output voltage UoutThe minimum value is approximately 0V. The output voltage range is 0V-2.5V, the device is suitable for being connected with an AD converter, the current signal of a first acquisition output end 1(WE) of the electrochemical detection sensor measured in the invention is only 0.4 muA-2 muA, and the feedback resistor R can be adjusted as long as the amplification factor is setfResistance value of (1) so that the maximum current flows through the output voltage UoutMore than 0V; the resistor R32, the resistor R33 and the resistor R34 in the transimpedance amplifier circuit of the present invention form a T-shaped feedback network. Its equivalent resistance RfThe magnitude of the values is: rf(1+ R33/R34) R32; wherein R32, R33 and R34 are resistance values of the resistor R32, the resistor R33 and the resistor R34 respectively, so the output of the comprehensive transimpedance amplifier circuit can be calculated to obtain the output voltage UoutAnd an input current Is(also for electrochemical detection sensing)The oxidation current output from the first collection output terminal) as shown below
Uout＝Ubas–Is*Rf；
Uout＝Ubas–Is*(1+R32/R33)*R1；
Therefore, a first collection output end 1(WE) of the electrochemical detection sensor is connected with a negative electrode input end of a fourth operational amplifier U30 of the transimpedance amplification circuit, output current of the first collection output end 1(WE) of the electrochemical detection sensor is connected into a second AD converter for digital-to-analog conversion processing and then is sent into an FIFO memory for storage, and a central processing unit reads data stored in the FIFO memory in a time-sharing mode and measures voltage, so that the output current of the first collection output end 1(WE) of the electrochemical detection sensor is obtained, glucose concentration of sample saliva solution is obtained, and accordingly relevant blood glucose concentration is obtained, output voltage error is small, and circuit performance is reliable and high in stability.
According to another aspect of the present invention, as shown in fig. 1, fig. 2, fig. 3, fig. 4 and fig. 5, the present invention also provides a non-invasive blood glucose detecting method comprising the steps of:
starting a noninvasive blood glucose detector, putting a saliva solution of a sample to be detected into a reaction area of a glucose test strip, putting an electrochemical detection sensor into the reaction area, detecting an oxidation current generated when the saliva solution of the sample to be detected reacts with the glucose test strip, and respectively sending the detected oxidation current into a constant potential circuit, a collapse resistance amplifying circuit and an exciting circuit by the electrochemical detection sensor for conditioning; the detection content of the noninvasive blood glucose detector is the same as that of a glucose solution with the saliva glucose concentration of a human body, the measured blood glucose concentration value is compared with the blood glucose concentration value corresponding to the saliva glucose concentration to obtain an error, so that the accuracy and the practicability of the whole noninvasive blood glucose detection can be judged, the noninvasive blood glucose detector can meet the daily blood glucose measurement requirement according to the national standard GB/T19634-2005 of blood glucose meter products, the measurement result is observed, and the measurement of the individual blood glucose of 4 mmol/L-11 mmol/L basically meets the requirement;
respectively performing AD conversion on a first voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the resistance-collapse amplifying circuit and a second voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the constant potential circuit, and transmitting the converted voltage signals into an FIFO memory in a time-sharing manner for storage;
step three, the central processing unit respectively reads the first voltage signal and the second voltage signal stored in the FIFO memory in a time-sharing manner, the central processing unit continuously detects and calculates the read first voltage signal, obtains glucose concentration data of the glucose test strip, sends the glucose concentration data to the OLED display for display, processes the first voltage signal read from the FIFO memory by using a Kalman filtering algorithm to calculate glucose concentration data in saliva, and calculates the glucose concentration in blood according to the glucose concentration data; as shown in fig. 4, the specific calculation process is:
step 31: processing the read voltage data through a Kalman filtering algorithm, and calculating a voltage estimation value, a voltage estimation error and a Kalman gain Kk according to the voltage data to obtain an optimal voltage value;
step 32: calculating the relation between the input current and the output voltage of the transimpedance amplification circuit, and then calculating the current data flowing through the working electrode 1(WE) and the auxiliary electrode 3 (CE);
step 33: storing the current data into an array until the array is full;
step 34: integrating the current data to obtain the data of the electric charge quantity flowing through the auxiliary electrode and the working electrode;
step 35: substituting the charge quantity into a chemical reaction equation to calculate the molecular weight of glucose participating in the reaction, and obtaining glucose concentration data in the solution, wherein the solution concentration data is saliva glucose concentration data Glc (saliva glucose concentration data Glc);
the chemical reaction equation is as follows:
Fe2+→Fe3++e-；
under the combined action of the constant potential circuit and the follower of the excitation voltage unit, the ferrocene (reduced state, Fe)2+) Oxidation to ferrocene (oxidation state, F)e3+) Generating oxidation current, wherein the magnitude of the oxidation current is in direct proportion to the concentration of glucose in the solution to be detected, and the concentration of the glucose in the saliva can be calculated by processing and collecting the current;
step 36: substituting the saliva sugar concentration data into a set linear correlation regression equation (blood glucose concentration and saliva glucose concentration function) of the saliva sugar concentration and the blood sugar concentration to obtain the blood sugar concentration; wherein the linear correlation regression equation satisfies:
Gls＝-3.7301*Glc*Glc*Glc+15.018*Glc*Glc-5.1045*Glc+2.2862；
where Gls is the glucose concentration in blood (Gls is the blood glucose concentration in blood), and Glc is the glucose concentration in saliva (salivary sugar concentration).
The central processing unit processes the first voltage signal read from the FIFO by using a Kalman filtering algorithm, processes the voltage data Vc of the read first voltage signal by using the Kalman filtering algorithm, and processes the voltage data Vc by using a voltage estimation value Vk, a voltage estimation error e _ EST and a measurement error e _ MEAkEstimating the actual voltage data with the Kalman gain Kk, as shown in FIG. 5, and then continuously updating the Kalman gain Kk, the over-voltage estimation value Vk and the measurement error e _ MEAkReturning to an estimated value of Kalman recursive operation, obtaining n operation values (taking 100 operation values), randomly screening partial operation values (20 operation values) to calculate an average value, and thus obtaining a final optimal voltage value;
wherein the voltage estimation value Vk satisfies:
namely, it is
VkIs time kThe voltage estimation value of (1) is updated once after each calculation, the voltage estimation value of each time needs to be updated by the value of the previous moment and is used as the power supply estimation value of the next moment, and the updated estimation value is used for the next calculation; therefore, the updated voltage estimated value V at each moment is obtained according to the voltage measured values at the moments from 1 to k-1kAnd a kalman gain Kk.
Vc1+Vc2+…+VckRepresents the sum of the voltage measurement values at the time points 1-k, Vk is the voltage estimation value at the time point k,
is the voltage measurement at time k-1;
the current estimate + coefficient (current measure-last estimate) can be expressed as: vk ═ Vck-1+Kk(Vck-Vck-1)；
Kk satisfies:
where Kk is the Kalman gain, e _ ESTk-1For the voltage estimation error at time k-1, e _ MEAkA measurement error at time k (measurement error at AD conversion);
updating the measurement estimation error, the voltage estimation error e _ ESTkSatisfies the following conditions:
e_ESTk＝(1-Kk)e_ESTk-1；
wherein e _ ESTkFor voltage estimation error at time k, Kk is Kalman gain, e _ ESTk-1The error is estimated for the voltage at time k-1.
The central processing unit performs PID regulation and control calculation processing on the second voltage signal, and sends a calculation processing result to the DA converter for conversion, so as to obtain a first excitation signal output to the excitation circuit, the first excitation signal is sequentially amplified by the second operational amplifier U11 and amplified and isolated by the triode T12 and then sent to the first operational amplifier U10 through the resistor R13 and the resistor R11 for processing, and the second excitation signal is simultaneously sent to the first operational amplifier U10 for comparison to generate an excitation voltage effect and the electrochemical detection sensor T1; with reference to fig. 6, the step of performing PID control calculation processing on the second voltage signal by the central processing unit includes the following steps:
step 41: initializing the P value, the I value and the D value of the incremental PID link;
step 42: the central processing unit continuously records a second voltage signal which is amplified, conditioned and output by the constant potential circuit to the oxidation current, takes the second voltage signal as an input comparison parameter and carries out digital filtering on the input comparison parameter;
step 43: sequentially arranging input comparison parameters acquired within the continuous recording time to obtain a voltage value deviation sequence, and comparing the continuously acquired voltage value deviation sequence with a preset voltage value to obtain a deviation value;
step 44: inputting the regulating deviation value into a P value, an I value and a D value in the regulating incremental PID link for calculation and outputting a regulating value, so that the output regulating value approaches to a preset voltage value;
step 45: sending the regulation value to a DA converter for conversion, and acquiring a first excitation signal output to an excitation circuit; the signal collected by the reference electrode 2(RE) is used as an input comparison parameter of an incremental PID link, and then the output of the DA converter is changed, so that the potential difference between the reference electrode 2(RE) and the auxiliary electrode 3(CE) is kept constant, and the constant potential control of the working electrode 1(WE) and the auxiliary electrode 3(CE) is realized;
step four, the detected oxidation current of the electrochemical detection sensor is used as a second excitation signal, then the first excitation signal and the second excitation signal are simultaneously sent to the excitation circuit for conditioning, the excitation voltage for the electrochemical detection sensor is output, the electrode surface of the electrochemical detection sensor is excited to generate chemical reaction, the detection is carried out under constant voltage, the amplified first excitation signal and the excitation voltage output by the oxidation current signal acquired by the electrochemical detection sensor through the conversion of the first operational amplifier U10 are fed back to the feedback input end 3(CE) of the electrochemical detection sensor; the voltage output by the voltage follower formed by the third operational amplifier U20 is input into the AD converter for conversion, and then is sent into the central processing unit for measuring the output voltage, and is used for regulating the output voltage of the DAC converter by following the central processing unit, the size of the excitation voltage can be controlled by the electrochemical detection sensor, the output voltage value is compared with the input voltage value, the voltage following stability is observed, the actual error between the measured input voltage and the output voltage is reduced, the potential difference is kept constant, the auxiliary electrode 3(CE) is used for outputting an oxidation current signal generated by the reaction, when the excitation voltage of the auxiliary electrode 3(CE) is stable, the stable oxidation current signal is output, along with the progress of the chemical reaction, the potential of the reference electrode 2(RE) can float, and the potential difference between the potential of the auxiliary electrode 3(CE) and the potential of the working electrode 1(WE) is changed, the measured data is directly free from authenticity and reference value, and the constant potential circuit has the function that the potential difference between the potential of the auxiliary electrode 3(CE) and the potential of the working electrode 1(WE) is constant, so that the authenticity and the reference value of the measured data are improved; the excitation voltage of the auxiliary electrode 3(CE) has the characteristic that the potential difference relative to the potential of the working electrode is a fixed value, and can effectively promote the chemical reaction to be carried out, so that free electrons generated in the chemical reaction move from the working electrode 1(WE) to the reference electrode 2(RE) to form a complete current loop, thereby generating the current flowing from the auxiliary electrode 3(CE) to the working electrode 1(WE), ensuring the stability of blood sugar detection and reducing the actual error between the measurement input voltage and the measurement output voltage. Therefore, the accuracy and the measurement precision of blood sugar detection can be effectively improved.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be construed as the protection scope of the present invention.
Claims (9)
1. A noninvasive blood glucose monitor is characterized in that: the blood glucose detector comprises an electrochemical detection sensor, an excitation circuit, a constant potential circuit, a transimpedance amplification circuit, an FIFO memory, a central processing unit and an OLED display, wherein a first acquisition output end of the electrochemical detection sensor is connected with an input end of the transimpedance amplification circuit, a second acquisition output end of the electrochemical detection sensor is respectively connected with an input end of the constant potential circuit and a first input end of the excitation circuit, an output end of the constant potential circuit is connected with a data input end of the FIFO memory through a first AD converter, an output end of the transimpedance amplification circuit is connected with a data input end of the FIFO memory through a second AD converter, the FIFO memory is connected with the central processing unit, a display output end of the central processing unit is connected with the OLED display, and a feedback output end of the central processing unit is connected with a second input end of the excitation circuit through a DA converter, the output end of the excitation circuit is connected with the excitation input end of the electrochemical detection sensor.
2. The non-invasive blood glucose monitor according to claim 1, wherein: the excitation circuit comprises a voltage amplification and isolation unit and an excitation voltage unit, a second acquisition output end of the electrochemical detection sensor is connected with a first input end of the excitation voltage unit and an input end of the constant potential circuit, a feedback output end of the central processing unit is connected with a second input end of the excitation voltage unit sequentially through the DA converter and the voltage amplification and isolation unit, and an output end of the excitation voltage unit is connected with an excitation input end of the electrochemical detection sensor.
3. A non-invasive blood glucose monitor according to claim 2, wherein: the excitation voltage unit comprises a first operational amplifier U10, a resistor R1, a resistor R2, a resistor R10, a resistor R11, a resistor R12, a resistor R13 and a capacitor C1, a second acquisition output end of the electrochemical detection sensor is respectively connected with one end of a capacitor C1, an input end of a constant potential circuit and a first input end of the first operational amplifier U10 through a resistor R1, an output end of the voltage amplification and isolation unit is respectively connected with one end of the resistor R2 and one end of a resistor R11 through a resistor R13, the other end of the resistor R11 is connected with a second input end of the first operational amplifier U10, an output end of the first operational amplifier U10 is respectively connected with one end of the capacitor C1 and one end of the resistor R2, the other end of the resistor R12 is connected with the ground, and the other end of the resistor R2 is connected with an excitation input end of the electrochemical detection sensor.
4. A non-invasive glucose monitor according to claim 3, wherein: the voltage amplification isolation unit comprises a second operational amplifier U11, a triode T12, a resistor R14, a resistor R15 and a resistor R16, wherein the positive electrode input end of the second operational amplifier U11 is connected with one end of a resistor R16, the other end of the resistor R16 is connected with the ground, the negative electrode input end of the second operational amplifier U11 is respectively connected with one end of a resistor R14 and the output end of the DA converter, the output end of the second operational amplifier U11 is respectively connected with the other end of a resistor R14 and the base electrode input end of the triode T12, and the output end of the triode T12 is connected with one end of the resistor R11 and one end of the resistor R12 through the resistor R13.
5. A non-invasive blood glucose monitor according to claim 1, 2 or 3, wherein: the constant potential circuit is an emitter follower circuit.
6. The non-invasive blood glucose monitor according to claim 1, wherein: the transimpedance amplification circuit comprises a reference voltage source, a fourth operational amplifier U30, a resistor R30, a resistor R31, a resistor R32, a resistor R33, a resistor R34, a resistor R35 and a capacitor C2; the negative input end of the fourth operational amplifier U30 is connected to one end of the resistor R30 and one end of the resistor R31, the other end of the resistor R30 is connected to a reference voltage source, the first acquisition output end of the electrochemical detection sensor is connected to the negative input end of the fourth operational amplifier U30 and one end of the resistor R32, the other end of the resistor R32 is connected to one end of the resistor R33 and one end of the resistor R34, the output end of the fourth operational amplifier U30 is connected to the other end of the resistor R33 and one end of the resistor R35, the other end of the resistor R35 is connected to one end of the capacitor C2 and the data input end of the second AD converter, and the other end of the resistor R31, the other end of the resistor R34 and the other end of the capacitor C2 are connected to ground.
7. A non-invasive blood glucose detection method is characterized in that: the non-invasive blood sugar detection method comprises the following steps:
starting a noninvasive blood glucose detector, putting a saliva solution of a sample to be detected into a reaction area of a glucose test strip, putting an electrochemical detection sensor into the reaction area, detecting an oxidation current generated when the saliva solution of the sample to be detected reacts with the glucose test strip, and respectively sending the detected oxidation current into a constant potential circuit, a collapse resistance amplifying circuit and an exciting circuit by the electrochemical detection sensor for conditioning;
respectively performing AD conversion on a first voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the resistance-collapse amplifying circuit and a second voltage signal which is output by amplifying and conditioning the oxidation current by the aid of the constant potential circuit, and transmitting the converted voltage signals into an FIFO memory in a time-sharing manner for storage;
step three, the central processing unit respectively reads a first voltage signal and a second voltage signal stored in the FIFO memory in a time-sharing manner, the central processing unit continuously detects and calculates the read first voltage signal, saliva glucose concentration data of the glucose test strip are obtained, the glucose concentration in blood is calculated according to the saliva glucose concentration data, the glucose concentration data in the blood is sent to the OLED display to be displayed, the central processing unit carries out PID (proportion integration differentiation) regulation and calculation processing on the second voltage signal, the calculation processing result is sent to the DA converter to be converted, and a first excitation signal output to the excitation circuit is obtained;
and step four, the detected oxidation current of the electrochemical detection sensor is used as a second excitation signal, the first excitation signal and the second excitation signal are simultaneously sent to the excitation circuit for conditioning, the excitation voltage for the electrochemical detection sensor is output, the surface of the electrode of the electrochemical detection sensor is excited to generate chemical reaction, and the electrode is detected under constant potential.
8. The method of non-invasive blood glucose measurement according to claim 7, wherein: calculating the glucose concentration in the blood from the saliva glucose concentration data comprises the steps of:
step 31: processing the read voltage data through a Kalman filtering algorithm, and calculating a voltage estimation value, a voltage estimation error and a Kalman gain Kk according to the voltage data to finally obtain an optimal voltage value;
step 32: calculating the relation between the input current and the output voltage of the transimpedance amplification circuit, and then calculating the current data flowing through the working electrode and the auxiliary electrode;
step 33: storing the current data into an array until the array is full;
step 34: integrating the current data to obtain the data of the electric charge quantity flowing through the auxiliary electrode and the working electrode;
step 35: substituting the charge quantity into a chemical reaction equation to calculate the molecular weight of glucose participating in the reaction, and obtaining the concentration Glc of the saliva sugar;
step 36: the saliva glucose concentration data is substituted into a set linear correlation regression equation of the saliva glucose concentration and the blood glucose concentration, and the blood glucose concentration in blood can be calculated, wherein the linear correlation regression equation satisfies the following conditions:
Gls＝-3.7301*Glc*Glc*Glc+15.018*Glc*Glc-5.1045*Glc+2.2862；
where Gls is the blood glucose concentration in blood and Glc is the glucose concentration in saliva.
9. The method of non-invasive blood glucose measurement according to claim 7, wherein: the central processing unit performs PID regulation and control calculation processing on the second voltage signal, and comprises the following steps:
step 41: initializing the P value, the I value and the D value of the incremental PID link;
step 42: the central processing unit continuously records a second voltage signal which is amplified, conditioned and output by the constant potential circuit to the oxidation current, takes the second voltage signal as an input comparison parameter and carries out digital filtering on the input comparison parameter;
step 43: sequentially arranging input comparison parameters acquired within the continuous recording time to obtain a voltage value deviation sequence, and comparing the continuously acquired voltage value deviation sequence with a preset voltage value to obtain a deviation value;
step 44: inputting the deviation value into a P value, an I value and a D value in an incremental PID (proportion integration differentiation) link for regulation and outputting a regulation value, so that the output regulation value approaches a preset voltage value;
step 45: and sending the regulating value to a DA converter for conversion, and acquiring a first excitation signal output to an excitation circuit.
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