WO2021238808A1

WO2021238808A1 - Test substance concentration monitoring circuit and system, and terminal device

Info

Publication number: WO2021238808A1
Application number: PCT/CN2021/095271
Authority: WO
Inventors: 宣佳杰; 于非
Original assignee: 微泰医疗器械(杭州)有限公司
Priority date: 2020-05-28
Filing date: 2021-05-21
Publication date: 2021-12-02
Also published as: CN111551594A; CN111551594B

Abstract

An electric-current test substance concentration monitoring circuit and system, and a terminal device. In the monitoring circuit, a biosensor signal pre-processing module is added. The module has two output ends such that the flow of a current signal can be controlled. When the current signal flows to an alternating-current impedance measurement module, the alternating-current impedance measurement model can be used to adjust the test substance concentration calculation method, thereby ensuring the accuracy of calculation of test substance concentration.

Description

Circuit, system and terminal equipment for detecting concentration monitoring

Technical field

The present invention relates to the technical field of biosensors, in particular to a detection substance concentration monitoring circuit, system and terminal equipment.

Background technique

The current-type biosensing system can be used to continuously monitor the concentration of a given detection substance in human tissue. Common current-type biosensing systems include continuous blood glucose monitoring systems. It can monitor the glucose concentration change in human tissue fluid through the current-type glucose sensor implanted in the body. The implementation of continuous and uninterrupted blood glucose monitoring can better control the blood glucose changes of diabetic patients. It has important guiding significance for life patterns, activities, exercise, diet and rational use of drugs, and can help patients find problems at any time and seek medical treatment in time.

The amperometric detection device concentration detection equipment is used for the detection of the concentration of the detection substance in the tissue fluid, blood or solution. The concentration of the electrochemically active detection substance can be measured by the electrochemical current, and the concentration of the detection substance can be recorded and transmitted And so on.

Summary of the invention

In view of this, the present invention provides a current type detection substance concentration monitoring circuit, system and terminal equipment, which realizes detection substance concentration monitoring, and adds a preprocessing module to the monitoring circuit, which can switch the current signal flow direction and increase the monitoring circuit Adjust the detection substance concentration algorithm function to ensure the accuracy of the detection substance concentration calculation.

One aspect of the present invention provides a detection substance concentration monitoring circuit, which includes an amperometric electrochemical sensor. The circuit also includes a current electrochemical sensor signal preprocessing module, a detection substance current acquisition and measurement module, and an AC impedance measurement module, wherein: current The input terminal of the signal preprocessing module of the current-type electrochemical sensor is connected with the current-type electrochemical sensor, the first output terminal is connected with the detection object current acquisition and measurement module, and the second output terminal is connected with the AC impedance measurement module; the current-type electrochemical sensor signal pre-processing The processing module is used to receive the current signal sent by the current-type electrochemical sensor, and to control the current signal to flow to the detection object current acquisition and measurement module or the AC impedance measurement module; the detection object current acquisition and measurement module is used to convert the current signal to A voltage signal for calculating the concentration of the detection object; the AC impedance measurement module is used to perform AC impedance detection according to the current signal, and adjust the algorithm for calculating the concentration of the detection object according to the AC impedance detection result.

Optionally, the current-type electrochemical sensor signal preprocessing module includes a switching circuit and a switching controller, wherein: the switching circuit includes 4 single-pole double-throw switches; the 4 input terminals of the switching circuit are respectively connected to the first of the current-type electrochemical sensor The working electrode, the second working electrode, the reference electrode and the counter electrode are connected; the 4 first output terminals of the switching circuit are connected with the detection object current acquisition and measurement module, and the 4 second output terminals are connected with the AC impedance measurement module; the switching controller is used for Control the closing direction of the single-pole double-throw switch.

Optionally, an electrostatic discharge circuit is respectively provided between the 4 input ends of the switching circuit and the first working electrode, the second working electrode, the reference electrode and the counter electrode of the current-type electrochemical sensor.

Optionally, the detection object current acquisition and measurement module includes an I/V conversion circuit, a dynamic feedback loop, and a bias circuit; the I/V conversion circuit includes a first operational amplifier circuit, a second operational amplifier circuit, and the first operational amplifier circuit is connected in parallel with the second operational amplifier circuit. A resistor, the second operational amplifier circuit is connected in parallel with the second resistor, the reverse input terminal of the first operational amplifier circuit is connected to the first output terminal of the single-pole double-throw switch connected to the first working electrode, and the output terminal of the first operational amplifier circuit Connected to the first voltage output terminal, the reverse input terminal of the second operational amplifier circuit is connected to the first output terminal of the single-pole double throw switch connected to the second working electrode, and the output terminal of the second operational amplifier circuit is connected to the second voltage output terminal ; The dynamic feedback loop includes a third operational amplifier circuit, the inverting input terminal of the third operational amplifier circuit is connected with the first output terminal of the single-pole double-throw switch connected to the reference electrode, and the output terminal of the third operational amplifier circuit is connected to the counter electrode. The first output terminal of the connected single-pole double-throw switch is connected, and the output terminal of the third operational amplifier circuit is also connected to the third voltage output terminal; the input terminal of the bias circuit is connected with the same direction input terminal of the third operational amplifier circuit to bias The output terminal of the circuit is connected to the fourth voltage output terminal.

Optionally, between the first voltage output terminal and the output terminal of the first operational amplifier circuit, between the second voltage output terminal and the output terminal of the second operational amplifier circuit, and between the third voltage output terminal and the third operational amplifier circuit Low-pass filters are respectively arranged between the output terminals and between the fourth voltage output terminal and the output terminal of the bias circuit.

Optionally, the AC impedance measurement module includes an AC excitation source and a signal receiving and processing module; the AC excitation source includes a series-connected phase accumulator, a sine read-only memory, a digital-to-analog converter, and a phase accumulator. The output terminal of the phase accumulator is connected to the phase accumulator. One of the 4 single-pole double-throw switches is connected to the second output terminal; the signal receiving and processing module includes a series-connected current-voltage conversion circuit, a phase accumulator, an anti-aliasing filter, an analog-to-digital converter and a discrete Fourier transform circuit, The input terminal of the current-voltage conversion circuit is connected to one of the other three second output terminals of the four single-pole double-throw switches.

Another aspect of the present invention also provides a detection substance concentration monitoring system, which includes the detection substance concentration monitoring circuit described above, and further includes a microcontroller, a memory, and a communication module; a detection substance current acquisition and measurement module and an AC impedance of the detection substance concentration monitoring circuit The measurement module is connected with the microcontroller, and the memory and the communication module are respectively connected with the microcontroller; the microcontroller is used to execute the algorithm for calculating the concentration of the detection object, or to execute the algorithm for calculating the concentration of the detection object after adjustment by the AC impedance measurement module.

Optionally, the memory is at least one of the following: program memory, data memory, or static random access memory.

Optionally, the communication module is an NFC communication module or a Bluetooth wireless communication module.

Another aspect of the present invention also provides a terminal device, including the above-mentioned detection substance concentration monitoring system.

Description of the drawings

For the purpose of illustration and not limitation, the present invention will now be described according to preferred embodiments of the present invention, particularly with reference to the accompanying drawings, in which:

Fig. 1 is a schematic diagram of a detection substance concentration monitoring circuit according to an embodiment of the present invention;

Fig. 2 is a schematic diagram of a detection substance current acquisition and measurement module in a detection substance concentration monitoring circuit;

Figure 3 is a schematic diagram of an AC impedance measurement module in a detection substance concentration monitoring circuit;

Fig. 4 is a schematic diagram of a detection substance concentration monitoring system according to an embodiment of the present invention.

Detailed ways

In the embodiment of the present invention, a current-type electrochemical sensor signal preprocessing module is added to the monitoring circuit. The module has two output terminals to control the flow of the current signal. When flowing to the AC impedance measurement module, the AC The impedance measurement module adjusts the detection object concentration algorithm to ensure the accuracy of the detection object concentration calculation, which will be described in detail below.

Fig. 1 is a schematic diagram of a detection substance concentration monitoring circuit provided according to an embodiment of the present invention. As shown in Figure 1, the current type electrochemical sensor includes 4 electrodes. The electrode W1 and the electrode W2 are the first working electrode and the second working electrode respectively, which are used to output current signals, and the electrode RE is the reference electrode for the current type. The electrochemical sensor provides a stable reference voltage, and the electrode CE is a counter electrode used to provide the working electrode with electrons required for the electrochemical reaction. The current type electrochemical sensor sends a current signal (analog signal) to the current type electrochemical sensor signal preprocessing module.

The current-type electrochemical sensor signal preprocessing module receives the current signal sent by the current-type electrochemical sensor, and controls the flow of the current signal through a switching circuit. As shown in Figure 1, the current-type electrochemical sensor signal preprocessing module includes a switching circuit and a switching controller. The switching circuit includes four single-pole double-throw switches respectively connected to the four working electrodes of the current-type electrochemical sensor. The switching control The device can control the closing direction of the single-pole double-throw switch, that is, two closing directions can be realized by the single-pole double-throw switch, one direction is to control the single-pole double-throw switch to connect with the first output terminal, and the current signal flow direction detection is in the closing direction The object current acquisition and measurement module, the other direction is to control the single-pole double-throw switch to be connected to the second output terminal, and the current signal flows to the AC impedance measurement module when in the closed direction. When the monitoring circuit is in use, the switching controller controls the single-pole double-throw switch to make it connect with the first output terminal in a normal state, and the current signal is kept for a long time and sent to the detection object current acquisition and measurement module. The single-pole double-throw switch only periodically switches to the AC impedance measurement module. After the switching is completed, the AC impedance measurement needs to be completed within a limited time (such as 200ms or other time that can be set by the user). After the measurement is completed, the single-pole double-throw switch Then switch back to the detection object current acquisition and measurement module.

As shown in Figure 1, between the 4 input terminals of the switching circuit and the 4 electrodes of the current-type electrochemical sensor, that is, between the first working electrode, the second working electrode, the reference electrode and the counter electrode, there are electrostatic discharges. Circuit ESD. The electrostatic discharge circuit ESD can discharge the static electricity transmitted by the human body, and prevent the static electricity from damaging the electronic components in the signal preprocessing module of the current-type electrochemical sensor.

Figure 2 is a schematic diagram of the detection object current acquisition and measurement module in the detection object concentration monitoring circuit. The AC impedance measurement module includes I/V conversion circuit, dynamic feedback loop and bias circuit. As shown in FIG. 2, the I/V conversion circuit includes a first operational amplifier circuit AMP1 and a second operational amplifier circuit AMP2. The first operational amplifier circuit AMP1 is connected in parallel with the first resistor R2, the inverting input terminal NEG of the first operational amplifier circuit AMP1 is connected to the first output terminal of the single-pole double-throw switch connected to the first working electrode W1, and the first operational amplifier circuit AMP1 The output terminal OUT of is connected to the first voltage output terminal W1F. The second operational amplifier circuit AMP2 is connected in parallel with the second resistor R1, the inverting input terminal NEG of the second operational amplifier circuit AMP2 is connected to the first output terminal of the single-pole double-throw switch connected to the second working electrode W2, and the second operational amplifier circuit AMP2 The output terminal OUT of is connected to the second voltage output terminal W2F. The dynamic feedback loop includes a third operational amplifier circuit AMP3, the inverting input terminal NEG of the third operational amplifier circuit AMP3 is connected to the first output terminal of the single-pole double-throw switch connected to the reference electrode RE, and the output terminal of the third operational amplifier circuit AMP3 OUT is connected to the first output terminal of the single-pole double-throw switch connected to the counter electrode CE, and the output terminal OUT of the third operational amplifier circuit AMP3 is also connected to the third voltage output terminal CEF. The input terminal of the bias circuit is connected to the same direction input terminal POS of the third operational amplifier circuit AMP3, and the output terminal of the bias circuit is connected to the fourth voltage output terminal BF.

As shown in Figure 2, the detection object current acquisition and measurement module in the detection object concentration monitoring circuit includes two bias circuits, namely the bias circuit RE BIAS and the bias circuit WE1/WE2 BIAS. The two bias circuits provide reference electrodes RE and The first working electrode W1 and the second working electrode W2 provide programmable bias voltages. The first operational amplifier circuit AMP1 and the second operational amplifier circuit AMP2 are used for converting current signals on the electrodes of the first working electrode W1 and the second working electrode W2 into voltage signals. The third operational amplifier circuit AMP3 is a dynamic feedback loop, which provides a stable reference voltage point for the current-type electrochemical sensor and a stable current source for the first working electrode W1 and the second working electrode W2. The resistors R1 and R2 in the I/V conversion circuit are used to configure the I/V conversion magnification of the first operational amplifier circuit AMP1 and the second operational amplifier circuit AMP2. The resistor Rf and the capacitor Cf form a passive first-order low-pass filter, Used to filter out the inherent noise of current-type electrochemical sensors.

Figure 3 is a schematic diagram of an AC impedance measurement module in a detection substance concentration monitoring circuit. As shown in Figure 3, the AC impedance measurement module includes an AC excitation source and a signal receiving and processing module. The AC excitation source includes a series-connected phase accumulator PhaseAccumulator, sine read-only memory SIN ROM, digital-to-analog converter DAC and programmable gain instrumentation amplifier PGA, the output of the phase accumulator and one of the 4 single-pole double-throw switches. The output terminal is connected. During AC impedance measurement, the phase accumulator generates the AC sine wave voltage signal value and stores it in the sine read-only memory SIN ROM. The analog-to-digital converter DAC reads the value and outputs the sine wave signal, which is passed through the programmable gain instrument amplifier The PGA is output to an electrode of the amperometric electrochemical sensor.

As shown in Figure 3, the signal receiving and processing module includes a series-connected current-voltage conversion circuit CurrentTovoltage, a programmable gain instrumentation amplifier PGA, an anti-alias filter, an analog-to-digital converter ADC, and a discrete Fourier transform circuit DFT. The input terminal of the current-voltage conversion circuit is connected to one of the other three second output terminals of the four single-pole double-throw switches. After the AC excitation signal passes through the human subcutaneous tissue fluid, it passes through the other electrode of the current-type electrochemical sensor and returns to the signal receiving and processing module. In this module, the AC excitation signal is first converted from current to voltage, and then amplified by the programmable gain instrument amplifier PGA After that, it enters the antialias filter, and finally sends it to the analog-to-digital converter ADC. The converted digital signal undergoes discrete Fourier transform to obtain an AC impedance including real and imaginary parts.

Fig. 4 is a schematic diagram of a detection substance concentration monitoring system according to an embodiment of the present invention; as shown in Fig. 4, the system includes the detection substance concentration monitoring circuit shown in Fig. 1, and also includes a microcontroller, a memory, and communication Module; the detection object current acquisition and measurement module and the AC impedance measurement module of the detection object concentration monitoring circuit are connected to the microcontroller, and the memory and communication module are respectively connected to the microcontroller; the microcontroller is used to execute the algorithm for calculating the concentration of the detection object, or execute An algorithm for calculating the concentration of the detected substance after the adjustment of the AC impedance measurement module.

The microcontroller used in the embodiments of the present invention has ultra-low sleep power consumption, low operating current, and Fourier transform processing capabilities; at the same time, the microprocessor also includes general-purpose input and output ports, timers, and general-purpose input and output ports. Asynchronous transceiver, monitoring software, internal clock, debugging port, etc. In terms of data transmission, the microcontroller can be connected with a Bluetooth chip or a Bluetooth module to realize the Bluetooth transmission function of the concentration data of the detected substance. The microcontroller will also monitor the working status of the chip and its peripherals, as well as the current-type electrochemical sensor, and provide alarm information if there is an abnormality.

The memory is at least one of a program memory, a data memory or a static random access memory. The program memory and the data memory need to be non-volatile memory, which must meet the erasing life of at least 200 times. The static random access memory has a general structure. The communication module is an NFC communication module or a Bluetooth wireless communication module, where the NFC communication module supports radio frequency non-contact communication, the power supply can be self-powered by NFC, and can wake up the microcontroller.

The embodiment of the present invention also provides a terminal device, including a detection substance concentration monitoring system, a display screen, a button, a battery, etc. The terminal device is used to receive target detection substance monitoring data, and perform operations such as display and storage.

The foregoing specific implementations do not constitute a limitation on the protection scope of the present invention. Those skilled in the art should understand that, depending on design requirements and other factors, various modifications, combinations, sub-combinations, and substitutions can occur. Any modification, equivalent replacement and improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

A detection substance concentration monitoring circuit includes an amperometric electrochemical sensor, characterized in that the circuit also includes a current electrochemical sensor signal preprocessing module, a detection substance current acquisition and measurement module, and an AC impedance measurement module, wherein:

The input terminal of the current-type electrochemical sensor signal preprocessing module is connected with the current-type electrochemical sensor, the first output terminal is connected with the detection object current acquisition and measurement module, and the second output terminal is connected with the AC impedance measurement module;

The current-type electrochemical sensor signal preprocessing module is used to receive the current signal sent by the current-type electrochemical sensor, and control the current signal to flow to the detection object current acquisition measurement module or AC impedance measurement module;

The detection object current acquisition and measurement module is used to convert the current signal into a voltage signal for calculating the concentration of the detection object;

The AC impedance measurement module is used to perform AC impedance detection according to the current signal, and adjust the algorithm for calculating the concentration of the detection object according to the AC impedance detection result.
The detection substance concentration monitoring circuit according to claim 1, wherein the current-type electrochemical sensor signal preprocessing module includes a switching circuit and a switching controller, wherein:

The switching circuit includes 4 single-pole double-throw switches;

The 4 input terminals of the switching circuit are respectively connected with the first working electrode, the second working electrode, the reference electrode and the counter electrode of the current type electrochemical sensor;

The 4 first output terminals of the switching circuit are connected with the detection object current acquisition and measurement module, and the 4 second output terminals are connected with the AC impedance measurement module;

The switching controller is used to control the closing direction of the single-pole double-throw switch.
The detection substance concentration monitoring circuit according to claim 2, wherein the four input terminals of the switching circuit and the first working electrode, the second working electrode, the reference electrode and the counter electrode of the current type electrochemical sensor are respectively provided There is an electrostatic discharge circuit.
The detection substance concentration monitoring circuit according to claim 2, wherein the detection substance current acquisition and measurement module includes an I/V conversion circuit, a dynamic feedback loop and a bias circuit;

The I/V conversion circuit includes a first operational amplifier circuit and a second operational amplifier circuit. The first operational amplifier circuit is connected in parallel with a first resistor, and the second operational amplifier circuit is connected in parallel with a second resistor. The first output terminal of a single-pole double-throw switch connected to a working electrode is connected, the output terminal of the first operational amplifier circuit is connected to the first voltage output terminal, and the reverse input terminal of the second operational amplifier circuit is connected to the second working electrode. The first output terminal of the single-pole double-throw switch is connected, and the output terminal of the second operational amplifier circuit is connected to the second voltage output terminal;

The dynamic feedback loop includes a third operational amplifier circuit. The inverting input terminal of the third operational amplifier circuit is connected to the first output terminal of the single-pole double-throw switch connected to the reference electrode. The output terminal of the third operational amplifier circuit is connected to the counter electrode. The first output terminal of the single-pole double-throw switch is connected, and the output terminal of the third operational amplifier circuit is also connected to the third voltage output terminal;

The input terminal of the bias circuit is connected to the same direction input terminal of the third operational amplifier circuit, and the output terminal of the bias circuit is connected to the fourth voltage output terminal.
The detection substance concentration monitoring circuit according to claim 4, wherein between the first voltage output terminal and the output terminal of the first operational amplifier circuit, and between the second voltage output terminal and the output terminal of the second operational amplifier circuit , Low-pass filters are respectively arranged between the third voltage output terminal and the output terminal of the third operational amplifier circuit, and between the fourth voltage output terminal and the output terminal of the bias circuit.
The detection substance concentration monitoring circuit according to claim 2, wherein the AC impedance measurement module includes an AC excitation source and a signal receiving and processing module;

The AC excitation source includes a series-connected phase accumulator, a sine read-only memory, a digital-to-analog converter, and a phase accumulator. The output end of the phase accumulator is connected to a second output end of the 4 single-pole double-throw switches;

The signal receiving and processing module includes series-connected current-voltage conversion circuit, phase accumulator, anti-aliasing filter, analog-to-digital converter and discrete Fourier transform circuit, the input end of the current-voltage conversion circuit and 4 single-pole double-throw switches Connect to one of the other 3 second output terminals.
A detection substance concentration monitoring system, characterized by comprising the detection substance concentration monitoring circuit according to any one of claims 1 to 6, and further comprising a microcontroller, a memory and a communication module;

The detection object current acquisition and measurement module and the AC impedance measurement module of the detection object concentration monitoring circuit are connected to the microcontroller, and the memory and communication module are respectively connected to the microcontroller;

The microcontroller is used to execute the algorithm for calculating the concentration of the detection substance, or to execute the algorithm for calculating the concentration of the detection substance after the adjustment of the AC impedance measurement module.
The detection substance concentration monitoring system according to claim 7, wherein the memory is at least one of the following: a program memory, a data memory, or a static random access memory.
The detection substance concentration monitoring system according to claim 7, wherein the communication module is an NFC communication module or a Bluetooth wireless communication module.
A terminal device, characterized by comprising the detection substance concentration monitoring system according to any one of claims 7 to 9.