An adaptive control system for a non-invasive subcutaneous tissue fluid extraction device

Abstract

The present invention discloses an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, which belongs to the technical field of medical diagnostic instruments. It includes: a host computer, a slave computer and a flexible electrode; wherein the host computer and the slave computer are connected via Bluetooth wireless communication to achieve parameter control, data transmission and reception of the slave computer by the host computer; the slave computer controls the voltage output at both ends of the flexible electrode and obtains the AC impedance detection signal through a digital-to-analog signal conversion module; the flexible electrode is attached to the skin surface to assist in the extraction of tissue fluid and impedance detection. The present invention provides a solution for effectively controlling the amount and rate of tissue fluid extracted by the existing non-invasive subcutaneous tissue fluid extraction device.

Description

Technical Field

[0001] The present invention relates to the technical field of medical diagnostic instruments, and more particularly to an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device. Background Art

[0002] At present, the non-invasive transdermal extraction technology of tissue fluid based on reverse ion electroosmosis is gradually showing its potential application value in wearable health monitoring sensors. This technology applies voltage to both ends of the extraction electrode, so that the charged ions in the tissue fluid move in a directional manner under the action of the external electric field, and drive the tissue fluid to the skin surface. Based on appropriate electrical extraction conditions, this technology can extract human tissue fluid to the skin surface for analysis and detection without causing damage to the human body, thereby realizing non-invasive diagnosis and monitoring of diseases such as diabetes and renal insufficiency.

[0003] In recent years, relevant research has focused on optimizing the electrical conditions for tissue fluid extraction, by determining the appropriate extraction voltage and controlling the extraction current density within the safe range of human skin to ensure the extraction rate of tissue fluid and skin safety. However, studies have shown that the extraction rate of tissue fluid is related to the permeability of individual skin, and the amount of tissue fluid extracted in the same time on different individuals under the same electrical conditions is different. Therefore, the use of a single fixed extraction voltage cannot guarantee efficient and sufficient extraction of tissue fluid under different skin conditions, resulting in problems such as decreased accuracy of biosensors based on tissue fluid detection.

[0004] Based on this, how to provide an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device that can solve the above-mentioned problems is an issue that technical personnel in this field urgently need to solve. Summary of the invention

[0005] In view of this, the present invention provides an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, which can effectively improve the extraction amount and extraction rate of tissue fluid and solve the technical problems existing in the above-mentioned prior art.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] An adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, comprising: a host computer, a slave computer and a flexible electrode;

[0008] The host computer and the slave computer are connected via Bluetooth wireless communication to achieve parameter control, data transmission and reception by the host computer over the slave computer;

[0009] The lower computer controls the voltage output at both ends of the flexible electrode and obtains the AC impedance detection signal through the digital-to-analog signal conversion module;

[0010] The flexible electrode is attached to the skin surface and is used for tissue fluid extraction and impedance detection.

[0011] Preferably, the upper computer establishes a relationship between the water content of the hydrogel and the low-frequency impedance through the low-frequency impedance values ​​of the hydrogel actually measured at different water contents, and quantitatively obtains the amount of tissue fluid extracted by measuring the low-frequency impedance of the hydrogel, and determines whether the extraction voltage needs to be changed based on the extraction amount. If change is required, a voltage adjustment instruction is sent to the lower computer.

[0012] Preferably, the upper computer also establishes a step function between different skin impedances and extraction voltages, obtains an extraction voltage suitable for the measured skin impedance within the safe extraction current density range through the step function, and transmits a voltage adjustment instruction to the lower computer.

[0013] More preferably, a step function is used to obtain an extraction voltage suitable for the current skin impedance within the safe extraction current density range, which can simultaneously ensure skin safety and tissue fluid extraction rate. The tissue fluid extraction rate is represented by the amount of tissue fluid extracted per unit time, and the amount of tissue fluid extracted is quantitatively obtained by measuring the low-frequency impedance of the hydrogel and the relationship between the water content of the hydrogel and the low-frequency impedance.

[0014] Preferably, the host computer also establishes a skin-hydrogel-electrode equivalent circuit model, and fits and analyzes the actual AC impedance detection signal uploaded by the slave computer based on the skin-hydrogel-electrode equivalent circuit model to obtain hydrogel and skin impedance values.

[0015] Preferably, the relationship between the water content of the hydrogel and the low-frequency impedance is established by actually measuring the low-frequency impedance values ​​of the hydrogel at different water contents:

[0016] y=37473.8873x -0.4732 ;

[0017] Wherein, y represents the water content of the hydrogel, in percentage %, and x represents the low-frequency impedance of the hydrogel, in ohm Ω.

[0018] Preferably, the expression for establishing the step function between different skin impedances and extraction voltages is:

[0019]

[0020] Where v represents the extraction voltage in volts (V), and r represents the skin impedance in ohms (Ω).

[0021] Preferably, the lower computer includes a microprocessor module, a tissue fluid extraction circuit and a mode switching switch;

[0022] Wherein, the microprocessor module is provided with a Bluetooth interface, an ADC analog-to-digital conversion interface, an IIC communication interface and an IO interface;

[0023] The microprocessor module communicates wirelessly with the host computer via the Bluetooth interface;

[0024] The microprocessor module is connected to the flexible electrode via the ADC analog-to-digital conversion interface;

[0025] The microprocessor module is connected to the tissue fluid extraction circuit via the IIC communication interface;

[0026] The microprocessor module is connected to the mode switching switch through the IO interface.

[0027] Preferably, the tissue fluid extraction circuit includes: a protection circuit, a current source, and an adjustable voltage source.

[0028] Preferably, the mode switching switch includes: a tissue fluid extraction mode and an impedance detection mode.

[0029] Preferably, the flexible electrode is reused as an extraction electrode for tissue fluid extraction or a flexible detection electrode for AC impedance spectrum detection, thereby assisting in completing tissue fluid extraction and impedance detection.

[0030] It can be known from the above technical scheme that, compared with the prior art, the present invention discloses an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device to ensure that the counter-ion electroosmosis extraction technology can be used for efficient quantitative extraction under different skin conditions, and further promote the application of non-invasive biosensors based on tissue fluid detection in the fields of blood glucose monitoring, renal function tests, and drug delivery guidance. Related studies have shown that there is an important relationship between skin permeability and skin impedance, and the skin will show different degrees of polarization under electrical stimulation conditions of different voltages, resulting in increased skin permeability. Since the skin permeability of different individuals and the same individual under different seasonal climatic conditions is different, it is not realistic to use the same electrical conditions for quantitative extraction of tissue fluid. The present invention uses a fast and non-invasive skin impedance detection technology to perform real-time quantitative analysis of skin permeability, and further regulates the size of the counter-ion electroosmosis extraction voltage. The experimental results show that the adaptive control method of the present invention can effectively improve the extraction amount and extraction rate of tissue fluid. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0032] Figure 1 It is a schematic diagram of the system structure of the present invention;

[0033] Figure 2 A diagram of the skin-hydrogel-electrode equivalent circuit model provided for this embodiment;

[0034] Figure 3 A schematic diagram of the execution flow of the system of the present invention provided for this embodiment;

[0035] Figure 4 A negative exponential power function relationship diagram between the water content and the impedance at low frequency provided for this embodiment;

[0036] Figure 5 A schematic diagram of a step function between different skin impedances and extraction voltages provided in this embodiment. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] The purpose of the present invention is to provide an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, comprising: a host computer, a slave computer and a flexible electrode; wherein the host computer and the slave computer are connected via Bluetooth wireless communication to achieve parameter control, data transmission and reception of the slave computer by the host computer; the slave computer controls the voltage output at both ends of the flexible electrode and obtains an AC impedance detection signal via a digital-to-analog signal conversion module; the flexible electrode is attached to the skin surface for tissue fluid extraction and impedance detection. A solution is provided for effectively controlling the amount and rate of tissue fluid extracted by the existing non-invasive subcutaneous tissue fluid extraction device.

[0039] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0040] See also Figure 1As shown, an embodiment of the present invention discloses an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, including three parts: a lower computer, a flexible electrode and a host computer.

[0041] The lower computer includes a microprocessor module, a tissue fluid extraction circuit and a mode switching switch;

[0042] Among them, the microprocessor module is provided with a Bluetooth interface, an ADC analog-to-digital conversion interface, an IIC communication interface and an IO interface;

[0043] The microprocessor module communicates wirelessly with the host computer via a Bluetooth interface;

[0044] The microprocessor module is connected to the flexible electrode via an ADC analog-to-digital conversion interface;

[0045] The microprocessor module is connected to the tissue fluid extraction circuit via an IIC communication interface;

[0046] The microprocessor module is connected to the mode switching switch through an IO interface.

[0047] The tissue fluid extraction circuit includes: a protection circuit, a current source, and an adjustable voltage source.

[0048] The mode switching switch includes: tissue fluid extraction mode and impedance detection mode.

[0049] In a specific embodiment, the upper computer functions are realized by controlling the lower computer equipment and the dynamic monitoring and extraction effect module.

[0050] In a specific embodiment, the flexible electrode is reused as an extraction electrode for tissue fluid extraction or a flexible detection electrode for AC impedance spectrum detection, thereby assisting in the completion of tissue fluid extraction and impedance detection. The two electrodes, the flexible detection electrode and the extraction electrode for tissue fluid extraction, are the same flexible electrode in use, but the functions are different. In a specific embodiment, the flexible electrode can be used to represent the extraction electrode for tissue fluid extraction or the flexible detection electrode for AC impedance spectrum detection. Impedance detection is achieved through this flexible electrode, and the flexible electrode is reused as an extraction electrode for tissue fluid extraction or a flexible detection electrode for AC impedance spectrum detection. Specifically, the host computer is an Android mobile application, the lower computer is a control device for tissue fluid extraction and impedance detection that can be worn on the wrist, and the flexible electrode is a flexible paper-based carbon electrode attached to the skin surface, which is reused in two scenarios of tissue fluid extraction and impedance detection. The upper computer and the lower computer are connected through Bluetooth wireless communication to realize the parameter control, data transmission and reception of the upper computer to the lower computer. The lower computer controls the voltage output at both ends of the flexible electrode and obtains the AC impedance detection signal through the digital-to-analog signal conversion module. The flexible electrode is attached to the skin surface, and under the action of a given external electric field, the tissue fluid is exported to the hydrogel in the negative electrode area of ​​the flexible electrode for storage.

[0051] In a specific embodiment, based on the low-frequency impedance of the hydrogel at different water contents actually measured by the system, a relationship between the water content of the hydrogel and its low-frequency impedance is established, so that the amount of tissue fluid extracted can be quantitatively analyzed by measuring the low-frequency impedance of the hydrogel. 5 ~9×10 5 For different individuals within the Ω range, when other counter ion electroosmosis extraction conditions such as output current size, current frequency, extraction duty cycle and extraction time remain constant, the extraction voltage required to achieve a certain amount of tissue fluid extraction (quantified by hydrogel water content) was established. A step function between different skin impedances and extraction voltages was established to ensure that the extraction current density was within a safe range while ensuring the tissue fluid extraction rate.

[0052] Specifically, the present invention measures the low-frequency impedance of hydrogels at different water contents, establishes a relationship between the water content of the hydrogel and its low-frequency impedance, and realizes quantitative analysis of the amount of tissue fluid extracted. The relationship between the two is obtained by fitting the measurement results as shown in formula (1):

[0053] y=37473.8873x -0.4732 (1)

[0054] Where y represents the water content of the hydrogel in percentage %, and x represents the low-frequency impedance of the hydrogel in ohm Ω. The water content of the hydrogel is in the range of 0-500%, and there is a negative exponential power function relationship between the water content and its impedance at low frequency, see Figure 4 It can be seen that there is a negative correlation.

[0055] Specifically, the conductive properties of the hydrogel are determined by the colloidal water molecules and free ion content therein, and the conductivity characteristics at low frequencies are mainly contributed by the electrolyte. The higher the water content of the hydrogel, the smaller the impedance, so this relationship is consistent with the theory.

[0056] Specifically, in the method provided by the present invention, the detection method of hydrogel and skin impedance is: based on the electrical properties of skin, hydrogel, and electrode, that is, the skin mainly presents the stratum corneum impedance property, the hydrogel presents the impedance and capacitive reactance properties, and the electrode presents the stable impedance property, and the Randles model at the electrode-electrolyte junction and the error caused by the diffusion effect of active skin cells are considered, and the attachment is established. Figure 2 The skin-hydrogel-electrode equivalent circuit model shown is used to fit the actual AC impedance detection signal and analyze the results based on the equivalent circuit model. From the model perspective, the impedance of the hydrogel and the skin can be simultaneously analyzed through a single AC impedance detection.

[0057] Specifically, the present invention determines that the skin impedance is 1×10 5 ~9×105 For different individuals within the range of Ω, when other counter ion electroosmosis extraction conditions such as output current, current frequency, extraction duty cycle and extraction time remain constant, the extraction voltage required to achieve a certain amount of tissue fluid extraction. The study found that the applicable extraction voltage of skin low-frequency impedance in a certain range is relatively stable, see Figure 5 As shown, a step function between different skin impedances and extraction voltages is established, as shown in formula (2), where r represents the human skin impedance in ohms, and v represents the extraction voltage in volts.

[0058]

[0059] In the example of the present invention, when the tissue fluid is extracted under the extraction conditions of extraction current frequency of 1 kHz, current size of 100 uA, duty cycle of 10%, and extraction time of 30 minutes, in order to achieve an extraction amount of about 1 mg, the skin impedance is 1×10 5 ~3×10 5 The applicable extraction voltage within Ω is 5V, and within 3×10 5 ~6×10 5 The applicable extraction voltage within Ω is 8.5V, and the 5 ~9×10 5 The applicable extraction voltage within Ω is 10V.

[0060] Specifically, the present invention achieves real-time measurement of skin impedance in a low-frequency range (1-1000Hz), and uses the skin low-frequency impedance value to realize adaptive regulation of the extraction voltage, so as to maximize the extraction efficiency of tissue fluid and ensure the stability and efficiency of the extraction process. 5 ~9×10 5 For an object to be extracted within the range of Ω, a 30-minute reverse ion electropermeation skin extraction is performed, and the amount of transdermal extraction of tissue fluid can reach 1 mg or more. At the same time, the adaptive voltage range of the present invention also fully considers the safety of the skin, ensuring that no damage to the skin is caused during the experiment.

[0061] In a specific embodiment, see the execution flow. Figure 3First, the extraction voltage is initialized and set by the host computer (usually initialized to the lowest extraction voltage), as well as the fixed settings of extraction cycle, extraction time, extraction duty cycle and other parameters. The parameter setting is completed by the host computer sending instructions to the lower computer, and the lower computer further controls the output electrical conditions of the extraction circuit. The extraction current is finally output from both ends of the flexible electrode and acts on the skin surface to extract tissue fluid during the extraction cycle. After the initial extraction, the system measures the low-frequency impedance of the hydrogel, and calculates the amount of tissue fluid extraction based on the hydrogel impedance-water content function relationship. The host computer determines whether the tissue fluid extraction is sufficient based on the extraction amount and performs negative feedback. If the detection threshold is not reached, the extraction voltage is adaptively adjusted based on the skin impedance and the step function between different skin impedances and the extraction voltage.

[0062] Specifically, the present invention can obtain the current tissue fluid extraction rate and the wearer's skin impedance through feedback by measuring the hydrogel impedance and the skin impedance, thereby adaptively regulating the extraction voltage to ensure efficient, sufficient and safe extraction of tissue fluid.

[0063] In summary, the present invention proposes an adaptive control system for a non-invasive subcutaneous tissue fluid extraction device to ensure efficient quantitative extraction of tissue fluid. The method is based on skin and hydrogel impedance measurement to achieve adaptive control of tissue fluid. In principle, the output extraction current acts on the flexible electrode and forms an electric field under the skin. The charged ions in the tissue fluid move in a directional manner under the action of the external electric field, and drive the neutral molecules in the tissue fluid to be exported to the skin surface through skin appendages such as hair follicles, sweat glands and sebaceous glands, and stored in the hydrogel under the electrode. Studies have shown that the conductivity of hydrogels is mainly affected by the conductive behavior of water molecules, ion transport in the gel, and electric field effects. Hydrogels with different water contents have large differences in conductivity, and the conductivity differences can be quantitatively analyzed by impedance. The impedance of the gel shows a complex frequency dependence, which is usually manifested as a low-frequency electrolyte region and a high-frequency charge transfer region. The low-frequency electrolyte region is mainly contributed by the electrolyte, while the high-frequency charge transfer region is mainly affected by the polymer network in the gel. Therefore, in terms of quantitative tissue fluid extraction, the change in water content can be calculated by measuring the low-frequency impedance of the hydrogel in real time during the extraction process, and then the amount of tissue fluid extracted within a certain period of time can be quantitatively analyzed. In addition, skin permeability can also be judged by measuring impedance. The amount of tissue fluid extracted within a certain period of time is determined by the skin permeability of different individuals, and skin permeability is mainly determined by the thickness of the stratum corneum of the skin. The stratum corneum is composed of inactivated keratinocytes tightly stacked, which is the biggest obstacle to the percutaneous extraction of tissue fluid. The low-frequency (1-1000Hz) skin impedance corresponding to the thicker stratum corneum is also larger. Therefore, there is an important relationship between the amount of tissue fluid extracted and the skin impedance. Since the thickness of the stratum corneum of different individuals and the same individual under different seasonal climatic conditions is different, it is not realistic to use the same electrical conditions for quantitative extraction of tissue fluid. Studies have shown that an appropriate increase in the applied electric field within a certain range will promote skin polarization, leading to the expansion of skin cell gaps and enhanced membrane permeability, thereby increasing skin permeability. In order to adapt to the tissue fluid extraction amount of individuals with different skin types to meet the detection requirements, the method of the present invention measures the individual skin impedance during extraction to determine the skin permeability, and adaptively adjusts the extraction voltage to promote the polarization of the skin, improve skin permeability and thus increase the tissue fluid extraction amount. Finally, hydrogel impedance analysis is used to ensure that the actual tissue fluid extraction amount meets the required detection requirements.

[0064] In this specification, each embodiment is described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the embodiments can be referred to each other. For the device disclosed in the embodiment, since it corresponds to the method disclosed in the embodiment, the description is relatively simple, and the relevant parts can be referred to the method part.

[0065] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An adaptive control system for a non-invasive subcutaneous tissue fluid extraction device, characterized in that: include: Upper computer, lower computer and flexible electrode; The host computer and the slave computer are connected via Bluetooth wireless communication to achieve parameter control, data transmission and reception by the host computer over the slave computer; The lower computer controls the voltage output at both ends of the flexible electrode and obtains the AC impedance detection signal through the digital-to-analog signal conversion module; The flexible electrode is attached to the skin surface to assist in tissue fluid extraction and impedance detection; The upper computer establishes a relationship between the water content of the hydrogel and the low-frequency impedance through the low-frequency impedance values ​​of the hydrogel actually measured at different water contents, and quantitatively obtains the amount of tissue fluid extracted by measuring the low-frequency impedance of the hydrogel, and determines whether the extraction voltage needs to be changed according to the extraction amount, and if so, sends a voltage adjustment instruction to the lower computer; The relationship between the water content of the hydrogel and the low-frequency impedance is established by actually measuring the low-frequency impedance values ​​of the hydrogel at different water contents: y=37473.8873x -0.4732 ; Wherein, y represents the water content of the hydrogel, in percentage %, and x represents the low-frequency impedance of the hydrogel, in ohm Ω; The upper computer also establishes a step function between different skin impedances and extraction voltages, obtains an extraction voltage suitable for the measured skin impedance within a safe extraction current density range through the step function, and transmits a voltage adjustment instruction to the lower computer; The expression for establishing the step function between different skin impedances and extraction voltages is: Where v represents the extraction voltage in volts (V), and r represents the skin impedance in ohms (Ω).

2. The adaptive control system of the non-invasive subcutaneous tissue fluid extraction device according to claim 1, characterized in that: The host computer also establishes a skin-hydrogel-electrode equivalent circuit model, and fits and analyzes the actual AC impedance detection signal uploaded by the slave computer based on the skin-hydrogel-electrode equivalent circuit model to obtain hydrogel and skin impedance values.

3. The adaptive control system of the non-invasive subcutaneous tissue fluid extraction device according to claim 1, characterized in that: The lower computer includes a microprocessor module, a tissue fluid extraction circuit and a mode switching switch; The microprocessor module is provided with a Bluetooth interface, an ADC analog-to-digital conversion interface, an IIC communication interface and an IO interface; The microprocessor module communicates wirelessly with the host computer via the Bluetooth interface; The microprocessor module is connected to the flexible electrode via the ADC analog-to-digital conversion interface; The microprocessor module is connected to the tissue fluid extraction circuit via the IIC communication interface; The microprocessor module is connected to the mode switching switch through the IO interface.

4. The adaptive control system of the non-invasive subcutaneous tissue fluid extraction device according to claim 3, characterized in that: The tissue fluid extraction circuit comprises: a protection circuit, a current source, and an adjustable voltage source.

5. The adaptive control system of the non-invasive subcutaneous tissue fluid extraction device according to claim 3, characterized in that: The mode switching switch includes: a tissue fluid extraction mode and an impedance detection mode.

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