Wearable sensing device for sweat calcium ion detection

Abstract

The invention relates to a wearable sensing device for sweat calcium ion detection. The wearable sensing device comprises a micro-fluidic chip and a signal processing and transmission module which can be matched with the sensing chip and is used for signal transmission and data processing, the micro-fluidic chip comprises a Janus fabric layer, a channel layer and a chip cover layer printed with an electrochemical electrode which are sequentially arranged in an attached manner; rapid sweat sampling and concentration refreshing can be realized, and the concentration of calcium ions in sweat can be directly and selectively measured; and the signal processing and transmission module is electrically connected with an electrochemical electrode for detecting the calcium ion concentration in the micro-fluidic chip and is used for data processing and transmission. By using a micro-fluidic chip, sweat secreted by skin continuously flows through an interface of the electrochemical sensor, so that the concentration of calcium ions in the sweat can be detected in real time; the sweat sample is small in size, detected sweat can be rapidly discharged through the micro-channel and the waste liquid discharging area, sweat accumulation is avoided, and the testing accuracy is guaranteed.

Description

Technical Field

[0001] The present invention relates to a measurement technology for diagnostic purposes, in particular to the field of electrochemical method testing technology, and specifically to a wearable sensor device for sweat calcium ion detection. Background Art

[0002] As people pay more attention to health and become more aware of disease prevention, more and more studies are beginning to focus on the relationship between changes in sweat calcium ion concentration and health. Testing for sweat calcium ion concentration can assess the loss of calcium in the body, more accurately guide an individual's calcium supplementation strategy, and help prevent calcium metabolism disorders, especially for athletes, the elderly, and people with calcium metabolism disorders. In short, sweat calcium ion concentration testing is important for assessing calcium metabolism status, detecting calcium imbalances, assessing human health, and guiding calcium supplementation strategies.

[0003] With the rapid development of wearable technology, wearable sweat sensors have become an important tool for studying sweat composition. For the detection of calcium ion concentration in sweat, researchers have begun to try to use wearable sweat sensors for real-time monitoring. These sensors can collect sweat samples non-invasively and measure the calcium ion concentration in sweat through miniaturized chemical sensors or biosensors. However, there are still some shortcomings in the current wearable sweat sensors for detecting calcium ion concentration in sweat. First, the sensitivity and selectivity of the sensor still need to be further improved to ensure that trace amounts of calcium ions in sweat can be accurately and quickly detected. Secondly, the stability and durability of the sensor are also a challenge, especially when worn for a long time and used multiple times, the performance of the sensor may change. In addition, sedentary healthy individuals are not easy to sweat, and the amount of sweat required for detection limits the on-site analysis of calcium ion concentration. The accuracy and real-time nature of the data are also a problem. It is necessary to ensure that the data collected by the sensor can accurately reflect the changes in the concentration of calcium ions in sweat and can be transmitted and analyzed in a timely manner.

[0004] Therefore, although wearable sweat sensors have potential in detecting calcium ion concentration in sweat, further research and improvement are still needed to improve the practical performance of the sensors and expand their application range. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a wearable sensor device for detecting calcium ions in sweat.

[0006] The technical solution adopted by the present invention is: a wearable sensor device for detecting calcium ions in sweat, comprising: The microfluidic chip comprises a flexible base layer, a channel layer and a chip cover layer which are sequentially laminated, wherein a collection and detection chamber is provided in the channel layer, and sweat can pass through the flexible base layer and enter the collection and detection chamber; An electrochemical sensing module, disposed on the chip cover layer, comprising electrically connected electrode points and connecting wires, wherein the electrode points are configured to be exposed in the collection and detection chamber; The signal processing and transmission module is connected to the connection line, receives the current signal and / or voltage signal detected by the electrochemical sensing module, and converts the electrochemical signal into a digital signal through the signal conversion module.

[0007] Preferably, the flexible base layer is a Janus fabric layer, which is based on cotton fabric, treated with a hydrophobic slurry, coated with a water-based polyacrylic acid pressure-sensitive adhesive on one side, and plasma treated on the other side; forming a Janus fabric layer with self-adhesiveness on one side and local super-hydrophilicity on the other side, wherein the hydrophilic part is a plurality of dots in an array; The hydrophobic slurry includes 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane (PFOTES) and TiO2 nanoparticles.

[0008] Preferably, a non-patterned tape mask is covered on one side of the hydrophobic cotton fabric coated with a water-based polyacrylic acid pressure-sensitive adhesive, and a patterned tape mask is covered on the other side of the hydrophobic cotton fabric, and oxygen plasma etching is performed to obtain a locally super-hydrophilic Janus fabric layer, wherein the shape of the hydrophilic part is consistent with the shape of the pattern in the patterned tape mask; The pattern is a circular array with a diameter of 0.8 mm and an interval of 3 mm; the pattern range of the hydrophilic part is not smaller than the range of the collection and detection chamber.

[0009] Preferably, a microchannel is further provided on the channel layer, and the microchannel connects the collection and detection chamber with the outer side of the edge of the channel layer.

[0010] Preferably, the electrochemical sensing module comprises a reference electrode and a calcium ion concentration detection electrode, and a calcium ion selective membrane is provided on the calcium ion concentration detection electrode.

[0011] Preferably, a sweat induction module is further included, the sweat induction module includes a hydrogel and an iontophoresis electrode; the hydrogel includes an anode hydrogel and a cathode hydrogel, the iontophoresis electrode is an iontophoresis connection line respectively connecting the anode hydrogel and the cathode hydrogel, and the iontophoresis electrode is printed on the chip cover layer; the iontophoresis electrode is connected to the microcontroller circuit and the power management circuit in the signal processing and transmission module, and is controlled by the microcontroller circuit; The channel layer is provided with a first gel through hole capable of accommodating the hydrogel; the Janus fabric layer is provided with a second gel through hole corresponding to the first gel through hole; The anode hydrogel contains carbachol, and the cathode hydrogel contains potassium chloride.

[0012] Preferably, an insulating layer is provided on the connection line between the calcium ion concentration detection electrode and the iontophoresis electrode; and electrode through holes are also provided on the chip cover layer, and the electrode through holes respectively correspond to the connection lines between the calcium ion concentration detection electrode and the iontophoresis electrode.

[0013] Preferably, the signal processing and transmission module includes a front-end analog circuit, a conversion circuit, a microcontroller circuit and a power management circuit. The front-end analog circuit, the conversion circuit and the microcontroller circuit are connected in sequence, and the power management circuit is electrically connected to the front-end analog circuit, the conversion circuit and the microcontroller circuit; the front-end analog circuit is electrically connected to the calcium ion concentration detection electrode; and a Bluetooth transmission module is provided in the microcontroller circuit.

[0014] Preferably, it further comprises a host housing, the signal processing and transmission module is arranged in the host housing, the microfluidic chip is attached to the outside of the host housing, the host housing is provided with metal spring pins, and the signal processing and transmission module is electrically connected to the electrochemical electrodes in the microfluidic chip through the metal spring pins; The host housing is also provided with a second metal spring pin, which is connected to the power management circuit and is used to charge the signal processing and transmission module; The host housing is provided with an alarm system, which includes a signal indicator light and an indication circuit for controlling the indicator light, and the indication circuit is electrically connected to the microcontroller circuit.

[0015] Wearable sensor device for sweat calcium ion detection Application in sweat calcium ion detection.

[0016] The advantages and positive effects of the present invention are: using skin-like Janus fabric as a substrate can promote the transport of sweat from the skin surface to the sensor chip, and anti-gravity and unidirectional transport of sweat can be achieved without additional holes, keeping the skin surface dry; unlike traditional Janus fabrics, the spatial distribution design of the hydrophilic gradient channel allows sweat to form droplets instead of being dispersed on the entire fabric surface, which is beneficial to the subsequent separation and refreshing of sweat; through the ion electroosmosis module, the induced production of sweat in a resting state can be achieved, which can meet the sweat volume requirements for in situ detection.

[0017] By using a microfluidic chip, the sweat secreted by the skin continuously flows through the electrochemical sensor interface, which can realize real-time detection of sweat calcium ion concentration; the sweat sample is small in size, and the sweat after detection can be quickly discharged through the waste liquid discharge area through the microchannel, and there will be no sweat accumulation, thereby ensuring the accuracy of the test; the wearable sweat sensor device can monitor the information changes of calcium ion concentration in sweat, which is convenient for scientific research or daily health care use; through the circuit control system, the concentration data in sweat is collected and processed in real time, and the data is effectively converted and transmitted, which not only ensures the accuracy and stability of the output signal, but also improves the integration of the wearable sweat detection device, and therefore has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic diagram of preparing a Janus fabric layer according to an embodiment of the present invention; Figure 2 A schematic diagram showing the relationship between calcium ion concentration and the open circuit voltage measurement value of the electrochemical sensor module, and a linear correlation curve diagram between the logarithm of calcium ion concentration and the open circuit voltage measurement value of the sensor; Figure 3 A schematic diagram of the structure of a flexible substrate layer of a microfluidic chip containing an electrode array according to an embodiment of the present invention; in the figure, 11, Janus fabric layer, 111, second hydrogel through hole, 12, channel layer, 121, collection detection chamber, 122, microchannel, 123, first hydrogel through hole, 131, calcium ion concentration detection electrode, 132, iontophoresis electrode, 133, insulating layer, 14, chip cover layer, 141, electrode through hole, 15, pattern mask, 16, hydrogel; Figure 4 A schematic diagram of the structure of a wearable sensor host housing according to an embodiment of the present invention; in the figure, 21 is a metal spring pin, 22 is a second metal spring pin; Figure 5 A schematic diagram of a wearable sensor host housing according to an embodiment of the present invention; in the figure, 23, an LED signal indicator light, 24, a watch strap; Figure 6 Schematic diagram of the structure of the wearable sensor circuit control system. DETAILED DESCRIPTION

[0019] The embodiments of the present invention are described below with reference to the accompanying drawings.

[0020] The present invention relates to a wearable sensor device for sweat calcium ion detection, which can be used to detect the calcium ion concentration in sweat, can quantitatively evaluate the calcium metabolism state, detect calcium imbalance, evaluate the health of the human body, and guide calcium supplementation. The wearable sensor device for sweat calcium ion detection includes a microfluidic chip, an electrochemical sensor module, and a signal processing and transmission module for signal transmission and data processing that can be matched with the sensor chip. Among them, the microfluidic chip includes a flexible substrate layer, a channel layer 12 and a chip cover layer 14 that are sequentially bonded, and a collection detection chamber 121 is provided in the channel layer 12. Sweat can pass through the flexible substrate layer into the collection detection chamber 121; the microfluidic chip can realize rapid sweat sampling and concentration refresh. The electrochemical sensor module is printed on the chip cover layer 14, including electrically connected electrode points and connecting lines, and the electrode points are set to be exposed in the collection detection chamber 121 to directly measure the calcium ion concentration in sweat. The signal processing and transmission module is electrically connected to the electrochemical electrode for detecting calcium ion concentration in the microfluidic chip for data processing and transmission, receives the current signal and / or voltage signal detected by the electrochemical sensing module, and converts the electrochemical signal into a digital signal through the signal conversion module.

[0021] The channel layer 12 is provided with a hollow area with adjustable geometric configuration, and the hollow area can be in various shapes such as circular, elliptical, semicircular, etc. After the flexible base layer, the channel layer 12 and the chip cover layer 14 are bonded to each other, the hollow area forms a collection detection chamber 121, and the sweat enters the collection detection chamber through the hydrophilic gradient channel in the flexible base layer. The collection detection chamber can be used to accommodate the accumulated sweat; the electrochemical electrode array is integrated on the chip cover layer 14 by screen printing technology, exposed in the collection detection chamber 121, and the calcium ion concentration detection electrode 131 is precisely exposed above the collection detection chamber 121, and can contact the sweat in the collection detection chamber 121. The electrochemical electrode is electrically connected to the signal processing and transmission module to feedback the calcium ion detection situation.

[0022] One embodiment of the present invention relates to a microfluidic chip. In the microfluidic chip, the flexible substrate layer is a skin-like Janus fabric layer 11. With the skin-like Janus fabric layer 11 as the substrate, sweat can be transported from one side of the skin to the chip collection and detection chamber without opening holes, achieving efficient, anti-gravity, unidirectional transport of sweat and keeping the skin surface dry. The Janus fabric layer 11 is prepared by woven cotton fabric, which is pretreated with 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane (PFOTES) and TiO2 nanoparticles to give the woven cotton fabric material superhydrophobic properties. A self-adhesive layer is constructed by coating one side of the hydrophobic cotton fabric with a water-based polyacrylic acid pressure-sensitive adhesive, so that it has self-adhesive properties, is easy to directly adhere to the skin surface, improves the closeness of contact with the skin, and can also form a permeable adhesive network, which is conducive to the directional transmission of sweat. The PI tape is processed by CO2 laser engraving technology to construct a pattern mask 15 containing a hollow dot array. After pasting the pattern mask 15 on the other side of the hydrophobic cotton fabric, a selective plasma treatment is performed in an oxygen plasma environment to form a local hydrophilic gradient channel on the hydrophobic fabric, which can quickly pump the sweat generated at the skin-patch interface to the back, acting as a local sweat gland, effectively improving the sweat collection efficiency, so that the sweat secreted by the skin can be quickly introduced into the collection and detection chamber. The mask pattern 15 is an array of dots; such a pattern mask makes only the hole spot area in the corresponding Janus fabric layer 11 hydrophilic, forming a hydrophilic gradient channel, and the remaining non-hollow areas still remain hydrophobic, so that the sweat pumped to the surface through the hydrophilic gradient channel can form droplets instead of being dispersed on the entire fabric surface, which is conducive to the separation and refreshing of sweat. The entire area covered by the mask is not less than the range of the collection and detection chamber, so that as many hydrophilic gradient channels as possible are distributed on one side of the Janus fabric layer in the collection and detection chamber.

[0023] The channel layer 12 is attached to the side of the Janus fabric layer 11 coated with anhydrous polyacrylic acid pressure-sensitive adhesive, i.e., the surface of the hydrophilic treated side, and is combined with the chip cover layer 14 to construct a microfluidic chip containing a hollow collection and detection chamber 121. In order to facilitate the circulation of sweat, a microchannel 122 is also provided on the channel layer 12, and the microchannel 122 connects the collection and detection chamber 121 and the outer side of the edge of the channel layer 12. When the collection and detection chamber is filled with sweat, the excess liquid will be discharged through the microchannel 122.

[0024] The electrochemical electrodes are printed on the chip cover layer 14, wherein the working electrode for detecting calcium ions can be exposed in the collection detection chamber 121; the electrochemical electrodes include a calcium ion concentration detection electrode 131 (including a reference electrode and a working electrode), and the electrochemical electrodes are obtained by sequentially printing Ag / AgCl slurry and conductive carbon slurry on a flexible PET substrate through screen printing technology. Unmodified electrode-based sensor devices (bare electrodes) can be mass-produced through the above process at low cost. Each working electrode in the calcium ion concentration detection electrode includes an electrode point and a connecting line, and the end of the connecting line forms an electrode foot line.

[0025] On the working electrode, Prussian blue was deposited and calcium ion selective membrane was drop-coated to construct an all-solid-state calcium ion selective electrode. 1% mass fraction of calcium ion carrier IV (tert-butyl-calix[4]arene tetrakis[2-(diphenylphosphinoyl)ethyl ether)), 0.55% sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), 33% polyvinyl chloride (PVC), and 65.45% 2-nitrophenyl octyl ether (DOS) were dissolved in 1 mL of tetrahydrofuran to prepare a calcium ion selective membrane solution. The electrochemical electrode was immersed in a mixed solution containing 5 mM FeCl3, 5 mM K3[Fe(CN)6] and 0.1 M KCl, and the reaction mixture was heated at 100 mV s between 0 and 1.0 V. -1 Prussian blue was electrodeposited at a scanning speed of , and a Prussian blue solid transduction layer was obtained after 30 cyclic voltammetry depositions. After washing with deionized water and drying, 10 μL of calcium ion selective membrane solution was added, and after drying, a fully solid-state calcium ion selective electrode was formed. Calcium ions can be selectively allowed to pass through, and other components in sweat can be prevented from passing through, so that only calcium ions can affect the potential difference at the electrode point. The experiment found that the logarithm of the calcium ion concentration is linearly related to the open circuit potential measurement value of the sensor. In the subsequent sweat measurement, the real-time concentration of calcium ions in sweat can be calculated according to the linear regression equation through the open circuit potential detected in the wearable signal processing and transmission module.

[0026] The collection and detection chamber 121 is located directly below the calcium ion concentration detection electrode 131 and directly above the porous gradient wettability channel, so that the sweat secreted from the skin surface is directly pumped into the collection and detection chamber 121 through the porous gradient wettability channel, causing the electrical signal of the calcium ion concentration detection electrode to change. After the detection chamber is filled with sweat, under the action of the pressure of the sweat glands and the Laplace pressure of the microchannel, the accumulated sweat flows toward the outlet through the microchannel, and the excess liquid is discharged through the microchannel on the straight side. Through such a process, a sweat circulation channel is formed to ensure that the sweat in the collection and detection chamber is constantly replaced, new sweat enters, and old sweat is discharged, so that the sweat contacted by the calcium ion concentration detection electrode is always the newly secreted sweat, and the concentration of sweat is refreshed, thereby realizing real-time monitoring of the calcium ion concentration of sweat.

[0027] Using skin-like Janus fabric as a substrate can promote the transport of sweat from the skin surface to the sensor chip, and anti-gravity, one-way transport of sweat can be achieved without additional holes, and the skin surface can be kept dry. Using Janus fabric including multiple hydrophilic gradient channels as the sweat inlet, the sweat generated at the skin-device interface can be quickly pumped to the back, increasing the sweat collection rate, simplifying the sweat collection structure, greatly reducing the volume of the entire device, and facilitating sweat refreshing. The sensor patch is flexible and can be used for a long time, and the sensor electrodes can be prepared in large quantities by screen printing technology. The microfluidic chip structure can also be mass-produced by CO2 laser engraving technology with better consistency and stability.

[0028] In certain embodiments of the present invention, in order to further promote sweating, a sweat induction module is also provided to achieve the induction of sweat in a resting state to meet the sweat volume requirements of in-situ detection. The sweat induction module includes a hydrogel 16 and an iontophoresis electrode 132. An agarose solution containing carbachol and an agarose solution containing potassium chloride are respectively dripped into the gel through hole, and the anode hydrogel and the cathode hydrogel are obtained after solidification at room temperature. The electrochemical electrode also includes an iontophoresis electrode, and the hydrogel 16 is connected to the iontophoresis electrode 132 of the electrode layer to form a sweat induction module. The iontophoresis connecting wire is prepared in the same manner as the connecting wire in the calcium ion concentration detection electrode 131. The hydrogel can release the sweat-promoting agent therein when the iontophoresis electrode provides current. When used, it can be implemented multiple times or at intervals as needed to promote sweat induction. For example, when used for monitoring the exercise process, the sweat induction module does not need to be started, and the sweat induction module can be activated when in a resting state. Based on this characteristic, the difference in sweat calcium ion changes between exercise and resting states can be compared by controlling the activation of the sweat induction module.

[0029] In order to accommodate the anode hydrogel and the cathode hydrogel, a pair of gel through holes are cut on the Janus fabric layer 11 and the channel layer 12 respectively by CO2 laser engraving technology. During preparation, the prepared hydrogel solution can be introduced into the gel through hole, and the hydrogel is formed after solidification; or it can be introduced into a mold of the corresponding shape in advance, and then assembled after solidification. The electrochemical electrode contacts the signal processing and transmission module through the electrode connecting wire foot line to realize signal transduction. At the same time, the iontophoresis electrode also directly contacts the anode gel and the cathode gel to form an iontophoresis anode and an iontophoresis cathode. After the power is turned on, the iontophoresis anode repels the positively charged carbachol drug from entering the skin to induce sweating and form a sweat sample to be detected. By promoting sweat discharge through carbachol hydrogel, the induction of sweat in a resting state and the real-time monitoring of sweat calcium ion concentration can be realized, which is highly practical and sensitive. By promoting sweating through the hydrogel 16, in cooperation with the Janus fabric layer 11, the sweat sample is quickly collected into the collection and detection chamber 121 for sweat calcium ion detection.

[0030] An insulating layer 133 is covered above the portion where the electrode array connection wires are located to prevent the connection wires in the electrode circuit from being electrically connected to the outside. The ends of the connection wires of the electrode circuit are not covered by the insulating layer 133 to achieve signal conduction. An electrode through hole 141 is also provided on the chip cover layer 14. The electrode through hole 141 corresponds to the end of the electrode foot line in a direction perpendicular to the sensor patch, so that the connection wire can be exposed within the range of the electrode through hole 141. The signal processing and transmission module can be electrically connected to the electrochemical electrode through the electrode through hole 141, and the end of the connection wire portion of the electrode circuit can be connected to the front-end analog circuit of the signal processing and transmission module.

[0031] When in use, first control the iontophoresis circuit, energize the anode hydrogel and cathode hydrogel, the iontophoresis current is 1 mA, the electroosmosis time is 5-10 min, release the permeation enhancer onto the skin, and promote the skin to discharge sweat; the discharged sweat sample is transported to the collection and detection chamber against gravity through the porous gradient wettability channel on the surface of the Janus fabric layer, causing the electrical signal of the calcium ion concentration detection electrode to change, thereby realizing the analysis of the target molecule concentration in the sweat sample, and the calcium ion concentration therein is obtained through electrochemical electrode detection, and then the calcium ion concentration information is fed back or further processed through the signal processing and transmission module; as the sweat continues to accumulate, the excess sweat will be discharged through the microchannel, and the fresh sweat sample enters the microchamber for detection.

[0032] On the other hand, the present invention also relates to a wearable sensor, including a microfluidic chip, a signal processing and transmission module and a host housing; the host housing can be prepared by 3D printing, or mass-produced by injection molding; the electrochemical electrode in the microfluidic chip is electrically connected to the signal processing and transmission module, the signal processing and transmission module is arranged in the host housing, and the microfluidic chip is bonded to the outside of the host housing. The host housing can be prepared by 3D printing, or mass-produced by injection molding. A metal spring needle 21 is provided on the host housing, and the metal spring needle 21 can contact the electrode connection line in the electrode through hole 141, and can control the release of the permeation enhancer in the sensing patch hydrogel and collect the open circuit voltage signal generated by the electrochemical electrode; the other end of the metal spring needle 21 is connected to the signal processing and transmission module circuit, thereby realizing the connection and information transmission between the electrochemical electrode in the microfluidic chip and the signal processing and transmission module.

[0033] The signal processing and transmission module circuit integrates the front-end analog circuit, conversion circuit, microcontroller circuit and power management circuit. The front-end analog circuit, conversion circuit and microcontroller circuit are connected in sequence. The power management circuit is electrically connected to the front-end analog circuit, conversion circuit and microcontroller circuit. The front-end analog circuit is connected to the electrode connection pin of the sweat sensor patch through the bottom spring pin; the iontophoresis electrode is connected to the microcontroller circuit, and the power management circuit is connected to the iontophoresis circuit to provide power for the iontophoresis. The wearable sweat sensor transmits the calcium ion concentration data wirelessly to the mobile terminal device through the Bluetooth transmission module in the signal processing and transmission module. The user can view the data in real time on the mobile device and conduct in-depth data analysis.

[0034] The wearable intelligent sensor has an internal alarm system. When an abnormal calcium ion concentration is detected, the color of the sensor's signal indicator light will change to help evaluate the calcium metabolism state, detect calcium imbalance, evaluate human health, and provide calcium supplementation strategies. Specifically, it can be set as an LED signal indicator light 23 integrated on the host housing. The metal spring needle 21 and the LED signal indicator light 23 are both electrically connected to the signal processing and transmission module. When the calcium ion concentration is detected to be beyond the normal threshold range, the color of the signal indicator light will change.

[0035] Two second metal spring pins 22 for charging are also provided at the bottom of the wearable sensor, which are also provided on the host housing. They are connected to the power management module in the circuit control system and can charge the sensor device to extend the service life of the device.

[0036] The host shell can be worn flexibly and can be directly worn on the wrist of the subject through the strap 24. In addition, it can be directly attached to the skin surface and fixed on the chest or back through low-sensitivity glue to collect sweat concentration data of different parts. When using low-sensitivity glue, a window is opened on the low-sensitivity glue layer, so that at least part of the Janus fabric layer 11 can directly contact the skin surface and pump the sweat on the skin surface into the collection and detection chamber.

[0037] By using a microfluidic chip, the sweat secreted by the skin continuously flows through the electrochemical sensor interface, which can realize real-time detection of sweat calcium ion concentration; the sweat sample is small in size, and the sweat after detection can be quickly discharged through the waste liquid discharge area through the microchannel, and there will be no sweat accumulation, ensuring the accuracy of the test; the wearable sweat signal processing and transmission module can monitor the information changes of calcium ion concentration in sweat, which is convenient for scientific research or daily health care use; through the circuit control system, the concentration data in sweat is collected and processed in real time, and the data is effectively converted and transmitted, which not only ensures the accuracy and stability of the output signal, but also improves the integration of the wearable sweat detection device, so it has good application prospects.

[0038] The scheme of the present invention is described below in conjunction with the accompanying drawings, wherein the experimental methods without specific operating steps are all carried out in accordance with the corresponding product instructions, and the instruments, reagents, and consumables used in the examples can all be purchased from commercial companies unless otherwise specified.

[0039] Sources of reagents and instruments: Calcium ionophore IV (ETH4324, tert-butyl-calix[4]arene tetrakis[2-(diphenylphosphinoyl)ethyl ether), sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), 2-nitrophenyl octyl ether (DOS), polyvinyl chloride (PVC), carbachol, agarose, and PFOTES were from Aladdin Reagent (Shanghai) Co., Ltd. Sodium chloride, potassium chloride, ferric chloride, potassium ferrocyanide (K4[Fe(CN)6]), and tetrahydrofuran were from Sinopharm Chemical Reagent Co., Ltd.; P25 TiO2 was purchased from Degussa (Shanghai) Trading Co., Ltd. Polyethylene terephthalate (PET) film and PET film with double-sided tape were purchased from Suzhou Lianshida Electronic Technology Co., Ltd. Electrochemical workstation: CHI1040C, Shanghai Chenhua Instrument Co., Ltd.

[0040] Example 1: Preparation of skin-like Janus fabric The cotton fabrics were subjected to superhydrophobic treatment, and the fabrics used were all woven cotton fabrics, which had gone through traditional desizing, refining and bleaching processes before use.

[0041] A super-hydrophobic coating was obtained by adding 2 mL PFOTES and 10 g P25 TiO2 nanoparticles to 198 mL ethanol solution and stirring vigorously for 2 h. Cotton fabric was immersed in the coating suspension, taken out after soaking for 5 min, and dried in air to obtain a super-hydrophobic cotton fabric. A water-based polyacrylic acid pressure-sensitive adhesive was coated on one side of the hydrophobic fabric surface and dried and cured at 50 ° C to obtain a super-hydrophobic cotton fabric with an adhesion effect.

[0042] The superhydrophobic cotton fabric was subjected to local plasma treatment. A tape mask with a laser-cut hole pattern (0.8 mm in diameter and 3 mm between holes) was tightly covered on the side of the superhydrophobic cotton fabric that was not coated with the pressure-sensitive adhesive, and the same tape mask without a hole pattern was covered on the side of the hydrophobic fabric that was coated with the pressure-sensitive adhesive. The masked fabric was placed in an oxygen plasma etcher and etched at an O2 flow rate of 50 cm 3 / min, and the power was 200 W for 4 min. Due to the presence of the tape mask, only the hole spot area on the top of the fabric was exposed to the plasma, forming a local super-hydrophilic property. After plasma treatment, a "skin-like" fabric with a unidirectional transport channel was obtained. During assembly, the collection and detection chamber corresponded to the position of the Janus fabric after plasma treatment.

[0043] Example 2: Preparation of iontophoretic hydrogel Anode gel: Add agarose (3% w / w) to deionized water and heat to 250°C with constant stirring. After the mixture is fully boiled and uniform without agarose particles, cool the mixture to 165°C and add 1% (w / w) carbachol to the above mixture. Then, slowly pour the cooled mixture into the pre-made mold or assembled microfluidic patch and cure at 4°C for 10 min.

[0044] Cathode gel: Add agarose (3% w / w) to deionized water and heat to 250°C with constant stirring. After the mixture is fully boiled and uniform without agarose particles, cool the mixture to 165°C and add 1% (w / w) KCl to the mixture. Then, slowly pour the cooled mixture into the pre-made mold or assembled microfluidic patch and cure at 4°C for 10 min.

[0045] Example 3: Preparation and assembly of microfluidic chip 3.1 Design of microfluidic chip The Janus fabric layer 11 was prepared according to the method of Example 1, the channel layer 12 was prepared with 3M double-sided adhesive with a thickness of 0.2 mm, and the chip cover layer 14 was prepared with flexible PET. The structure of each component of the microfluidic chip was designed using AutoCAD drawing software, and the Janus fabric layer 11, the channel layer 12, and the chip cover layer 14 were patterned by CO2 laser engraving, and the laser power was 50 W.

[0046] Among them, a semicircular collection and detection chamber 121 is provided in the middle of the channel layer 12, and a microchannel is opened on the straight edge thereof, and the microchannel is connected to the edge of the channel layer; first hydrogel through holes 123 are provided on both sides of the collection and detection chamber 121, which can accommodate arc-shaped anode hydrogel and cathode hydrogel. The chip cover layer is provided with electrode through holes that can expose the electrochemical electrode connection line. The Janus fabric layer is also provided with a second hydrogel through hole 111, which is consistent with the first hydrogel through hole 123 in shape and position.

[0047] 3.2 Design of electrochemical electrode for sweat calcium concentration detection Electrochemical electrodes are printed on the chip cover layer 14. The electrochemical electrodes include a group of calcium ion concentration detection electrodes 131 and a pair of iontophoresis electrodes 132. The calcium ion concentration detection electrodes 131 include a working electrode and a reference electrode, each of which includes an electrode point and a detection connection line, and the iontophoresis electrode 132 includes an iontophoresis connection line.

[0048] The chip cover layer of PET material is used as the electrode substrate. Ag / AgCl paste is printed on the flexible substrate at the detection electrode points, detection connection lines and iontophoresis connection lines by screen printing technology; conductive carbon paste is printed on the detection electrode points. The electrode basic sensor device is printed layer by layer using screen printing technology, from bottom to top, respectively, PET substrate, conductive silver paste, conductive carbon paste, and the upper part of the detection connection line and iontophoresis connection line is covered with an insulating layer. The pins of the detection connection line and iontophoresis connection line are exposed in the electrode through-hole.

[0049] The calcium ion working electrode needs to be superimposed with a calcium ion selective membrane after printing Ag / AgCl slurry and conductive carbon slurry. 1% by mass of calcium ion carrier IV (tert-butyl-calix[4]arene tetrakis[2-(diphenylphosphinoyl)ethyl ether)), polyvinyl chloride (PVC), 0.55% sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), 33% PVC, and 65.45% DOS were dissolved in 1 mL of tetrahydrofuran to form a calcium ion selective membrane solution. The electrochemical electrode was immersed in a mixed solution containing 5 mM FeCl3, 5 mM K3[Fe(CN)6], and 0.1 M KCl, and the reaction mixture was heated at 100 mV s between 0 and 1.0 V. -1Prussian blue was electrodeposited at a scanning speed of , and a Prussian blue solid transduction layer was obtained after 30 cyclic voltammetry depositions. After washing with deionized water and drying, 10 μL of calcium ion selective membrane solution was added dropwise, and after drying, a fully solid calcium ion selective electrode was formed. The prepared electrode can selectively allow calcium ions to pass through and prevent other components in sweat from passing through, so that only calcium ions can affect the potential difference at the electrode point.

[0050] 3.3 Linear relationship between calcium ion concentration and calcium ion selective electrode 100 μL of calcium chloride solution (0.1 - 250 mM) of different concentrations was dripped onto the surface of the electrode array, and the open circuit voltage between the calcium ion working electrode and the reference electrode at different calcium ion concentrations was recorded. Figure 2 The diagram shows the relationship between calcium ion concentration and the open circuit potential measurement value of the sensor. Figure 5 It can be seen that the logarithm of calcium ion concentration is linearly related to the open circuit potential measurement value of the sensor, and the linear regression equation is E =27.217 ln C Ca +138.52. In the subsequent sweat measurement, the open circuit potential detected in the wearable signal processing and transmission module can be used to calculate the real-time concentration of calcium ions in sweat according to the linear regression equation.

[0051] 3.4 Assembly of microfluidic chip The Janus fabric layer, the channel layer and the chip cover layer printed with electrochemical electrodes are bonded in sequence, and the electrode points of the calcium ion concentration detection electrode are exposed in the collection detection chamber; the anode gel and the cathode gel prepared in Example 2 are placed in the first gel through hole, and the ion electrophoresis connection line can contact the anode gel and the cathode gel.

[0052] Example 4: Wearable Sweat Sensor 4.1 Assembly of wearable sweat sensor The wearable sweat sensor comprises a microfluidic chip, a signal processing and transmission module and a host housing prepared and assembled as in Example 3; the electrochemical electrodes in the microfluidic chip are electrically connected to the signal processing and transmission module, the signal processing and transmission module is arranged in the host housing, and the microfluidic chip is bonded to the outside of the host housing. Figure 4 As shown, a metal spring pin 21 is provided at the bottom of the main housing, which can contact the electrode connection wire in the electrode through hole; Figure 5 As shown, an LED signal indicator light 23 is also integrated on the main housing. The metal spring needle 21 and the LED signal indicator light 23 are electrically connected to the signal processing and transmission module. When the calcium ion concentration is detected to be beyond the normal threshold range, the color of the signal indicator light will change.

[0053] The circuit system in the signal processing and transmission module is used for signal processing and transmission, including front-end analog circuits, conversion circuits, microcontroller circuits and power management circuits, such as Figure 6 As shown; the front-end analog circuit is electrically contacted with the end of the electrode pin exposed at the electrode through-hole through the spring pin at the bottom of the host housing, collects the open-circuit voltage signal and sends the signal to the conversion circuit. The conversion circuit will generate the reference voltage required for electrochemical measurement and perform differential processing on the collected voltage signal, and send the differentially processed data to the microcontroller circuit; the microcontroller circuit also includes an MCU and a Bluetooth module, wherein the MCU and the Bluetooth module are connected, and the MCU is used to control the conversion circuit to process the data collected by the front end, and to control the power management to power the front-end analog circuit, the conversion circuit and the iontophoresis module. The MCU is also used to run the protocol stack program required for Bluetooth communication; the Bluetooth module is used to transmit the data to the mobile terminal, and the mobile terminal receives the signal and outputs the sweat detection result corresponding to the signal, presenting the sweat detection result in a visual and simplified manner, so that the user can monitor the physiological condition reflected by the sweat detection result in real time. The above circuit modules are powered by the power management circuit.

[0054] 4.2 Wearable electrochemical sensor for sweat calcium concentration detection Before the test, the subject's skin was wiped with alcohol and the wearable sweat sensor was attached to the subject's forearm; due to the self-adhesive properties of the Janus fabric layer, the Janus fabric layer could be directly adhered to the skin surface.

[0055] In actual measurement, a constant current of 1 mA is applied between the cathode and anode electrodes of the ion introduction electrode for 10 min to induce sweat production; the sweat secreted from the skin surface is collected into the collection and detection chamber through the unidirectional channel of the Janus fabric layer, which can make the electrode array printed on the back of the microfluidic chip cover generate a corresponding electrical signal. The electrical signal is expressed in the form of open circuit voltage, and there is a positive correlation between the open circuit voltage and the calcium ion concentration in the sweat. Figure 2 The corresponding relationship shown in the figure; through the processing of the signal processing and transmission module, the calculated concentration data is directly fed back to the mobile phone terminal.

[0056] The embodiments of the present invention are described in detail above, but the contents described are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.

Claims

1. A wearable sensor device for detecting calcium ions in sweat, characterized in that: include, The microfluidic chip comprises a flexible base layer, a channel layer and a chip cover layer which are sequentially laminated, wherein a collection and detection chamber is provided in the channel layer, and sweat can pass through the flexible base layer and enter the collection and detection chamber; An electrochemical sensing module, disposed on the chip cover layer, comprising electrically connected electrode points and connecting wires, wherein the electrode points are configured to be exposed in the collection and detection chamber; The signal processing and transmission module is connected to the connection line, receives the current signal and / or voltage signal detected by the electrochemical sensing module, and converts the electrochemical signal into a digital signal through the signal conversion module.

2. The wearable sensor device for detecting calcium ions in sweat according to claim 1, characterized in that: The flexible base layer is a Janus fabric layer. The Janus fabric layer is based on cotton fabric. After being treated with a hydrophobic slurry, one side is coated with a water-based polyacrylic acid pressure-sensitive adhesive and the other side is plasma treated. This forms a Janus fabric layer with self-adhesiveness on one side and local super-hydrophilicity on the other side. The hydrophilic part is in the form of multiple dots in an array. The hydrophobic slurry includes 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane (PFOTES) and TiO2 nanoparticles.

3. The wearable sensor device for detecting calcium ions in sweat according to claim 2, characterized in that: A non-patterned tape mask is covered on one side of the hydrophobic cotton fabric coated with a water-based polyacrylic acid pressure-sensitive adhesive, and a patterned tape mask is covered on the other side of the hydrophobic cotton fabric, and oxygen plasma etching is performed to obtain a locally super-hydrophilic Janus fabric layer, and the shape of the hydrophilic part is consistent with the pattern shape in the patterned tape mask; The pattern is a circular array with a diameter of 0.8 mm and an interval of 3 mm; the pattern range of the hydrophilic part is not smaller than the range of the collection and detection chamber.

4. The wearable sensor device for detecting calcium ions in sweat according to claim 1, characterized in that: A microchannel is also provided on the channel layer, and the microchannel connects the collection and detection chamber with the outer side of the edge of the channel layer.

5. The wearable sensor device for detecting calcium ions in sweat according to any one of claims 1 to 4, characterized in that: The electrochemical sensing module comprises a reference electrode and a calcium ion concentration detection electrode, on which a calcium ion selective membrane is arranged.

6. The wearable sensor device for detecting calcium ions in sweat according to claim 5, characterized in that: It also includes a sweat induction module, which includes a hydrogel and an iontophoresis electrode; the hydrogel includes an anode hydrogel and a cathode hydrogel, the iontophoresis electrode is an iontophoresis connection line respectively connecting the anode hydrogel and the cathode hydrogel, and the iontophoresis electrode is printed on the chip cover layer; the iontophoresis electrode is connected to the microcontroller circuit and the power management circuit in the signal processing and transmission module, and is controlled by the microcontroller circuit; The channel layer is provided with a first gel through hole capable of accommodating the hydrogel; the Janus fabric layer is provided with a second gel through hole corresponding to the first gel through hole; The anode hydrogel contains carbachol, and the cathode hydrogel contains potassium chloride.

7. The wearable sensor device for detecting calcium ions in sweat according to claim 6, characterized in that: An insulating layer is provided on the connection line between the calcium ion concentration detection electrode and the iontophoresis electrode; and electrode through holes are also provided on the chip cover layer, and the electrode through holes correspond to the connection lines between the calcium ion concentration detection electrode and the iontophoresis electrode respectively.

8. The wearable sensor device for detecting calcium ions in sweat according to claim 1, characterized in that: The signal processing and transmission module includes a front-end analog circuit, a conversion circuit, a microcontroller circuit and a power management circuit. The front-end analog circuit, the conversion circuit and the microcontroller circuit are connected in sequence, and the power management circuit is electrically connected to the front-end analog circuit, the conversion circuit and the microcontroller circuit; the front-end analog circuit is electrically connected to the calcium ion concentration detection electrode; and a Bluetooth transmission module is provided in the microcontroller circuit.

9. The wearable sensor device for detecting calcium ions in sweat according to claim 8, characterized in that: It also includes a host housing, the signal processing and transmission module is arranged in the host housing, the microfluidic chip is attached to the outside of the host housing, the host housing is provided with metal spring pins, and the signal processing and transmission module is electrically connected to the electrochemical electrodes in the microfluidic chip through the metal spring pins; The host housing is also provided with a second metal spring pin, which is connected to the power management circuit and is used to charge the signal processing and transmission module; The host housing is provided with an alarm system, which includes a signal indicator light and an indication circuit for controlling the indicator light, and the indication circuit is electrically connected to the microcontroller circuit.

10. Use of the wearable sensor device for sweat calcium ion detection according to any one of claims 1 to 9 in sweat calcium ion detection.

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