CN109374713A - Sweat monitoring sensor system, patch and preparation method thereof - Google Patents

Abstract

The invention provides a sweat monitoring sensing system, a patch and a preparation method thereof, wherein the method comprises: preparing a flexible and extensible substrate; making a hydrophilic open-pore silicone sponge; making a plurality of sensing chips; The sensor chips are transferred onto a flexible and extensible substrate, and a hydrophilic open-pored silicone sponge is placed on top of each sensor chip. The invention has the advantages of simple structure and convenient preparation, and is beneficial to meet the monitoring requirements.

Description

Sweat monitoring sensor system, patch and preparation method thereof

technical field

The invention relates to the technical field of monitoring, in particular to a sweat monitoring sensing system, a patch and a preparation method thereof.

Background technique

With the rapid development of science and technology and the improvement of living standards, the demand for physiological monitoring is also increasing, and the requirements are also increasing. Then the existing monitoring products and methods are often complicated in operation, high in cost, and insufficient in practicability. The monitoring efficiency is not high, and it cannot be worn on the human body to obtain physiological parameter indicators in real time and non-invasively at the molecular level, which cannot well meet the needs of use.

SUMMARY OF THE INVENTION

(1) Technical problems to be solved

In view of the above technical problems, the purpose of the present invention is to provide a sweat monitoring sensor system, a patch and a preparation method thereof, so as to solve at least one of the above problems.

(2) Technical solutions

According to one aspect of the present invention, a preparation method of a sweat monitoring sensor patch is provided, comprising:

Prepare flexible and extensible substrates;

Making hydrophilic open-pore silicone sponge;

Make multiple sensor chips;

Each of the sensing chips is transferred onto the flexible and extensible substrate, and the hydrophilic open-pore silicone sponge is arranged on top of each of the sensing chips.

In some embodiments, the manufacturing of the hydrophilic open-pore silicone sponge includes:

Addition type platinum-catalyzed silica gel is used to make open-cell sponge matrix;

The surface of the open-cell sponge substrate is modified by using a super-hydrophilic coating to obtain the hydrophilic open-cell silicone sponge.

In some embodiments, the plurality of the sensor chips include: a sodium ion sensor chip, a potassium ion sensor chip, a calcium ion sensor chip, a chloride ion sensor chip, a glucose sensor chip and a lactate sensor chip; making The sensor chip includes:

Making a basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface;

The working electrode in the basic electrode is modified to obtain the sensor chip.

In some embodiments, the plurality of sensor chips include: a sweat pH value sensor chip and a sweat perspiration sensor chip; making the sensor chips includes: making a basic electrode, a magnetic output interface, and connecting a The basic electrode and the horseshoe-shaped line of the magnetic output interface to obtain the sensor chip; or

The plurality of the sensor chips include: a skin temperature sensor chip; and the fabrication of the sensor chip includes: fabrication of a magnetic output interface and a horseshoe-shaped wire connected to the magnetic output interface, so as to obtain the sensor chip .

In some embodiments, the base electrode includes a reference electrode, and the fabrication of the base electrode, the magnetic output interface and the horseshoe-shaped wire connecting the base electrode and the magnetic output interface includes:

Spin-coating a lower insulating layer on the copper foil, connecting the lower insulating layer and the metal layer substrate;

sputtering a titanium layer on the copper foil, and sputtering a gold layer on the titanium layer;

forming the reference electrode by electroplating on the gold layer;

The basic electrode, the magnetic output interface and the horseshoe-shaped wire except the reference electrode are fabricated by using photolithography technology and various etching solutions;

Making an upper insulating layer on the horseshoe wire;

The base electrode, the magnetic output interface, the horseshoe wire, the lower insulating layer and the upper insulating layer are peeled off from the metal layer substrate.

In some embodiments, if the sensor chip is the sodium ion sensor chip, the potassium ion sensor chip, the calcium ion sensor chip or the chloride ion sensor chip, the The working electrode in the basic electrode is modified to obtain the sensor chip, including:

making a conductive organic polymer electron transfer layer on the working electrode;

Use ion-selective carriers, membrane substrates, plasticizers and ion-exchangers to configure ion-selective membranes;

The ion-selective membrane is disposed on the conductive organic polymer electron transport layer.

In some embodiments, if the sensor chip is the glucose sensor chip or the lactate sensor chip, the working electrode in the base electrode is modified to obtain the sensor chip, comprising: :

forming an electron transfer layer on the working electrode;

drop-coating the oxidase solution on the electron transfer layer, and let it stand to dry to form an oxidase layer;

An active material protective layer is formed on the oxidase layer.

In some embodiments, the reference electrode of the sodium ion sensing chip, the potassium ion sensing chip, the calcium ion sensing chip and the chloride ion sensing chip and the same magnetic output The reference electrodes of the glucose sensing chip and the lactic acid sensing chip are connected to the same magnetic suction output interface.

According to another aspect of the present invention, there is provided a sweat monitoring sensor patch, comprising:

Flexible and extensible substrate;

a plurality of sensor chips on the flexible extensible substrate; and

A hydrophilic open-pore silicone sponge on top of each of the sensor chips.

According to yet another aspect of the present invention, a sweat monitoring sensing system is provided, comprising: a terminal, a flexible signal processing and transmission circuit, and the sweat monitoring sensing patch; wherein,

The sweat monitoring sensing patch is connected to the flexible signal processing and transmission circuit, and is used for sending the signal detected by the sweat monitoring sensing patch to the flexible signal processing and transmission circuit;

The flexible signal processing and transmission circuit is connected to the terminal for receiving the signal sent by the sweat monitoring sensor patch, converting the signal into sweat component information, and sending the sweat component information to the the terminal;

The terminal is configured to receive and analyze the sweat component information sent by the flexible signal processing and transmission circuit.

(3) Beneficial effects

As can be seen from the above technical solutions, the sweat monitoring sensing system, patch and preparation method thereof provided by the present invention have the following beneficial effects:

(1) The sweat monitoring sensor patch of the present invention includes a flexible and extensible substrate; a plurality of sensor chips on the flexible and extensible substrate; and a hydrophilic open-pored silicone sponge on top of each of the sensor chips , the structure is simple, the preparation is convenient, and it is beneficial to meet the monitoring needs.

(2) The present invention can alleviate the technical problem existing in the prior art that cannot meet the requirement of real-time non-invasive acquisition of physiological parameter indicators on the human body from the molecular level, and achieves the real-time non-invasive requirement of the wearable on the human body from the molecular level. The technical effect of the demand for obtaining physiological parameter indicators.

(3) In the present invention, the horseshoe-shaped wire is used to connect the basic electrode and the magnetic suction output interface, which removes the sharp angle, avoids the pressure concentration effect, improves the pressure resistance, and reduces the short circuit of the connecting wire caused by various mechanical factors. occurs, bending in various directions can be achieved, increasing ductility and practicability;

(4) In the present invention, the reference electrodes of the sodium ion sensing chip, potassium ion sensing chip, calcium ion sensing chip and chloride ion sensing chip are connected to the same magnetic suction output interface, and the glucose sensing chip and the lactic acid sensing chip are connected to the same magnetic suction output interface. The reference electrode of the sensor chip is connected to the same magnetic output interface, which can reduce the volume of the sweat monitoring sensor patch, make the sweat monitoring sensor patch easier to wear and move, and also save production materials. Reduced cost of making sweat-monitoring sensor patches;

(5) In the present invention, the sweat monitoring sensor patch is connected to the flexible signal processing transmission circuit through the magnetic suction output interface, and the magnetic suction output interface can quickly and conveniently realize the connection or disconnection operation, which saves the operation time and improves the efficiency of use;

(6) The hydrophilic open-pore silicone sponge made by the present invention collects sweat by capillary action, removes grease, avoids direct contact of metal electrodes with human epidermis, and can improve sweat monitoring efficiency;

(7) In the present invention, each sensor chip is a high-channel integrated chip, and each sensor chip is transferred to a flexible and extensible substrate, so that the sweat monitoring sensor patch can simultaneously monitor various physiological conditions of the human body in real time. Parameter indicators to improve monitoring efficiency and practicability;

(8) In the present invention, each sensor chip is fabricated by using CMOS technology and materials such as copper, titanium, gold, silver, and polyimide, so that the sensor chip has high precision, low power consumption, high speed and integration. High degree of characteristics.

Description of drawings

In order to illustrate the specific embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that need to be used in the description of the specific embodiments or the prior art. Obviously, the accompanying drawings in the following description The drawings are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative efforts.

1 is a flowchart of a method for preparing a sweat monitoring sensor patch provided by an embodiment of the present invention;

2 is a schematic diagram of a manufacturing process of a basic electrode, a magnetic output interface and a horseshoe wire provided by an embodiment of the present invention;

3 is a schematic diagram of a working electrode modification process of a sodium ion sensing chip, a potassium ion sensing chip, a calcium ion sensing chip, and a chloride ion sensing chip provided in an embodiment of the present invention;

4 is a schematic structural diagram of a reference electrode of a sodium ion sensor chip, a potassium ion sensor chip, a calcium ion sensor chip, and a chloride ion sensor chip being connected to the same magnetic output interface provided in an embodiment of the present invention;

5 is a schematic diagram of a working electrode modification process of a glucose sensor chip and a lactate sensor chip provided by an embodiment of the present invention;

6 is a schematic structural diagram of the connection between the reference electrodes of the glucose sensor chip and the lactate sensor chip provided by the embodiment of the present invention and the same magnetic suction output interface;

7 is a schematic diagram of the layout of a sweat monitoring sensor patch provided by an embodiment of the present invention;

FIG. 8 is a cross-sectional view of a sweat monitoring sensor patch provided by an embodiment of the present invention.

Detailed ways

In order to make the purposes, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, but not all of them. example. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

The embodiments of the present invention provide a sweat monitoring sensing system, a patch, and a preparation method thereof, which can alleviate the existing technologies that cannot meet the needs of being wearable on the human body to obtain physiological parameter indicators in real time and non-invasively at the molecular level. The technical effect is that it can meet the needs of real-time and non-invasive acquisition of physiological parameter indicators on the human body from the molecular level.

In order to facilitate the understanding of this embodiment, a method for preparing a sweat monitoring sensor patch disclosed in the embodiment of the present invention is first introduced in detail. As shown in FIG. 1 , the method may include the following steps.

In step S101, a flexible and extensible substrate is prepared.

Wherein, the flexible and extensible substrate can be a flexible and extensible epidermal film structure, and the flexible and extensible substrate can be composed of ultra-thin polymer materials with ultra-high elasticity and ultra-high ductility, which can be deformed and extended with human skin. The movement of human skin is not hindered. The flexible and extensible substrate can be adsorbed on the surface of human skin through natural intermolecular affinity.

Specifically, the flexible and extensible substrate may be 5% spandex 95% polyester four-way stretch polyester fabric.

Step S102, making a hydrophilic open-pore silicone sponge.

Further, step S102 may include the following steps:

Addition type platinum-catalyzed silica gel is used to make open-cell sponge matrix.

Specifically, using the silica gel foaming process, the addition-type platinum-catalyzed silica gel is stirred and mixed at a ratio of 1:1, and foamed in a container with pores to avoid flatulence. The gas phase is air, the liquid phase is deionized water, and the droplet is 2 μL. At this point, the hydrophilicity can be tested using a contact angle meter. The contact angle can be 130 degrees in a hydrophobic state.

The surface of the open-cell sponge substrate is modified by using a super-hydrophilic coating to obtain the hydrophilic open-cell silicone sponge.

Exemplarily, methods such as plasma surface modification and graft surface modification can also be used to modify the surface of the open-cell sponge substrate. For example, in the grafting surface modification method, plasma etching can be performed on the open-cell sponge substrate, then the etched open-cell sponge substrate can be soaked under the action of a catalyst, and finally dried in an oven at 80 degrees, and the The soaking and drying steps were repeated 5 times to obtain the hydrophilic open-pore silicone sponge.

Among them, in the process of use, the hydrophilic open-pore silicone sponge is in contact with human skin, and the hydrophilic open-pore silicone sponge has the function of collecting and filtering sweat, which can collect sweat by capillary action, remove grease at the same time, and transport sweat to the transmission system. The sensor chip is used to prevent the metal electrode in the sensor chip from directly contacting the human skin.

Step S103, fabricating a plurality of sensor chips.

Wherein, the plurality of sensor chips may include: sodium ion sensor chip, potassium ion sensor chip, calcium ion sensor chip, chloride ion sensor chip, glucose sensor chip, lactic acid sensor chip, sweat pH value sensor chip , perspiration sensor chip and skin temperature sensor chip.

(1) If the sensor chip is a sodium ion sensor chip, a potassium ion sensor chip, a calcium ion sensor chip or a chloride ion sensor chip, then making the sensor chip, including:

A basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface are fabricated.

Further, as shown in FIG. 3 , the basic electrode includes: a working electrode 7 and a reference electrode 6 . The working electrode can be a gold electrode, and the working electrode is an inert metal gold. Gold has the characteristics of excellent electrical conductivity, stable chemical properties, and the reaction that occurs on the electrode surface cannot affect the electrochemical reaction to be studied. At the same time, high-purity gold is easy to obtain and process technology. Simpler. The reference electrode may be an Ag/AgCl electrode. The potential of Ag/AgCl is close to ideal, non-polarized, constant potential, and less affected by external forces, which can provide a stable control potential, and its solid phase will not dissolve in the electrolyte, with good reproducibility.

Wherein, the manufacturing of the basic electrode, the magnetic output interface 4 and the horseshoe wire 5 connecting the basic electrode and the magnetic output interface 4 may include the following steps:

As shown in FIG. 2 , a lower insulating layer is spin-coated on the copper foil, and the lower insulating layer and the metal layer substrate 1 are connected.

Exemplarily, the metal layer substrate includes a glass sheet and polydimethylsiloxane, and the polydimethylsiloxane is disposed above the glass sheet. The lower insulating layer may be polyimide.

Specifically, PDMS (polydimethylsiloxane, polydimethylsiloxane) was spin-coated on a glass slide at 500 rpm for 45 seconds, and NMP (N-Methyl pyrrolidone, N-methyl siloxane) was spin-coated on a copper foil with a thickness of 3 μm at 2,000 rpm for 45 seconds. The diluted weight ratio of pyrrolidone is 8% of PI (Polyimide, polyimide) of Sigma Company. The PI and PDMS were adsorbed together by van der Waals force, and the copper foil was on it.

A titanium layer is sputtered on the copper foil, and a gold layer is sputtered on the titanium layer.

Specifically, a titanium layer with a thickness of 5 nm can be sputtered using a magnetron sputtering apparatus of Shenyang Kejing, and then a gold layer with a thickness of 25 nm is sputtered on the titanium layer. Among them, the titanium layer can be used as the adhesion layer.

The reference electrode is formed by electroplating on the gold layer.

Specifically, using photolithography technology, after exposure and development, the position of the reference electrode is exposed on the gold layer, and silver electroplating is performed. The process of electroplating silver can be as follows: soak in the pre-silver plating solution for 1 minute, observe and rinse thoroughly with deionized water to ensure that each part of the reference electrode can be silver-plated. Then, the sputtered gold layer is used as the cathode, and a piece of pure silver with the same size as the glass piece is used as the anode, which is immersed in the electroplating silver solution for 4 minutes. The reaction principle is shown in formula 1.1 and formula 1.2.

The anode reacts: Ag-e ^- →Ag ⁺ (1.1)

The cathode reacts: Ag ⁺ +e ^- → Ag (1.2)

The base electrode, the magnetic output interface and the horseshoe-shaped wire except the reference electrode are fabricated by using photolithography technology and various etching solutions.

Specifically, photolithography is performed in alignment with the electroplated silver formed above, the reference electrode and the working electrode are partially covered with photoresist, and gold etching solution, titanium etching solution and copper etching solution are used in sequence, and wet etching solution is used. The metal is patterned by etching to form the working electrode, the magnetic output interface and the horseshoe-shaped line. A metal layer 2 as shown in FIG. 2 is formed, and the metal layer 2 is a lower insulating layer PI, a copper foil, a titanium layer and a gold layer in order from bottom to top.

An upper insulating layer is made on the horseshoe wire.

Specifically, as shown in FIG. 2 , PI is spin-coated on the patterned gold layer again as the upper insulating layer 3 . Using the photolithography process, the base electrode and the magnetic output interface are protected by photoresist, and the hollow structure is formed by dry etching using the oxygen plasma etching technology. The components of the horseshoe wire from bottom to top are copper foil, titanium layer and gold layer in order. The copper foil is located above the lower insulating layer PI, and the upper insulating layer 3 is located above the gold layer.

The base electrode, the magnetic output interface, the horseshoe wire, the lower insulating layer and the upper insulating layer are peeled off from the metal layer substrate.

The working electrode in the basic electrode is modified to obtain the sensor chip.

Wherein, the modification of the working electrode in the base electrode to obtain the sensor chip may include the following steps:

As shown in FIG. 3 and FIG. 4 , a conductive organic polymer electron transfer layer 11 is formed on the working electrode 7 .

Exemplarily, the conductive organic polymer electron transfer layer 11 may be a conductive polymer poly-3,4-ethylenedioxythiophene/polystyrene sulfonate (PEDOT:PSS). PEDOT: PSS is an aqueous solution of high molecular polymer with high conductivity. According to different formulations, aqueous solutions with different conductivity can be obtained. PEDOT: PSS is composed of two substances, PEDOT and PSS. PEDOT is a polymer of EDOT (3,4-ethylenedioxythiophene monomer) and PSS is polystyrene sulfonate. These two substances together greatly improve the solubility of PEDOT.

Specifically, PEDOT:PSS was drop-coated on the working electrode and left to dry.

The ion-selective membrane 12 is configured using an ion-selective carrier, a membrane matrix, a plasticizer and an ion-exchanger; the ion-selective membrane 12 is disposed on the conductive organic polymer electron transfer layer 11 .

Among them, the fabricated conductive organic polymer electron transfer layer can improve the sensitivity of monitoring and increase the current and voltage responses.

(1) If the sensor chip is a sodium ion sensor chip, the specific can be:

The ion selective membrane of the sodium ion sensing chip is a sodium ion selective membrane, so the ion exchanger of the sodium ion sensing chip is a cation exchanger. The configuration ratio is as follows: every 100 mg of cation-selective membrane contains 2 mg of ion-selective carrier, 33 mg of membrane matrix, 64.5 mg of plasticizer and 0.5 mg of cation exchanger.

Preferably, the ion-selective carrier is ETH2120. The membrane matrix is polyvinyl chloride. The plasticizer, diisooctyl sebacate, was used to increase the flexibility of the ion-selective membrane. The cation exchanger was sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.

Among them, when the sodium ion sensing chip is in contact with a solution containing sodium ions, the sodium ion selective membrane only allows sodium ions to enter the sodium ion sensing chip from the membrane-water interface, and the process causes the inhomogeneous charge at the membrane-water interface. The distribution produces phase-to-phase potentials. The electrode potential between the working electrode and the reference electrode reflects the activity of ions in a solution containing sodium ions.

(2) If the sensor chip is a potassium ion sensor chip, the specific can be:

The ion selective membrane of the potassium ion sensing chip is a potassium ion selective membrane, so the ion exchanger of the potassium ion sensing chip is a cation exchanger. The configuration ratio is as follows: every 100 mg of cation-selective membrane contains 2 mg of ion-selective carrier, 33 mg of membrane matrix, 64.5 mg of plasticizer and 0.5 mg of cation exchanger.

Preferably, the ion-selective carrier is valinomycin. The membrane matrix is polyvinyl chloride. The plasticizer, diisooctyl sebacate, was used to increase the flexibility of the ion-selective membrane. The cation exchanger was sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.

Among them, when the potassium ion sensing chip is in contact with a solution containing potassium ions, the potassium ion selective membrane only allows potassium ions to enter the potassium ion sensing chip from the membrane-water interface, and this process causes the inhomogeneous charge at the membrane-water interface. The distribution produces phase-to-phase potentials. The electrode potential between the working electrode and the reference electrode reflects the activity of the ions in the solution containing potassium ions.

(3) If the sensor chip is a calcium ion sensor chip, the specific can be:

The ion-selective membrane of the calcium ion sensing chip is a calcium ion-selective membrane, so the ion exchanger of the calcium ion sensing chip is a cation exchanger. The configuration ratio is as follows: every 100 mg of cation-selective membrane contains 2 mg of ion-selective carrier, 33 mg of membrane matrix, 64.5 mg of plasticizer and 0.5 mg of cation exchanger.

Preferably, the ion-selective carrier is A23187. The membrane matrix is polyvinyl chloride. The plasticizer, diisooctyl sebacate, was used to increase the flexibility of the ion-selective membrane. The cation exchanger was sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.

Among them, when the calcium ion sensing chip is in contact with a solution containing calcium ions, the calcium ion selective film only allows calcium ions to enter the calcium ion sensing chip from the membrane-water interface. The distribution produces phase-to-phase potentials. The electrode potential between the working electrode and the reference electrode reflects the activity of the ions in the solution containing calcium ions.

(4) If the sensor chip is a chloride ion sensor chip, the specific can be:

The ion selective membrane of the chloride ion sensing chip is a chloride ion selective membrane, so the ion exchanger of the chloride ion sensing chip is an anion exchanger. The configuration ratio is as follows: every 100 mg of anion-selective membrane contains 2 mg of ion-selective carrier, 33 mg of membrane matrix, 64.5 mg of plasticizer and 0.5 mg of anion exchanger.

Preferably, the ion-selective carrier is tetraphenylporphine manganese chloride. The membrane matrix is polyvinyl chloride. The plasticizer, diisooctyl sebacate, was used to increase the flexibility of the ion-selective membrane. The anion exchanger was tetrakis(dodecyl)ammonium tetrakis(4-chlorophenyl)borate.

Among them, when the chloride ion sensor chip is in contact with a solution containing chloride ions, the chloride ion selective film only allows chloride ions to enter the chloride ion sensor chip from the membrane-water interface, and the charge caused by this process is uneven at the membrane-water interface. The distribution produces phase-to-phase potentials. The electrode potential between the working and reference electrodes reflects the activity of ions in solutions containing chloride ions.

Among them, the cation exchanger contains a large number of anionic groups, which can eliminate the interference of anions. Anion exchangers contain a large number of cationic groups, which can exclude cationic interference.

It is worth noting that, as shown in FIG. 4 , the reference electrode 6 of the sodium ion sensing chip, the potassium ion sensing chip, the calcium ion sensing chip and the chloride ion sensing chip can be Connect with the same magnetic output interface 30 .

Preferably, the sodium ion sensing chip, the potassium ion sensing chip, the calcium ion sensing chip and the chloride ion sensing chip can be fabricated at the same time. All the magnetic output interfaces, then make a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface, and finally modify the working electrode of each sensor chip.

(2) If the sensor chip is a glucose sensor chip or a lactate sensor chip, then manufacturing the sensor chip, including:

A basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface are fabricated.

Further, as shown in FIG. 6 , the basic electrode includes: a working electrode 9 , a reference electrode 10 and a counter electrode 8 . The reference electrode may be an Ag/AgCl electrode, and both the working electrode and the counter electrode may be gold electrodes. The counter electrode should have a large surface area so that externally applied polarization acts mainly on the working electrode, thereby preventing damage to the counter electrode.

The specific process of making the base electrode, the magnetic output interface, and the horseshoe-shaped wire connecting the base electrode and the magnetic output interface has been mentioned above, and will not be repeated here.

The working electrode in the basic electrode is modified to obtain the sensor chip.

Wherein, the modification of the working electrode in the base electrode to obtain the sensor chip may include the following steps:

As shown in FIGS. 5 and 6 , an electron transfer layer 13 is formed on the working electrode 9 .

Wherein, nanoporous gold can be electroplated on the working electrode by chronopotentiometry. Specifically, a current with a duty ratio of 3: ⁷ and a current density of 1.99 mA/cm is applied between the working electrode and the counter electrode, and the deposition time is 200s. Next, Prussian blue was electroplated on the nanoporous gold. Specifically, the plating solution was 2.5mM potassium ferricyanide, 2.5mM ferric chloride, 100mM potassium chloride and 100mM hydrochloric acid, using cyclic voltammetry, using 0.01V The scanning speed of /s and the scanning range of 0V-0.3V were cycled 2 times, thus forming the electron transfer layer. Alternatively, a 1:1 mixed solution of graphene and carbon nanotubes can be used as the electron transfer layer, and the mixed droplets can be applied on the working electrode and left to dry.

Among them, the role of nanoporous gold can be to increase the surface area of the working electrode and improve the sensitivity of the sensor chip. The role of Prussian blue can be to catalyze the decomposition of hydrogen peroxide and reduce the bias voltage.

An oxidase solution is drop-coated on the electron transfer layer 13 and left to dry to form an oxidase layer 14 ; an active material protective layer 15 is formed on the oxidase layer 14 .

Among them, the fabricated electron transfer layer can improve the sensitivity of monitoring and increase the current and voltage response.

(1) If the sensor chip is a glucose sensor chip, the specific can be:

The oxidase solution is drop-coated on the electron transfer layer and left to dry to form an oxidase layer.

Wherein, the oxidase solution is 60 mg/ml glucose oxidase, and the solvent is PBS (phosphate buffersaline, phosphate buffered saline). Preferably, in the process of standing to dry, the storage temperature may be set to 4 degrees Celsius.

An active material protective layer is formed on the oxidase layer.

Specifically, chitosan can be dissolved in 2% acetic acid, magnetically stirred for 1 hour, added with a cation exchanger, and then left to dry after dripping. Alternatively, a film-forming substance such as perfluorosulfonic acid (Nafion) can be used as the active material protective layer. The active substance protective layer can exclude the interference of ascorbic acid on glucose.

(2) If the sensor chip is a lactic acid sensor chip, the specific can be:

The oxidase solution is drop-coated on the electron transfer layer and left to dry to form an oxidase layer.

Wherein, the oxidase solution can be 40 mg/ml lactate oxidase solution, and the solvent is PBS. Preferably, in the process of standing to dry, the storage temperature may be set to 4 degrees Celsius.

An active material protective layer is formed on the oxidase layer.

Specifically, chitosan can be dissolved in 2% acetic acid, magnetically stirred for 1 hour, added with a cation exchanger, and then left to dry after dripping. Alternatively, a film-forming substance such as perfluorosulfonic acid (Nafion) can be used as the active material protective layer. The active substance protective layer can exclude the interference of ascorbic acid with lactic acid.

The principle of the glucose sensor chip and the lactate sensor chip is: the enzyme catalyzes the redox reaction of the reactant, and generates electron transfer with the working electrode. The potentiostat provides a bias voltage between the working electrode and the reference electrode, and the working electrode and the counter electrode. The current between them increases with the concentration of the analyte.

It is worth noting that, as shown in FIG. 6 , the reference electrodes 10 of the glucose sensor chip and the lactate sensor chip are connected to the same magnetic output interface 29 .

Preferably, the glucose sensor chip and the lactate sensor chip can be fabricated at the same time. First, the overall basic electrodes and all the magnetic output interfaces of the two sensor chips are fabricated, and then the connection basic electrodes and the magnetic output interfaces are fabricated. The horseshoe-shaped line of the interface, which finally modifies the working electrode of each sensor chip.

(3) If the sensor chip is a sweat PH value sensor chip, manufacturing the sensor chip, including:

A basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface are fabricated to obtain the sensor chip. Wherein, the basic electrode includes: a reference electrode and a working electrode. The working electrode can be a hydrogen ion-sensitive polymer such as polyaniline. The reference electrode may be an Ag/AgCl electrode. The sweat pH voltage signal changes with the change of sweat pH.

Specifically, the lower insulating layer is spin-coated on the copper foil, and the lower insulating layer and the metal layer substrate are connected. A titanium layer is sputtered on the copper foil, and a gold layer is sputtered on the titanium layer. The reference electrode is formed by electroplating on the gold layer. The working electrode, the magnetic suction output interface and the horseshoe-shaped wire are fabricated by using photolithography technology and various etching solutions. An upper insulating layer is made on the horseshoe wire. The base electrode, the magnetic output interface, the horseshoe wire, the lower insulating layer and the upper insulating layer are peeled off from the metal layer substrate.

(4) If the sensor chip is a perspiration sensor chip, manufacturing the sensor chip, including:

A basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface are fabricated to obtain the sensor chip. Wherein, the basic electrode includes: a reference electrode and a working electrode.

Wherein, the perspiration sensor chip may be a resistive sensor chip or a capacitive sensor chip. The resistive sensor chip converts humidity changes into resistance changes, and uses materials sensitive to humidity as electrodes, such as ceramics and polymers; capacitive sensor chips convert humidity changes into capacitance changes, and the dielectric coefficient of the dielectric increases with The humidity changes as a function, and it is necessary to select suitable dielectric materials as electrodes, such as ceramics, polyamides and other polymers.

Specifically, spin-coating a lower insulating layer on the copper foil, connecting the lower insulating layer and the metal layer substrate; sputtering a titanium layer on the copper foil, and sputtering a gold layer on the titanium layer; The reference electrode is formed by electroplating on the gold layer; the base electrode, the magnetic output interface and the horseshoe-shaped wire except the reference electrode are fabricated by using photolithography technology and various etching solutions; forming an upper insulating layer on the horseshoe-shaped wire; peeling off the base electrode, the magnetic output interface, the horseshoe-shaped wire, the lower insulating layer and the upper insulating layer from the metal layer substrate.

(5) If the sensing chip is a skin temperature sensing chip, manufacturing the sensing chip includes: making a magnetic output interface and a horseshoe-shaped wire connected to the magnetic output interface to obtain the sensing chip. Wherein, the line width of the skin temperature sensing chip part can be 20 μm, and the resistance value of the wires of the skin temperature sensing chip part changes with the change of the skin temperature of the human body.

Specifically, the lower insulating layer is spin-coated on the copper foil, and the lower insulating layer and the metal layer substrate are connected. A titanium layer is sputtered on the copper foil, and a gold layer is sputtered on the titanium layer. The magnetic suction output interface and the horseshoe-shaped wire are fabricated by using photolithography technology and various etching solutions. The base electrode, the magnetic output interface, the horseshoe wire, the lower insulating layer and the upper insulating layer are peeled off from the metal layer substrate.

It should be noted that the skin temperature sensor chip needs to be powered by a flexible thin-film battery in the flexible signal processing transmission circuit during use. After the human skin temperature changes, the resistance value of the skin temperature sensor chip will also change. Therefore, the skin temperature sensor chip can output the skin temperature voltage signal in real time.

Step S104 , transferring each of the sensing chips onto the flexible and extensible substrate, and disposing the hydrophilic open-pore silicone sponge on top of each of the sensing chips.

Wherein, as shown in FIG. 7 , before transferring each of the sensing chips to the flexible and extensible substrate 16 , the lower insulating layer of each of the sensing chips is deposited by electron beam evaporation of dioxide silicon, and each sensor chip is then bonded to a flexible, malleable substrate containing a thin layer of PDMS, which is UV-ozone treated. The flexible and extensible substrate can carry the electrochemical and bioelectrical reactions generated between the sensor chip and sweat.

8 is a cross-sectional view of a sweat monitoring sensor patch provided by an embodiment of the present invention. A PDMS thin layer 26 is provided on the flexible and extensible substrate 16. The PDMS thin layer 26 is connected to the sensor chip 27 through silicon dioxide. The sensor chip 27 is provided with a hydrophilic open-pore silicone sponge 28 .

In the embodiment of the present invention, after the sweat monitoring sensor patch is worn on the human body, the hydrophilic open-pore silicone sponge on each sensor chip absorbs sweat, and transports the sweat to the sensor chip, and the sodium ion sensor chip After 18 comes into contact with sweat, it outputs a voltage signal of sodium ion content in real time; after the potassium ion sensing chip 17 comes into contact with sweat, it outputs a voltage signal of potassium ion content in real time; after the calcium ion sensing chip 20 comes into contact with sweat, it outputs a voltage signal of calcium ion content in real time After the chloride ion sensing chip 19 comes into contact with sweat, it outputs a voltage signal of chloride ion content in real time; after the glucose sensing chip 23 comes into contact with sweat, it outputs a current signal of glucose content in real time; after the lactic acid sensing chip 24 comes into contact with sweat, it outputs a real-time signal. The current signal of lactic acid content; the sweat PH value sensor chip 22 outputs the sweat PH value voltage signal in real time after it touches the sweat; the sweat volume sensor chip 21 outputs the sweat volume voltage signal in real time after it touches the sweat; the epidermal temperature sensor chip 25 After being exposed to sweat, the skin temperature voltage signal is output in real time.

In the embodiment of the present invention, the external dimension of each sensor chip may be: 18mm*10mm*5μm, and the overall package size of the sweat monitoring sensor patch may be: 100mm*50mm*5mm. In this way, the sensor chip and the sweat monitoring The outer dimensions of the sensing patches are relatively small, so that the sweat monitoring sensing patches have good ductility.

In the embodiment of the present invention, each sensor chip is fabricated by a CMOS processing method, and a variety of sensor chips are transferred onto a flexible and extensible substrate to obtain a sweat monitoring sensor patch with small size, good ductility and high sensitivity , can be worn on human epidermis without burden.

In yet another embodiment of the present invention, the sweat monitoring sensor patch of the present invention is described in detail, including: a flexible and extensible substrate and a plurality of sensing chips disposed on the flexible and extensible substrate, each of which is a flexible and extensible substrate. The top of the sensor chip is provided with a hydrophilic open-pore silicone sponge. The sweat monitoring sensor patch of this embodiment can be prepared by using the preparation method.

The flexible and extensible substrate is in contact with the human epidermis, and is used for fixing a plurality of the sensing chips between the human epidermis and the flexible and extensible substrate.

The hydrophilic open-pored silicone sponge is located between the human epidermis and the sensor chip, and the hydrophilic open-pored silicone sponge is in contact with the human epidermis for absorbing the sweat of the human epidermis and transporting the sweat to the sensor. chip.

The sensor chip is used to output a voltage signal or a current signal after being in contact with sweat.

Among them, the hydrophilic open-pore silicone sponge on each sensor chip absorbs sweat and transports the sweat to the sensor chip. After the sodium ion sensor chip 18 contacts the sweat, it outputs a voltage signal of sodium ion content in real time; potassium ion sensor After the chip 17 comes into contact with sweat, it outputs a voltage signal of potassium ion content in real time; after the calcium ion sensing chip 20 comes into contact with sweat, it outputs a voltage signal of calcium ion content in real time; after the chloride ion sensing chip 19 comes into contact with sweat, it outputs the content of chloride ion in real time. voltage signal; after the glucose sensing chip 23 contacts sweat, it outputs a current signal of glucose content in real time; after the lactic acid sensor chip 24 contacts sweat, it outputs a current signal of lactic acid content in real time; after the sweat pH sensor chip 22 contacts sweat, it outputs a real-time current signal of lactic acid content. Output the sweat PH value voltage signal; after the perspiration sensor chip 21 touches the sweat, it outputs the sweat volume voltage signal in real time; after the skin temperature sensor chip 25 touches the sweat, it outputs the skin temperature voltage signal in real time.

In another embodiment of the present invention, a sweat monitoring and sensing system disclosed in the embodiment of the present invention is introduced in detail, including: a terminal, a flexible signal processing and transmission circuit, and the sweat monitoring sensor sticker as described in the above embodiment piece.

The sweat monitoring sensor patch is connected to the flexible signal processing and transmission circuit for sending the acquired voltage signal and current signal to the flexible signal processing and transmission circuit.

The voltage signals may include: sodium ion content voltage signal, potassium ion content voltage signal, calcium ion content voltage signal, chloride ion content voltage signal, sweat pH voltage signal, perspiration volume voltage signal and epidermal temperature voltage signal. The current signals may include: a glucose content current signal and a lactate content current signal.

The flexible signal processing and transmission circuit is connected to the terminal for receiving the voltage signal and the current signal sent by the sweat monitoring sensor patch, and converting the voltage signal and the current signal into sweat components information, and send the sweat composition information to the terminal.

Wherein, the flexible signal processing and transmission circuit can wirelessly transmit the sweat composition information to the terminal through Bluetooth. The flexible signal processing transmission circuit may include: a flexible stretchable substrate and a flexible thin film battery. Flexible thin-film batteries can be used to power epidermal temperature sensing chips. The flexible signal processing and transmission circuit can be connected to each sensor chip through a magnetic output interface.

Specifically, the processing process of the current signal of glucose content and the current signal of lactic acid content can be as follows: using a two-channel 2:1 multiplexer or two LMP91000 chips (using an operational amplifier to form a potentiostat and a transimpedance amplifier) It receives the current signal of glucose content and the current signal of lactate content, and is controlled by CC2541. Among them, CC2541 is a single chip integrated with a Bluetooth transceiver. CC2541 is also used to control the ADC to convert the current signal of glucose content and the current signal of lactic acid content into glucose content information and lactic acid content information respectively. CC2541 controls Bluetooth to convert glucose content information and lactic acid content information is transmitted to the terminal.

Specifically, for the processing process of the voltage signal of sodium ion content, the voltage signal of potassium ion content, the voltage signal of calcium ion content, the voltage signal of chloride ion content and the voltage signal of sweat pH value, it can be as follows: using a 5-to-1 multiplexer to respectively Receive the voltage signal of sodium ion content, potassium ion content voltage signal, calcium ion content voltage signal, chloride ion content voltage signal and sweat pH value voltage signal, use an operational amplifier to amplify the voltage signal, CC2541 controls the ADC to amplify the sodium ion signal respectively Content voltage signal, potassium ion content voltage signal, calcium ion content voltage signal, chloride ion content voltage signal and sweat pH value voltage signal are converted into sodium ion content information, potassium ion content information, calcium ion content information, chloride ion content information and sweat PH value information, and finally, CC2541 controls Bluetooth to transmit sodium ion content information, potassium ion content information, calcium ion content information, chloride ion content information and sweat PH value information to the terminal.

Specifically, for the processing process of the perspiration voltage signal and the skin temperature voltage signal, the following can be: use the Huygens bridge to measure the perspiration voltage signal and the skin temperature voltage signal respectively, and the CC2541 controls the ADC to respectively measure the perspiration voltage signal and the skin temperature voltage signal. The volume voltage signal and the skin temperature voltage signal are converted into the sweat volume information and the skin temperature information, and then CC2541 controls the Bluetooth to transmit the sweat volume information and the skin temperature information to the terminal. Preferably, the time interval for receiving the perspiration volume voltage signal can be set, and the perspiration volume information and the time interval are used to determine the perspiration rate information, and the CC2541 controls the Bluetooth to transmit the perspiration rate information to the terminal.

Wherein, the sweat composition information may include: sodium ion content information, potassium ion content information, calcium ion content information, chloride ion content information, sweat pH value information, glucose content information, lactic acid content information, perspiration volume information and epidermal temperature information. Preferably, the sweat component information may include: sodium ion content information, potassium ion content information, calcium ion content information, chloride ion content information, sweat pH value information, glucose content information, lactic acid content information, perspiration volume information, epidermis information Temperature information and perspiration rate information.

The terminal is configured to receive the sweat component information sent by the flexible signal processing and transmission circuit, input the sweat component information into a model (such as a disease model), and generate analysis data corresponding to the sweat component information.

Exemplarily, the terminal may be a desktop computer, a notebook computer, a mobile phone or a tablet computer. Analysis data can include: sports, training recommendations, etc.

As can be seen from the above technical solutions, the sweat monitoring sensing system, patch and preparation method thereof provided by the present invention have the following beneficial effects:

(1) In the present invention, the preparation method of the sweat monitoring sensor patch includes: preparing a flexible and extensible substrate; making a hydrophilic open-pore silicone sponge; making a plurality of sensor chips; transferring each sensor chip to a flexible extensible On the extension substrate, a hydrophilic open-pore silicone sponge is arranged on the top of each sensor chip. When in use, the flexible and extensible substrate is adsorbed on the surface of the human skin, and multiple sensor chips are sandwiched between the surface of the human skin and the flexible and extensible substrate. During the process, the hydrophilic open-pored silicone sponge contacts the human epidermis, absorbs the sweat of the human epidermis, transports the sweat to the sensor chip, and the sensor chip outputs the physiological parameter indicators. The technical problem of the demand for real-time non-invasive acquisition of physiological parameter indicators from the molecular level has achieved the technical effect of meeting the needs of wearable wearables on the human body to acquire physiological parameter indicators in real time and non-invasively from the molecular level.

(2) In the present invention, the horseshoe-shaped wire is used to connect the basic electrode and the magnetic suction output interface, which removes the sharp corner, avoids the pressure concentration effect, improves the pressure resistance, and reduces the short circuit of the connecting wire caused by various mechanical factors. occurs, bending in various directions can be achieved, increasing ductility and practicability;

(3) In the present invention, the reference electrodes of the sodium ion sensing chip, potassium ion sensing chip, calcium ion sensing chip and chloride ion sensing chip are connected to the same magnetic suction output interface, and the glucose sensing chip and the lactic acid sensing chip are connected to the same magnetic suction output interface. The reference electrode of the sensor chip is connected to the same magnetic output interface, which can reduce the volume of the sweat monitoring sensor patch, make the sweat monitoring sensor patch easier to wear and move, and also save production materials. Reduced cost of making sweat-monitoring sensor patches;

(4) In the present invention, the sweat monitoring sensor patch is connected to the flexible signal processing transmission circuit through the magnetic suction output interface, and the magnetic suction output interface can quickly and conveniently realize the connection or disconnection operation, which saves the operation time and improves the efficiency of use;

(5) The hydrophilic open-pore silicone sponge made by the present invention collects sweat by capillary action, removes grease, avoids direct contact of metal electrodes with human epidermis, and can improve sweat monitoring efficiency;

(6) In the present invention, each sensor chip is a high-channel integrated chip, and each sensor chip is transferred to a flexible and extensible substrate, so that the sweat monitoring sensor patch can simultaneously monitor various physiological conditions of the human body in real time. Parameter indicators to improve monitoring efficiency and practicability;

(7) In the present invention, each sensor chip is fabricated by using CMOS process and materials such as copper, titanium, gold, silver, and polyimide, so that the sensor chip has high precision, low power consumption, high speed and integration. High degree of characteristics.

The specific embodiments described above further describe the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention, and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims (10)

1. a preparation method of sweat monitoring sensor patch, is characterized in that, comprises: Prepare flexible and extensible substrates; Making hydrophilic open-pore silicone sponge; Make multiple sensor chips; Each of the sensing chips is transferred onto the flexible and extensible substrate, and the hydrophilic open-pore silicone sponge is arranged on top of each of the sensing chips. 2. The preparation method of the perspiration monitoring sensor patch according to claim 1, wherein the making of the hydrophilic open-pore silicone sponge comprises: Addition type platinum-catalyzed silica gel is used to make open-cell sponge matrix; The surface of the open-cell sponge substrate is modified by using a super-hydrophilic coating to obtain the hydrophilic open-cell silicone sponge. 3. The method for preparing a sweat monitoring sensor patch according to claim 1, wherein the plurality of sensor chips comprise: a sodium ion sensor chip, a potassium ion sensor chip, a calcium ion sensor chip, Chloride ion sensing chip, glucose sensing chip and lactic acid sensing chip; making the sensing chip, including: Making a basic electrode, a magnetic output interface and a horseshoe-shaped wire connecting the basic electrode and the magnetic output interface; The working electrode in the basic electrode is modified to obtain the sensor chip. 4. The preparation method of sweat monitoring sensor patch according to claim 1, is characterized in that, The plurality of sensor chips include: a sweat pH value sensor chip and a perspiration amount sensor chip; making the sensor chips includes: making a basic electrode, a magnetic output interface, and connecting the basic electrode and the The horseshoe-shaped line of the magnetic output interface to obtain the sensor chip; or The plurality of the sensor chips include: a skin temperature sensor chip; and the fabrication of the sensor chip includes: fabrication of a magnetic output interface and a horseshoe-shaped wire connected to the magnetic output interface, so as to obtain the sensor chip . 5. The method for preparing a sweat monitoring sensor patch according to claim 3 or 4, wherein the base electrode comprises a reference electrode, and the base electrode, the magnetic suction output interface and the base electrode are connected to the base electrode. The electrode and the horseshoe-shaped line of the magnetic output interface, including: Spin-coating a lower insulating layer on the copper foil, connecting the lower insulating layer and the metal layer substrate; sputtering a titanium layer on the copper foil, and sputtering a gold layer on the titanium layer; forming the reference electrode by electroplating on the gold layer; The basic electrode, the magnetic output interface and the horseshoe-shaped wire except the reference electrode are fabricated by using photolithography technology and various etching solutions; Making an upper insulating layer on the horseshoe wire; The base electrode, the magnetic output interface, the horseshoe wire, the lower insulating layer and the upper insulating layer are peeled off from the metal layer substrate. 6. The method for preparing a sweat monitoring sensor patch according to claim 3, wherein if the sensor chip is the sodium ion sensor chip, the potassium ion sensor chip, the calcium ion sensor If the sensor chip or the chloride ion sensor chip is used, the working electrode in the base electrode is modified to obtain the sensor chip, including: making a conductive organic polymer electron transfer layer on the working electrode; Use ion-selective carriers, membrane substrates, plasticizers and ion-exchangers to configure ion-selective membranes; The ion-selective membrane is disposed on the conductive organic polymer electron transport layer. 7. The method for preparing a sweat monitoring sensor patch according to claim 3, wherein, if the sensor chip is the glucose sensor chip or the lactate sensor chip, the The working electrode in the basic electrode is modified to obtain the sensor chip, including: forming an electron transfer layer on the working electrode; drop-coating the oxidase solution on the electron transfer layer, and let it stand to dry to form an oxidase layer; An active material protective layer is formed on the oxidase layer. 8. The method for preparing a sweat monitoring sensor patch according to claim 5, wherein the sodium ion sensor chip, the potassium ion sensor chip, the calcium ion sensor chip and the chlorine ion sensor chip The reference electrode of the ion sensor chip is connected to the same magnetic output interface, and the reference electrodes of the glucose sensor chip and the lactic acid sensor chip are connected to the same magnetic output interface. 9. A sweat monitoring sensor patch, characterized in that, comprising: Flexible and extensible substrate; a plurality of sensor chips on the flexible extensible substrate; and A hydrophilic open-pore silicone sponge on top of each of the sensor chips. 10. A sweat monitoring sensing system, comprising: a terminal, a flexible signal processing and transmission circuit, and the sweat monitoring sensing patch according to claim 9; wherein, The sweat monitoring sensing patch is connected to the flexible signal processing and transmission circuit, and is used for sending the signal detected by the sweat monitoring sensing patch to the flexible signal processing and transmission circuit; The flexible signal processing and transmission circuit is connected to the terminal for receiving the signal sent by the sweat monitoring sensor patch, converting the signal into sweat component information, and sending the sweat component information to the the terminal; The terminal is configured to receive and analyze the sweat component information sent by the flexible signal processing and transmission circuit.