Cortisol sensor and preparation method thereof

Abstract

The invention provides a cortisol sensor and a preparation method thereof, and belongs to the technical field of cortisol sensor manufacturing. The cortisol sensor comprises a micro-channel unit, a sweat induction unit and a cortisol detection unit. The micro-channel unit is provided with a sweat collection area and a sweat confluence area which are distributed at an interval and communicate with each other, the sweat collection area is configured to be capable of collecting sweat secreted by skin, and the sweat confluence area is used for confluence of the sweat collected by the sweat collection area; the sweat induction unit is located above the sweat collection area and is configured to induce the skin to secrete sweat by utilizing heat released by the phase change material in the phase change process; the cortisol detection unit and the sweat induction unit are located on the same side of the micro-channel unit and located above the sweat confluence area, and an electrode assembly of the cortisol detection unit is configured to be capable of making contact with sweat in the sweat confluence area. The cortisol level of a human body is detected by painless and real-time induction of the skin to secrete sufficient sweat.

Description

Technical Field

[0001] The present application relates to the technical field of cortisol sensor manufacturing, and in particular to a cortisol sensor and a preparation method thereof. Background Art

[0002] Stress comes from psychological confusion or threats caused by various stimulating events and adverse factors in daily life. Excessive or long-term stress can have a negative impact on mental health, leading to symptoms such as tension, discomfort, anxiety and depression. Technicians have found that stress can affect the endocrine system and prompt the adrenal glands to release cortisol and other hormones through the regulatory mechanism of the hypothalamus-pituitary-adrenal glands. Among them, cortisol can pass through the lipid bilayer membrane into the blood and be excreted with sweat through passive diffusion. Therefore, changes in cortisol levels in sweat are important for objectively assessing stress levels. Based on this, it is crucial to develop effective cortisol sensors to assess stress-related healthcare needs, especially wearable cortisol biosensors that can conduct timely assessments of stress in order to provide real-time feedback on the body's mental health level.

[0003] When using a cortisol sensor, inducing the cortex to secrete sufficient sweat is a key step in testing cortisol levels. Currently, methods for inducing sweat secretion mainly include exercise and electrical stimulation. Exercise-induced sweating consumes a lot of energy, and the sweating rate fluctuates greatly. Furthermore, this form of sweating can easily interfere with the assessment of stress levels. Electrical stimulation-induced sweating can cause adverse reactions such as stinging and itching on the skin. Therefore, how to painlessly and in real time induce the skin to secrete sufficient sweat to detect cortisol levels while the human body is at rest is a major challenge currently faced. Summary of the Invention

[0004] The purpose of this application is to provide a cortisol sensor and a preparation method thereof, which can induce the skin to secrete sufficient sweat painlessly and in real time when the human body is in a resting state to detect the human body's cortisol level, thereby accurately reflecting the human body's current stress level.

[0005] The embodiment of the present application is implemented as follows:

[0006] In a first aspect, embodiments of the present application provide a cortisol sensor comprising a microfluidic unit, a sweat induction unit, and a cortisol detection unit. The microfluidic unit is configured to be attached to the skin and has a sweat collection area and a sweat confluence area that are spaced and connected. The sweat collection area is configured to collect sweat secreted by the skin, and the sweat confluence area is configured to converge the sweat collected by the sweat collection area. The sweat induction unit is connected to the surface of the microfluidic unit and is located above the sweat collection area. The sweat induction unit is configured to use the heat released by the phase change material during the phase change process to induce the skin in the area corresponding to the sweat collection area to secrete sweat. The cortisol detection unit is located on the same side of the microfluidic unit as the sweat induction unit. The cortisol detection unit is connected to the surface of the microfluidic unit and is located above the sweat confluence area. The electrode group of the cortisol detection unit is configured to contact sweat in the sweat confluence area to detect the cortisol concentration in the sweat.

[0007] In the above technical solution, the cortisol sensor includes a microfluidic unit, a sweat induction unit, and a cortisol detection unit. The sweat induction unit is arranged above the sweat collection area and is configured to use the heat released by the phase change material during the phase change process to induce sweat secretion from the skin in the corresponding area of the sweat collection area. This sweat induction method does not require the human body to exercise and can be achieved when the human body is in a resting state. This sweat induction method is relatively gentle on the skin and is not likely to cause adverse reactions such as stinging and itching on the skin during the sweat induction process. The microfluidic unit is used to collect sweat produced by the sweat induction unit and converge the collected sweat. The cortisol detection unit is configured to contact the sweat in the sweat convergence area to detect the cortisol concentration in the sweat. Through the mutual cooperation of the microfluidic unit, the sweat induction unit, and the cortisol detection unit, the skin can be induced to secrete sufficient sweat in real time when the human body is in a resting state to detect the human body's cortisol level, thereby accurately reflecting the human body's current stress level.

[0008] In some optional embodiments, the sweat inducing unit includes a phase change material encapsulation layer, which is bonded to the surface of the microfluidic unit through a first adhesive layer and is located above the sweat collection area. The phase change material encapsulation layer is a hollow structure and is filled with phase change material. The phase change material is liquid and can undergo phase change through extrusion.

[0009] In the above technical solution, the phase change material encapsulation layer is bonded above the sweat collection area through the first adhesive layer, which has the advantage of being easy to assemble; at the same time, the liquid phase change material is used and the material can undergo phase change by extrusion, which has the advantage of being easy to trigger.

[0010] In some optional embodiments, the phase change material includes a phase change material body and a diluent. The phase change material body can undergo phase change and can release heat and induce the skin to secrete sweat during the phase change process. The diluent is used to lower the upper temperature limit of the phase change material body after the phase change.

[0011] In the above technical solution, the phase change material is set in the form of a phase change material body and a diluent cooperating with each other, so that the upper temperature limit of the phase change material after phase change is within an appropriate range, thereby taking into account the amount of sweat secretion of the skin while improving the comfort of the skin.

[0012] In some optional embodiments, the mass ratio of the phase change material body and the diluent is 100:(1-15); optionally, the phase change material body is selected from at least one of sodium acetate trihydrate, sodium sulfate, nickel chloride, cobalt nitrate, iron nitrate and cadmium nitrate; optionally, the diluent is selected from at least one of water, acetic acid, urea, ethylene glycol and erythritol.

[0013] In the above technical solution, the mass ratio of the phase change material body and the diluent is limited within the above range so that the two have a more appropriate mass ratio, which can better take into account the amount of skin sweat secretion and the skin comfort in the process of inducing skin sweat secretion; further, the material of the phase change material body with phase change function is limited within the above range, which has the advantages of being able to be triggered at room temperature (no additional heating is required, which is easy to trigger) and having high latent heat (sustainable heat release time is long, which can increase sweat secretion); limiting the type of diluent within the above range can more effectively reduce the temperature upper limit of the phase change material after the phase change by forming intermolecular hydrogen bonds with the phase change material.

[0014] In some optional embodiments, the sweat inducing unit further includes a thermal insulation layer, and the side of the phase change material encapsulation layer facing away from the first adhesive layer and the circumferential side wall of the phase change material encapsulation layer both have the thermal insulation layer.

[0015] In the above technical solution, a thermal insulation layer is added to the top and side walls of the phase change material packaging layer, which can reduce heat loss of the phase change material packaging layer, thereby improving its effect of inducing skin sweat secretion.

[0016] In some optional embodiments, the cortisol detection unit is bonded to the surface of the microfluidic unit through a first adhesive layer, and a first through hole is provided in the area of the first adhesive layer corresponding to the electrode group, and the first through hole is connected to the sweat confluence area, so that the electrode group can contact the sweat in the sweat confluence area through the first through hole; optionally, in the thickness direction of the microfluidic unit, the orthographic projection of the electrode group is located within the orthographic projection of the sweat confluence area, and the electrode group is accommodated in the first through hole.

[0017] In the above technical solution, the cortisol detection unit is also bonded to the surface of the microfluidic unit via a first adhesive layer. This connection method facilitates the assembly of the sweat induction unit and the cortisol detection unit on the same side of the microfluidic unit. Furthermore, this connection method provides a relatively closed space between the sweat induction unit and the cortisol detection unit, thereby facilitating the directional flow of sweat from the sweat collection area to the sweat confluence area. Furthermore, in the thickness direction of the microfluidic unit, the orthographic projection of the electrode group lies within the orthographic projection of the sweat confluence area, and the electrode group is accommodated within the first through-hole. This arrangement allows the electrode group to easily and fully contact sweat in the sweat storage area, thereby helping to improve the detection sensitivity of the cortisol sensor.

[0018] In some optional embodiments, the working electrode in the electrode group has a plurality of grooves distributed in an array on one side close to the sweat confluence area; optionally, the grooves are circular grooves with an inner diameter of 100 to 600 μm, a distance between any two adjacent grooves of 100 to 600 μm, and a depth of 10 to 500 μm.

[0019] In the above technical solution, an array of grooves is provided on the side of the working electrode in the electrode group close to the sweat confluence area, which helps to increase the contact area between the working electrode and the sweat, thereby improving the test sensitivity of the cortisol sensor; further, the grooves are provided as circular grooves and the inner diameter of the grooves, the spacing between any two adjacent grooves, and the depth of the grooves are respectively limited to the above ranges, which helps the working electrode to contact the sweat more fully, thereby further improving the test sensitivity of the cortisol sensor.

[0020] In some optional embodiments, the cortisol detection unit includes a flexible substrate, a working electrode and a counter electrode. The flexible substrate is bonded to the surface of the microfluidic unit through a first adhesive layer. The working electrode and the counter electrode are both located on the side of the flexible substrate close to the first adhesive layer and are spaced apart. The working electrode and the counter electrode are both accommodated in the first through hole. The working electrode includes a first transition layer, a first conductive layer, a Prussian blue layer and a molecular imprinting layer stacked in sequence. The counter electrode includes a second transition layer and a second conductive layer stacked in sequence, wherein the first transition layer and the second transition layer are both connected to the side of the flexible substrate close to the first adhesive layer, and the materials of both are selected from silicon dioxide.

[0021] In the above technical solution, the working electrode and the counter electrode together constitute an electrode group, wherein a transition layer made of silicon dioxide is added to both the working electrode and the counter electrode. The transition layer made of this material has a high bonding force with the conductive layer and the flexible substrate, so that the conductive layer can be more firmly bonded to the flexible substrate, thereby improving the structural stability of the cortisol detection unit.

[0022] In some optional embodiments, the microfluidic unit is provided with a plurality of sweat collection holes in the sweat collection area, the plurality of sweat collection holes are all connected to the sweat confluence area, and the spacing between the plurality of sweat collection holes and the sweat confluence area is the same; optionally, a second adhesive layer is provided on the side of the microfluidic unit away from the sweat inducing unit, the second adhesive layer is used to fit with the skin, and the second adhesive layer is provided with a plurality of second through holes corresponding one to one with the areas corresponding to the plurality of sweat collection holes.

[0023] In the above technical solution, the microfluidic unit is provided with a plurality of sweat collection holes in the sweat collection area, which are connected to the sweat confluence area and are distributed at equal intervals. This has the advantages of high sweat collection efficiency and easy manufacturing. Furthermore, a second adhesive layer for adhering to the skin is provided on the side of the microfluidic unit facing away from the sweat induction unit, which facilitates the installation of the cortisol sensor on the area to be detected on the skin.

[0024] In a second aspect, an embodiment of the present application provides a method for preparing a cortisol sensor as provided in the embodiment of the first aspect, comprising the following steps:

[0025] A microfluidic unit is provided; a sweat induction unit is provided and connected to the surface of the microfluidic unit, so that the sweat induction unit is located above the sweat collection area; a cortisol detection unit is provided and connected to the surface of the microfluidic unit, so that the cortisol detection unit and the sweat induction unit are located on the same side of the microfluidic unit, and the cortisol detection unit is located above the sweat confluence area and the electrode group is in contact with the sweat in the sweat confluence area.

[0026] In the above technical solution, by preparing according to the above process, a cortisol sensor as provided in the first embodiment can be prepared. Using this cortisol sensor, when the human body is in a resting state, the skin can be induced to secrete sufficient sweat painlessly and in real time to detect the human body's cortisol level, thereby accurately reflecting the human body's current stress level. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without creative work.

[0028] Figure 1 This is a schematic structural diagram of the first cortisol sensor provided in an embodiment of the present application;

[0029] Figure 2 A schematic structural diagram of a microfluidic unit provided in an embodiment of the present application;

[0030] Figure 3 This is a schematic structural diagram of a second cortisol sensor provided in an embodiment of the present application;

[0031] Figure 4 A schematic structural diagram of a cortisol detection unit provided in an embodiment of the present application;

[0032] Figure 5 A process flow chart of a method for preparing a cortisol sensor provided in an embodiment of the present application;

[0033] Figure 6 This is a scanning electron microscope image of the working electrode after the first conductive layer is formed in Example 1 of the present application;

[0034] Figure 7 This is a scanning electron microscope image of the interior of the groove after the molecular imprinting layer is formed on the working electrode in Example 1 of the present application;

[0035] Figure 8 This is a temperature change curve of the phase change material encapsulation layer in Example 1 of the present application;

[0036] Figure 9 This is a temperature change curve of the phase change material encapsulation layer in Example 2 of the present application;

[0037] Figure 10 This is a temperature change curve of the phase change material encapsulation layer in Example 3 of the present application;

[0038] Figure 11 This is a physical diagram of the cortisol sensor in Example 1 of the present application being attached to the skin;

[0039] Figure 12 This is a statistical graph of the amount of sweating induced by the cortisol sensor in Example 1 of the present application;

[0040] Figure 13 This is a performance test diagram of the cortisol detection unit in Example 1 of the present application.

[0041] Icon: 10-cortisol sensor; 100-microfluidic unit; 110-sweat collection area; 111-sweat collection hole; 120-sweat confluence area; 200-sweat induction unit; 210-phase change material encapsulation layer; 220-insulation layer; 300-cortisol detection unit; 310-flexible substrate; 320-electrode group; 321-working electrode; 3211-first transition layer; 3212-first conductive layer; 3213-gold conductive layer; 3214-Prussian blue layer; 3215-molecular imprinting layer; 322-counter electrode; 3221-second transition layer; 3222-second conductive layer; 400-first adhesive layer; 410-first through hole; 500-second adhesive layer; 510-second through hole. DETAILED DESCRIPTION

[0042] To make the objectives, technical solutions, and advantages of the embodiments of the present application more clear, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Generally, the components of the embodiments of the present application described and shown in the drawings herein can be arranged and designed in various different configurations.

[0043] Therefore, the following detailed description of the embodiments of the present application provided in the accompanying drawings is not intended to limit the scope of the present application for protection, but merely represents selected embodiments of the present application. All other embodiments obtained by persons of ordinary skill in the art based on the embodiments in the present application without making any creative efforts shall fall within the scope of protection of the present application.

[0044] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not need to be further defined or explained in subsequent drawings.

[0045] In the description of this application, it should be noted that the terms "upper," "lower," "inner," and "outer," etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the product of this application is typically placed when in use. These terms are intended solely to facilitate the description of this application and simplify the description, and are not intended to indicate or imply that the devices or components referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on this application. Furthermore, the terms "first," "second," etc., etc., are used solely to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0046] It should also be noted that, in the description of this application, unless otherwise expressly specified or limited, the terms "disposed," "installed," "connected," and "connected" should be understood broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to direct connections, indirect connections through an intermediate medium, or internal connections between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on the specific circumstances.

[0047] The following is a detailed description of a cortisol sensor and a preparation method thereof provided in this application.

[0048] See Figure 1 and Figure 2In a first aspect, the embodiment of the present application provides a cortisol sensor 10, comprising a microfluidic unit 100, a sweat inducing unit 200, and a cortisol detection unit 300. The microfluidic unit 100 is used to fit with the skin, and the microfluidic unit 100 has a sweat collecting area 110 and a sweat confluence area 120 that are spaced and connected. The sweat collecting area 110 is configured to collect sweat secreted by the skin, and the sweat confluence area 120 is used to converge the sweat collected by the sweat collecting area 110; the sweat inducing unit 200 is connected to the surface of the microfluidic unit 100 and is located above the sweat collecting area 110, and the sweat inducing unit 200 is configured to be able to utilize The heat released by the phase change material during the phase change process is used to induce the skin in the corresponding area of the sweat collection area 110 to secrete sweat; the cortisol detection unit 300 and the sweat induction unit 200 are located on the same side of the microfluidic unit 100, and the cortisol detection unit 300 is connected to the surface of the microfluidic unit 100 and is located above the sweat confluence area 120, and the electrode group of the cortisol detection unit 300 is configured to be able to contact the sweat in the sweat confluence area 120 to detect the cortisol concentration in the sweat.

[0049] In the present application, the cortisol sensor 10 includes a microfluidic unit 100, a sweat induction unit 200, and a cortisol detection unit 300. The sweat induction unit 200 is disposed above the sweat collection area 110 and is configured to utilize the heat released by the phase change material during the phase change process to induce sweat secretion from the skin in the area corresponding to the sweat collection area 110. This sweat induction method does not require human exercise and is less likely to cause adverse reactions such as stinging and itching on the skin during the sweat induction process. The microfluidic unit 100 is used to collect sweat generated by the sweat induction unit 200 and to converge the collected sweat. The cortisol detection unit 300 is configured to contact sweat in the sweat confluence area 120 to detect the cortisol concentration in the sweat. Through the mutual cooperation of the microfluidic unit 100, the sweat induction unit 200, and the cortisol detection unit 300, the skin can be painlessly and in real time induced to secrete sufficient sweat when the human body is at rest to detect the human body's cortisol level, thereby accurately reflecting the human body's current stress level.

[0050] See Figure 2 As an example, the microfluidic unit 100 has multiple sweat collecting holes 111 in the sweat collecting area 110, and the multiple sweat collecting holes 111 are all connected to the sweat confluence area 120, and the distances between the multiple sweat collecting holes 111 and the sweat confluence area 120 are the same.

[0051] In this embodiment, the microfluidic unit 100 has a plurality of sweat collection holes 111 in the sweat collection area 110 , which are connected to the sweat confluence area 120 and are distributed at equal intervals. This has the advantages of high sweat collection efficiency and easy manufacturing.

[0052] It should be noted that the number and size of the sweat collection holes 111 are not limited and can be adaptively adjusted according to actual needs.

[0053] As an example, the aperture of a single sweat collection hole 111 is 3 to 10 mm, for example but not limited to an aperture of any point value of 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm and 10 mm, or a range of values between any two of them; the spacing between any two adjacent sweat collection holes 111 is 3 to 10 mm, for example but not limited to a spacing of any point value of 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm and 10 mm, or a range of values between any two of them.

[0054] It should be noted that the shape and specifications of the sweat confluence area 120 are not limited. For example, it can be in the form of a circular pit, wherein the inner diameter of the pit is 5 to 30 mm, for example, but not limited to the inner diameter of any one of 5 mm, 10 mm, 15 mm, 20 mm, 25 mm and 30 mm, or a range of values between any two of them; the depth of the pit is 1 to 5 mm, for example, but not limited to the depth of any one of 1 mm, 2 mm, 3 mm, 4 mm and 5 mm, or a range of values between any two of them.

[0055] See Figure 1 As an example, a second adhesive layer 500 is provided on the side of the microfluidic unit 100 facing away from the sweat inducing unit 200. The second adhesive layer 500 is used to adhere to the skin, and a plurality of second through holes 510 corresponding to each other are opened in the area of the second adhesive layer 500 corresponding to the plurality of sweat collection holes 111.

[0056] In this embodiment, a second adhesive layer 500 for adhering to the skin is provided on the side of the micro-channel unit 100 facing away from the sweat inducing unit 200 , so as to facilitate installation of the cortisol sensor 10 on the area to be detected on the skin.

[0057] As an example, the sweat collection hole 111 is connected to the sweat confluence area 120 through a flow channel, and the width of the flow channel is 50 to 300 μm, for example but not limited to a width of any one of 50 μm, 100 μm, 150 μm, 200 μm, 250 μm and 300 μm, or a range of values between any two of them; the depth of the flow channel is 100 to 500 μm, for example but not limited to a depth of any one of 100 μm, 200 μm, 300 μm, 400 μm and 500 μm, or a range of values between any two of them.

[0058] It should be noted that the type of phase change material is not limited, as long as it can undergo phase change and release heat. For example, it can be liquid or solid, and can be adaptively adjusted according to actual needs.

[0059] See Figure 1 As an example, the sweat inducing unit 200 includes a phase change material encapsulation layer 210, which is bonded to the surface of the microfluidic unit 100 through a first adhesive layer 400 and is located above the sweat collection area 110. The phase change material encapsulation layer 210 is a hollow structure and is filled with a phase change material. The phase change material is liquid and can undergo phase change through extrusion.

[0060] It should be noted that, to better understand the technical solution, the state of the phase change material during use is used for auxiliary explanation. Specifically, the phase change material is initially stored in the phase change material encapsulation layer 210 in a room temperature liquid state. When squeezed to trigger the phase change, the liquid phase change material undergoes a phase change to a solid state and continuously releases heat. When the temperature drops, it still exists in a room temperature solid state. If it is to be reused, it needs to be reheated to the phase change temperature to convert it from solid to liquid, then cooled to room temperature, and then squeezed again to trigger it.

[0061] In this embodiment, the phase change material encapsulation layer 210 is bonded to the sweat collection area 110 through the first adhesive layer 400, which has the advantage of being easy to assemble; at the same time, the liquid phase change material is used and the material can undergo phase change by extrusion, which has the advantage of being easy to trigger.

[0062] It should be noted that the material of the phase change material encapsulation layer 210 is not limited, and can be, for example, at least one of PVB, PE, and PP.

[0063] It should be noted that the composition of the phase change material is not limited. For example, it may contain only materials with phase change function, and may also contain some auxiliary functional components. The specific composition can be adaptively adjusted according to actual needs.

[0064] As an example, the phase change material includes a phase change material body and a diluent. The phase change material body can undergo phase change and can release heat and induce the skin to secrete sweat during the phase change process. The diluent is used to lower the upper temperature limit of the phase change material body after the phase change.

[0065] In this embodiment, the phase change material is provided in the form of a phase change material body and a diluent cooperating with each other so that the upper temperature limit of the phase change material after the phase change is within an appropriate range, thereby improving the comfort of the skin while taking into account the amount of sweat secretion of the skin.

[0066] As an example, the mass ratio of the phase change material body and the diluent is 100:(1~15), for example, but not limited to, the mass ratio is any one of 100:1, 100:2, 100:3, 100:4, 100:5, 100:6, 100:7, 100:8, 100:9, 100:10, 100:11, 100:12, 100:13, 100:14 and 100:15, or a range value between any two of them.

[0067] In this embodiment, the mass ratio of the phase change material body and the diluent is limited to the above range so that the two have a more appropriate mass ratio, which can better take into account the amount of skin sweat secretion and the skin comfort during the process of inducing skin sweat secretion.

[0068] As an example, the phase change material body is selected from at least one of sodium acetate trihydrate, sodium sulfate, nickel chloride, cobalt nitrate, iron nitrate and cadmium nitrate.

[0069] In this embodiment, the material of the phase change material body with phase change function is limited to the above range, which has the advantages of being able to be triggered at room temperature (no additional heating is required, which is easy to trigger) and having high latent heat (can continuously release heat for a long time, which can increase sweat secretion).

[0070] As an example, the diluent is selected from at least one of water, acetic acid, urea, ethylene glycol and erythritol.

[0071] In this embodiment, by limiting the type of diluent to the above range, the upper temperature limit of the phase change material after phase change can be more effectively lowered by forming intermolecular hydrogen bonds with the phase change material.

[0072] See Figure 3 As an example, the sweat inducing unit 200 further includes a thermal insulation layer 220 , and the side of the phase change material encapsulation layer 210 facing away from the first adhesive layer 400 and the circumferential side wall of the phase change material encapsulation layer 210 both have the thermal insulation layer 220 .

[0073] In this embodiment, the thermal insulation layer 220 is added to the top and side walls of the phase change material packaging layer 210 to reduce heat loss of the phase change material packaging layer 210, thereby improving its effect of inducing skin sweat secretion.

[0074] See Figure 3 As an example, the cortisol detection unit 300 is bonded to the surface of the microfluidic unit 100 through a first adhesive layer 400, and a first through hole 410 is opened in the area corresponding to the first adhesive layer 400 and the electrode group 320. The first through hole 410 is connected to the sweat confluence area 120, so that the electrode group 320 can contact the sweat in the sweat confluence area 120 through the first through hole 410.

[0075] In this embodiment, the cortisol detection unit 300 is also bonded to the surface of the microfluidic unit 100 through the first adhesive layer 400. This connection method facilitates the assembly of the sweat induction unit 200 and the cortisol detection unit 300 on the same side surface of the microfluidic unit 100. At the same time, this connection method makes the space between the sweat induction unit 200 and the cortisol detection unit 300 relatively closed, thereby facilitating the directional convergence of sweat in the sweat collection area 110 to the sweat confluence area 120.

[0076] See Figure 3 As an example, in the thickness direction of the micro-channel unit 100 , the orthographic projection of the electrode group 320 is located within the orthographic projection of the sweat confluence area 120 , and the electrode group 320 is accommodated in the first through hole 410 .

[0077] In this embodiment, in the thickness direction of the microfluidic unit 100, the orthographic projection of the electrode group 320 is located within the orthographic projection of the sweat confluence area 120 and the electrode group 320 is accommodated in the first through hole 410. This arrangement enables the electrode group 320 to easily and fully contact the sweat in the sweat storage area, thereby helping to improve the detection sensitivity of the cortisol sensor 10.

[0078] As an example, the working electrode 321 in the electrode group 320 has a plurality of grooves distributed in an array on a side close to the sweat confluence area 120 (not shown in the figure).

[0079] In this embodiment, an array of grooves is provided on the side of the working electrode 321 in the electrode group 320 close to the sweat confluence area 120, which helps to increase the contact area between the working electrode 321 and sweat, thereby improving the test sensitivity of the cortisol sensor 10.

[0080] In other possible implementations, the side of the working electrode 321 close to the sweat confluence area 120 may also be in the form of a plane.

[0081] It should be noted that the shape and specifications of the groove are not limited and can be adaptively adjusted according to actual needs.

[0082] As an example, the groove is a circular groove, and the inner diameter of the groove is 100 to 600 μm, for example, but not limited to, the inner diameter is any one of 100 μm, 200 μm, 300 μm, 400 μm, 500 μm and 600 μm, or a range of values between any two of them; the distance between any two adjacent grooves is 100 to 600 μm, for example, but not limited to, the distance is any one of 100 μm, 200 μm, 300 μm, 400 μm, 500 μm and 600 μm, or a range of values between any two of them; the depth of the groove is 10 to 500 μm, for example, but not limited to, the depth is any one of 10 μm, 50 μm, 100 μm, 200 μm, 300 μm, 400 μm and 500 μm, or a range of values between any two of them.

[0083] In this embodiment, the groove is set as a circular groove and the inner diameter of the groove, the distance between any two adjacent grooves and the depth of the groove are respectively limited within the above ranges, which helps the working electrode 321 to contact the sweat more fully, thereby further improving the test sensitivity of the cortisol sensor 10.

[0084] See Figure 4 As an example, the cortisol detection unit 300 includes a flexible substrate 310, a working electrode 321 and a counter electrode 322. The flexible substrate 310 is bonded to the surface of the microfluidic unit 100 through a first adhesive layer 400. The working electrode 321 and the counter electrode 322 are both located on the side of the flexible substrate 310 close to the first adhesive layer 400 and are spaced apart. The working electrode 321 and the counter electrode 322 are both accommodated in the first through hole 410. The working electrode 321 includes a first transition layer 3211, a first conductive layer 3212, a Prussian blue layer 3214 and a molecular imprinting layer 3215 stacked in sequence. The counter electrode 322 includes a second transition layer 3221 and a second conductive layer 3222 stacked in sequence. The first transition layer 3211 and the second transition layer 3221 are both connected to the side of the flexible substrate 310 close to the first adhesive layer 400 and both are made of silicon dioxide.

[0085] In this embodiment, the working electrode 321 and the counter electrode 322 together constitute the electrode group 320, wherein a transition layer of silicon dioxide material is added to the working electrode 321 and the counter electrode 322. The transition layer of this material has a high bonding force with the conductive layer and the flexible substrate 310, so that the conductive layer can be more firmly combined with the flexible substrate 310, thereby improving the structural stability of the cortisol detection unit 300.

[0086] It should be noted that the materials of the first conductive layer 3212 and the second conductive layer 3222 are not limited, and may be silver or copper, for example.

[0087] See Figure 4As an example, a gold conductive layer 3213 is further provided between the first conductive layer 3212 and the Prussian blue layer 3214 .

[0088] In this embodiment, a gold conductive layer 3213 is further provided between the first conductive layer 3212 and the Prussian blue layer 3214. Since gold has good chemical inertness, the chemical stability during the detection process can be improved. At the same time, the provision of the gold conductive layer 3213 can also make it easier and more secure to fix the Prussian blue layer 3214 on the first conductive layer 3212. In addition, the surface of the gold conductive layer 3213 is relatively rough, which can improve the detection sensitivity by increasing the contact area.

[0089] As an example, the material of the flexible substrate 310 is selected from at least one of polydimethylsiloxane, polyimide and hydrogel.

[0090] It should be noted that any structural or functional units not specifically described or limited in the cortisol sensor 10 may be configured according to conventional selections in the art.

[0091] In a second aspect, an embodiment of the present application provides a method for preparing a cortisol sensor as provided in the embodiment of the first aspect, comprising the following steps:

[0092] A microfluidic unit is provided; a sweat induction unit is provided and connected to the surface of the microfluidic unit, so that the sweat induction unit is located above the sweat collection area; a cortisol detection unit is provided and connected to the surface of the microfluidic unit, so that the cortisol detection unit and the sweat induction unit are located on the same side of the microfluidic unit, and the cortisol detection unit is located above the sweat confluence area and the electrode group is in contact with the sweat in the sweat confluence area.

[0093] In the present application, by preparing according to the above process, a cortisol sensor as provided in the first embodiment can be prepared. Using this cortisol sensor, when the human body is in a resting state, the skin can be induced to secrete sufficient sweat painlessly and in real time to detect the human body's cortisol level, thereby accurately reflecting the human body's current stress level.

[0094] It should be noted that the sweat induction unit and the microfluidic unit can be connected to the same side surface of the microfluidic unit synchronously, or can be connected to the same side surface of the microfluidic unit in sequence, and can be adaptively adjusted according to actual needs.

[0095] It should be noted that the preparation method of the microfluidic unit is not limited and can be prepared according to conventional processes in the art. For example, a microfluidic template can be prepared by 3D printing, photolithography or inductively coupled plasma etching, and then the microfluidic unit can be prepared by template transfer.

[0096] It should be noted that the type of phase change material in the sweat inducing unit is not limited, as long as it can release heat through phase change and induce the skin to secrete sweat. In the embodiments of the present application, a material that exists in liquid form and can trigger phase change by extrusion is used as an example for illustration.

[0097] As an example, the preparation method of the sweat inducing unit includes the following steps: heating the phase change material to completely liquefy it to obtain a phase change material solution; transferring the phase change material solution into a phase change material encapsulation layer having an opening, and then sealing it to obtain the sweat inducing unit.

[0098] To better understand the technical solution, the following description will be provided in conjunction with the states of the phase change material during its preparation and use. Specifically, during the preparation of the sweat induction unit, the phase change material is heated to a liquid state. It is then encapsulated within a phase change material encapsulation layer and remains in liquid form even after its temperature drops to room temperature. Subsequently, after the cortisol sensor is assembled, the liquid phase change material is triggered by squeezing during use. This triggers the phase change, converting it from liquid to solid and releasing heat. After the heat release is complete, the phase change material remains in a solid state and only after being reheated to the phase transition temperature and cooled to room temperature does it convert back to liquid and be retriggered. As an example, the phase change material includes a phase change material body and a diluent, wherein the phase change material body is selected from at least one of sodium acetate trihydrate, sodium sulfate, nickel chloride, cobalt nitrate, ferric nitrate, and cadmium nitrate; and the diluent is selected from at least one of water, acetic acid, urea, ethylene glycol, and erythritol.

[0099] As an example, after the step of preparing the sweat inducing unit is completed and before the step of connecting it to the surface of the microfluidic unit, the step of installing an insulation layer on the top and side walls of the phase change material packaging layer is also included.

[0100] It should be noted that the preparation method of the cortisol detection unit is not limited and can be prepared according to conventional processes in the art.

[0101] As an example, the preparation method of a cortisol detection unit includes the following steps: providing a template and pasting a patterned mask on the template to divide the template into a mask-covered area and an exposed area; forming a first conductive layer and a second conductive layer spaced apart in the exposed area, and then removing the mask; transferring the first conductive layer and the second conductive layer to a flexible substrate using a template transfer method; and then forming a Prussian blue layer and a molecular imprinting layer in sequence on the side of the first conductive layer facing away from the flexible substrate to obtain a cortisol detection unit.

[0102] It should be noted that the material of the mask is not limited, and for example, it can be at least one of polyethylene terephthalate, polypropylene, polyimide, and vinyl plastic.

[0103] As an example, the step of forming a first conductive layer and a second conductive layer distributed at intervals in the exposed area includes: first forming a first transition layer and a second transition layer distributed at intervals in the exposed area, and then forming a first conductive layer and a second conductive layer respectively on the side of the first transition layer and the second transition layer away from the template, wherein the materials of the first transition layer and the second transition layer are both selected from silicon dioxide.

[0104] In this embodiment, the conductive layer is prepared after the transition layer is prepared. In the subsequent transfer process, the conductive layer can be easily separated from the template and is not easily damaged.

[0105] As an example, after the step of removing the mask is completed and before the step of forming the Prussian blue layer, the method further includes forming a gold conductive layer on the surface of the first conductive layer.

[0106] It should be noted that, in the step of forming the transition layer and the conductive layer, they can be prepared by drop coating, spin coating, spray coating, blade coating, dispensing or screen printing.

[0107] As an example, the exposed area of the template has array-distributed protrusions, so that array-distributed grooves can be formed on the surface of the working electrode in the electrode group after subsequent transfer.

[0108] It should be noted that any process or step not specifically described or limited in the preparation process of the cortisol sensor may be configured according to conventional methods in the art.

[0109] As an example, the process flow chart of the preparation method of the cortisol sensor is shown in FIG. Figure 5 .

[0110] The features and performance of the present application are further described in detail below with reference to the embodiments.

[0111] Example 1

[0112] The present invention provides a method for preparing a cortisol sensor, comprising the following steps:

[0113] S1 uses 3D printing technology to prepare a microfluidic template, and then uses template transfer technology to prepare a microfluidic unit; among them, the material of the microfluidic unit is polydimethylsiloxane, and the microfluidic unit has a connected sweat collection area and sweat confluence area. The sweat collection area has 6 sweat collection holes (pore diameter is 3mm) that are spaced apart and equidistant from the sweat confluence area. The sweat confluence area is a circular pit with an inner diameter of 6mm and a depth of 2mm. The sweat collection holes and the sweat confluence area are connected through a flow channel with a width of 200μm and a depth of 100μm.

[0114] S2 mixes sodium acetate trihydrate, acetic acid and deionized water in a mass ratio of 100:1:1 and heats them under stirring (temperature is 90°C) until the sodium acetate trihydrate is completely liquefied; then, while maintaining the stirring and heating conditions, adds urea to the mixed solution (added in a mass ratio of sodium acetate trihydrate to urea of 100:6) until a clear and transparent solution is formed to obtain a phase change material solution; then, the phase change material solution is transferred to a phase change material encapsulation layer (made of PVB) with an opening and sealed; then, an insulation layer is installed on the top and side walls of the phase change material encapsulation layer to obtain a sweat induction unit.

[0115] S3 uses photolithography technology to prepare a template with array units. The array units have multiple array-distributed protrusions (the protrusions are cylinders with a diameter of 200 μm and a height of 13 μm, and the spacing between adjacent cylinders is 200 μm). Then, a patterned PET mask is pasted on the template (the patterned mask is obtained by cutting with a laser marking machine, and the pattern is consistent with the shape of the required electrode group) to divide the template into a mask-covered area and an exposed area, and the array units are located in the exposed area; a first transition layer and a second transition layer are formed in the exposed area by spraying. A transition layer (the transition layer is made of silicon dioxide), and then a first conductive layer and a second conductive layer (both silver conductive layers) are formed on the surface of the first transition layer and the second transition layer respectively by spraying, and then the PET mask is removed; the first conductive layer and the second conductive layer are transferred to a flexible substrate (polydimethylsiloxane) by template transfer; then a gold conductive layer, a Prussian blue layer, and a molecular imprinting layer are sequentially formed on the side of the first conductive layer away from the flexible substrate to obtain a cortisol detection unit; wherein, the scanning electron microscope image of the working electrode after the first conductive layer is formed can be found in Figure 6 (It can be seen that there are array-distributed grooves on the surface of the working electrode). The scanning electron microscopy image of the grooves inside the working electrode after the molecular imprinting layer is formed can be found in Figure 7 (It can be seen that the surface inside the groove has a molecular imprinting layer).

[0116] S4 lays the patterned first and second adhesive layers flat on both side surfaces of the microfluidic unit and covers the entire surface respectively, wherein the area of the first adhesive layer corresponding to the pit has a first through hole, and then connects the sweat induction unit directly above the first adhesive layer corresponding to the sweat collection area. At the same time, connects the cortisol detection unit directly above the first adhesive layer corresponding to the sweat confluence area, and makes the working electrode and the counter electrode both accommodated in the first through hole so that they can subsequently contact the sweat in the pit; the area of the second adhesive layer corresponding to the sweat collection area is respectively provided with 6 second through holes that correspond one-to-one to and are connected to the sweat collection holes, thereby obtaining a cortisol sensor.

[0117] Example 2

[0118] The embodiment of the present application provides a method for preparing a cortisol sensor, which differs from Example 1 only in that: in step S2, urea is added according to a mass ratio of sodium acetate trihydrate to urea of 100:9.

[0119] Example 3

[0120] This embodiment of the present application provides a method for preparing a cortisol sensor, which differs from Example 1 only in that, in step S2, the phase change material contains only sodium acetate trihydrate.

[0121] Test example

[0122] (1) Heat release performance test

[0123] The phase change material encapsulation layers containing liquid phase change material prepared in Examples 1 to 3 were used as samples, and the heat release performance of each sample was tested.

[0124] See Figure 8 、 Figure 9 and Figure 10 It can be seen that after adding diluent to the phase change material, the upper temperature limit of the phase change material after the phase change can be effectively lowered, so that the upper temperature limit is controlled at around 45°C, so as to take into account the comfort of the skin while inducing the skin to secrete sweat; and it takes about 4000 seconds for the phase change material to cool down from the upper temperature limit to 35°C, and the heat release lasts for a long time, which can more effectively induce the skin to secrete sweat.

[0125] (2) Performance test of inducing sweat secretion

[0126] The cortisol sensor prepared in Example 1 was used as a sample, and then four test subjects were randomly selected and the sweat volume at the back of the hand, forearm and palm was tested (the actual picture of the cortisol sensor installed on the skin can be found in Figure 11 ), each subject was tested twice.

[0127] See Figure 12 It can be seen (wherein the four colors represent four test subjects), the cortisol sensor provided in the embodiment of the present application can induce the skin to secrete enough sweat at different positions of different test subjects, so as to accurately detect the current stress level of the human body.

[0128] (3) Performance test of cortisol detection unit

[0129] The cortisol detection unit prepared in Example 1 was used as a sample, and its sensitivity, regeneration, selectivity and service life were tested.

[0130] The test steps for sensitivity and reproducibility are as follows:

[0131] The cortisol detection unit was immersed in phosphate-buffered saline (pH 7) containing varying concentrations of cortisol ranging from 10 to 1000 nM at room temperature, and the resulting current was measured by applying an external voltage of 0.16 V. The sensitivity test procedure included: first, immersing the cortisol detection unit in 1 mL of a 10 nM solution and measuring the corresponding current. Then, test solutions containing cortisol were added dropwise to achieve cortisol concentrations of 25 nM, 75 nM, 150 nM, 450 nM, and 1000 nM, and the current at each concentration was measured and the results plotted as a curve. The regeneration test procedure included: first, following the sensitivity test procedure, rinsing the regenerated cortisol detection unit with ethanol after completing a sensitivity test until all residual cortisol was rinsed away. The procedure was then repeated four times, and the current corresponding to cortisol concentrations ranging from 10 to 1000 nM was measured again to determine the performance of the regenerated cortisol detection unit.

[0132] The optional testing steps are as follows:

[0133] When interfering substances such as glucose, lactic acid and steroid hormones with similar structures to cortisol (including dehydroepiandrosterone, β-estradiol, estriol and progesterone) are added to the cortisol solution in sequence, the current change of the cortisol detection unit is tested.

[0134] The test steps for service life are as follows:

[0135] Every 15 days, the cortisol detection unit was immersed in a solution with a cortisol concentration of 25nM, and the changes in the current generated within 1 hour were tested. The test lasted for a total of 90 days.

[0136] See Figure 13 It can be seen that when the cortisol detection unit provided in the embodiment of the present application is used as a sample, its current change curve during the detection process is basically the same, the sensitivity in the range of 10 to 1000 nM is almost the same (the left figure above), and the current change curve after four regenerations is also basically the same (the right figure above), which proves that the cortisol detection unit provided in the embodiment of the present application has good sensitivity and regeneration; at the same time, the presence of interfering substances in cortisol has little effect on the current (the left figure below), indicating that the cortisol detection unit provided in the embodiment of the present application has good selectivity for cortisol; under a test period of 90 days, the standard deviation of the current change is about 3.98% (the right figure below), showing that it has a long service life.

[0137] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A cortisol sensor, characterized in that include: a microfluidic unit, the microfluidic unit being adapted to be attached to the skin, the microfluidic unit comprising sweat collection areas and sweat confluence areas that are spaced and connected to each other, the sweat collection areas being configured to collect sweat secreted by the skin, and the sweat confluence area being configured to converge the sweat collected by the sweat collection areas; a sweat inducing unit connected to a surface of the microfluidic unit and located above the sweat collection area, and configured to utilize heat released by the phase change material during a phase change process to induce sweat secretion from the skin in an area corresponding to the sweat collection area; A cortisol detection unit, wherein the cortisol detection unit and the sweat induction unit are located on the same side of the microfluidic unit, the cortisol detection unit is connected to the surface of the microfluidic unit and is located above the sweat confluence area, and the electrode group of the cortisol detection unit is configured to be able to contact the sweat in the sweat confluence area to detect the cortisol concentration in the sweat.

2. The cortisol sensor according to claim 1, wherein The sweat inducing unit includes a phase change material encapsulation layer, which is bonded to the surface of the microfluidic unit through a first adhesive layer and is located above the sweat collection area. The phase change material encapsulation layer is a hollow structure and is filled with the phase change material. The phase change material is liquid and can undergo phase change through extrusion.

3. The cortisol sensor according to claim 2, wherein The phase change material includes a phase change material body and a diluent. The phase change material body can undergo phase change and release heat and induce the skin to secrete sweat during the phase change process. The diluent is used to reduce the upper temperature limit of the phase change material body after the phase change.

4. The cortisol sensor according to claim 3, characterized in that The mass ratio of the phase change material body to the diluent is 100:(1-15); Optionally, the phase change material body is selected from at least one of sodium acetate trihydrate, sodium sulfate, nickel chloride, cobalt nitrate, iron nitrate and cadmium nitrate; Optionally, the diluent is selected from at least one of water, acetic acid, urea, ethylene glycol and erythritol.

5. The cortisol sensor according to claim 2, wherein The sweat inducing unit further includes a heat-insulating layer. The heat-insulating layer is provided on a side of the phase-change material encapsulation layer facing away from the first adhesive layer and on a circumferential sidewall of the phase-change material encapsulation layer.

6. The cortisol sensor according to any one of claims 2 to 5, characterized in that The cortisol detection unit is bonded to the surface of the microfluidic unit via the first adhesive layer, and a first through-hole is formed in an area of the first adhesive layer corresponding to the electrode group, the first through-hole being in communication with the sweat confluence area, so that the electrode group can contact sweat in the sweat confluence area through the first through-hole; Optionally, in the thickness direction of the micro-channel unit, the orthographic projection of the electrode group is located within the orthographic projection of the sweat confluence area, and the electrode group is accommodated in the first through hole.

7. The cortisol sensor according to claim 6, characterized in that The working electrode in the electrode group has a plurality of grooves distributed in an array on a side close to the sweat confluence area; Optionally, the groove is a circular groove, the inner diameter of the groove is 100-600 μm, the distance between any two adjacent grooves is 100-600 μm, and the depth of the groove is 10-500 μm.

8. The cortisol sensor according to claim 7, characterized in that The cortisol detection unit includes a flexible substrate, a working electrode and a counter electrode. The flexible substrate is bonded to the surface of the microfluidic unit through the first adhesive layer. The working electrode and the counter electrode are both located on the side of the flexible substrate close to the first adhesive layer and are spaced apart. The working electrode and the counter electrode are both accommodated in the first through hole. The working electrode includes a first transition layer, a first conductive layer, a Prussian blue layer and a molecular imprinting layer stacked in sequence. The counter electrode includes a second transition layer and a second conductive layer stacked in sequence. The first transition layer and the second transition layer are both connected to the side of the flexible substrate close to the first adhesive layer, and the materials of both are selected from silicon dioxide.

9. The cortisol sensor according to any one of claims 2 to 5, characterized in that The micro-channel unit is provided with a plurality of sweat collecting holes in the sweat collecting area, the plurality of sweat collecting holes are all connected to the sweat confluence area, and the spacing between the plurality of sweat collecting holes and the sweat confluence area is the same; Optionally, a second adhesive layer is provided on a side of the microchannel unit away from the sweat inducing unit, the second adhesive layer is used to adhere to the skin, and the second adhesive layer has a plurality of second through holes corresponding to each other in areas corresponding to the plurality of sweat collection holes.

10. A method for preparing a cortisol sensor according to any one of claims 1 to 9, characterized in that: The following steps are involved: Providing the microfluidic unit; Providing the sweat inducing unit and connecting it to the surface of the microfluidic channel unit, so that the sweat inducing unit is located above the sweat collecting area; The cortisol detection unit is provided and connected to the surface of the microfluidic unit, so that the cortisol detection unit and the sweat induction unit are located on the same side of the microfluidic unit, and the cortisol detection unit is located above the sweat confluence area and the electrode group is in contact with the sweat in the sweat confluence area.

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