Bionic patch for quickly collecting sweat of human body and preparation method of bionic patch

Abstract

The invention relates to the technical field of sweat detection, in particular to a bionic patch for rapidly collecting human sweat and a preparation method thereof.The bionic patch comprises a microfluid layer and a bonding layer, the microfluid layer is provided with a microfluid channel of a high-low ridge structure, and the microfluid layer and the bonding layer are prepared from PDMS materials; in the microfluid channel with the high-low edge structure, the high edge is 50 microns, the low edge is 25 microns, and the channel width is 50 microns; the microfluid channel with the high-low edge structure can utilize capillary action and surface tension difference to accelerate flowing of sweat in the channel, prevent sweat accumulation and mixing of new sweat and old sweat and efficiently collect sweat, and meanwhile, the used PDMS material has good flexibility and biocompatibility and can better adapt to bending and deformation of human skin, so that the sweat collection efficiency is improved. And the fitting degree and the comfort are improved.

Description

Technical Field

[0001] The invention relates to the technical field of sweat detection, and in particular to a bionic patch for quickly collecting human sweat and a preparation method thereof. Background Art

[0002] Sweat is a bodily fluid secreted by the eccrine and apocrine sweat glands in the human skin. It primarily functions to regulate body temperature and excrete metabolic waste. Exocrine glands are distributed throughout the body and secrete watery, electrolyte-rich sweat. Apocrine glands, concentrated in areas such as the axillae, secrete lipids and proteins, along with electrolytes (such as Na⁺, K⁺, and Cl⁻), metabolites (lactate, urea, and glucose), hormones (cortisol), proteins (such as cytokines), and trace amounts of drugs. Sweat is considered the most meaningful and abundant source of analytes, making it ideal for noninvasive sampling and continuous monitoring. Currently, a common approach is to use sweat sensors, which can be attached to the surface of human skin to enable real-time and continuous monitoring of individual biochemical parameters without interfering with individual behavior. Sweat sensors often utilize sweat collection patches to extract sweat.

[0003] Although sweat collection patches have great application prospects in the field of sweat extraction, there are still major shortcomings. Existing sweat collection patches have problems such as contamination, sweat accumulation, and mixing of new and old sweat during the sweat extraction process, resulting in inaccurate test results. Specifically, there are mainly the following aspects: 1. Paper-based microfluidic channels have insufficient anti-interference ability. The evaporation of water in sweat will leave dry salt deposits, hindering the operation of the equipment. Impurities such as sebum and salt in sweat may contaminate the microfluidic channels or sensing layers, affecting detection accuracy; 2. Paper-based microfluidic channels have paper wetting problems during long-term monitoring. Hydrophobic paper has a certain shelf life, which limits long-term in situ sweat detection. Paper materials may suffer structural damage after mechanical stretching or repeated bending; 3. The sensitivity and selectivity of paper-based microfluidic channels are limited. The pore structure and chemical background of paper-based materials may interfere with signal acquisition, especially the colorimetric method is easily affected by environmental factors such as light and distance, resulting in uneven detection results; 4. Although wearable devices based on plastics / elastomers have certain flexibility, it is still difficult to fully adapt to the bending and deformation of human skin, affecting the sweat collection effect. Summary of the Invention

[0004] In order to solve the above problems, the present invention provides a bionic patch for quickly collecting human sweat and a preparation method thereof.

[0005] A bionic patch for quickly collecting human sweat comprises a microfluidic layer and an adhesive layer. The microfluidic layer is provided with a microfluidic channel with a high-low ridge structure, and the microfluidic layer and the adhesive layer are made of PDMS material.

[0006] Furthermore, in the microfluidic channel with the high-low-edge structure, the high edge is 50 μm, the low edge is 25 μm, and the channel width is 50 μm.

[0007] Furthermore, the microfluidic layer and the adhesive layer of the patch are bonded by oxygen plasma surface treatment.

[0008] The present invention also provides a method for preparing a bionic patch for rapid collection of human sweat, comprising the preparation of a photolithography template and PDMS mold casting. The preparation of the photolithography template comprises the following steps: designing a photolithography pattern → cleaning a silicon wafer → coating → pre-baking → exposing → post-baking → developing → hardening the film. The exposure dose during the exposure process is 160 mJ / cm 2 .

[0009] Furthermore, the designed photolithography pattern is a double-layer structure, and the exposure metering correction parameters of the double layers are set to 0.2 and 1 respectively.

[0010] Furthermore, the mixing ratio of PDMS to curing agent during the PDMS molding process is 10:1.

[0011] Furthermore, the coating process includes high-speed coating and low-speed coating. The rotation speed of the high-speed coating is 1750±50 rmp and the time is 10s; the rotation speed of the low-speed coating is 500±50 rmp and the time is 30s.

[0012] Furthermore, the negative photoresist is any one of SU-8 2000.5, SU-8 2002, SU-8 2005, SU-8 2007, SU-82010, SU-8 2015, SU-8 2025, SU-8 2035, SU-8 2050, SU-8 2075, SU-8 2100, and SU-8 2150, preferably SU-8 2025, SU-8 2035, SU-8 2050, and SU-8 2075, and more preferably SU-8 2025.

[0013] Furthermore, the pre-baking process and the post-baking process are both gradient temperature control stages. The first pre-baking temperature of the pre-baking stage is 65±5°C, the holding time is 120±10s, and the second pre-baking temperature is 95±5°C, the holding time is 420±20.

[0014] Furthermore, in the post-baking stage, the first post-baking temperature is 65° C., and the holding time is 60±10 s; the second post-baking temperature is 95° C., and the holding time is 360±20 s.

[0015] Furthermore, the developing time in the developing process is 5-6 minutes; the heating temperature in the hardening process is 150° C., and the heating time is 10-15 minutes.

[0016] The advantages of the present invention are: The bionic patch for rapid human sweat collection provided by the present invention prepares a microfluidic channel with a high-low ridge structure by changing the exposure dose, so that the shape of the ridges becomes smoother, reducing the obstruction to the flow of sweat and ensuring that sweat can smoothly enter the microfluidic channel; the microfluidic channel with a high-low ridge structure can utilize capillary action and surface tension difference to accelerate the flow of sweat in the channel, prevent sweat accumulation and mixing of new and old sweat, and the PDMS material used in it has good flexibility and biocompatibility, can better adapt to the bending and deformation of human skin, and improve fit and comfort. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a physical picture of the bionic patch for quickly collecting human sweat according to the present invention; Figure 2 This is a diagram of the preparation process of the bionic patch for rapid collection of human sweat according to the present invention; Figure 3 This is a schematic diagram of a microfluidic channel with high and low ridge structures designed by AutoCAD during the preparation process of the present invention; Figure 4 Schematic diagram of the PDMS homogeneous bonding mechanism of the present invention; Figure 5 1 is a comparison chart of sweat collection effects of the patches of Example 1 of the present invention and Comparative Example 1; Figure 6 is a graph showing the relationship between exposure dose and mold edge height in Test Example 2 of the present invention; Figure 7 Graph showing the relationship between exposure measurement and PDMS edge height in Test Example 2 of the present invention. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0019] It should be noted that the various installation methods and technical terms mentioned in the present invention are technical terms that have long been clearly known in the relevant technical field and therefore will not be further explained. In addition, the same reference numerals are used for the same components, but this does not affect nor constitute an accurate understanding of the technical solution by those skilled in the art.

[0020] Example 1 This example provides a bionic patch for rapid collection of human sweat, as shown in the following example: Figure 1 As shown, it includes a microfluidic layer and an adhesive layer. The microfluidic layer is provided with a microfluidic channel with a high-low ridge structure. The microfluidic layer and the adhesive layer are made of PDMS material.

[0021] like Figure 2 As shown, the preparation process is as follows: Step 1. Photolithography template preparation: (1) Drawing photolithography patterns: Use AutoCAD's polyline to draw, set up two layers, draw the channel part and the low edge part of the lithography pattern respectively, and close the drawn graphics (such as Figure 3 As shown, Figure 3 aThe fan-shaped area is the channel, Figure 3 b blue is low edge, Figure 3 c (red indicates high edges), save as a .DWF file, and then import it into CleWin6 software and save it as a .cif file. (Through layered design, the size and shape of the high and low edge structures can be precisely controlled, helping to create more precise microfluidic channel structures.) (2) Cleaning the silicon wafer (to avoid the influence of dust, the whole process is carried out in a clean room): Place the silicon wafer in a piranha solution consisting of a mixture of concentrated sulfuric acid and 30% hydrogen peroxide in a volume ratio of 3:1. Shake for 10 seconds, remove the wafer, rinse with deionized water, clean with ultrapure water, and blow dry with high-purity nitrogen. Repeat this step three times. Then, place the wafer in a plasma cleaner for 2 minutes, and perform hydrophilic treatment on the surface of the wafer. Finally, place the wafer in a clean watch glass for later use. (3) Silicon wafer coating: First, place a clean two-inch single crystal silicon wafer on a spin coater and pour SU-8 2000 series negative photoresist (negative photoresist can be SU-8 2000.5, SU-8 2002, SU-8 2005, SU-82007, SU-8 2010, SU-8 2015, SU-8 2025, SU-8 2035, SU-8 2050, SU-8 2075, SU-8 2100, SU-8 2150, in this embodiment, SU8-2025 glue is selected), then close the glue machine cover; adjust the glue machine speed to 500±50rpm for 10s, 1750±50rpm for 30s on the digital display screen, and perform centrifugal glue spinning (in this process, to ensure uniform glue spinning, it is necessary to control the generation of bubbles when adding photoresist, and to prevent photoresist denaturation, all operations need to be performed under yellow light); (4) Pre-baking: Prepare two heating plates in advance and set the temperature of the two heating plates to 65℃ and 95℃ respectively. Take out the silicon wafer coated with photoresist and place it on the 65±5℃ heating plate for 120±10s. Then place it on the 95±5℃ heating plate and keep it for 420±20s (the purpose is to enhance the adhesion between the photoresist and the silicon wafer and relieve internal stress). Then cool it naturally to room temperature for use. (5) Exposure: A silicon wafer was placed in a maskless lithography machine (MicroWriter ML3, UK). The focus was first performed to find the surface of the silicon wafer, and then the center of the silicon wafer was determined to avoid engraving the pattern outside or at the edge of the silicon wafer. The drawn pattern was imported into the lithography machine software, and two layers were set. The exposure metering correction parameter of one layer was set to 1 and the other to 0.2. The exposure dose was 160 mJ / cm 2 , then began to be exposed; (6) Post-baking: Post-baking should be done immediately after exposure. Take out the silicon wafer and place it on a 65℃ hot plate for 60±10s, then place it on a 95℃ hot plate for 360±20s.

[0022] (7) Development: Place the silicon wafer in a beaker of SU8 developer and shake it slowly for about 5-6 minutes (do not shake it too long, as it will overdevelop). Carefully remove the wafer with tweezers and observe the pattern development. Rinse with fresh developer, as overdevelopment can cause pattern deformation. Rinse the surface with deionized water. Once the surface is smooth and free of residue, blow dry the wafer with a nitrogen gun. (8) Hard membrane: Place the silicon wafer on a 150°C heating plate for 10-15 minutes and poke the pattern lightly with tweezers. The pattern will become hard and not easily deformed after the film is hardened. Step 2. PDMS mold: First, prepare a mixed solution of polydimethylsiloxane (PDMS) (Sylgard 184) and a curing agent in a mass ratio of 5 g:0.5 g = 10:1. Stir thoroughly in a glass until the mixture resembles saliva. Then, place the mixture in a vacuum oven and evacuate. Repeat the evacuation and degassing process 2-3 times to completely remove any bubbles. Casting: Pour the mixed solution onto the prepared silicon mold and spin coat it using a spin coater at 500 rpm (the thickness of the spin-coated PDMS is approximately 100 μm, allowing the resulting patch to better conform to human skin). Place the mixture in a vacuum oven and evacuate to remove any bubbles. Place the mold in a drying oven, level it using a spirit level, set the temperature to 75°C, and cure for 1 hour. Demolding: After curing, remove the mold. Once the temperature has cooled to room temperature, peel the edges of the PDMS with a blade, then gently peel it off with tweezers. Note that the peeling angle should conform to the stress gradient of the pattern to avoid damage to the PDMS. The peeled PDMS is designated the microfluidic layer and placed in a clean Petri dish for later use.

[0023] Then take a blank silicon wafer and repeat the operation to prepare a PDMS without pattern. Put it into a plasma cleaner for oxygen plasma treatment, adhere the treated side with double-sided tape, and punch holes on it to leave a sweat inlet. The prepared PDMS is named the adhesive layer.

[0024] The patterned surface of the microfluidic layer and the PDMS surface of the adhesive layer were placed facing up and placed in a plasma cleaner for plasma treatment for 2 minutes. After taking them out, they were immediately bonded together. It can be observed that the surface gradient was tightly attached to the exhaust, and then the chip bonding was completed. Finally, the microfluidic channel of the high-low-edge structure of the bionic patch for rapid collection of human sweat was obtained, in which the high edge was 50 μm, the low edge was 25 μm, and the channel width was 50 μm.

[0025] In this embodiment, the homogeneous bonding between the two PDMS layers can be achieved by oxygen plasma surface treatment (plasma treatment), such as Figure 4 As shown in Figure 2, the bonding mechanism is as follows: During oxygen plasma treatment, the contact angle of the PDMS surface decreases rapidly over time. Hydrophilic -OH groups are introduced to the surface, replacing -CH groups, making the PDMS surface extremely hydrophilic. During the bonding process, atoms in the two layers are gradually pushed toward the interface, even penetrating each other, forming a reliable bond at the interface.

[0026] Comparative Example 1 The preparation method of this comparative example 1 is the same as that of Example 1, except that the microfluidic channel in the patch of this comparative example is not provided with a high-low ridge structure.

[0027] Test Example 1 The patches prepared in Example 1 and Comparative Example 1 can be easily attached to the back of the hand, arm, forehead, etc., and can efficiently collect sweat. A peristaltic pump is used to simulate sweat secretion, and the position where the liquid flows is recorded every 5 minutes. Figure 5 As shown, Figure 5 a is a schematic diagram of a common microfluidic channel patch. Figure 5 b is a real picture of a common microfluidic channel patch. Figure 5 c is a schematic diagram of a high-low-edge microfluidic channel patch. Figure 5 d is a real picture of the high-low ridge microfluidic channel patch; it can be seen from the figure that compared with the comparative example 1 of the same size, the patch structure of Example 1 with the high-low ridge structure can transport liquid to the central collection area faster, and the sweat collection effect is significantly higher than that of comparative example 1.

[0028] Test Example 2 Under the condition of 50μm thickness, this test example changes the exposure dose to obtain the relationship diagram of different exposure doses corresponding to different edge heights, as shown in the figure below: Figure 6 and Figure 7 As shown, it can be seen that by adjusting the exposure dose and precisely controlling the degree of photoresist cross-linking in different parts, precise manufacturing of high-low ridge structures can be achieved.

[0029] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention may be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the present invention is defined by the appended claims rather than the foregoing description. It is intended that all variations that fall within the meaning and range of equivalents of the claims be embraced within the present invention. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

[0030] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any minor modifications, equivalent replacements, and improvements made to the above embodiments based on the technical essence of the present invention shall be included in the scope of protection of the technical solution of the present invention.

Claims

1. A bionic patch for rapid collection of human sweat, characterized in that: The invention comprises a microfluid layer and an adhesive layer. The microfluid layer is provided with a microfluid channel with a high-low ridge structure. The microfluid layer and the adhesive layer are made of PDMS material.

2. The bionic patch for rapid collection of human sweat according to claim 1, characterized in that: In the microfluidic channel with a high-low-edge structure, the high edge is 50 μm, the low edge is 25 μm, and the channel width is 50 μm.

3. The bionic patch for rapid collection of human sweat according to claim 1, characterized in that: The microfluidic layer and adhesive layer of the patch are bonded by oxygen plasma surface treatment.

4. A method for preparing a bionic patch for rapid collection of human sweat based on claim 1, comprising preparing a photolithography template and PDMS mold casting, characterized in that: The preparation of the photolithography template includes the following steps: designing the photolithography pattern → cleaning the silicon wafer → coating → pre-baking → exposure → post-baking → development → hardening. The exposure dose during the exposure process is 160 mJ / cm 2 .

5. The method for preparing a bionic patch for rapid collection of human sweat according to claim 4, characterized in that: The designed photolithography pattern is a double-layer structure, and the exposure metering correction parameters of the double layers are set to 0.2 and 1 respectively.

6. The method for preparing a bionic patch for rapid collection of human sweat according to claim 4, characterized in that: The mixing ratio of PDMS to curing agent during the PDMS molding process is 10:

1.

7. The method for preparing a bionic patch for rapid collection of human sweat according to claim 4, characterized in that: The coating process includes high-speed coating and low-speed coating. The rotation speed of the high-speed coating is 1750±50 rmp and the time is 10s; the rotation speed of the low-speed coating is 500±50 rmp and the time is 30s.

8. The method for preparing a bionic patch for rapid collection of human sweat according to claim 7, characterized in that: The negative photoresist used in the spin coating process is any one of SU-8 2000.5, SU-8 2002, SU-8 2005, SU-8 2007, SU-82010, SU-8 2015, SU-8 2025, SU-8 2035, SU-8 2050, SU-8 2075, SU-8 2100, and SU-8 2150.

9. The method for preparing a bionic patch for rapid collection of human sweat according to claim 4, characterized in that: The pre-baking process and the post-baking process are both gradient temperature control stages. The first pre-baking temperature of the pre-baking stage is 65±5°C, the holding time is 120±10s, and the second pre-baking temperature is 95±5°C, the holding time is 420±20s; the first post-baking temperature of the post-baking stage is 65°C, the holding time is 60±10s, and the second post-baking temperature is 95°C, the holding time is 360±20s.

10. The method for preparing a bionic patch for rapid collection of human sweat according to claim 4, characterized in that: The developing time in the developing process is 5-6 minutes; the heating temperature in the hardening process is 150° C. and the heating time is 10-15 minutes.

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