Sweat glucose detection bandage and preparation method thereof

Abstract

The invention discloses a sweat glucose detection bandage and a preparation method thereof, a hydrophobic layer OTS film and a UVO or plasma surface treatment technology are introduced to enhance the comparison between a hydrophobic region and a hydrophilic region, and an accurate patterned wettability surface can be simply and conveniently obtained, so that PEDOT: PSS is accurately deposited in a channel region and a grid region. In addition, due to the fact that the OTS treatment is conducted on the two faces of the bandage, after the UVO treatment is conducted on the single face of the bandage, the hydrophilic and hydrophobic difference is formed on the two faces of the bandage. Due to the structure, retention and diffusion of liquid on the surface are reduced, one-way flow of the detected liquid is effectively guided, and accuracy and stability of sweat glucose detection are ensured.

Description

Technical Field

[0001] The present invention relates to the technical field of flexible wearable biosensors, and in particular to a sweat glucose detection bandage and a preparation method thereof. Background Art

[0002] Diabetes is a metabolic disease whose main characteristic is long-term abnormal increase in blood sugar levels. The number of diabetes patients continues to grow worldwide. Blood sugar monitoring, as an important means of diabetes management, is crucial for controlling the disease and preventing complications. Traditional blood sugar monitoring methods are mainly performed through fingertip blood sampling or implanted sensors. These invasive methods are not only complicated to operate, but may also cause infection, pain and other discomfort, limiting their long-term use. Therefore, the development of a non-invasive, convenient and efficient detection method has become a research hotspot.

[0003] Sweat, as an easily accessible biological fluid, contains a variety of chemical components related to human metabolism, including glucose, lactic acid, urea and electrolytes, among which the glucose concentration has a certain correlation with blood sugar levels. Since sweat collection is painless and real-time, non-invasive blood sugar monitoring technology based on sweat has attracted widespread attention. However, the concentration of glucose in sweat is low and is easily affected by factors such as environmental humidity and volatility, which puts higher requirements on the sensitivity, selectivity and stability of the detection equipment.

[0004] Organic electrochemical transistor (OECT) is a new type of biosensor device. With its high sensitivity, low operating voltage and flexible wearable characteristics, it shows great potential in the field of health monitoring. OECT can significantly improve the detection ability of low-concentration target molecules through electrical signal amplification. However, in the complex sweat detection environment, the signal stability and liquid transport efficiency of OECT sensors are still difficult problems that need to be solved urgently. For example, the detection liquid is retained or diffused unevenly on the sensor surface, which may cause the detection signal to be unstable, thus affecting the accuracy and reliability of the equipment.

[0005] Therefore, in view of the shortcomings of the existing non-invasive blood glucose detection technology, it is necessary to develop a sweat glucose detection bandage and a preparation method thereof to solve the above problems. Summary of the invention

[0006] The purpose of the present invention is to design a sweat glucose detection bandage and a preparation method thereof in order to solve the above problems.

[0007] The present invention achieves the above-mentioned purpose through the following technical solutions: The sweat glucose detection bandage includes, from bottom to top, a bandage base, an OTS hydrophobic layer, a conductive electrode layer, a channel layer, a semiconductor-modified gate layer, platinum nanoparticles, glucose enzyme, and an electrolyte layer; the conductive electrode layer includes a source electrode, a drain electrode, and a gate electrode; the gate electrode, the semiconductor-modified gate layer, platinum nanoparticles, and glucose enzyme constitute a functionalized gate.

[0008] Preferably, the conductive electrode layer is an Au electrode.

[0009] Preferably, the channel layer is made of PEDOT:PSS.

[0010] Preferably, the semiconductor of the semiconductor-modified gate layer is PEDOT:PSS.

[0011] The preparation method of the sweat glucose detection bandage comprises the following steps: Step 1: In a vacuum of 1×10 -4 Pa conditions, a Cr adhesion layer and Au electrodes were evaporated on the bandage surface as the source electrode, drain electrode and gate electrode of the detection bandage; Step 2: Hang the bandage in an OTS atmosphere oven to complete surface modification and prepare an OTS hydrophobic layer; Step 3: Cover the bandage with a mask and perform UV ozone treatment on the channel area and the gate area to change their hydrophilicity and hydrophobicity; Step 4: Make a channel layer and a semiconductor modified gate layer, drop a PEDOT:PSS solution on the channel and gate regions that have been treated with UV ozone, and then perform an annealing treatment. The mass ratio of the PEDOT:PSS solution is PEDOT:PSS:EG:GPOS=100:5:1. Step 5: Cover the bandage with a mask and perform UV-ozone treatment on the electrolyte domain to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer by depositing platinum nanoparticles on the semiconductor-modified gate electrode using an electrochemical deposition method, using a mixed solution of 5 mM H2PtCl6 and 50 mM HCl; Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase, acetic acid, chitosan, and glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

[0012] Preferably, in step 2, the temperature in the oven is 100-150° C., and the time range is 150-220 min.

[0013] Preferably, in step 3 and step 4, the UV-ozone treatment time ranges from 20 to 25 min.

[0014] Preferably, the annealing method adopts at least one of constant temperature hot plate heating, oven heating, far infrared heating and hot air heating.

[0015] The beneficial effects of the present invention are: 1. By introducing a hydrophobic layer OTS film and UVO or plasma surface treatment technology to enhance the contrast between hydrophobic and hydrophilic areas, a precise patterned wettability surface can be easily obtained, so that PEDOT:PSS can be accurately deposited in the channel and gate areas. In addition, since both sides of the bandage in the present invention are treated with OTS, after UVO treatment of one side of the bandage, a difference in hydrophilicity and hydrophobicity is formed on both sides of the bandage. Such a structure reduces the retention and diffusion of liquid on the surface, effectively guides the unidirectional flow of the detection liquid, and ensures the accuracy and stability of sweat glucose detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a schematic diagram of the structure of the present invention; Figure 2 is a microscope image of the device in the present invention; Figure 3 It is a transfer curve diagram of the device prepared in Example 1 measured at a drain voltage (VD) = -0.1V and a gate voltage (VG) scanning interval of -0.2 to 0.8V; Figure 4 This is a graph of drain current obtained by sequentially adding glucose solutions of different concentrations to the device prepared in Example 1 when the drain voltage (VD) = -0.1V and the gate voltage (VG) = 0.4V.

[0017] Description of the reference numerals in the accompanying drawings: 1-bandage substrate, 2-OTS hydrophobic layer, 3-source electrode, 4-drain electrode, 5-gate electrode, 6-channel layer, 7-semiconductor modified gate layer, 8-platinum nanoparticles, 9-glucose enzyme, 10-electrolyte layer. DETAILED DESCRIPTION

[0018] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.

[0019] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0020] 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, further definition and explanation thereof is not required in subsequent drawings.

[0021] In the description of the present invention, it should be understood that the terms "upper", "lower", "inside", "outside", "left", "right", etc. indicate directions or positional relationships based on the directions or positional relationships shown in the accompanying drawings, or are directions or positional relationships in which the product of the invention is usually placed when in use, or are directions or positional relationships commonly understood by those skilled in the art. These directions or positional relationships are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation on the present invention.

[0022] Furthermore, the terms “first”, “second”, etc. are merely used for distinguishing descriptions and should not be understood as indicating or implying relative importance.

[0023] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms such as "setting" and "connection" should be understood in a broad sense. For example, "connection" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0024] The specific implementation modes of the present invention are described in detail below in conjunction with the accompanying drawings.

[0025] like Figure 1-2 As shown, the sweat glucose detection bandage includes, from bottom to top, a bandage substrate 1, an OTS hydrophobic layer 2, a conductive electrode layer, a channel layer, a semiconductor modified gate layer 7, platinum nanoparticles 8, glucose enzyme 9, and an electrolyte layer 10; wherein the conductive electrode layer includes a source electrode 3, a drain electrode 4, and a gate electrode 5; the gate electrode 5, the semiconductor modified gate layer 7, platinum nanoparticles 8, and glucose enzyme 9 constitute a functionalized gate. The conductive electrode layer is an Au electrode. The channel layer is made of PEDOT:PSS. The semiconductor of the semiconductor modified gate layer is PEDOT:PSS.

[0026] The preparation method of the sweat glucose detection bandage comprises the following steps: Step 1: In a vacuum of 1×10 -4 Pa conditions, a Cr adhesion layer and Au electrodes were evaporated on the bandage surface as the source electrode, drain electrode and gate electrode of the detection bandage; Step 2: Hang the bandage in an OTS atmosphere oven to complete surface modification and prepare an OTS hydrophobic layer; Step 3: Cover the bandage with a mask and perform UV ozone treatment on the channel area and the gate area to change their hydrophilicity and hydrophobicity; Step 4: Prepare the channel layer and the semiconductor modified gate layer, drop the PEDOT:PSS solution on the channel and gate regions treated with UV ozone, and then perform annealing (100°C, 20min), the mass ratio of PEDOT:PSS:EG:GPOS in the PEDOT:PSS solution is PEDOT:PSS:EG:GPOS=100:5:1; Step 5: Cover the bandage with a mask and perform UV-ozone treatment on the electrolyte domain to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer by depositing platinum nanoparticles on the semiconductor-modified gate electrode using an electrochemical deposition method, using a mixed solution of 5 mM H2PtCl6 and 50 mM HCl; Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase, acetic acid, chitosan, and glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

[0027] In step 2, the temperature in the oven is 100-150° C., and the time range is 150-220 min.

[0028] In step 3 and step 5, the ultraviolet ozone (UVO) treatment time ranges from 20 to 25 min.

[0029] The annealing method adopts at least one of constant temperature hot plate heating, oven heating, far infrared heating and hot air heating.

[0030] Example 1 (control group): Step 1: In a vacuum of 1×10 -4 Under Pa conditions, a Cr adhesion layer and an Au electrode are sequentially evaporated on the surface of the bandage as the source electrode, drain electrode and gate electrode of the detection bandage. The thickness of the Cr adhesion layer is about 3nm, the thickness of the Au electrode is about 80nm, the channel length is 30um, and the channel width is 300um. Step 2: Prepare an OTS hydrophobic layer and hang the bandage in an OTS atmosphere oven for 210 min to complete the surface modification; Step 3: Cover the bandage with a mask and treat the channel and gate regions with ultraviolet ozone (UVO) for 20 minutes to change their hydrophilicity and hydrophobicity; Step 4: Prepare the channel layer and the semiconductor modified gate layer, drop the PEDOT:PSS solution (mass ratio PEDOT:PSS:EG:GOPS=100:5:1) on the channel and gate areas treated with UVO, and then perform annealing (100°C, 20min); Step 5: Cover the bandage with a mask and treat the electrolyte area with ultraviolet ozone (UVO) for 20 minutes to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer. Deposit platinum nanoparticles on the semiconductor-modified gate electrode using an electrochemical deposition method. The solution used is a mixed solution of 5 mM H2PtCl6 and 50 mM HCl. The steps are to first apply 0.7 V for 10 s, and then apply a voltage of -0.3 V for 60 s.

[0031] Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase / acetic acid / chitosan / glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

[0032] Step 8: Under test conditions: Drain voltage (V D ) = -0.1V, gate voltage (V G ) scanning range is -0.2~0.8V, and the basic performance switching ratio of the device (I on / I off ) = 3.4 × 10 3 , transconductance (gm) = 5.34 ± 0.21 mS, and the device yield is 90%.

[0033] Step 9: Under test conditions: Drain voltage (V D ) = -0.1V, gate voltage (V G ) = 0.4 V, and the lowest glucose concentration that the device can detect is 100 nM.

[0034] Step 10: Place 30 ml of deionized water in a 50 ml bottle (15 mm diameter) and seal it completely with the sample. After 12 h, measure the water mass loss. The water permeability of the sample was measured to be 5.6 ± 0.3 ml cm -2 min -1 .

[0035] Figure 3 As shown, a transfer curve diagram of the device prepared in Example 1 is measured when the drain voltage (VD) is -0.1V and the gate voltage (VG) is scanned in the range of -0.2 to 0.8V; Figure 4 , which shows the drain current diagram of the device prepared in Example 1 obtained by sequentially adding glucose solutions of different concentrations when the drain voltage (VD) = -0.1V and the gate voltage (VG) = 0.4V.

[0036] Embodiment 2: Step 1: In a vacuum of 1×10 -4 Under Pa conditions, a Cr adhesion layer and an Au electrode are sequentially evaporated on the surface of the bandage as the source electrode, drain electrode and gate electrode of the detection bandage. The thickness of the Cr adhesion layer is about 3nm, the thickness of the Au electrode is about 80nm, the channel length is 30um, and the channel width is 300um. Step 2: Prepare an OTS hydrophobic layer and hang the bandage in an OTS atmosphere oven for 150 min to complete the surface modification; Step 3: Cover the bandage with a mask and treat the channel and gate regions with ultraviolet ozone (UVO) for 20 minutes to change their hydrophilicity and hydrophobicity; Step 4: Prepare the channel layer and the semiconductor modified gate layer, drop the PEDOT:PSS solution (mass ratio PEDOT:PSS:EG:GOPS=100:5:1) on the channel and gate areas treated with UVO, and then perform annealing (100°C, 20min); Step 5: Cover the bandage with a mask and treat the electrolyte area with ultraviolet ozone (UVO) for 20 minutes to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer. Deposit platinum nanoparticles on the semiconductor-modified gate electrode using an electrochemical deposition method. The solution used is a mixed solution of 5 mM H2PtCl6 and 50 mM HCl. The steps are to first apply 0.7 V for 10 s, and then apply a voltage of -0.3 V for 60 s.

[0037] Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase / acetic acid / chitosan / glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

[0038] Step 8: Under the test conditions: drain voltage (VD) = -0.1V, gate voltage (VG) scanning range is -0.2~0.8V, and the basic performance switching ratio (Ion / Ioff) of the device is measured = 6.4×10 2 , transconductance (gm) = 3.34 ± 0.61 mS, and the device yield is 60%.

[0039] Step 9: Under the test conditions: drain voltage (VD) = -0.1V, gate voltage (VG) = 0.4V, the lowest glucose concentration that the device can detect is 100uM.

[0040] Step 10: Place 30 ml of deionized water in a 50 ml bottle (15 mm diameter) and seal it completely with the sample. After 12 h, measure the water mass loss. The water permeability of the sample was measured to be 3.4 ± 0.3 ml cm -2 min -1 .

[0041] Embodiment 3: Step 1: In a vacuum of 1×10 -4 Under Pa conditions, a Cr adhesion layer and an Au electrode are sequentially evaporated on the surface of the bandage as the source electrode, drain electrode and gate electrode of the detection bandage. The thickness of the Cr adhesion layer is about 3nm, the thickness of the Au electrode is about 80nm, the channel length is 30um, and the channel width is 300um. Step 2: Prepare an OTS hydrophobic layer, and hang the bandage in an OTS atmosphere oven for 210 min to complete the double-sided surface modification of the bandage; Step 3: Cover the bandage with a mask and treat the channel area and the gate area with ultraviolet ozone (UVO) for 20 minutes to change their hydrophilicity and hydrophobicity; Step 4: Make the channel layer, drop the PEDOT:PSS solution (mass ratio PEDOT:PSS:EG:GOPS=100:5:1) on the channel area treated with UVO, and then perform annealing (100℃, 20min); Step 5: Cover the bandage with a mask and treat the electrolyte area with ultraviolet ozone (UVO) for 20 minutes to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer. Deposit platinum nanoparticles on the PEDOT:PSS-modified gate electrode using an electrochemical deposition method. The solution used is a mixed solution of 5 mM H2PtCl6 and 50 mM HCl. The steps are to first apply 0.7 V for 10 s, and then apply a voltage of -0.3 V for 60 s.

[0042] Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase / acetic acid / chitosan / glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

[0043] Step 8: Under the test conditions: drain voltage (VD) = -0.1V, gate voltage (VG) scanning interval is -0.2~0.8V, and the basic performance switching ratio of the device (I on / I off ) = 8.4 × 10 1 , transconductance (gm) = 1.34 ± 0.61 mS, and the device yield is 80%.

[0044] Step 9: Under the test conditions: drain voltage (VD) = -0.1V, gate voltage (VG) = 0.4V, the lowest glucose concentration that the device can detect is 100uM.

[0045] Step 10: Place 30 ml of deionized water in a 50 ml bottle (15 mm diameter) and seal it completely with the sample. After 12 h, measure the water mass loss. The water permeability of the sample was measured to be 5.3 ± 0.3 ml cm -2 min -1 .

[0046] It can be seen from Examples 1-3 that: 1-bandage substrate, 2-OTS hydrophobic layer, 3-source electrode, 4-drain electrode, 5-gate electrode, 6-channel layer, 7-PEDOT:PSS modified gate layer, 8-platinum nanoparticles, 9-glucose enzyme, 10-electrolyte layer 5; the upper part of the OTS hydrophobic layer 2 is removed after UVO treatment to form a patterned wettability surface, and the PEDOT:PSS solution will be precisely retained in the hydrophilic area on the OTS hydrophobic layer 2, and the excess material will be removed along the OTS surface. The OTS hydrophobic layer 2 exists above and below the flexible substrate. After UVO treatment, the detected sweat can be directionally transported from the lower part of the bandage (hydrophobic area) to the upper part of the bandage (hydrophilic area after UVO treatment).

[0047] Compared with the glucose detection bandage based on organic electrochemical transistor with smaller wettability difference prepared by reducing the OTS treatment time (i.e., the organic electrochemical transistor prepared in Example 2), the glucose detection bandage based on organic electrochemical transistor with larger wettability difference prepared by increasing the OTS treatment time (i.e., the organic electrochemical transistor prepared in Example 2) can realize more accurate patterned device preparation, and the size of its switching ratio is improved, the transconductance difference between devices is improved, and the detection accuracy of glucose is also improved. This is because the increase in wettability difference ensures that the semiconductor and electrolyte sizes of each device are consistent, reducing the crosstalk between devices, and the wettability difference on both sides of the bandage also provides a stable signal for detection. Compared with the glucose detection bandage based on the organic electrochemical transistor prepared by modifying the gate with PEDOT:PSS (i.e., the organic electrochemical transistor prepared in Example 1), the glucose detection bandage based on the organic electrochemical transistor prepared by modifying the gate with PEDOT:PSS (i.e., the organic electrochemical transistor prepared in Example 3) has a greatly improved switching ratio, a greatly improved transconductance difference between devices, and a greatly improved glucose detection accuracy. This is because PEDOT:PSS provides good interfacial electrochemical properties, which is conducive to the combination with catalysts and biomolecules, thereby improving the sensing performance and signal response capability of the gate.

[0048] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A sweat glucose detection bandage, characterized in that: From bottom to top, it includes a bandage base, an OTS hydrophobic layer, a conductive electrode layer, a channel layer, a semiconductor-modified gate layer, platinum nanoparticles, glucose enzyme, and an electrolyte layer; the conductive electrode layer includes a source electrode, a drain electrode, and a gate electrode; the gate electrode, the semiconductor-modified gate layer, platinum nanoparticles, and glucose enzyme constitute a functionalized gate.

2. The sweat glucose detection bandage according to claim 1, characterized in that: The conductive electrode layer is an Au electrode.

3. The sweat glucose detection bandage according to claim 1, characterized in that: The channel layer is made of PEDOT:PSS.

4. The sweat glucose detection bandage according to claim 1, characterized in that: The semiconductor of the semiconductor-modified gate layer is PEDOT:PSS.

5. The method for preparing the sweat glucose detection bandage according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step 1: In a vacuum of 1×10 -4 Pa conditions, a Cr adhesion layer and Au electrodes were evaporated on the bandage surface as the source electrode, drain electrode and gate electrode of the detection bandage; Step 2: Hang the bandage in an OTS atmosphere oven to complete surface modification and prepare an OTS hydrophobic layer; Step 3: Cover the bandage with a mask and perform UV ozone treatment on the channel area and the gate area to change their hydrophilicity and hydrophobicity; Step 4: Make a channel layer and a semiconductor modified gate layer, drop a PEDOT:PSS solution on the channel and gate regions that have been treated with UV ozone, and then perform annealing. The mass ratio of the PEDOT:PSS solution is PEDOT:PSS:EG:GPOS=100:5:

1. Step 5: Cover the bandage with a mask and perform UV-ozone treatment on the electrolyte domain to change its hydrophilicity and hydrophobicity; Step 6: Prepare a platinum nanoparticle layer by depositing platinum nanoparticles on the semiconductor-modified gate electrode using an electrochemical deposition method, using a mixed solution of 5 mM H2PtCl6 and 50 mM HCl; Step 7: Prepare a glucose enzyme layer, drip a mixed solution of glucose oxidase, acetic acid, chitosan, and glutaraldehyde onto the gate area, and dry it at room temperature for 2 hours to obtain a sweat glucose detection bandage based on an organic electrochemical transistor.

6. The method for preparing the sweat glucose detection bandage according to claim 5, characterized in that: In step 2, the temperature in the oven is 100-150° C., and the time range is 150-220 min.

7. The method for preparing the sweat glucose detection bandage according to claim 5, characterized in that: In step 3 and step 5, the UV-ozone treatment time ranges from 20 to 25 min.

8. The method for preparing the sweat glucose detection bandage according to claim 5, characterized in that: The annealing method adopts at least one of constant temperature hot plate heating, oven heating, far infrared heating and hot air heating.

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