Flexible field effect transistor sensing device for real-time sweat monitoring

Abstract

The application provides a flexible field effect transistor sensing device for real-time sweat monitoring, which comprises, from bottom to top, a skin adhesion layer, a sweat collection layer, a sensor device layer, a micro flow transmission layer and a cover plate layer, wherein the adjacent two layers are vertically stacked and penetrated by a through hole for gathering sweat, the sweat reaches a detection microcavity through the micro flow channel, a biological enzyme on the surface of a sensitive gate electrode of the sensor device layer and noble metal nanoparticles are modified and produce cascade catalysis on target molecules, a signal of a change in a gate interface potential is amplified by a field effect transistor, and high-sensitivity detection of the target molecules is realized. The sensing device of the application can autonomously collect sweat, update and synchronously detect multiple targets in real time, and has important significance for human health monitoring.

Description

Technical Field

[0001] This invention relates to the field of biosensing technology, and more specifically to a flexible field-effect transistor sensing device for real-time monitoring of sweat. Background Technology

[0002] Human sweat, as the most common and readily available epidermal biofluid, is rich in various small-molecule biomarkers that can reflect human health status, such as glucose, lactic acid, and cortisol. Therefore, detecting the levels of specific molecules in sweat can non-invasively obtain real-time information on human physiological health, which has special potential and significance in the field of healthcare.

[0003] Traditional sweat testing typically involves collecting a certain amount of sweat from the skin using absorbent pads or plastic microtubes, followed by offline testing and analysis using large laboratory instruments. These methods are susceptible to sample collection issues due to sweat evaporation and contamination, and rely on expensive equipment, failing to meet the requirements for remote monitoring, on-site testing, and continuous analysis. Therefore, an increasing number of studies are employing flexible patches based on colorimetric or electrochemical detection techniques to collect and analyze sweat. However, the accuracy of colorimetric analysis based on colorimetric reactions is easily affected by ambient light intensity and is primarily used for qualitative analysis.

[0004] Electrochemical sensors are two- or three-electrode devices based on potential or current signal monitoring. In electrochemical sensors, conventional flexible electrodes do not have the function of amplifying electrical signals. When faced with sweat, a complex physiological mixture, they often exhibit characteristics such as high detection limit, small signal response, and low sensitivity, making it difficult to detect ultra-low concentration targets in sweat.

[0005] Furthermore, the pathological information obtained from detecting a single biological target molecule is limited. Therefore, it is often necessary to construct a sensor array to detect multiple targets simultaneously in order to achieve better prediction and diagnosis of diseases. However, since the signal intensity of detection technology based on electrochemical current is related to the electrode area, the electrode area must be reduced in the array structure for multi-target detection, resulting in a weaker signal response.

[0006] Therefore, real-time, high-resolution, and simultaneous detection of multiple target molecules remains a significant challenge for current sweat monitoring. Summary of the Invention

[0007] The purpose of this invention is to address the importance, challenges, and current technological limitations of sweat monitoring by providing a highly sensitive flexible field-effect transistor (FET) sensing device for autonomous sweat collection and real-time monitoring. This device utilizes the autonomous collection function of flexible microfluidic channels and the exponential amplification of weak voltage signal changes in the output current by FETs to achieve highly sensitive and real-time monitoring of specific target molecules in sweat.

[0008] According to a first aspect of the present invention, a flexible field-effect transistor sensing device for real-time sweat monitoring is provided, comprising a skin adhesion layer, a sweat collection layer, a sensor layer, a microfluidic transmission layer, and a cover layer stacked from bottom to top;

[0009] The skin adhesion layer is provided with multiple first through holes for collecting sweat;

[0010] The sweat collection layer is provided with a second through hole for collecting sweat and a third through hole for collecting sweat. The second through hole is provided corresponding to the first through hole, and the third through hole is connected to the second through hole through a first channel.

[0011] The sensor layer includes an insulating flexible substrate, on which a fourth through-hole for collecting sweat is provided, and a field-effect transistor biosensor array, wherein the fourth through-hole is provided corresponding to the third through-hole.

[0012] Among them, the field-effect transistor biosensor array uses semiconductor single-walled carbon nanotubes as the channel material and adopts a coplanar gate structure. The gate electrode surface is modified with a composite layer of noble metal nanoparticles and biological enzymes.

[0013] The microfluidic transport layer is provided with a fifth through hole for collecting sweat, multiple detection microcavities, and a sixth through hole for expelling sweat. The fifth through hole is correspondingly arranged with the fourth through hole and is connected to the first end of the detection microcavity through a second channel. The second end of the detection microcavity is connected to the sixth through hole through a third channel. The detection microcavities are arranged in a one-to-one correspondence with the field-effect transistor biosensors.

[0014] The cover plate layer is provided with a seventh through hole for venting sweat, and the seventh through hole is provided in correspondence with the sixth through hole;

[0015] The first through hole to the seventh through hole form a through-hole, forming a transmission channel for sweat to diffuse and be transmitted from the bottom of the sweat collection layer to the top of the sensor layer. The sweat to be tested enters the detection microcavity along the transmission channel, and the sweat is detected in real time by the field-effect transistor biosensor array, and continues to be discharged along the transmission channel.

[0016] As an optional implementation, the sensing unit structure in the field-effect transistor biosensor array includes:

[0017] An insulating flexible substrate, one side of which serves as a surface layer for subsequent fabrication;

[0018] The source electrode, drain electrode, and gate electrode are located on one side surface of an insulating flexible substrate. The source electrode, drain electrode, and gate electrode are arranged sequentially and alternately on the same planar layer and are made of the same material.

[0019] A semiconductor-type single-walled carbon nanotube network thin film active layer is located on one side surface of an insulating flexible substrate, wherein the semiconductor-type single-walled carbon nanotube network thin film active layer is located between the source electrode and the drain electrode.

[0020] A passivation layer covers the entire area except for the active layer of the semiconductor single-walled carbon nanotube network thin film and the gate sensitive region, so that when the biosensor measures target molecules, only the active layer of the semiconductor single-walled carbon nanotube network thin film and the gate sensitive region are connected through the liquid electrolyte.

[0021] The composite layer of noble metal nanoparticles and biological enzyme molecules is located on the surface of the gate electrode, away from the substrate, and has a cascade catalytic effect on the target molecules to be tested.

[0022] As an optional implementation, in the active layer of the semiconductor single-walled carbon nanotube network thin film, the purity of the semiconductor single-walled carbon nanotubes is not less than 99.9%, and the linear density is 30-100 nanotubes / square micrometer.

[0023] As an optional implementation, the noble metal nanoparticles are Pt or Pd, with a particle size of 0.5-12 nm.

[0024] As an optional implementation, the biological enzyme includes any one of lactate oxidase, glucose oxidase, uricase oxidase, and cholesterol oxidase.

[0025] As an optional implementation, the insulating flexible substrate includes any one of polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polychloro-p-xylene (parylene C), polydimethylsiloxane (PDMS), and polyimide (PI).

[0026] As an optional implementation, the source electrode, drain electrode, and gate electrode are all formed by sequentially depositing three metals: Ti, Pd, and Au.

[0027] As an optional implementation, the first through hole and the second through hole have the same structure, the third through hole, the fourth through hole and the fifth through hole have the same structure, and the sixth through hole and the seventh through hole have the same structure.

[0028] As an optional implementation, in the flexible field-effect transistor sensing device, a double-sided adhesive tape layer is provided between two adjacent layers. The hollow structure on the double-sided adhesive tape layer is correspondingly set with the through holes of the two adjacent layers, and the first through hole to the seventh through hole are interconnected by the double-sided adhesive tape assembly.

[0029] In a second aspect of the present invention, an application is provided of the aforementioned flexible field-effect transistor sensing device for real-time sweat monitoring in the real-time synchronous monitoring of multiple target molecules in sweat.

[0030] As can be seen from the above technical solution of the present invention, the flexible field-effect transistor sensing device for real-time sweat monitoring proposed in this invention collects epidermal sweat through a sweat collection layer and diffuses the collected sweat to the sensor layer. The device utilizes a bio-enzyme on the gate electrode surface to catalyze the reaction of the target molecules in the sweat. The catalytic products are further catalyzed by noble metal nanoparticles in a cascade catalytic process, changing the gate interface potential. Based on the double-layer capacitance regulation mechanism, this causes changes in the effective gate voltage and channel current of the transistor, thereby generating an electrical signal change dependent on the concentration of the target analyte. Through the signal amplification effect of the integrated flexible field-effect transistor, the detection sensitivity is effectively improved, enabling simultaneous real-time monitoring and quantitative analysis of multiple trace target molecules in sweat.

[0031] The flexible field-effect transistor sensing device for real-time sweat monitoring of the present invention uses ultra-thin semiconductor single-walled carbon nanotubes with extremely high carrier mobility as the channel material, which greatly improves the response speed and sensitivity of the sensor. At the same time, the sensor adopts a sensitive gate design to avoid modifying biological probes in the channel region and fully utilize the intrinsic properties of carbon nanotubes. The sensor is based on a double-layer capacitance control mechanism, which enables the device to have a high gain response at extremely low operating voltage, thereby improving the detection efficiency, sensitivity, stability and reliability of the flexible field-effect transistor sensing device.

[0032] The flexible field-effect transistor sensing device for real-time sweat monitoring of the present invention autonomously collects sweat from the skin surface using multiple sweat collection holes at the bottom, and completes sweat detection by guiding the sweat to the sensor layer at the top, and promptly discharges the sweat. This effectively avoids the problems of skin irritation and device instability caused by direct contact between sensitive materials and human skin in traditional adhesive sweat monitoring devices. At the same time, it realizes the flow of sweat and prevents the mixing of new and old sweat from interfering with the detection results. Attached Figure Description

[0033] Figure 1 This is a structural diagram of the sensing unit in an exemplary field-effect transistor biosensor array of the present invention.

[0034] Figure 2 This is a schematic diagram illustrating the fabrication process of the sensing unit in the exemplary field-effect transistor biosensor array of the present invention.

[0035] Figure 3 This is a schematic diagram illustrating the chemical covalent cross-linking modification of bioenzyme molecules on the gate electrode surface, as exemplified by the present invention.

[0036] Figure 4 This is a schematic diagram of the three-dimensional structure of each functional layer in the flexible field-effect transistor sensing device for real-time sweat monitoring, which is an exemplary embodiment of the present invention.

[0037] Figure 5 This is an assembly schematic diagram of an exemplary flexible field-effect transistor sensing device for real-time sweat monitoring according to the present invention.

[0038] Figure 6 This is a scanning electron microscope image of a semiconductor-type single-walled carbon nanotube network thin film deposited on a polyimide substrate in Example 1 of the present invention.

[0039] Figure 7 The transfer characteristic curves (A) and corresponding current-concentration linear fits (B) of the glucose and lactic acid sensing device of Embodiment 1 of the present invention for glucose standard solutions of different concentrations, and the transfer characteristic curves (C) and corresponding current-concentration linear fits (D) for lactic acid standard solutions of different concentrations.

[0040] Figure reference numerals: 100, skin adhesion layer; 110, first through-hole; 200, sweat collection layer; 210, second through-hole; 220, third through-hole; 230, first channel; 300, sensor layer; 310, fourth through-hole; 320, field-effect transistor biosensor array; 321, insulating flexible substrate; 322, semiconductor-type single-walled carbon nanotube network thin film active layer; 323, drain electrode; 324, source electrode; 325 326. Gate electrode; 327. Passivation layer; 328. Noble metal nanoparticles; 400. Bio-enzyme molecule; 410. Microfluidic transport layer; 420. Fifth through hole; 420. Detection microcavity; 430. Sixth through hole; 440. Second channel; 450. Third channel; 500. Cover plate layer; 510. Seventh through hole; 600. Sweat; 700-1. First double adhesive layer; 700-2. Second adhesive layer; 700-3. Third adhesive layer. Detailed Implementation

[0041] To better understand the technical content of the present invention, specific embodiments are described below in conjunction with the accompanying drawings.

[0042] Various aspects of the invention are described in this disclosure with reference to the accompanying drawings, in which numerous illustrative embodiments are shown. The embodiments of this disclosure are not necessarily intended to encompass all aspects of the invention. It should be understood that the various concepts and embodiments described above, as well as those described below in more detail, can be implemented in any of a number of ways.

[0043] Coplanar gate-sensitive carbon nanotube transistor enzyme sensor

[0044] Combination Figure 1The exemplary embodiment shown includes a coplanar gate-sensitive carbon nanotube transistor enzyme sensor comprising an insulating flexible substrate 321, a semiconductor-type single-walled carbon nanotube network thin film active layer 322, a drain electrode 323, a source electrode 324, a gate electrode 325, a passivation layer 326, a composite layer of noble metal nanoparticles 327 and biological enzyme molecules 328.

[0045] Among them, the gate electrode 325, the source electrode 324, and the drain electrode 323 are all disposed on the surface of the insulating flexible substrate 321, arranged in sequence at intervals and made of the same metal material.

[0046] The active layer 322 of the semiconductor-type single-walled carbon nanotube network thin film is located on one side surface of the insulating flexible substrate 321 and is situated between the source electrode 324 and the drain electrode 323.

[0047] All regions except the active layer 322 of the semiconductor-type single-walled carbon nanotube network thin film and the gate electrode 325 are covered by the passivation layer 326, so that when the sensor measures the target molecules, only the active layer and the gate are connected through sweat.

[0048] Noble metal nanoparticles 327 and bio-enzyme molecules 328 are modified on the surface of the gate electrode to form a composite layer of noble metal nanoparticles and bio-enzymes, and the noble metal nanoparticles and bio-enzyme molecules have a cascade catalytic effect on the target molecules.

[0049] During detection, the gate electrode 325 and the active layer 322 of the semiconductor single-walled carbon nanotube network film are connected by the sweat to be tested 600, forming a "double-layer capacitor" structure. By applying a constant bias voltage to the gate electrode 325, the bio-enzyme molecules 328 on the surface of the gate electrode catalyze the reaction of the target molecules in the sweat. The catalytic products are further catalyzed by noble metal nanoparticles 327, changing the gate interface potential, resulting in the effective gate voltage of the transistor channel and the generation of a current signal between the source electrode and the drain electrode that depends on the concentration of the target substance.

[0050] As an optional implementation, in the active layer of the semiconductor single-walled carbon nanotube network thin film, the purity of the semiconductor single-walled carbon nanotubes is not less than 99.9%, and the linear density is 30-100 nanotubes / square micrometer.

[0051] As an optional implementation, the noble metal nanoparticles are Pt or Pd, with a particle size of 0.5-12 nm.

[0052] As an optional implementation, the biological enzyme includes any one of lactate oxidase, glucose oxidase, uricase oxidase, and cholesterol oxidase.

[0053] Understandably, the choice of biological enzyme is determined based on the target molecule to be detected. For example, if glucose needs to be detected, only glucose oxidase needs to be selected as the modified biological enzyme; if lactate needs to be detected, only lactate oxidase needs to be selected as the modified biological enzyme.

[0054] As an optional implementation, the insulating flexible substrate includes any one of polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polychloro-p-xylene (parylene C), polydimethylsiloxane (PDMS), and polyimide (PI).

[0055] As an optional implementation, the source electrode, drain electrode, and gate electrode are all formed by sequentially depositing three metals: Ti, Pd, and Au.

[0056] Fabrication method of coplanar gate-sensitive carbon nanotube transistor enzyme sensor

[0057] Combination Figure 2 , Figure 3 The flowchart illustrating the fabrication process of the coplanar gate-sensitive carbon nanotube transistor bio-enzyme sensor in the exemplary embodiment shown specifically includes the following steps:

[0058] 1. Preparation of semiconductor-type single-walled carbon nanotube network thin films by solution deposition:

[0059] The clean polyimide substrate was completely immersed in a dispersion of semiconductor single-walled carbon nanotubes with a purity of 99.9% and allowed to stand. It was then rinsed sequentially with toluene, acetone, ethanol and deionized water, dried with a nitrogen gun and then baked on a hot plate.

[0060] 2. Fabrication of metal source, drain, and gate electrodes, and channel etching:

[0061] Ti, Pd, and Au metal layers were sequentially deposited on a semiconductor-type single-walled carbon nanotube network thin film using photolithography and electron beam deposition techniques, and then the carbon nanotubes in the non-channel region were etched using an etching process.

[0062] 3. Magnetron sputtering of Pt nanoparticles:

[0063] Pt particles are sputtered onto a planar metal gate using photolithography and magnetron sputtering techniques.

[0064] 4. Passivation layer encapsulation protection for non-test areas:

[0065] A layer of S1813 photoresist is uniformly deposited on the sensor using a spin coater. The test window is exposed by photolithography. Then, the photoresist in the test area is removed using a developer to expose the test area and prevent the source and drain electrodes from coming into contact with the test liquid.

[0066] 5. Modification of biological enzymes by chemical covalent cross-linking:

[0067] like Figure 3 As shown, taking modified glucose oxidase or lactate oxidase as an example.

[0068] For glucose sensing

[0069] First, add 3-mercaptopropionic acid to the gate electrode and let it stand. Then, rinse it thoroughly with a mixture of water and ethanol. Add a mixture of 1-ethyl-3-(3-methylaminopropyl)carbodiimide and N-hydroxysuccinimide to the gate electrode and let it stand. Rinse it thoroughly with PBS and immediately add glucose oxidase solution to cause covalent cross-linking. Let it stand at 4°C for 12 hours.

[0070] For lactate sensing

[0071] First, add dihydrolipoic acid to the gate electrode, then rinse it thoroughly with a mixture of water and ethanol. Then, drop a mixture of 1-ethyl-3-(3-methylaminopropyl)carbodiimide and N-hydroxysuccinimide onto the gate electrode and place it in place. Rinse it thoroughly with PBS and immediately add lactate oxidase solution to induce covalent cross-linking. Place it at 4°C for 8 hours.

[0072] Flexible field-effect transistor sensing device for real-time sweat monitoring

[0073] Combination Figure 4 As shown, the aforementioned coplanar gate-sensitive carbon nanotube transistor enzyme sensor is used as the sensor unit of the field-effect transistor biosensor array. Different target molecules of bioenzymes are simultaneously modified on the field-effect transistor biosensor array. For example, they are arranged in sequence, with the first type of bioenzyme molecule modified on the first sensing unit, the second type of bioenzyme molecule modified on the second sensing unit, and so on, alternatingly, until the entire sensing array is modified with bioenzyme molecules. It is understood that the order and type of modification, including but not limited to the above situations, can be made according to actual needs.

[0074] Thus, the flexible field-effect transistor sensing device for real-time sweat monitoring in an exemplary embodiment of the present invention includes a skin adhesion layer 100, a sweat collection layer 200, a sensor layer 300, a microfluidic transmission layer 400, and a cover plate layer 500 stacked from bottom to top.

[0075] The skin adhesion layer 100 is provided with a plurality of first through holes 110 for collecting sweat; the skin adhesion layer 100 is preferably medical double-sided tape, which can be directly adhered to the skin.

[0076] The sweat collection layer 200 is provided with a second through hole 210 for collecting sweat and a third through hole 220 for collecting sweat. The second through hole 210 is provided in correspondence with the first through hole 110, and the third through hole 220 is connected to the second through hole 210 through a first channel 230.

[0077] It is understandable that the second through hole 210 is in the same position as the first through hole 110, and the shape can also be the same. Meanwhile, the first channel 230 is preferably a hollow channel.

[0078] The sensor layer 300 includes an insulating flexible substrate, on which a fourth through hole 310 for collecting sweat is provided, and a field-effect transistor biosensor array 320, wherein the fourth through hole 310 is correspondingly provided with the third through hole 220.

[0079] Among them, the field-effect transistor biosensor array 320 uses semiconductor single-walled carbon nanotubes as the channel material and adopts a coplanar gate structure. The gate electrode surface is modified with a composite layer of noble metal nanoparticles and biological enzymes.

[0080] It is understandable that the fourth through hole 310 and the third through hole 220 are in the same position and can also have the same shape.

[0081] The microfluidic transmission layer 400 is provided with a fifth through hole 410 for collecting sweat, multiple detection microcavities 420, and a sixth through hole 430 for expelling sweat. The fifth through hole 410 is correspondingly arranged with the fourth through hole 310 and is connected to the first end of the detection microcavity 420 through a second channel 440, so that the fifth through hole 410 and the detection microcavity 420 are connected. The second end of the detection microcavity 420 is connected to the sixth through hole 430 through a third channel 450. The detection microcavities are arranged one-to-one with the sensor unit structure.

[0082] Understandably, the fifth through hole 410 and the fourth through hole 310 are in the same position and can also have the same shape; the detection microcavity is the cavity that is fitted into the sensor unit structure. The sweat that is collected in the fifth through hole 410 flows through the second channel 440 to the surface of the sensor unit structure fitted into the detection microcavity, forming a cover for detection.

[0083] The cover plate layer 500 is provided with a seventh through hole 510 for venting sweat, and the seventh through hole 510 is provided in correspondence with the sixth through hole 430;

[0084] It is understandable that the seventh through hole 510 and the sixth through hole 430 are in the same position and can also have the same shape.

[0085] Thus, a through-hole 110 to a through-hole 510 are formed, creating a transmission channel for sweat to diffuse and be transmitted from the bottom of the sweat collection layer to the top of the sensor layer. The sweat to be tested enters the detection microcavity 420 through the transmission channel, and the sweat is detected in real time by the field-effect transistor biosensor array, and continues to be discharged along the transmission channel.

[0086] As an optional implementation, in the flexible field-effect transistor sensing device, a double-sided adhesive tape layer is provided between two adjacent layers. The hollow structure on the double-sided adhesive tape layer is correspondingly set with the through holes of the two adjacent layers, and the first through hole to the seventh through hole are formed through the double-sided adhesive tape assembly.

[0087] As an optional implementation, the sweat collection layer, microfluidic transport layer, and cover layer can be made of PET material.

[0088] To better understand, Figure 5 The diagram shows the assembly of each functional layer of the device. The hollow structure of each functional layer and the double-sided adhesive layer are prepared by laser cutting. Adjacent layers are bonded together by the double-sided adhesive layer. The assembly process is not limited by the order of assembly.

[0089] In one embodiment, the layers are assembled in the following order from bottom to top: skin adhesion layer 100, sweat collection layer 200, sensor layer 300, microfluidic transmission layer 400, and cover plate layer 500.

[0090] In another embodiment, such as Figure 5 As shown, the skin adhesion layer 100 and the sweat collection layer 200 are assembled together to obtain the first part (1). Figure 5 In step (1), the sensor layer 300 and the microfluidic transport layer 400 are assembled together through the prepared first adhesive layer 700-1 to obtain part (2). Figure 5 In step (2), the second part and the cover plate 500 are then assembled together using the prepared second adhesive layer 700-2 to obtain the third part. Figure 5 In step (3), the third part and the first part are finally assembled together using the third adhesive layer 700-3 to obtain the desired sensing device. Figure 5 Step (4) in the process.

[0091] In another exemplary embodiment of the present invention, an application of the aforementioned flexible field-effect transistor sensing device for real-time sweat monitoring is provided in the real-time synchronous monitoring of multiple target molecules in sweat. The gate electrode and the semiconductor active layer are connected by the test liquid to form a "double-layer capacitor" structure. By applying a constant bias voltage to the gate electrode, the bio-enzyme molecules on the gate electrode surface catalyze the reaction of the target molecules in the electrolyte. The catalytic products are further catalyzed by noble metal nanoparticles, changing the gate interface potential, resulting in the effective gate voltage of the transistor channel and the generation of a current signal between the source electrode and the drain electrode that depends on the concentration change of the target substance.

[0092] Based on the above description, the fabrication process of the exemplary flexible field-effect transistor sensing device for real-time sweat monitoring of the present invention is as follows:

[0093] Example 1

[0094] {Fabrication of Field-Effect Transistor Biosensor Arrays}

[0095] 1. Preparation of semiconductor single-walled carbon nanotube network thin films by solution deposition: A clean polyimide substrate was completely immersed in a dispersion of semiconductor single-walled carbon nanotubes with a purity of 99.9% and allowed to stand for 8 hours. Then, it was rinsed with toluene, acetone, ethanol and deionized water for 1 minute each, dried with a nitrogen gun and then baked at 120 degrees Celsius for 5 minutes.

[0096] Scanning electron microscope (SEM) image of a semiconductor-type single-walled carbon nanotube network thin film fabricated on a polyimide substrate is shown below. Figure 6 As shown, the carbon nanotubes are densely and uniformly distributed, with no obvious impurities.

[0097] 2. Fabrication of metal source, drain and gate electrodes and channel etching: A 0.3 nm thick Ti, a 20 nm thick Pd and a 40 nm thick Au metal layer are sequentially deposited on a semiconductor single-walled carbon nanotube network film using photolithography and electron beam deposition technology. Then, the carbon nanotubes in the non-channel region are etched using an etching process.

[0098] 3. Magnetron sputtering of Pt nanoparticles: Pt particles with a thickness of 2 to 10 nm are sputtered on a planar metal grid using photolithography and magnetron sputtering techniques.

[0099] 4. Passivation layer encapsulation protection for non-test areas: A layer of S1813 photoresist is uniformly deposited on the sensor array using a spin coater. The test window is exposed by photolithography. Then, the photoresist in the test area is removed using a developer to expose the test area and prevent the source and drain electrodes from coming into contact with the test liquid.

[0100] A field-effect transistor biosensor array with four sensing units was obtained.

[0101] 5. Modification of biological enzymes by chemical covalent cross-linking:

[0102] The device obtained in step 4 is simultaneously modified with glucose oxidase and lactate oxidase, with glucose oxidase modified on two sensing units on the same side and lactate oxidase modified on two opposing sensing units.

[0103] Modified glucose oxidase

[0104] First, 3-mercaptopropionic acid was added to the grid electrode and allowed to stand for 8 hours. Then, it was thoroughly rinsed with a 1:3 mixture of water and ethanol. 40 μL of a 1:1 mixture of 1-ethyl-3-(3-methylaminopropyl)carbodiimide (EDC, 100 mM) and N-hydroxysuccinimide (NHS, 40 mM) was added to the grid electrode and allowed to stand for 1 hour. The electrode was then thoroughly rinsed with PBS and glucose oxidase solution was immediately added to induce covalent cross-linking. The electrode was then placed at 4 degrees Celsius for 12 hours.

[0105] Modified lactate oxidase

[0106] First, add dihydrolipoic acid to the grid electrode and let it stand for 5 hours. Then, rinse it thoroughly with a 1:3 mixture of water and ethanol. Add 40 μL of a 1:1 mixture of 1-ethyl-3-(3-methylaminopropyl)carbodiimide (EDC, 100 mM) and N-hydroxysuccinimide (NHS, 40 mM) to the grid electrode and let it stand for 1 hour. Rinse it thoroughly with PBS and immediately add lactate oxidase solution to induce covalent crosslinking. Let it stand at 4 degrees Celsius for 8 hours.

[0107] {Assembly of a flexible field-effect transistor sensor for real-time sweat monitoring}

[0108] Patterned PET cut by laser is used as the sweat collection layer, microfluidic transmission layer, cover layer, and double-sided adhesive tape layer. The layers are stacked in the order of sweat collection layer, sensor layer, microfluidic transmission layer and cover layer from bottom to top, and are assembled by double-sided adhesive tape. Medical double-sided adhesive tape is attached to the side of the sweat collection layer away from the sensor layer as a skin adhesion layer to obtain a glucose and lactic acid sensing device.

[0109] Example 2

[0110] Simultaneously monitor the glucose and lactic acid content in sweat in real time.

[0111] The glucose and lactic acid sensing device obtained according to the method of Example 1 is adhered to the surface of human skin. After a period of time, sweat collected through the microfluidic channel flows to the detection microcavity. A constant voltage V is applied between the source electrode and the drain electrode of the sensor. DS A scanning voltage V within a certain range is applied to the gate electrode. GS As the concentration of the target molecules varies, the current between the source and drain electrodes also differs. By scanning the transfer curves of target molecules at different concentrations, the transfer curves will show differences, as shown in the following figures. Figure 7 As shown.

[0112] Figure 7(A) illustrates the relationship between the transfer characteristic curve of the glucose sensing device and the glucose concentration. As the glucose concentration increases, the threshold shifts to the right. The gate voltage V is selected as the threshold voltage. GS = -0.6V, source-drain voltage V DS = -0.1V, the current Ids is extracted, and the relationship between Ids and glucose concentration is obtained as follows: Figure 7 As shown in (B), the linear response range is 50–200 μM, the detection limit is 50 μM, and the sensitivity is 1.7 μA / μM.

[0113] like Figure 7 (C) illustrates the relationship between the shift characteristic curve of the lactic acid sensor and the lactic acid concentration. As the lactic acid concentration increases, the threshold shifts to the right. The selected gate voltage V... GS = -0.6V, source-drain voltage V DS = -0.1V, the current Ids is extracted to obtain the relationship between Ids and lactic acid concentration. Figure 7 As shown in (D), the linear response range is 1–20 mM, the detection limit is 1 mM, and the sensitivity is 4.3 μA / mM.

[0114] As can be seen from the above, the flexible field-effect transistor sensing device of the present invention can realize real-time monitoring and quantitative analysis of multiple trace target molecules in sweat, while exhibiting good sensitivity and detection limit.

[0115] While the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. Those skilled in the art can make various modifications and refinements without departing from the spirit and scope of the invention. Therefore, the scope of protection of the present invention shall be determined by the claims.

Claims

1. A flexible field-effect transistor sensing device for real-time sweat monitoring, characterized in that, It includes a skin adhesion layer (100), a sweat collection layer (200), a sensor layer (300), a microfluidic transmission layer (400), and a cover plate layer (500) stacked from bottom to top. The skin adhesion layer (100) is provided with a plurality of first through holes (110) for collecting sweat; The sweat collection layer (200) is provided with a second through hole (210) for collecting sweat and a third through hole (220) for collecting sweat. The second through hole (210) is provided corresponding to the first through hole (110), and the third through hole (220) is connected to the second through hole (210) through a first channel (230). The sensor layer (300) includes an insulating flexible substrate, on which a fourth through hole (310) for collecting sweat is provided, and a field-effect transistor biosensor array (320), wherein the fourth through hole (310) is correspondingly provided with the third through hole (220); Among them, the field-effect transistor biosensor array (320) uses semiconductor single-walled carbon nanotubes as channel material and adopts a coplanar gate structure. The gate electrode surface is modified with a composite layer of noble metal nanoparticles and biological enzymes. The microfluidic transport layer (400) is provided with a fifth through hole (410) for collecting sweat, multiple detection microcavities (420), and a sixth through hole (430) for expelling sweat. The fifth through hole (410) is correspondingly arranged with the fourth through hole (310) and is connected to the first end of the detection microcavity (420) through a second channel (440) to form a communication. The second end of the detection microcavity (420) is connected to the sixth through hole (430) through a third channel (450). The detection microcavity (420) is correspondingly arranged with the field-effect transistor biosensor. The cover plate layer (500) is provided with a seventh through hole (510) for venting sweat, and the seventh through hole (510) is provided in correspondence with the sixth through hole (430); Among them, the first through hole (110) has the same structure as the second through hole (210), the third through hole (220), the fourth through hole (310) and the fifth through hole (410) have the same structure, and the sixth through hole (430) has the same structure as the seventh through hole (510). A through-hole (110) is formed between the first through-hole (510) and the seventh through-hole (510), forming a transmission channel for sweat to diffuse and be transmitted from the bottom of the sweat collection layer to the top surface of the sensor layer (300). The sweat collected in the fifth through-hole (410) flows through the second channel (440) to the surface of the sensor unit structure embedded in the detection microcavity, forming a cover for detection. The sweat is detected in real time by the field-effect transistor biosensor array (320) and continues to be discharged along the transmission channel.

2. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 1, characterized in that, In the field-effect transistor biosensor array, the sensing unit structure includes: An insulating flexible substrate (321), wherein one side surface is used as a surface layer to be subsequently prepared; The source electrode (324), drain electrode (323) and gate electrode (325) are located on one side surface of the insulating flexible substrate (321). The source electrode (324), drain electrode (323) and gate electrode (325) are arranged sequentially on the same planar layer and are made of the same material. A semiconductor-type single-walled carbon nanotube network thin film active layer (322) is located on one side surface of an insulating flexible substrate (321), the semiconductor-type single-walled carbon nanotube network thin film active layer (322) is located between the source electrode and the drain electrode; A passivation layer (326) covers the entire region except for the active layer (322) of the semiconductor single-walled carbon nanotube network thin film and the gate sensitive region, so that when the biosensor measures the target molecule, only the active layer (322) of the semiconductor single-walled carbon nanotube network thin film and the gate sensitive region are connected through the liquid electrolyte. The composite layer of noble metal nanoparticles (327) and bio-enzyme molecules (328) is located on the surface of the gate electrode (325), away from the substrate, and has a cascade catalytic effect on the target molecules to be tested.

3. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 2, characterized in that, In the active layer of the semiconductor single-walled carbon nanotube network thin film, the purity of the semiconductor single-walled carbon nanotubes is not less than 99.9%, and the linear density is 30-100 nanotubes / square micrometer.

4. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 2, characterized in that, The noble metal nanoparticles are Pt or Pd, with a particle size of 0.5-12 nm.

5. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 2, characterized in that, Biological enzymes include any one of lactate oxidase, glucose oxidase, uricase oxidase, and cholesterol oxidase.

6. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 2, characterized in that, The insulating flexible substrate includes any one of polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polychloroparaxylene (parylene C), polydimethylsiloxane (PDMS), and polyimide (PI).

7. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 2, characterized in that, The source electrode, drain electrode, and gate electrode are all formed by sequential deposition of three metals: Ti, Pd, and Au.

8. The flexible field-effect transistor sensing device for real-time sweat monitoring according to claim 1, characterized in that, In the flexible field-effect transistor sensing device, a double-sided adhesive tape layer is provided between two adjacent layers. The hollow structure on the double-sided adhesive tape layer is correspondingly set with the through holes of the two adjacent layers. The first through hole (110) to the seventh through hole (510) are interconnected by the double-sided adhesive tape bonding assembly.

9. The application of the flexible field-effect transistor sensing device for real-time sweat monitoring as described in any one of claims 1-8 in the real-time synchronous monitoring of multiple target molecules in sweat.

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