Body fluid-based biological detection devices and methods

Abstract

To provide a body fluid-based biological detection device and method.SOLUTION: A device includes, from bottom to top, a water-filtering layer, a molecularly imprinted polymer layer, and a flexible substrate layer. A biochemical sensor is integrated on the flexible substrate layer. In one state, the water-filtering layer filters water from the body fluid. The molecularly imprinted polymer layer recognizes and binds to biomarkers within the filtered body fluid. The binding of the biomarkers to the molecularly imprinted polymer layer changes the current of the biochemical sensor, thereby converting the biological signal in the body fluid into a physical signal. The present invention provides a body fluid-based biological detection device and method with high sensitivity and stable detection results.SELECTED DRAWING: Figure 6

Description

[Technical Field]

[0001] The present invention relates to the technical field of biomarker testing, and in particular to body fluid-based biological detection devices and methods. [Background technology]

[0002] Biological fluids are various fluids secreted by humans, such as saliva, blood, urine, phlegm, sweat, gastric juice, semen, feces, etc. With the advancement of medical science, testing these bodily fluids not only helps subjects to find diseased areas, but also enables early detection of potential risks of disease.

[0003] Currently, blood is the most common biological fluid sample. However, conventional blood sample testing has the following drawbacks: First, blood sample collection is invasive. Second, blood sample testing and analysis must be performed in a laboratory, which naturally places high demands on the testing environment and instruments. Third, testing is not continuous.

[0004] In recent years, an increasing number of researchers have been working to develop non-invasive, easily collected, real-time, and continuous biological fluid samples for health monitoring. Patent Document 1 (Patent Document 1) discloses a wearable sweat testing system, method, and wearable device. The system includes a microfluidic chip, electrochemical electrodes, a circuit acquisition system, and a mobile terminal system. The microfluidic chip has a sweat collection area on the side that comes into contact with the skin. The other side of the microfluidic chip has a sweat collection space. The sweat collection space is in contact with the electrochemical electrodes. The circuit acquisition system converts the electrical signals of sweat components detected by the electrochemical electrodes into digital signals and transmits them to a mobile terminal system. The mobile terminal system receives, analyzes, and processes the digital signals, and then outputs the sweat test results. The wearable sweat testing system, method, and wearable device provided by this invention are easy to operate and portable. They collect, detect, analyze, and output a subject's sweat in real time, enabling real-time monitoring of human health status information and prompt early warning. However, the testing system provided by this technical solution has the following drawbacks: First, it does not detect biomarkers, and second, it uses microfluidics to collect sweat samples, which requires a certain amount of sweat.

[0005] In addition, although sweat testing can avoid the drawbacks of blood testing, conventional sweat testing devices have drawbacks such as low sensitivity and unstable detection results. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Chinese Patent Application Publication No. 111671437A Summary of the Invention [Problem to be solved by the invention]

[0007] In response to the above-mentioned problems, the present invention provides a biological detection device and method based on body fluids that has high sensitivity and stable detection results. [Means for solving the problem]

[0008] To achieve this goal, the present invention provides the following technical solutions:

[0009] In a first aspect, the present invention provides a biological detection device based on bodily fluids. The device includes, from bottom to top, a water-permeable layer, a molecularly imprinted polymer layer, and a flexible substrate layer. A biochemical sensor is integrated on the flexible substrate layer. In one state, the water-permeable layer filters water from the bodily fluid. The molecularly imprinted polymer layer recognizes and binds to a biomarker in the filtered bodily fluid. Binding of the biomarker to the molecularly imprinted polymer layer changes the current of the biochemical sensor, thereby converting a biological signal in the bodily fluid into a physical signal.

[0010] In the present invention, the water-filtering layer can filter out water from body fluids. For example, sweat contains approximately 99% water, while the biomarker content is extremely low. Through extensive experiments, the inventors of the present application have found that filtering the water from the sample liquid before detection can improve the sensitivity and accuracy of the detection results.

[0011] In the present invention, the molecularly imprinted polymer layer can accurately bind to the biomarkers that need to be detected, which makes the detection results of the detection device more accurate.

[0012] In the present invention, multiple electronic components can be integrated on the flexible substrate layer, and the functions can be expanded according to the actual needs of users.

[0013] In the present invention, the detection device includes, from bottom to top, but is not limited to, a water-permeable layer, a molecularly imprinted polymer layer, and a flexible substrate layer. In practical use, a housing may be added to the outside of the substrate layer to protect the electronic components on the substrate layer, and a water-permeable layer may be added to the outside of the substrate layer.

[0014] Preferably, the flexible substrate layer further includes a humidity sensor integrated therein. In one state, the humidity sensor monitors the humidity around the detection device and transmits humidity data to the biochemical sensor in real time. The biochemical sensor uses the humidity data as a volume parameter of body fluid and analyzes and calculates the concentration of biomarkers in combination with the biomarker data transmitted from the molecularly imprinted polymer layer.

[0015] Preferably, the humidity sensor comprises an MXene-based humidity sensor.

[0016] In the present invention, the humidity sensor may be any one or more types of miniature sensors, including, but not limited to, MXene-based humidity sensors, where miniature sensors are selected to control the overall volume of the sensing device and facilitate its use, especially for wearable or adhesive applications.

[0017] Preferably, the drainage layer comprises a UHMWPE film.

[0018] In the present invention, the drainage layer can be any one or more compounds with a highly porous and breathable structure. For wearable or adhesive applications of the detection device, the drainage layer is selected from green materials that are non-toxic and harmless to living organisms.

[0019] Preferably, the biochemical sensor comprises an organic electrochemical transistor-based biochemical sensor.

[0020] Preferably, the smart device further includes a smart terminal, which is connected to the flexible substrate layer through a network signal. More preferably, the smart terminal includes a mobile phone, a computer, an iPad (registered trademark), etc.

[0021] Preferably, the detection device is a wearable or adhesive type. More preferably, if the detection device is a wearable type, the detection device further includes a mounting ring. Furthermore, if the detection device is an adhesive type, the detection device can be attached to the skin only by van der Waals forces without using a separate adhesive.

[0022] In the present invention, the detection device is a wearable or adhesive type, which has the advantages of being easy to use and having good market prospects.

[0023] Preferably, the biomarkers include biological metabolites, hormones, electrolytes, and proteins. More preferably, biological metabolites include, but are not limited to, lactic acid, uric acid, and glucose. Furthermore, hormones include, but are not limited to, cortisol. Electrolytes include, but are not limited to, sodium, chloride, and hydrogen ions. Proteins include, but are not limited to, C-reactive protein.

[0024] Preferably, the bodily fluids include sweat and sweat vapor.

[0025] In the present invention, by detecting biomarkers in sweat vapor, it is possible to avoid interference with the detection results due to unconsciously excreted sweat.

[0026] Preferably, the thickness of the detection device is 100 to 500 nm, and more preferably, the thickness of the detection device is 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, or 450 nm.

[0027] Preferably, the detection device further includes an early warning system, which has a threshold value stored therein. When the detection result of the biochemical sensor is higher or lower than the threshold value, the early warning system is activated to issue a warning. More preferably, the early warning system is externally connected to a smart terminal of a hospital or a family doctor via a wireless network. When the early warning system is activated to issue a warning, the smart terminal of the hospital or family doctor can obtain the early warning information in real time and intervene promptly.

[0028] In a second aspect, the present invention provides a biological detection method based on a body fluid, the method comprising the steps of:

[0029] S1: The body fluid is passed through a filter layer to filter out the water.

[0030] S2: The molecularly imprinted polymer layer recognizes and binds to biomarkers in the filtered body fluid.

[0031] S3: The binding of a biomarker to the molecularly imprinted polymer layer changes the current of the biochemical sensor, thereby converting the biological signal in the body fluid into a physical signal.

[0032] S4: Biochemical sensors analyze the physical signals of biomarkers in body fluids.

[0033] Preferably, the body fluid includes sweat and sweat vapor, and the method further includes a step of correcting the detection result of the biomarker in the subject's sweat using the detection result of the biomarker in the sweat vapor when sweat is involuntarily excreted.

[0034] Preferably, the detection method uses a biological detection device based on body fluids provided by the present invention. The detection device includes, from bottom to top, a water-permeable layer, a molecularly imprinted polymer layer, and a flexible substrate layer. A biochemical sensor is integrated on the flexible substrate layer. In one state, the water-permeable layer filters water from the body fluid. The molecularly imprinted polymer layer recognizes and binds to a biomarker in the filtered body fluid. Binding of the biomarker to the molecularly imprinted polymer layer changes the current of the biochemical sensor, thereby converting a biological signal in the body fluid into a physical signal.

[0035] Preferably, the flexible substrate layer further includes a humidity sensor integrated therein. In one state, the humidity sensor monitors the humidity around the detection device and transmits humidity data to the biochemical sensor in real time. The biochemical sensor uses the humidity data as a volume parameter of body fluid and analyzes and calculates the concentration of biomarkers in combination with the biomarker data transmitted from the molecularly imprinted polymer layer.

[0036] Preferably, the humidity sensor comprises an MXene-based humidity sensor.

[0037] Preferably, the drainage layer comprises a UHMWPE film.

[0038] Preferably, the biochemical sensor comprises an organic electrochemical transistor-based biochemical sensor.

[0039] Preferably, the smart terminal is connected to the flexible substrate layer through a network signal.

[0040] Preferably, the detection device is wearable or adhesive.

[0041] Preferably, the biomarkers include biological metabolites, hormones, electrolytes and proteins.

[0042] Preferably, the thickness of the detection device is 100 to 500 nm. [Effects of the Invention]

[0043] Compared with the prior art, the beneficial effects and significant advances achieved by using the technical solution of the present invention are as follows:

[0044] 1. The body fluid-based biological detection device of the present invention is much thinner, 100-500 nm, making it more suitable for wearable or adhesive applications.

[0045] 2. The biological detection device based on body fluids of the present invention can remove water from body fluids using a drainage layer. The biomarkers in sweat pass through the film and remain on the molecularly imprinted polymer layer, binding to the molecularly imprinted polymer layer. This allows the molecularly imprinted polymer layer to more accurately capture the biomarkers, ultimately making the detection device more sensitive and accurate. In addition, while most conventional products on the market use microfluidics to test sweat, the device of the present invention can detect biomarkers using sweat vapor. Therefore, the detection results of the present invention are more accurate.

[0046] 3. The biological detection device based on bodily fluids of the present invention newly includes a humidity sensor that can estimate the concentration of biomarkers. Furthermore, the biological detection device based on bodily fluids of the present invention can also detect unconscious sweating. By comparing data on biomarkers in sweat and sweat vapor, it is possible to avoid interference with data from unconscious sweating.

[0047] In order to more clearly describe the technical solution of the present invention, the following briefly describes the drawings that need to be used in the embodiments of the present invention.

[0048] It goes without saying that the drawings described below are merely drawings of some embodiments of the present invention, and those skilled in the art can obtain other drawings from these drawings without requiring creative work, but the other drawings also belong to the drawings required for use in the embodiments of the present invention. [Brief explanation of the drawings]

[0049] [Figure 1] FIG. 1 is a schematic structural diagram of a biological detection device based on body fluids in accordance with a first embodiment of the present invention. [Figure 2] FIG. 2 is a schematic structural diagram of a part of a biological detection device based on body fluids in Example 1 of the present invention. [Figure 3] FIG. 3 is a diagram showing a state in which a conventional body fluid detection device according to a second embodiment of the present invention is used. [Figure 4] FIG. 4 is a microscopic view of the materials of the biological detection device based on body fluids in Example 2 of the present invention. [Figure 5] FIG. 5 is a diagram showing a skin compatibility experiment of the biological detection device based on body fluid in Example 3 of the present invention. [Figure 6] FIG. 6 is a principle diagram of a biological detection device based on body fluid in Examples 4 and 5 of the present invention. [Figure 7] FIG. 7 is a flow chart of the biological detection device based on body fluids in Examples 4 and 5 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0050] The present invention will be further described below in conjunction with specific examples. It should be noted that the examples are merely for the purpose of illustrating the present invention and are not intended to limit the scope of the present invention. It should also be understood that after reading the contents of the present invention, those skilled in the art may make various changes and modifications to the present invention, and these equivalent forms are also included in the scope defined by the claims of this application.

[0051] In order that the present invention may be more fully understood, the terminology of the invention will now be explained and defined.

[0052] Biochemical sensors, also known as electrochemical sensors, are devices or equipment that can convert biochemical quantities into measurable physical signals (e.g., optical or electrical signals) based on certain rules. Biochemical sensors are a research field that interpenetrates many academic fields, including biology, chemistry, physics, electronics, medicine, and semiconductor technology. Biochemical sensors possess characteristics such as excellent selectivity, high sensitivity, fast analysis speed, and low cost, and are capable of performing online continuous monitoring in complex systems. Therefore, they are widely used in fields such as chemistry, life science, biomedical science, environmental monitoring, food, medicine, and military. Structurally, biosensors mainly comprise two parts: a sensitive membrane (a modified membrane with high sensitivity) and a transducer. The sensitive membrane (a modified membrane with high sensitivity) responds to the analyte and can recognize the biological or chemical quantity of the target substance. Changes in the analyte quantity are converted into measurable changes via the sensitive membrane. The transducer can convert the analyte signal detected by the sensitive membrane into a physical signal, facilitating measurement.

[0053] Molecularly imprinted polymers are compounds that mimic biological systems and are used to study molecular recognition. Polymers with specific recognition and selective adsorption properties synthesized using molecular imprinting techniques are called molecularly imprinted polymers. Molecular imprinting can be achieved by the following methods:

[0054] (1) A template molecule and a functional monomer are bound by covalent or π and non-covalent bonds to form a template-monomer complex.

[0055] (2) A crosslinker is added to the complex, and a polymerization reaction is initiated around the template molecule-monomer complex by heat or light initiation with an initiator. During this process, the polymer chains "trap" the template molecule-monomer complex within the polymer's three-dimensional structure through free radical polymerization.

[0056] (3) The template molecule in the polymer is extracted or dissociated by an appropriate method to form a binding site that recognizes the template molecule.

[0057] In MXene-based humidity sensors, the MXene material is a metal carbide and metal nitride material with a two-dimensional layered structure, similar in appearance to stacked potato chips. The chemical formula of the MXene material is M n+1 AX nwhere n = 1-3, and M is an early transition metal such as Sc, Ti, Zr, V, Nb, Cr, or Mo. A typically represents a group 3 or 4 element, and X represents C or N. MXene-based humidity sensors utilize the excellent hydrophilicity and electrical conductivity of MXene. MXene nanosheets are coated onto chitosan-modified TPU electrospun nanofibers via electrostatic interactions to form an MXene / TPU composite film, which is then used to fabricate a humidity sensor. A joint research team from the First Affiliated Hospital of Xi'an Jiaotong University and the School of Advanced Materials and Nanotechnology of Xidian University of Electronic Science and Technology published a paper titled "MXene / TPU Composite Film for Humidity Sensing and Human Respiration Monitoring" in Advanced Sensor Research. In this research, we took advantage of the excellent hydrophilicity and conductivity of MXene to coat MXene nanosheets onto chitosan-modified TPU electrospun nanofibers through electrostatic interactions to create an MXene / TPU composite film, and then fabricated a humidity sensor based on this film. Based on the principle that changes in the concentration of water molecules affect the spacing of MXene nanosheets, thereby changing the tunneling resistance, the MXene / TPU humidity sensor exhibits many properties, including a fast response time (12 s), a wide humidity response range (11% to 94% relative humidity (RH)), low latency (<7% RH), and high reproducibility.

[0058] Among organic electrochemical transistor-based biochemical sensors, organic electrochemical transistors (OECTs) have the characteristic of being highly sensitive. Typically, OECTs-based sensors are controlled by two interfaces: gate / electrolyte and electrolyte / channel, and changes in either interface change the device performance.

[0059] In UHMWPE film, ultra-high molecular weight polyethylene (UHMWPE) is abbreviated as UHMWPE and has properties such as low cost, flexibility, stretchability, and porosity. Chinese Patent No. 113263747B discloses that a new type of 100 nm UHMWPE film, which is strong and mechanically flexible, has a polygonal pore structure for easy expansion, using an initial UHMWPE film with low entanglement. This new nanofilm has a tensile strength of up to 900 MPa and a ductility of 26%, making it widely applicable in many important technological fields. [Example]

[0060] As shown in Figure 1, the biological detection device based on body fluids includes, from bottom to top, a water filtering layer 1, a molecularly imprinted polymer layer 2, and a flexible substrate layer 3. A biochemical sensor 3.1 is integrated on the flexible substrate layer 3. The water filtering layer 1 filters water from the body fluid. The molecularly imprinted polymer layer 2 recognizes and binds to biomarkers in the filtered body fluid. The binding of the biomarkers to the molecularly imprinted polymer layer 2 changes the current flowing through the biochemical sensor 3.1, thereby converting the biological signals in the body fluid into physical signals.

[0061] As shown in Figure 2, a humidity sensor 3.2 is further integrated on the flexible substrate layer 3. The humidity sensor 3.2 monitors the humidity around the detection device and transmits the humidity data to the biochemical sensor 3.1 in real time. The biochemical sensor 3.1 uses the humidity data as a volume parameter of the body fluid and combines it with the biomarker data transmitted from the molecularly imprinted polymer layer 2 to analyze and calculate the concentration of the biomarker.

[0062] In this embodiment, the humidity sensor includes an MXene-based humidity sensor.

[0063] In this example, the drainage layer comprises a UHMWPE film.

[0064] In this embodiment, the biochemical sensor comprises an organic electrochemical transistor-based biochemical sensor.

[0065] This embodiment further includes a smart terminal, which is connected to the flexible substrate layer through a network signal.

[0066] In this embodiment, the detection device is adhesive.

[0067] In this example, biomarkers include biological metabolites, hormones, electrolytes and proteins.

[0068] In this embodiment, the bodily fluids include sweat and sweat vapor.

[0069] In this example, the thickness of the detector is 150 nm. [Example]

[0070] A comparative sweat test experiment was conducted using the biological detection device based on body fluids (experimental group) of Example 1 and a commercially available sweat test device (control group). The devices of the experimental group and the control group were attached to the left and right arms of the subjects, respectively, and statistics were recorded on the time until the devices of the experimental group and the control group first detected a biological signal, the total amount of detected biological signals, and the skin condition around the device.

[0071] As a result, as shown in Figure 3, a large number of obvious air bubbles appeared around the commercially available sweat test device. This was thought to be due to sweat moisture stagnation in that area. In contrast, no obvious air bubbles were observed around the body fluid-based biological detection device of Example 1. Furthermore, when the permeation layer of the body fluid-based biological detection device of Example 1 was observed under a microscope, a large number of gaps were found in the permeation layer, as shown in Figure 4. These gaps may have increased moisture evaporation. Furthermore, sweat interference from other areas (non-test areas) was largely avoided, ensuring cleanliness around the device. In addition, compared to the control group, the experimental group had a shorter time to first acquire biosignals and acquired more biosignals. Analysis of the reasons for this suggested that the permeation layer filtered out most of the moisture in sweat in the experimental group, resulting in a higher concentration of biomarkers in the test sample. Furthermore, the molecularly imprinted polymer layer of the experimental group was able to accurately recognize biomarkers. [Example]

[0072] Skin compatibility test

[0073] The material for manufacturing the drainage layer of the biological detection device based on body fluids in Example 1 was applied to the skin surface of a subject, and the condition of the skin surface was observed for a certain period of time, and the subject's sensation was recorded.

[0074] As a result, as shown in Figure 5, no red swelling or spots appeared on the subjects' skin, and the subjects did not complain of any discomfort. [Example]

[0075] In this example, sweat was detected and analyzed using the biological detection device based on body fluids of Example 1.

[0076] As shown in Figures 6 and 7, it mainly includes the following steps:

[0077] Step 1: In any biological fluid (body fluid) analysis, the first step was to accurately collect the test sample from the subject's body. This was crucial because accurate quantification of biomarkers is difficult without accurate collection of the test sample. Accurate collection is especially important for sweat, which contains 99% water and only 1% biomarkers. Therefore, we used a highly porous and breathable material (UHMWPE film drainage layer) to allow rapid evaporation of water, leaving only the biomarkers in the ultra-high molecular weight polyethylene film.

[0078] Step 2: However, the desired biomarker may only account for a small fraction (e.g., 0.1%) of the total biomarkers. Therefore, we needed a more sophisticated molecular recognition capability. In our example, we added a molecularly imprinted polymer (MIP) capable of specifically binding to the desired molecule and connected it to the organic electrochemical transistor (OECT) of the biochemical sensor.

[0079] Step 3: The biological signal was converted into an electrical signal and passed through the OECT. The biochemical sensor detected the electrical signal and performed analysis.

[0080] Step 4: To capture the volume of sweat collected and calibrate it for each user, we also measured humidity using an MXene-based sensor, which correlated the change in resistance with the collected sweat vapor. This allowed us to combine the collected biomarkers with the volume to obtain accurate sweat biomarker concentrations.

[0081] Step 5: Finally, a software system was developed that could process and build personalized algorithms to track biomarkers in real time and provide measurements for each individual. [Example]

[0082] In this example, the body fluid-based biological detection device of Example 1 was used to detect and analyze sweat and sweat vapor.

[0083] As shown in Figures 6 and 7, it mainly includes the following steps:

[0084] Step 1: In any biological fluid (body fluid) analysis, the first step was to accurately collect the test sample from the subject's body. This was crucial because accurate quantification of biomarkers is difficult without accurate collection of the test sample. Accurate collection is especially important for sweat, which contains 99% water and only 1% biomarkers. Therefore, we used a highly porous and breathable material (UHMWPE film drainage layer) to allow rapid evaporation of water, leaving only the biomarkers in the ultra-high molecular weight polyethylene film.

[0085] Step 2: However, the desired biomarker may only account for a small fraction (e.g., 0.1%) of the total biomarkers. Therefore, we needed a more sophisticated molecular recognition capability. In our example, we added a molecularly imprinted polymer (MIP) capable of specifically binding to the desired molecule and connected it to the organic electrochemical transistor (OECT) of the biochemical sensor.

[0086] Step 3: The biological signal was converted into an electrical signal and passed through the OECT. The biochemical sensor detected the electrical signal and performed analysis.

[0087] Step 4: To capture the volume of sweat collected and calibrate it for each user, we also measured humidity using an MXene-based sensor, which correlated the change in resistance with the collected sweat vapor. This allowed us to combine the collected biomarkers with the volume to obtain accurate sweat biomarker concentrations.

[0088] Step 5: Finally, a software system was developed that could process and build personalized algorithms to track biomarkers in real time and provide measurements for each individual.

[0089] Step 6: Using the methods of steps 1 to 5, biomarkers were detected in the sweat (sweat vapor) unconsciously excreted by the subject.

[0090] Step 7: The data obtained in Step 5 and Step 6 were compared and analyzed.

[0091] The applicant declares the following: In the above specification, the terms "this embodiment," "an embodiment of the present invention," "as shown in ...," "further," "a further improved technical solution," etc., mean that the specific features, structures, materials, or characteristics described in the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, general descriptions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described can be combined or fused in any suitable manner in any one or more embodiments or examples. Furthermore, those skilled in the art can combine or fused different embodiments or examples and features of different embodiments or examples described in this specification, provided that no contradiction arises.

[0092] Finally, it should be noted that the above embodiments are only for illustrating the technical solutions of the present invention, and are not restrictive.

[0093] Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions described in the above embodiments may be modified or some or all of the technical features may be replaced with equivalents, and such modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention. Any non-essential improvements, adjustments or replacements made by those skilled in the art based on the contents of this specification fall within the scope of the protection claimed by the present invention. [Explanation of symbols]

[0094] 1 Drainage layer 2. Molecularly imprinted polymer layer 3 Flexible PCB Layers 3.1 Biochemical sensors 3.2 Humidity sensor

Claims

1. The flexible substrate includes a water-filtering layer, a molecularly imprinted polymer layer, and a flexible substrate layer, in this order from bottom to top, and a biochemical sensor is integrated on the flexible substrate layer; A biological detection device based on bodily fluids, characterized in that the drainage layer filters water from the bodily fluid, the molecularly imprinted polymer layer recognizes and binds to a biomarker in the filtered bodily fluid, and the binding of the biomarker to the molecularly imprinted polymer layer changes the current of the biochemical sensor, thereby converting a biological signal in the bodily fluid into a physical signal.

2. The flexible substrate layer further includes an integrated humidity sensor. The biological detection device based on bodily fluids of claim 1, characterized in that the humidity sensor monitors the humidity around the detection device and transmits humidity data to the biochemical sensor in real time, and the biochemical sensor uses the humidity data as a volume parameter of the bodily fluid and combines it with the data of the biomarker transmitted from the molecularly imprinted polymer layer to analyze and calculate the concentration of the biomarker.

3. The body fluid-based biological detection device of claim 2 , wherein the humidity sensor comprises an MXene-based humidity sensor.

4. 10. The body fluid-based biological detection device of claim 1, wherein the drainage layer comprises an UHMWPE film.

5. 10. The body fluid-based biological sensing device of claim 1, wherein the biochemical sensor comprises an organic electrochemical transistor-based biochemical sensor.

6. The body fluid-based biological detection device of claim 1 , further comprising a smart terminal, the smart terminal being connected to the flexible substrate layer through a network signal.

7. The biological detection device based on bodily fluids of claim 1 , wherein the detection device is wearable or adhesive.

8. 10. The body fluid-based biological detection device of claim 1, wherein the biomarkers include biological metabolites, hormones, electrolytes, and proteins.

9. 8. The bodily fluid-based biological detection device of claim 7, wherein the bodily fluid includes sweat and sweat vapor.

10. 10. The biological detection device based on body fluids of claim 1, wherein the thickness of the detection device is 100-500 nm.

11. S1: Pass the body fluid through the drainage layer to filter the water, S2: The molecularly imprinted polymer layer recognizes and binds to biomarkers in the filtered body fluid; S3: The current of the biochemical sensor changes due to the binding of the biomarker with the molecularly imprinted polymer layer, thereby converting the biological signal in the body fluid into a physical signal; S4: The biochemical sensor analyzes the physical signal of the biomarker in the body fluid. a biological detection method based on a body fluid, comprising the steps of:

12. the bodily fluids include sweat and sweat vapor; Furthermore, 12. The method of claim 11, further comprising the step of correcting the detection results of biomarkers in the subject's sweat using the detection results of biomarkers only in sweat vapor.

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