Sperm motility characteristic-based disease risk prediction micro-fluidic chip and experimental method thereof

Abstract

The invention discloses a disease risk prediction micro-fluidic chip based on sperm motility characteristics and an experimental method thereof.The micro-fluidic chip comprises a substrate disc, a heightening layer, a sperm suspension-serum incubation layer and a sperm suspension-serum sample adding layer which are arranged in a laminated mode, and each layer is correspondingly provided with a sperm suspension channel and a plurality of serum channels; the precise co-incubation of the sperm suspension and the serum is realized; according to the invention, sperms are used as a natural high-sensitivity living body biosensor, pathological changes of a body fluid microenvironment are reflected by detecting sperm motility changes, and the problems of low specificity, high cost, complex operation and difficulty in early screening in the existing diagnosis technology are solved; the chip is high in diagnosis accuracy, high in specificity, simple and convenient to operate and low in cost, can be widely applied to early screening and risk prediction of various high-risk diseases such as malignant tumors, cardiovascular and cerebrovascular diseases and metabolic diseases, and has extremely high clinical popularization value and social significance.

Description

Technical Field

[0001] This invention belongs to the field of disease risk prediction technology, specifically relating to a microfluidic chip for disease risk prediction based on sperm motility characteristics and its experimental method, which is particularly suitable for early screening and risk prediction of high-risk diseases. Background Technology

[0002] High-risk diseases such as cardiovascular and cerebrovascular diseases, malignant tumors, and severe inflammatory or metabolic diseases have become major challenges in the global public health field due to their high incidence, mortality, and disability rates, imposing a heavy burden on human health and socioeconomic development. Cardiovascular disease, for example, is one of the leading causes of death worldwide; malignant tumors are equally serious, with common cancers such as lung cancer, stomach cancer, and colorectal cancer having particularly high mortality rates, and lung cancer consistently ranking first among cancer-related deaths. These diseases generally have long latency periods and rapid progression, often lacking obvious clinical symptoms in the early stages. Most patients are diagnosed at middle or late stages, at which point treatment becomes significantly more difficult, and the disease has already caused irreversible damage to the body.

[0003] Early detection, diagnosis, and intervention are crucial for improving patient prognosis and reducing mortality and healthcare costs. However, current mainstream diagnostic technologies have significant limitations in early, accurate, and accessible screening, failing to meet the needs of large populations. Specifically, while imaging diagnosis plays an important role in clinical practice, it has significant shortcomings. Its specificity is limited; for example, low-dose CT scans may have a high false-positive rate in lung cancer screening, causing unnecessary anxiety for patients and potentially leading to subsequent invasive examinations, increasing the medical burden and patient suffering. Equipment such as CT and MRI pose ionizing radiation risks, and long-term or frequent use may cause potential harm to the human body. Furthermore, the equipment is expensive, making it difficult to popularize in areas with limited medical resources, resulting in extremely low early diagnosis rates in these regions. Both imaging diagnosis and biochemical marker testing rely on specialized, large-scale equipment and highly skilled operators; the testing procedures are complex and time-consuming, hindering rapid screening and widespread adoption. Therefore, there is an urgent need to develop innovative, economical, non-invasive, and easily deployable early disease screening and diagnostic technologies to overcome the limitations of existing methods, improve the ability to detect and intervene in major diseases early, and reduce the social healthcare burden. Summary of the Invention

[0004] To address the problems of low specificity, high cost, complex operation, and difficulty in early screening and widespread adoption of existing disease diagnostic technologies, this invention provides a microfluidic chip for disease risk prediction based on sperm motility characteristics. This microfluidic chip uses sperm as a natural, highly sensitive living biosensor to predict disease risk by detecting changes in sperm motility. It aims to achieve high diagnostic accuracy, strong specificity, simple operation, low cost, and ease of promotion, providing a new and effective means for the early screening of high-risk diseases.

[0005] To achieve the above-mentioned objectives, the technical solution adopted by the present invention is as follows:

[0006] A microfluidic chip for predicting disease risk based on sperm motility characteristics includes a substrate disk (1), a padding layer (2), a sperm suspension-serum incubation layer (3), and a sperm suspension-serum loading layer (4) stacked from top to bottom, with each layer bonded together by plasma treatment;

[0007] The sperm suspension-serum loading layer (4) has one sperm suspension loading well (4-1) and multiple serum loading wells (4-2) evenly distributed around the sperm suspension loading well (4-1); the sperm suspension-serum incubation layer (3) has a first sperm suspension docking well (3-1) aligned with the sperm suspension loading well (4-1), multiple first serum docking wells (3-2) aligned one-to-one with the serum loading wells (4-2), and a connection between the first sperm suspension docking well (3-1) and each of the sperm suspension loading wells (4-2). The first serum docking hole (3-2) has a connecting channel (3-3); the padding layer (2) is provided with a second sperm suspension docking hole (2-1) aligned with the first sperm suspension docking hole (3-1) and a plurality of second serum docking holes (2-2) aligned one-to-one with the first serum docking hole (3-2); the substrate disk (1) is provided with a central groove (1-1) aligned with the second sperm suspension docking hole (2-1) and a plurality of edge grooves (1-2) aligned one-to-one with the second serum docking hole (2-2);

[0008] The sperm suspension sample application well (4-1), the first sperm suspension docking well (3-1), the second sperm suspension docking well (2-1), and the central groove (1-1) together constitute a sperm suspension channel; each serum sample application well (4-2), the corresponding first serum docking well (3-2), the corresponding second serum docking well (2-2), and the corresponding edge groove (1-2) constitute an independent serum channel, and each serum channel is connected to the sperm suspension channel through the connecting channel (3-3).

[0009] In a preferred embodiment of the present invention, the number of serum sample wells (4-2) is 4-8, and the central angle between two adjacent serum sample wells (4-2) is equal; the width of the connecting channel (3-3) is 50-100μm, the length is 200-500μm, and the depth is 30-50μm.

[0010] In a preferred embodiment of the present invention, the depth of the central groove (1-1) is 100-200 μm and the inner diameter is 200-300 μm; the depth of the edge groove (1-2) is 100-200 μm and the inner diameter is 150-250 μm, and the number of the edge grooves (1-2) is the same as the number of the serum sample wells (4-2).

[0011] In a preferred embodiment of the present invention, the pore diameter of the sperm suspension loading well (4-1) and the serum loading well (4-2) are both 300-500 μm, and the pore depth is 200-300 μm; the pore diameters of the first sperm suspension docking well (3-1), the first serum docking well (3-2), the second sperm suspension docking well (2-1), and the second serum docking well (2-2) are all consistent with the pore diameter of the corresponding loading well, and the pore depth is 50-100 μm.

[0012] In a preferred embodiment of the present invention, the thickness of the padding layer (2) is 100-200μm, the padding layer (2) is provided with a positioning pin, and the substrate disk (1) and the sperm suspension-serum incubation layer (3) are provided with positioning holes that cooperate with the positioning pin.

[0013] In a preferred embodiment of the present invention, the material of the microfluidic chip body is one or more of the following materials with good biocompatibility: polydimethylsiloxane (PDMS), polycarbonate (PC), polymethyl methacrylate (PMMA), and pure glass.

[0014] This invention provides an experimental method based on the above-mentioned disease risk prediction microfluidic chip, comprising the following steps:

[0015] Step 1: Inject the sperm suspension sample to be tested through the sperm suspension loading hole (4-1), so that it flows into the central groove (1-1) through the first sperm suspension docking hole (3-1) and the second sperm suspension docking hole (2-1).

[0016] Step 2: Inject the serum sample to be tested through each serum loading well (4-2) and let it flow into the corresponding edge groove (1-2) through the corresponding first serum docking well (3-2) and second serum docking well (2-2).

[0017] Step 3: Incubate the microfluidic chip in a constant temperature environment of 35-37℃ for 10-20 minutes to allow the sperm in the sperm suspension to come into full contact with the serum sample through the connecting channel (3-3);

[0018] Step 4: Observe the motility parameters of sperm in the central groove using a microscope or sperm motility analysis equipment. The motility parameters include the active sperm rate, curve rate, linear rate, average path rate, average angular displacement, linearity, oscillation, forward movement, lateral swing amplitude, and whipping frequency.

[0019] Step 5: Compare the detected sperm motility parameters with the standard values ​​of sperm motility parameters in healthy individuals. If there is a significant difference, it is determined that the subject may have a related disease.

[0020] In a preferred embodiment of the present invention, in step 4, the detection accuracy of the sperm motility analysis device is 0.1 μm / s, and the detection field covers the intersection of the central groove (1-1) and the connecting channel (3-3).

[0021] In a preferred embodiment of the present invention, in step 5, the criterion for determining significant difference is P<0.05, where P represents the difference between sperm motility parameters and healthy standard values. This difference is not accidental but is likely caused by changes in the body fluid microenvironment due to disease.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) High diagnostic accuracy and specificity. This invention innovatively uses sperm as a natural, highly sensitive live biosensor. Sperm is extremely sensitive to changes in the overall microenvironment in human body fluids related to disease, and can respond rapidly and directly manifest as changes in motility. This detection mechanism based on cellular functional responses can capture complex pathological information that is difficult to reflect by a single biomarker, effectively overcoming the limitations of traditional biochemical marker detection methods in early diagnosis, such as multiple cross-reactions and weak signals, while avoiding the problem of high false positive rates in imaging diagnostic methods.

[0024] (2) Simple operation, low cost, and easy to promote. The microfluidic chip of this invention does not rely on expensive large-scale imaging equipment or complex molecular detection platforms. The core detection steps only include the addition of sperm suspension and serum samples, constant temperature incubation, and sperm motility analysis. The entire process is simple and quick, taking no more than 2 hours. The chip has low requirements for the professional background of the operators. It can be operated after simple training, without the need for professional medical testing personnel. At the same time, sperm sources are wide-ranging and the acquisition cost is extremely low. The chip is made of common biocompatible polymers, and the production cost is low. The production cost of a single chip can be controlled within 10 yuan. These advantages enable the technology to be widely promoted and applied in primary medical institutions, community health service centers, and resource-limited areas, effectively improving the accessibility of advanced diagnostic technologies and alleviating the current problem of uneven distribution of medical diagnostic resources.

[0025] (3) It has the potential to become a universal early screening tool. Based on the high sensitivity of sperm to the body fluid microenvironment, the technical solution of this invention can not only respond to specific diseases, but also effectively respond to early serological changes in a variety of high-risk diseases (such as malignant tumors, inflammation, metabolic abnormalities, cardiovascular and cerebrovascular diseases, etc.). By establishing a database of sperm motility changes corresponding to different diseases, this chip can achieve simultaneous screening and preliminary diagnosis of multiple diseases, and is expected to be developed into a low-cost, non-invasive, universal early screening tool. This tool is suitable for large-scale population health screening, and can help achieve "early detection and early intervention" of high-risk diseases, significantly reducing the medical costs and social burden caused by disease progression, and has great public health value.

[0026] (4) Non-invasive testing with high patient acceptance. The test samples of this invention only require sperm suspension and a small amount of serum. The sperm suspension sample is obtained non-invasively, and the serum sample only requires blood from the fingertip or earlobe (the amount does not exceed 50 μL). Compared with traditional venous blood collection and invasive examinations, it greatly reduces the pain and psychological burden on patients, and has high patient acceptance, which is conducive to improving the participation rate of population screening. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments or prior art, the drawings used in the description of the embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 This is a cross-sectional view of a microfluidic chip for predicting disease risk based on sperm motility characteristics, provided in an embodiment of the present invention.

[0029] Figure 2This is a schematic diagram of the substrate disk of a microfluidic chip for predicting disease risk based on sperm motility characteristics, provided as an embodiment of the present invention.

[0030] Figure 3 This is a schematic diagram of the padding layer of a microfluidic chip for predicting disease risk based on sperm motility characteristics, provided as an embodiment of the present invention.

[0031] Figure 4 This is a schematic diagram of a sperm suspension-serum incubation layer in a microfluidic chip for disease risk prediction based on sperm motility characteristics, provided as an embodiment of the present invention.

[0032] Figure 5 This is a schematic diagram of a sperm suspension-serum loading layer in a microfluidic chip for disease risk prediction based on sperm motility characteristics, provided as an embodiment of the present invention. Detailed Implementation

[0033] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application. The terms "upper," "lower," "front," "rear," "left," and "right," etc., used when describing the installation position or direction of the structure or components in this embodiment are based on the orientation shown in the accompanying drawings. They are merely for convenience of description, used to distinguish the relative positions of various components or directions, and do not represent the orientation of the device or functional component in this embodiment during use.

[0034] like Figures 1-5 As shown, this embodiment of the invention provides a microfluidic chip for predicting disease risk based on sperm motility characteristics, comprising a substrate disk 1, a padding layer 2, a sperm suspension-serum incubation layer 3, and a sperm suspension-serum sample application layer 4 stacked from top to bottom. Each layer is fixed together by laser bonding or ultrasonic welding to ensure tight connection and prevent liquid leakage.

[0035] The sperm suspension-serum loading layer 4 is a circular sheet structure with a diameter of 20-30 mm and a thickness of 200-300 μm. It has one sperm suspension loading well 4-1 and multiple serum loading wells 4-2 evenly distributed around the sperm suspension loading well 4-1. The sperm suspension loading well 4-1 is located at the center of the layer, and the serum loading wells 4-2 are evenly distributed around its periphery. Preferably, there are 4-8 serum loading wells 4-2, with equal central angles between adjacent wells 4-2 to ensure a consistent mixing ratio of serum samples with sperm suspension. The pore size of both the sperm suspension loading well 4-1 and the serum loading wells 4-2 is 300-500 μm, and the pore depth is 200-300 μm, facilitating sample loading and flow.

[0036] The sperm suspension-serum incubation layer 3 has the same diameter as the sperm suspension-serum loading layer 4, and a thickness of 100-150 μm. The sperm suspension-serum incubation layer 3 has a first sperm suspension docking well 3-1 aligned with the sperm suspension loading well 4-1, multiple first serum docking wells 3-2 aligned one-to-one with the serum loading wells 4-2, and connecting channels 3-3 connecting the first sperm suspension docking wells 3-1 and each of the first serum docking wells 3-2. The first sperm suspension docking well 3-1 is located at the center of the sperm suspension-serum incubation layer 3, vertically aligned with the sperm suspension loading well 4-1, with the same pore diameter and depth as the sperm suspension loading well 4-1. The number of first serum docking wells 3-2 is the same as the number of serum loading wells 4-2, and they are vertically aligned one-to-one with the serum loading wells 4-2, with the same pore diameter and depth as the serum loading wells 4-2. The connecting channel 3-3 is used to connect the first sperm suspension docking hole 3-1 to each of the first serum docking holes 3-2. Each first serum docking hole 3-2 is connected to the first sperm suspension docking hole 3-1 through an independent connecting channel 3-3. The connecting channel 3-3 has a width of 50-100μm, a length of 200-500μm, and a depth of 30-50μm. This size design ensures both smooth flow of sperm and serum components and sufficient contact and reaction between them.

[0037] The diameter of the padding layer 2 is the same as that of the sperm suspension-serum incubation layer 3, and its thickness is 100-200 μm. Its function is to provide support for the sperm suspension-serum incubation layer 3 and form a channel space for sample flow. The padding layer 2 has a second sperm suspension docking hole 2-1 aligned with the first sperm suspension docking hole 3-1, and a plurality of second serum docking holes 2-2 aligned one-to-one with the first serum docking hole 3-2. The second sperm suspension docking hole 2-1 is located at the center of the padding layer 2, vertically aligned with the first sperm suspension docking hole 3-1, with the same pore diameter and a depth of 50-100 μm. The number of second serum docking holes 2-2 is the same as the number of first serum docking holes 3-2, and they are vertically aligned one-to-one with the first serum docking holes 3-2, with the same pore diameter and a depth of 50-100 μm. Positioning pins are provided on the padding layer 2, and positioning holes that cooperate with the positioning pins are provided on the substrate disk 1 and the sperm suspension-serum incubation layer 3 to ensure accurate alignment when the layers are stacked and to avoid channel displacement.

[0038] The substrate disk 1 serves as the base structure for the entire chip, with a diameter of 20-30 mm and a thickness of 300-500 μm, providing stable support. The substrate disk 1 has a central groove 1-1 aligned with the second sperm suspension docking hole 2-1 and multiple edge grooves 1-2 aligned one-to-one with the second serum docking holes 2-2. The central groove 1-1 is located at the center of the substrate disk 1, vertically aligned with the second sperm suspension docking hole 2-1. The depth of the central groove 1-1 is 100-200 μm, and the inner diameter is 200-300 μm. It is used to store sperm suspension samples and provide space for sperm motility. The number of edge grooves 1-2 is the same as the number of second serum docking holes 2-2, and they are vertically aligned one-to-one with the second serum docking holes 2-2. The depth of the edge grooves 1-2 is 100-200 μm, and the inner diameter is 150-250 μm. They are used to store serum samples.

[0039] The sperm suspension sample loading well 4-1, the first sperm suspension docking well 3-1, the second sperm suspension docking well 2-1, and the central groove 1-1 together constitute the sperm suspension channel; each serum sample loading well 4-2, the corresponding first serum docking well 3-2, the corresponding second serum docking well 2-2, and the corresponding edge groove 1-2 constitute an independent serum channel, and each serum channel is connected to the sperm suspension channel through the connecting channel 3-3.

[0040] The substrate disk 1, padding layer 2, sperm suspension-serum incubation layer 3, and sperm suspension-serum sample application layer 4 are all made of biocompatible polymer materials, such as polydimethylsiloxane (PDMS), polycarbonate (PC), polymethyl methacrylate (PMMA), or pure glass, or a combination of one or more of these materials. These materials exhibit good biocompatibility, do not inhibit sperm motility, and possess excellent processing performance and chemical stability, ensuring the structural precision and lifespan of the chip.

[0041] This invention provides an experimental method based on the above-mentioned disease risk prediction microfluidic chip, comprising the following steps:

[0042] Step 1: Inject the sperm suspension sample to be tested through the sperm suspension loading hole 4-1, so that it flows into the central groove 1-1 through the first sperm suspension docking hole 3-1 and the second sperm suspension docking hole 2-1;

[0043] Step 2: Inject the serum sample to be tested through each serum sample application well 4-2, so that it flows into the corresponding edge groove 1-2 through the corresponding first serum docking well 3-2 and second serum docking well 2-2;

[0044] Step 3: Incubate the microfluidic chip in a constant temperature environment of 35-37℃ for 10-20 minutes to allow the sperm in the sperm suspension to come into full contact with the serum sample through the connecting channel 3-3;

[0045] Step 4: Observe the sperm motility parameters within the central groove using a microscope or sperm motility analysis device. These parameters include the percentage of active sperm, forward motility rate, curvilinear motility rate, and whiplash frequency. In Step 4, the sperm motility analysis device has a detection accuracy of 0.1 μm / s, and the detection field covers the intersection of the central groove 1-1 and the connecting channel 3-3.

[0046] Step 5 involves comparing the detected sperm motility parameters with the standard values ​​for sperm motility parameters in healthy individuals. If a significant difference exists, the subject is deemed to potentially have a related disease. In Step 5, the criterion for a significant difference is P < 0.05, where P represents the probability that the difference between the sperm motility parameters and the standard values ​​for healthy individuals is not accidental but rather a result of changes in the body fluid microenvironment caused by a disease.

[0047] This invention relates to a microfluidic chip for disease risk prediction based on sperm characteristics. Through an innovative layered structure design, it achieves precise co-incubation of sperm suspension and serum samples, utilizing sperm as a natural, highly sensitive biosensor to effectively overcome many limitations of existing disease diagnostic technologies. This chip boasts advantages such as high diagnostic accuracy, strong specificity, ease of operation, low cost, and non-invasiveness. It can be widely applied to the early screening and diagnosis of various high-risk diseases, particularly suitable for primary healthcare institutions and resource-limited areas, significantly improving the early detection rate of high-risk diseases and reducing medical costs. Simultaneously, it allows for the expansion of clinical trials, the establishment of a more comprehensive disease-sperm motility change database, and the realization of accurate diagnosis for more diseases, promoting the widespread application of this technology in the field of disease diagnosis.

[0048] The specific implementation of the experimental method for disease risk prediction is as follows:

[0049] Sample preparation: Collect 100 μL of sperm suspension from the subject to be tested. The sample should be used within 1 hour after collection to avoid a decrease in sperm motility. Collect 50 μL of finger prick blood from the subject to be tested and add an anticoagulant (EDTA) to prevent serum coagulation.

[0050] For sample injection, the sperm suspension sample is slowly injected through the sperm suspension loading well 4-1. The sperm suspension sample flows into the central groove 1-1 through the first sperm suspension docking well 3-1 and the second sperm suspension docking well 2-1. The injection is stopped after the central groove 1-1 is filled. The serum sample is divided into 6 equal parts, each about 8 μL, and slowly injected through the 6 serum loading wells 4-2. The serum sample flows into the corresponding edge groove 1-2 through the corresponding first serum docking well 3-2 and the second serum docking well 2-2.

[0051] The microfluidic chip, which has been assembled and injected with the sample, is placed in a constant temperature incubator. The temperature is set to 37°C and the incubation time is 15 minutes. This allows the sperm in the sperm suspension to come into full contact with the serum sample through the connecting channel 3-3, and the sperm responds to the pathological components in the serum.

[0052] After sperm motility testing and incubation, the microfluidic chip is placed under an inverted microscope and used with a sperm motility analysis device (detection accuracy of 0.1 μm / s) to observe the sperm motility parameters within the central groove 1-1, including the active sperm rate, curvilinear velocity, linear velocity, average path velocity, average angular displacement, linearity, oscillation, forward motion, lateral swing amplitude, and whiplash frequency. During testing, the detection field covers the intersection of the central groove 1-1 and the connecting channel 3-3, observing more than 30 sperm in each field, and taking the average value as the test result.

[0053] Result Interpretation: The detected sperm motility parameters were compared with the standard values ​​for sperm motility parameters in healthy individuals. The standard values ​​for healthy individuals were obtained by statistically analyzing the test data of healthy volunteers. If any two or more of the sperm motility parameters of the tested subject were lower than the standard values, and the difference was statistically significant (P<0.05), the tested subject was deemed to have a related high-risk disease, and further clinical diagnostic examinations were recommended.

[0054] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples and are not intended to limit the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A microfluidic chip for predicting disease risk based on sperm motility characteristics, characterized in that, It includes a substrate disk (1), a padding layer (2), a sperm suspension-serum incubation layer (3), and a sperm suspension-serum loading layer (4) stacked from top to bottom, and each layer is bonded together by plasma treatment; The sperm suspension-serum loading layer (4) has one sperm suspension loading well (4-1) and multiple serum loading wells (4-2) evenly distributed around the sperm suspension loading well (4-1); the sperm suspension-serum incubation layer (3) has a first sperm suspension docking well (3-1) aligned with the sperm suspension loading well (4-1), multiple first serum docking wells (3-2) aligned one-to-one with the serum loading wells (4-2), and a connection between the first sperm suspension docking well (3-1) and each of the sperm suspension loading wells (4-2). The first serum docking hole (3-2) has a connecting channel (3-3); the padding layer (2) is provided with a second sperm suspension docking hole (2-1) aligned with the first sperm suspension docking hole (3-1) and a plurality of second serum docking holes (2-2) aligned one-to-one with the first serum docking hole (3-2); the substrate disk (1) is provided with a central groove (1-1) aligned with the second sperm suspension docking hole (2-1) and a plurality of edge grooves (1-2) aligned one-to-one with the second serum docking hole (2-2); The sperm suspension sample application well (4-1), the first sperm suspension docking well (3-1), the second sperm suspension docking well (2-1), and the central groove (1-1) together constitute a sperm suspension channel; each serum sample application well (4-2), the corresponding first serum docking well (3-2), the corresponding second serum docking well (2-2), and the corresponding edge groove (1-2) constitute an independent serum channel, and each serum channel is connected to the sperm suspension channel through the connecting channel (3-3).

2. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The number of serum sample wells (4-2) is 4-8, and the central angle between two adjacent serum sample wells (4-2) is equal; the width of the connecting channel (3-3) is 50-100μm, the length is 200-500μm, and the depth is 30-50μm.

3. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The substrate disk (1), the padding layer (2), the sperm suspension-serum incubation layer (3), and the sperm suspension-serum sample application layer (4) are all made of biocompatible polymer materials, which are one of polydimethylsiloxane, polymethyl methacrylate, polycarbonate, or cyclic olefin copolymers.

4. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The depth of the central groove (1-1) is 100-200μm and the inner diameter is 200-300μm; the depth of the edge groove (1-2) is 100-200μm and the inner diameter is 150-250μm, and the number of the edge grooves (1-2) is the same as the number of the serum sample wells (4-2).

5. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The pore diameter of the sperm suspension loading well (4-1) and the serum loading well (4-2) is 300-500 μm, and the pore depth is 200-300 μm; the pore diameter of the first sperm suspension docking well (3-1), the first serum docking well (3-2), the second sperm suspension docking well (2-1), and the second serum docking well (2-2) is consistent with the pore diameter of the corresponding loading well, and the pore depth is 50-100 μm.

6. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The thickness of the padding layer (2) is 100-200μm. The padding layer (2) is provided with positioning pins. The substrate disk (1) and the sperm suspension-serum incubation layer (3) are provided with positioning holes that cooperate with the positioning pins.

7. The microfluidic chip for disease risk prediction based on sperm motility characteristics according to claim 1, characterized in that, The material of the microfluidic chip body is one or more of the following materials with good biocompatibility: polydimethylsiloxane (PDMS), polycarbonate (PC), polymethyl methacrylate (PMMA), and pure glass.

8. An experimental method based on a disease risk prediction microfluidic chip according to any one of claims 1-7, characterized in that, Includes the following steps: Step 1: Inject the sperm suspension sample to be tested through the sperm suspension loading hole (4-1), so that it flows into the central groove (1-1) through the first sperm suspension docking hole (3-1) and the second sperm suspension docking hole (2-1). Step 2: Inject the serum sample to be tested through each serum loading well (4-2) and let it flow into the corresponding edge groove (1-2) through the corresponding first serum docking well (3-2) and second serum docking well (2-2). Step 3: Incubate the microfluidic chip in a constant temperature environment of 35-37℃ for 10-20 minutes to allow the sperm in the sperm suspension to come into full contact with the serum sample through the connecting channel (3-3); Step 4: Observe the motility parameters of sperm in the central groove using a microscope or sperm motility analysis equipment. The motility parameters include the active sperm rate, curve rate, linear rate, average path rate, average angular displacement, linearity, oscillation, forward movement, lateral swing amplitude, and whipping frequency. Step 5: Compare the detected sperm motility parameters with the standard values ​​of sperm motility parameters in healthy individuals. If there is a significant difference, it is determined that the subject may have a related disease.

9. The experimental method according to claim 8, characterized in that, In step 4, the sperm motility analysis device has a detection accuracy of 0.1 μm / s, and the detection field covers the intersection of the central groove (1-1) and the connecting channel (3-3).

10. The experimental method according to claim 8, characterized in that, In step 5, the criterion for determining a significant difference is P<0.05, where P represents the difference between sperm motility parameters and the healthy standard value. This difference is not accidental but is likely caused by changes in the body fluid microenvironment due to disease.

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