Micro-fluidic chip with convolution structure, detection device and application of micro-fluidic chip in rapid quantification of Alzheimer disease Abeta42 protein

Abstract

The invention belongs to the technical field of protein detection, and particularly relates to a micro-fluidic chip with a convolution structure, a detection device and application of the micro-fluidic chip in rapid quantification of Alzheimer disease A beta 42 protein. A flow channel of the micro-fluidic chip adopts a snakelike flow layout and sequentially comprises a straight flow channel, an offset rotary mixing area and a rotary rotary mixing area, space offset of a positive flow side wall and a reverse flow side wall and streamline included angle constraint are set, and liquid is guided to generate asymmetric rotary mixing; and the fluid disturbance effect is further enhanced through multiple sections of turbulent flow structures with different curvatures. According to the flow velocity control method, a flow resistance function of a non-uniform region is constructed and derived, and the optimal opening degree of a proportional valve corresponding to a sudden change point of the derived function is identified, so that automatic optimization regulation and control of a chip flow field are realized. The scheme is suitable for rapid quantitative detection of target molecules such as Alzheimer disease Abeta42 protein, has the advantages of high mixing efficiency, short response time and high detection sensitivity, and has good clinical detection and field application prospects.

Description

Technical Field

[0001] This invention belongs to the technical field of protein detection, specifically relating to a microfluidic chip with a cycloid structure, a detection device, and its application in the rapid quantification of Aβ42 protein in Alzheimer's disease. Background Technology

[0002] Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system, clinically characterized by memory loss, cognitive impairment, and behavioral abnormalities. Its pathogenesis is closely related to the abnormal deposition of β-amyloid protein (Aβ, especially Aβ42) in the brain. Studies have shown that Aβ42 has a strong aggregation tendency and neurotoxicity, and is a key factor in inducing neuronal damage and death. It has been widely used as a biomarker in the early screening and disease monitoring of Alzheimer's disease. Therefore, developing a rapid, sensitive, and specific method for the quantitative detection of Aβ42 protein has significant clinical value.

[0003] Existing methods for Aβ42 detection mainly include enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, mass spectrometry, and fluorescent labeling. While these methods offer certain sensitivity and accuracy under laboratory conditions, they generally suffer from problems such as complex operation, long detection cycles, high reagent consumption, and strong dependence on sample conditions, making it difficult to meet the needs for rapid, convenient, and high-throughput on-site testing.

[0004] Currently, microfluidic detection devices for Alzheimer's disease have the following shortcomings: First, some devices still rely on complex pretreatment processes, which are not conducive to rapid on-site application; second, existing chip structure designs are relatively simple, limiting the sufficiency and sensitivity of antibody binding reactions; third, the integration of detection signal reading systems is insufficient, making it difficult to achieve automated and visualized operation. Therefore, there is an urgent need to develop a structurally optimized, highly integrated microfluidic chip-based rapid quantitative detection device for Aβ42 protein suitable for preclinical screening. Summary of the Invention

[0005] To address the above problems, the present invention aims to provide a microfluidic chip with a swirling structure. The flow channels of the microfluidic chip adopt a serpentine flow layout, including: a direct current channel 11, an offset swirling mixing region 12, and a swirling mixing region 13. The offset mixing zone 12 has a forward flow sidewall 121 and a reverse flow sidewall 122. The two ends of the forward flow sidewall 121 and the reverse flow sidewall 122 are respectively connected to the direct flow channel 11, and the two direct flow channels are offset from each other by a preset distance e in a direction perpendicular to the liquid streamline. The offset vortex mixing region 12 satisfies the following conditions:

[0006] in, The angle between the tangent at the outlet point of the positive flow sidewall 121 and the direct flow channel 11; The angle between the tangent at the outlet point of the reverse flow sidewall 122 and the direct flow path 11.

[0007] In a preferred embodiment, the DC channel 11 on the outlet side of the offset mixing zone 12 is offset to the left relative to the DC channel 11 on the inlet side, perpendicular to the direction of liquid flow.

[0008] In a preferred embodiment, the swirling mixing zone 13 includes an inlet turbulence structure 131, a mid-section turbulence structure 132, and an outlet turbulence structure 133; the inlet turbulence structure 131, the mid-section turbulence structure 132, and the outlet turbulence structure 133 are all arc-shaped structures protruding into the inside of the swirling mixing zone 13.

[0009] In a preferred embodiment, the radius of curvature of the outlet turbulence structure 133 is smaller than the radius of curvature of the inlet turbulence structure 131.

[0010] In a preferred embodiment, the radius of curvature of the mid-section turbulence structure 132 is greater than the radius of curvature of the outlet turbulence structure 133 and the inlet turbulence structure 131.

[0011] The present invention also provides a rapid quantitative antigen detection device, comprising: a microfluidic chip with a gyratory structure, a housing, a central controller, a circulating pump, a proportional valve, an inlet pressure sensor, an outlet pressure sensor, a flow rate sensor, an excitation light source, and an optical camera.

[0012] The present invention also provides a microfluidic chip flow rate control method, implemented based on the aforementioned rapid antigen quantitative detection device, comprising the following steps: S1, Constructing flow resistance in non-uniform regions ,satisfy:

[0013] in, and These are the detection values ​​from the inlet pressure sensor and the outlet pressure sensor, respectively, representing the pressure values ​​at the inlet and outlet ends of the microfluidic chip. The difference between them is the pressure loss along the flow path. The value detected by the flow sensor represents the flow rate of the fluid. Darcy's coefficient of friction is the pre-determined value. D and D are the length and diameter of the flow channel, respectively; For fluid density; This represents the number of offset vortex mixing zones 12 and rotary vortex mixing zones 13; S2. Inject a simulated solution into the microfluidic chip; the simulated solution is PBS liquid with the same composition as the liquid to be detected but without the antigen to be detected; S3. Start the circulating pump and execute vortex excitation control to determine the optimal opening of the proportional valve; S4. Set the proportional valve to the optimal opening and inject the test liquid; S5. Start the excitation light source and optical camera to perform fluorescence detection.

[0014] In a preferred embodiment, step S3 includes the following steps: S31. Set the proportional valve to start from zero opening, with a preset opening step size. Increase the opening degree and obtain the detection values ​​at each opening degree, including the detection values ​​of the inlet pressure sensor, outlet pressure sensor and flow rate sensor; S32. Calculate the corresponding flow resistance in the non-uniform zone based on the detection values ​​at each opening degree. ,in, and And means in the sequence number Simulated liquid flow velocity and flow resistance in non-uniform regions under proportional valve opening; S33. Constructing a set of flow resistance in non-uniform regions ,satisfy:

[0015] in, The number of proportional valve openings represents the number of sampling calculations for flow resistance in the non-uniform region; S34. Function Fitting: Based on the set of flow resistance in non-uniform regions The fitting yields the flow resistance function in the non-uniform region with liquid velocity as the independent variable. ; S35. Finding the derivative function: for the flow resistance function in a non-uniform region. Take the derivative, the derivative function The slope of the tangent line to the flow resistance function in the non-uniform region represents the rate of increase of flow resistance in the non-uniform region. S36. Calculate the vortex excitation point: Obtain the derivative function. The proportional valve opening corresponding to the mutation point This is the optimal opening degree for the proportional valve.

[0016] The present invention also provides the application of the aforementioned microfluidic chip with a gyroscopic structure in the rapid quantitative detection of Aβ42 protein in Alzheimer's disease.

[0017] This invention also provides the application of the aforementioned microfluidic chip flow rate control method in the rapid quantitative detection of Aβ42 protein in Alzheimer's disease.

[0018] Beneficial effects This invention provides a microfluidic chip with a swirling structure and its application in rapid quantitative antigen detection. It effectively excites liquid to form swirling mixing disturbances within the chip, significantly enhancing mixing efficiency and fluorescence signal intensity in the reaction zone. By designing offset and rotary swirling mixing zones in the flow channel and further controlling the geometric parameters of the disturbance structure, asymmetric swirling mixing of the fluid is achieved in localized areas, while avoiding excessive resistance and energy consumption caused by high flow velocities.

[0019] This invention introduces for the first time a mechanism for modeling the flow resistance function in non-uniform regions and identifying the abrupt change point of the derivative function, which enables precise mathematical positioning of the swirling excitation point and determines the optimal opening of the proportional valve. This ensures that the chip is in the optimal flow field state before detection, significantly improving the accuracy and sensitivity of subsequent fluorescence detection.

[0020] The detection device constructed in this invention has real-time flow rate monitoring, adaptive adjustment and quantitative response functions. It is suitable for rapid and quantitative detection of biomarkers such as Aβ42 protein in Alzheimer's disease. It has significant advantages such as high integration, high sensitivity and automatic optimization control, and has good industrialization prospects. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the main structure of the microfluidic chip of the present invention; Figure 2 This is a schematic diagram of the steps of the flow rate control method of the present invention. Detailed Implementation

[0022] To enhance understanding of the present invention, the present invention will be further described in detail below with reference to embodiments. These embodiments are only used to explain the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0023] Example 1 like Figure 1 As shown, this embodiment provides a microfluidic chip structure suitable for rapid biomolecular reactions and fluorescence detection. Its feature is that it integrates an offset mixing region and a rotary mixing region in a serpentine flow layout, which effectively improves the liquid mixing efficiency and microscopic perturbation excitation capability, and is suitable for molecular-level reaction systems such as antigens and nucleic acids.

[0024] First, the main structure of the microfluidic chip was fabricated on a PDMS substrate using photolithography-soft etching technology. The overall chip size is approximately 20 mm × 20 mm × 2 mm, with an internal microchannel width of 200 μm and a depth of 80 μm. The channels include a DC channel 11, an offset swirl mixing region 12, and a rotary swirl mixing region 13 connected in sequence.

[0025] In the offset mixing zone 12, two sidewall structures of equal length are designed, namely the forward flow sidewall 121 and the reverse flow sidewall 122. The two are arranged in an alternating flow direction at the connection of the direct flow channel 11. The direct flow channels connected at both ends are offset from each other by a preset distance e in the direction perpendicular to the liquid streamline, and the specific value of e is 200 μm.

[0026] This region satisfies the following geometric configuration constraints: the angle between the outflow tangent of the positive flow sidewall 121 and the direct flow path 11. satisfy The angle between the outflow tangent of the counterflow sidewall 122 and the direct flow channel 11 satisfy ,and This ensures that the liquid generates asymmetric shear disturbances as it passes through the offset swirling zone.

[0027] in, The angle between the tangent at the outlet point of the positive flow sidewall 121 and the direct flow channel 11; The angle between the tangent at the outlet point of the counterflow sidewall 122 and the direct current channel 11.

[0028] The mixture then enters the swirling mixing zone 13, which contains three consecutively arranged turbulence structures: an inlet turbulence structure 131, a mid-section turbulence structure 132, and an outlet turbulence structure 133. All three structures employ an arc-shaped, inwardly convex design to enhance local backflow and tangential disturbance. Specifically, the radius of curvature of the inlet turbulence structure 131 is 600 μm, that of the mid-section turbulence structure 132 is 900 μm, and that of the outlet turbulence structure 133 is set to 400 μm. The three turbulence structures work synergistically to generate rotational acceleration gradients at different locations, causing multiple lateral backflows and vertical mixing of the liquid, significantly improving the mixing efficiency of the reactants.

[0029] During the test, PBS buffer and sample solution containing fluorescent labels were injected into the chip, and their mixing effect in the channels was observed. The fluid mixing behavior was recorded using a fluorescence microscopy system, and high-frequency streamline perturbations and uniform fluorescence distribution were clearly observed in the vortex mixing region, proving that the structure can effectively induce strong vortex mixing, shorten the molecular diffusion path, and improve the overall reaction efficiency of the chip.

[0030] After being equipped with optical detection components and a micropump control system, this chip is suitable for rapid quantitative analysis of target molecules such as Aβ42 protein, CRP, and IL-6. It has comprehensive performance advantages such as high integration, high throughput, and high sensitivity, which verifies the effectiveness and engineering feasibility of the structural design of this invention.

[0031] Example 2 This embodiment provides a device for rapid quantitative detection of target antigens. It integrates a microfluidic chip control module, a liquid driving and monitoring module, an optical detection module and other multifunctional units. It has high sensitivity, high stability and rapid response capabilities, and is suitable for rapid quantitative detection of biomarkers such as Aβ42 protein and C-reactive protein in Alzheimer's disease.

[0032] The core of the device is a microfluidic chip with a swirling structure. The chip's flow channels adopt a serpentine layout, including a direct current channel, an offset swirling mixing region, and a rotary swirling mixing region. The chip is made of a composite of PDMS and a glass substrate, exhibiting excellent optical transparency and biocompatibility. The chip is encapsulated in a sealed housing, which is injection-molded from polycarbonate material. The housing has internally reserved fluid interfaces, optical windows, and sensor mounting holes to facilitate liquid entry and exit, data acquisition, and optical signal acquisition.

[0033] The fluid control module consists of a miniature circulating pump and a proportional valve. The circulating pump is connected to the chip inlet via a hose to provide a stable drive flow; the proportional valve is located at the front end of the flow path and is used to precisely adjust the injection flow rate. Its opening is controlled in real time by the main control unit to meet the vortex mixing excitation conditions.

[0034] To enable real-time monitoring of fluid parameters, inlet and outlet pressure sensors are respectively configured at the chip inlet and outlet to monitor changes in fluid pressure difference; a flow velocity sensor is configured in the middle section of the chip's main flow channel to collect real-time flow velocity data for calculating the flow resistance g(v) in the non-uniform region and subsequent derivative function analysis.

[0035] In the detection module, a blue LED array (wavelength 480 nm) is used as the excitation source, located below the chip detection area; the optical camera is positioned above the chip, perpendicular to the excitation source, and captures fluorescence signals through a bandpass filter. The camera output signal is converted into grayscale values ​​by the image processing module and then quantitatively analyzed.

[0036] In practice, a simulated solution (PBS buffer) is first injected into the chip. The opening of the proportional valve is adjusted, and various pressure and flow rate values ​​are collected. The flow resistance function G(v) in the non-uniform region is constructed and differentiated to determine the optimal opening of the proportional valve corresponding to the mutation point. Then, the chip is switched to the detection liquid (containing the target antigen), and fluorescence excitation and data acquisition are performed at this optimal opening. Finally, the quantitative concentration value of the target antigen is output.

[0037] Repeated experiments have verified that this device exhibits a good linear response to Aβ42 antigen within a concentration range of 100–1000 pg / mL, with a detection limit as low as 80 pg / mL, a response time of less than 8 minutes, and a deviation of less than 5% compared to ELISA results, demonstrating good accuracy and stability. The device is compact in structure and highly automated in operation, making it suitable for rapid screening and on-site testing scenarios.

[0038] Example 2 This embodiment discloses a rapid quantitative detection device for Aβ42 protein in Alzheimer's disease based on a microfluidic chip, which aims to achieve rapid and accurate detection of Aβ42 protein concentration. It also realizes intelligent scheduling and automatic execution of the detection process through a mathematical model-driven control method, and is suitable for hospital clinical testing, home portable screening or smart medical systems.

[0039] The microfluidic chip with a gyratory structure, housing, central controller, circulating pump, proportional valve, inlet pressure sensor, outlet pressure sensor, flow rate sensor, excitation light source, and optical camera are described.

[0040] During use, the proportional valve is controlled by the central processing unit, and the control current of the proportional valve is R(R). in, for The control current of the proportional valve at any given time. The system is set to a target flow rate range of [value missing]. When the actual flow rate deviates from this range, the main control circuit adjusts the pump speed using a PID control algorithm, calculated as follows:

[0041] Among them, error amount , For the target current, For proportionality coefficient, For integral coefficients, These are the differential coefficients; and They are respectively Time and The current control quantity output by the main control circuit at any given time.

[0042] The detection process is executed based on system status parameters. Control, its values ​​are as follows:

[0043] The main control circuit follows external instructions and detection timing The state transition and state update function are as follows:

[0044] satisfy: This indicates the running time in the current state; This indicates the threshold time required for incubation; Indicates the time required for washing; This indicates that the fluorescence signal acquisition was successful. This means that if any condition is not met, the system will remain in its original state.

[0045] Taking the actual testing process as an example, after the user sends the "START (Start Testing)" command through an external device, the system state changes from S=0 to S=1, and the pump injects the test liquid into the microfluidic chip; after the incubation time is reached, the system automatically enters S=2, the pump switches the channel to inject cleaning liquid, rinses the chip and separates the magnetic beads in the magnetic area; after cleaning is completed, the system enters the S=3 state and starts fluorescence detection and signal acquisition; after the fluorescence signal is successfully acquired, the system enters the S=4 state, and after receiving the "RESET (Reset)" command, the system returns to the S=0 state.

[0046] Example 3 like Figure 2 As shown, this embodiment provides a flow rate control method suitable for swirling excitation optimization in microfluidic systems. It is based on the aforementioned rapid antigen quantitative detection device and determines the optimal opening of the proportional valve through a derivative function mutation point identification mechanism, thereby achieving efficient mixing and stable detection.

[0047] First, based on the configuration of the detection device, the microfluidic chip is connected to a circulating pump, a proportional valve, inlet and outlet pressure sensors, and a flow rate sensor. The chip internally contains multiple offset vortex mixing regions and rotary vortex mixing regions, specifically numbered N.

[0048] S1. Construct the flow resistance function for the non-uniform region. Collect real-time values ​​from the inlet pressure sensor P_in and the outlet pressure sensor P_out to obtain the pressure difference along the fluid path; simultaneously record the values ​​from the velocity sensor. Based on the pre-determined Darcy friction coefficient, chip channel length, diameter, and fluid density, substitute these values ​​into the following formula to calculate the unit resistance value for the non-uniform region. :

[0049] in, and These are the detection values ​​from the inlet pressure sensor and the outlet pressure sensor, respectively, representing the pressure values ​​at the inlet and outlet ends of the microfluidic chip. The difference between them is the pressure loss along the flow path. The value detected by the flow sensor represents the flow rate of the fluid. Darcy's coefficient of friction is the pre-determined value. D and D are the length and diameter of the flow channel, respectively; For fluid density; This represents the number of offset vortex mixing zones 12 and rotary vortex mixing zones 13; S2. Inject PBS simulation solution into the microfluidic chip. The simulation solution does not contain the target antigen, but its composition is the same as that of the detection liquid, and it is used for calibration experiments.

[0050] S3. Start the circulating pump and execute the vortex excitation control process. The following sub-steps are performed during this process: S31. Set the initial opening of the proportional valve to 0, and gradually increase the valve opening by step size. (e.g., 1%) Incremental opening, data collected after each change. , and Real-time data, and numbered as Continue until the maximum safe opening is reached.

[0051] S32. For each opening degree, based on the data collected... , and The value is substituted into the formula to calculate the corresponding value. .

[0052] S33. Constructing a set of flow resistance in non-uniform regions ,satisfy:

[0053] in, The number of proportional valve openings represents the number of sampling calculations for flow resistance in the non-uniform region.

[0054] S34, For sets Polynomial or piecewise fitting is used to construct the flow resistance function in the non-uniform region. This makes it continuous and differentiable, reflecting the overall trend of resistance changing with flow velocity.

[0055] S35, Regarding the function Take the derivative to obtain the derivative function. This function characterizes the growth rate of resistance at different flow rates, making it easier to identify abnormal trends in resistance changes.

[0056] S36, Calculation The point of sudden change is used to identify the flow velocity where the rate of change of the derivative suddenly increases. This allows us to map the corresponding proportional valve opening. This is denoted as the swirling excitation point, which is the optimal opening setting value in this system.

[0057] S4, Set the proportional valve to At the corresponding opening degree, close the simulation liquid injection port, switch and inject the detection liquid containing the target antigen.

[0058] S5. Activate the excitation light source (such as a 480 nm blue LED) and optical camera to perform fluorescence detection and record the signal response, thereby achieving quantitative analysis of the antigen.

[0059] This method, by introducing differentiable function modeling and mutation point analysis techniques, achieves mathematical positioning of the optimal vortex mixing state, avoiding the inefficiency and error accumulation of traditional empirical debugging, and significantly improving the fluid control accuracy and fluorescence detection reliability of microfluidic chips. It is especially suitable for the early parameter optimization and standardized operation process construction of high-sensitivity bioanalysis platforms.

[0060] 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 illustrative of the principles of 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 having a spiral structure, characterized in that, The flow channel of the microfluidic chip adopts a serpentine flow layout, and comprises a straight flow channel (11), a deflected spiral mixing area (12), and a rotating spiral mixing area (13); The deflected spiral mixing area (12) has a normal flow side wall (121) and a reverse flow side wall (122), two ends of the normal flow side wall (121) and the reverse flow side wall (122) are connected with the straight flow channel (11) respectively, and the two straight flow channels connected with each other are offset by a preset distance e in a direction perpendicular to the liquid flow line; The deflected spiral mixing area (12) satisfies the following condition: ； wherein, is the angle between the tangent to the outflow point of the positive flow side wall (121) and the straight flow channel (11); is the angle between the tangent to the outflow point of the negative flow side wall (122) and the straight flow channel (11).

2. The microfluidic chip with a spiral structure according to claim 1, wherein, The straight flow channel (11) on the outlet side of the deflected spiral mixing area (12) is offset to the left side perpendicular to the liquid flow direction relative to the straight flow channel (11) on the inlet side.

3. The microfluidic chip with a spiral structure according to claim 1, wherein, The rotating spiral mixing area (13) comprises an inlet disturbance structure (131), a middle disturbance structure (132), and an outlet disturbance structure (133); The inlet disturbance structure (131), the middle disturbance structure (132), and the outlet disturbance structure (133) are all circular arc structures protruding inwardly to the rotating spiral mixing area (13).

4. The microfluidic chip with a spiral structure according to claim 3, characterized in that, The curvature radius of the outlet disturbance structure (133) is smaller than that of the inlet disturbance structure (131).

5. The microfluidic chip with a rotating structure according to claim 3 or 4, characterized in that, The curvature radius of the middle disturbance structure (132) is greater than that of the outlet disturbance structure (133) and the inlet disturbance structure (131).

6. A rapid quantitative antigen detection device, characterized by, Comprise: The microfluidic chip with a rotating structure, the housing, the central controller, the circulating pump, the proportional valve, the inlet pressure sensor, the outlet pressure sensor, the flow rate sensor, the excitation light source, and the optical camera according to any one of claims 1-5.

7. A microfluidic chip flow rate control method based on the rapid quantitative detection device of claim 6, characterized in that, Comprise the following steps: S1. Constructing non-uniform zone flow resistance , satisfies: ； wherein, and are the detection values of the inlet pressure sensor and the outlet pressure sensor, respectively, representing the pressure values at the inlet end and the outlet end of the microfluidic chip, and the difference between them is the pressure loss along the flow path; is the detection value of the flow rate sensor, representing the flow rate of the fluid; is the Darcy friction factor, which is a pre-determined value; and D are the length and diameter of the flow path, respectively; is the fluid density; is the number of offset spiral mixing zones (12) and rotating spiral mixing zones (13). S2, inject the simulation liquid into the microfluidic chip; the simulation liquid adopts a PBS liquid which is the same as the liquid component to be detected but does not contain the antigen to be detected; S3, start the circulating pump and perform the spiral mixing excitation control to determine the best opening degree of the proportional valve; S4, set the proportional valve to the best opening degree and inject the detection liquid; S5, start the excitation light source and the optical camera and perform the fluorescence detection.

8. The microfluidic chip flow rate control method of claim 7, wherein, Step S3 comprises the following steps: S31, set the proportional valve from zero opening degree to preset opening degree step Increase the opening degree and obtain the detection value at each opening degree, including: the detection value of the inlet pressure sensor, the outlet pressure sensor and the flow rate sensor; S32、According to the detection value under each opening, calculate the corresponding non-uniform zone flow resistance wherein, and and represent the analog liquid flow rate and non-uniform zone flow resistance under the proportional valve opening of serial number . S33, constructing a set of non-uniform zone flow resistances , satisfies: ； wherein, is the number of open degrees of the proportional valve, indicating the number of sampling calculations of the non-uniform zone flow resistance; S34, function fitting: from the set of heterogeneous zone flow resistances fitting results in a function of the heterogeneous zone flow resistance as a function of the liquid flow rate ; S35, Derivation: Derivation of the flow resistance function of the non-uniform region Derivation is the tangent slope of the flow resistance function of the non-uniform region, indicating the increasing rate of the flow resistance of the non-uniform region; S36, calculate the spin-mixing excitation point: find the derivative function The proportional valve opening corresponding to the mutation point , as the best opening of the proportional valve.

9. The application of the microfluidic chip with a rotating structure according to any one of claims 1-5 in rapid quantitative detection of Aβ42 protein for Alzheimer's disease.

10. The application of the microfluidic chip flow rate control method according to any one of claims 7-8 in rapid quantitative detection of Aβ42 protein for Alzheimer's disease.

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