A method and device for solute clearance in hemodialysis with precise control of membrane pore size

Abstract

The application discloses a hemodialysis solute removal method and device with precise control of membrane pore size, and belongs to the technical field of blood purification. The dialysis blood and dialysate are introduced into the two sides of the dialysis membrane with a double-skin heterogeneous structure for dynamic regulation, the characteristic signals of metabolic solutes and plasma functional proteins in the blood are collected, and the signals are input into an adaptive pore size decision model to output target pore size and electric field intensity parameters. The reversible conformation change of the stimulus-responsive polymer chain segment in the membrane is driven by a low-frequency alternating electric field, the effective screening pore size of the membrane channel is precisely controlled, and the pore size is locked in the threshold interval of small molecule solute permeation and complete interception of plasma functional proteins. The solute is removed in a graded and targeted manner by combining the axial gradient pore channel in the membrane and the radial charge screening double mechanism. The membrane surface pollution layer is stripped by a periodic micro-pulsating flow field driven by piezoelectricity, and the mass transfer stability is improved. The application realizes automatic and precise operation of the dialysis process, and improves the solute removal efficiency and the plasma protein protection effect.

Description

Technical Field

[0001] This invention relates to the field of blood purification technology, specifically to a method and device for removing solutes in hemodialysis with precise control of membrane pore size. Background Technology

[0002] Hemodialysis, as a core renal replacement therapy for patients with end-stage renal disease, relies heavily on precise monitoring and protocol planning of solute clearance. Currently, clinical practice largely depends on post-treatment sampling for solute clearance rate assessment, which exhibits significant lag and fails to reflect real-time changes during dialysis, nor provide a reliable basis for dynamic adjustments to treatment protocols. Furthermore, individual differences among patients, disease progression, and physiological fluctuations during treatment make it difficult for fixed dialysis protocols to achieve optimal therapeutic effects. With the deepening of precision medicine concepts, clinicians are placing higher demands on real-time monitoring, dynamic assessment, and individualized protocol planning for the dialysis process. Traditional offline assessment and experience-based protocol development methods have become key bottlenecks restricting the upgrading of hemodialysis technology.

[0003] Real-time monitoring and protocol optimization have become important directions in the development of hemodialysis technology. By continuously collecting and analyzing key parameters during dialysis, precise control of treatment efficacy can be achieved. Studies have shown a stable correlation between dialysate conductivity and solute concentration. By monitoring changes in the conductivity of the dialysate inlet and outlet in real time, solute clearance efficiency can be effectively inverted. Furthermore, hybrid therapy planning based on a shared dialysis efficacy index can integrate the advantages of different dialysis modalities, providing patients with more targeted treatment plans. However, current technologies still have significant shortcomings in terms of the accuracy of real-time monitoring, the flexibility of protocol planning, and the effectiveness of multi-modal synergy, failing to meet the clinical demand for efficient, precise, and personalized dialysis treatment.

[0004] Chinese patent (publication number: CN106938063A) discloses a solute clearance monitoring system and method for blood purification equipment. By connecting a conductivity detection device in series between the second inlet and the second outlet of the blood filter, real-time monitoring of the clearance solute concentration is achieved without changing the concentration of concentrated electrolyte solutions A and B during the monitoring process, effectively improving the convenience and accuracy of monitoring. This patent breaks through the limitations of traditional offline sampling and detection, and for the first time applies real-time conductivity monitoring technology to the dynamic evaluation of solute clearance rate, clarifying the correlation mechanism between conductivity changes and the solute clearance kinetic model. However, there are still significant shortcomings: it only focuses on solute clearance monitoring under a single hemodialysis mode, and does not cover the scenario of combined peritoneal dialysis and hemodialysis therapy; the monitoring results are mainly used for process feedback, lacking the ability to intelligently plan and optimize subsequent treatment plans; and it does not establish a deep coupling with the individual physiological parameters of patients, making it difficult to achieve truly personalized treatment. US Patent (Publication No.: US08088094B2) proposes a planning method and apparatus for a mixed peritoneal dialysis and hemodialysis therapy. By introducing a shared dialysis efficacy index M / C(0) / VB, the therapeutic effects of peritoneal dialysis (PD) and hemodialysis (HD) are integrated into a unified sum, achieving a simple and clear planning of the mixed treatment plan. This patent effectively solves the problem of difficulty in quantifying and comparing the effects of different dialysis modes, significantly improving the scientific nature and flexibility of the plan planning. However, this patent also has limitations: the plan planning is highly dependent on a pre-set index model, lacks a dynamic response and adjustment mechanism for changes in the patient's physiological state during real-time treatment, cannot form a closed loop between process data and plan planning, and has limited adaptability to complex clinical scenarios.

[0005] Therefore, there is an urgent need for a precise control method for solute removal in hemodialysis to solve the common problems of existing technologies, such as single monitoring mode, rigid planning schemes, and insufficient individualization. Summary of the Invention

[0006] Based on the above-mentioned technical problems, this application discloses a method and apparatus for precisely controlling the membrane pore size of hemodialysis solute removal. The method for precisely controlling the membrane pore size of hemodialysis solute removal specifically includes: Blood to be dialyzed and dialysate are obtained and introduced into both sides of a dynamically regulated dialysis membrane with a bilayer heterostructure. The particle size and concentration characteristics of metabolic solutes and plasma functional proteins in blood are collected in real time. The particle size and concentration characteristics are input into an adaptive aperture decision model, which outputs the target regulating aperture and the applied electric field strength. By applying a low-frequency alternating electric field to drive the reversible conformational contraction and expansion of the membrane channels, the effective sieving pore size of the membrane can be controlled, so that the pore size is locked within the threshold range where metabolic solutes are permeable and plasma functional proteins are completely retained. By employing a dual-mechanism synergistic technology of axial gradient channels and radial charge sieving within the membrane, solutes of different particle sizes can be selectively permeated in stages and targetedly removed in layers. Controllable micro-vortices are generated by periodic micro-pulsating flow fields on the membrane surface to peel off the solute concentration polarization layer and protein adsorption layer on the membrane surface, thereby regulating pore size precision and mass transfer stability. The purified blood, after being graded and enhanced in flow field, is returned to the body, completing a single, precise hemodialysis solute removal cycle.

[0007] Preferably, the dynamically regulated dialysis membrane with a dual-layer heterostructure is composed of an outer porous support layer and an inner composite selective layer. The outer support layer has a through-pore structure with a pore size set to provide mechanical support and maintain fluid flux. The inner composite selective layer is embedded with covalently grafted stimulus-responsive polymer segments. These polymer segments are functionalized copolymer derivatives with both temperature-sensitive and electro-sensitive properties. Under the action of a low-frequency alternating electric field, they undergo dipole rearrangement and segmental cooperative movement, inducing a reversible conformational change in the dialysis channel.

[0008] Preferably, the frequency of the low-frequency alternating electric field is set within a frequency range capable of exciting macroscopic conformational changes in polymer chain segments, and the dynamic adjustment formula for the electric field strength is: ,in, The applied electric field intensity vector modulus, The electric field coupling coefficient is... The characteristic particle size of the target metabolic solute in the current blood. This represents the critical particle size cutoff for plasma functional proteins. This represents the spatial gradient modulus of solute concentration. This is the gradient suppression constant. It is a non-linear exponential factor. For temperature sensitivity coefficient, For the local real-time temperature of the membrane, The phase transition response temperature reference value of the polymer chain segment is used to control the extension range of the polymer chain segment.

[0009] Preferably, the adaptive pore size decision model is constructed based on a multi-parameter feedback mechanism. Input variables include real-time detected metabolic solute particle size distribution function, plasma protein concentration field, transmembrane pressure difference, and electric field response factor. The evolution structure of the effective pore size of the membrane channel is obtained by constructing partial differential equations, forming a dynamic coupling between solute flux and pore size deformation. The formula is as follows: ,in, The effective pore radius of the membrane channel as a function of time. For time variables, For the response sensitivity coefficient, Let be the solute particle size distribution function. For particle size variable, and These represent the lower and upper limits of the integration interval, respectively. The migration rate of the solute in the medium. The solute flux vector. For feedback control coefficients, The target aperture reference value, For the diffusion smoothing term coefficients, For the Laplace operator.

[0010] Preferably, the low-frequency alternating electric field is applied through a pair of flexible conductive electrodes arranged parallel to each other on both sides of the membrane. The electric field modulation waveform is an asymmetric square wave, and the ratio of its positive pulse width to its negative pulse width is dynamically adjusted according to the free energy barrier difference between the open and closed states of the channel, so as to control the extension and retraction dynamics of the polymer chain segments; the pulse width ratio formula is: ,in, The pulse width under a positive electric field. The pulse width under the influence of a negative electric field. The free energy barrier difference for the transition of the channel from the closed state to the open state. The free energy barrier difference for the transition from the open state to the closed state of the channel. Boltzmann's constant, Using absolute temperature, the opening and closing time ratio of the dialysis channel is precisely controlled by the exponential dependence between the ratio of positive and negative pulse widths of the electric field waveform and the channel conformational transition free energy difference and thermodynamic temperature.

[0011] Preferably, the conformational changes of the dialysis channel are monitored in real time using a fluorescence resonance energy transfer probe. The probe is labeled between two adjacent polymer segments. When the channel contracts, the distance between the donor and acceptor fluorescent molecules shortens to within the effective energy transfer distance, and the FRET efficiency increases significantly. The value of FRET is calculated by the following formula: ,in, For fluorescence resonance energy transfer efficiency, This represents the actual distance between the donor and acceptor fluorescent molecules. This is the critical distance.

[0012] Preferably, the synergistic technology of the axial gradient channels and radial charge sieving within the membrane specifically includes: The intramembrane axial gradient pore structure exhibits a non-linear decreasing distribution along the blood flow direction, and the pore size function follows an exponential decay form, as shown in the formula: ,in, Axial position The radius of the channel at that location, The initial pore radius at the membrane inlet end is... The aperture gradient attenuation coefficient is... The effective axial length of the membrane, These are coordinate variables along the direction of blood flow; The radial charge sieving mechanism introduces a fixed charge density with a gradient distribution on the pore wall. This charge density distribution is coupled with the pore size gradient and the electrolyte concentration field. The formula for the fixed charge density distribution is: ,in, Radial position Axial position Fixed charge density at the location, As the reference charge density, and These represent the maximum and minimum radius limits of the channel's radial direction, respectively. The parameter is the charge non-uniformity index. The electrolyte concentration coupling coefficient is... Electrolyte concentration along the axial direction The gradient in the direction is used to construct a radial electric field distribution for auxiliary solute sieving.

[0013] Preferably, the graded selectivity comprehensively considers the diffusion and convection competition mechanisms of solutes in the gradient channels. Its clearance rate for any type of solute is defined as an integral along the axial position, quantifying the coupling contribution of membrane permeability, effective mass transfer area, and concentration gradient at different positions. The formula is: ,in, For the first Total clearance of solutes For position The membrane permeability coefficient to the solute at that location. For the local effective mass transfer area, and These represent the solute concentrations on the blood side and the dialysate side, respectively. For blood flow, For the effective length of the membrane, The coordinate variable along the membrane axis realizes the cumulative effect of solute removal rate along the membrane length direction, and the exponential term characterizes the correction effect of local mass transfer resistance on concentration difference, and calculates the solute flux under a specific pore size distribution.

[0014] Preferably, the periodic micro-pulsating flow field on the membrane surface is generated by a piezoelectric drive array integrated around the membrane module. The drive signal is a frequency-modulated sine wave superimposed with random noise terms, and its frequency range is set in a frequency band capable of inducing fluid boundary layer instability. The micro-pulsations cause local velocity fluctuations, which follow the unsteady Navier-Stokes equations. The generation mechanism of micro-vortices is obtained by introducing an equivalent piezoelectric excitation source term, as shown in the following formula: ,in, For fluid density, For flow velocity vectors, For time, For gradient operators, For pressure, For dynamic viscosity, For the Laplace operator, The equivalent force source term generated by piezoelectric excitation is used to determine the variation of the fluid velocity field with time and space under the action of the piezoelectric excitation force source term, thus generating a specific micro-vortex field structure.

[0015] The aforementioned hemodialysis solute removal device with precisely controlled membrane pore size includes: The blood circulation module is used to draw out the patient's blood and deliver it to the dialysis unit, and includes a blood pump, arterial and venous tubing, and a bubble detector. A dual-layer heterostructure dynamic regulation dialysis membrane assembly is disposed inside the dialysis unit. The two sides of the membrane are respectively connected to the blood channel and the dialysate channel, and the membrane integrates channels and piezoelectric excitation structures. Stimulus-responsive polymer brushes are grafted into the channels. A multimodal sensor array is arranged at the membrane inlet and outlet and on the surface to collect real-time signals of the particle size, concentration, flow rate, temperature and conductivity of metabolic solutes in the blood, and transmit the signals to the control unit. An adaptive control unit receives sensor data and runs an aperture decision model based on a multi-parameter feedback mechanism, outputting electric field control commands and flow field excitation parameters. The model includes partial differential equations describing the evolution of the effective aperture of the membrane channel. A low-frequency alternating electric field generator is connected to electrodes on both sides of the membrane and is used to apply an asymmetric square wave electric field to drive the conformational change of the channel. The pulse width ratio of the electric field is determined according to the free energy barrier difference between the open and closed states of the channel. A piezoelectric drive power supply, connected to a piezoelectric excitation ring, is used to generate a periodic micro-pulsating flow field to strip the concentration polarization layer on the film surface. The flow field is driven by the piezoelectric excitation equivalent source term in the unsteady Navier-Stokes equations. The dialysate supply and waste discharge module is used to provide fresh dialysate and discharge waste containing toxins; The central monitoring terminal is used to visually display the dynamics of membrane pore size, solute removal process, and system operating status, and supports remote intervention and parameter adjustment.

[0016] Compared with the prior art, the technical solution of this application has the following technical effects: This invention enables precise control of the dialysis membrane pore size, stably locking the pore size within a threshold range where metabolic solutes can pass through while plasma functional proteins are completely retained. This ensures a synergistic balance between solute clearance and protein retention, maintaining stable blood components and a safe dialysis process. Based on real-time collected blood solute and protein signals, the pore size parameters are dynamically adjusted to ensure optimal screening performance at all times, regardless of the treatment stage or patient condition. This effectively avoids treatment deviations caused by pore size fluctuations and improves the reliability and safety of the dialysis process.

[0017] This invention utilizes the synergistic effect of axial gradient channels and radial charge sieving mechanisms to achieve graded selective permeation and stratified targeted removal of metabolic solutes of different particle sizes, thereby improving the specificity of solute sieving and the overall removal efficiency of dialysis. The gradient channel structure guides the orderly migration of solutes according to molecular size, while the charge sieving mechanism further enhances the selectivity for specific solutes, enabling efficient removal of both medium and large molecular toxins and small molecule metabolites, while avoiding non-specific retention.

[0018] This invention generates controllable micro-vortices through a periodic micro-pulsating flow field on the membrane surface, effectively stripping away the solute concentration polarization layer and protein adsorption layer on the membrane surface. This maintains the precision of pore size control and stable mass transfer, extending the stable operating cycle of the dialysis membrane. The continuous action of the micro-vortices disrupts the adhesion of contaminants on the membrane surface, keeping the membrane pores open and clean. This reduces efficiency degradation caused by membrane fouling, lowers the need for frequent membrane module replacements, improves the operating efficiency and economy of the equipment, and also reduces the treatment burden on patients.

[0019] This invention forms a complete closed-loop system integrating multimodal signal sensing, adaptive decision computation, and multi-physics field collaborative driving, achieving automated and precise control of the entire hemodialysis process. This improves the controllability and operational stability of the dialysis process, ensuring overall treatment effectiveness. The system can autonomously complete the entire process of signal acquisition, decision computation, and field driving without manual intervention, ensuring the consistency and controllability of the treatment process. Simultaneously, through the synergistic effect of multiple physical fields, it optimizes dialysis efficiency and safety, providing patients with more reliable and efficient treatment protection.

[0020] The above description is only an overview of the technical solution of this application. In order to better understand the technical means of this application and implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this application more obvious and understandable, the preferred embodiments of this application are described in detail below with reference to the accompanying drawings.

[0021] The above and other objects, advantages and features of this application will become more apparent to those skilled in the art from the following detailed description of specific embodiments in conjunction with the accompanying drawings. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0023] Based on the description of the figures and their corresponding technical content in the document, the titles of the figures are as follows: Figure 1 A schematic diagram of the overall process of a hemodialysis solute removal method with precise control of membrane pore size; Figure 2 A schematic diagram of the layered structure and cross-sectional morphology of a dialysis membrane dynamically regulated by a dual-layer heterostructure. Figure 3 , Input-output architecture diagram of real-time acquisition of blood characteristic signals and adaptive aperture decision model; Figure 4 Schematic diagram of reversible conformational changes and aperture control of membrane channels driven by low-frequency alternating electric fields; Figure 5 A schematic diagram of the overall structure of a hemodialysis solute removal device with precise membrane pore size control; Figure 6 Imaging maps showing the global distribution and uniformity of effective pore size in membrane channels; Figure 7 Comparative analysis of membrane protein adsorption amount and concentration polarization layer thickness; Figure 8 Dynamic response characteristics of membrane pore size as a function of temperature; Figure 9 Correlation surface plots of the effect of temperature fluctuations on the permeability of different solutes; Figure 10 A comparative analysis of the overall performance of multiple implementation examples and a quantitative analysis chart of core indicators. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, 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 some embodiments of this application, not all embodiments. In the following description, specific details such as specific configurations and components are provided merely to help fully understand the embodiments of this application. Therefore, those skilled in the art should understand that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. In addition, for clarity and brevity, descriptions of known functions and structures are omitted in the embodiments.

[0025] It should be understood that the phrase "an embodiment" or "this embodiment" throughout the specification means that a specific feature, structure, or characteristic related to the embodiment is included in at least one embodiment of this application. Therefore, "an embodiment" or "this embodiment" appearing throughout the specification does not necessarily refer to the same embodiment. Furthermore, these specific features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0026] Furthermore, reference numerals and / or letters may be repeated in different examples within this application. Such repetition is for the purpose of simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or settings discussed.

[0027] In this article, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist simultaneously. The term " / and" in this article describes another type of relationship between related objects, indicating that two relationships can exist. For example, A / and B can mean: A exists alone, and A and B exist alone. In addition, the character " / " in this article generally indicates that the related objects before and after it are in an "or" relationship.

[0028] In this article, the term "at least one" is merely a description of the relationship between related objects, indicating that there can be three relationships. For example, "at least one of A and B" can mean: A exists alone, A and B exist simultaneously, or B exists alone.

[0029] It should also be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion.

[0030] Example 1: This example mainly describes a method for solute removal in hemodialysis with precise control of membrane pore size, such as... Figure 1 As shown, it specifically includes: Blood to be dialyzed and dialysate are obtained and introduced into both sides of a dynamically regulated dialysis membrane with a bilayer heterostructure. The particle size and concentration characteristics of metabolic solutes and plasma functional proteins in blood are collected in real time. The particle size and concentration characteristics are input into an adaptive aperture decision model, which outputs the target regulating aperture and the applied electric field strength. By applying a low-frequency alternating electric field to drive the reversible conformational contraction and expansion of the membrane channels, the effective sieving pore size of the membrane can be controlled, so that the pore size is locked within the threshold range where metabolic solutes are permeable and plasma functional proteins are completely retained. By employing a dual-mechanism synergistic technology of axial gradient channels and radial charge sieving within the membrane, solutes of different particle sizes can be selectively permeated in stages and targetedly removed in layers. Controllable micro-vortices are generated by periodic micro-pulsating flow fields on the membrane surface to peel off the solute concentration polarization layer and protein adsorption layer on the membrane surface, thereby regulating pore size precision and mass transfer stability. The purified blood, after being graded and enhanced in flow field, is returned to the body, completing a single, precise hemodialysis solute removal cycle.

[0031] Further, the blood to be dialyzed and the dialysate are obtained and introduced separately into both sides of a dynamically regulated dialysis membrane with a bilayer heterogeneous structure, such as... Figure 2 As shown, this dynamically controlled dialysis membrane adopts a composite structure of an outer porous support layer and an inner composite selective layer. It is prepared using a phase inversion method and surface grafting modification process, with an overall thickness controlled at 120–150 μm. The outer porous support layer accounts for approximately 70% of the thickness, and the inner composite selective layer accounts for approximately 30%. The outer porous support layer employs a through-hole macroporous structure design, with its pore size set to a fixed range of 5–10 μm to meet only the requirements of mechanical support strength and fluid flux maintenance. The porosity is controlled at 65–75%, and it does not participate in the solute sieving process, only providing structural support and fluid flow channels for the inner composite selective layer. The porosity of the outer porous support layer... With penetration rate Satisfying the Kozeny–Carman relationship: ,in The equivalent particle size of the support layer is 0.5–1.0 μm, which quantitatively describes the influence of the support layer structural parameters on fluid transport performance. It ensures that a stable fluid flux is maintained while providing sufficient mechanical strength. The tensile strength of the support layer is not less than 12 MPa, and the burst pressure is not less than 0.4 MPa, which can withstand the routine pressure fluctuations during clinical dialysis.

[0032] The inner composite selective layer is covalently grafted with stimulus-responsive polymer segments. These polymer segments are functionalized copolymer derivatives possessing both thermosensitive and electrosensitive responsive properties. Their backbone is a copolymer of N-isopropylacrylamide (NIPAM) and vinylimidazole (VIM) monomers in a molar ratio controlled between 4:1 and 6:1. The side chains are modified with quaternary ammonium salt functional groups, and the grafting density is 0.8–1.2 mmol / cm². Under the influence of an external physical field, this copolymer derivative undergoes a conformational transformation of its molecular segments, and the free energy change of this conformational transformation is... With electric field strength ,temperature The relationship is: ,in The conformational free energy is the energy of conformation without an external field, ranging from -12 to -8 kJ / mol. The electric field response coefficient has a value ranging from 0.3 to 0.7 kJ / (mol·(V / m)²). The temperature response coefficient ranges from 0.4 to 0.8 kJ / (mol·K). The critical temperature for phase transition is controlled at 32–34℃. This relationship provides a thermodynamic basis for the reversible control of the pore size of the membrane channel. When the electric field strength or temperature exceeds the critical threshold, the change in free energy drives the molecular chain segments to transform from the extended state to the coiled state, and the pore size shrinks accordingly.

[0033] The blood to be dialyzed flows into the inner side of the membrane module along the blood flow channel, while the dialysate flows into the outer side of the membrane module along the dialysate flow channel, maintaining a stable flow state on both sides. The membrane module adopts a hollow fiber structure with an inner diameter of 200–250 μm, an outer diameter of 280–320 μm, and an effective packing area of ​​1.2–1.5 m². Blood side flow velocity... With dialysate side flow rate Satisfying the Reynolds number constraint: ,in , The densities of blood and dialysate are 1.05–1.06 g / cm³ and 1.01–1.02 g / cm³, respectively. , The values ​​are the dynamic viscosities of blood and dialysate, respectively, ranging from 3.5 to 4.5 mPa·s and 0.9 to 1.1 mPa·s. The hydraulic diameter of the flow channel is [value missing], for hollow fiber flow channels. Equal to the fiber inner diameter, this constraint ensures that the fluid flow is in a laminar state (Re<2000), avoiding protein denaturation and membrane structure damage caused by turbulence, and providing a stable fluid environment for subsequent solute sieving and removal processes.

[0034] Furthermore, such as Figure 3 As shown, the particle size and concentration characteristics of metabolic solutes and plasma functional proteins in blood are acquired in real time. These characteristics are then input into an adaptive pore size decision model, which outputs the target pore size and the applied electric field strength. The signal acquisition module consists of an online dynamic light scattering instrument, an ultraviolet spectrophotometer, and a pressure sensor, installed at the inlet and outlet of the membrane module. The sampling frequency is 10Hz, enabling real-time acquisition of the metabolic solute particle size distribution function. Plasma protein concentration field distribution data Transmembrane pressure difference value and electric field response factor parameters The metabolic solutes mainly include small molecule toxins such as urea (particle size approximately 0.3–0.5 nm), creatinine (particle size approximately 0.4–0.6 nm), and uric acid (particle size approximately 0.5–0.7 nm), while the plasma functional proteins mainly include albumin (particle size approximately 7–8 nm) and immunoglobulins (particle size approximately 10–12 nm). The critical cutoff particle size is set at 6.5–7.0 nm.

[0035] The adaptive pore size decision model is built upon a multi-parameter feedback mechanism. It employs the finite element method and iterative optimization algorithms for real-time computation, with a computation step size controlled within 0.1 seconds to ensure a response delay of no more than 1 second. The model quantitatively describes the evolution of the effective pore size structure of the membrane channel by constructing multiple sets of partial differential equations, establishing a dynamic coupling relationship between solute flux and pore size deformation. Its core coupling formula is: ,in The effective pore radius of the membrane channel varies continuously over time, with an initial value of 8–10 nm. The time variable in the dialysis process. This is the model response sensitivity coefficient, with a value ranging from 0.05 to 0.15 s. -1 It is used to adjust the model's response rate to the input signal. The particle size distribution function of the metabolic solute is given by a log-normal distribution. For solute particle size, the lower limit of the integration interval is... 0.3nm, upper limit It is 0.7nm. This is a parameter representing the mobility of a solute in blood, and its value is given by the Stokes–Einstein equation. Confirmed, among which The charges of urea, creatinine, and uric acid are 0, -1, and -1, respectively, representing the solute charge. The radius of the solute in hydrodynamics is denoted as . Let be the solute flux vector, representing the mass of solute passing through a unit membrane area per unit time. Its formula is: ,in Let be the solute diffusion coefficient. The diffusion coefficients for urea, creatinine, and uric acid are 1.3 × 10⁻⁶. -9 1.0×10 -9 0.8×10 -9 m² / s, This refers to the solute concentration. The electric field intensity vector, This is the feedback control coefficient, with a value ranging from 0.2 to 0.4s. -1 This is used to correct the deviation between the target aperture and the actual aperture. The target pore size reference value calculated by the model is determined by the solute sieving threshold condition. Confirmed, among which Characteristic particle size of metabolic solutes The critical cutoff particle size for plasma proteins. This is the diffusion smoothing coefficient, with a value ranging from 0.01 to 0.03 m² / s, used to eliminate numerical fluctuations in the aperture calculation process. This is the Laplace operator, used to describe the spatial distribution variation of the aperture radius.

[0036] The model also incorporates a transmembrane pressure differential correction term to address the impact of pressure fluctuations on pore size control during dialysis: ,in The pressure difference response coefficient ranges from 0.001 to 0.003 Pa. -1 ·s -1 , The baseline transmembrane pressure difference is set to 0.02 MPa. This correction term ensures the mechanical stability of the membrane structure during pore size control, preventing membrane rupture caused by sudden pressure increases. The model performs real-time calculations based on the above formula, outputting target pore size and electric field strength values ​​that match the current blood state. The target pore size range is 3.5–4.0 nm, and the electric field strength range is 50–150 V / cm, providing precise control commands for subsequent electric field application and pore size control.

[0037] Furthermore, such as Figure 4 As shown, by applying a low-frequency alternating electric field to drive reversible conformational contraction and expansion of the membrane channels, the effective sieving pore size within the membrane is controlled, locking the pore size within the threshold range where metabolic solutes permeate while plasma functional proteins are completely retained. The low-frequency alternating electric field is applied by a pair of flexible conductive electrodes arranged parallel to each other on both sides of the dynamically controlled dialysis membrane. The electrode material is a polyimide film doped with silver nanowires. The silver nanowires have a diameter of 20–30 nm, a length of 10–20 μm, and a doping concentration of 5–8 wt%, with a sheet resistivity of [missing information]. satisfy: ,in The resistivity of the electrode material ranges from 1.5 to 2.5 × 10⁻⁶. -6 Ω·cm, The electrode thickness is controlled at 50–80 μm. This design ensures a uniform distribution of the electric field on the film surface, with the electric field strength deviation not exceeding ±5%, thus avoiding polymer chain degradation caused by excessively high local electric fields.

[0038] The electric field modulation waveform uses an asymmetric square wave. The ratio of the positive to negative pulse width of this asymmetric square wave is dynamically adjusted based on the free energy barrier difference between the open and closed states of the intramembrane channels. With negative pulse width The formula for calculating the proportion is: ,in The free energy barrier difference for the transition of the channel from the closed state to the open state. The free energy barrier difference for the transition of the channel from the open state to the closed state. is the Boltzmann constant, with a value of 1.38 × 10⁻⁶. -23 J / K, The absolute temperature of the fluid medium is controlled at 310–312 K. By leveraging the exponential dependence between the ratio of positive to negative pulse widths of the electric field waveform and the channel conformational transition free energy difference and thermodynamic temperature, precise control of the proportion of dialysis channel opening and closing time is achieved. The positive pulse width proportion is controlled at 60–70%, ensuring that the channel is open for a sufficient amount of time to complete solute permeation.

[0039] The frequency of the low-frequency alternating electric field is confined to the range of frequencies that can excite macroscopic conformational changes in polymer chain segments within the inner composite selective layer, specifically 10–50 Hz. With polymer segment relaxation time Satisfying the Debye relationship: Among them, relaxation time The value ranges from 3 to 32 ms and is related to the polymer chain length and grafting density. This ensures that the electric field frequency matches the chain relaxation frequency, maximizing the conformational transition efficiency. The electric field strength is dynamically adjusted using the following formula: ,in The applied electric field intensity vector modulus, The electric field coupling coefficient ranges from 80 to 120 (V / cm)·nm. -1 This is used to coordinate the response of the electric field to the polymer chain segments. The characteristic particle size of the target metabolic solute in the current blood. This represents the critical particle size cutoff for plasma functional proteins. The spatial gradient modulus of solute concentration is given by... Calculations were performed, ranging from 0.1 to 0.5 mol / (m4 ), This is the gradient suppression constant, with a value ranging from 0.05 to 0.15 mol / (m). 4 This is used to weaken the interference of the concentration gradient on the electric field modulation. This is a nonlinear exponential factor, ranging from 0.6 to 0.8, used to describe the nonlinear relationship between electric field strength and particle size difference and concentration gradient. This is the temperature sensitivity coefficient, with a value ranging from 0.02 to 0.04 K. -2 , For the local real-time temperature of the membrane, The phase change response temperature of the polymer chain segment is set as the reference value, controlled within 32–34℃.

[0040] The model also introduces an electric field attenuation correction term to accurately describe the distribution characteristics of the electric field within the membrane: ,in The electric field strength on the electrode surface. The electric field attenuation coefficient has a value ranging from 0.02 to 0.04 μm. -1 , The distance from the electrode surface, ranging from 0 to 150 μm, is used to ensure that the electric field strength at the inner composite selective layer reaches the control threshold, avoiding insufficient conformational transformation caused by electric field decay. This formula achieves real-time dynamic adjustment of the electric field strength through the coupling calculation of multiple physical field parameters, enabling precise matching of the membrane channel pore size to the current blood solute clearance requirements, with a pore size control accuracy of ±0.1 nm.

[0041] Furthermore, a dual-mechanism synergistic technology combining intramembrane axial gradient pores and radial charge sieving is employed to selectively permeate solutes of different particle sizes, enabling stratified targeted removal. The intramembrane axial gradient pore structure is achieved through an asymmetric pore arrangement in the inner composite selective layer, prepared by controlling the solvent evaporation rate and coagulation bath temperature gradient during the phase transition process. The intramembrane axial gradient pore structure exhibits a nonlinear decreasing distribution along the blood flow direction, with the pore size function exhibiting exponential decay. The pore size evolution function of this gradient distribution is: ,in, Axial position The radius of the channel at that location, The initial pore radius at the membrane inlet end is... The aperture gradient attenuation coefficient is... The effective axial length of the membrane, As the coordinate variable along the blood flow direction, this gradient structure allows large-particle solutes to be preferentially retained in the upstream section of the membrane channel, while small-particle metabolic solutes can gradually migrate downstream along the axial direction, preventing large-particle solutes from clogging the pore inlet and improving the membrane's antifouling performance.

[0042] Solute transport within the gradient channels satisfies the convection-diffusion equation, taking into account the effects of solute adsorption, concentration gradient, and flow rate changes. ,in The fluid velocity varies along the axial direction and is inversely proportional to the aperture gradient. is the solute adsorption rate constant, with a value ranging from 0.001 to 0.005 s. -1 This equation quantitatively describes the concentration distribution and transport kinetics of solute in the gradient pores. The solute concentration at different locations can be obtained through numerical solution, providing a theoretical basis for staged removal.

[0043] The radial charge sieving mechanism introduces a fixed charge density with a gradient distribution on the pore wall. This charge density distribution is coupled with the pore size gradient and the electrolyte concentration field. The formula for the fixed charge density distribution is: ,in, Radial position Axial position Fixed charge density at the location, As the reference charge density, and These represent the maximum and minimum radius limits of the channel's radial direction, respectively. The parameter is the charge non-uniformity index. The electrolyte concentration coupling coefficient is... Electrolyte concentration along the axial direction The gradient in the direction is used to construct a radial electric field distribution for auxiliary solute sieving.

[0044] membrane surface charge density With charge of solute The electrostatic interaction energy between them is: ,in The vacuum permittivity is 8.85 × 10⁻⁶. -12 F / m, The relative permittivity of blood is 78–80. The distance between the solute and the membrane surface is the electrostatic interaction energy, which can repel or attract the charged solute. When the interaction energy exceeds the thermal kinetic energy ( When ), the solute is effectively retained.

[0045] The effective range of electrostatic interaction is determined by the Debye length. describe: ,in The ionic strength of the solution should be controlled between 0.15 and 0.20 mol / L. Let be the elementary charge, with a value of 1.60 × 10⁻⁶. -19C, the Debye length ranges from 0.8 to 1.0 nm. This length determines the effective range of charge sieving, ensuring that the sieving effect occurs only near the membrane surface and does not affect the overall fluid transport. The axial gradient channels and radial charge sieving work together to achieve graded selective permeation of solutes with different particle sizes and charge properties. The permeability of urea, creatinine, and uric acid can reach over 90%, while the albumin retention rate remains above 99.5%, completing the stratified targeted removal.

[0046] The graded selectivity, by comprehensively considering the diffusion and convection competition mechanisms of solutes in the gradient channels, defines the clearance rate for any class of solutes as an integral form along the axial position. This quantifies the coupling contribution of membrane permeability, effective mass transfer area, and concentration gradient at different positions, as shown in the formula: ,in, For the first Total clearance of solutes For position The membrane permeability coefficient to the solute at that location. For the local effective mass transfer area, and These represent the solute concentrations on the blood side and the dialysate side, respectively. For blood flow, For the effective length of the membrane, The coordinate variable along the membrane axis realizes the cumulative effect of solute removal rate along the membrane length direction, and the exponential term characterizes the correction effect of local mass transfer resistance on concentration difference, and calculates the solute flux under a specific pore size distribution.

[0047] Furthermore, the periodic micro-pulsating flow field on the membrane surface is generated by a piezoelectric drive array integrated around the membrane module. The drive signal is a frequency-modulated sine wave superimposed with random noise terms, and its frequency range is set in the frequency band that can induce fluid boundary layer instability. The micro-pulsations cause local velocity fluctuations, which follow the unsteady Navier-Stokes equations. The generation mechanism of micro-vortices is obtained by introducing an equivalent piezoelectric excitation source term, as shown in the following formula: ,in, For fluid density, For flow velocity vectors, For time, For gradient operators, For pressure, For dynamic viscosity, For the Laplace operator, The equivalent force source term generated by piezoelectric excitation is used to determine the variation of the fluid velocity field with time and space under the action of the piezoelectric excitation force source term, thus generating a specific micro-vortex flow field structure. Controllable micro-vortices are generated by periodically pulsating flow fields on the membrane surface to strip away the solute concentration polarization layer and protein adsorption layer, thereby controlling pore size precision and mass transfer stability. The periodic micro-pulsating flow field on the membrane surface is driven by a pulsation generator built into the membrane module. The generator uses a piezoelectric ceramic oscillator with a vibration frequency range of 5–20 Hz and an amplitude range of 10–50 μm. The pulsation frequency of the flow field... With amplitude Based on the thickness of the concentration polarization layer on the membrane surface Dynamic adjustment is performed, and the adjustment relationship is as follows: ,in The baseline flow velocity at the membrane surface ranges from 0.05 to 0.10 m / s. The amplitude coefficient is the pulsation coefficient, ranging from 0.5 to 1.0, and the concentration polarization layer thickness is... Sherwood Sure: ,in The mass transfer coefficient has a value range of 1.0 × 10⁻⁶. -5 –2.0×10 -5 m / s, The hydraulic diameter of the flow channel. For the Schmitt number, The value ranges from 1000 to 3000, and the thickness of the concentration polarization layer ranges from 50 to 150 μm. This adjustment relationship ensures that the frequency and amplitude of the pulsating flow field match the thickness of the concentration polarization layer, maximizing the eddy current stripping effect.

[0048] This flow field generates controllable micro-vortices on the membrane surface, and the vorticity field of the vortices... From the velocity gradient of the flow field The evolution equation of the vorticity field is described as follows: ,in The velocity vector of the flow field. The fluid kinematic viscosity has a value range of 3.3 × 10⁻⁶. -6 –4.3×10 -6 m² / s, The external driving force vector, provided by the vibration of the piezoelectric oscillator, allows the micro-eddy currents to peel away the solute concentration polarization layer and protein adsorption layer on the membrane surface through shear force and disturbance. : ,in The coordinates are perpendicular to the membrane surface, and the shear force ranges from 0.5 to 1.5 Pa. This shear force can effectively disrupt the structure of the concentration polarization layer, reduce membrane surface resistance, increase the mass transfer coefficient by 20-30%, and at the same time reduce the amount of protein adsorption, keeping the protein adsorption rate below 5%. This maintains the precise control of the membrane channel pore size and the stability of the mass transfer process, ensuring that the pore size accuracy deviation during dialysis does not exceed ±0.2 nm.

[0049] Furthermore, the purified blood, after graded removal and enhanced flow field, is returned to the body, completing a single, precise hemodialysis solute removal cycle. Before returning, the purified blood passes through an online detection module at the membrane module outlet. This module consists of a high-performance liquid chromatograph, a protein integrity analyzer, and a biosensor, which monitors the concentration of residual metabolic solutes in the blood in real time. With plasma protein integrity The detection accuracy can reach ±1%. The detection data is fed back to the adaptive pore size decision model through the wireless transmission module, providing initial parameters for pore size adjustment in the next dialysis cycle, thus forming a closed-loop control.

[0050] Time cycle of a single dialysis cycle Initial concentration of metabolic solutes in the blood With target clearance rate The target clearance rate is set at 70-80%, and the quantitative relationship is as follows: ,in This is the solute removal rate constant, whose value is determined by the membrane permeability coefficient. Effective aperture With transmembrane pressure difference Joint decision: The membrane permeability coefficient The value range is 5.0 × 10 -8 –8.0×10 -8 m / (s·Pa), effective pore size Controlled within 3.5–4.0 nm, transmembrane pressure difference The pressure was controlled at 0.02–0.03 MPa, and the solute scavenging rate constant ranged from 0.002–0.005 s⁻¹. -1 The time range of a single dialysis cycle is 120–180 minutes. This time range ensures the precise removal of metabolic solutes and the effective protection of plasma functional proteins within a single dialysis cycle, thus completing the process of precise solute removal in a single hemodialysis session.

[0051] After the dialysis cycle is completed, the system automatically enters the flushing mode, using physiological saline and dialysate to flush the membrane assembly alternately. The flushing pressure is 0.05 MPa and the flushing time is 10–15 min to remove residual solutes and protein adsorbates, restore the membrane's initial performance, and prepare for the next dialysis cycle.

[0052] This invention achieves nanometer-level precise control of dialysis membrane pore size, stably locking the solute permeability and protein retention ranges to ensure stable blood composition. Through the synergistic effect of axial gradient channels and radial charge sieving, it achieves graded and targeted removal of solutes, improving dialysis efficiency. Furthermore, by using a piezoelectrically driven micro-pulsating flow field to remove the fouling layer on the membrane surface, it maintains stable mass transfer and extends the membrane's lifespan.

[0053] Example 2: This example details a hemodialysis solute removal device with precisely controlled membrane pore size, used to implement a hemodialysis solute removal method with precisely controlled membrane pore size, such as... Figure 5 As shown, it specifically includes: The blood circulation module is used to draw out the patient's blood and deliver it to the dialysis unit, and includes a blood pump, arterial and venous tubing, and a bubble detector. A dual-layer heterostructure dynamic regulation dialysis membrane assembly is disposed inside the dialysis unit. The two sides of the membrane are respectively connected to the blood channel and the dialysate channel, and the membrane integrates channels and piezoelectric excitation structures. Stimulus-responsive polymer brushes are grafted into the channels. A multimodal sensor array is arranged at the membrane inlet and outlet and on the surface to collect real-time signals of the particle size, concentration, flow rate, temperature and conductivity of metabolic solutes in the blood, and transmit the signals to the control unit. An adaptive control unit receives sensor data and runs an aperture decision model based on a multi-parameter feedback mechanism, outputting electric field control commands and flow field excitation parameters. The model includes partial differential equations describing the evolution of the effective aperture of the membrane channel. A low-frequency alternating electric field generator is connected to electrodes on both sides of the membrane and is used to apply an asymmetric square wave electric field to drive the conformational change of the channel. The pulse width ratio of the electric field is determined according to the free energy barrier difference between the open and closed states of the channel. A piezoelectric drive power supply, connected to a piezoelectric excitation ring, is used to generate a periodic micro-pulsating flow field to strip the concentration polarization layer on the film surface. The flow field is driven by the piezoelectric excitation equivalent source term in the unsteady Navier-Stokes equations. The dialysate supply and waste discharge module is used to provide fresh dialysate and discharge waste containing toxins; The central monitoring terminal is used to visually display the dynamics of membrane pore size, solute removal process, and system operating status, and supports remote intervention and parameter adjustment.

[0054] Furthermore, this application employs a dual-path connection layout of fluid pathway and electrical control. The blood circulation module is connected to the blood channel inlet and outlet of the dialysis membrane assembly via sterile arteriovenous tubing, forming an extracorporeal blood circulation pathway. The dialysate supply and waste discharge modules are correspondingly connected to the dialysate channel of the dialysis membrane assembly, enabling continuous dialysate supply and timely waste discharge. The multimodal sensor array is connected to the signal acquisition port of the adaptive control unit via signal cables. The control output of the adaptive control unit is electrically connected to the low-frequency alternating electric field generator and the piezoelectric drive power supply, respectively, and is also bidirectionally connected to the central monitoring terminal via a communication bus. The output of the low-frequency alternating electric field generator is reliably connected to the flexible conductive electrodes on both sides of the dialysis membrane, and the piezoelectric drive power supply is directly connected to the piezoelectric excitation structure integrated within the membrane. Furthermore, the blood circulation module provides stable extracorporeal blood delivery, the blood pump provides continuous and adjustable hemodynamics, the arterial and venous tubing uses highly biocompatible, anticoagulant medical materials, and the bubble detector can monitor the gas in the tubing in real time and quickly activate the protection mechanism to avoid safety risks during blood delivery. This module provides basic fluid support for the entire dialysis process. The dialysate supply and waste fluid discharge module stably supplies fresh dialysate according to set parameters, while rapidly discharging waste fluid containing metabolic solutes, maintaining the concentration gradient between blood and dialysate, and providing a basic environment for solute mass transfer. Furthermore, the dual-layer heterogeneous structure dynamic regulation dialysis membrane module adopts a dual-layer heterogeneous structure composed of an outer porous support layer and an inner composite selective layer. The outer layer has a through-hole macroporous structure, which can provide sufficient mechanical support strength for the membrane, while ensuring a stable flow flux of blood and dialysate. It does not participate in the solute sieving process and only undertakes the functions of structural support and fluid channel. The inner composite selective layer uses covalent grafting to fix a stimulus-responsive polymer brush with both temperature and electrosensitivity properties. Under the action of an external electric field, the polymer brush can undergo orderly dipole rearrangement and chain segment cooperative movement, thereby driving reversible contraction and expansion conformational changes in the membrane channel. The integrated channel structure within the membrane provides a precise path for the sieving of metabolic solutes and plasma proteins. Combined with the piezoelectric excitation structure, a micro-perturbation flow field can be formed on the membrane surface, effectively suppressing solute concentration polarization and protein adsorption. At the structural level, it simultaneously achieves three major functions: dynamic pore size control, particle size classification and sieving, and membrane surface anti-fouling, providing a core functional carrier for precision hemodialysis.

[0055] The dual-layer heterostructure dialysis membrane module with dynamic pore size control can stably lock within a target range, strictly distinguishing the permeability characteristics of metabolic solutes and plasma functional proteins. This ensures the smooth passage of small-molecule metabolic solutes while completely retaining plasma functional proteins, maintaining stable blood composition. The stimulus-responsive polymer brush grafted within the membrane possesses highly reversible conformational change capabilities, rapidly adjusting the pore size under field influence. The adjustment process is uniform and stable, without localized pore size anomalies. This module highly integrates structural design, responsive functional materials, and excitation structures, enabling a single membrane module to simultaneously possess dynamic control, high-efficiency sieving, and enhanced anti-fouling capabilities. This significantly improves the stability and clearance efficiency of the dialysis process and is the key structural foundation for the entire device to achieve precise operation.

[0056] Furthermore, the adaptive control unit, based on an adaptive pore size decision model constructed using a multi-parameter feedback mechanism, can simultaneously receive multi-dimensional real-time signals such as solute particle size, concentration, flow rate, temperature, and conductivity transmitted by a multi-modal sensor array, unifying the dispersed detection data into a coupled calculation system. The model solves the temporal evolution and spatial distribution of the effective pore size of the membrane channel in real time through preset partial differential equations, establishing a precise dynamic correlation between solute flux, protein retention status, and pore size deformation, providing a quantitative basis for the output of control commands.

[0057] The adaptive control unit possesses high-speed real-time computing capabilities, enabling it to complete parameter analysis, model calculation, and command generation in an extremely short time. It outputs precise control commands, such as target aperture, electric field strength, electric field pulse width ratio, and piezoelectric excitation frequency, tailored to the current blood state. The unit continuously adjusts control parameters based on changes in blood composition, concentration gradient fluctuations, and temperature shifts during treatment, always maintaining the control strategy in its optimal state, transforming passive execution into proactive adaptive decision-making. This unit, based on a multi-physics coupling algorithm, constructs a complete closed-loop decision-making logic, serving as the intelligent core for achieving precise aperture control, targeted solute removal, and stable system operation.

[0058] Furthermore, the low-frequency alternating electric field generator is adapted to the field response characteristics of the in-membrane stimulus-responsive polymer brush. Using an asymmetric square wave as the electric field modulation waveform, the ratio of the positive to negative pulse widths is strictly determined based on the free energy barrier difference between the open and closed states of the channel. This allows for precise matching of the dynamic processes of polymer chain extension and retraction, improving driving efficiency and response consistency. The generator's output electric field frequency is within a frequency band capable of stably exciting macroscopic conformational changes in polymer chain segments, fully triggering reversible adjustments to the channel aperture and avoiding driving failure or response hysteresis caused by frequency mismatch.

[0059] The output electric field strength of the low-frequency alternating electric field generator is continuously and dynamically adjusted according to the instructions of the adaptive control unit. It can accurately output an electric field of corresponding intensity according to the real-time aperture requirement, ensuring that the aperture is stably locked within the target threshold range. The generator's output electric field has high uniformity and small field strength deviation at various points on the membrane surface, ensuring that all membrane channels undergo synchronous and uniform conformational changes, avoiding sieving errors caused by uneven local control. At the same time, the generator has stable output characteristics and a safety protection mechanism, and will not produce sudden changes in field strength during continuous operation, thus not causing adverse effects on blood components and membrane materials. It provides a stable, accurate, and gentle field drive guarantee for dynamic aperture control.

[0060] This embodiment describes in detail how a dual-layer heterogeneous membrane assembly, an adaptive control unit, and a low-frequency alternating electric field generator work together to achieve precise nanoscale control and reversible actuation of the membrane pore size. This enables targeted removal of metabolic solutes and complete retention of plasma proteins. Combined with enhanced flow field to combat contamination, a closed-loop precise control is formed, improving dialysis clearance efficiency, blood safety, and operational stability.

[0061] Based on Example 1 or 2, this example details the implementation and verification of the hemodialysis solute clearance method with precise membrane pore size control of this application. In the clinical extracorporeal circulation purification system for end-stage renal disease (ESRD), hemodialysis (HD) relies on the dialysis membrane to achieve particle size sieving of small molecule metabolic solutes (urea 0.33 nm, creatinine 0.41 nm, uric acid 0.52 nm) and plasma functional proteins (albumin HSA 6.5–7.2 nm, IgG 10.5 nm). Clinical requirements include HSA retention rate ≥99.5%, small molecule solute clearance rate Ke ≥70%, and mass transfer coefficient MC decay ≤10% after 240 min of continuous operation. Current electric field-driven smart separation membranes suffer from common defects such as insufficient pore size control precision (±0.3 nm), low electric field-polymer chain coupling efficiency (η<65%), temperature response drift rate ΔT>0.1 nm / ℃, concentration polarization layer (CPT)>150 μm, and protein adsorption capacity (PA)>35 μg / cm². Furthermore, they lack systematic quantitative verification data for the coordinated control of multiple parameters such as NPF, TSC, E0, and t₊ / t₋, and the closed-loop control mechanism of the adaptive decision model and asymmetric square wave electric field has not been experimentally supported. To systematically reveal the precise pore size control mechanism synergistically achieved by the dual-skin heterostructure membrane, adaptive pore size decision model, and low-frequency alternating electric field generator in this application, this verification adopts a fixed baseline parameter and single-factor gradient fine-tuning paradigm, monitoring core indicators such as AP, SR, AR, MC, CPT, PA, and AD throughout the process to determine the optimal electric field control range and material response parameter combination.

[0062] Example 3: Focusing on the optimization of core response parameters driven by the electric field, the core basic parameters and material reference parameters of the low-frequency alternating electric field are fixed. The field strength of the low-frequency alternating electric field is set to 12V / cm, the initial value of the positive pulse width is 8ms, the initial value of the negative pulse width is 4ms, the reference value of the polymer chain segment phase transition response temperature is fixed at 37℃ (human core temperature), the critical cutoff particle size threshold of plasma functional proteins is set to 6.5nm, and the electric field coupling coefficient is fixed at 100 (V / cm)·nm. -1By finely adjusting the gradient of the nonlinear exponential factor (NPF), which characterizes the coupling degree between the electric field and the polymer chain segment response, to 0.60, the adaptive control unit and the low-frequency alternating electric field generator were activated to complete the dynamic regulation of the membrane channel conformation and the 4-hour continuous dialysis simulation experiment. During the experiment, pore size data, inlet and outlet solute concentration data, and membrane fouling layer thickness data were collected in real time at 16 detection points on the membrane surface using a multimodal sensor array. After calculation by the adaptive control unit, the core quantitative data of this embodiment were obtained: the average effective sieving pore size (AP) inside the membrane was 3.42 nm, the standard deviation of the pore size was 0.038 nm, and the control accuracy was ±0.04 nm; the average permeability (SR) of small molecule metabolic solutes (urea, creatinine, and uric acid) were 89.2%, 90.5%, and 90.6%, respectively, with a comprehensive average permeability of 90.1%; the rejection rate (AR) of plasma albumin (HSA) was 99.52%, and the rejection rate of globulin was 99.67%; the average concentration polarization layer thickness (CPT) was 112 μm, and the average solute mass transfer coefficient (MC) was 1.52 × 10⁻⁶. -5 m / s; after 4 hours of experiment, the average protein adsorption (PA) on the membrane surface was 28.6 μg / cm².

[0063] To accurately represent the global uniformity of membrane pore size in this embodiment, a global distribution map of the effective pore size of the membrane channel was constructed based on data from 16 detection points of a multimodal sensing array and combined with global imaging results from a laser confocal scanning microscope. Figure 6 As shown, a medical-grade color calibration system is used, with a color gradient of dark blue—light blue—light yellow—orange-red. Dark blue corresponds to the region with an pore size ≤ 3.38 nm, and orange-red corresponds to the region with an pore size ≥ 3.46 nm. The intermediate color gradient accurately maps the pore size range of 3.38 nm–3.46 nm. Precise pore size numerical color scales and standard deviation annotations are provided on the right side of the graph. It can be clearly observed from this graph that 98.7% of the membrane surface has an pore size distribution within the 3.38 nm–3.46 nm range, with only a small area of ​​0.01–0.02 nm at the membrane edge (0.5 mm). There are no local abrupt changes or abnormal areas in pore size, directly demonstrating that the electric field-driven pore size control of this application's technical solution exhibits excellent global uniformity at NPF=0.60.

[0064] Example 4: Continuing with the core fixed parameter settings of Example 3, namely, low-frequency alternating electric field strength of 12V / cm, positive pulse width of 8ms, negative pulse width of 4ms, polymer chain segment phase transition response temperature reference value of 37℃, critical cutoff particle size of plasma functional protein of 6.5nm, and electric field coupling coefficient of 100 (V / cm)·nm. -1Only the nonlinear exponential factor (NPF) gradient was finely adjusted to 0.70. Under the same experimental platform, dialysate formulation, and simulated blood components (urea concentration 18 mmol / L, creatinine concentration 700 μmol / L, uric acid concentration 450 μmol / L, albumin concentration 40 g / L), three rounds of parallel experiments were conducted, each lasting 4 hours, to ensure the uniqueness of experimental variables and the comparability of data. Through multimodal sensor array acquisition and data processing, the core quantitative data of this embodiment show a significant optimization trend: the average effective sieving pore size (AP) within the membrane stabilizes at 3.75 nm, the standard deviation of the pore size decreases to 0.032 nm, and the control precision is improved to ±0.03 nm; the average permeability of small molecule metabolic solutes is significantly improved, with urea permeability at 92.1%, creatinine permeability at 92.5%, and uric acid permeability at 92.3%, and the overall average permeability reaching 92.3%, an increase of 2.2 percentage points compared to Example 3; the plasma albumin rejection rate (AR) remains at 99.50%, and the globulin rejection rate is 99.65%, with no significant decrease in the core protein rejection performance; the average concentration polarization layer thickness (CPT) of the membrane surface decreases to 98 μm, a reduction of 14 μm compared to Example 3; and the average solute mass transfer coefficient (MC) increases to 1.76 × 10⁻⁶. -5 m / s, an increase of 15.8% compared to Example 3; after the 4-hour test, the average protein adsorption (PA) on the membrane surface decreased to 22.4 μg / cm², a decrease of 21.7% compared to Example 3.

[0065] The experimental data clearly demonstrate that a moderate increase in the nonlinear exponential factor enhances the coupling efficiency between the low-frequency alternating electric field and the membrane-responsive polymer brush, allowing for more complete conformational extension of the polymer segments and thus achieving precise pore size expansion. Simultaneously, it preserves the sieving selectivity of the bilayer heterostructure, effectively maintaining a high plasma protein rejection rate while improving the permeation efficiency of small molecule solutes. Furthermore, pore size optimization reduces membrane concentration polarization, decreases protein adsorption, and further improves mass transfer efficiency; the standard deviation of all data is ≤0.5%.

[0066] Example 5: Using the fixed parameter system of Examples 3 and 4, namely, a low-frequency alternating electric field strength of 12 V / cm, a positive pulse width of 8 ms, a negative pulse width of 4 ms, a polymer chain segment phase transition response temperature reference of 37℃, a critical cutoff particle size of plasma functional protein of 6.5 nm, and an electric field coupling coefficient of 100 (V / cm)·nm. -1The nonlinear exponential factor (NPF) was further fine-tuned to 0.80, and the same experimental procedures, number of parallel experiments and experimental duration were strictly followed to complete the full-cycle dialysis simulation test. Through comprehensive monitoring and data aggregation analysis using a multimodal sensor array, the core quantitative data of this embodiment exhibit performance inflection point characteristics: the average effective sieving pore size (AP) within the membrane further increased to 4.01 nm, the standard deviation of the pore size increased to 0.045 nm, and the control precision decreased back to ±0.05 nm; the overall average permeability of small molecule metabolic solutes was 91.7%, a slight decrease of 0.6 percentage points compared to Example 4, with urea permeability at 91.5%, creatinine permeability at 91.8%, and uric acid permeability at 91.8%; the plasma albumin rejection rate (AR) showed a significant decrease, dropping to 99.41%, a decrease of 0.09 percentage points compared to Example 4, and the globulin rejection rate decreased to 99.58%; the average concentration polarization layer thickness (CPT) further decreased to 89 μm, a reduction of 9 μm compared to Example 4; and the average solute mass transfer coefficient (MC) increased to 1.81 × 10⁻⁶. -5 m / s, an increase of 2.8% compared to Example 4; after the 4-hour test, the average protein adsorption (PA) on the membrane surface decreased to 18.7 μg / cm², a decrease of 16.5% compared to Example 4.

[0067] To further analyze the mechanism of membrane antifouling performance enhancement, a comparison spectrum of membrane protein adsorption amount and concentration polarization layer thickness was constructed by combining the membrane fouling detection data from this embodiment and Example 3, as shown below. Figure 7 As shown, the figure is an advanced combined chart containing two sub-charts. Figure 7 (a) is a graph showing the change in protein adsorption on the membrane surface. The horizontal axis represents the eight core detection areas (R1–R8) on the membrane surface, and the vertical axis represents the protein adsorption amount. The two curves represent the test data of Example 3 (NPF=0.60) and this example (NPF=0.80), respectively, and the standard deviation error band of each data set is marked. Figure 7 (b) is a profile curve of the concentration polarization layer thickness, using a smoothed line graph format. The horizontal axis represents the radial distance of the membrane surface, and the vertical axis represents the thickness of the concentration polarization layer. The two lines correspond to the profile data of Example 3 and this example, respectively, and the lines are distinguished by different line types and colors. It can be intuitively seen from the figure that the protein adsorption curve of the entire detection area in this example is significantly lower than that in Example 3, with an overall decrease of 20%–25%. The radial distribution of the concentration polarization layer thickness is more uniform, and the overall thickness is significantly reduced. This confirms the effect of the optimized flow field characteristics after pore size expansion on the improvement of the membrane surface antifouling performance. However, it also reflects that excessive pore size expansion has begun to affect the plasma protein retention performance.

[0068] Based on all the core quantitative data from Examples 3, 4, and 5 above, and considering the core needs of clinical dialysis, and comprehensively weighing the three key indicators of small molecule solute permeability, plasma protein rejection rate, and pore size control precision, it can be clearly determined that when the nonlinear exponential factor (NPF) = 0.70, the overall performance of the technical solution in this application reaches an optimal balance state. This achieves both high permeability of small molecule solutes and maintains a high rejection rate of plasma proteins, while ensuring excellent pore size control precision. Table 1 shows the performance differences of the first three sets of examples quantified systematically.

[0069] Table 1. Quantitative Comparison of Solute Sieving Performance Based on Nonlinear Exponential Factor Gradient Regulation 3 0.60 3.42 90.1 99.52 1.52 112 28.6 0.04 4 0.70 3.75 92.3 99.50 1.76 98 22.4 0.03 5 0.80 4.01 91.7 99.41 1.81 89 18.7 0.05 Note: NPF = Nonlinear Proportional Factor; AP = Effective Aperture; SD = Standard Deviation; SR = Solute Permeability Rate; AR = Albumin Retention Rate; MC = Mass Transfer Coefficient; CPT = Concentration Polarization Thickness; PA = Protein Adsorption Amount.

[0070] This embodiment uses the optimal nonlinear exponent factor (NPF=0.70) determined in the first three embodiments as the core fixed parameter, while retaining the basic parameter system from embodiments 3–5, namely, a low-frequency alternating electric field strength of 12 V / cm, a positive pulse width of 8 ms, a negative pulse width of 4 ms, a polymer chain segment phase transition response temperature reference value of 37℃, a critical cutoff particle size of plasma functional proteins of 6.5 nm, and an electric field coupling coefficient of 100 (V / cm)·nm. -1 The focus is on the temperature adaptability of membrane materials, with the temperature sensitivity coefficient (TSC), which characterizes the temperature sensitivity of polymer segments, finely tuned to 0.02K. -2 Three rounds of parallel dialysis simulation experiments were conducted, each lasting 4 hours. During the experiments, the temperature fluctuation scenario of clinical dialysis was simulated, with the ambient temperature gradually increased from 35℃ to 39℃ and adjusted by 1℃ every 0.5 hours to accurately monitor the dynamic response characteristics of the pore size.

[0071] Example 6: Based on real-time acquisition by a multimodal sensor array and dynamic calculation by an adaptive control unit, the core quantitative data of this example are as follows: the average effective sieving pore size (AP) within the membrane is 3.68 nm, and the standard deviation of the pore size is 0.029 nm; within a temperature fluctuation range of 35℃–39℃, the pore size fluctuation value (AD) is only ±0.03 nm, demonstrating excellent pore size temperature stability; the overall average permeability (SR) of small molecule metabolic solutes is 92.7%, with urea permeability at 92.6%, creatinine at 92.8%, and uric acid at 92.7%; the plasma albumin rejection rate (AR) is 99.53%, and the globulin rejection rate is 99.68%; the average concentration polarization layer thickness (CPT) is 92 μm, and the average solute mass transfer coefficient (MC) is 1.80 × 10⁻⁶. -5 m / s; after 4 hours of experiment, the average protein adsorption (PA) on the membrane surface was 20.6 μg / cm².

[0072] To quantify the impact of temperature sensitivity coefficient on the dynamic response characteristics of pore size, a dynamic response spectrum of membrane pore size as a function of temperature was constructed based on the temperature fluctuation test data of this embodiment, as shown below. Figure 8 The aperture-temperature dynamic response curve shown is presented in a scatter plot format with a fitted line graph. The horizontal axis represents the experimental temperature, and the vertical axis represents the effective pore size. The scatter points represent real-time acquired data, and the line graph represents the fitting trend line. The goodness of fit R² = 0.987 is also indicated. Figure 9 The permeability-temperature correlation surface plot shown visually illustrates the impact of temperature fluctuations on the permeability of different solutes. It is clearly visible from the plot that at TSC=0.02K... -2 At that time, the membrane pore size changes gradually with temperature fluctuations, and the slope of the fitted trend line is only 0.0075 nm / ℃. Moreover, the pore size fluctuation curves in different temperature ranges are generally at a low level, which proves that the temperature sensitivity coefficient of this embodiment can enable the membrane material to have good temperature adaptability and meet the needs of temperature fluctuation scenarios in clinical dialysis.

[0073] Example 7: This example continues the core fixed parameter system of Example 6, namely, the nonlinear exponential factor (NPF=0.70), the low-frequency alternating electric field strength of 12V / cm, the positive pulse width of 8ms, the negative pulse width of 4ms, the polymer chain segment phase transition response temperature reference value of 37℃, the critical cutoff particle size of plasma functional proteins of 6.5nm, and the electric field coupling coefficient of 100 (V / cm)·nm. -1 Only the temperature sensitivity coefficient (TSC) gradient was fine-tuned to 0.03K. -2Under the same experimental conditions, temperature fluctuation scenarios, and parallel experimental settings as Example 6, a full-cycle dialysis simulation test was completed. Through comprehensive monitoring and data aggregation analysis using a multimodal sensor array, the core quantitative data of this example showed a further optimization trend: the average effective sieving pore size (AP) within the membrane stabilized at 3.75 nm, consistent with the optimal pore size in Example 4, with a pore size standard deviation of 0.031 nm; within a temperature fluctuation range of 35℃–39℃, the pore size fluctuation value (AD) was ±0.05 nm, slightly higher than in Example 6; the overall average permeability (SR) of small molecule metabolic solutes increased to 93%. The permeability was 0.2%, with urea permeability at 93.1%, creatinine permeability at 93.3%, and uric acid permeability at 93.2%, an increase of 0.5 percentage points compared to Example 6; the plasma albumin rejection rate (AR) was 99.51%, and the globulin rejection rate was 99.66%, maintaining excellent clinical performance in core protein retention; the average concentration polarization layer thickness (CPT) decreased to 87 μm, a reduction of 5 μm compared to Example 6; and the average solute mass transfer coefficient (MC) increased to 1.87 × 10⁻⁶. -5 m / s, an increase of 3.9% compared to Example 6; after the 4-hour test, the average protein adsorption (PA) on the membrane surface decreased to 19.2 μg / cm², a decrease of 6.8% compared to Example 6.

[0074] Experimental data show that a moderate increase in the temperature sensitivity coefficient can further enhance the response efficiency of polymer segments to an electric field. While maintaining the pore size within the clinically optimal range (3.75 nm), it improves the mass transfer efficiency of small molecule solutes. Although the pore size temperature fluctuation value increases slightly, it is still within the clinically acceptable range. The overall performance of this embodiment is superior to that of Example 6, further narrowing the optimal parameter range of the temperature sensitivity coefficient.

[0075] Example 8: The optimal nonlinear exponent factor (NPF=0.70) determined in the first three groups was fixed, while retaining the core basic parameters, namely, low-frequency alternating electric field strength of 12V / cm, positive pulse width of 8ms, negative pulse width of 4ms, polymer chain segment phase transition response temperature reference value of 37℃, critical cutoff particle size of plasma functional protein of 6.5nm, and electric field coupling coefficient of 100 (V / cm)·nm. -1 The temperature sensitivity coefficient (TSC) gradient was fine-tuned to 0.04K. -2Strictly following the experimental procedures outlined in the aforementioned embodiments, three rounds of parallel dialysis simulation experiments were conducted, each lasting four hours, simulating more complex clinical temperature fluctuation scenarios (34℃–40℃). Long-term stability monitoring was also implemented, collecting 144 sets of real-time data throughout the experiment to ensure data comprehensiveness and reliability. Through precise acquisition by the multimodal sensor array and efficient computation by the adaptive control unit, the core quantitative data of this embodiment reached the optimal level across the entire series of validations: the mean effective pore size (AP) within the membrane was precisely locked at 3.75 nm, and the standard deviation of the pore size was reduced to 0.022 nm, the minimum value among the six embodiments; within a wide temperature fluctuation range of 34℃–40℃, the pore size fluctuation value (AD) was only ±0.02 nm, achieving optimal pore size temperature stability; the overall average permeability of small molecule metabolic solutes (…) was… The permeability of urea (SR) surged to 93.5%, with urea permeability at 93.4%, creatinine at 93.6%, and uric acid at 93.5%, a further increase of 0.3 percentage points compared to Example 5; the plasma albumin rejection rate (AR) remained stable at 99.52%, and the globulin rejection rate at 99.67%, achieving optimal regression of protein rejection rates; the average concentration polarization layer thickness (CPT) decreased to 82 μm, the lowest among the six examples; and the average solute mass transfer coefficient (MC) increased to 1.90 × 10⁻⁶. -5 The mass transfer efficiency was 1.6% higher than that of Example 5, and the mass transfer efficiency reached the optimal level. After the 4-hour test, the average protein adsorption (PA) on the membrane surface dropped to 17.5 μg / cm², which was 8.9% lower than that of Example 5, and the antifouling performance reached the optimal level.

[0076] To comprehensively present a comparison of the overall performance of the six embodiments, a quantitative comparison chart of the overall performance of all embodiments is constructed, such as... Figure 10 As shown, Figure 10 (a) is a curve showing the average change of effective pore size. The horizontal axis represents the numbers of the 6 sets of examples, and the vertical axis represents the effective pore size. The trend of pore size change is shown by a smooth curve, and the standard deviation error band is superimposed simultaneously. Figure 10 (b) is a curve comparing the overall permeability of small molecule solutes. The horizontal axis represents the example number, and the vertical axis represents the permeability. A smooth curve is used to mark the values ​​of key nodes. Figure 10 (c) is a curve showing the area of ​​plasma albumin retention rate. The horizontal axis represents the example number, and the vertical axis represents the retention rate. The trend of the retention rate is presented visually using a filled curve. Figure 10 (d) is a radar chart showing both mass transfer coefficient and antifouling performance, with the example number as the radar chart dimension. It simultaneously presents the normalized indicators of mass transfer coefficient and protein adsorption amount. A larger radar chart area indicates better overall performance. Figure 10 It can be clearly determined that Example 6 has reached the optimal level of the six examples in all core indicators, and has achieved comprehensive and synergistic optimization of pore size accuracy, screening efficiency, protein protection, mass transfer stability and anti-fouling.

[0077] To systematically summarize the performance change patterns of the last three sets of embodiments based on temperature sensitivity coefficient gradient control, clarify the quantitative basis of the optimal temperature sensitivity coefficient, and construct an advanced multi-dimensional performance summary analysis table, as shown in Table 2, two new core indicators, temperature fluctuation range and pore size fluctuation value, are added based on Table 1, comprehensively covering 11 indicators in 6 categories, including parameter control, pore size performance, sieving performance, mass transfer performance, anti-fouling performance, and temperature adaptability performance. Table 2 Summary Analysis of Multi-Dimensional Performance Based on Gradient Control of Temperature Sensitivity Coefficient 6 0.70 0.02 35–39 3.68 ±0.03 92.7 99.53 1.80 92 20.6 7 0.70 0.03 35–39 3.75 ±0.05 93.2 99.51 1.87 87 19.2 8 0.70 0.04 34–40 3.75 ±0.02 93.5 99.52 1.90 82 17.5 Note: TSC = Temperature Sensitivity Coefficient; AD = Aperture Deviation; the meanings of other English abbreviations are the same as in Table 1.

[0078] The six-group implementation verification clearly established the nonlinear exponential factor (NPF) = 0.70 and the temperature sensitivity coefficient (TSC) = 0.04 K. -2 The optimal combination of electric field and material response parameters was determined. Under this optimal parameter combination, the hemodialysis solute removal method with precise membrane pore size control of this application can precisely lock the effective pore size of the dynamically controlled dialysis membrane with a bilayer heterostructure within the clinically optimal range of 3.75 nm. Within a wide temperature fluctuation range of 34℃–40℃, the pore size control accuracy reaches ±0.02 nm, achieving highly efficient permeability to small molecule metabolic solutes (overall permeability 93.5%) and near-complete retention of plasma albumin (retention rate 99.52%), while simultaneously increasing the solute mass transfer coefficient to 1.90 × 10⁻⁶. -5 m / s, the thickness of the concentration polarization layer on the membrane surface was reduced to 82 μm, and the protein adsorption capacity on the membrane surface was reduced to 17.5 μg / cm². All core performance indicators have reached the top level of clinical dialysis. This method can quickly adjust the electric field control parameters according to the blood composition, metabolic level, and body temperature of different patients, so as to achieve customized pore size control, breaking the application limitations of fixed pore size and fixed parameters in conventional dialysis technology.

[0079] The above are merely preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any changes, modifications, substitutions, integrations, and parameter changes made to these embodiments within the spirit and principles of the present invention, without departing from the principles and spirit of the present invention, through conventional substitutions or to achieve the same function, fall within the scope of protection of the present invention.

Claims

1. A method for precisely controlling the membrane pore size to remove solutes in hemodialysis, characterized in that, include: Blood to be dialyzed and dialysate are obtained and introduced into both sides of a dynamically regulated dialysis membrane with a bilayer heterostructure. The particle size and concentration characteristics of metabolic solutes and plasma functional proteins in blood are collected in real time. The particle size and concentration characteristics are input into an adaptive pore size decision model, and the target regulating pore size and applied electric field strength are output. By applying a low-frequency alternating electric field to drive the reversible conformational contraction and expansion of the membrane channels, the effective sieving pore size of the membrane can be controlled, so that the pore size is locked within the threshold range where metabolic solutes are permeable and plasma functional proteins are completely retained. By employing a dual-mechanism synergistic technology of axial gradient channels and radial charge sieving within the membrane, solutes of different particle sizes can be selectively permeated in stages and targetedly removed in layers. Controllable micro-vortices are generated by periodic micro-pulsating flow fields on the membrane surface to peel off the solute concentration polarization layer and protein adsorption layer on the membrane surface, thereby regulating pore size precision and mass transfer stability. The purified blood, after being graded and enhanced in flow field, is returned to the body to complete a single precise hemodialysis solute removal cycle. The dynamically regulated dialysis membrane with a dual-layer heterostructure consists of an outer porous support layer and an inner composite selective layer. The outer support layer has a through-pore structure with a pore size set to provide mechanical support and maintain fluid flux. The inner composite selective layer is embedded with covalently grafted stimulus-responsive polymer segments. These polymer segments are functionalized copolymer derivatives with both temperature-sensitive and electrosensitive properties. Under the action of a low-frequency alternating electric field, they undergo dipole rearrangement and segmental cooperative movement, inducing reversible conformational changes in the dialysis channel. The frequency of the low-frequency alternating electric field is set within a frequency range capable of exciting macroscopic conformational changes in polymer chain segments, and the dynamic adjustment formula for the electric field strength is: ,in, The applied electric field intensity vector modulus, The electric field coupling coefficient is... The characteristic particle size of the target metabolic solute in the current blood. This represents the critical particle size cutoff for plasma functional proteins. This represents the spatial gradient modulus of solute concentration. This is the gradient suppression constant. It is a non-linear exponential factor. For temperature sensitivity coefficient, For the local real-time temperature of the membrane, The phase transition response temperature reference value of polymer chain segments is used to control the extension range of polymer chain segments; The adaptive pore size decision model is constructed based on a multi-parameter feedback mechanism. Input variables include real-time detected metabolic solute particle size distribution function, plasma protein concentration field, transmembrane pressure difference, and electric field response factor. The evolution structure of the effective pore size of the membrane channel is obtained by constructing partial differential equations, forming a dynamic coupling between solute flux and pore size deformation. The formula is as follows: ,in, The effective pore radius of the membrane channel as a function of time. For time variables, For the response sensitivity coefficient, Let be the solute particle size distribution function. For particle size variable, and These represent the lower and upper limits of the integration interval, respectively. The migration rate of the solute in the medium. The solute flux vector. For feedback control coefficients, The target aperture reference value, For the diffusion smoothing term coefficients, For the Laplace operator.

2. The method for precisely controlling the membrane pore size to remove solutes in hemodialysis according to claim 1, characterized in that, The low-frequency alternating electric field is applied through a pair of flexible conductive electrodes arranged parallel to each other on both sides of the membrane. The electric field modulation waveform adopts an asymmetric square wave, and the ratio of its positive pulse width to its negative pulse width is dynamically adjusted according to the free energy barrier difference between the open and closed states of the channel, so as to control the extension and retraction dynamics of the polymer chain segments; the pulse width ratio formula is: ,in, The pulse width under a positive electric field. The pulse width under the influence of a negative electric field. The free energy barrier difference for the transition of the channel from the closed state to the open state. The free energy barrier difference for the transition from the open state to the closed state of the channel. Boltzmann's constant, Using absolute temperature, the opening and closing time ratio of the dialysis channel is precisely controlled by the exponential dependence between the ratio of positive and negative pulse widths of the electric field waveform and the channel conformational transition free energy difference and thermodynamic temperature.

3. The method for precisely controlling the membrane pore size to remove solutes in hemodialysis according to claim 2, characterized in that, The conformational changes of the dialysis channel are monitored in real time using a fluorescence resonance energy transfer probe. The probe is labeled between two adjacent polymer segments. When the channel contracts, the distance between the donor and acceptor fluorescent molecules shortens to within the effective energy transfer distance, and the FRET efficiency increases significantly. The value is calculated by the following formula: ,in, For fluorescence resonance energy transfer efficiency, This represents the actual distance between the donor and acceptor fluorescent molecules. This is the critical distance.

4. The method for precisely controlling the membrane pore size to remove solutes in hemodialysis according to claim 1, characterized in that, The synergistic technology of axial gradient channels and radial charge sieving within the membrane is specifically as follows: The intramembrane axial gradient pore structure exhibits a non-linear decreasing distribution along the blood flow direction, and the pore size function follows an exponential decay form, as shown in the formula: ,in, Axial position The radius of the channel at that location, The initial pore radius at the membrane inlet end is... The aperture gradient attenuation coefficient is... The effective axial length of the membrane, These are coordinate variables along the direction of blood flow; The radial charge sieving mechanism introduces a fixed charge density with a gradient distribution on the pore wall. This charge density distribution is coupled with the pore size gradient and the electrolyte concentration field. The formula for the fixed charge density distribution is: ,in, Radial position Axial position Fixed charge density at the location, As the reference charge density, and These represent the maximum and minimum radius limits of the channel's radial direction, respectively. The parameter is the charge non-uniformity index. The electrolyte concentration coupling coefficient is... Electrolyte concentration along the axial direction The gradient in the direction is used to construct a radial electric field distribution for auxiliary solute sieving.

5. The method for precisely controlling the membrane pore size to remove solutes in hemodialysis according to claim 4, characterized in that, The graded selectivity comprehensively considers the diffusion and convection competition mechanisms of solutes in the gradient channels. Its clearance rate for any type of solute is defined as an integral along the axial position, quantifying the coupling contribution of membrane permeability, effective mass transfer area, and concentration gradient at different positions. The formula is as follows: ,in, For the first Total clearance of solutes For position The membrane permeability coefficient to the solute at that location. For the local effective mass transfer area, and These represent the solute concentrations on the blood side and the dialysate side, respectively. For blood flow, For the effective length of the membrane, The coordinate variable is along the membrane axis, realizing the cumulative effect of solute removal rate along the membrane length direction, and the exponential term characterizes the correction effect of local mass transfer resistance on concentration difference, and calculates the solute flux under a specific pore size distribution.

6. The method for precisely controlling the membrane pore size to remove solutes in hemodialysis according to claim 1, characterized in that, The periodic micro-pulsating flow field on the membrane surface is generated by a piezoelectric drive array integrated around the membrane module. The drive signal is a frequency-modulated sine wave superimposed with random noise terms, and its frequency range is set in a frequency band that can induce fluid boundary layer instability. The micro-pulsations cause local velocity fluctuations, which follow the unsteady Navier-Stokes equations. The generation mechanism of micro-vortices is obtained by introducing an equivalent piezoelectric excitation source term, as shown in the following formula: ,in, For fluid density, For flow velocity vectors, For time, For gradient operators, For pressure, For dynamic viscosity, For the Laplace operator, The equivalent force source term generated by piezoelectric excitation is used to determine the variation of the fluid velocity field with time and space under the action of the piezoelectric excitation force source term, thus generating a specific micro-vortex field structure.

7. A hemodialysis solute removal device with precisely controlled membrane pore size, employing the hemodialysis solute removal method with precisely controlled membrane pore size as described in any one of claims 1-6, characterized in that, include: The blood circulation module is used to draw out the patient's blood and deliver it to the dialysis unit, and includes a blood pump, arterial and venous tubing, and a bubble detector. A dual-layer heterostructure dynamic regulation dialysis membrane assembly is disposed inside the dialysis unit. The two sides of the membrane are respectively connected to the blood channel and the dialysate channel. The membrane integrates channels and piezoelectric excitation structures. Stimulus-responsive polymer brushes are grafted into the channels. A multimodal sensor array is arranged at the membrane inlet and outlet and on the surface to collect real-time signals of the particle size, concentration, flow rate, temperature and conductivity of metabolic solutes in the blood, and transmit the signals to the control unit. An adaptive control unit receives sensor data and runs an aperture decision model based on a multi-parameter feedback mechanism, outputting electric field control commands and flow field excitation parameters. The model includes partial differential equations describing the evolution of the effective aperture of the membrane channel. A low-frequency alternating electric field generator is connected to electrodes on both sides of a membrane and is used to apply an asymmetric square wave electric field to drive a conformational change in the channel. The pulse width ratio of the electric field is determined based on the free energy barrier difference between the open and closed states of the channel. A piezoelectric drive power supply, connected to a piezoelectric excitation ring, is used to generate a periodic micro-pulsating flow field to strip the concentration polarization layer on the film surface. The flow field is driven by the piezoelectric excitation equivalent source term in the unsteady Navier-Stokes equations. The dialysate supply and waste discharge module is used to provide fresh dialysate and discharge waste containing toxins; The central monitoring terminal is used to visually display the dynamics of membrane pore size, solute removal process, and system operating status, and supports remote intervention and parameter adjustment.

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