COMSOL-based nanopore array detection flux and precision optimization method and system

Abstract

The invention discloses a nanopore array detection flux and precision optimization method and system based on COMSOL, and the method comprises the steps: determining simulation parameters of a nanopore array based on the geometrical shape and size of a to-be-detected molecule; the method comprises the following steps of: utilizing an electrostatic field and a dilute substance transmission physical field in COMSOL Multiphysics, coupling a Poisson equation and a Nernst-Planck equation, and combining simulation parameters, an ion diffusion coefficient of an electrolyte solution, electric field intensity and chemical concentration to finish three-dimensional simulation modeling of a nanopore array; in the nanopore array model, the influence of different arrangement structures on nanopore array current is analyzed by adjusting the center distance, the arrangement mode and the number of adjacent nanopores, and simulation results of nanopore array current characteristics under different designs are obtained; and calculating through hole currents of different nanopore array structures based on simulation results, and carrying out optimization design to finish optimization.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanopore sensors, and in particular relates to a method and system for optimizing the detection flux and precision of a nanopore array based on COMSOL. Background Art

[0002] As a new detection method, nanopore technology has been widely used in the fields of biosensors, environmental monitoring, and material analysis. In particular, the design and optimization of nanopore arrays play a vital role in high-throughput and high-sensitivity molecular detection. By adjusting the size, arrangement, and spacing of the nanopores, the efficiency and accuracy of the detection can be significantly improved. However, since traditional experimental methods are difficult to accurately simulate the effects of different array structures on detection performance, the optimization process of nanopore arrays often relies on a large number of experimental verifications, which is inefficient and difficult to achieve precise parameter adjustment.

[0003] In recent years, the emergence of multi-physics simulation software such as COMSOL Multiphysics has provided new solutions for the design and optimization of nanopore arrays. By simulating parameters such as the geometry, arrangement, and electrolyte solution concentration of the nanopore array, the effects of different designs on current characteristics and molecular detection performance can be theoretically predicted. This simulation method not only greatly improves the efficiency of optimization, but also provides a more accurate design basis for subsequent actual experiments, solving the problem of accurate simulation in traditional methods. However, there is still a lack of a simulation method that comprehensively considers multiple factors and can accurately predict the detection performance of nanopore arrays. Summary of the invention

[0004] The present invention aims to solve the deficiencies of the prior art and provides the following solutions:

[0005] A method for optimizing the detection flux and accuracy of a nanopore array based on COMSOL, comprising the following steps:

[0006] Determining simulation parameters of the nanopore array based on the geometric shape and size of the molecule to be detected, wherein the simulation parameters include geometric parameters and physical parameters;

[0007] Using the electrostatic field and dilute material transport physics field in COMSOL Multiphysics, coupling the Poisson equation and the Nernst-Planck equation, and combining the simulation parameters, the ion diffusion coefficient, the electric field strength and the chemical concentration of the electrolyte solution, the three-dimensional simulation modeling of the nanopore array is completed to obtain a nanopore array model;

[0008] In the nanohole array model, by adjusting the center distance, arrangement mode and number of adjacent nanoholes, the influence of different arrangement structures on the nanohole array current is analyzed and calculated, and the simulation results of the nanohole array current characteristics under different designs are obtained;

[0009] Based on the simulation results, the through-hole currents of different nanopore array structures are calculated and optimized designs are performed to complete the optimization.

[0010] Preferably, the Poisson equation is:

[0011]

[0012] in, represents the control potential in the nanopore, ε represents the relative dielectric constant, ρv represents the space charge density, F represents the Faraday constant, and z i represents the valence of ion species i, c i represents the concentration of ion species i.

[0013] Preferably, the Nernst-Planck equation is:

[0014] N i =N i，D +N i，M +N i，C

[0015]

[0016] N i , C =c i u

[0017] Among them, N i,D represents the flux due to diffusion caused by the Brownian motion of molecules, D i represents the diffusion coefficient of ion i, N i,M represents the migration flux caused by the movement of charged ions when an external voltage is applied, K B represents the Boltzmann constant, T represents the temperature, e represents the elementary charge, Used to express the gradient of the electric field strength V, Used to express concentration gradient, N i,c represents the convective flux and u represents the fluid velocity.

[0018] Preferably, in the nanopore array model,

[0019] The actual total current of the nanopore array is:

[0020]

[0021] The total current of the nanopore array without mutual interference of nanopores is:

[0022] I lim =4rz i FD 1 Nc 0

[0023] Where N is the number of nanopores, c 1 represents the concentration of cations, c 0 represents the initial concentration of cations, r represents the radius of the nanopore, z 1 Indicates the valence of the cation, D 1 represents the diffusion coefficient of the cation, and m represents the coordinate of the nanopore in the y direction.

[0024] Preferably, in the nanopore array model,

[0025] The total resistance of a single nanopore is composed of the resistance inside the pore and two resistances at the pore mouth in series:

[0026]

[0027] R=R channel +2*R access

[0028] Among them, R channel Represents the resistance inside the hole, R access represents the pore resistance, R represents the total resistance, ρ represents the resistivity of the electrolyte solution, l represents the length of the nanopore, d represents the diameter of the nanopore, and C represents the capacitance generated between the pore and the electrode.

[0029] Preferably, in the nanopore array model, the reference current of the nanopore is:

[0030]

[0031] Where I is the reference current, σ is the conductivity of the electrolyte solution, and U is the applied voltage.

[0032] The present invention also provides a nanopore array detection flux and precision optimization system based on COMSOL, the system applying any of the above methods, including: a parameter acquisition module, a model building module, a simulation module and an optimization module;

[0033] The parameter acquisition module determines the simulation parameters of the nanopore array based on the geometric shape and size of the molecule to be detected, and the simulation parameters include geometric parameters and physical parameters;

[0034] The model building module uses the electrostatic field and the dilute material transport physical field in COMSOL Multiphysics, couples the Poisson equation and the Nernst-Planck equation, and combines the simulation parameters, the ion diffusion coefficient, the electric field strength and the chemical concentration of the electrolyte solution to complete the three-dimensional simulation modeling of the nanopore array and obtain the nanopore array model;

[0035] The simulation module is used to analyze and calculate the influence of different arrangement structures on the nanopore array current by adjusting the center distance, arrangement mode and number of adjacent nanopores in the nanopore array model, and obtain simulation results of the current characteristics of the nanopore array under different designs;

[0036] The optimization module calculates the through-hole current of different nanopore array structures based on the simulation results and performs optimization design to complete the optimization.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] (1) The present invention uses a simulation method based on COMSOL Multiphysics to accurately predict the impact of different nanopore array designs on current characteristics and detection performance, optimize the structure and arrangement of the nanopore array, and thus greatly improve the accuracy and efficiency of detection;

[0039] (2) It is difficult for traditional experimental methods to accurately simulate the effect of the spacing between adjacent nanopores in a nanopore array on the current, resulting in the optimization process relying on a large number of experimental verifications. The simulation method of the present invention can theoretically solve this problem, reducing experimental costs and time;

[0040] (3) The present invention ensures the independence of each nanopore by systematically simulating the spacing, arrangement, number, etc. of adjacent nanopores, avoids the overlap of diffusion layers, improves the independence and overall performance of the nanopore array, and thus optimizes the design of the high-throughput detection system;

[0041] (4) The present invention can adjust the structure, size and concentration of the electrolyte solution of the nanopore array according to different detection requirements, and is widely applicable to high-sensitivity detection of complex samples such as biological molecules and environmental pollutants;

[0042] (5) Through simulation results, the present invention provides a solid theoretical basis for the experimental design and optimization of nanopore arrays, reduces the uncertainty in traditional experimental methods, and ensures the repeatability and reliability of experimental results. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] In order to more clearly illustrate the technical solution of the present invention, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0044] Figure 1 A schematic diagram of a method flow chart of an embodiment of the present invention;

[0045] Figure 2 A schematic diagram of mesh division of the overall model of an embodiment of the present invention;

[0046] Figure 3 A schematic diagram of mesh division of a single nanopore according to an embodiment of the present invention;

[0047] Figure 4 A schematic diagram of the steady-state electric field of a nanopore model according to an embodiment of the present invention;

[0048] Figure 5 This is a schematic diagram of the effect of the spacing of 5 nm nanopores on the current in an embodiment of the present invention;

[0049] Figure 6 Schematic diagram of the effect of the spacing of 10 nm nanopores on current in an embodiment of the present invention;

[0050] Figure 7 Schematic diagram of the effect of the spacing of 15 nm nanopores on current in an embodiment of the present invention. DETAILED DESCRIPTION

[0051] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0052] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0053] Embodiment 1

[0054] In this embodiment, if Figure 1 As shown, a method for optimizing the detection flux and accuracy of a nanopore array based on COMSOL includes the following steps:

[0055] S1. Based on the geometric shape and size of the molecule to be detected, the simulation parameters of the nanopore array are determined, and the simulation parameters include geometric parameters and physical parameters.

[0056] In this embodiment, the geometric parameters include the radius and length of each nanopore and the center distance between adjacent nanopores. The center distance is greater than or equal to 20 times the radius of the nanopore to ensure that the current transmission of each nanopore in the nanopore array is independent of each other and avoid overlap of the diffusion layers between adjacent nanopores.

[0057] S2. Using the electrostatic field and dilute material transport physics field in COMSOL Multiphysics, coupling the Poisson equation with the Nernst-Planck equation, and combining the simulation parameters, the ion diffusion coefficient of the electrolyte solution, the electric field strength, and the chemical concentration, the three-dimensional simulation modeling of the nanopore array was completed to obtain the nanopore array model.

[0058] In this embodiment, considering that the nanopore needs to work in a charged environment, the Poisson equation is used to describe the control potential in the nanopore. The Poisson equation is:

[0059]

[0060] in, represents the control potential in the nanopore, ε represents the relative dielectric constant, ρv represents the space charge density, F represents the Faraday constant, and z i represents the valence of ion species i, c i represents the concentration of ion species i.

[0061] Considering that the nanopore needs to work in a concentration field, the Nernst-Planck equation is used to describe the total flux of ion species i, which is used to construct the control equation for material transfer and reaction in the liquid. The Nernst-Planck equation consists of three parts. The ion flux generated by the ion concentration gradient can be expressed by Fick's first law; when an external voltage is applied to the electrolyte solution, the movement of charged ions will migrate the flux, and the flux is the convection flux. The Nernst-Planck equation is:

[0062]

[0063] N i，C =c i u

[0064] Among them, N i,D represents the flux due to diffusion caused by the Brownian motion of molecules, D i represents the diffusion coefficient of ion i, N i,M It represents the migration flux caused by the movement of charged ions when an external voltage is applied in the electrolyte solution, K B represents the Boltzmann constant, T represents the temperature, e represents the elementary charge, Used to express the gradient of the electric field strength V, Used to express concentration gradient, N i,c represents the convective flux and u represents the fluid velocity.

[0065] In the nanohole array model, the actual total current of the nanohole array is:

[0066]

[0067] The total current of the nanopore array without mutual interference of nanopores is:

[0068] I lim =4rz i FD 1 Nc 0

[0069] Where N is the number of nanopores, c 1 represents the concentration of cations, c 0 represents the initial concentration of cations, r represents the radius of the nanopore, z 1 Indicates the valence of the cation, D 1 represents the diffusion coefficient of the cation, and m represents the coordinate of the nanopore in the y direction.

[0070] In the nanopore array model, the nanopore structure can be divided into a wider pore opening at both ends and a narrower pore inner part in the middle. The total resistance of a single nanopore is composed of the pore inner resistance and two pore opening resistances in series:

[0071]

[0072] R=R channel +2*R access

[0073] Among them, R channel Represents the resistance inside the hole, R access represents the pore resistance, R represents the total resistance, ρ represents the resistivity of the electrolyte solution, l represents the length of the nanopore, d represents the diameter of the nanopore, and C represents the capacitance generated between the pore and the electrode. In the nanopore array model, the conductance is related to the above-mentioned total resistance of the nanopores. The conductance of a single nanopore is the inverse of the total resistance of the nanopore. The reference current of the nanopore is:

[0074]

[0075] Where I is the reference current, σ is the conductivity of the electrolyte solution, and U is the applied voltage.

[0076] In this embodiment, the electrostatic field and dilute species transport physics field in the COMSOL Multiphysics software are used to simulate the ion concentration distribution, electric field distribution and ion current in the electrolyte solution, and the simulation process takes into account parameters such as the temperature, pH value, ion diffusion coefficient, and Faraday constant of the electrolyte solution.

[0077] S3. In the nanohole array model, by adjusting the center distance, arrangement mode and number of adjacent nanoholes, the influence of different arrangement structures on the nanohole array current is analyzed and calculated, and the simulation results of the nanohole array current characteristics under different designs are obtained.

[0078] In this embodiment, the position distribution of each nanopore is optimized by changing the arrangement of the nanopore array to improve the detection flux and sensitivity of the overall array. The optimization includes adjusting the two-dimensional or three-dimensional arrangement of the nanopore array to maximize the independence of the nanopores and reduce mutual interference of the electric field.

[0079] The analysis and calculation methods include studying the effects of different electrolyte concentrations, the electric field between adjacent nanopores, and the center distance on the ion current through multi-physics field simulation, and obtaining a quantitative relationship between the spacing between adjacent nanopores and the detection accuracy and efficiency.

[0080] The simulation model is solved by coupling three-dimensional modeling with the COMSOL solver. The boundary conditions used include setting the potential of the liquid pool cavity to a constant and setting the ion concentration conditions of the electrolyte solution to ensure that the simulation model accurately simulates the actual situation of the ion current in the nanopore array.

[0081] S4. Calculate the through-hole current of different nanohole array structures based on the simulation results and optimize the design to complete the optimization.

[0082] In this embodiment, the simulation results provide a theoretical basis for subsequent nanopore array experiments, which can effectively guide the design and optimization of nanopore arrays in experiments to achieve the construction of high-sensitivity and high-throughput detection systems. 2 O 3 / Au / Si 3 N 4 The sandwich structure is used for high-sensitivity and high-throughput detection of biomolecules or pollutants.

[0083] The optimized nanopore array can adjust the center distance, number of nanopores and arrangement according to specific application requirements to meet the requirements of high-throughput and high-efficiency molecular detection. It is especially suitable for high-precision detection of complex samples such as tumor markers and environmental pollutants.

[0084] Embodiment 2

[0085] In this embodiment, based on the first embodiment, the process of modeling using COMSOL Multiphysics includes:

[0086] According to the nanopore manufacturing technology and the geometric shape and size of the molecules to be tested, the simulation geometric parameters and related physical parameters of the nanopore array are determined. The geometric parameters include the diameter, length and arrangement of the nanopores. The geometric model of the nanopore simulation is constructed in the AUTOCAD software. The radius and length of the two liquid pool cavities are set to 1000nm, a 3×3 nanopore array is set, the radius and length of the nanopores are set to 15nm, and the center distance between adjacent nanopores is L, such as Figure 2 shown.

[0087] Select a two-dimensional graph and add a multi-physics interface: use the "electrostatics (es)" interface to simulate the electrostatic field in the nanopore, use the "transport of dilute species (tds)" to simulate the concentration field of liquid material transfer and reaction in the nanopore, set parameter properties and use initial conditions and boundary conditions to constrain the equations, where the potential and grounding are set in the electrostatic field interface, the potential is set to 200mV, the spatial charge density is added to the model and the Faraday constant is set, the electric field migration is added to the dilute species transport interface and the material charge transfer is set, the concentration of the transferred electrolyte solution is set to 1mol / L, the material concentration of the nanopore array model interaction and its velocity field, diffusion coefficient, temperature and other experimental parameters. Add the multi-physics coupling function to couple the two physical fields of "transport of dilute species (tds)" and "electrostatics (es)";

[0088] Custom meshing and free tetrahedral meshing are performed on the nanopore molecular via model to generate a mesh model. The overall mesh model is as follows: Figure 2 As shown, the single nanopore mesh model is Figure 3 As shown;

[0089] Add a steady-state study, adjust the nanopore spacing in the solver as needed (see Table 1 for examples), and obtain the nanopore model potential (such as Figure 4 As shown), concentration streamline distribution of dilute substances, and space charge distribution;

[0090] Table 1

[0091]

[0092] The investigation explores the influence mechanism of the center distance between adjacent nanopores, electric field distribution, pH value, ion diffusion coefficient, Faraday constant, number of nanopore arrays, arrangement of nanopore arrays and electrolyte concentration on the nanopore ion current. According to the model simulation results and design requirements, the voltage and concentration combination of the nanopores, the nanopore spacing and other parameters are adjusted to maximize the independence of the nanopores, providing a scientific basis for the optimization of nanopore detection. Figure 5 , Figure 6 , Figure 7 The effect of nanopore size and their spacing on the current.

[0093] Embodiment 3

[0094] In this embodiment, a nanopore array detection flux and precision optimization system based on COMSOL includes: a parameter acquisition module, a model building module, a simulation module and an optimization module.

[0095] The parameter acquisition module determines the simulation parameters of the nanopore array based on the geometric shape and size of the molecules to be tested, and the simulation parameters include geometric parameters and physical parameters.

[0096] The model building module uses the electrostatic field and dilute material transport physics field in COMSOL Multiphysics, couples the Poisson equation with the Nernst-Planck equation, and combines simulation parameters, ion diffusion coefficient of the electrolyte solution, electric field strength and chemical concentration to complete the three-dimensional simulation modeling of the nanopore array and obtain the nanopore array model.

[0097] The simulation module is used to analyze and calculate the effects of different arrangement structures on the nanohole array current by adjusting the center distance, arrangement mode and number of adjacent nanoholes in the nanohole array model, and obtain the simulation results of the nanohole array current characteristics under different designs.

[0098] The optimization module calculates the through-hole current of different nanohole array structures based on the simulation results and performs optimization design to complete the optimization.

[0099] The embodiments described above are only descriptions of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for optimizing the detection flux and accuracy of nanopore arrays based on COMSOL, characterized in that: The following steps are involved: Determining simulation parameters of the nanopore array based on the geometric shape and size of the molecule to be detected, wherein the simulation parameters include geometric parameters and physical parameters; Using the electrostatic field and dilute material transport physics field in COMSOL Multiphysics, coupling the Poisson equation and the Nernst-Planck equation, and combining the simulation parameters, the ion diffusion coefficient, the electric field strength and the chemical concentration of the electrolyte solution, the three-dimensional simulation modeling of the nanopore array is completed to obtain a nanopore array model; In the nanohole array model, by adjusting the center distance, arrangement mode and number of adjacent nanoholes, the influence of different arrangement structures on the nanohole array current is analyzed and calculated, and the simulation results of the nanohole array current characteristics under different designs are obtained; Based on the simulation results, the through-hole currents of different nanopore array structures are calculated and optimized designs are performed to complete the optimization.

2. According to claim 1, a COMSOL-based nanopore array detection flux and accuracy optimization method, characterized in that: The Poisson equation is: in, represents the control potential in the nanopore, ε represents the relative dielectric constant, ρv represents the space charge density, F represents the Faraday constant, and z i represents the valence of ion species i, c i represents the concentration of ion species i.

3. The method for optimizing the detection flux and precision of a nanopore array based on COMSOL according to claim 2, characterized in that: The Nernst-Planck equation is: N i =N i，D +N i，M +N i，C N i，C =c i u Among them, N i,D represents the flux due to diffusion caused by the Brownian motion of molecules, D i represents the diffusion coefficient of ion i, N i,M represents the migration flux caused by the movement of charged ions when an external voltage is applied, K B represents the Boltzmann constant, T represents the temperature, e represents the elementary charge, Used to express the gradient of the electric field strength V, Used to express concentration gradient, N i,c represents the convective flux and u represents the fluid velocity.

4. The method for optimizing the detection flux and precision of a nanopore array based on COMSOL according to claim 3, characterized in that: In the nanopore array model, The actual total current of the nanopore array is: The total current of the nanopore array without mutual interference of nanopores is: I lim =4rz i FD1Nc0 Wherein, N represents the number of nanopores, c1 represents the concentration of cations, c0 represents the initial concentration of cations, r represents the radius of the nanopore, z1 represents the valence of the cations, D1 represents the diffusion coefficient of the cations, and m represents a coordinate of the nanopore in the y direction.

5. The method for optimizing the detection flux and precision of a nanopore array based on COMSOL according to claim 4, characterized in that: In the nanopore array model, The total resistance of a single nanopore is composed of the resistance inside the pore and two resistances at the pore mouth in series: R=R channel +2*R access Among them, R channel Represents the resistance inside the hole, R access represents the pore resistance, R represents the total resistance, ρ represents the resistivity of the electrolyte solution, l represents the length of the nanopore, d represents the diameter of the nanopore, and C represents the capacitance generated between the pore and the electrode.

6. The method for optimizing the detection flux and precision of a nanopore array based on COMSOL according to claim 5, characterized in that: In the nanopore array model, the reference current of the nanopore is: Where I is the reference current, σ is the conductivity of the electrolyte solution, and U is the applied voltage.

7. A nanopore array detection flux and precision optimization system based on COMSOL, the system applying the method described in any one of claims 1 to 6, characterized in that: include: Parameter acquisition module, model building module, simulation module and optimization module; The parameter acquisition module determines the simulation parameters of the nanopore array based on the geometric shape and size of the molecule to be detected, and the simulation parameters include geometric parameters and physical parameters; The model building module uses the electrostatic field and the dilute material transport physical field in COMSOL Multiphysics, couples the Poisson equation and the Nernst-Planck equation, and combines the simulation parameters, the ion diffusion coefficient, the electric field strength and the chemical concentration of the electrolyte solution to complete the three-dimensional simulation modeling of the nanopore array and obtain the nanopore array model; The simulation module is used to analyze and calculate the influence of different arrangement structures on the nanopore array current by adjusting the center distance, arrangement mode and number of adjacent nanopores in the nanopore array model, and obtain simulation results of the current characteristics of the nanopore array under different designs; The optimization module calculates the through-hole current of different nanopore array structures based on the simulation results and performs optimization design to complete the optimization.

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