A microfluidic metamaterial structure design method and microfluidic metamaterial structure

Abstract

The present invention discloses a method for designing a microfluidic metamaterial structure, comprising the following steps: setting a microfluidic environment; calculating equivalent parameters of the microfluidic metamaterial; parametrically designing a microcell structure; constructing a control performance database; and constructing a microcell spatial topology. The present invention also discloses a microfluidic metamaterial structure fabricated based on this design method. The present invention achieves a microfluidic flow control effect by synergistically regulating the flow velocity and direction of a microfluid within a specific region.

Description

Technical Field

[0001] The present invention relates to the field of microfluidic technology, and in particular to a microfluidic metamaterial structure design method and a microfluidic metamaterial structure. Background Art

[0002] Microfluidic chips based on microfluidics have become an important technical tool in biomedical engineering due to their high precision, low cost, fast analysis speed, and modular functional integration. With the introduction of the concepts of precision medicine and precision medicine, microfluidics has provided important technical means for the rapid cultivation and detection of cells and microorganisms such as bacteria, the construction of organ-on-a-chip models and bioscaffolds, the targeted delivery of anticancer drugs, the precision treatment of tumors, and the in vitro pathological reproduction of organs such as the uterus and intestine. In recent years, with the rapid development of aerospace technology and space science and technology, microfluidic chip technology has not only undertaken the regular and rapid monitoring of various biochemical indicators in astronauts' body fluids under special circumstances, but also provided strong technical support for the exploration of life in outer space and the detection of human habitable environments.

[0003] Microfluidic chips are emerging micro-total analysis systems that integrate multiple functional modules, including reagent inlets, sample inlets, microvalves, mixing devices, reactors, exhaust systems, and sensors, boasting extremely high production precision and reaction resolution. Microfluidic chip technology precisely manipulates microfluidics to integrate complex analytical processes such as sample pretreatment, preparation, reaction, detection, and diagnosis involved in biochemical reactions and biological experiments onto microfluidic chips on the millimeter to centimeter scale. This minimizes human interference and allows for rapid automated amplification and diagnosis of substances such as nucleic acids. The microscale channel structure of microfluidic chips increases the chip's specific reaction surface area, resulting in very high mass transfer efficiency. This also enhances the chip's high-throughput screening capabilities, enabling faster and more sensitive detection.

[0004] However, due to the low Reynolds number and laminar flow characteristics, achieving high-precision microfluidic control in microscale flows remains a significant challenge. Existing active microfluidic control technologies can achieve precise control of microfluidics by applying external forces to low-Reynolds number fluids. However, active microfluidic devices can damage biological samples due to high-frequency mixing and high-energy radiation. In addition, the design and production processes of active microfluidic devices are complex, difficult to operate, and require high professional expertise. At the same time, the impact of the applied physical field on the physicochemical properties of microfluidic reagents must also be considered. Passive methods do not require additional energy and do not involve any complex active energy excitation mechanisms. Instead, they utilize the flow of fluid through certain structural obstacles to improve the efficiency of precise microfluidic control. However, existing passive microfluidic structures have complex designs, extremely high machining precision requirements, and are difficult to manufacture. They are prone to microstructure clogging and difficult to clean, and have extremely poor reusability. It is difficult to obtain microfluidic devices with optimal performance and it is difficult to meet the demand for multifunctional integrated microfluidic devices in modern biomedicine and other fields.

[0005] In addition, because biofilms and biological tissues are very sensitive to fluid flow rate and direction, cells or biological tissue cultures in a co-culture environment must be independent of each other and do not interfere with each other. Currently, biomedicine uses a method of setting up multiple channels in parallel on a microfluidic chip to achieve co-culture of bacteria, cells and organ tissues. For multi-inlet parallel channel devices, more microvalve structures must be used to strictly control the flow rate, flow direction and input of nutrients in different channels to eliminate the influence of irrelevant factors. This requires higher skills and experience of microfluidic device operators.

[0006] Currently, the design of microfluidic devices is mostly based on experience and intuition, or relies on repeated attempts by microfluidic researchers to continuously improve the performance of the device. There is a lack of systematic understanding of the underlying mechanism of flow control of the micro-unit structure (microstructure shape, characteristic scale, microstructure layout angle, spatial topological distribution) in microfluidic devices.

[0007] Therefore, those skilled in the art are committed to providing a microfluidic metamaterial chip structure design method and the resulting microfluidic metamaterial structure, so as to realize the microfluidic metamaterial topological structure design with coordinated regulation of microfluid flow rate and flow direction space. Summary of the Invention

[0008] In view of the deficiencies in the prior art, the technical problem to be solved by the present invention is how to provide a microfluidic metamaterial structure design method and a microfluidic material structure that can achieve coordinated regulation of microfluid flow rate and flow direction space.

[0009] To achieve the above object, the present invention provides a method for designing a microfluidic metamaterial structure, comprising the following steps:

[0010] Step 1: Setting up the microfluidic environment;

[0011] Step 2, calculating the equivalent parameters of the microfluidic metamaterial;

[0012] Step 3: parametrically design the micro unit structure;

[0013] Step 4: Build a control performance database;

[0014] Step 5: Construct the micro-unit spatial topology structure.

[0015] Furthermore, step 1 specifically includes:

[0016] Step 1.1, pre-define the key parameters of microfluidic flow rate and flow path in the microfluidic culture environment;

[0017] Step 1.2: Establish a spatial transformation theoretical model based on the key parameters.

[0018] Furthermore, the spatial transformation theoretical model includes: a spatial distortion transformation model, a spatial expansion transformation model, and a spatial compression-stretching transformation model.

[0019] Furthermore, in step 2, according to the spatial transformation theoretical model of step 1, an equivalent mapping between spatial transformation and microfluidic metamaterial is completed to obtain model parameters of the microfluidic metamaterial.

[0020] Furthermore, in step 3, the characteristic size and rotational arrangement angle of the micro unit structure are determined through finite element simulation and parametric scanning.

[0021] Furthermore, in step 4, numerical analysis and statistical methods are used to establish a microstructure flow field control performance database.

[0022] Furthermore, in step 5, a micro-unit spatial topological structure of the microfluidic metamaterial is constructed according to the control performance requirements.

[0023] Preferably, the method further comprises: verifying the precise control performance of the flow rate and flow direction of the topological structure.

[0024] Preferably, the method further comprises: performing multi-scale coupling control analysis to optimize the overall fluid control performance of the microfluidic metamaterial.

[0025] The present invention also provides a microfluidic metamaterial structure, which is designed by the above-mentioned design method.

[0026] The present invention has at least the following beneficial technical effects:

[0027] The microfluidic metamaterial structure design method of the present invention constructs a design method that unifies the multi-scale collaborative coupling of "microstructure shape-characteristic scale-rotation angle-spatial topological structure" of microfluidic metamaterials and microfluidic performance, thereby achieving a microfluidic flow control effect of collaboratively regulating the microfluidic flow velocity and flow direction in a specific area.

[0028] The microfluidic metamaterial structure of the present invention regulates the flow rate and direction of the microfluid in a specific local area, provides a micro-culture environment in which each culture area is independent and does not interfere with each other, and meets the co-culture requirements in biomedical engineering.

[0029] The concept, specific structure and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, characteristics and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 1 is a schematic flow chart of a method for designing a microfluidic metamaterial structure according to an embodiment of the present invention;

[0031] Figure 2 is a schematic diagram of a theoretical model of spatial transformation according to an embodiment of the present invention;

[0032] Figure 3 Schematic diagram of a multifunctional coupling design with adjustable flow pattern according to an embodiment of the present invention;

[0033] Figure 4 Schematic diagram of the spatial topology design of the microfluidic metamaterial structure according to an embodiment of the present invention;

[0034] Figure 5 Schematic diagram of a microfluidic metamaterial rotating mixing structure according to an embodiment of the present invention;

[0035] Figure 6 Schematic diagram of precise control of flow velocity of metamaterial micro-flow according to an embodiment of the present invention;

[0036] Figure 7 Schematic diagram of a coupling model for precise control of microfluid flow rate and flow direction according to an embodiment of the present invention. DETAILED DESCRIPTION

[0037] The following describes preferred embodiments of the present invention to make its technical content clearer and easier to understand. The present invention can be embodied in many different forms of embodiments, and the scope of protection of the present invention is not limited to the embodiments mentioned herein.

[0038] In the drawings, components with identical structures are denoted by the same reference numerals, and components with similar structures or functions are denoted by similar reference numerals. The size and thickness of each component shown in the drawings are arbitrary and are not limited by the present invention. For clarity, the thickness of components in some places in the drawings is appropriately exaggerated.

[0039] The present invention provides a method for designing microfluidic metamaterial structures. Starting from the basic control equations of fluid dynamics, a design method is constructed that unifies the multi-scale collaborative coupling of "microstructure shape-characteristic scale-rotation angle-spatial topological structure" and microfluidic performance of microfluidic metamaterials, thereby achieving a microfluidic flow control effect in which the microfluidic flow velocity and flow direction are coordinated in a specific area.

[0040] like Figure 1 As shown, the implementation process of a specific embodiment of the microfluidic metamaterial structure design method of the present invention is as follows.

[0041] Step 1: Set up the microfluidic environment. This step specifically includes the following processes:

[0042] Step 1.1: predefine key parameters of the microfluid flow rate and flow path in the microfluidic culture environment, wherein the key parameters include the microfluid flow rate, flow path, etc.

[0043] Step 1.2: Establish a spatial transformation theoretical model based on the above key parameters, wherein the spatial transformation theoretical model includes: a spatial distortion transformation model, a spatial expansion transformation model, and a spatial compression-stretching transformation model.

[0044] Establishing a tunable microfluidic theoretical model of microfluidic metamaterials is the basis for precise regulation and control of the flow state of microfluids. As the main control equation of fluid flow, the Navier-Stokes equation must first be kept invariant in form when performing coordinate transformation operations; then, the flow trajectory of the fluid is pre-set according to the needs of flow field regulation, and the coordinate transformation theoretical model between the original fluid space and the transformed space is established by transforming the original space by twisting, expanding, compressing and stretching. Due to the laminar flow and low Reynolds number characteristics of microfluidics, how to establish a microfluidic control model that is not restricted by the external pressure field or velocity field and can quickly produce tunable high flow rate and high rotation effect is the key to achieving efficient mixing of microfluids. The spatial transformation theoretical model of this embodiment is as follows:

[0045] like Figure 2As shown in Figure A, a microfluidic rotation mixing and flow direction control are achieved through a space distortion transformation model. In this model, first, the rotation angle of the flow field in a specific target area is determined according to the mixing requirements of microfluidics. Specifically, assuming that the two-dimensional space is divided into three regions by shell-shaped metamaterials, according to the space transformation theory, to achieve the rotation mixing effect of the microfluidic field, the corresponding coordinate mapping transformation is as follows:

[0046] Region I: r < R1, r' = r, z' = z, θ' = θ + θ0;

[0047] Region II: r > R2, r' = r, z' = z, θ' = θ;

[0048] Region III: R1 < r < R2, r' = r, z' = z,

[0049] where,

[0050] This set of space mapping transformation relationships causes a θ0 angle difference in the flow fields of Region I and Region III. The rotation angle θ0 can be increased or decreased according to the mixing requirements. When r = R1 = R2, the flow field will not have a rotation mixing effect; when r = R1 = 0, the rotation mixing effect will occur in the entire flow field area where r < R2.

[0051] Then, based on the above mapping transformation, a transformation mapping relationship corresponding to a specific rotation area in the original coordinate space and the transformation space is established.

[0052] As Figure 2 shown in Figure B, a microfluidic flow rate regulation and co-culture model are achieved through a space expansion transformation model. Specifically, assuming that the two-dimensional space is divided into three regions by shell-shaped metamaterials: Region I (r < R1) is the static regulation area of the microfluidic field; Region II (R1 < r < R2) is the functional area of the microfluidic metamaterials; Region III (r > R2) is the background flow field area outside the metamaterial structure, that is, the area where no space transformation operation is required. To achieve the effect of specific area isolation, the corresponding coordinate mapping transformation is as follows:

[0053]

[0054] In the formula,

[0055] At this time, at the center point 0 of the original coordinate space, through the execution of the transformation operation, it expands into an annular area with a radius of R1 in the transformation space. Using this area, the function of static isolation culture of the microfluidic field can be achieved. Using this model, a static culture area can be created, in which the fluid is almost static, so as to store the targeted drug for directional drug delivery.

[0056] Through the space expansion transformation model, a microfluidic metamaterial cloak region that isolates the mutual influence of the internal and external flow fields of a specific region is constructed, making multiple regions in the same culture microenvironment independent of each other and non-interfering. This plays a crucial role in implanting in-vivo micro-devices and ensuring that they do not interfere with and damage the original flow and functions in the body, as well as for monitoring and comparison during co-culture of cells, bacteria, and organ tissues.

[0057] As Figure 2 shown in Figure C in [reference], the microfluidic flow rate control and culture medium concentration regulation are achieved through the space compression-stretching transformation model. Specifically, assume that the two-dimensional space is divided into four regions by the shell-shaped metamaterial: Region I (r < R1) is the micro-flow state control region; Regions II (R1 < r < R2) and Region III (R2 < r < R3) are the microfluidic metamaterial regulation structure regions; Region IV (r > R3) is the background flow field region outside the metamaterial structure. To achieve dynamic regulation of the flow state, the corresponding coordinate transformation relationship is:

[0058]

[0059] The specific process is as follows: First, the space defined by the green dashed line R2 is uniformly compressed into the inner layer R1; second, the space between the green R2 and red R3 boundaries is non-uniformly stretched into the middle and outer layers, that is, stretched into Regions II and III (R1 < r < R3). After this operation, the flow field with a radius of R2 in the original space is compressed into the region enclosed by the transformed space R1, and the flow field between R2 and R3 in the original space is stretched into the region between spaces R1 and R3. This theoretical model can dynamically adjust the flow velocity magnitude in the core flow field control Region I by adjusting the relative proportional relationship between the characteristic scales of R1, R2, and R3.

[0060] Through the space compression-stretching transformation model, a functional region that can dynamically adjust the flow state of the microfluidic field according to the actual control requirements of microfluids can be constructed. Since the growth of bacterial biofilms, cells, and biological tissues is very sensitive to changes in fluid flow, and there are also significant differences in the requirements for the flow environment at different stages of their cultivation; during the cultivation of microorganisms and biological tissues, the exchange of nutrients and the discharge of waste in the cultivation device can be achieved by adjusting the flow state of specific regions. When an increase in drug dosage is required, this theoretical model precisely controls the drug release rate by regulating the flow state of the drug storage region and can be dynamically adjusted according to the patient's treatment stage, providing a solution for achieving high-precision and efficient targeted drug delivery.

[0061] Step 2: Calculate the equivalent parameters of the microfluidic metamaterial. In this step, according to the space transformation theoretical model in Step 1, the space transformation and the equivalent mapping of the microfluidic metamaterial are completed to obtain the model parameters of the microfluidic metamaterial.

[0062] Specifically, coupling the spatial compression-stretching transformation model with the spatial expansion transformation model can collaboratively achieve targeted drug delivery and sustained release therapy to the lesion; coupling the spatial compression-stretching transformation model with the spatial distortion transformation model can collaboratively achieve coordinated regulation of flow velocity and flow direction in the core process control area. This coupling process is as follows: Figure 3 shown.

[0063] Step 3: Parametric design of micro-unit structure: In this step, the characteristic dimensions and rotation angles of the micro-unit structure are determined through finite element simulation and parametric scanning.

[0064] After obtaining the theoretical model of tunable microfluidic control of microfluidics metamaterials, in actual physical space, according to the transformation tensor distribution of the target geometric area, the microfluidics metamaterial technology is used to design the anisotropic microscale equivalent medium required for spatial transformation, completing the equivalence of metamaterials and spatial transformation operations, thereby realizing the required flow regulation function and enhancing the control over the fluid motion process.

[0065] After the spatial transformation, the constant material properties (fluid density, dynamic viscosity) in the original Navier-Stokes equations are transformed into tensor form. Ignoring the body force source term, the conservation form of the original governing equation Navier-Stokes is simplified to:

[0066]

[0067] By adopting the space transformation processing, the Navier-Stokes equations in the transformation space are expressed as follows:

[0068]

[0069] Among them, the density in the transformation space and dynamic viscosity coefficient is transformed into the form of an inhomogeneous anisotropic tensor. ρ and μ in the original space and μ in the new transformed space and The corresponding relationship between them is:

[0070]

[0071] The expression obtained by agreement is: and in,

[0072] In three-dimensional space, the transformation tensor It has multiple off-diagonal elements and exhibits spatial anisotropy. With the help of the basic properties of matrix theory, it is clear that the transformation tensor is a real symmetric matrix. The transformation tensor after matrix diagonalization has 3 remaining diagonal elements. The diagonalized matrix consists of 5 diagonal elements. Reduced to 3 The complexity of metamaterial structure design is reduced. In order to solve the continuous change of the properties of the transformation tensor space, the fluid metamaterial is constructed using piecewise integral approximation and hierarchical design using numerical analysis and discrete methods.

[0073] like Figure 4 As shown in Figure 1, the diagonalized matrix and the original transformation tensor matrix introduce a spatial rotation angle α between the coordinate axes. Therefore, after processing the real symmetric transformation tensor matrix, it is necessary to confirm the rotation correspondence α between the spatial coordinate axes before and after the matrix diagonalization. In other words, the rotation angle α of the coordinate axis needs to be incorporated into the design process of the metamaterial micro-unit structure.

[0074] In addition to the micro-unit structure, this step also characterizes the rectangular micro-column units required for the microfluidic functional area, as well as the micro-cylinders to maintain uniform flow outside the functional area. The purpose of the micro-cylinders is to match the surrounding flow field, thereby maintaining the microfluidic areas without affecting each other. The characteristic scales of the micro-rectangular unit and micro-cylinder structures are based on It is obtained by finite element numerical simulation.

[0075] Finite element numerical simulations are combined with the concept of equivalent hydrodynamic properties from porous media theory to characterize the microfluidic field perturbations induced by the shape, characteristic scale, and rotation angle of the metamaterial's microcells. When constructing a microfluidic metamaterial, a corresponding number of microstructured unit cells (a concept of spatial discretization) are divided within each layer of the metamaterial structure. Each unit cell is filled with a micropillar structure of some form at a specific rotation angle, creating the metamaterial structure required for microfluidic control. The effective hydrodynamic performance of the metamaterial's microcell structure is determined by factors such as the microcell scale, the shape, characteristic scale, and rotation angle of the microelement columns within the unit cell, and is independent of the material properties of the microcell composite material itself.

[0076] Step 4: Constructing a control performance database: In this step, numerical analysis and statistical methods are used to establish a microstructure flow field control performance database.

[0077] Specifically, the microcell structures of the parametric scan in step 3 are grouped according to the requirements for precise microfluidic control. For example, if microfluidic flow direction control requires 15°, 30°, 60°, and 90°, the sizes and spatial rotation angles of the microcells correspond to these, respectively.

[0078] The microfluid flow direction of a specific embodiment of the present invention is regulated by a micro unit structure characteristic size (x l ,yl ), rotation angle (α), and the diameter (d_c) of the uniform micro-cylinder array to maintain the flow fields between functional areas without affecting each other are shown in Table 1.

[0079] Table 1

[0080]

[0081] Step 5: Constructing the micro-unit spatial topology structure. In this step, the micro-unit spatial topology structure of the microfluidic metamaterial is constructed according to the control performance requirements.

[0082] like Figure 5 As shown in the figure, the differences in the types of microfluidic chips used to culture different microorganisms or biomacromolecules lead to significant differences in the degree and intensity of microfluidic mixing required. Therefore, based on the flow rate and direction control performance requirements, micro-unit structures with specific shapes, characteristic scales, and rotation angles are selected. For example, micro-unit structures can be layered in the form of concentric rings at equal intervals to obtain the micro-unit spatial topology.

[0083] Some embodiments of the present invention further include the following steps.

[0084] Step 6: Verify the topology structure's precise control performance of flow rate and flow direction.

[0085] In order to effectively solve the problem of sensitivity of microbial culture, organ chip construction, and biomaterial amplification in micro-culture environments to flow velocity and direction in biomedical engineering, as well as to reduce the damage caused by implantable micro-devices to the original flow and function in the body, it is necessary to construct a functionally tunable micro-flow precision control metamaterial structure. For a static culture environment, based on the microstructure characterization results in step 3, a static culture metamaterial structure, namely a cylindrical array, can be constructed to isolate a specific area from the external flow field or the interaction between regions. The results are as follows: Figure 6 shown.

[0086] Some other embodiments of the present invention further include the following steps.

[0087] Step 7: Conduct multi-scale coupling control analysis to optimize the overall fluid control performance of the microfluidic metamaterial.

[0088] For a dynamically tunable microfluidic culture environment, it is necessary to construct a specific area that can dynamically adjust the microfluidic flow velocity according to the actual flow requirements based on the established compression-stretch transformation theoretical model between the original space and the transformed space. In order to effectively solve the problem of the sensitivity of living matter to flow direction, by coupling the spatial coordinate compression-stretch transformation model and the rotation transformation theoretical model, and then based on the above characterization results, a microfluidic metamaterial structure model with dynamically tunable microfluidic flow velocity and flow direction is finally obtained. The results are shown in the figure below. Figure 7As shown, the innermost layer is a micro-rectangular array with a microfluidic rotation effect and a constant angle with the radial direction; outside the innermost layer is a micro-rectangular column layered array with the main axis of the rectangular microcolumns parallel to the radial direction (no angle) for regulating the fluid flow rate; the functional area is surrounded by a micro-cylinder array.

[0089] This application proposes a design method for a microfluidic metamaterial structure, and the microfluidic metamaterial structure obtained by this design method is also within the protection scope of this application.

[0090] The present invention presets the fluid flow trajectory according to the flow field regulation requirements, and establishes a coordinate transformation theoretical model between the original fluid space and the transformation space by rotating, expanding, compressing and stretching the original space. At the same time, a compression-stretching transformation relationship model is constructed to achieve dynamic adjustment of the flow state of the microfluidic field, and to collaboratively complete the regulation of the flow velocity and flow direction in the core flow field control area. The spatial variation theoretical models of the present invention are all limited to a specific or multiple functional areas, so they only perform regulation of the microfluid flow velocity and flow direction in specific local areas. The culture areas will not interfere with each other, nor will they affect the culture environment outside the functional area. All established control mechanisms and theoretical models can meet the co-cultivation requirements in biomedical engineering.

[0091] The above describes in detail the preferred embodiments of the present invention. It should be understood that those skilled in the art can make numerous modifications and variations based on the concepts of the present invention without inventive effort. Therefore, any technical solutions that can be derived by those skilled in the art through logical analysis, reasoning, or limited experimentation based on the concepts of the present invention and the prior art should be within the scope of protection defined by the claims.

Claims

1. A method for designing a microfluidic metamaterial structure, characterized in that: The following steps are involved: Step 1: Set up the microfluidic environment, including: Step 1.1, pre-define the key parameters of microfluidic flow rate and flow path in the microfluidic culture environment; Step 1.2: establishing a spatial mapping transformation theoretical model based on the key parameters, wherein the spatial mapping transformation theoretical model includes: a spatial distortion transformation model, a spatial expansion transformation model, a spatial compression-stretching transformation model and a coupled model thereof; Step 2: Calculate the equivalent parameters of the microfluidic metamaterial. According to the spatial mapping transformation theoretical model described in step 1, complete the equivalent mapping between the spatial transformation and the microfluidic metamaterial to obtain the model parameters of the microfluidic metamaterial. Specifically, couple the spatial compression-stretching transformation model with the spatial expansion transformation model to collaboratively achieve targeted drug delivery and sustained release therapy to the lesion. Couple the spatial compression-stretching transformation model with the spatial distortion transformation model to collaboratively achieve coordinated regulation of flow velocity and flow direction in the core process control area. Step 3: parametrically design the micro-unit structure, and determine the characteristic size and rotation angle of the micro-unit structure through finite element simulation and parametric scanning; Step 4: Construct a control performance database, using numerical analysis and statistical methods to establish a microstructure flow field control performance database; Step 5: constructing a micro-unit spatial topology structure, and constructing a micro-unit spatial topology structure of the microfluidic metamaterial according to the control performance requirements; Step 6: Verify the precise control performance of flow rate and flow direction of the topological structure; Step 7: Conduct multi-scale coupling control analysis to optimize the overall fluid control performance of the microfluidic metamaterial.

2. A microfluidic metamaterial structure, characterized in that: The design is obtained using the design method described in claim 1.

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