磁靶向系统中磁流体动态特性和行为控制研究
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摘要
近年来随着磁纳米材料和多功能高分子材料研究的深入,基于纳米磁流体的磁靶向系统因具有高靶向性和可控性而成为一种重要的靶向递送系统,在药物/基因靶向输运、肿瘤治疗、磁分离及微流控等领域引起广泛关注,具有重要的研究价值和应用前景。但由于磁靶向系统涉及到电磁学、流体力学、及纳米技术等多学科交叉研究内容,目前国内外磁靶向技术的整体发展水平仍处于基础研究阶段,特别是在靶向递送机理、靶向行为控制和靶向系统优化等方面亟需开展进一步的研究。
靶向递送机理方面,本文基于电磁学和流体力学基本原理,建立了磁流体靶向递送过程中的磁场-流场-浓度场多场耦合动力学模型,考虑了磁场作用下磁流体的非线性磁化特性和磁体积力对流体流动行为的影响。在此基础上对外加梯度磁场作用下管道中磁流体浓度分布特征和变化规律进行了数值模拟,并探讨了流速、磁场源结构和磁参数对磁流体动力学行为的影响,进一步加强了对动力学数学模型的理解。
同时针对磁流体靶向递送过程中的磁团聚现象,本文采用Cluster-moving蒙特卡罗方法研究了不同磁场方向和磁能大小下磁性粒子在均匀磁场下的随机团聚行为,在此基础上提出磁团聚行为降低磁性颗粒在运动过程中所受到的流体粘滞阻力是造成实验中粒子靶向聚集速度加快的可能原因。后基于磁偶极子模型,通过对双/三粒子模型磁作用能和力的分析,定性地揭示了磁性粒子在磁场作用下团聚形成机理。
靶向行为控制方面,本文从磁场力的数学模型出发,提出通过独立控制磁场强度和梯度参数可实现磁场力大小和方向可调,在此基础上为微流控靶向系统设计了一套由外部均匀场源和内部梯度场源构成的组合磁场源方案,并开展了组合磁场源作用下微管道内磁流体靶向行为的可控性研究。同时基于该磁场源方案设计了一套微混合器系统,研究了该系统作用下电流时变频率、入口速度及磁体积力等参数对微管道中流体混合规律及效率的影响,为磁力式微混合器的优化设计提供了一定的依据和指导。
靶向系统优化方面,本文基于Comsol和Matlab联合仿真技术对磁场源进行了优化设计。以Maxwell梯度线圈为例分析了其结构参数对磁场梯度和均匀度的影响,指出厚壁线圈体系下传统Maxwell线圈设计思路的不合理性及结构参数优化的必要性。在此基础上提出并建立了基于有限元和自适应混合遗传算法的磁源系统电磁优化模型,实现了厚壁梯度线圈系统和永磁体阵列式均匀场系统高性能优化。
最后本文针对现有药物筛选体系中药物与受体激活效率低这一难题,本文提出采用磁靶向技术来提高细胞表面受体附近的有效药物浓度,进而有效增强药物与受体的激活效率。在此基础上,分析和设计了一套可在96孔板区域内产生均匀磁场力的磁靶向系统,并初步开展了该系统作用下药物与GPCR激活特性的实验研究。
With the development of magnetic nano-materials and multi-functional polymer materials in recent years, the magnetic targeting system based on nano-magnetic fluid has become an important delivery system for high target and controllable performance, which can be an effective research tool in drug/gene targeting delivery, cancer therapy, magnetic separation and microfluidic chip. However, due to the fact that the magnetic targeting system involves an interdisciplinary research of electromagnetics, fluid mechanics, and nano-technology, the magnetic targeting technology at home and abroad is still under development, especially in the fields of targeting mechanism, targeting behavior control and targeting system optimzation.
In the respect of the targeting mechanism, the paper has established a coupling mathematical model of magnetic field, flow field, and concentration field for the hydrodynamics of magnetic fluid under magnetic field based on the basic principles of electromagnetism and fluid mechanics, taking into account the non-linearity magnetization performance of the magnetic fluid and the effect of magnetic body force on the fluid flow behavior. On this basis, a numerical simulation is presented to study the variation law of the magnetic fluid in the pipe under gradient magnetic field and the effects of flow velocity, magnetic field source structure and magnetic parameters on the magnetic fluid dynamic behavior, which can be used to further understand the mathmatical model.
In view of the aggregation phenomenon of magnetic particles under magnetic field, the paper studies the particle aggregation phenomenon by simulating the random movement behavior of magnetic particles under magnetic field with Cluster-moving Monte Carlo method. And the effects of magnetic field direction and magnetic energy on the aggregation morphology are analyzed. On the basis, the paper points out that the possible main reason for the increase of the particle speed in the experiment is that the viscous-fluid drag force acting on the particles is reduced due to the aggregation behavior. Meanwhile, the aggregation mechanism is studied by analyzing the magnetic interaction energy and force in magnetic particle system under magnetic field.
In the respect of the targeting behavior control, through the mathematical model of the magnetic force, the paper points out that the magnitude and direction of magnetic force can be controlled by independently adjusting magnetic field strength and magnetic field gradient parameters. And a compound magnetic field source system with one uniform magnetic field and one gradient magnetic field is proposed. Based on the field source, the dynamic targeting behavior of magnetic fluid in the microfludic system is studied and an effective micro-mixer system is designed. Then the effects of current frequency, inlet velocity and magnetic body force on the regularity and efficiency of fluid mixing in the microchannel are investigated, which can be used as basis and instruction for the optimum design of magnetic micro-mixer.
In the respect of optimum design for magnetic targeting system, the paper firstly investigates the influence of coil's parameters on the gradient and uniformity of the target field for the thick-wall Maxwell coils by the co-simulation method of Comsol and Matlab. Then it points out that the traditional design method for thick coils is not reasonable and the optimum design for the coil is very necessary. On this basis, an electromagnetic optimization model of magnetic source system with finite element analysis and adaptive hybrid genetic algorithm is set up. And then the paper realizes the optimizations of thick-wall Maxwell coils and permanent array system well.
Finally, due to the fact that the drug and receptor activation efficiency is low in existing drug screening system, this paper introduces the magnetic targeting technique to improve the effective drug concentration in the vicinity of the cell surface receptor. And thus it can effectively enhance the efficiency of drug and receptor activation. On this basis, a magnetic targeting system, which can generate the uniform magnetic force in the region of96-well plates force, is designed and used to carry out preliminary experimental study of drug and GPCR activation characteristics.
靶向递送机理方面,本文基于电磁学和流体力学基本原理,建立了磁流体靶向递送过程中的磁场-流场-浓度场多场耦合动力学模型,考虑了磁场作用下磁流体的非线性磁化特性和磁体积力对流体流动行为的影响。在此基础上对外加梯度磁场作用下管道中磁流体浓度分布特征和变化规律进行了数值模拟,并探讨了流速、磁场源结构和磁参数对磁流体动力学行为的影响,进一步加强了对动力学数学模型的理解。
同时针对磁流体靶向递送过程中的磁团聚现象,本文采用Cluster-moving蒙特卡罗方法研究了不同磁场方向和磁能大小下磁性粒子在均匀磁场下的随机团聚行为,在此基础上提出磁团聚行为降低磁性颗粒在运动过程中所受到的流体粘滞阻力是造成实验中粒子靶向聚集速度加快的可能原因。后基于磁偶极子模型,通过对双/三粒子模型磁作用能和力的分析,定性地揭示了磁性粒子在磁场作用下团聚形成机理。
靶向行为控制方面,本文从磁场力的数学模型出发,提出通过独立控制磁场强度和梯度参数可实现磁场力大小和方向可调,在此基础上为微流控靶向系统设计了一套由外部均匀场源和内部梯度场源构成的组合磁场源方案,并开展了组合磁场源作用下微管道内磁流体靶向行为的可控性研究。同时基于该磁场源方案设计了一套微混合器系统,研究了该系统作用下电流时变频率、入口速度及磁体积力等参数对微管道中流体混合规律及效率的影响,为磁力式微混合器的优化设计提供了一定的依据和指导。
靶向系统优化方面,本文基于Comsol和Matlab联合仿真技术对磁场源进行了优化设计。以Maxwell梯度线圈为例分析了其结构参数对磁场梯度和均匀度的影响,指出厚壁线圈体系下传统Maxwell线圈设计思路的不合理性及结构参数优化的必要性。在此基础上提出并建立了基于有限元和自适应混合遗传算法的磁源系统电磁优化模型,实现了厚壁梯度线圈系统和永磁体阵列式均匀场系统高性能优化。
最后本文针对现有药物筛选体系中药物与受体激活效率低这一难题,本文提出采用磁靶向技术来提高细胞表面受体附近的有效药物浓度,进而有效增强药物与受体的激活效率。在此基础上,分析和设计了一套可在96孔板区域内产生均匀磁场力的磁靶向系统,并初步开展了该系统作用下药物与GPCR激活特性的实验研究。
With the development of magnetic nano-materials and multi-functional polymer materials in recent years, the magnetic targeting system based on nano-magnetic fluid has become an important delivery system for high target and controllable performance, which can be an effective research tool in drug/gene targeting delivery, cancer therapy, magnetic separation and microfluidic chip. However, due to the fact that the magnetic targeting system involves an interdisciplinary research of electromagnetics, fluid mechanics, and nano-technology, the magnetic targeting technology at home and abroad is still under development, especially in the fields of targeting mechanism, targeting behavior control and targeting system optimzation.
In the respect of the targeting mechanism, the paper has established a coupling mathematical model of magnetic field, flow field, and concentration field for the hydrodynamics of magnetic fluid under magnetic field based on the basic principles of electromagnetism and fluid mechanics, taking into account the non-linearity magnetization performance of the magnetic fluid and the effect of magnetic body force on the fluid flow behavior. On this basis, a numerical simulation is presented to study the variation law of the magnetic fluid in the pipe under gradient magnetic field and the effects of flow velocity, magnetic field source structure and magnetic parameters on the magnetic fluid dynamic behavior, which can be used to further understand the mathmatical model.
In view of the aggregation phenomenon of magnetic particles under magnetic field, the paper studies the particle aggregation phenomenon by simulating the random movement behavior of magnetic particles under magnetic field with Cluster-moving Monte Carlo method. And the effects of magnetic field direction and magnetic energy on the aggregation morphology are analyzed. On the basis, the paper points out that the possible main reason for the increase of the particle speed in the experiment is that the viscous-fluid drag force acting on the particles is reduced due to the aggregation behavior. Meanwhile, the aggregation mechanism is studied by analyzing the magnetic interaction energy and force in magnetic particle system under magnetic field.
In the respect of the targeting behavior control, through the mathematical model of the magnetic force, the paper points out that the magnitude and direction of magnetic force can be controlled by independently adjusting magnetic field strength and magnetic field gradient parameters. And a compound magnetic field source system with one uniform magnetic field and one gradient magnetic field is proposed. Based on the field source, the dynamic targeting behavior of magnetic fluid in the microfludic system is studied and an effective micro-mixer system is designed. Then the effects of current frequency, inlet velocity and magnetic body force on the regularity and efficiency of fluid mixing in the microchannel are investigated, which can be used as basis and instruction for the optimum design of magnetic micro-mixer.
In the respect of optimum design for magnetic targeting system, the paper firstly investigates the influence of coil's parameters on the gradient and uniformity of the target field for the thick-wall Maxwell coils by the co-simulation method of Comsol and Matlab. Then it points out that the traditional design method for thick coils is not reasonable and the optimum design for the coil is very necessary. On this basis, an electromagnetic optimization model of magnetic source system with finite element analysis and adaptive hybrid genetic algorithm is set up. And then the paper realizes the optimizations of thick-wall Maxwell coils and permanent array system well.
Finally, due to the fact that the drug and receptor activation efficiency is low in existing drug screening system, this paper introduces the magnetic targeting technique to improve the effective drug concentration in the vicinity of the cell surface receptor. And thus it can effectively enhance the efficiency of drug and receptor activation. On this basis, a magnetic targeting system, which can generate the uniform magnetic force in the region of96-well plates force, is designed and used to carry out preliminary experimental study of drug and GPCR activation characteristics.
引文
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