IMECH-IR
多孔介质 中 纳米颗粒反常扩散的研究
Alternative TitleAnomalous Diffusion of Nanoparticles in Porous Media
黄艺荣
Thesis Advisor胡国庆
2019-05-28
Degree Grantor中国科学院大学
Place of Conferral北京
Subtype硕士
Degree Discipline流体力学
Keyword纳米颗粒 反常扩散 多孔介质 穿透概率 位移 概率密度
Abstract

微纳米流体力学是研究微米、亚微米直至纳米尺度下的流体流动及物质输运规律的一门学科。微纳米流体力学与生物医学高度交叉,在人体复杂生理微环境下,作为药物输运及治疗功能载体的纳米颗粒 的 动力学特征,是亟须深入研究的重要科学问题。在微纳米尺度下,表征对流与扩散之比的 Peclet数 通常 小于 1可 知 扩散是主要的物质输运的机制。而人体生理微环境以各种复杂 介质 为重要组
成部分,具有 明显的多孔介质属性 ,因此纳米颗粒在人体内的运动 呈现出吸引人们关注的 反常扩散 特征 。理解纳米药物在多孔介质内部的扩散 特征和机理 对纳米药物的使用大有裨益,例如强化药物的扩散 以穿透肿瘤组织的多孔介质屏障 。 以往关于多孔介质中反常扩散的 研究往往 只关注 均方位移 (mean square displacement,以下简称 MSD)的 亚线性 ,然而 纳米颗粒在复杂生物 多孔介质中反常扩散有可能呈现出乎意料的复杂规律。因此本文 将 围绕多孔介质中 纳米 颗粒的反常扩散开展相关研究。直接在人体 内研究扩散现象十分困难,因此我们用水凝胶系统模拟具有多孔介质结构特征的 人体组织 微环境开展体外实验。 水凝胶具有重要的生物医学作用,常被用于筛选生物分子。琼脂凝胶是自然界中最为常见的水凝胶,结构简单,易于制备。本文首先选取琼脂凝 胶作为介质,对纳米颗粒在多孔介质中的反常扩散进行实验测量。 我们 用粒子追踪 观测不同尺寸的 牛血清蛋白 包裹的球形 纳米 颗粒在 不同孔隙尺寸的 琼脂凝胶内部的扩散。发现了颗粒尺寸和凝胶 孔洞结构和尺寸共同影响 颗粒 的 统计扩散特征。系综平均的均方位移 (ensemble mean square displacement,以下简称 eMSD)随着时间的变化会出现 三 个不同阶段的典型特征,时间平均的均方位移 (time-varied mean square displacement,以下简称 tMSD)显示了 颗粒 有很小的概率能够 在孔洞之间穿透 ,随着时间的增加 位移概率密度分布(displacement probability distribution 以下简称 DPD)的长尾在 上抬 ,最后稳定成固定的 Λ型。 传统的受限扩散模型不能够描述该现象。
为解释该 反常现象,我们 开展了 纳米颗粒 在 琼脂凝胶内部的扩散模拟研究。
构造了基于碰撞和小穿透概率的物理模型,并通过计算机进行蒙特卡洛模拟 给出
数值解。通过对比模拟和实验的 DPD和 MSD 我们 得出 凝胶中 纳米颗粒 穿透孔洞 的概率 发现 纳米颗粒 和凝胶壁面的碰撞是 DPD和 MSD反常的主要影响因
素 凝胶的浓度和 纳米颗粒 尺寸的大小差异影响 穿透的概率 。 该模型为描述纳米药物在复杂生物多孔介质中的扩散提供了有效的定量分析手段 。当纳米颗粒的尺寸与孔洞 相比 很小时,小概率的穿透模型无法 很好地 解释颗粒的扩散特征 。为了解决该问题, 并进一步 扩 展 理论 模型的应用范围,我们 构建多孔介质中纳米颗粒反常扩散的研究

II 了完整的多孔介质中了完整的多孔介质中纳米颗粒纳米颗粒扩散的理论模型扩散的理论模型。我们。我们提出提出等效孔洞理论,近似描等效孔洞理论,近似描述了多孔介质中通道对述了多孔介质中通道对纳米颗粒纳米颗粒运动的空间的影响运动的空间的影响;;提出了处理壁面和提出了处理壁面和纳米颗粒纳米颗粒水动力新方法,即结合经典的水动力公式和凝胶的空间结构给出全空间平均的水水动力新方法,即结合经典的水动力公式和凝胶的空间结构给出全空间平均的水动力学影响因子动力学影响因子。我们基于纳米颗粒。我们基于纳米颗粒不同运动模式不同运动模式的的叠加,推导出了叠加,推导出了的的DPD和和MSD的的解析解析表达式。该工作对多孔介质内部反常扩散机理作了详细表达式。该工作对多孔介质内部反常扩散机理作了详细的的分析,分析用全新的方法。

Other Abstract

Micro/Nanofluidics studies the fluid flow and transport of substance in the micro and nanoscale. Micro/Nanofluidics is an interdisciplinary research that can serves as a fundamental part in many biomedicine applications. The dynamics of nanoparticles in the complex microenviroment inside human body needs to be explored urgently due to the emerging technology of nanomedicine. Diffusion is the main mechanism of transport of nanomedicine on nanoscale, as the Peclet number become smaller than 1. The microenviroment of human body is complex and inhomogenous, which contain similar structures as porous media. Thus, the nanoparticle’s diffusion inside is normally anomalous. The understanding of the characteristics and the dynamics of diffusion in such media is significant to the application of nanomedicine. For example, it may help researchers to understand how to enhance the drug nanoparticles’ penetration of interstitial matrix of the tumor tissue. In previous studies, researchers only used non-linear mean square displacement (MSD) to describe the nanoparticle’s diffusion in porous media. However, recent advances has revealed extraordinary the anomaly of the diffusion. In this thesis, we focus on the anomalous diffusion of nanoparticles in such porous media.
To directly investigate the motion of nanoparticles in human body is difficult. Thus, we choose agargel gel to simulate the microenviroment in biological systems, which is a common hydrogel and is esily to fabricate. We firstly investigate the diffusion of BSA(bovine serum albumin)-coated nanoparticles in agarose gel with different pore sizes. The particle size and the structure of gel influence the statistical characteristic of the diffusion. The eMSD(ensemble mean square displacement) is found to manifest three typical stages, the slow increasing of the tMSD(time-varied mean square displacement) indicates that the nanoparticles has small probability to penetrate through pores. Futher, the value of tail part of the DPD increase with time and display a Λ shape at long time. The previous model of confined diffusion fail to explain these characteristics.
To explain such anomaly, we perform simulation to investigate nanoparticles’s diffusion in agarose gel. We pay special attention to particle-wall collision and the low probability of penetration. Comparing the simulation results with the experiment one, we draw the conclusion that the collision result in the anomaly of DPD andMSD and the probability of penrtration is low and depends on the size of nanoparticles and the mass fraction of gel. Our results demonstrate dynamics of nanoparticles in agarose gel, and our model offer a method to quantitatively analyze the drug nanoparticles’ diffsion in porous media.
However, the above simulation based on penetration does not work well when the particles are small compared with the pores. Thus, we establish a comprehensive theoretical model to demonstrate the nanoparticles’ motion in porous media. This includes: (1) equivalent-pore theory (2) ensemble hydrodynamic friction in a pore (3) a new method to calculate DPD. The equivalent-pore theory describes the interaction between the structure of porous media and the nanoparticles. The ensemble hydrodynamic model describes how the wall slows down the nanoparticles. Furthermore, we deduce an analytic solution of DPD and MSD by dividing the motion of nanoparticle in a pore into different modes. This works offers novel physical approach and a thorough analysis of the dynamic of nanoparticles’ diffusion in porous media.

Language中文
Document Type学位论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/79097
Collection中国科学院力学研究所
非线性力学国家重点实验室
Recommended Citation
GB/T 7714
黄艺荣. 多孔介质 中 纳米颗粒反常扩散的研究[D]. 北京. 中国科学院大学,2019.
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