Development of a multi-scale model for the adsorption of molecular target substances to magnetic carrier particles using the Lattice-Boltzmann methods

使用格子-玻尔兹曼方法开发分子目标物质吸附到磁性载体颗粒的多尺度模型

• 批准号: 256075891
• 负责人: Privatdozent Dr. Mathias Joachim Krause
• 金额: --
• 依托单位: Arbeitsgruppe Verfahrenstechnische Maschinen (VM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/256075891?language=en
• 关键词: Development; multi; scale; model; adsorption

Biotechnology is considered a key technology for the production of pharmaceuticals, specialty chemicals and food. Many pharmaceutical products are produced by expression in genetically modified bacteria or cells. Thereby, the separation of the desired products from fermentation broth plays an important role. The separation process is difficult. Besides the target protein, there are different contaminating proteins which behave similarly and which are separated only by means of highly selective methods taking advantage of differences in isoelectric point or specific binding sites. Magnetic particles with functionalized surface are an efficient option for the separation. Currently there are no detailed investigations of the adsorption process and its influence on the whole separation process, specifically on the maximum volume flow. However, they are necessary to develop efficient procedures for industrial use.The aim of the project is to investigate the process of adsorption and separation of molecular target substances on magnetic functionalized particles. The different physical phenomena in different orders of magnitude (adsorption, inter-particular effects and separation from fluid) are challenging concerning modeling as well as simulation. The process is usually described separately by micro- and macroscopic models and coupled via boundary conditions. The relationships are complex and have not been described in a single approach. Due to high computational costs simulations were limited both locally to small areas and partially to sub-processes. In the proposed project, the physical phenomena are linked by mesoscopic modeling using Lattice Boltzmann methods (LBM) for simulation. Thus, the model to be developed links molecular phenomenon in Ångström scale with macroscopic fluid effects as well as their influence on the particle motion in the mm scale. A common approach is the microscopic description of particle dynamics, discretized by a Discrete Element Method, and a macroscopic model, discretized by a Finite Volume Method. The new approach allows a more efficient simulation and thus the simulation of a larger geometric scale, including the entire separation apparatus. The modeling approach of the calibration and validation takes place by simulation of adsorption processes in a static mixer. Then the model is reduced with sensitivity-based approaches, the process is simulated on a modern magnetic separator and experimentally validated. To final Euler-Euler-Euler model is transferable and may be used for other multi-scale issues like e.g. the simulation of photo- bioreactors in the future.

生物技术被认为是生产药品、特种化学品和食品的关键技术。许多药品都是通过转基因细菌或细胞的表达而生产的。因此，从发酵液中分离所需产物起着重要的作用。分离的过程是困难的。除了靶蛋白外，还有不同的污染蛋白，它们的行为相似，只能通过利用等电点或特定结合位点的差异的高选择性方法来分离。具有功能化表面的磁性颗粒是一种有效的分离方法。目前还没有详细的研究吸附过程及其对整个分离过程的影响，特别是对最大体积流量的影响。然而，它们对于开发工业使用的有效程序是必要的。本项目旨在研究磁性功能化颗粒对分子靶物质的吸附和分离过程。不同数量级的不同物理现象（吸附、特殊间效应和从流体中分离）在建模和模拟方面具有挑战性。该过程通常由微观和宏观模型分别描述，并通过边界条件耦合。它们之间的关系是复杂的，并没有用单一的方法来描述。由于计算成本高，模拟既局限于局部小区域，又部分局限于子过程。在提出的项目中，物理现象通过使用晶格玻尔兹曼方法（LBM）进行模拟的介观建模联系起来。因此，待建立的模型将Ångström尺度下的分子现象与宏观流体效应及其对mm尺度下粒子运动的影响联系起来。常用的方法是用离散元法离散粒子动力学的微观描述和用有限体积法离散宏观模型。新的方法允许更有效的模拟，从而模拟更大的几何尺度，包括整个分离装置。标定和验证的建模方法是通过模拟静态混合器中的吸附过程来实现的。然后采用基于灵敏度的方法对模型进行化简，在现代磁选机上进行了仿真，并进行了实验验证。最终，欧拉-欧拉-欧拉模型是可转移的，并可用于其他多尺度问题，如未来光生物反应器的模拟。

项目成果

Three-dimensional protein structure prediction based on memetic algorithms

• DOI: 10.1016/j.cor.2017.11.015
• 发表时间: 2018-03
• 期刊: Comput. Oper. Res.
• 作者: L. Corrêa;Bruno Borguesan;M. Krause;M. Dorn

Fluid flow simulations verified by measurements to investigate adsorption processes in a static mixer

通过测量验证流体流动模拟，以研究静态混合器中的吸附过程

• DOI: 10.1016/j.camwa.2018.08.066
• 发表时间: 2018
• 期刊: Comput. Math. Appl.
• 作者: M.-L. Maier;S. Milles;S. Schuhmann;G. Guthausen;H. Nirschl;M. J. Krause
• 通讯作者: M. J. Krause

Multiscale Simulation with a Two‐Way Coupled Lattice Boltzmann Method and Discrete Element Method

• DOI: 10.1002/ceat.201600547
• 发表时间: 2017-09
• 期刊: Chemical Engineering & Technology
• 影响因子: 2.1
• 作者: Marie-Luise Maier;T. Henn;Gudrun Thaeter;H. Nirschl;M. Krause

Everyone Is a Protagonist: Residue Conformational Preferences in High-Resolution Protein Structures

每个人都是主角：高分辨率蛋白质结构中的残基构象偏好

• DOI: 10.1089/cmb.2017.0182
• 发表时间: 2018
• 期刊: Journal of computational biology : a journal of computational molecular cell biology
• 作者: R. Ligabue-Braun;B. Borguesan;H. Verli;M. J. Krause;M. Dorn
• 通讯作者: M. Dorn