Behavior of proteins inside microfluidic channels

微流体技术是一个快速发展的交叉学科研究领域，它结合了物理学、化学、材料科学和生物技术。新的微流体技术能够有效地处理、分析和分离蛋白质聚集体。这提供了几种微流体方法，用于快速，温和和高分辨率地分离液体介质中的颗粒，尺寸从1 nm到100 µm。这就是微流体通道在过滤技术、色谱和生化分析中越来越重要的原因。该项目的目的是优化微流控池设计，以最大限度地减少蛋白质分离过程中的机械应力。基于此结果，确定的分离效率和过程输出可以提高工业和分析过程的质量和数量。应力强度和频率可以通过通道的过程导向轮廓来操纵。例如，由于与管道壁的碰撞，低机械应力作用在具有增加的横截面和光滑壁的通道内的附聚物上。在这种情况下，聚集体不改变它们的状态，通过微流体通道。这种行为对于蛋白质的聚集体是重要的，其对机械负荷具有增加的敏感性。另一方面，附聚物的有效分级在低机械负荷下是不可能的。为了将有效的分级与低机械应力联合收割机相结合，必须控制整个通道路径上的机械应力和团聚体状态的分布。目前的测量技术只允许对微流体通道内所有颗粒的平均状况进行一般性陈述。然而，申请人在通过阻抗谱法开发用于微流体通道内的颗粒表征的方法方面具有经验。利用阻抗测量系统内部的微电极，可以制造和集成不同尺寸和几何形状的微流体通道。为了确定试验段的应力分布或颗粒状态，将扩展申请人已经使用的分析方法。在这种情况下，允许通过集成传感器元件同时进行蛋白质分离和分析的微流体系统提供了具有成本效益的分级系统的开发。以这种方式，这种分级系统在宏观药物大规模生产水平上的整合成为可能。

Microfluidics is a rapidly developing interdisciplinary research field that combines physics, chemistry, materials science and biotechnology. Novel microfluidic technologies enable an effective handling, analysis and fractionation of protein agglomerates. This provides several microfluidic methods for fast, gentle and high-resolution fractionation of particles in liquid media, with sizes from 1 nm to 100 µm. This is the reason for an increasing importance of microfluidic channels in filtration technology, chromatography and biochemical analysis. The aim of the project is an optimization of microfluidic cell design to minimize mechanical stress during the separation process of proteins. Based on this results, the determined separation efficiency and process output can increase the quality and quantity of industrial and analytical processes. Stress intensity and frequency can be manipulated by means of a process-oriented profile of the channel. For example, low mechanical stress is acting on the agglomerates inside a channel with an increasing cross-section and smooth walls as a result of collisions with the duct walls. In this case the agglomerates do not change their state, passing the microfluidic channel. This behavior is important for agglomerates of proteins, which have an increased sensitivity to mechanical loads. On the other hand, an effective fractionation of agglomerates is not possible at low mechanical loads. In order to combine an effective fractionation with low mechanical stress, the distributions of the mechanical stresses and states of agglomerates on the entire channel path have to be controlled. Current measurement techniques allow just a general statement about the average condition of all particles inside microfluidic channels. However, the applicant has experience in development of methods for particle characterization inside microfluidic channels by means of impedance spectroscopy. Microfluidic channels with different sizes and geometrical shapes become manufactured and integrated by means of microelectrodes inside impedance measurement system. In order to determine the distribution of the stresses or particle states at the test section, the analysis method, which is already used by the applicant, will be extended. In this context, microfluidic systems, which permit simultaneous protein separation and analysis by means of integrated sensor elements, provide the development of cost-effective fractionation systems. In this way an integration of such fractioning systems at macroscopic pharmaceutical mass production level becomes possible.