Behavior of proteins inside microfluidic channels

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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.