Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis

For the improved production of vaccines and therapeutic proteins, a detailed understanding of the metabolic dynamics during batch or fed-batch production is requested. To study the new human cell line AGE1.HN, a flexible metabolic flux analysis method was developed that is considering dynamic changes in growth and metabolism during cultivation. This method comprises analysis of formation of cellular components as well as conversion of major substrates and products, spline fitting of dynamic data and flux estimation using metabolite balancing. During batch cultivation of AGE1.HN three distinct phases were observed, an initial one with consumption of pyruvate and high glycolytic activity, a second characterized by a highly efficient metabolism with very little energy spilling waste production and a third with glutamine limitation and decreasing viability. Main events triggering changes in cellular metabolism were depletion of pyruvate and glutamine. Potential targets for the improvement identified from the analysis are (i) reduction of overflow metabolism in the beginning of cultivation, e.g. accomplished by reduction of pyruvate content in the medium and (ii) prolongation of phase 2 with its highly efficient energy metabolism applying e.g. specific feeding strategies. The method presented allows fast and reliable metabolic flux analysis during the development of producer cells and production processes from microtiter plate to large scale reactors with moderate analytical and computational effort. It seems well suited to guide media optimization and genetic engineering of producing cell lines

The future of short-range high-speed data transmission: Printed polymer optical waveguides (POW) innovation, fabrication, and challenges

One of today's megatrends in the industrial environment is additive manufacturing. Faster prototyping, customized products like hearing devices, integrated functions like heatsinks and many other opportunities are offered by this technological development. The opportunity of using different materials and build up 3-D structures is virtually infinite. Another one is the digitalization of almost any product to build up a smart world. This trend leads to a tremendously rising amount of data to be transferred from one place to another. If a wireless transmission is not possible and if the distance is over 100 m glass fiber is the fastest and most secure way for these requirements. In case of most short-range applications up to 100 m primary copper cables or circuit paths are in use because the electrical data transfer is well known. The limited bandwidth of copper asks for new inventions to meet the demands of tomorrow. Regarding both megatrends, the solution for this upcoming bottleneck could be 3-D printed photonic packages. This paper shows a new and innovative way for the customized fabricating of short-range data transmission networks. By Aerosol Jet Printing (AJP) the so called polymer optical waveguides (POW), it is possible to build up 3-D printed light guiding structures with low attenuation on almost any three-dimensional surface. The main advantages of the here presented research are high flexibility, low weight and low costs. After three years of intensive studies the most important key facts (machine settings, geometry, performance) are summarized in this publication. © 2018 SPIE