Conventional Bioreactor systems for cultivating cells in Life Science have been widely used for decades. An in vitro cell cultivation bioreactor should reliably and reproducibly mimic the in vivo microenvironment of the cultured cells. Normally, mammalian cell cultures are performed in conventional bioreactor devices such as culture flasks and culture-dishes. However, these tools have fundamental limitations due to being inappropriate for high throughput screening and consume a considerable amount of resources and time [1]. Therefore, there is a trend towards miniaturization, disposables and even micro platforms that fulfill increasing demands strongly aiming for production and testing of novel pharmaceutical products. Here we present the development and manufacture of a disposable miniaturized flow-through bioreactor system that can be produced in large numbers at low costs. nanoporous hollow fibers are located at the fluidic sources and drains of the miniaturized bioreactors and retain cells. The necessary mixture of oxygen and carbon dioxide is provided via diffusion through a semi-permeable membrane. Fluidic connections allow the continuous feeding of the cells adding nutrient solution at constant rates at the inlet of the micro bioreactor and removing the solution at the same rate at the outlet. This medium can be collected and used for subsequent analysis. Different designs and concepts for such bioreactors were carried out with varying numbers of plates, and integrated or joined miniaturized reactor chambers. First tests show full technical and biological functionality, cells could successfully be cultivated at high viability rates for some days.
Over the course of the last decade 3D printing has become a more established technology in terms of prototype development (rapid prototyping). The current effort is focused on transferring this knowhow into a product driven approach in order to manufacture even small batch sizes more economic. In terms of this work, this idea is adapted for the development of injection molds (rapid manufacturing). Hereby, a hardened polymer is used to create a forming cavity instead of tool-steel. In order to fulfil the mechanical process requirements of micro injection molding such as form stability under temperature and pressure this cavity is nevertheless integrated into a metal housing. A first set of experiments has been carried out using this develop mold to verify the capabilities of the developed prototype as well as molding process. Based on these first results, an optimization is carried out to improve the next iteration of this molding tool.
Bioreactor systems for cultivating cells in Life Sciences have been widely used for decades. Recently, there is a trend towards miniaturization, disposables and even micro platforms that fulfill increasing demands strongly aiming for production and testing of novel pharmaceutical products. Miniaturized bioreactors allow low power consumption, portability and reduced space requirements and utilize smaller volumes of reagents and samples [1,2]. A recursive strategy is necessary for optimizing the design and the manufacture of such miniaturized bioreactors. For the fabrication of these prototypes utilized micro-milling. Micro milling is a mechanical process which is commonly applied to create micro-structures in metals, e.g. aluminum and steel, or polymers, e.g. poly carbonate substrates. The structures and geometries are generated by utilizing computer aided design. By means of computer-aided manufacturing, the machining operations are implemented and then transferred to the machine tool. The machine tool moves the cutting tools with certain speeds, feeds and traverse ranges to the substrate. Micro milling has the advantage that the materials are generally not degraded by chemical substances, heating procedures or electromagnetic radiation.
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