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Many pharmaceuticals are proteins or their development is based on proteins. Cell-free protein synthesis (CFPS) is an innovative alternative to conventional cell based systems which enables the production of proteins with complex and even new characteristics. However, the short lifetime, low protein production and expensive reagent costs are still limitations of CFPS. Novel automated microfluidic systems might allow continuous, controllable and resource conserving CFPS. The presented microfluidic TRITT platform (TRITT for Transcription - RNA Immobilization & Transfer - Translation) addresses the individual biochemical requirements of the transcription and the translation step of CFPS in separate compartments, and combines the reaction steps by quasi-continuous transfer of RNA templates to enable automated CFPS. In detail, specific RNA templates with 5' and 3' hairpin structures for stabilization against nucleases were immobilized during in vitro transcription by newly designed and optimized hybridization oligonucleotides coupled to magnetizable particles. Transcription compatibility and reusability for immobilization of these functionalized particles was successfully proven. mRNA transfer was realized on-chip by magnetic actuated particle transfer, RNA elution and fluid flow to the in vitro translation compartment. The applicability of the microfluidic TRITT platform for the production of the cytotoxic protein Pierisin with simultaneous incorporation of a non-canonical amino acid for fluorescence labeling was demonstrated. The new reaction mode (TRITT mode) is a modified linked mode that fulfills the precondition for an automated modular reactor system. By continual transfer of new mRNA, the novel procedure overcomes problems caused by nuclease digestion and hydrolysis of mRNA during TL in standard CFPS reactions.

A technology was developed for the fabrication of very thin, chip-sized lithium secondary micro batteries. Based on wafer level processing the batteries can be directly implemented into silicon chips, 3D chip stacks or MEMS devices. The batteries were packaged in 200 µm deep cavities of the silicon wafer and encapsulated with a glass substrate. Battery demonstrators with 7 and 12 mm2 and round foot print were realized.

Novel approaches in cell based and cell free micro reactors promise a new generation of high quality, high purity and on top personalized synthesis of drugs like antibiotics and functional proteins. These concepts are - however-relying on very specific conditions, under which the cells need to work and therefore require advanced sensing for e.g. ionic content, pH value and temperature. Also, the creation of product itself needs to be monitored to extract the valuable drug from the reactor, before side reactions start to deteriorate quality and yield. Microfluidics has come a long way since, resulting in advanced Point of Care devices nowadays, which can run complex protocols/1/. However, these reactions are time based and the process conditions are fixed and not monitored at all. To leverage the capability to drug production, monitoring sensors need to be integrated into the fluidic system, creating a complex electronic-optical microfluidic device. Exemplary techniques for the integration of sensors are provided in this paper, technological approaches and experimental results are given.

Background Tests for drug development require an almost perfect fit with the human (patho-) physiological microenvironment. The majority of skin equivalents currently commercially available are based on static culture systems emulating only human epidermis, or combining epidermis and dermis in so-called full thickness skin equivalents. None of the existing systems contain important elements, such as vasculature, skin appendices or an immune system. Therefore, current in vitro and animal tests are failing to accurately predict drug toxicity. Our Multi-Organ-Chip (MOC) platform is a micro scale bioreactor providing pulsatile dynamic perfusion for microscale organoids. Here, we combine skin equivalents with vasculature in our two-organ variant (2OC). This would be needed for physiological-like interactions, regulation and, eventually, homeostasis within the chip.