Glucose hypometabolism is the earliest symptom observed in the brains of Alzheimer disease (AD) patients. In a former study, we analyzed the cortical proteome of the APP23 mouse model of AD at presymptomatic age (1 month) using a 2-D electrophoresis-based approach. Interestingly, long before amyloidosis can be observed in APP23 mice, proteins associated with energy metabolism were predominantly altered in transgenic as compared to wild-type mice indicating presymptomatic changes in energy metabolism. In the study presented here, we analyzed whether the observed changes were associated with oxidative stress and confirmed our previous findings in primary cortical neurons, which exhibited altered ADP/ATP levels if transgenic APP was expressed. Reactive oxygen species produced during energy metabolism have important roles in cell signaling and homeostasis as they modify proteins. We observed an overall up-regulation of protein oxidation status as shown by increased protein carbonylation in the cortex of presymptomatic APP23 mice. Interestingly, many carbonylated proteins, such as Vilip1 and Syntaxin were associated to synaptic plasticity. This demonstrates an important link between energy metabolism and synaptic function, which is altered in AD. In summary, we demonstrate that changes in cortical energy metabolism and increased protein oxidation precede the amyloidogenic phenotype in a mouse model for AD. These changes might contribute to synaptic failure observed in later disease stages, as synaptic transmission is particularly dependent on energy metabolism.

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This paper presents a microfluidic device addressing the field of ambulant diagnostics in rural areas. Often, the diagnostic approach of micro-channel based point of care devices (PoCD) will target a certain marker - if e.g. on site another marker is to be checked against, the visiting doctor needs to use another test device. With the number of markers growing on a steady basis this will incur the need to transport a large number of individual test strips/cartridges, making the PoCD concept useless for this specific setting. The basis of the proposed novel device is a hybrid system combining the advantages of conventional channel-based fluidics with those of digitally controlled droplet-based fluidics. This hybrid concept uses a micro-channel based delivery partition for stored reagents with a disposable reaction partition based on electrowetting-on-dielectric to run the actual test protocol. It promises to realize a low cost approach for a Point-of-Care system with easy deployability. Conceptual implementation was done by roll embossing for the microchannels and direct structuring of the electrode elements for the EWOD substrate. The latter was laminated with a PTFE-film or coated with a nanoparticle loaded lacquer for hydrophobization. A variety of reagents were handled using a two-phase containment on the EWOD substrate, overcoming the issues associated with low surface energy fluids

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