Simulation of droplet-based microfluidic lab-on-a-chip applications

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.Miniaturization of biological and chemical assays in lab-on-a-chip systems is a highly topical field of research. Droplet-based microfluidic chips are types of these miniaturized systems. They expand the capability of assays with special features that are unreached by traditional workflows. In particular, small sample volumes, independent separated reaction units, high throughput, automation and parallelization of assays are prominent features of droplet-based microfluidic devices. Full custom centric design of droplet-based microfluidic lab-on-a-chip technology implicates a high system integration level and design complexity. Therefore advanced development methodologies are needed, comparable with the methods in electronic design automation. Our design and simulation toolkit meets these requirements for an agile and low-risk development of custom lab-on-a-chip devices. The system simulation approach enables a fast and precise prediction of complex microfluidic networks. This fact is confirmed by reference and benchmark experiments. The results show that the simulation correctly reproduces the experimental measurements.The German BMBF and the EU in the projects DiNaMiD, signature 0315591B and NoE Photonics4Life, Grant Agreement number: 224014

Real-time image processing for label-free enrichment of Actinobacteria cultivated in picolitre droplets

The majority of today's antimicrobial therapeutics is derived from secondary metabolites produced by Actinobacteria. While it is generally assumed that less than 1% of Actinobacteria species from soil habitats have been cultivated so far, classic screening approaches fail to supply new substances, often due to limited throughput and frequent rediscovery of already known strains. To overcome these restrictions, we implement high-throughput cultivation of soil-derived Actinobacteria in microfluidic pL-droplets by generating more than 600000 pure cultures per hour from a spore suspension that can subsequently be incubated for days to weeks. Moreover, we introduce triggered imaging with real-time image-based droplet classification as a novel universal method for pL-droplet sorting. Growth-dependent droplet sorting at frequencies above 100 Hz is performed for label-free enrichment and extraction of microcultures. The combination of both cultivation of Actinobacteria in pL-droplets and real-time detection of growing Actinobacteria has great potential in screening for yet unknown species as well as their undiscovered natural products

Photoactivatable prodrugs of antimelanoma agent Vemurafenib

In this study, we report on novel photoactivatable caged prodrugs of vemurafenib. This kinase inhibitor was the first approved drug for the personalized treatment of BRAF-mutated melanoma and showed impressive results in clinical studies. However, the occurrence of severe side effects and drug resistance illustrates the urgent need for innovative therapeutic approaches. To conquer these limitations, we implemented photoremovable protecting groups into vemurafenib. In general, this caging concept provides spatial and temporal control over the activation of molecules triggered by ultraviolet light. Thus, higher inhibitor concentrations in tumor tissues might be reached with less systemic effects. Our study describes the first development of caged vemurafenib prodrugs useful as pharmacological tools. We investigated their photochemical characteristics and photoactivation. <i>In vitro</i> evaluation proved the intended loss-of-function and the light-dependent recovery of efficacy in kinase and cellular assays. The reported vemurafenib photo prodrugs represent a powerful biological tool for novel pharmacological approaches in cancer research

Arbeitsbericht der Zentralabteilung Strahlenschutz 1973

The "Zentralabteilung Strahlenschutz - ZST" (Health Physics Division) of the Nuclear Research Establishment Jülich is responsible for an adequate and a proper perfomance of the radiation protection of installations, personnel and environment. This does include the introduction of the necessary organizing conditions as well as the permanent development of the measuring methods and procedures according to the most recent knowledge of science and research. The chapters 1 to 6 of the present annual report refer to the service activities done in 1973 as well as to the results of research and developments in connection with the improvement of methods and procedures. Chapter 7 gives a complete bibliography of all the published and internal literature of the ZST in 1973