Miniaturising biology and chemistry in microfluidic systems
The Merten group develops novel approaches in microfluidic technology to address complex, multidisciplinary questions at the interface of biology, chemistry and engineering.
Previous and current research
Working on the micro scale offers some unique advantages:
- Drastically increased throughput (processing up to a million samples an hour).
- Superb spatio-temporal resolution (assays can be carried out on micrometer length scales and sub-millisecond timescales).
- Low material consumption, enabling single organism, single cell, or even single molecule assays.
During the past couple of years we have developed powerful microfluidic platforms for cell-based and (bio)chemical assays. In our laboratory, we perform all steps ranging from the design/manufacturing of microfluidic chips and detection systems to the cultivation and study of human cells and multicellular organisms (prior knowledge in microfluidics is not obligatory for joining the group). Furthermore, we are interested in combinatorial chemistry, perform computational fluid dynamics simulations, and develop novel software controlling our microfluidic systems.
For many applications we use two-phase microfluidics, in which aqueous droplets within an immiscible oil phase serve as miniaturised reaction vessels. As they can be generated at kilohertz frequencies, they are of particular interest for high-throughput screens. Furthermore, the small assay volumes (pico- to nanoliters) facilitate the obtainment of high concentrations of nucleic acids (mRNA, DNA) or proteins (for instance secreted antibodies) from individually encapsulated cells, paving the way for single cell assays. On the other hand, we use continuous-phase microfluidics to generate laminar flow patterns, where we expose cells and organisms (or even small parts thereof) to different chemical environments. Amongst other applications, this allows the analysis of signalling events in developing embryos.
Future projects and goals
Having a comprehensive microfluidic toolbox at hand (and expanding it continuously), we are now focusing on applications in three different research fields:
- Cell biology: We are planning large-scale chemical pertubations to analyse stem cell differentiation and to map the interactions between different cellular pathways with a special focus on cellular senescence. In particular, we will analyse the crosstalk between autophagy, insulin signalling and mitochondrial activity.
- Biomedical applications: Droplet-based microfluidics enables antibody screening at very high throughput (~50 samples/sec). We want to use this technology to identify therapeutic antibodies, starting with primary plasma cell samples from human disease (such as HIV and HCV) survivors. In parallel, we exploit a reversed experimental setup to derive potential HIV vaccine candidates (in close collaboration with the International AIDS Vaccine Initiative).
- Combinatorial chemistry: The possibility of rapidly generating, mixing and analysing huge sample numbers allows exploration of large areas of chemical structure space. Focusing on click chemistry and one-bead-one-compound libraries, we are interested in identifying novel bioactive molecules such as antimicrobial peptides and enzyme inhibitors.
Encapsulation of HEK293T cells (left) and C. Elegans (right) into aqueous microcompartments. Subsequent to an incubation step a fluorescence readout of individual microcompartments can be performed.
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