Merten Group

Previous and current research

We are conducting multidisciplinary research at the interface between biology, chemistry and engineering. The overall goal is to develop enabling technology for large-scale screens in the field of medical biotechnology, developmental biology and synthetic chemistry.

The research in our group is focussing on novel microfluidic approaches for biological and chemical applications. Recently, we have established droplet-based microfluidic platforms for the incubation and screening of human cells and multicellular organisms. In these systems, aqueous droplets within an immiscible oil phase serve as miniaturized reaction vessels. Compared to conventional microtiter plate formats, this technology allows massively increased throughput (up to 500 samples per second can be processed) and more than 1000-fold smaller sample volumes (pico- to nanoliters). The miniaturization not only enables the use of highly valuable samples which generally cannot be obtained on the scale required for high-throughput screening (e.g. primary cells, patient material), but also facilitates assays on the single cell/single animal level. For screening purposes, we have also developed systems allowing the co-encapsulation of different biomolecules or chemical compounds into the droplets. This can be achieved by using cell libraries in which each individually encapsulated cell releases a different protein variant (e.g. antibodies, peptides), by interfacing robotic systems injecting different compounds into the microfluidic chips, or by encapsulating beads displaying immobilized compound libraries (one-bead-one-compound libraries).

Future projects and goals

Now that we can rapidly generate chemically-distinct droplets, our future research will focus on applications in biology and chemistry. Since the droplet-based technology allows the mixing of high sample numbers in a truly combinatorial fashion (by droplet fusion), we will put special emphasis on combinatorial screens. In particular, we plan:

• Combinatorial drug screens. We want to identify drug combinations minimizing the number of non-responding cells. This is of special interest for highly heterogeneous populations such as tumour cells, in which individual cells that do not respond to a given drug can give rise to a lethal outcome (e.g. tumour regrowth).
• Combinatorial RNAi screens. Our systems should allow monitoring systematic double knockouts on a genome-wide scale. Hence interactions that can not be revealed by silencing individual genes become visible.
• Combinatorial chemistry. The possibility of rapidly generating and mixing huge sample numbers should allow exploring large areas of chemical structure space in search of new bioactive molecules.