Merten Group

Microfluidic approaches in drug discovery and personalised medicine

The Merten group develops microfluidic technology to address complex questions in biomedical sciences and developmental biology.

Previous and current research

Working on the micro-scale offers some unique advantages:

  • Drastically increased throughput (processing up to a million samples an hour).
  • Possibility of performing assays on the single-cell level.
  • Low sample consumption, enabling the use of patient material.

During the past couple of years we have established powerful microfluidic platforms for cell-based and biochemical assays. We continuously develop novel microfluidic chips, detection systems and software (mainly LabVIEW) for the discovery of new drugs and antibodies, partially in collaboration with large pharma industry. Furthermore, we use microfluidic technology to predict optimal (personalised) drug cocktails for cancer therapy. The group is very interdisciplinary and consists of people with various backgrounds, including engineers, programmers and biologists. However, prior knowledge in microfluidics is not mandatory for joining!

For most 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 (such as secreted antibodies) from individually encapsulated cells, paving the way for single-cell assays. Sometimes we also use continuous-phase microfluidics, for example to generate laminar flow patterns, to apply spatial constrictions, or to provide cells sequentially with different stimuli. This has turned out to be particularly useful for various developmental biology applications.

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:

Therapeutic antibodies: Droplet based microfluidics enables to screen a large fraction of the murine and human immune repertoire in a single experiment. We are actively exploiting this for novel therapeutic approaches.

Personalised medicine: We use microfluidic devices to test drug combinations directly on human tumor samples and to predict optimal therapies.

Genomics: We are actively developing microfluidic modules for single-cell barcoding and sequencing. This will enable the study of the mechanisms of drug resistance in great detail.

moviecells

movieworms

 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.

Recently highlighted research

El Debs B, Utharala R, Balyasnikova IV, Griffiths AD, Merten CA (2012)
Functional single-cell hybridoma screening using droplet-based microfluidics
Proc. Natl. Acad. Sci. U.S.A. 109(29):11570-11575. doi:10.1073/pnas.1204514109
Europe PMC | doi

Highlighted in:

Lab-on-a-chip: Functional single-cell screening (2012)
Nature Methods 9(9):866. doi: 10.1038/nmeth.2162
doi

Clausell-Tormos J, Lieber D, Baret JC, El-Harrak A, Miller OJ, Frenz L, Blouwolff J, Humphry KJ, Köster S, Duan H, Holtze C, Weitz DA, Griffiths AD, Merten CA (2008)
Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms
Chem. Biol. 15(5):427-437. doi: 10.1016/j.chembiol.2008.04.004
Europe PMC | doi

Highlighted in:

Evanko D (2008)
Living droplets
Nature Methods 5(7):580-581. doi: 10.1038/nmeth0708-580a
doi