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 micrometre 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 and 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. We also 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:
- Biomedical applications: Droplet-based microfluidics enables functional antibody screening at very high throughput (several hundred thousand antibodies per experiment). We want to use this technology to identify therapeutic antibodies, starting with primary plasma cells from immunised mice or even 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). Furthermore, we are actively developing microfluidic approaches for personalised cancer therapy.
- Cell biology: We will perform large-scale chemical perturbations to identify pathway interactions in stem cell differentiation and carcinogenesis. These microfluidic chemical genetics approaches require only minute numbers of cells and are hence compatible with primary cells or even patient biopsies.
- Genomics: We are developing microfluidic modules for single-cell barcoding and sequencing. Furthermore, we are setting up integrated microfluidic ChIPseq platforms allowing for the analysis of less than 5000 cells. Notably, some of our modules (such as our microfluidic sonicator for the shearing of gDNA and cross-linked chromatin) have already been commercialised.
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
Lab-on-a-chip: Functional single-cell screening (2012)
Nature Methods 9(9):866. doi: 10.1038/nmeth.2162
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
Evanko D (2008)
Nature Methods 5(7):580-581. doi: 10.1038/nmeth0708-580a