The Multifunctional Pipette. A Microfluidic Technology for the Biosciences

Doctoral thesis, 2013

The theme of the work described in this thesis is the generation and application of liquid microenvironments in chemistry and bioscience using microfluidic devices. First, a computer controlled multi-stage dilution system to generate time-dependent chemical waves was developed, and its application was demonstrated on model biomembranes. Thereafter the focus was shifted towards spatial control of chemistry. Using a hydrodynamic flow confinement concept in an open liquid volume, we created a device coined “Multifunctional Pipette”. It features localized liquid handling at the single-cell size scale together with fast solution exchange. The technology has been refined and optimized to provide a feature-rich tool for biologists working with cells and tissues in microscopy experiments. Application examples include cell zeiosis, single-cell dose-response determination and ion-channel stimulation. Subsequent studies cover modifications and applications of this device, such as on-chip electrodes and electroporation, as well as uses in cell cultures, on tissue slices, and as an optofluidic thermometer. Finally, localized liquid handling has been applied to assemble 2-dimensional fluidic networks consisting of directly written supported lipid bilayers. This "Lab on a Membrane" toolbox allows rapid prototyping of 2D-fluidic circuits, to modify their chemistry and connectivity on-demand and to apply them in studies of molecular interactions.