The Multifunctional Pipette. A Microfluidic Technology for the Biosciences

Abstract: 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.