Project leader Karlsruhe Institute of technology, Baden-Wurttemberg, Germany
Droplet Microarray is a technology based on precise fabrication of arrays of hydrophilic spots on hydrophobic background. Such surfaces allow for formation of arrays of separated and stable droplets of nanoliter volumes either by using low volume dispensers or by discontinuous dewetting, the process of spontaneous formation of droplet arrays upon application of aqueous solution onto the surface. Each of such nano droplets serves as a well for cell culturing and screening. We have successfully adopted the DMA platfrom for culturing and screening of multiple cells types including adherent and suspension cell line, stem cells and primary patient derived cells. In addition to standard 2D culture models, the DMA platform is compatible with 3D cell culture. By simply inverting the DMA slide upside down, imitating the method of hanging droplet, we can observe formation of single-spheroid arrays. Taking advantage of two features of DMA, the fact that it is an open system and that it does not have physical barriers between the spots, we have demonstrated the possibility to combine droplets containing different types of spheroids by adding the liquid resulting in merging of neighbouring droplets in controlled way. This method opens new possibilities for co-culture models, complex screening models, tissue engineering and others. One of the main advantages of the DMA platform is miniaturization of culturing volumes, resulting in up to 2 orders of magnitude reduction of amount of cell material needed for experiment. This is especially beneficial for highly miniaturized Drug Sensitivity and Resistance Test on patient-derived cancer cells. In collaboration with University Hospital in Heidelberg, DKFZ and NCT, we developing models for screening of CLL and MM cells and had performed a screening of about 3000 FDA approved compounds on patient-derived glioma tumorspheres. In addition to phenotypic read-out based on microscopy and colorimetric based methods, we are working on developing of a toolbox of methods, which will allow us to get detailed information about the molecular changes in cells upon the treatment. We are developing protocols allowing performing MALDI, proteomic and transcriptomic analysis of live cells in individual droplets directly on the DMA chip. Considering all the advantages and the multifunctionality of the DMA platform, we are convinced that this kind of technology will represent new generation platforms of the future for miniaturization and parallezation of biological, as well as chemical experiments.