Droplet Microarray chip: towards functional personalized oncology

Droplet Microarray chip: towards functional personalized oncology

Pavel Levkin, Maryam Salarian, Razan Faraj, Joaquin Urrutia, Meijun, Zhou, Sascha Dietrich, Heinz-Georg Jahnke, Marc Schneider, Daria Gaykalova

Droplet Microarray (DMA) platform is based on hydrophilic-superhydrophobic patterning, and represents a planar transparent chip capable of formation of arrays of hundreds stable and separated droplets of nanolitre volumes. In the past few years we have demonstrated the potential of DMA chips for cell- and bacteria-based drug screening applications. The uniqueness of this technology is in compatibility with unlimited miniaturization of droplets thanks to the flat surface. In addition to that, it is an open platform accessible for transferring and retrieving the samples, temperature steps and PCR cyclers, and on-chip readout methods, like MALDI for example.
Miniaturization of screening assays is enabling in cases where the availability of cells is a limiting factor. We are working on establishing workflows for culturing and screening of primary patient derived cancer cells for their sensitivities to drugs on DMA chip. Our ultimate goal is to establish DMA chip for the use in functional personalized oncology for the empirical identification of suitable therapy for the patients. Our working hypothesis is testing the cells immediately after isolation without a need for establishing a long-term in vitro cultures. Therefore, we are focusing on short tests within 24 to 48 hours. Cell culture models have an influence on cell drug response, with our platform we are able to culture cells in 2D and 3D environments, including scaffold-free and scaffold-based approaches, which we utilize for culturing primary samples. In addition, it is crucial to enable in depth analysis of cell behaviour and drug response in this short time on unique patient samples. For that we are developing various on chip methods, and automation suitable for handling nanolitre volumes.
Here I will present our last results on optimisation of culture and screening of primary cells derived from non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and chronic lymphocytic leukemia (CLL). I will present the development of two new on chip read-out methods enabling real time monitoring of cell proliferation using electrical impedance, as well as isolation of mRNA from cultured cells and conversion to cDNA on chip in high throughout manner for subsequent differential gene expression analysis. Finally, I will present our last development on building automated solutions for handling small volumes on DMA.