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One of the first steps in cell assay experiments is the cell preparation. One step of cell preparation often is the introduction of genetic material into cells. This process is called transfection, and causes cells to express proteins of other species. For example in drug discovery, to receive valuable results for human drugs, these cells are equipped with human membrane proteins by transfecting the cell with the coding messenger RNA. About two thirds of currently available drugs depend on such membrane proteins. Various transfection methods evolved over the past decades, spanning from biological methods like viral transfection to chemical methods like transfection by synthetic compounds over electrical methods known as electroporation to a mechanical method called microinjection, where a glass needle is used to transfer the genes into the cell. Advantages of microinjection over the competitive methods are its high yield and its highest flexibility of introducing even a combination of compounds into various different cell types. However, microinjection has a low throughput and the yield is highly user dependent. These two drawbacks call for automation. In the past, various systems were presented which focused solely on the microinjection process. Injection needles can automatically be detected, injection volumes can be calibrated, and forces applied to the cell during microinjection can be measured. Even do methods exist which are able to detect blocked or broken needles. These systems help to increase the throughput and minimize human error during microinjection. However, analyzing the complete cycle of cell preparation identifies another bottleneck. This is the identification of viable cells for later microinjection. In many laboratories this step is done manually because none or only highly expensive systems can perform such tasks. To rule out human errors on the final microinjected cell, not only the microinjection but also the upfront cell sorting has to be automated and put into one system. Therefore, the scope of this thesis was widened from only automating microinjection to automated sorting and microinjecting. Finally, a system could be presented where the user only has to add a cell suspension and a prefilled injection needle. The sorting, microinjection and collection were then performed automatically by the system. Along this novel approach of combining sorting, injection and collection into one system, the sorting system uses a continuous sorting principle which moves cells in a circle continuously, so delivery of cells on demand is now for the first time possible. Furthermore, the microinjection system was equipped with a carousel stage, which now enables one to perform repetitive steps as cell immobilization, cell injection and cell

Automated microinjection with integrated cell sorting, immobilization and collection