Nucleic acid synthesis and intracellular delivery on microelectrode arrays.

Functional genetic screening, including CRISPR screening, is an important tool in drug discovery and cancer research. These experiments test large libraries of genetic changes in cells to identify genes involved in behaviours such as drug resistance or cell migration, and therefore reveal potential therapeutic targets. However, current screening technologies involve a trade-off between the scalability of pooled screens and the direct link between genetic change and phenotype offered by arrayed screens. This PhD project aims to combine the scalability of pooled approaches and the determinism of arrayed screenings by developing a spatially encoded platform for deterministic and rapidly reconfigurable nucleic-acid screening. Short DNA oligonucleotides will be synthesized at defined locations on a microelectrode array, released on demand and delivered into cells by localized electroporation.

In this project, you will fabricate microdevices in imec’s cleanrooms and study the surface chemistry, DNA-release methods and electrode designs needed for efficient delivery while keeping the cells healthy. As a proof of concept, DNA barcodes will be used to show that cells receive specific DNA sequences based on their position on the chip, including combinations of sequences at the border between adjacent regions. The resulting platform would be an important step towards automated, high-throughput CRISPR screening, where the identity and combination of nucleic acids are directly linked to their position on the chip.