Design of a Microfluidic Device for Chromatin Immunoprecipitation (ChIP-on-Chip)

Early detection of disease contributes significantly to treatment success and patient survival. Chromatin immunoprecipitation coupled with sequencing (ChIP-seq) was shown to be a suitable method for detecting various diseases, such as cancer, from small blood or tissue samples. However, ChIP is currently a multi-step benchtop assay, exploiting the surface area of microbeads for chromatin capture and working at minimum volume of about 10 µL. Here we show the design of a microfluidic pillar chip with a surface area of 130 mm², a pillar density of 55 pillars per mm² and a total volume of 3 µL. The pillar chip is fabricated in PDMS and modified with a silane-based surface chemistry to immobilize antibodies for chromatin capture. Chromatin binds specifically to the antibodies and is released and further purified on the pillar chip following the standard ChIP-protocol. By performing ChIP on a micro-scale level, we aim to improve chromatin capture efficiency due to the spatial vicinity of antibodies and target molecules. Furthermore, reagent volumes are reduced and possibilities for operating the chip automatically are enhanced.