Agarose-assisted micro-contact printing for high-quality biomolecular micro-patterns

Micro-contact printing has been developed to print biomolecules, such as cell adhesive molecules, proteins, or DNAs, on a substrate, which can serve as experimental platforms for investigating biological issues and engineering biosensors. Despite the popularity of this method, it has been technically challenging to use a conventional stamp made of a hydrophobic polydimethoxysilane (PDMS) elastomer that often requires surface treatments to facilitate the inking and stamping of biomolecules. In this work, we proposed a new surface modification method for a PDMS stamp using agarose hydrogel and demonstrated the applications to the design of micro-patterned substrates with biomolecules. By using a simple bench-top dip-coating method with a commercial syringe pump to steadily pull out the stamp from boiled agarose solution, we coated an agarose layer on the stamp. It consequentially enhanced the transferability of ink molecules to the target substrate and the uniformity of printed patterns compared to the traditional methods for treating stamp surface such as surfactant coating and temporary oxidation with air plasma. In addition, this microstamping method was also used to produce patterns of proteins with the preservation of bioactivity, which could guide neuronal growth. Thus, we demonstrated the applicability to the interface designs of biochips and biosensors.