Layer-by-layer Adhesion of Hydrogels for Constructing Heterogeneous Microfluidic Chips

Abstract

Hydrogel-based microfluidics offer an in vivo-relevant micro-environments for construction of organs-on-chips. However, the fabrication of heterogeneous microchannels using hydrogels is challenging and fails to mimic the complex structures of organs in vivo. Here we present a new methodology called “layer-by-layer adhesion” for the construction of complex microfluidic chips. A hydrosoluble and photo-crosslinkable adhesive, chitosan methacryloyl (CS-MA), was used to stitch various hydrogels together layer-by-layer to form perfusable microchannels. Our results show that CS-MA can bond different types of hydrogels with adhesion energy ranging from 1.2-140 N/m. Using the layer-by-layer adhesion approach, we constructed heterogeneous hydrogel-based microchannels with various morphologies of snail, spiral, vascular-like, and bilayer. Based on this methodology, liver-on-a-chip was established by entrapping hepatic cells inside a biocompatible Gel-MA layer and covering it with the perfusable microchannels in tough F127-DA layer. The “layer-by-layer adhesion” provides a facile and cytocompatible approach for engineering user-defined hydrogel-based chips potentially for organs-on-chips.