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.