Figure 1 Schematic diagram showing the fabrication of hydrogel-based chip via sacrificial templates (A) and layer-by-layer adhesion (B).
To address these limitations, a new and simple strategy of “layer-by-layer adhesion” has been proposed to construct hydrogel-based microfluidics with accurate 3D microchannels and hybrid materials (Figure 1B). The approach involves preparing predefined microgrooves on the hydrogel surface using soft lithography techniques18 and bonding other hydrogels layer-by-layervia an adhesive. By sealing two or more hydrogel layers, closed and perfusable microchannels are formed inside the chip. This approach is simple and allows for the assembly of various materials into a single chip, greatly improving its designability. The choice of adhesive is critical for this new concept. Commercial glues are unsuitable due to their fragility, toxicity and incompatibility with the wet surfaces of hydrogels11,19. To address this issue, this paper synthesizes a wet-surface adhesive based on the biopolymer chitosan20. To improve the solubility and stability of native chitosan, a hydrosoluble and UV-crosslinkable chitosan methacryloyl (CS-MA) will be prepared at physiological pH via N-acylation reaction. Finally, the CS-MA adhesive will be used to stitch various hydrogel layers and construct liver-on-a-chip to compare with that made using sacrificial templates.