Self-folding shell microfluidic arrays (SMFAs) for 3D spatiotemporal chemistry

Three-dimensional (3D) spatiotemporal chemistry plays a crucial role in self-organization, morphogenesis, tissue engineering, and developmental biology. Several microfluidic systems can create chemical gradients and manipulate reaction-diffusion systems, but they typically utilize channels in inherently planar geometries. Here, we describe self-folding biocompatible shell microfluidic arrays (SMFAs) to enable precise chemical patterning and chemistry within 3D curved microenvironments. We fabricated these SMFAs by self-folding crosslinked SU8 films with embedded sacrificial fillers, which were patterned using conventional photolithography. We interfaced the SMFAs with programmable flow controllers, enabling precise spatiotemporal delivery of chemicals in a spherical geometry around millimeter-sized 3D structures. We highlight the utility of the SMFAs by generating tunable 3D chemical gradients, performing multi-chemical patterning, and facilitating 3D chemical reactions within gel beads. Also, we verified the biocompatibility of SMFAs and used them for the chemical patterning of live neural organoids. Our findings suggest a reproducible and biocompatible approach for generating dynamic chemical patterns and conducting chemical reactions within 3D microenvironments, with broad relevance to chemistry, embryogenesis, and microphysiological systems.