Facile Production of Large-Area Cell Arrays Using Surface-Assembled Microdroplets

Abstract

Techniques that enable the spatial arrangement of living cells into defined patterns are broadly applicable to tissue engineering, drug screening, and cell–cell investigations. Achieving large-scale patterning with single-cell resolution while minimizing cell stress/damage is, however, technically challenging using existing methods. Here, a facile and highly scalable technique for the rational design of reconfigurable arrays of cells is reported. Specifically, microdroplets of cell suspensions are assembled using stretchable surface-chemical patterns which, following incubation, yield ordered arrays of cells. The microdroplets are generated using a microfluidic-based aerosol spray nozzle that enables control of the volume/size of the droplets delivered to the surface. Assembly of the cell-loaded microdroplets is achieved via mechanically induced coalescence using substrates with engineered surface-wettability patterns based on extracellular matrices. Robust cell proliferation inside the patterned areas is demonstrated using standard culture techniques. By combining the scalability of aerosol-based delivery and microdroplet surface assembly with user-defined chemical patterns of controlled functionality, the technique reported here provides an innovative methodology for the scalable generation of large-area cell arrays with flexible geometries and tunable resolution.