Controllable and Scaffold-Free Formation of 3D Multicellular Architectures Using a Bipolar Electrode Array

The natural environment of cells in vivo is a 3D network in which cellular responses are determined by influences from surrounding cells on all sides. This complex system is hard to be recapitulated in a conventional way. It is highly desirable to replace 2D models with 3D cell culture models. Microfluidic technology offers a variety of advantageous approaches for the long-term 3D cell culture. Herein, a new cell patterning approach for generating cell clusters of specified size and shape by exploiting induced charge electroosmosis (ICEO) flow at a bipolar electrode array is exploited. Cell or particle clusters can be produced at the edges or centers of bipolar electrodes (BPEs) with controlled organization, by designing electrodes with arbitrary shapes. This platform is further extended to flexibly organize biological units with different properties via the ICEO or dielectrophoresis (DEP) based assembly. Heterotypic cell clusters can be produced at the bipolar electrode (BPE) by adjusting the applied frequencies and the sample injection sequence. This hybrid approach by integrating ICEO flow vortexes and DEP properties of the cells, allows the wireless generation of high-throughput 3D clusters or spheroids with size adjustability and biocompatibility, which shows great potential in tissue engineering, drug discovery, and tumor research.