Automation of Batch Spatial Manipulation and Assembly of Vells through Dielectrophoresis for Tissue Engineering

Dielectrophoresis (DEP) is regarded as one of the most non-invasive mechanisms for batch manipulation of dielectric particles. In this proposed project, we will conduct a dielectrophoresis research beyond the two-dimensional lab-on-a-chip spatial environment and investigate an automated technique for batch manipulation of cells for constructing intricate, three-dimensional (3D) cellular patterns with a novel electrode-integrated structure. The proposed spatial cell manipulation and microassembly technique will permit the development of 3D cell structures fulfilling both the physical (e.g. cell density and defined 3D geometry) and the biological (e.g. cell viability) requirements, which is currently a great technical challenge in the field of tissue engineering. The following three important issues will be addressed in this proposed research.First, we will design a multi-layer, multi-electrode structure that will enable effective biological cell assembly. Through modeling and computational analysis, we can optimize the design parameters of the 3D electrode architecture and its micro-electrode layers and thereby, the resulting electric field gradient for automated spatial manipulation of cells.Second, we will implement a microfabrication technique to construct the multi-layer electrode structure with high design complexity. This electrode must be fabricated from a bio-compatible, yet conductive material with layers of dielectric coating. Due to the unique requirements, it is not practical to manufacture the structure with conventional rapid prototyping techniques. Hence, we propose to use the combined micromolding and robotic microassembly technique to construct the 3D electrode.Third, we will evaluate the electrode structure as a 3D engineered scaffold for cell incubation in tissue engineering. Novel strategies such as the incorporation of specially designed voltage waveform shapes and the dispersion of micro-scale particulates will be investigated to maximize the initial distribution of cells within the scaffold. A 3D culture environment will be established for optimal cell growth. Studies will be carried out to characterize the density and the viability of cells on the scaffold, which provides important insights to the 3D cell assembly and culture applications.Our proposed dielectrophoresis-based cell manipulation and assembly technique can precisely define deposition locations in the scaffold with maximal initial seed cell density, allowing high-quality artificial tissues grown on the scaffold. Success of this research will facilitate the new development of artificial tissues and organs for transplantation purposes.