3D acoustic tweezers-based bio-fabrication

Open Access
Author:
Chen, Kejie
Graduate Program:
Engineering Science and Mechanics
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
March 16, 2016
Committee Members:
  • Jun Huang, Thesis Advisor
  • Joseph Rose, Thesis Advisor
  • Bernhard R Tittmann, Thesis Advisor
  • Judith Todd Copley, Thesis Advisor
Keywords:
  • Acoustic Tweezers
  • bio-fabrication
  • spheroid
  • tissue engineering
Abstract:
The ability to create 3D in vivo-like tissue models raises new possibility in studying complex physiology and pathophysiological process in vitro, and enabling the development of new therapy strategies for underlying diseases. Recent observations showed that gene expression in 3D cell assembles was much closer to clinical expression profile than those in 2D cases, which generated hope in manufacturing artificial 3D tissue for therapy test platforms with a better prediction of clinical effects. In this work, we developed a 3D acoustic tweezers-based method for rapid fabrication of multicellular cell spheroids and spheroid-based co-culture models. Our 3D acoustic tweezers method used drag force from acoustic microstreaming to levitate cells in vertical direction, and used acoustic radiation force from Gov’kov potential field to aggregate cells in horizontal plane. After optimizing the device geometry and input power, we demonstrated the rapid and high- throughput characteristics of our method by continuously fabricating more than 150 size- controllable spheroids and transferring them to Petri dishes every 30 minutes. The spheroids fabricated by our 3D acoustic tweezers can be cultured for a whole week with good cell viability. We further demonstrated that spheroids fabricated by this method could be used for drug testing. Unlike the 2D monolayer model, HepG2 spheroids fabricated by the 3D acoustic tweezers manifested distinct drug resistance, which matched existing reports. By co-culturing HepG2 spheroids with HMVEC cells, we found that spheroids tended to accelerate angiogenesis and tube formation process in Matrigel compared with isolated single cells. The 3D acoustic tweezers based method can serve as a novel bio-manufacturing tool to fabricate complex 3D cell models for tissue engineering, drug development, and fundamental biological research.