Biomedical Microdevices

, Volume 14, Issue 2, pp 313–323

Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates

  • Amy Y. Hsiao
  • Yi-Chung Tung
  • Chuan-Hsien Kuo
  • Bobak Mosadegh
  • Rachel Bedenis
  • Kenneth J. Pienta
  • Shuichi Takayama
Article

DOI: 10.1007/s10544-011-9608-5

Cite this article as:
Hsiao, A.Y., Tung, Y., Kuo, C. et al. Biomed Microdevices (2012) 14: 313. doi:10.1007/s10544-011-9608-5

Abstract

Using stereolithography, 20 different structural variations comprised of millimeter diameter holes surrounded by trenches, plateaus, or micro-ring structures were prepared and tested for their ability to stably hold arrays of microliter sized droplets within the structures over an extended period of time. The micro-ring structures were the most effective in stabilizing droplets against mechanical and chemical perturbations. After confirming the importance of micro-ring structures using rapid prototyping, we developed an injection molding tool for mass production of polystyrene 3D cell culture plates with an array of 384 such micro-ring surrounded through-hole structures. These newly designed and injection molded polystyrene 384 hanging drop array plates with micro-rings were stable and robust against mechanical perturbations as well as surface fouling-facilitated droplet spreading making them capable of long term cell spheroid culture of up to 22 days within the droplet array. This is a significant improvement over previously reported 384 hanging drop array plates which are susceptible to small mechanical shocks and could not reliably maintain hanging drops for longer than a few days. With enhanced droplet stability, the hanging drop array plates with micro-ring structures provide better platforms and open up new opportunities for high-throughput preparation of microscale 3D cell constructs for drug screening and cell analysis.

Keywords

Micro-ringSpheroidHigh-throughput3D cultureHanging dropStereolithography

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Amy Y. Hsiao
    • 1
  • Yi-Chung Tung
    • 1
    • 2
  • Chuan-Hsien Kuo
    • 1
  • Bobak Mosadegh
    • 1
  • Rachel Bedenis
    • 3
  • Kenneth J. Pienta
    • 3
    • 4
  • Shuichi Takayama
    • 1
    • 5
    • 6
  1. 1.Department of Biomedical EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Research Center for Applied SciencesAcademia SinicaTaipeiTaiwan
  3. 3.Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA
  4. 4.Department of UrologyUniversity of Michigan Medical SchoolAnn ArborUSA
  5. 5.Macro Molecular Science and EngineeringUniversity of MichiganAnn ArborUSA
  6. 6.School of Nano-Biotechnology and Chemical Engineering WCU ProjectUNISTUlsanRepublic of Korea