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

Authors

  • Amy Y. Hsiao
    • Department of Biomedical EngineeringUniversity of Michigan
  • Yi-Chung Tung
    • Department of Biomedical EngineeringUniversity of Michigan
    • Research Center for Applied SciencesAcademia Sinica
  • Chuan-Hsien Kuo
    • Department of Biomedical EngineeringUniversity of Michigan
  • Bobak Mosadegh
    • Department of Biomedical EngineeringUniversity of Michigan
  • Rachel Bedenis
    • Department of Internal MedicineUniversity of Michigan Medical School
  • Kenneth J. Pienta
    • Department of Internal MedicineUniversity of Michigan Medical School
    • Department of UrologyUniversity of Michigan Medical School
    • Department of Biomedical EngineeringUniversity of Michigan
    • Macro Molecular Science and EngineeringUniversity of Michigan
    • School of Nano-Biotechnology and Chemical Engineering WCU ProjectUNIST
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