Biomedical Microdevices

, Volume 10, Issue 2, pp 309–319

A high throughput perfusion-based microbioreactor platform integrated with pneumatic micropumps for three-dimensional cell culture

  • Min-Hsien Wu
  • Song-Bin Huang
  • Zhanfeng Cui
  • Zheng Cui
  • Gwo-Bin Lee
Article

DOI: 10.1007/s10544-007-9138-3

Cite this article as:
Wu, MH., Huang, SB., Cui, Z. et al. Biomed Microdevices (2008) 10: 309. doi:10.1007/s10544-007-9138-3

Abstract

This study reports a new perfusion-based, micro three-dimensional (3-D) cell culture platform for high-throughput cell culture using enabling microfluidic technologies. In this work, the micro 3-D cell culture platform is fabricated based on SU-8 lithography and polydimethylsiloxane replication processes. The micro cell culture platform can maintain homogenous and stable culture environments, as well as provide pumping of multiple mediums and efficient cell/agarose (scaffold) loading functions, which allows realization of more precise and high-throughput cell culture-based assays. In this study, the design of a high-throughput medium pumping mechanism was especially highlighted. A new serpentine-shaped pneumatic micropump was used to provide the required medium pumping mechanism. Pneumatic microchannels with a varied length and U-shape bending corners were designed to connect three rectangular pneumatic chambers such that one can fine-tune the pumping rate of the S-shape micropump by using the fluidic resistance. To achieve a high-throughput medium pumping function, a pneumatic tank was designed to simultaneously activate all of the 30 pneumatic micropumps with a uniform pumping rate. Results show that the pumping rates of the 30 integrated micropumps were statistically uniform with a flow rate ranging from 8.5 to 185.1 μl h-1, indicating the present multiple medium pumping mechanism is feasible for high-throughput medium delivery purposes. Furthermore, as a demonstration case study, 3-D culture of oral cancer cell was successfully performed, showing that the cell viability remained as high as 95% - 98% during the 48 h cell culture. As the result of miniaturization, this perfusion-based 3-D cell culture platform not only provides a well-defined and stable culture condition, but also greatly reduces the sample/reagent consumption and the need for human intervention. Moreover, due to the integrated capability for multiple medium pumping, high-throughput research work can be achieved. These traits are found particularly useful for high-precision and high-throughput, 3-D cell culture-based assay.

Keywords

Microfluidics Micropumps Microbioreactors Perfusion cell culture 3-D cell culture MEMS 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Min-Hsien Wu
    • 1
  • Song-Bin Huang
    • 2
  • Zhanfeng Cui
    • 3
  • Zheng Cui
    • 4
  • Gwo-Bin Lee
    • 2
  1. 1.Graduate Institute of Biochemical and Biomedical EngineeringChang Gung UniversityTaoyuanTaiwan
  2. 2.Department of Engineering ScienceNational Cheng Kung UniversityTainanTaiwan
  3. 3.Department of Engineering ScienceUniversity of OxfordOxfordUK
  4. 4.Central Microstructure FacilityCCLRC Rutherford Appleton LaboratoryOxfordshireUK