Robust, microfabricated culture devices with improved control over the soluble microenvironment for the culture of embryonic stem cells

• Published in: Biotechnology journal 2014-06, Vol.9 (6), p.805-813
• Main Authors: Macown, Rhys J., Veraitch, Farlan S., Szita, Nicolas
• Format: Article
• Language: English
• Subjects: Animals; Cell culture; Cell Culture Techniques - instrumentation; Cell Culture Techniques - methods; Cell Differentiation; Cell Proliferation; Cellular Microenvironment; Embryonic Stem Cells - cytology; Mice; Microfluidic Analytical Techniques - instrumentation; Microfluidic culture device; Microreactor; Microtechnology - instrumentation; Pluripotent Stem Cells - cytology; Process development; Stem cells; Stress, Mechanical
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.201300245

The commercial use of stem cells continues to be constrained by the difficulty and high cost of developing efficient and reliable production protocols. The use of microfabricated systems combines good control over the cellular microenvironment with reduced use of resources in process optimization. Our previously reported microfabricated culture device was shown to be suitable for the culture of embryonic stem cells but required improvements to robustness, ease of use, and dissolved gas control. In this report, we describe a number of improvements to the design of the microfabricated system to significantly improve the control over shear stress and soluble factors, particularly dissolved oxygen. These control improvements are investigated by finite element modeling. Design improvements also make the system easier to use and improve the robustness. The culture device could be applied to the optimization of pluripotent stem cell growth and differentiation, as well as the development of monitoring and control strategies and improved culture systems at various scales. Stem cells are a promising new research area constrained by the difficulty of processing. This report presents a microfabricated device for the adherent culture of stem cells, which was designed for increased robustness, ease of use, and control over the soluble microenvironment. The presented culture device is a powerful tool for the advancement of stem cell processing.