Microfluidic 3D cell culture for high throughput screening

Trietsch, S.J. (2017)

Doctoral Thesis

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.
This thesis describes the development of the OrganoPlate, a microfluidic platform that enables enhanced physiology in cell culture models by combining 3D cell culture, co-culture and perfusion flow, whilst maintaining ease of use, compatibility and throughput.
Phaseguides are capillary pressure barriers that enable microfluidic liquid routing and patterning without the use of membrane or other physical barriers. This technology was further developed to enable complex liquid routing using only a standard pipette
Phaseguide technology was implemented for gel patterning in a dedicated 3D cell culture device embedded in a standard 384 wells plate. Each plate contains up to 96 microfluidic networks that enable perfusion culture of extracellular matrix embedded tissues and perfused epithelial or endothelial tubules. The standard dimensions and high quality optical readout allows interrogation of these tissues using high content readers as well as other standard readout equipment.
The platform has been used for the culture of a variety of tissue types and disease models by the authors, but has also been adopted by expert and non-expert users across the field.

• Organ-on-a-chip
• Microfluidics
• 3D cell culture
• High throughput screening
• Phaseguide
• OrganoPlate

• All authors: Trietsch, S.J.
• Supervisor: Hankemeier, T.
• Co-supervisor: Vulto, P.
• Committee: Irth, H.; Bouwstra, J.; Duijn, C. van; Manz, A.; Masereew, R.; Zonneveld, A.J. van
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Science, Leiden University
• Date: 2017-12-18
• ISBN (print): 9789462338319