Abstract

Microbioreactors for Stem Cell Bioprocessing

Nicolas Szita, Professor, University College London

Microfabricated bioreactors have been successfully applied to the fields of microbial fermentation and mammalian suspension cell cultures. Key advantages that make microfabricated bioreactors a cost-effective proposition for early bioprocess development include: significant reduction in reagent use, real-time monitoring and control of process variables, ease of sterilisation via disposable polymer technology, reduced labour due to automation, and the capability to rapidly test different processing conditions. Clearly, a microfabricated, adherent culture device that could translate these advantages to stem cell culture would be of great value to the fields of regenerative medicine and cell therapy where more insight into cell culture processes is direly needed. However, a link must be maintained with conventional culture methods and production systems for the purposes of validation and scale up studies. Further, the device must be highly versatile to facilitate evaluation and optimisation of the wide range of process variables that affect stem cell fate. In particular, this versatility must extend beyond the control of the physico-chemical properties of the culture medium to include auto/paracrine factors, growth surfaces, shear forces, and cell seeding densities. Finally, rapid online assessment of the product (cells) is crucial. In this presentation, I will explain how my group at UCL Biochemical Engineering has begun to address some of these challenges. Using human and mouse embryonic stem cell expansion protocols as a model system, we investigated microfluidic design concepts to enable controlled and low-shear perfusion culture of stem cells that maintain the expression of pluripotency markers. Characterisation of our microfabricated cell culture device (‘microbioreactor’) included fluid flow modeling, device reliability testing, verification of autoclavation as a means of sterilization for our device, and also the careful establishment of protocols to prime t