Next Generation Microfilter: Large-scale, Continuous Mammalian Cell Perfusion Bioreactors

Technology #17183

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Inventors
Professor Jongyoon Han
Research Laboratory of Electronics, EECS, MIT
External Link (www.rle.mit.edu)
Guofeng Guan
National University of Singapore
Majid Ebrahimi Warkiani
National University of Singapore
Kah Ping Andy Tay
National University of Singapore
Managed By
Michelle Hunt
MIT Technology Licensing Officer
Patent Protection

Microfluidic Systems and Method for Perfusion Bioreactor Cell Retention

PCT Patent Application WO 2016-044537
Publications
Membrane-less microfiltration using inertial microfluidics
Scientific Reports, 2015. 5: p. 11018.
NEXT-GENERATION MICROFILTER: LARGE SCALE, CONTINUOUS MAMMALIAN CELL RETENTION FOR PERFUSION BIOREACTORS
MicroTAS, 2014 p. 2474-2476.

Applications

  • Cell retention for perfusion cell culture/bioreactors
  • Brewing – yeast removal
  • Pharmaceutical applications (bioreactor)
  • Water filtration

Problem Addressed

This technology provides a clog-less, continuous cell retention technology for small and large scale bioreactors. 

Technology

Mammalian cells are useful in synthesizing large and complex chemicals for diagnostic and therapeutic products. Examples include monoclonal antibodies, recombinant proteins, and viral vaccines against polio, hepatitis B and measles. Additionally, certain cells can be effectively used for generating biofuels. Perfusion bioreactors are one approach for manufacturing large quantities of cellular or cell-derived material, as they can sustain high cell numbers with continual feeding of nutrients and removal of waste and product. A key parameter for successful perfusion is the retention of the majority of the cells producing the product of interest in the bioreactor. This technology is the first example to demonstrate the use of microfluidics for large-scale perfusion applications. The device is a novel integrated microfluidic system consisting of multiple layers of PDMS sheets with embossed micro-channels bonded together for continuous, label and clog-free cell separation from large volumes of clinical biological samples. The channels of the system are connected internally where fluid flow can be distributed through all spiral channels via a shared inlet. Fluid exits the system through collective outlets. The system can be can be tailored to two distinct applications: filtration (for large particle separation; via fluid focus at microchannel walls) and fractionation (small particle separation via Dean vortices flow). Separation efficiency was tested for three different cell lines widely used in industry for antibody production.

Advantages

  • Low cost
  • Reliability of cell retention in the device; high throughput
  • Minimal protein/cellular fouling/ No clogging
  • Filter can be operated non-stop over long periods of time, without need for filter exchange
  • Scalability (enabling lab scale perfusion culture, while scalable up to very large throughput)
  • High cell and protein concentrations 
  • Excellent cell viability after the sorting; tested with mesenchymal stem cells and other sensitive cells with no observable adverse effect due to sorting