The process flow for the strain screening and evaluation with high throughput μBR positioned in the middle directly before scaling-up to the bioreactor.
Some of the complications that are facing scaling down process of bioreactors.
Schematic steps of microfabrication by soft lithography. (a) Using computer-aided design tool to draw photomasks, which then printed on transparency films. (b) Photoresist-coated silicon wafers are exposed through the photomask. (c) The photomask design is translated to the silicon surface. (d) The silicon then acts as a master mold for casting replicas of transparent PDMS polymer. (e) PDMS can be drilled to create inlets and outlets and bonded to a glass substrate to create closed microfluidic devices or (f) used to create stencils with micro-patterned through-holes. Reprinted with permission from M. L. Yarmush and K. R. King, Annu. Rev. Biomed. Eng. 11, 235 (2009). Copyright 2009 Annual Reviews.
The main chronological milestones of microfluidic cell bioreactors development. (a) Reprinted with permission from Zanzotto et al., Biotechnol. Bioeng. 87, 243 (2004). Copyright 2004 Wiley. (b) Reprinted with permission from Balagadde et al., Science 309, 137 (2005). Copyright 2005 The American Association for the Advancement of Science (AAAS). (c) Reprinted with permission from Boccazzi et al., Biotechnol. Prog. 22, 710 (2006). Copyright 2006 Wiley. (d) Reprinted with permission from Steinhaus et al., Appl. Environ. Microbiol. 73, 1653 (2007). Copyright 2007 American Society for Microbiology (ASM). (e) Reprinted with permission from Li et al., Chem. Eng. Sci. 63, 3036 (2008). Copyright 2008 Elsevier. (f) Reprinted with permission from Buchenauer et al., J. Micromech. Microeng. 19, 8 (2009). Copyright 2009 IOPscience. (g) Reprinted with permission from Schäpper et al., Chem. Eng. J. 160, 891 (2010). Copyright 2010 Elsevier. (h) Reprinted with permission from Holcomb et al., Anal. Bioanal. Chem. 400, 245 (2011). Copyright 2011 Springer. (i) Reprinted with permission from Seo et al., Process Biochem. 47, 1011 (2012). Copyright 2012 Elsevier.
Simulation result of the concentration profile of oscillation mixing in the reactor at different times: (a) t = 0 s, (b) t = 1 s, (c) t = 2 s, and (d) t = 4 s and with different pulling and pushing linear flow rates: (e) 0.005 m s−1, (f) 0.01 m s−1, (g) 0.02 m s−1, and (h) 0.06 m s−1. Reprinted with permission from Li et al., AIChE J. 55, 2725 (2009). Copyright 2009 Wiley. FEM simulation results of velocity fields around the piezoelectric transducer array and the culture chamber of models: (i) D100 and (j) D50, and arrows indicate the flow direction. Reprinted with permission from Y.-H. Hsu and W. Tang, Microfluid. Nanofluid. 11, 459 (2011). Copyright 2011 Springer.
Fabricated μBRs devices and their main characteristics.
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