101 Pharm. Bioprocess. (2015) 3(2), 101–113 ISSN 2048-9145 Steady-state biofilm cultivation of Aspergillus niger D15 in a ceramic capillary membrane bioreactor Christian Endres 1,2 , Sheena Janet Fraser 2 , Wade Edwards 2 , Sascha Beutel 1 & Thomas Scheper* ,1 1 Institut für Technische Chemie, Leibniz Universität Hannover, Callinstr. 5, 30167 Hannover, Germany 2 Quorusbiotech (Pty) Ltd, PO Box 13236, Mowbray 7705, Cape Town, Western Cape, South Africa *Author for correspondence: scheper@iftc.uni-hannover.de Pharmaceutical Research Article part of 10.4155/PBP.14.61 © 2015 Future Science Ltd Aim: Bioreactors are an essential component in every biotechnological process. Due to the multitude of different microbial and mammalian organisms used for production of complex products, novel concepts for customized cultivations are necessary. Results: A ceramic capillary-based bioreactor enabling a novel approach for steady- state biofilm cultivation is presented. A model for the determination of the efficiency of this system was developed by comparing its productivity to conventional stirred tank reactors using the production of recombinant xylanase by Aspergillus niger D15 ( xyn2) as a model process. Conclusion: The presented bioreactor provides an ideal platform for the cultivation of shear-sensitive, filamentous growing microorganisms producing valuable secreted secondary metabolites or recombinant products. Background Compared with conventional stirred tank reactors (STRs), an important advantage of membrane-based bioreactors is the provision of an artificial environment for an increased bio- mass density and enhanced productivity. This artificial environment can further be speci- fied as a platform, which combines biological reactions with membrane separations [1] . Membrane-based bioreactors are gener- ally comprised of independent delivery and removal streams, allowing cell retention and product extraction. Two individual com- partments, the extracapillary space (ECS) and intracapillary space (ICS), are separated by the membranes [2,3] . Cells are predomi- nantly grown in the ECS. Additionally, two distinct cycling pathways ensure consistent operation: one is used for medium delivery through or from the ICS and the other is used for inoculation or product removal from the ECS (Figure 1) . Major advantages of this configuration are the possibilities of immedi- ate product removal and adjustment of prod- uct concentration through variation of the delivery rate. Constant and immediate prod- uct removal can additionally be of significant importance when the products are either unstable or lead to product inhibition [4] . First-generation membrane bioreactors relied on diffusion-based mass transfer through the membranes. This operating principle, however, can lead to insufficient aeration, inhomogeneous production and insuffi- cient removal of toxic by-products. To cir- cumvent these problems, second-generation membrane reactors have been developed [5] . These systems are comprised of additional expansion compartments for each supply and removal pathway. However, a disadvantage of such a closed-loop operation is the inabil- ity to extract sufficient amounts of biomass to determine growth and viability [5] . These factors can only be assessed indirectly by measuring metabolic activities such as oxy- gen and glucose consumption. Cell counts can only be performed in end point analysis negating online batch-to-batch comparisons. Industrial applications for membrane bio- reactors have increased significantly over the past two decades and originate from appli- cations such as hemodialysis [6] , desalina- tion of seawater or wastewater treatment [7] . Applications for other areas of biotechnology are promising, however, to date only a few examples have been reported [8] . Such bio- technological processes utilize membrane