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26 | AUGUST 2014 | GENengnews.com | Genetic Engineering & Biotechnology News of international sales and marketing. "What- ever we do at smaller scales must be directly transferrable to larger scales." As in many micro- and minireactors, each reactor well has individual control of temperature and pH. In addition, each of the 24 wells has PID (proportional-integral- derivative) control similar to benchtop re- actors. "They're real bio- reactors," Kakes says. To preserve volumetric fdelity during pH, media, and feed adjustments, Applikon also developed a microvale liq- uid dispenser that provides nanoliter-scale additions. Applikon has run k L a (a measure of bioreactor per- formance) and scalability studies comparing its mi- crobioreactors, minireactors, and lab-scale reactors, and it has "achieved exactly the same results," according to Kakes. "In the near future, the majority of all new cell culture processes will run in single- use format," says Davy De Wilde, director of marketing, fermentation technologies at Sartorius Stedim Biotech. Adoption will occur based on the usual benefts of lower costs and improved fexibil- ity, and is further supported by the availabil- ity of single-use bioreactors founded on con- ventional stirred-tank design. These vessels will apply established design principles, ac- counting for vessel geometry in the design of impellers and spargers. This, De Wilde says, will shorten scaleup time and ultimately re- duce time to market. The Sartorius Stedim Biotech single-use portfolio stretches from 250 mL to 2,000 L, enabling a fully disposable process from devel- opment through commercial manufacturing. While process development was typically con- ducted at 2–10 L scale, development-stage re- actors have trended downward in volume. The ambr bioreactor family from TAP Biosystems, a Sartorius Stedim Biotech company, provides fully automated workstations operating up to 24 bioreactors in parallel at 250 mL. "Its conventional design ensures that the data generated are representative of pilot- scale bioreactors," De Wilde says. "Good comparability to production scale is expect- ed as well." The minibioreactor, provided experimen- tal tools are designed for smart experimental planning, allows process development at reduced material cost, resource need, and development time. Multivariate data analysis provides real-time feedback on batch perfor- mance in comparison to a model batch. For media or clone selection, working volumes as small as 15 mL enable rapid screening while producing consistent data. "This ultimately will help to reduce variability, deviations, and lost batches," De Wilde observes. Fermentation and Single Use Xcellerex-GE's Ken Clapp calls microbial fermentation the new frontier in single-use process equipment. By contrast, single-use stirred-tank reactor technology is widely ad- opted in cell culture. "Biologics manufactur- ing, at scale, has never relied so heavily on the technology as it does today." Single-use bioreactors have not caught on with fermentation to the degree they have with cell culture. "Achieving heat removal ca- pacity and rates of mass transfer and oxygen transfer adequate for high-density fermenta- tions has been diffcult," notes Richard Mir- ro, executive director, portfolio management for bioprocess at Eppendorf. "Bioprocessors have had to rely on exhaust gas cooling to avoid flter fouling or high evaporation." Mammalian cell culture is more forgiving. The relatively gentle conditions required are achievable in either rigid-walled or fexible con- tainers, whereas the extreme agitation, baffed mixing, and gas-fow requirements demanded by high density microbial cultures is much bet- ter suited to a rigid-walled container. Eppendorf's BioBLU f vessels combine the advantages of disposability with the reliability of conventional glass or stainless-steel bioreac- tors for fermentation. "They are the frst single- use bioreactors designed to mimic traditional stirred-tank fermentation vessels," Mirro adds. BioBLU f features Rushton-type impel- lers and high-performance magnetic agita- tion for effcient mass transfer and improved mixing; cooling baffes for heat removal; and innovative liquid-free Peltier exhaust condensers to enable cultivation of bacteria, yeast, and fungi, even at high densities. The rigid-walled stirred-tank design, sensor tech- nology, and scalable geometries can allow for smooth process transfer and transition between reusable and single-use systems. Thermo Fisher Scientifc launched its frst single-use bioreactor for mammalian cell culture in 2006. "Since then, we have seen a demand from the market where custom- ers have been asking for single-use fermenta- We bring life to your laboratory. www.infors-ht.com Optimise your bioprocess with an INFORS HT bioreactor! • Clear path to scale up • Optimised handling for faster results • Flexible and application oriented setup • Touch screen with integrated OPC server • Automatic cleaning (CIP) and sterilisa tion (SIP) from 0.5 L – 1000 L to get a Would you like step ahead? Multifors Techfors Labfors NEW! CIP/SIP for bench- top bioreactors! Single-Use Bioreactors Continued from page 24 BIOPROCESSING A schematic of an Applikon micro-Matrix bioreactor. Each micro-Matrix cassette has 24 of these bioreactors on the standard SBS format plate. The total volume per bioreactor is 10 mL with working volumes from 1 – 7 mL.