Bioreactors aim for versatility and reliability

The latest generation of bioreactors have smaller footprints, are more versatile, reliable and user friendly, and minimise scale up risks.

Applikon Biotechnology has launched micro-Matrix, describing it as the next generation in microbioreactors.

Micro-Matrix offers total control over 24 independent bioreactors in a simple microtitre plate footprint. Each of the 24 bioreactors on a plate offer independent controls similar to their larger stirred-tank relatives, including pH, temperature, dissolved oxygen control, individual liquid additions and up to four separate, individually controlled gas additions.

Advanced control strategies are also available to users interested in cascade controls (up to five actuators per process variable), time-based setpoint changes, and event-triggered liquid feeds. Liquid feeding is available using varying types of addition profiles, too.

A major feature of the instrument is the software for processing, data storage, data presentation and data analysis. The micro-Matrix software offers an easy way to operate 24 bioreactors in parallel, plus simple comparisons of large numbers of experimental cultures. Using an instinctive left-to-right progression, the interface guides operators through experimental setup, instrument configuration, control strategy definition, and data visualisation. It is also possible to define time- and event-based control actions, and all data can be exported from the instrument post or during the experiment.

The polystyrene bioreactor cassettes conform to the SBS standard for 24 well culture plates (128 x 86mm). The total volume per bioreactor is 10 ml with working volumes from 1 to 7ml (recommended working volume is 5ml). The square bioreactors are designed based upon the company's popular 24-well microtitre plate design to optimise mixing and gas transfer, and Applikon has characterised these plates to offer advice on proper selection of working volume and agitation to achieve users' process goals. Cassettes are delivered beta-sterilised and sealed in a light shielding package.

A microbial bioreactor

Eppendorf says its new BioBLU 0.3f is the first fully-instrumented single-use bioreactor designed specifically for microbial applications (Fig.1).

The BioBLU 0.3f joins the BioBLU 0.3c which was launched last year and is designed for the cultivation of animal and human cells. Both the BioBLU 0.3c and BioBLU 0.3f are specifically designed for use with the compact DASbox mini bioreactor system.

DASbox is a novel mini bioreactor system for parallel operation of four, eight or more mini-bioreactors and is well suited for design of experiment (DoE), bioprocess development screening and for use as a scale-down model.

With the new BioBLU 0.3f, the company says it is paving the way for users of conventional microbial-based biotechnology to take advantage of the time and cost benefits of single-use bioreactor technology - for example in pharmaceutical product development.

The fully-instrumented BioBLU 0.3f single-use bioreactor features working volumes of 65 to 250 ml and meets all requirements for microbial applications. The rigid-wall, single-use bioreactor includes two Rushton impellers achieving oxygen intake levels comparable to industrial glass and stainless steel bioreactors.

All critical parameters, such as temperature, pH and dissolved oxygen, can be monitored and regulated using industry standard sensors. Integrated dip tubes permit the controlled feeding of liquids, easy sampling and massflow-controlled gassing. The specially developed, magnetically-coupled overhead drive safely operates up to 2000rpm, ensuring that the BioBLU 0.3f supports the high agitation rates required for microbial applications. The innovative liquid-free Peltier technology ensures that the temperature of the culture is precisely controlled, even with modern high cell density processes that generate extraordinarily high levels of heat.

A culture sparger

According to Thermo Scientific, its next-generation sparger technology sets new standards for cell culture performance in its proprietary HyPerforma single-use bioreactor (SUB) BioProcess Container systems.

Cell growth is dependent on the availability of the right amount of oxygen in the bioprocess. Sparging controls the air and gas flow to create the optimal environment for cell growth. Thermo's new sparger is engineered to produce a consistent bubble size for predictable scale up and performance from the company's 50l to its 2000l SUB. The new dual sparger design consists of a micro- and macro-sparger integrated into the standard SUB BioProcess Container systems.

"This new micro- and macro-sparge configuration is gentle on cell cultures at high gas flow rates, provides sufficient O2 delivery and dramatically increases CO2 stripping capacity," said Millie Ullah, senior product manager for single-use systems at Thermo Fisher Scientific. "This next-generation design sets a new standard of performance, flexibility, and ease of use during scale-up for all cell culture applications."

Meanwhile Electrolab Biotech says its FerMac 310/60, 320 and 200 fermenter series of bioreactors are also ideal for microbial research.

For example, the FerMac 310/60 is designed with modern multi-function laboratories in mind and born out of the most rigorous testing. This stirred tank bioreactor offers the control and footprint of a perfectly integrated system combined with the flexibility of a modular system, including: powerful, intuitive measurement and control system; a wide range of fully autoclavable vessels with a novel, easily replaceable drive shaft system; four pumps fitted as standard (additional two pump module available); and the fermenter system can efficiently tackle batch, fed-batch and continuous flow fermentations.

Electrolab's FerMac 320 is its new mid-priced bioreactor system. By combining a specially designed range of vessels with a variation on its established 360 controller, the company says FerMac 320 gives users outstanding value-for-money with the reassurance of proven reliability. Features include: a vessel-mounted motor with easy coupling system; intuitive measurement and control system; and it can be used as a batch bioreactor in fed-batch or continuous culture mode.

Low maintenance costs

The FerMac 200 bioreactor is a modular system which is marketed as having the perfect combination of performance and ease-of-use. For example, all modules are totally independent and stackable for a neat, combined unit; low purchase and maintenance costs maximise benefits from a limited budget; and modules are available individually for specific control requirements.

Alongside other bioreactor technologies, GE Healthcare Life Sciences offers the Xcellerex XDR stirred-tank bioreactor systems that are designed to minimise scale-up risks and facilitate the goal of achieving a robustness, purity, and potency of the final manufacturing-scale process that is comparable to the process in development scale.

Technology transfer using XDR bioreactor systems is straightforward, minimising the need for costly and time-consuming process redesign.

The design of XDR systems is based on the same principles as conventional stainless steel bioreactors. A traditional scaling methodology, based on measures such as shear, tip speed, power, and fluid velocity, is used. Consistent vessel geometries and efficient mass transfer combine for an easily scalable, single-use system.

The XDR-50 single use vessel offers standard accessories that can be adapted to various process requirements. For example there are gas mass flow and liquid pump options for highly productive cultures. Complete, turn-key bioreactors and fermenters with dedicated X-Station controllers are also available.

The company says that as the XDR-50 single-use bioreactors are a modular platform with scalable working volumes up to 2000l, they offer smooth transfer from process development to manufacturing scale, with the convenience and cost-effectiveness of single-use technology.

For its part the XDR-10 single-use bioreactor system is sized for the bench top, yet allows smooth scale-up to full production. It includes a low shear, high input-power impeller for gentle, efficient mixing for sensitive cells or media. Sparging flexibility offers excellent adaptability to a broad range of cell lines.Handling volumes from 4.5l to 10l, this model is suitable for GMP clinical and commercial manufacture of biotherapeutics, vaccines, and other biologics.

Automation essential for batch predictatbility

Bioreactor or fermentation processes are the core manufacturing process in the biotech industry. Implementation delays and process upsets can result in the loss of millions of dollars in revenue through lost product and downtime.

Automation helps companies using bioreactors or fermenters as the key equipment in a manufacturing process achieve predictable execution of each batch. Whether a single vessel or large train, bench top or production scale, automation reduces project and production risk to achieve dependability in bioreactor operations.

For bioreactor manufacturers, producing customised equipment and getting it quickly to the market is important to success in the biotechnology industry.

Easy and predictable integration into a plant-wide installation may set bioreactor manufacturers apart from the competition.

To ensure dependable and consistent operation, biotech companies need reliable control solutions that can be installed quickly allowing them to confidently manage the throughput and integrity of each batch

Rockwell Automation enables OEMs to provide a world class turn-key solution on their own or provide a turn-key bioreactor control solution.

To do this the company utilises its engineering team, which has vast experience in life sciences implementations and validations, and which also can help reduce project and production risk while achieving reliability.

Rockwell cites a number of benefits associated with using this team, including: GAMP-4 methodology in design, implementation and testing provides a solution that is easily validated; design based on S88 methodology provides process flexibility, repeatability, and accountability; and it enables compliance with 21 CFR Part 11 requirements and, by validating production process and auditing, with IND and NDA/BLA approvals.

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