A single-use bioreactor or disposable bioreactor is a bioreactor with a disposable bag instead of a culture vessel. Typically, this refers to a bioreactor in which the lining in contact with the cell culture will be plastic, and this lining is encased within a more permanent structure (typically, either a rocker or a cuboid or cylindrical steel support). Commercial single-use bioreactors have been available since the end of the 1990s and are now made by several well-known producers (See below) .
Single-use at bioreactors Single-use bioreactors are widely used in the field of mammalian cell culture and are now rapidly replacing conventional bioreactors. Instead of a culture vessel made from stainless steel or glass, a single-use bioreactor is equipped with a disposable bag. The disposable bag is usually made of a three-layer plastic foil. One layer is made from Polyethylene terephthalate or LDPE to provide mechanical stability. A second layer made using PVA or PVC acts as a gas barrier. Finally, a contact layer is made from PVA or PP. For medical applications the single-use materials that contact the product must be certified by the European Medicines Agency or similar authorities responsible for other regions.
Types of single-use bioreactors In general there are two different approaches for constructing single-use bioreactors, differing in the means used to agitate the culture medium. Some single-use bioreactors use stirrers like conventional bioreactors, but with stirrers that are integrated into the plastic bag. The closed bag and the stirrer are pre-sterilized. In use the bag is mounted in the bioreactor and the stirrer is connected to a driver mechanically or magnetically. Other single-use bioreactors are agitated by a rocking motion. This type of bioreactor does not need any mechanical agitators inside the single-use bag.,. Both the stirred and the rocking motion single-use bioreactors are used up to a scale of 1000 Liters volume. Several variations on these two methods exist. The Kuhner Shaker, was originally designed for media preparation, but is also useful for cell cultivation. The PBS Biotech Air Wheel technology uses buoyancy from the air feed to provide rotational power to a stirrer.
Measurement and control Measurement and control of a cell culture process using a single-use bioreactor is challenging, as the bag in which the cultivation will be performed is a closed and pre-sterilized system. Sensors for measuring the temperature, conductivity, glucose, oxygen, or pressure must be built into the bag during the manufacturing prior to sterilization. The sensors can’t be installed prior to use of the bioreactor as in the conventional case. Consequently, some challenges must be taken into consideration. The bag is assembled, delivered and stored dry, with the consequence that the usual pH-electrodes can not be used. Calibration or additional assembly is not possible. These constraints have led to the development of preconfigured bags with new types of analytical probes. The pH value can be measured using a patch that is just a few millimeters in size. This patch consists of a protecting membrane with a pH-sensitive dye behind it. Changing pH in the culture medium changes the pH, and the color, of the dye. The color change can be detected with a laser external to the bag. This and other methods of non-invasive measurement have been developed for single-use bioreactors.
Single-use bioprocessing Decreasing product contact with parts/systems decreases qualification and validation times when changing from one drug process to another. Since the biopharmaceutical manufacturing process includes many steps other than just the use of bioreactors, single-use technologies are utilized throughout the manufacturing process due to its advantages. Single-use bioprocessing (SUS) steps available are: media and buffer preparation, cell harvesting, filtration, purification and virus inactivation. The major innovation of single-use technologies in this area of processing has been in the construction of 2D/3D bags and tubing wielding- reducing the contact of product to non-single-use parts/systems.
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