Single-use bioreactors in various designs have been introduced onto the market over the last decade. At small scale, there are many potential solutions, including classic shake flasks in single-use design, roller bottles, T flasks, and so on.
These offer little or no control over cell growth and production. However, they do provide a simple means of small-scale screening and cell cultivation. The introduction of two-dimensional rocking bioreactors over a decade ago brought a larger scale seed cultivation vessel to the market. These systems offer gentle mixing by rocking back and forth with low shear. They also provide surface aeration that is well suited to most cell culture applications. The sensors, which are reusable and offer some control, also have some limitations in terms of handling and accuracy.
The introduction of Sartorius Stedim Biotech’s Biostat® CultiBag RM in 2006 represented a new and advanced version of the rocking bioreactor. By applying control systems similar to classical reusable bioreactors, and employing single-use sensors for pH and dissolved oxygen (DO), good feedback control loops are now available in a single-use system. These single-use sensors are patches that have been gamma irradiated inside the bag at manufacture as a closed system.
A reusable fiber optic cable is placed into the sensor sheath and passes a light of known wavelength through the bag to the patches and excites the fluorescent molecules within. The excitation response is sent back to the measuring amplifier and is converted to measurable pH and DO.
The key advantage here is the presence of a single-use sensor in a single-use bioreactor. The insertion of reusable sensors into a single-use system introduces additional handling and risk issues involving the bioreactor chamber in terms of sterility and leaks.
In recent years the disposable bioreactor market has featured stirred-tank configurations that can replace traditional stirred tank bioreactors. The control systems required to operate these novel designs usually have to be sourced from a second supplier. In some cases this can be advantageous as existing controllers from various manufacturers can be connected without much difficulty. However, when things go wrong, as often happens, two vendors are involved in trouble shooting problems.