- The WAVE Bioreactor is a single-use, rocking motion bioreactor system designed for the cultivation of suspension and some adherent cells under controlled conditions.
- It is especially favored in the biopharmaceutical industry for its scalability, closed system design, and gentle mixing, making it ideal for high-density cultures of sensitive mammalian or insect cells.
- The core of the WAVE system is a pre-sterilized disposable cell bag that rests on a rocking platform. This platform creates a wave-like motion in the liquid, facilitating effective mixing and gas exchange with minimal shear stress, which is crucial for maintaining cell viability and productivity.
- Cell cultivation in a WAVE bioreactor can be carried out using various strategies depending on the desired application. The simplest is batch culture, where cells are inoculated into a fresh medium and allowed to grow until nutrients are exhausted or waste accumulation inhibits growth. This method is easy to perform and suitable for early-stage process development.
- More advanced strategies include fed-batch culture, in which nutrients such as glucose and amino acids are added during cultivation to sustain cell growth and productivity over a longer period.
- For processes requiring extended cultivation and very high cell densities, perfusion culture is employed. In perfusion, fresh medium is continuously added while waste and spent medium are removed, allowing cells to remain in the bioreactor. This method often requires a cell retention device such as an alternating tangential flow (ATF) filter or a spin filter.
- Various cell types can be cultivated in WAVE systems, including CHO, HEK293, Jurkat, hybridomas, and insect cells like Sf9. Adherent cell lines, such as Vero or MDCK, can also be grown in WAVE bioreactors when attached to microcarriers.
- Cultures are typically initiated at a seeding density around 0.3–0.5 million cells/mL and may reach densities of 10 million cells/mL or higher, especially under fed-batch or perfusion conditions. The system is well-suited for use as a seed train step before inoculation into larger stirred-tank bioreactors or for full production at clinical or commercial scales.
- Operational parameters are critical to success in WAVE systems. The rocking angle and speed are adjusted to ensure optimal mixing without causing foam or damaging cells. Temperature, pH, and dissolved oxygen (DO) are tightly controlled through external sensors and gas overlay. Commonly, temperatures are maintained at 36–38°C, pH around 7.0, and DO levels between 30–60%, depending on the cell line. Sampling ports allow regular monitoring of key parameters such as cell viability, nutrient concentrations, and product expression levels.
- One of the main advantages of the WAVE bioreactor is its low shear environment, which makes it especially suitable for shear-sensitive mammalian and stem cells.
- Additionally, the single-use format reduces the risk of cross-contamination, eliminates the need for cleaning and sterilization, and allows rapid turnover between batches.
- The system is relatively easy to set up and operate, requiring minimal training compared to more complex stirred-tank bioreactors. For these reasons, WAVE bioreactors are commonly used in clinical manufacturing, vaccine production, and early-stage bioprocess development.
- If desired, detailed protocols can be adapted for specific cell lines or cultivation strategies, such as CHO cells in fed-batch mode or mesenchymal stem cells on microcarriers in perfusion.
