Disposable Bioreactors Based on Wave Agitation Technology

Disposable bioreactors save costs in time and capital by reducing the time-to-market needed for cell cultivation processes.
May 02, 2007

Over the past decade, disposable technologies have become a reality in biotech processes. The use of disposables in research and manufacturing allows high flexibility.

The aim of cultivation in a bioreactor is to produce biomolecules using animal or plant cells, microorganisms, yeast, and insect cells.

Biomolecules are divided into four main classes: carbohydrates, lipids, nucleic acids and proteins.1 The latter is the most common in biotech processes: manufacturing of vaccines, diagnostics, or therapeutic preparations.

Mammalian cells constitute a demanding system for the production of heterologous proteins. Two main formats have been employed for the production of recombinant proteins in mammalian cells: cultures of adherent cells and suspension cultures. The latter is by far the most common.2 In 2004, mammalian cell-based therapeutic proteins reached a market share of 59% followed by 27% for E. coli-based products.3

Before production can start, the right cell line is screened out and the cultivation process must be optimized, for example, scaled-up, starting cultivation with a few milliliters and ending up with several cubic metres' cultivation volume.

For more than 40 years, typical bioreactors for cell cultivation have been made of glass or stainless steel and have been used in research and commercial production processes. This traditional bioreactor was characterized by substantial investment cost resulting from the necessity for aseptic bioprocess technology, sterilization in place (SIP), cleaning in place (CIP) and validation, all requiring sophisticated instrumentation.

Disposable bioreactors with mechanical energy input represent modern alternatives to such traditional cultivation systems for some applications in lab- and pilot-scale.

The main characteristics of the single-use bioreactor are low cost, ease of operation, time saving and high process security. These parameters shorten the time-to-market.

Disposable bioreactors can be divided into two groups:

  • Bag reactors with mechanical energy input where the cells are directly in contact with growth media. The most common bag reactor is based on rocking motion, where the wave-induced motion guarantees the energy input.
  • Membrane cultivation systems with two chambers separated by a semipermeable membrane. The membrane enables the passage of nutrients to the cells, yet the metabolites can leave the cell chamber. High cell densities can be reached, but up-scale capability is limited to the low lab-scale level.

This article aims to outline the potential and limits of the disposable bioreactor based on wave-induced agitation for biotechnology use, while considering the working principle.

The working principle

This disposable bioreactor with wave agitation can be used for batch, fed-batch and a perfusion operation mode. It is shown that even fragile cells such as animal cells (CHO, NS0, fibroblasts and hybridoma) human cells (T-Lymphocytes, HEK and Perc.6), insect cells (Sf9, High5 with baculovirus) and plant cells (hairy root culture, suspension cultures and embryo culture) can be grown in sealed bags made of polyethylene.6–8

Figure 1. BIOSTAT CultiBag RM optical.
Disposable bioreactors based on the rocking motion principle are mechanically-driven reactor systems, which are available in lab- (up to 25 L) and pilot-scale (up to 300 L) versions. They consist of three components:
  • A rocker base unit containing a bag holder with heating capabilities.
  • The biocompatible disposable chamber with integrated, single use, sensors for pH and DO.
  • The measuring and control unit (Figure 1).

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