Question 5 of 10: Bioreactor Design Data and Operating-Mode Selection

Question 5: Bioreactor Design Data and Operating-Mode Selection (20 marks)

Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.

(a) Data needed to design a bioreactor. A complete bioreactor design draws on data from four domains — biological kinetics, stoichiometry/thermodynamics, transport, and mechanical/regulatory constraints:

1. Growth kinetics — maximum specific growth rate $\mu_{\max}$, substrate-saturation constant $K_S$ (Monod parameters), and any substrate/product inhibition constants.
2. Yield coefficients — $Y_{XS}$, $Y_{PS}$, $Y_{XO_2}$, and maintenance-energy coefficient $m_S$.
3. Stoichiometry — the balanced elemental equation (C, H, N, O atom balances) linking substrate, oxygen, biomass and product.
4. Oxygen transfer requirements — oxygen uptake rate (OUR) and the volumetric mass-transfer coefficient $k_La$ needed to supply it, since O₂ solubility in broth is very low.
5. Heat generation and removal — metabolic heat load (from OUR, via the kJ/mol-O₂ rule) and the cooling-jacket/coil area needed to hold the setpoint temperature.
6. Rheology of the broth — viscosity (Newtonian vs. shear-thinning, e.g. filamentous fungal broths), which sets impeller power draw and mixing time.
7. Sterility and containment requirements — sterilization method (in-situ steam, continuous), seal/port design, containment level for the organism.
8. pH control requirements — optimal pH range and buffering/acid–base dosing capacity.
9. Foam control needs — antifoam dosing and headspace/disengagement volume.
10. Scale-up criteria — the chosen basis for scale-up (constant $P/V$, constant $k_La$, constant tip speed, or constant mixing time), plus the target production capacity (batch size, annual throughput) that fixes overall vessel volume.

(b) Reasons to choose each operating mode.

Batch: (i) Simplicity and low contamination risk — the vessel is charged, sterilized, run to completion and emptied as one closed cycle, minimizing the number of open connections through which contaminants can enter, which matters most for products with strict sterility requirements (pharmaceuticals, some enzymes). (ii) Flexibility for multi-product facilities — the same vessel can be cleaned and re-used for a different product/strain between runs, an advantage where production volumes for any single product are too small to justify a dedicated continuous line.

Fed-batch: (i) Avoids substrate inhibition and catabolite repression — feeding substrate incrementally keeps its concentration low throughout the run, which is essential when high initial substrate (e.g. glucose) would either inhibit growth directly or trigger repression of a desired product pathway (classic case: recombinant-protein or antibiotic production, where glucose repression must be avoided). (ii) Extends the productive phase and raises final cell/product density beyond what a single batch charge could sustain, without the added complexity (and contamination exposure) of true continuous operation.

Chemostat (continuous): (i) Steady-state operation at a fixed, operator-chosen growth rate (set by the dilution rate $D=\mu$) gives constant product quality/composition and high volumetric productivity over long runs, valuable for commodity products (single-cell protein, some organic acids) where throughput and consistency matter more than per-run flexibility. (ii) It is the standard tool for physiological/kinetic research — because $\mu$ is held constant and independent of substrate concentration, it is the only mode that lets $\mu_{\max}$, $K_S$ and yield coefficients be measured cleanly at a chosen, reproducible growth rate.