Process control in bioreactors: Which feeding strategy helps prevent excessive lactate generation in mammalian cell culture?

Difficulty: Medium

Correct Answer: Maintain low glucose concentration (controlled feed)

Explanation:


Introduction / Context:
In fed-batch mammalian cultures, excessive glycolytic flux leads to lactate accumulation, which harms growth and productivity. Process engineers therefore modulate substrate feeds to steer metabolism.



Given Data / Assumptions:

  • Lactate primarily arises from glucose catabolism via glycolysis.
  • Glutamine catabolism produces ammonium, a different inhibitory metabolite.
  • Objective is to minimize lactate buildup without starving cells.


Concept / Approach:
Keeping extracellular glucose at modest levels (for example, 0.5–2 g/L) reduces overflow metabolism and favors oxidative pathways. Feedback-controlled feeding maintains steady, lower glucose concentrations, decreasing lactate formation while sustaining growth.



Step-by-Step Solution:

Identify the metabolite of concern: lactate from glucose.Control the precursor: lower extracellular glucose concentration by controlled feeding.Select the option that directly addresses glucose moderation.


Verification / Alternative check:
Publications and industrial guidelines show lactate reduction when glucose is maintained at low, non-saturating levels, often combined with pH/base control and alternative carbon sources.



Why Other Options Are Wrong:

Low glutamine: primarily impacts ammonium, not lactate.High glutamine or high glucose: exacerbate by-product accumulation.Large bolus pulses: promote metabolic overflow and by-product spikes.


Common Pitfalls:
Over-restricting glucose so cells starve; controlled feeding should sustain but not saturate.



Final Answer:
Maintain low glucose concentration (controlled feed).

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