185. In a fed batch cultivation, a specific growth rate of 0.2/h needs to be maintained. At the start of fedbatch
cultivation, 200 mL/h of media is fed to 1000 mL of working volume. Quasi steady state shall be obtained if:
1. flow rate/volume is kept constant at 0.2/h
2. flow rate/volume increases exponentially with time
3. flow rate increases linearly with time
4. flow rate is kept constant

---

Introduction:

Fed-batch cultivation is a widely used technique in bioprocessing, where nutrients are continuously fed to a bioreactor to support cell growth while limiting byproduct formation. In this method, maintaining a specific growth rate and a quasi-steady state is crucial for optimal cell growth and product formation. One of the key aspects of achieving a steady state is controlling the flow rate of the feeding medium.

This article explores how the flow rate and volume should be managed in a fed-batch culture to maintain a specific growth rate of 0.2/h and achieve a quasi-steady state.

Key Concepts in Fed-Batch Cultivation:

1. Specific Growth Rate (μ): The specific growth rate (μ) is a measure of the rate at which the biomass (cells) in the bioreactor grows. In this case, we are aiming to maintain a specific growth rate of 0.2 h⁻¹.

2. Fed-Batch Cultivation: In fed-batch cultivation, a constant supply of nutrients is added to the bioreactor to avoid nutrient limitation. Unlike batch cultivation, where nutrients are consumed in a closed system, fed-batch allows for the continuous addition of nutrients to support sustained growth.

3. Quasi-Steady State: A quasi-steady state refers to a condition where the rate of nutrient input and cell growth balance each other out, resulting in stable growth conditions without significant accumulation of unused nutrients or metabolites.

Flow Rate and Volume Relationship:

The relationship between the flow rate and volume is essential in maintaining the specific growth rate (0.2/h) and ensuring a quasi-steady state. Here are the options for how the flow rate and volume can be adjusted:

1. Flow Rate/Volume Kept Constant at 0.2/h: In a fed-batch system, if the flow rate is kept constant at a value that maintains the specific growth rate (0.2/h), the nutrient addition should match the rate of cell consumption. This will help achieve a stable growth rate over time and maintain the quasi-steady state. This is a common approach in fed-batch systems, especially when the growth rate is consistent.

2. Flow Rate/Volume Increases Exponentially with Time: Increasing the flow rate exponentially would lead to rapid accumulation of nutrients in the reactor, which could overwhelm the cells and lead to undesirable conditions such as nutrient excess or inhibitory effects. This would disrupt the steady-state maintenance, making it unsuitable for controlled growth.

3. Flow Rate Increases Linearly with Time: A linear increase in flow rate would imply a gradual rise in nutrient concentration, which might result in imbalance between the growth rate and nutrient availability over time. This could cause instability in the system, preventing the achievement of a quasi-steady state.

4. Flow Rate is Kept Constant: If the flow rate is kept constant but does not match the rate of growth (0.2/h), the system could experience either nutrient depletion or nutrient accumulation, leading to suboptimal growth conditions. A constant flow rate might not be sufficient to maintain the desired specific growth rate, making this less ideal than adjusting it appropriately.

Conclusion:

To achieve a quasi-steady state in fed-batch cultivation while maintaining a specific growth rate of 0.2/h, the flow rate/volume ratio must be adjusted so that it matches the cell growth needs and nutrient consumption. The best approach is to keep the flow rate/volume constant at 0.2/h, ensuring that the system is balanced and stable.

Answer:

The correct answer is 1. flow rate/volume is kept constant at 0.2/h.