Theoretical considerations of scale-up MCQs With Answer

Introduction: This quiz set on “Theoretical considerations of scale-up” is tailored for M.Pharm students studying Bioprocess Engineering and Technology. It focuses on core theoretical principles used when moving laboratory or pilot-scale bioprocesses to production scale. Questions cover dimensionless numbers, mixing and mass transfer, scale-up criteria (constant P/V, tip speed, kLa, etc.), oxygen transfer and uptake, shear effects, power and impeller considerations, and scale-down strategies. The aim is to reinforce conceptual understanding required for designing, evaluating, and troubleshooting scale-up operations in microbial and cell culture processes. Use these MCQs to test and deepen your grasp of the theoretical foundations guiding rational scale-up decisions.

Q1. What is the primary objective when scaling up a bioreactor process?

• To increase the reactor volume regardless of process performance
• To maintain similar hydrodynamic, mass transfer and physiological conditions for the cells
• To change the bioreactor geometry to suit manufacturing constraints
• To maximize gas flow rate at large scale

Correct Answer: To maintain similar hydrodynamic, mass transfer and physiological conditions for the cells

Q2. Which dimensionless number is most directly associated with the relative importance of inertial to viscous forces in stirred tanks?

• Froude number
• Reynolds number
• Péclet number
• Sherwood number

Correct Answer: Reynolds number

Q3. A common empirical correlation for volumetric oxygen transfer coefficient (kLa) in stirred tanks often relates kLa to which two measurable variables?

• Power per unit volume (P/V) and superficial gas velocity (or gas flow rate)
• Temperature and pH
• Cell concentration and substrate concentration
• Impeller diameter and vessel height only

Correct Answer: Power per unit volume (P/V) and superficial gas velocity (or gas flow rate)

Q4. If a scale-up strategy fixes constant P/V (power per unit volume), what is the expected effect on mixing time when increasing reactor volume assuming geometric similarity?

• Mixing time will decrease proportionally with volume
• Mixing time will remain exactly constant
• Mixing time will generally increase, but less than proportional to volume
• Mixing time becomes independent of impeller speed

Correct Answer: Mixing time will generally increase, but less than proportional to volume

Q5. Which scale-up criterion is most appropriate when the primary limitation is oxygen transfer to high-density aerobic cultures?

• Constant geometric similarity only
• Constant tip speed
• Constant kLa
• Constant power number

Correct Answer: Constant kLa

Q6. The tip speed of an impeller is calculated using which parameters?

• Impeller diameter and rotational speed
• Vessel diameter and liquid density
• Gas flow rate and impeller blade angle
• Power input and viscosity

Correct Answer: Impeller diameter and rotational speed

Q7. Which effect becomes increasingly important for sensitive mammalian cells during scale-up and can be exacerbated by high tip speed or gas sparging?

• Increased fermentation temperature
• Shear-induced cell damage
• Improved substrate uptake
• Reduced oxygen solubility

Correct Answer: Shear-induced cell damage

Q8. The power number (Np) for an impeller is a function of which dimensionless groups or conditions?

• Only fluid compressibility
• Reynolds number and impeller geometry
• pH and osmolarity
• Cell growth rate

Correct Answer: Reynolds number and impeller geometry

Q9. When scaling up using constant tip speed as the criterion, what typically happens to power per unit volume (P/V) as reactor size increases under geometric similarity?

• P/V increases proportionally with volume
• P/V remains constant
• P/V decreases
• P/V becomes independent of speed

Correct Answer: P/V decreases

Q10. Which dimensionless number is often used in gas-liquid mass transfer analogies to relate mass transfer to momentum transfer?

• Péclet number
• Schmidt number (Sc)
• Biot number
• Damköhler number

Correct Answer: Schmidt number (Sc)

Q11. In scale-up, gas holdup generally affects kLa because gas holdup influences which of the following?

• Surface tension only
• Interfacial area available for mass transfer and residence time of bubbles
• Protein folding
• Impeller blade wettability

Correct Answer: Interfacial area available for mass transfer and residence time of bubbles

Q12. For high-viscosity fermentations, which scaling parameter becomes less reliable and often requires rheology-specific adjustments?

• Reynolds number
• Temperature
• pH
• Color of the medium

Correct Answer: Reynolds number

Q13. Which of the following is NOT typically a reason to use scale-down models?

• To reproduce large-scale gradients and investigate their effects
• To reduce development cost and time while testing process robustness
• To intentionally make the lab process perform better than the plant
• To study hydrodynamic or mass transfer limitations observed at scale

Correct Answer: To intentionally make the lab process perform better than the plant

Q14. The oxygen uptake rate (OUR) of the culture is important for scale-up because it defines which requirement?

• Required reactor wall thickness
• Required oxygen transfer capacity (OTR) to meet culture demand
• Buffer composition
• Color of the sparger

Correct Answer: Required oxygen transfer capacity (OTR) to meet culture demand

Q15. Which practice helps to preserve similar bubble size distribution when scaling up sparged bioreactors?

• Using the same impeller material only
• Maintaining similar superficial gas velocity and similar sparger design
• Doubling the gas flow rate without changing anything else
• Reducing liquid viscosity to zero

Correct Answer: Maintaining similar superficial gas velocity and similar sparger design

Q16. In stirred-tank fermenters, the empirical relationship kLa ∝ (P/V)^α·(Qg/V)^β indicates that increasing P/V typically affects kLa primarily by changing what?

• Reaction stoichiometry
• Turbulent dissipation and bubble breakup increasing interfacial area
• Cell genetic expression
• Evaporation rate

Correct Answer: Turbulent dissipation and bubble breakup increasing interfacial area

Q17. Which of the following dimensionless numbers is most relevant for predicting free-surface effects such as vortex formation in stirred tanks?

• Reynolds number
• Froude number
• Schmidt number
• Damköhler number

Correct Answer: Froude number

Q18. When maintaining constant volumetric power input (P/V) during scale-up, what is a likely implication for impeller rotational speed as vessel diameter increases?

• Rotational speed must increase proportionally to diameter
• Rotational speed must decrease, often roughly proportional to D^(-2/3) under geometric similarity
• Rotational speed must be doubled for all scales
• Rotational speed remains unchanged

Correct Answer: Rotational speed must decrease, often roughly proportional to D^(-2/3) under geometric similarity

Q19. Computational Fluid Dynamics (CFD) is increasingly used in scale-up because it can provide insights into which of the following?

• Detailed local hydrodynamics, shear fields, and concentration gradients that are hard to measure experimentally
• Cell mutation rates
• Exact product yield independent of process conditions
• Nutrient composition of media

Correct Answer: Detailed local hydrodynamics, shear fields, and concentration gradients that are hard to measure experimentally

Q20. Which scaling approach is most conservative when the aim is to minimize shear exposure for fragile animal cell cultures?

• Maintain constant impeller tip speed
• Maintain constant power per volume
• Maintain constant kLa regardless of shear
• Maintain constant dissolved oxygen concentration by aggressive sparging

Correct Answer: Maintain constant impeller tip speed

Download