Scale-down theory MCQs With Answer

Scale-down theory MCQs With Answer

Introduction: Scale-down theory is an essential topic for M.Pharm students specializing in bioprocess engineering and technology. This blog presents focused multiple-choice questions that probe principles used to design lab-scale systems which faithfully reproduce large-scale bioreactor behaviour. Questions emphasize similarity criteria (geometric, kinematic, dynamic), dimensionless numbers (Reynolds, Froude, power number), oxygen transfer and mixing scaling, hydrodynamic stress, and practical scale-down strategies for shear-sensitive biologics. These MCQs will strengthen conceptual understanding and help apply quantitative scaling rules when developing representative small-scale models for process development, troubleshooting, and regulatory submissions.

Q1. What is the primary objective of scale-down model development in bioprocess engineering?

• To build the smallest possible reactor regardless of performance
• To replicate critical large-scale process performance and stresses in a controlled laboratory system
• To reduce cost by changing process chemistry at small scale
• To eliminate the need for pilot-scale testing entirely

Correct Answer: To replicate critical large-scale process performance and stresses in a controlled laboratory system

Q2. Which similarity criterion is most appropriate when the main concern is matching mixing intensity and shear exposure between scales?

• Geometric similarity
• Constant impeller tip speed
• Constant power per unit volume (P/V)
• Constant residence time distribution

Correct Answer: Constant power per unit volume (P/V)

Q3. Which dimensionless number is most useful to compare inertial and viscous forces and to characterize flow regime in stirred bioreactors?

• Froude number
• Power number
• Reynolds number
• Schmidt number

Correct Answer: Reynolds number

Q4. When oxygen transfer is limiting and must be preserved at small scale, which parameter is commonly conserved during scale-down?

• Impeller diameter
• Volumetric mass transfer coefficient (kLa)
• Pump head
• Vessel wall thickness

Correct Answer: Volumetric mass transfer coefficient (kLa)

Q5. For turbulent stirred tanks, scaling based on constant P/V typically implies what relationship between agitation speed (N) and vessel volume (V)?

• N scales proportional to V^(1/3)
• N scales proportional to V^(-1/3)
• N does not change with V
• N scales proportional to V^(-1)

Correct Answer: N scales proportional to V^(-1/3)

Q6. Which of the following is a limitation of simple geometric similarity when scaling down bioreactors?

• It guarantees identical hydrodynamic stress distribution
• It ensures identical oxygen transfer coefficients across scales
• It often fails because power input and mass transfer do not scale linearly with size
• It automatically preserves mixing times

Correct Answer: It often fails because power input and mass transfer do not scale linearly with size

Q7. Which criterion would you prioritize when scale-down aims to reproduce shear-sensitive cell damage observed at production scale?

• Constant kLa
• Constant volumetric power input (P/V)
• Constant oxygen concentration in off-gas
• Constant sampling frequency

Correct Answer: Constant volumetric power input (P/V)

Q8. The power number (Np) for an impeller is defined as which combination of variables made dimensionless?

• P/(ρ N^3 D^5)
• P/(μ N^2 D^3)
• P/(ρ g H^2)
• P/(N D)

Correct Answer: P/(ρ N^3 D^5)

Q9. When scale-down targets constant impeller tip speed, what is a likely consequence for oxygen transfer (kLa) as scale decreases?

• kLa will necessarily remain constant
• kLa tends to decrease if power per unit volume drops
• kLa will increase proportional to tip speed squared
• kLa is independent of tip speed

Correct Answer: kLa tends to decrease if power per unit volume drops

Q10. Which similarity approach explicitly accounts for gravitational effects important for free-surface flows and gas dispersion?

• Reynolds scaling
• Froude scaling
• Geometric scaling
• Thermal scaling

Correct Answer: Froude scaling

Q11. In scale-down design for oxygen-limited aerobic cultures, why might one simulate sparger performance at small scale?

• Sparger design does not affect gas-liquid mass transfer
• Gas bubble size distribution and dispersion affect kLa and local DO gradients
• Spargers only impact sterility and not mass transfer
• Spargers affect only heat transfer

Correct Answer: Gas bubble size distribution and dispersion affect kLa and local DO gradients

Q12. What is the typical effect of non-Newtonian rheology on scale-down similarity choices?

• Non-Newtonian behavior simplifies scaling because viscosity is constant
• It requires consideration of local shear rates and apparent viscosity, making simple P/V scaling unreliable
• It allows use of Froude number as the sole scaling metric
• Rheology has no effect on kLa or mixing

Correct Answer: It requires consideration of local shear rates and apparent viscosity, making simple P/V scaling unreliable

Q13. Which experimental measurement is often used to validate a scale-down model of mixing performance?

• Protein sequence analysis
• Mixing time measured by tracer decay or pH step
• Gas chromatogram of off-gas components
• Vessel wall thermal conductivity

Correct Answer: Mixing time measured by tracer decay or pH step

Q14. In population balance approaches integrated with scale-down, what phenomenon is typically being modeled?

• Heat transfer across the vessel wall
• Particle/bubble size distribution dynamics including breakage and aggregation
• Genomic variation in cell line
• Electrical conductivity of medium

Correct Answer: Particle/bubble size distribution dynamics including breakage and aggregation

Q15. Computational Fluid Dynamics (CFD) is increasingly used in scale-down design because it can:

• Replace all physical experiments with perfect accuracy
• Provide detailed local fields of velocity, shear and gas hold-up to guide scale-down decisions
• Guarantee identical kLa across scales without validation
• Negate the need to understand dimensionless numbers

Correct Answer: Provide detailed local fields of velocity, shear and gas hold-up to guide scale-down decisions

Q16. Which of the following is a common practical compromise when exact similarity cannot be achieved at small scale?

• Change the biological system to fit the scale
• Prioritize reproducing the most critical performance attributes (e.g., kLa or shear) and accept deviations in less critical metrics
• Ignore scale effects entirely
• Run production-scale fermentations at lab environmental conditions

Correct Answer: Prioritize reproducing the most critical performance attributes (e.g., kLa or shear) and accept deviations in less critical metrics

Q17. For shear-sensitive mammalian cells, which scale-down parameter is often limited to minimize damage while attempting to match large-scale conditions?

• Sterility assurance level
• Maximum local energy dissipation rate
• Culture medium osmolarity
• Sampling interval

Correct Answer: Maximum local energy dissipation rate

Q18. When replicating gas-liquid mass transfer using constant superficial gas velocity at different scales, what must also be considered to ensure similarity?

• Impeller geometry, mixing regime and bubble coalescence dynamics
• Only the vessel color
• Protein molecular weight
• Ambient room temperature alone

Correct Answer: Impeller geometry, mixing regime and bubble coalescence dynamics

Q19. Which monitoring strategy can improve the relevance of a scale-down model by ensuring comparable process dynamics?

• Real-time monitoring of DO, pH and off-gas combined with feedback control to match large-scale profiles
• Only end-point sampling
• Monitoring only external temperature
• Weekly manual cell counts

Correct Answer: Real-time monitoring of DO, pH and off-gas combined with feedback control to match large-scale profiles

Q20. What is a recommended first step when designing a scale-down model for a new production bioprocess?

• Assume geometric similarity is sufficient and proceed with the smallest vessel
• Perform risk assessment to identify critical large-scale attributes (e.g., kLa, P/V, shear) and select similarity criteria accordingly
• Immediately run full-scale batches to get data
• Change the strain to a more robust organism

Correct Answer: Perform risk assessment to identify critical large-scale attributes (e.g., kLa, P/V, shear) and select similarity criteria accordingly

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