Q.1 What is the primary purpose of scale‑up in bioprocess engineering?
To increase product purity
To reduce the number of steps in the process
To reproduce laboratory results at commercial production volumes
To change the type of organism used
Explanation - Scale‑up aims to translate the performance obtained in a lab‑scale reactor to larger, industrial‑scale equipment while maintaining product quality and yields.
Correct answer is: To reproduce laboratory results at commercial production volumes
Q.2 Which of the following is a common scale‑up criterion for aerobic fermentations?
Constant substrate concentration
Constant power input per unit volume (P/V)
Constant reactor height
Constant agitation blade width
Explanation - Maintaining a constant P/V helps to keep the oxygen transfer rate (OTR) similar across scales, which is critical for aerobic microbes.
Correct answer is: Constant power input per unit volume (P/V)
Q.3 In scale‑down studies, which phenomenon is typically replicated to mimic large‑scale bioreactors?
Uniform temperature distribution
Perfect mixing
Gradients in substrate concentration
Absence of shear stress
Explanation - Scale‑down models often reproduce the substrate, oxygen, and pH gradients that occur in large reactors due to imperfect mixing.
Correct answer is: Gradients in substrate concentration
Q.4 Which dimensionless number is most useful for comparing mixing efficiency between bioreactors of different sizes?
Reynolds number (Re)
Péclet number (Pe)
Damköhler number (Da)
Biot number (Bi)
Explanation - Reynolds number indicates the ratio of inertial to viscous forces, helping to assess whether flow regimes (laminar or turbulent) are comparable across scales.
Correct answer is: Reynolds number (Re)
Q.5 When scaling up a stirred‑tank bioreactor, which parameter is kept constant to preserve shear conditions?
Impeller tip speed
Agitation frequency (rpm)
Gas flow rate
Liquid volume
Explanation - Tip speed (π·D·N) directly influences shear forces experienced by cells; keeping it constant helps protect shear‑sensitive organisms during scale‑up.
Correct answer is: Impeller tip speed
Q.6 What is the typical relationship between oxygen transfer coefficient (kLa) and agitation speed (N) in a well‑mixed bioreactor?
kLa ∝ N
kLa ∝ N²
kLa ∝ N³
kLa is independent of N
Explanation - Empirically, kLa often scales with the cube of the impeller speed in turbulent regimes, reflecting increased gas‑liquid interfacial area.
Correct answer is: kLa ∝ N³
Q.7 Which of the following is NOT a typical limitation encountered during scale‑up of a bioprocess?
Oxygen limitation
Heat removal constraints
Increased substrate concentration
Mixing time elongation
Explanation - Substrate concentration is usually kept the same; scale‑up issues arise from physical transport phenomena, not intentional changes in feed composition.
Correct answer is: Increased substrate concentration
Q.8 The term ‘geometric similarity’ in scale‑up means:
All dimensions are scaled by the same factor
The ratio of height to diameter is doubled
Only the impeller diameter is changed
The volume is increased tenfold
Explanation - Geometric similarity requires that all linear dimensions (height, diameter, impeller size) maintain the same proportions across scales.
Correct answer is: All dimensions are scaled by the same factor
Q.9 In a scale‑down model, a “plug‑flow” reactor is often used to simulate:
Perfect mixing
Large‑scale gradient formation
Heat removal
Aeration efficiency
Explanation - Plug‑flow reactors create concentration gradients along the reactor length, mimicking the non‑ideal mixing observed in large vessels.
Correct answer is: Large‑scale gradient formation
Q.10 Which parameter is most directly related to the heat transfer capability of a bioreactor?
kLa
U·A (overall heat transfer coefficient × area)
P/V (power per volume)
pH control range
Explanation - The product of the overall heat transfer coefficient (U) and the heat transfer area (A) determines the reactor's ability to remove or add heat.
Correct answer is: U·A (overall heat transfer coefficient × area)
Q.11 During scale‑up, why is it important to keep the ratio of impeller diameter to tank diameter (D_i/D_t) constant?
To maintain the same surface area for gas exchange
To ensure similar flow patterns and mixing zones
To keep the reactor temperature constant
To preserve the same number of baffles
Explanation - The D_i/D_t ratio influences the flow field generated by the impeller; keeping it constant helps replicate mixing behavior across scales.
Correct answer is: To ensure similar flow patterns and mixing zones
Q.12 Which of the following is a valid approach to design a scale‑down model for a 10,000‑L fermenter?
Operate a 1‑L reactor at the same rpm as the large reactor
Match the oxygen transfer rate (OTR) by adjusting agitation and aeration
Reduce the substrate feed rate by a factor of 10,000
Increase the temperature by 5 °C
Explanation - A scale‑down model should replicate critical transport phenomena like OTR, often achieved by changing agitation speed and gas flow to match the large‑scale OTR.
Correct answer is: Match the oxygen transfer rate (OTR) by adjusting agitation and aeration
Q.13 When scaling up a fed‑batch process, which control strategy is most commonly adjusted?
pH set‑point
Feed rate profile
Cooling water flow
Impeller shape
Explanation - Feed rate determines substrate availability and can be tuned to avoid overflow metabolism or oxygen limitation in larger reactors.
Correct answer is: Feed rate profile
Q.14 The Damköhler number (Da) in a bioreactor is a ratio of:
Convective transport to diffusive transport
Reaction rate to mass transfer rate
Inertial forces to viscous forces
Heat generation to heat removal
Explanation - Da compares the time scale of chemical/biological reactions to that of mass transfer; a high Da indicates reaction‑limited conditions.
Correct answer is: Reaction rate to mass transfer rate
Q.15 Which type of impeller is preferred for shear‑sensitive mammalian cell cultures during scale‑up?
Rushton turbine
Marine propeller
Pitch‑blade turbine
Flat‑blade turbine
Explanation - Marine propellers generate lower shear and are thus gentler on fragile mammalian cells compared to high‑shear Rushton turbines.
Correct answer is: Marine propeller
Q.16 In bioprocess scale‑down, the term “harsh‑environment simulator” refers to:
A system that increases temperature above optimal levels
A reactor that reproduces the high‑shear zones of large reactors
A device that removes all dissolved oxygen
A setup that eliminates pH fluctuations
Explanation - Harsh‑environment simulators mimic extreme conditions such as high shear or low oxygen that cells may encounter in large‑scale vessels.
Correct answer is: A reactor that reproduces the high‑shear zones of large reactors
Q.17 Which of the following is the most accurate definition of ‘scale‑down’ in bioprocess engineering?
Reducing the volume of a reactor without changing any parameters
Creating a small‑scale model that mimics the key transport phenomena of a large‑scale process
Running a pilot plant at half the industrial capacity
Lowering the temperature of the process to save energy
Explanation - Scale‑down models are deliberately designed to reproduce the physical and biochemical stresses of large reactors in a lab‑scale system.
Correct answer is: Creating a small‑scale model that mimics the key transport phenomena of a large‑scale process
Q.18 What is the main advantage of using a “segmented” scale‑down reactor for studying metabolic responses?
It provides uniform mixing
It allows separate control of temperature in each segment
It creates distinct zones with different substrate concentrations
It reduces the need for oxygen
Explanation - Segmented reactors can generate controlled gradients, enabling investigation of how cells respond to localized nutrient limitations.
Correct answer is: It creates distinct zones with different substrate concentrations
Q.19 When scaling up a process that is limited by oxygen transfer, which of the following strategies is most effective?
Increase the impeller diameter only
Raise the fermentation temperature
Increase both agitation speed and aeration rate
Decrease the pH set‑point
Explanation - Both agitation (increasing kLa) and aeration (increasing gas flow) directly improve oxygen transfer capacity.
Correct answer is: Increase both agitation speed and aeration rate
Q.20 In the context of scale‑up, what does the term ‘specific power input (P/V)’ represent?
Power delivered per unit mass of cells
Power delivered per unit reactor volume
Power lost due to friction
Power required for temperature control
Explanation - P/V (W·m⁻³) is a key scale‑up criterion that reflects the energy density supplied to the broth for mixing and mass transfer.
Correct answer is: Power delivered per unit reactor volume
Q.21 Which parameter is most commonly used to assess mixing efficiency in a bioreactor?
Mixing time
Viscosity of the broth
pH variation
Impeller blade count
Explanation - Mixing time, the time required for a tracer to become uniformly distributed, directly quantifies the mixing performance.
Correct answer is: Mixing time
Q.22 What does the term ‘critical shear stress’ refer to in bioprocess scale‑up?
The minimum shear needed to break cell aggregates
The maximum shear that cells can tolerate without damage
The shear required for complete mixing
The shear generated by gas sparging
Explanation - Critical shear stress is the threshold beyond which cell viability or product quality is adversely affected.
Correct answer is: The maximum shear that cells can tolerate without damage
Q.23 Which of the following is a typical method for measuring kLa in a stirred bioreactor?
Using a conductivity probe
Dynamic gassing‑out method
Measuring torque on the impeller
Observing foam height
Explanation - The dynamic gassing‑out method tracks dissolved oxygen concentration after stopping aeration, allowing calculation of kLa.
Correct answer is: Dynamic gassing‑out method
Q.24 In a scale‑up from 5 L to 500 L, keeping the Reynolds number constant ensures:
Identical temperature profiles
Similar flow regime (laminar or turbulent)
The same oxygen concentration
The same substrate consumption rate
Explanation - Reynolds number governs the transition between laminar and turbulent flow; keeping it constant maintains the same flow characteristics.
Correct answer is: Similar flow regime (laminar or turbulent)
Q.25 Which of the following statements about scale‑down models is TRUE?
They always use the same reactor geometry as the large scale.
They are designed to exaggerate all process stresses.
They aim to replicate the most limiting phenomena of the large‑scale process.
They eliminate the need for pilot‑scale testing.
Explanation - Scale‑down models focus on reproducing critical limitations (e.g., oxygen, substrate gradients) to study their impact on performance.
Correct answer is: They aim to replicate the most limiting phenomena of the large‑scale process.
Q.26 What is the typical effect of increasing the impeller tip speed during scale‑up?
Decreased oxygen transfer
Reduced mixing time
Lowered temperature
Increased pH stability
Explanation - Higher tip speed enhances turbulent mixing, shortening the time needed to homogenize the broth.
Correct answer is: Reduced mixing time
Q.27 When designing a scale‑down model for a high‑cell‑density yeast fermentation, which parameter is most critical to reproduce?
Foam formation rate
Viscosity increase due to high cell concentration
Impeller clearance
Color of the broth
Explanation - High cell density raises broth viscosity, affecting mixing, mass transfer, and power consumption; a scale‑down model must capture this effect.
Correct answer is: Viscosity increase due to high cell concentration
Q.28 Which of the following best describes the purpose of a “parallel” scale‑down experiment?
Running multiple reactors at different temperatures
Running several identical small reactors simultaneously to increase data reliability
Using a single reactor to test many variables sequentially
Connecting reactors in series for continuous operation
Explanation - Parallel experiments provide statistical confidence and allow assessment of reproducibility under identical conditions.
Correct answer is: Running several identical small reactors simultaneously to increase data reliability
Q.29 In a fed‑batch scale‑up, the ‘exponential feeding strategy’ is used to:
Maintain constant substrate concentration
Keep the specific growth rate constant
Avoid oxygen limitation
Reduce temperature spikes
Explanation - Exponential feeding supplies substrate at a rate that matches the desired specific growth rate, preventing substrate accumulation or depletion.
Correct answer is: Keep the specific growth rate constant
Q.30 Which factor primarily influences the choice of gas sparger design during scale‑up?
Desired dissolved oxygen concentration
Reactor height
Impeller diameter
pH control strategy
Explanation - The sparger design (e.g., pore size, number of holes) determines bubble size and gas‑liquid interfacial area, directly affecting oxygen transfer.
Correct answer is: Desired dissolved oxygen concentration
Q.31 In scale‑up, the term ‘process intensification’ refers to:
Increasing the reactor size without changing any parameters
Achieving higher product yields per unit volume or time
Using more expensive equipment
Reducing the number of quality control tests
Explanation - Process intensification seeks to boost productivity, often by improving mass/heat transfer or optimizing operating conditions.
Correct answer is: Achieving higher product yields per unit volume or time
Q.32 Which mathematical model is frequently used to predict substrate concentration profiles in a scale‑down reactor?
Michaelis‑Menten kinetics
Plug‑flow model
Monod model
Logistic growth model
Explanation - Plug‑flow models describe concentration changes along the reactor length, suitable for representing gradients in scale‑down systems.
Correct answer is: Plug‑flow model
Q.33 When scaling up a micro‑bubble aeration system, the most important parameter to keep constant is:
Bubble diameter
Gas flow rate
Liquid viscosity
pH of the medium
Explanation - Bubble size determines interfacial area; maintaining it ensures comparable oxygen transfer efficiency across scales.
Correct answer is: Bubble diameter
Q.34 Which type of baffle arrangement is recommended for large‑scale stirred tanks to avoid vortex formation?
Four equally spaced baffles
Two baffles opposite each other
No baffles (smooth walls)
Six baffles with varying heights
Explanation - Four baffles placed at 90° intervals are standard for breaking the flow and preventing vortex formation in large vessels.
Correct answer is: Four equally spaced baffles
Q.35 In a scale‑down study, a “pseudo‑continuous” reactor mimics which large‑scale operation mode?
Batch fermentation
Fed‑batch fermentation
Continuous perfusion
Solid‑state fermentation
Explanation - Pseudo‑continuous reactors operate with intermittent feeding and harvesting, reproducing the steady‑state conditions of continuous perfusion.
Correct answer is: Continuous perfusion
Q.36 Which of the following is the most reliable indicator that a scale‑up has successfully maintained product quality?
Identical reactor dimensions
Same agitation speed (rpm)
Comparable impurity profile of the final product
Equal power consumption
Explanation - Product quality is assessed by impurity levels, potency, and activity; matching these confirms successful scale‑up.
Correct answer is: Comparable impurity profile of the final product
Q.37 When scaling up a process that is limited by heat removal, which design change is most effective?
Increasing impeller diameter
Adding external cooling coils
Reducing aeration rate
Increasing substrate concentration
Explanation - External cooling coils increase the heat transfer area, enhancing the reactor’s ability to dissipate metabolic heat.
Correct answer is: Adding external cooling coils
Q.38 What does the term ‘critical volume’ refer to in bioprocess scale‑up?
The volume at which oxygen limitation first occurs
The maximum reactor volume that can be operated with the existing equipment
The volume at which mixing time equals the residence time
The volume where power consumption exceeds the plant’s capacity
Explanation - Critical volume is reached when the mixing time becomes comparable to the residence time, leading to non‑uniform conditions.
Correct answer is: The volume at which mixing time equals the residence time
Q.39 In scale‑up, the term ‘hydrodynamic similarity’ means:
Keeping temperature constant
Maintaining the same Reynolds, Froude, and Péclet numbers across scales
Using the same type of impeller
Ensuring identical pH control loops
Explanation - Hydrodynamic similarity requires matching dimensionless groups that govern flow, buoyancy, and mass transfer phenomena.
Correct answer is: Maintaining the same Reynolds, Froude, and Péclet numbers across scales
Q.40 Which of the following strategies is commonly used to reduce shear stress in large‑scale mammalian cell cultures?
Increasing agitation speed
Using low‑shear impellers such as marine or axial flow designs
Increasing sparger gas flow
Raising the temperature
Explanation - Low‑shear impellers minimize mechanical damage while still providing adequate mixing and oxygen transfer.
Correct answer is: Using low‑shear impellers such as marine or axial flow designs
Q.41 What is the main benefit of employing a “cascade” scale‑down system?
It reduces the need for temperature control
It mimics sequential gradients that cells encounter in large reactors
It eliminates foam formation
It increases the overall reactor volume
Explanation - A cascade of reactors creates a series of environments, reproducing the progressive changes in substrate, oxygen, and pH seen at large scale.
Correct answer is: It mimics sequential gradients that cells encounter in large reactors
Q.42 During scale‑up, the term ‘tip speed’ (U_tip) is calculated as:
π × impeller diameter × rpm
Impeller diameter ÷ rpm
π × (impeller diameter ÷ 2) × rpm
rpm ÷ (π × impeller diameter)
Explanation - Tip speed = π·D·N where D is impeller diameter and N is revolutions per second; this formula expresses the linear velocity at the blade tip.
Correct answer is: π × (impeller diameter ÷ 2) × rpm
Q.43 In a scale‑down experiment, a “temperature shift” is introduced to study:
The effect of temperature on gas solubility
The robustness of the process to temperature fluctuations
The impact of temperature on impeller wear
The influence of temperature on foam stability
Explanation - Temperature shifts help evaluate how cells and reactions respond to deviations from the set‑point, informing control strategies for large plants.
Correct answer is: The robustness of the process to temperature fluctuations
Q.44 Which of the following is a typical scale‑up rule for maintaining similar mixing characteristics?
Keep impeller diameter constant
Keep the ratio of impeller speed to reactor volume (N/V) constant
Maintain the same gas flow rate
Use the same number of baffles
Explanation - Keeping N/V constant helps maintain comparable mixing times and energy input per unit volume across scales.
Correct answer is: Keep the ratio of impeller speed to reactor volume (N/V) constant
Q.45 In a scale‑down model that replicates large‑scale oxygen limitation, which parameter is typically reduced?
Aeration rate
Agitation speed
pH set‑point
Temperature
Explanation - Lowering the aeration rate reduces dissolved oxygen, reproducing the limitation observed in larger reactors.
Correct answer is: Aeration rate
Q.46 Which of the following is a common metric for evaluating the performance of a scale‑down model?
Relative standard deviation of product titer between runs
Number of impeller blades
Volume of the reactor
Length of the sparger
Explanation - Consistency in product titer indicates that the scale‑down model reliably reproduces the large‑scale behavior.
Correct answer is: Relative standard deviation of product titer between runs
Q.47 When scaling up a bioprocess, why is it important to monitor the specific growth rate (µ) of the organism?
To adjust the reactor’s color
To ensure that the organism does not outgrow the reactor’s capacity
To maintain product quality and avoid overflow metabolism
To keep the pH constant
Explanation - A controlled µ prevents accumulation of by‑products and ensures consistent product formation across scales.
Correct answer is: To maintain product quality and avoid overflow metabolism
Q.48 Which of the following best explains why scale‑down models often use higher agitation speeds than the corresponding large‑scale process?
To compensate for reduced gas flow
To achieve similar P/V values in a smaller volume
To increase the temperature
To reduce foam formation
Explanation - Higher agitation in small reactors raises the power density, allowing the model to match the energy input of the large system.
Correct answer is: To achieve similar P/V values in a smaller volume
Q.49 In the context of scale‑up, the term ‘mass transfer coefficient (kLa)’ is primarily influenced by:
Impeller material
Impeller speed, gas flow rate, and liquid properties
pH control strategy
Reactor wall thickness
Explanation - kLa depends on agitation, aeration, and properties such as viscosity and surface tension that affect gas‑liquid interfacial area.
Correct answer is: Impeller speed, gas flow rate, and liquid properties
Q.50 Which of the following is NOT a typical scale‑down strategy for simulating large‑scale temperature gradients?
Using a jacketed reactor with differential heating zones
Applying external cooling coils in only part of the reactor
Increasing the ambient room temperature
Running a two‑compartment reactor with separate temperature controls
Explanation - Ambient temperature changes affect the whole system uniformly and do not create internal gradients like the other methods.
Correct answer is: Increasing the ambient room temperature
Q.51 When scaling up a high‑cell‑density process, why might the viscosity of the broth become a limiting factor?
Viscosity reduces the solubility of oxygen
Viscosity increases the power required for mixing
Viscosity changes the pH of the medium
Viscosity enhances foam formation
Explanation - Higher viscosity hampers mixing and mass transfer, requiring more power to achieve the same mixing intensity, which may exceed equipment limits.
Correct answer is: Viscosity increases the power required for mixing
Q.52 Which dimensionless number is most useful for evaluating the relative importance of buoyancy forces during scale‑up?
Froude number (Fr)
Reynolds number (Re)
Péclet number (Pe)
Damköhler number (Da)
Explanation - Froude number compares inertial to gravitational forces, indicating the significance of buoyancy-driven flows.
Correct answer is: Froude number (Fr)
Q.53 In a scale‑down model, which type of sensor is most commonly used to monitor dissolved oxygen (DO) in real time?
pH electrode
Clark‑type polarographic sensor
Thermocouple
Turbidity meter
Explanation - Clark sensors provide rapid, accurate DO measurements essential for controlling oxygen transfer in bioprocesses.
Correct answer is: Clark‑type polarographic sensor
Q.54 During scale‑up, the term ‘critical mixing time’ is defined as the time required for:
The reactor to reach the set temperature
A tracer to become uniformly distributed within a specified tolerance
The impeller to complete one revolution
The dissolved oxygen to reach saturation
Explanation - Critical mixing time quantifies the speed at which homogeneity is achieved, often measured using a tracer such as sodium hydroxide.
Correct answer is: A tracer to become uniformly distributed within a specified tolerance
Q.55 Which of the following best describes the ‘cascade’ approach for scale‑down modeling?
Using a series of reactors with decreasing volumes to simulate decreasing shear
Connecting several reactors in series to mimic gradients encountered along the height of a large reactor
Running multiple parallel reactors with identical conditions
Employing a single reactor with intermittent feeding
Explanation - The cascade approach replicates spatial variations (e.g., oxygen, substrate) that occur from bottom to top in a large vessel.
Correct answer is: Connecting several reactors in series to mimic gradients encountered along the height of a large reactor
Q.56 Which of the following process parameters is most directly linked to the formation of foam in aerobic fermentations?
pH set‑point
Aeration rate
Impeller blade shape
Cooling water temperature
Explanation - Higher gas flow rates increase bubble formation, which can lead to foam if surfactants are present.
Correct answer is: Aeration rate
Q.57 In the context of scale‑up, what does the term ‘power number (Np)’ represent?
The ratio of impeller tip speed to reactor diameter
The dimensionless coefficient linking power consumption to impeller geometry and speed
The number of blades on the impeller
The power required to maintain temperature
Explanation - Power number (Np) = P/(ρ N³ D⁵) and characterizes the impeller’s hydraulic performance independent of scale.
Correct answer is: The dimensionless coefficient linking power consumption to impeller geometry and speed
Q.58 Which of the following is a typical reason for conducting a scale‑down experiment before full‑scale production?
To validate the color of the final product
To identify potential scale‑related issues such as gradients or shear effects
To reduce the size of the bioreactor
To change the microbial strain
Explanation - Scale‑down studies help anticipate problems that may arise only at large volumes, enabling proactive mitigation.
Correct answer is: To identify potential scale‑related issues such as gradients or shear effects
Q.59 When scaling up a process with a high demand for oxygen, which of the following modifications is LEAST likely to improve oxygen transfer?
Increasing the sparger pore size
Raising the agitation speed
Using pure oxygen instead of air
Increasing the liquid volume
Explanation - Larger liquid volumes dilute the effect of added gas and generally reduce the oxygen transfer rate per unit volume.
Correct answer is: Increasing the liquid volume
Q.60 In scale‑up, the concept of ‘constant volumetric mass transfer coefficient (kLa)’ is used to ensure:
Same temperature profile across scales
Identical mixing time
Similar oxygen transfer capacity per unit volume
Equal pH fluctuations
Explanation - Keeping kLa constant helps maintain the same oxygen availability for the microbes regardless of reactor size.
Correct answer is: Similar oxygen transfer capacity per unit volume
Q.61 Which of the following best describes a “mini‑bioreactor” used for scale‑down studies?
A reactor with a volume less than 1 mL used for high‑throughput screening
A small, well‑controlled stirred tank (e.g., 1–5 L) that replicates key large‑scale parameters
A disposable plastic bag used for single‑use applications
A fermenter without any agitation
Explanation - Mini‑bioreactors are designed to mimic the physical environment of large reactors while being manageable for laboratory work.
Correct answer is: A small, well‑controlled stirred tank (e.g., 1–5 L) that replicates key large‑scale parameters
Q.62 Which of the following is a common technique to assess whether a scale‑down model faithfully reproduces the large‑scale shear environment?
Measuring torque on the impeller
Recording the color of the broth
Measuring dissolved carbon dioxide
Counting the number of bubbles
Explanation - Torque correlates with the shear forces experienced by the fluid and can be compared across scales to assess similarity.
Correct answer is: Measuring torque on the impeller
Q.63 During scale‑up, the term ‘heat generation rate (Q)’ is most directly related to:
Microbial metabolic activity
Impeller geometry
Aeration rate
pH control strategy
Explanation - Metabolic reactions release heat; the rate of heat generation scales with cell density and specific growth rate.
Correct answer is: Microbial metabolic activity
Q.64 Which of the following statements about the use of pure oxygen in large‑scale aerobic fermentations is TRUE?
It eliminates the need for agitation
It reduces the required gas flow rate to achieve a given DO level
It increases the solubility of oxygen beyond its maximum in water
It has no effect on kLa
Explanation - Pure oxygen contains a higher O₂ partial pressure, so less gas flow is needed to reach the same dissolved oxygen concentration.
Correct answer is: It reduces the required gas flow rate to achieve a given DO level
Q.65 In a scale‑down reactor, a “step‑change” in substrate concentration is used to study:
The effect of gradual temperature increase
The dynamic response of cells to sudden nutrient availability
The impact of constant pH control
The influence of continuous aeration
Explanation - Step‑change experiments abruptly alter substrate levels, revealing how metabolism adjusts to fluctuations.
Correct answer is: The dynamic response of cells to sudden nutrient availability
Q.66 Which of the following best explains why scaling up from 10 L to 10,000 L often requires a change in impeller type?
Larger reactors cannot accommodate the same impeller diameter
Shear forces become less important at larger volumes
Power consumption scales linearly with volume
Different impeller designs provide better oxygen transfer and lower shear at large scales
Explanation - Impeller selection balances oxygen transfer efficiency with acceptable shear; large reactors often use axial‑flow or low‑shear designs.
Correct answer is: Different impeller designs provide better oxygen transfer and lower shear at large scales
Q.67 When scaling up a process, which of the following is a primary reason to maintain the same gas‑liquid interfacial area (a) per unit volume?
To keep the reactor temperature constant
To ensure comparable oxygen transfer rates
To reduce the amount of foam generated
To simplify cleaning procedures
Explanation - Oxygen transfer rate is proportional to kLa·C*, and kLa depends on the interfacial area; maintaining ‘a’ helps preserve OTR.
Correct answer is: To ensure comparable oxygen transfer rates
Q.68 Which of the following is an advantage of using a computational fluid dynamics (CFD) model in bioprocess scale‑up?
It eliminates the need for any experimental data
It provides detailed insight into flow patterns, shear fields, and mass transfer without building physical prototypes
It reduces the cost of raw materials
It guarantees 100 % success of the scale‑up
Explanation - CFD simulations can predict hydrodynamics and help optimize design before constructing large‑scale equipment.
Correct answer is: It provides detailed insight into flow patterns, shear fields, and mass transfer without building physical prototypes
Q.69 In scale‑down, a “high‑throughput” system typically refers to:
A single large reactor with many sensors
A set of many small parallel bioreactors enabling rapid screening of conditions
A reactor operating at very high agitation speeds
A system that continuously recycles media
Explanation - High‑throughput platforms allow simultaneous testing of multiple variables, accelerating process development.
Correct answer is: A set of many small parallel bioreactors enabling rapid screening of conditions
Q.70 Which of the following best characterises a ‘mass transfer‑limited’ regime in a bioreactor?
The substrate is completely consumed before the end of the feed
The rate of substrate uptake by cells is slower than its delivery by mixing
The oxygen transfer rate is lower than the cellular oxygen consumption rate
The temperature is lower than the optimal growth temperature
Explanation - When OTR < OUR, cells experience oxygen limitation, indicating a mass‑transfer‑limited condition.
Correct answer is: The oxygen transfer rate is lower than the cellular oxygen consumption rate
Q.71 When scaling up a fed‑batch process, the term ‘feed‑rate scaling factor (FSF)’ is defined as:
The ratio of feed volume in large scale to that in small scale
The ratio of agitation speed between scales
The ratio of substrate concentration in the feed between scales
The ratio of reactor height between scales
Explanation - FSF adjusts the amount of feed added to maintain the same substrate availability per cell mass across scales.
Correct answer is: The ratio of feed volume in large scale to that in small scale
Q.72 Which of the following is the most common cause of pH drift in large‑scale aerobic fermentations?
Temperature fluctuations
CO₂ accumulation from respiration
Excessive agitation
Impeller wear
Explanation - Respiratory CO₂ dissolves to form carbonic acid, lowering pH if not properly controlled.
Correct answer is: CO₂ accumulation from respiration
Q.73 In a scale‑down study, which experimental design is most suitable for investigating the combined effect of oxygen limitation and high shear?
One‑factor‑at‑a‑time (OFAT)
Full factorial design with varying aeration and agitation
Sequential batch reactor
Simple batch without control
Explanation - A factorial design allows simultaneous assessment of interactions between oxygen supply and shear stress.
Correct answer is: Full factorial design with varying aeration and agitation
Q.74 Which of the following statements best describes the purpose of a “heat‑exchange jacket” in large‑scale bioreactors?
To increase the reactor’s volume
To provide efficient temperature control by adding or removing heat
To improve oxygen solubility
To reduce foam formation
Explanation - Heat‑exchange jackets enable precise heating or cooling of the reactor contents, crucial for maintaining optimal process temperatures.
Correct answer is: To provide efficient temperature control by adding or removing heat
Q.75 When scaling up a process that uses a temperature‑sensitive enzyme, which parameter must be tightly controlled?
Impeller blade material
Reactor pressure
Temperature uniformity throughout the vessel
Gas sparger location
Explanation - Temperature gradients can cause local enzyme deactivation; uniform temperature ensures consistent activity across the reactor.
Correct answer is: Temperature uniformity throughout the vessel
Q.76 Which of the following is a typical method for measuring mixing time in a bioreactor?
Adding a pulse of sodium hydroxide and monitoring pH change
Measuring dissolved oxygen after stopping aeration
Recording the torque on the impeller
Weighing the reactor before and after operation
Explanation - A tracer (e.g., NaOH) creates a measurable concentration gradient; the time for pH to homogenize reflects mixing time.
Correct answer is: Adding a pulse of sodium hydroxide and monitoring pH change
Q.77 In scale‑down, the term ‘pseudo‑steady‑state’ refers to:
A condition where temperature fluctuates rapidly
A situation where average process variables remain constant despite underlying fluctuations
A state where the reactor is completely static
A period of constant pH drift
Explanation - Pseudo‑steady‑state mimics the average behavior of a continuous process while still experiencing short‑term disturbances.
Correct answer is: A situation where average process variables remain constant despite underlying fluctuations
Q.78 Which of the following is the most appropriate scaling rule when the aim is to preserve the same shear rate in a stirred tank?
Keep impeller tip speed constant
Keep the ratio of impeller diameter to tank diameter constant
Keep the Reynolds number constant
Keep the power per unit volume (P/V) constant
Explanation - Power per volume is directly related to the energy input and therefore to the shear rate experienced by the fluid.
Correct answer is: Keep the power per unit volume (P/V) constant
Q.79 When a large‑scale bioreactor operates at a constant gas‑liquid mass transfer coefficient (kLa), which of the following must also be maintained?
Constant gas flow rate
Constant agitation speed
Constant volumetric gas‑liquid interfacial area
Constant reactor height
Explanation - kLa is proportional to the interfacial area per unit volume; keeping this area constant preserves the mass transfer capability.
Correct answer is: Constant volumetric gas‑liquid interfacial area
Q.80 Which of the following phenomena is most likely to be exacerbated in a scale‑up from 100 L to 10,000 L if mixing time is not properly addressed?
Increased product colour variability
Formation of substrate and oxygen gradients leading to heterogeneous growth
Higher temperature uniformity
Reduced foaming
Explanation - Longer mixing times allow gradients to persist, causing cells in different zones to experience distinct conditions.
Correct answer is: Formation of substrate and oxygen gradients leading to heterogeneous growth
Q.81 In a scale‑down model, a “dual‑impeller” configuration is often employed to:
Increase the reactor’s volume
Simulate both high‑shear and low‑shear zones present in large reactors
Reduce the need for temperature control
Eliminate the need for gas sparging
Explanation - Dual impellers can create distinct flow regions, reproducing the shear heterogeneity observed in large‑scale vessels.
Correct answer is: Simulate both high‑shear and low‑shear zones present in large reactors
Q.82 Which of the following is the most suitable method for validating a scale‑down model’s ability to predict product quality at large scale?
Comparing the colour of the broth
Measuring the same product titer and impurity profile in both scale‑down and large‑scale runs
Ensuring the same reactor height
Checking that the impeller blades are identical
Explanation - Product titer and impurity profiles directly reflect process performance and quality, making them key validation metrics.
Correct answer is: Measuring the same product titer and impurity profile in both scale‑down and large‑scale runs
Q.83 In scale‑up, the term ‘critical oxygen transfer rate (OTR)’ is defined as:
The maximum OTR the reactor can achieve
The OTR at which the organism’s specific growth rate begins to decline due to oxygen limitation
The OTR required to keep temperature constant
The OTR needed to maintain pH
Explanation - When OTR falls below the organism’s demand, oxygen becomes limiting, reducing growth and productivity.
Correct answer is: The OTR at which the organism’s specific growth rate begins to decline due to oxygen limitation
Q.84 Which of the following reactor designs is most commonly used for scale‑down studies of high‑cell‑density perfusion processes?
Stirred‑tank reactor with a membrane module
Fixed‑bed reactor
Bubble column reactor
Rotating drum reactor
Explanation - Membrane‑based stirred tanks can mimic cell retention and perfusion while allowing control of mixing and mass transfer.
Correct answer is: Stirred‑tank reactor with a membrane module
Q.85 When scaling up a bioprocess, why is it important to consider the ‘solvent capacity’ of the reactor?
It determines the maximum temperature the reactor can reach
It defines the maximum amount of dissolved gases the broth can hold
It affects the ability to dissolve substrates or products that are poorly soluble
It controls the reactor’s pH stability
Explanation - Solvent capacity influences the solubility limits of substrates/products; scaling up may expose solubility issues not seen at lab scale.
Correct answer is: It affects the ability to dissolve substrates or products that are poorly soluble
Q.86 Which of the following is a key advantage of using a “continuous‑flow” scale‑down system over a batch system?
It eliminates the need for temperature control
It better replicates the steady‑state conditions of large‑scale continuous processes
It reduces the need for impellers
It guarantees higher product yields
Explanation - Continuous‑flow systems maintain constant environmental conditions, matching the operation mode of many industrial plants.
Correct answer is: It better replicates the steady‑state conditions of large‑scale continuous processes
Q.87 In the context of scale‑up, which parameter is directly linked to the formation of shear‑induced cell damage?
Reactor wall thickness
Power number (Np)
Specific growth rate (µ)
Dissolved oxygen concentration
Explanation - Higher Np values indicate more power is being dissipated as shear, increasing the risk of cell damage.
Correct answer is: Power number (Np)
Q.88 Which of the following is a typical reason for employing a “temperature gradient” in a scale‑down reactor?
To increase the rate of foam formation
To study the effect of temperature heterogeneity on product formation
To reduce the need for aeration
To simplify pH control
Explanation - Temperature gradients can affect enzyme activity and metabolic pathways; scale‑down models help evaluate these effects.
Correct answer is: To study the effect of temperature heterogeneity on product formation
Q.89 When scaling up a bioprocess that uses a high‑viscosity medium, which parameter must be reconsidered to ensure adequate mixing?
Impeller blade material
Impeller tip speed
Gas sparger pore size
pH set‑point
Explanation - Higher viscosity demands greater tip speed to generate sufficient turbulence for mixing.
Correct answer is: Impeller tip speed
Q.90 In scale‑down, the use of “micro‑bubbles” is primarily intended to:
Increase the color intensity of the broth
Enhance the oxygen transfer efficiency by increasing interfacial area
Reduce the temperature of the reactor
Decrease the agitation speed
Explanation - Micro‑bubbles provide a larger gas‑liquid interfacial area, thereby improving kLa and oxygen availability.
Correct answer is: Enhance the oxygen transfer efficiency by increasing interfacial area
Q.91 Which of the following statements best describes ‘constant tip speed scaling’?
Impeller diameter is kept constant while rpm is varied with scale
Both impeller diameter and rpm are changed to keep the linear velocity at the tip unchanged
Only the reactor height is altered
The gas flow rate is kept constant
Explanation - Constant tip speed scaling adjusts rpm inversely with impeller diameter to maintain the same tip velocity, preserving shear characteristics.
Correct answer is: Both impeller diameter and rpm are changed to keep the linear velocity at the tip unchanged
Q.92 Which of the following is the most common reason to employ a “dual‑stage feeding strategy” in a scale‑up fed‑batch process?
To reduce the need for pH control
To supply nutrients at a lower rate initially and a higher rate later, matching the changing metabolic demand
To increase foam formation
To simplify the control system
Explanation - Dual‑stage feeding aligns substrate availability with the cell’s growth phases, preventing overflow metabolism and improving yields.
Correct answer is: To supply nutrients at a lower rate initially and a higher rate later, matching the changing metabolic demand
Q.93 In scale‑up, which parameter is most directly affected by the reactor’s aspect ratio (height/diameter)?
Impeller tip speed
Oxygen solubility
Gas hold‑up and circulation patterns
pH control range
Explanation - Aspect ratio influences bubble rise paths, gas distribution, and overall circulation, affecting mass transfer and mixing.
Correct answer is: Gas hold‑up and circulation patterns
Q.94 When scaling up a process that uses a temperature‑sensitive recombinant protein, which scale‑up criterion is most critical to preserve?
Constant impeller blade material
Constant temperature uniformity (ΔT) throughout the reactor
Constant aeration rate
Constant pH set‑point
Explanation - Temperature gradients can cause protein misfolding; ensuring uniform temperature across the vessel preserves product integrity.
Correct answer is: Constant temperature uniformity (ΔT) throughout the reactor
Q.95 Which of the following statements correctly describes the relationship between Reynolds number (Re) and mixing time (t_m) in turbulent regimes?
As Re increases, t_m decreases
As Re increases, t_m increases
Re and t_m are unrelated
t_m is independent of Re in turbulent flow
Explanation - Higher Re indicates stronger turbulence, which reduces mixing time.
Correct answer is: As Re increases, t_m decreases
Q.96 In a scale‑down experiment, why might a researcher introduce a “pulsed‑aeration” regime?
To simulate intermittent oxygen limitations experienced in large reactors
To increase the temperature rapidly
To reduce the impeller speed
To improve pH stability
Explanation - Pulsed aeration creates fluctuating DO levels, mimicking the heterogeneous oxygen environment of large‑scale vessels.
Correct answer is: To simulate intermittent oxygen limitations experienced in large reactors
Q.97 When scaling up a process that uses a highly shear‑sensitive cell line, which of the following design choices is most appropriate?
Use a Rushton turbine at high rpm
Employ a low‑shear axial flow impeller and reduce tip speed
Increase gas sparging to the maximum
Eliminate baffles entirely
Explanation - Low‑shear impellers and reduced tip speeds minimize mechanical damage to delicate cells.
Correct answer is: Employ a low‑shear axial flow impeller and reduce tip speed
Q.98 Which of the following is a primary benefit of using a “scaled‑down CFD model” before building a physical scale‑down reactor?
It eliminates the need for any experimental validation
It provides rapid insight into flow and mass‑transfer patterns, helping to design an effective physical model
It reduces the cost of raw materials
It ensures 100 % product purity
Explanation - CFD simulations allow engineers to predict hydrodynamics and identify critical zones, streamlining the design of physical scale‑down setups.
Correct answer is: It provides rapid insight into flow and mass‑transfer patterns, helping to design an effective physical model
Q.99 In scale‑up, which of the following is the most direct indicator that the oxygen transfer capacity has been preserved?
Identical impeller shape
Same dissolved oxygen concentration profile over time
Same reactor wall material
Same pH control algorithm
Explanation - A matching DO profile demonstrates that OTR is comparable between scales, indicating successful oxygen transfer scaling.
Correct answer is: Same dissolved oxygen concentration profile over time
Q.100 Which scale‑up criterion is most appropriate when the primary limitation is heat removal?
Constant impeller tip speed
Constant volumetric heat transfer coefficient (U·A/V)
Constant Reynolds number
Constant substrate feed rate
Explanation - Maintaining U·A/V ensures that the heat removal capacity per unit volume is similar across scales.
Correct answer is: Constant volumetric heat transfer coefficient (U·A/V)
Q.101 Which of the following best explains why scale‑down models often operate at higher agitation speeds than the corresponding large‑scale process?
To compensate for the reduced surface‑to‑volume ratio and achieve similar power density (P/V)
To increase the temperature of the broth
To reduce foam formation
To lower the pH set‑point
Explanation - Higher agitation in small reactors raises P/V, matching the energy input of larger vessels.
Correct answer is: To compensate for the reduced surface‑to‑volume ratio and achieve similar power density (P/V)
Q.102 When scaling up a process that uses a volatile organic compound (VOC) as a substrate, which scale‑up factor becomes critically important?
Impeller blade material
Gas‑liquid mass transfer area
Reactor color
Number of baffles
Explanation - VOC transfer is limited by interfacial area; scaling must preserve this area to maintain substrate availability.
Correct answer is: Gas‑liquid mass transfer area
Q.103 Which of the following is NOT typically a goal of bioprocess scale‑down studies?
Identifying critical scale‑up parameters
Optimising downstream purification steps
Evaluating the impact of large‑scale heterogeneities on cell physiology
Testing control strategies before large‑scale implementation
Explanation - Scale‑down focuses on upstream process behavior; downstream optimisation is generally addressed separately.
Correct answer is: Optimising downstream purification steps
Q.104 In scale‑up, the term ‘constant volumetric gas flow rate (Qg/V)’ is used to maintain:
Temperature uniformity
Consistent shear stress
Similar gas residence time and mass transfer characteristics per unit volume
Constant pH
Explanation - Keeping Qg/V constant helps preserve the gas‑liquid contact time and mass transfer per unit volume across scales.
Correct answer is: Similar gas residence time and mass transfer characteristics per unit volume
Q.105 Which of the following is a typical indicator that a scale‑up has failed due to insufficient mixing?
Uniform product titer across the reactor
Consistent pH throughout the run
Presence of hot spots and localized substrate depletion
Constant temperature reading
Explanation - Insufficient mixing leads to spatial variations in temperature, substrate, and oxygen, causing performance inconsistencies.
Correct answer is: Presence of hot spots and localized substrate depletion
Q.106 When designing a scale‑down model to mimic the high‑shear environment of a large reactor, which feature is most useful?
Large baffles only
A high‑speed axial impeller placed close to the tank wall
A low‑speed marine impeller
No sparger
Explanation - Positioning a fast‑rotating impeller near the wall generates strong shear zones similar to those in large reactors.
Correct answer is: A high‑speed axial impeller placed close to the tank wall
Q.107 Which of the following best describes the term “critical power input per volume (P/V)_crit”?
The minimum power needed to start the impeller
The power per volume at which cell damage begins to occur
The power required to heat the reactor to the set temperature
The power needed to maintain pH
Explanation - Exceeding (P/V)_crit can cause shear‑induced cell lysis or loss of product quality.
Correct answer is: The power per volume at which cell damage begins to occur
Q.108 In a scale‑down experiment, which approach is most appropriate to study the effect of fluctuating pH on product formation?
Maintain pH at a constant value throughout the run
Introduce controlled pH oscillations using a programmable controller
Increase temperature instead of pH
Remove all pH sensors
Explanation - Deliberate pH shifts allow assessment of the cellular response to pH variability.
Correct answer is: Introduce controlled pH oscillations using a programmable controller
Q.109 When scaling up a bioprocess, which of the following is the primary reason to keep the gas‑liquid interfacial area (a) constant per unit volume?
To maintain consistent foam formation
To ensure similar oxygen transfer capability
To keep the temperature stable
To simplify reactor cleaning
Explanation - Interfacial area directly influences kLa; maintaining it per unit volume helps preserve oxygen transfer rates across scales.
Correct answer is: To ensure similar oxygen transfer capability