OBJECTIVES

1. Briefly discuss what process variables are.

2. Discuss the physical variables of a bioreactor and their respective sensors.
INTRODUCTION
Variables are those properties of the system which vary in time, and whose dynamic
properties are therefore determined by the values of the parameters. A process variable is a
parameter of the current status of a process under operation, and, therefore, the measurement
of process variables is a key to understanding what is happening in a bioreactor and to being
able to control the process. Most of the sensors used for the measurements of process
variables are inserted into the culture broth of a bioreactor. These must have qualities that
will allow them to be repeatedly sterilized (autoclavable) in order to prevent microbial
contamination in bioreactors. Naturally, all the sensors must be calibrated before sterilization
(Katoh, Horiuchi, & Yoshida, 2015).
PHYSICAL SENSORS
Process variables measured in bioprocess instrumentation can be categorized into one
of three groups: physical, chemical, and biochemical variables. Table 1 summarizes these
three types of variables. In this report, sensors used to measure physical variables will be
discussed. Physical variables are those that describe the physical system of the bioreactor.
 Table 1: Process variables measured and estimated in bioprocess instrumentation.
Temperature
The temperature in a bioreactor is an important parameter in any bioprocess, because
all microorganisms and enzymes have an optimal temperature at which they function most
efficiently. For example, optimal temperature for cell growth is 37 °C for Escherichia coli
and 30 ºC for Saccharomyces sp, respectively. The data of temperature is sufficiently reliable
and mainly used for the temperature control of bioreactors and for the estimation of the heat
generation in a large-scale aerobic fermentor such as in yeast production or in industrial beer
fermentation (Katoh, Horiuchi, & Yoshida, 2015).
 Thermocouples are the most widely used temperature sensors since they are cheap,
provide rapid response, and may be used to measure both high and low temperatures. They
are less accurate (± 0.5 ºC to ± 2.2 ºC) than other sensors however, and must be calibrated
periodically (Doelle, Rokem, & Berovic, 2009).

Figure 1: Thermocouple
The Resistance Temperature Detector (RTD) is a popular device as it provides
more precise temperature measurement (± 0.1 ºC) than thermocouples, and does not need
periodic calibration. These devices are more expensive and are suitable over a narrower
temperature range than thermocouples (Doelle, Rokem, & Berovic, 2009).

Figure 2: RTD Sensors

Power Consumption
Power consumption sometimes becomes important in industrial bioprocesses, because
the power used for aeration and agitation can be highly expensive. The cost of power
consumption occupies approximately 15–20% of total production cost in aerobic
fermentation processes. A wattmeter is used to measure the power consumption of a
bioreactor (Katoh, Horiuchi, & Yoshida, 2015).
 Figure 3: Wattmeter
Pressure
Most bioreactors are operated at normal atmospheric pressure; however, in some
cases with high oxygen requirements, such as high-density cultivation, a bioreactor must be
pressurized in order to enhance the oxygen transfer rate. In such cases, the control of vessel
pressure is essential. Pressure gauges are installed to measure the pressure in bioreactors
(Katoh, Horiuchi, & Yoshida, 2015).

Figure 4: Pressure Gauge

Agitation
The speed of agitation is closely related to the mixing characteristics of a bioreactor
and to the oxygen transfer rate (kLa). Careful control of agitation speed is required when
using filamentous microorganisms or animal cells, because they are very sensitive to shearing
stress (Katoh, Horiuchi, & Yoshida, 2015).

Figure 5: Motor Controller

Foaming
The appearance of foam is a very undesirable phenomenon, since, in the course of its
appearance, there is a risk to lose an essential part of the fermentation broth. During the
foaming, it is not possible to perform high-quality analyses and measurements. In most
aerobic microbial processes, some foaming is inevitable. To limit the amount of foaming, an
anti-foaming agent (silicone type or alcohol type) is intermittently added into the culture
broth (Doelle, Rokem, & Berovic, 2009).
A foaming sensor is required for proper addition of the anti-foaming agent. Without
foaming prevention, microorganisms in a fermentation broth will be washed out with foam
along with exhaust gas. It is noted that the addition of an anti-foaming agent temporarily
decreases the oxygen transfer rate (kLa) of a bioreactor because anti-foaming agents depress
the generation of dispersed bubbles, which means the decrease of “a” in kLa (Katoh,
Horiuchi, & Yoshida, 2015).

Figure 6: Foam Sensor

Viscosity
The viscosity of a broth is monitored by a rotational viscometer in some
fermentation processes that use filamentous bacteria such as in antibiotics production where
the viscosity of the culture broth increases as fermentation progresses. Increase in the
viscosity of a culture broth results in a decrease in the oxygen transfer rate and the increase of
power consumption (Katoh, Horiuchi, & Yoshida, 2015).

Figure 7: Rotational Viscometer

Turbidity
Many studies have been focused on developing a sterilizable probe to measure the
turbidity of the culture broth, because the turbidity can be an index of cell concentration,
which is one of the most important parameters in bioprocess operations. Sterilizable laser or
optical turbidity probes are now available and are being used successfully. However, the
accuracy of the measurements is insufficient for industrial applications, because the outputs
from the probes are affected by some factors including the absorbance of the broth and the
bubbles caused by aeration (Katoh, Horiuchi, & Yoshida, 2015).

Figure 8: Optical Turbidity Probe

Gas-Flow Rate
Gas flow rate is measured by a floating meter or a mass flow meter that can measure
flow rate independent of pressure and temperature effects. Based on the measurements by
flow meters, the flow rate is controlled manually or automatically by manipulating a flow
control valve. Gas-flow rate is used to calculate the oxygen uptake rate, the RQ (respiratory
quotient) and the CO2 evolution rate. Biogas-generation rate is measured using a volumetric
flow meter in anaerobic digestion (methane fermentation) to monitor methane generation
(Katoh, Horiuchi, & Yoshida, 2015).

Figure 9: Floating Meter

Liquid-Flow Rate
Liquid flow rate is measured when a medium is fed into a bioreactor in continuous
and fed-batch operation. The flow rate of cooling water is also monitored in industrial
bioprocessing plants (Katoh, Horiuchi, & Yoshida, 2015).
Figure 10: Liquid Flow Meter
REFERENCES
Doelle, H., Rokem, S., & Berovic, M. (2009). Biotechnology: Fundamentals in
Biotechnology (Volume II). Oxford, UK: EOLSS Publishers.
Katoh, S., Horiuchi, J.-i., & Yoshida, F. (2015). Biochemical Engineering: A Textbook for
Engineers, Chemists and Biologists (2nd ed). Weinheim, Germany: Wiley-VCH
Verlag GmbH & Co.