BIOREACTOR INSTRUMENTATION AND CONTROL

Objectives:

• To discuss the relevance of instrumentation and control for bioreactors.

• To disscuss the bioreactor instrumentation and control.

• To enumerate and discuss some of the various process variables that should be

monitored in a bioreactor.

• To discuss the characteristics of biosensors.

Introduction

The widespread use of advanced control and process automation for biochemical

applications has been lagging as compared with industries such as refining and

petrochemicals whose feedstocks are relatively easy to characterize and whose chemistry is

well understood and whose measurements are relatively straightforward.

Ideal cell development and metabolite creation, just as biocatalyst action, is

accomplished distinctly through a thin scope of natural conditions. Accordingly, in order to

develop, optimize and assure the most efficient biological reactor operation, it is crucial that

the state of the cell or enzyme environment be monitored and controlled. Furthermore, cell

response to the environment must also be determined. The bioreactor (sometimes called

fermenter) is the main part of any biochemical process in which microbial, mammalian or

plant cell systems are employed for the manufacture of a wide range of useful biological

products.
 The following steps are used to operate a bioreactor:

1) A control strategy is established, and set-points for control variables are determined

(pH, temperature, feed rate, dissolved oxygen (DO), etc.). These are predetermined

through laboratory experiments and day-to-day operation.

2) Process variables are measured via instrumentation and the use of sensors and

measuring devices.

3) Deviation between the set-point and the measured process variable must be strictly

monitored.

4) Deviation between set-point and variables is mitigated via control of the process.

Bioreactor Instrumentation

In process industries, the following variables are usually measured and monitored

through instrumentation.

1) Quality and quantity of raw material and products

2) Utility consumption (power, steam, water, etc.)

3) Process variables (temperature, pH, etc.)

4) Analyses of process safety and environmental protection.

These data are utilized for process control, improvement of product quality, the saving

of raw material and energy, and an assurance of safety. In this section, we focus on the

measurement of process variables as the basis of bioprocess control. The instrumentation of

processing plants is fully computerized these days, and the use of distributed control systems

(DCS) along with advanced network systems makes plant operations highly reliable.
 A well-stirred liquid tank, one of the most commonly employed bioreactors,

approximates reasonably well to the idealized state of perfect mixing. It ensures a very short

mixing time and a high gas-liquid mass transfer on a small scale. In the CSTR bioreactor, the

routine measurement of temperature, pressure, pH and dissolved oxygen condition is carried

out through a set of experimental runs. In equipped bioreactors, the basic instrumentation

may provide sufficient information to determine the total mass or volume of the bioreactor

contents, the agitation speed, power and torque, redox potential, dissolved carbon dioxide

concentration, gas and liquid flow rates into the fermentation vessel, with analysis of oxygen

and carbon dioxide contents of the exhaust gas. Basic control facilities normally consist of

temperature control, pH and dissolved oxygen content, control foaming and level control for

steady operation. The vessel is jacketed for cooling and heating, with a separate side unit of a

temperature-controlled bath. Steam is used for sterilisation and elimination of contaminants.

air and the exhaust gas). The simplest instrument is a flow meter for measuring flow rates,

such as a rotameter, which provides a visual readout or is fitted with a transducer to give an

electrical output. Thermal mass flow meters are increasingly popular, especially for

laboratory- and pilot-scale reactors. In these devices, gas flows through a heated section of

tubing and the temperature differences across this heated section are directly related to the

mass flow rate. The flow rate of the liquid can be monitored with electromagnetic flow

meters, but it is very costly. Use of a normal rotameter for low flow rate may cause some

error. Therefore a level sensor is used. As the liquid level reaches the probe, the conductivity

of the media surrounding the probe changes, so monitoring is based on the conductance of the

liquid level. Such capacitance probes or conductance probes are used to detect foam on the

surface of the bioreactor.

The figure above is a schematic representation of a fully instrumented

bioreactor system for an industrial-scale fed-batch culture. The system comprises a

that is linked to a DCS.The current status of a bioreactor is monitored by various

sensors as previously mentioned. The analog signal from sensors are converted to

digital data by the A/D converter, and sent to the local controller that performs a

control action to control a process variable properly. The digital data are also logged

or sent to a LAN system through the DCS.

A set-point control is mainly used to control process variables such as

temperature and pH. For example, temperature is controlled by heating and cooling by

cooling water, and pH is maintained by the addition of acid and alkali. The

modification of a set-point will be done manually or by the DCS, which works as a

supervisory system

Bioreactor Control

The goal of bioprocess control is to maintain important process variables in a

bioreactor at a desired level regardless of time-dependent environmental changes. Process

control will be performed by the following two steps based on the information obtained

through the instrumentation.

1) A check of the deviation between the set point and the measured process variable.

2) Manipulation of the control variable so as to dissolve the deviation.

Measurements are the key to understanding and therefore controlling any process. As

it relates to biochemical engineering, measurement technology can be separated into three

broad categories. These are biological, such as cell growth rate, florescence, and protein

synthesis rate; chemical, such as glucose concentration, dissolved oxygen, pH and offgas
concentrations of CO, O, N, ethanol, ammonia and various other organic substances; and

physical, such as temperature, level, pressure, flow rate and mass. The most prevalent are the

physical sensors while the most promising for the field of biotechnology are the biological

sensors.

Process Variables

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.

complex interaction between the physical, chemical and biological conditions of the

living environment of fermentation and the biochemical processes inside the cells.

The most important part of the instrumentation is concerned with physical factors

such as temperature, pressure, agitation rate, power input, flow rates and mass

quantities. Such measurements are standard in all industrial bioprocesses. Chemical

factors are utilised for measuring oxygen and carbon dioxide concentrations in the

exit gas and by aqueous phase pH. However, for measurements of redox potential,

dissolved oxygen and dissolved carbon dioxide concentration, dependability is more

important in the instrumentation of controlled units.

Biosensors provides knowledge and information on the state of the process and also

supplies suitable operational data for the process variables. Some of the physical and

chemical effects on the bioreactor have to be translated to electrical signals, which can be

amplified and then displayed on a monitor or recorder and used as an input signal for a

controlling unit. The basic principle is first to immobilize one of the interacting molecules,

the ligand, onto an inert substrate such as a dextran matrix which is bonded (covalently

bound) to a metal surface such as gold or platinum. This reaction must then be converted into

a measurable signal typically by taking advantage of some transducing phenomenon. Four

popular transducing techniques are:

 Potentiometric or amperometric, where a chemical or biological reaction produces a

potential difference or current flow across a pair of electrodes.

 Enzyme thermistors, where the thermal effect of the chemical or biological reaction is

transduced into an electrical resistance change.

 Optoelectronic, where a chemical or biological reaction evokes a change in light

transmission.

 Electrochemically sensitive transistors whose signal depends upon the chemical

reactions underway.
References:

Najafpour, G. D. (2007). Biochemical Engineering and Biotechnology. Oxford,

UK: Elsevier. Retrieved July 08, 2019 from https://www.u-

cursos.cl/ingenieria/2009/2/IQ53D/1/material_docente/bajar?id_material=

252108.

G.A. Montague , A.J. Morris & A.C. Ward (1989) Fermentation Monitoring and

Control: A Perspective, Biotechnology and Genetic Engineering Reviews,

7:1, 147-188, DOI: 10.1080/02648725.1989.10647858. Retrieved July

08,2019 from https://doi.org/10.1080/02648725.1989.10647858