BIOSENSORS

LESSON 22: BIOPROCESS CONTROL AND METHODS

Objective
At the end of the lesson, you must be aware of :

The concepts of Bioprocess control The methods of Bioprocess control Its advantages & benefits Its challenges and optimisation

Introduction
What does Bioprocess Control Mean? Control of a chemical or biochemical process involves regulating dependent process variables (such as cell growth rate, product concentration, etc.) by making calculated adjustments to independent process variables (such as feed rate, agitation speed, etc.). In biochemical processes, the length of time required for biochemical assays to indicate the effect of an adjustment frequently makes control a challenging task. Real-time monitoring of carbon sources, dissolved gases, cell density, or product concentration in fermentation processes provides a great advantage in process optimization, leading to increased yields at decreased materials cost. While real-time monitoring with feedback control involving automated systems does exist, currently only a few common variables are measured on-line (e.g. pH, temperature, CO2, O2) which are often only indirectly related with the process under control. The development of biosensors will increase our ability to perform rapid and continuous measurements of various compounds. Methods Three different methods of controlling a bioreactor are: 1. Off-line distant: central laboratory coarse control with significant time lapse 2. Off-line local: fine control with short time lapse 3. On-line: real-time monitoring and control Off-Line Control Considerable advantage can be gained in moving from Method 1 to Method 2 giving a rapid analysis and thus enabling finer control of the fermentation. The demands of the sensor are perhaps not as stringent in Method 2 as in Method 3. On-Line Control Method 3 is most desirable, which allows the process to follow an ideal pre-programmed fermentation profile to give maximum output. However, many problems exist with on-line measurements including in situ sterilization, sensor life-time, sensor fouling, etc. Some of the problems can be overcome if the sensor is situated so that the sample is run to waste, but this causes a volume loss, which can be particularly critical with small volume fermentations.

Benefits of Control The benefits which are achievable with Bio-process control technology are considerable: Increased product yield Improved product quality Reduction in rejection rate following manufacture Improved ability to maintain optimum conditions throughout operation time Increased tolerance to quality variation of some raw materials Reduced reliance on human perception to control process Improved plant processing rate Optimized energy efficiency Decreased analysis and overall costs Challenges To date, these instruments have not seen wide spread use because as a class they exibit many disadvantages. These include: They cannot be steam sterilized They react with the product And are oversensitive Bioprocess Control and Optimization Using Biosensors Biosensors, optical sensors, and immunosensors are all gaining in importance. At present, the development of correct/adequate interfacing of biosensors to bioprocesses is the major limitation on progress. On the basis of new analytical data, a more precise modeling and control of fermentations can now be performed. Recent research efforts attest to the increasing importance of this area in biotechnology. Major research efforts in mammalian cell culture focuses partially on the need to implement control policies for fed-batch and perfusion cultures for ensuring product quality and process consistency. Increased efforts in process monitoring and control address this problem. Integrating innovative biosensing techniques with process control methods should provide improved performance of fermentation processes. In addition to non-invasive blood-glucose measurement in humans, this lesson reviews progress made in using nearinfrared spectroscopy as a non-invasive probe for continuous bioreactor monitoring during fermentation processes. It mentions that five critical fermentation components, including glucose, may be measured simultaneously.

Summary
The development of biosensors will increase our ability to perform rapid and continuous measurements of various

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compounds. Three different methods of controlling a bioreactor are Off-line distant, Off-line local & On-line.

BIOSENSORS

Reference
http://userpages.umbc.edu/~jshull1/ench772/intro http://userpages.umbc.edu/~jshull1/ench772/intro http://www.inapg.inra.fr/ens_rech/siab/asteq/elba/ introbio.htm

Notes

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