Chromatography bioprocess monitoring

Off -line control by local equipment also here the analysis is made on a sample, which is taken out from the process, but the response time can be much lesser, which ensure more reliable adjustments on the process. The advantage compared to the distance control is obvious. The analysis methods can be expensive and complicated, but it can be as simple as thin layer chromatography (TLC) [22, 23], Chromatographic methods such as HPLC and GC have been commonly used as off line methods for bioprocess monitoring [24, 25] and HPLC is described in section 2.5. 

HPLC-UV diode-array detection (DAD) or HPLC-MS techniques take advantage of chromatography as a separation method and DAD or MS as identification and/or quantification methods. Both DAD and MS can rapidly provide on-line UV and MS information for each individual peak in a chromatogram. In most cases, the identification of the peaks can be made directly on-line by comparison with literature data or with standard compounds. However, when no standard compounds are available, the rapid preliminary identification process becomes significantly more complex. The general identification problem in bioprocess monitoring described below exists in all cases when a new biotechnological process is initiated and when the product is not available as a reference substance. 

There are several methods to monitor the off-gas analysis. Online gas chromatography is commonly used. The daily operation for inlet and outlet gases is balanced to project growth in the bioprocess. High operating cost is the disadvantage of the online system. 

In any case, both biosensors and biosensing devices have been coupled to microdialysis and are considered among the non-separation-based methods [83]. The drawback of biosensing approaches is that they are usually able to measure just one analyte at a time, in contrast with separation-based methods such as chromatography and electrophoresis, which allow the detection of several analytes. However, if the primary interest is not the identification of unknown compounds, but, for example, the monitoring of variations in a single metabolite or drug, the optimization of therapeutic responses, or the control of a bioprocess via a marker analyte, the use of a specific sensor, which can be employed in a continuous manner, can provide useful information, and can also help to avoid the analysis of hundreds of samples or to reduce the number of animals necessary for a study. 

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