Application Note                                                                                              Zaptron Systems, Inc.

Optimal Fermentation of Penicillin Anti-biotics

Goal:  Increase yield of penicillin (and tetracycline) production – fermentation method.

Objective: Improve the feeding curve of glucose – by optimizing glucose feed. Since glucose is added continuously to the biochemical reaction in a fermentation tank, the best curve of glucose feed is very important and therefore was chosen as the target for optimization.

Features Influencing Penicillin Yield:

In fermentation of penicillin, glucose solution is fed to the tank every 30 minutes. A fermentation process may take 20-30 or more hours. Measurements of glucose feed form a long time-series of data which are divided into several segments, each having tens of features. To compress information, these segments are averaged to produce a representative segment with a number of useful features. At the same time, the composition of the gas in the biochemical reactor is detected by a gas sensor, and glucose concentration in liquid phase is measured by a glucose sensor. Major controlling factors in optimal control of drug fermentation are:

(1) Glucose feed rate: in fermentation production, glucose is added every 30 minutes in the full period of fermentation. The measurements on glucose feed form a time series with many data samples

(2) Measurement (reading) of the gas sensor indicating the gas phase composition in the bio-reactor

(3) Glucose sensor output expressing the glucose concentration in liquid phase

(4) PH value of liquid

(5) Air flow rate

(6) Tank temperature

The above measurements are treated as the original features (factors) in the optimization problem. Since there were many features, it was necessary to select and reduce them before data analysis.

Result:

After optimization, the yield of penicillin was increased by 8% and saving in glucose was about US $120,000 per year.

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