Online monitoring of microbioreactor arrays via 2D-fluorescence spectra analysis

应开发一种系统，以允许通过二维荧光光谱分析的并行化和自动化的微生物反应器的在线监测。应使用该系统在线定量基本工艺参数（底物、活性成分、中间体和产品）。在本项目中，将采用基于微量滴定板的BioLector技术作为培养系统，并将实施2D荧光光谱仪。基于测量的二维光谱，将开发创新的在线方法来建立生物过程的化学计量学模型。首先，将改进BioLector技术以测量二维荧光光谱。此外，还将开发软件包，以便进行高含量的测量和有效的数据处理。之后，传统的离线方法来建立化学计量学模型将被应用通过使用大量的并行培养。因此，建立这种模型的时间和精力可以大大减少。最后，创新的在线方法建立化学计量学模型将被开发。因此，将通过改变初始培养参数进行校准-不再需要离线样品分析。因此，可以在培养过程中建立化学计量学模型。此外，开发的在线方法将通过使用实验设计方法进行升级：（1）实时调整测量时间以及分辨率;（2）通过脉冲实验修改运行培养。

A system should be developed to allow the online monitoring of parallelized and automated microbioreactors via 2D-fluorescence spectra analysis. Essential process parameters (substrate, active ingredient, intermediates, and product) should be quantified online by using this system. Within this project, the microtiter plate based BioLector-technique will be applied as a cultivation system and a 2D-fluorescence spectrometer will be implemented. Based on the measured 2D-spectra, innovative online methods will be developed to establish chemometric models for biological processes.First, the BioLector-technique will be modified in order to measure 2D-fluorescence spectra. In addition, software packages will be developed to allow high content measurements and efficient data processing. Afterwards, the conventional offline method to establish chemometric models will be applied by using a multitude of parallelized cultivations. Thus, the time and effort to establish such models can be significantly reduced.Finally, innovative online methods to establish chemometric models will be developed. Thereby, calibrations will be performed by varying initial cultivation parameters - offline sample analysis is no longer required. Consequently, chemometric models can be established during cultivation. Moreover, the developed online methods will be upgraded by using experimental design approaches: (1) Real-time adjustment of measuring time as well as resolution; (2) Modification of running cultivations via pulse-experiments.