570 Biowissenschaften, Biologie
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Continuous manufacturing is becoming more important in the biopharmaceutical industry. This processing strategy is favorable, as it is more efficient, flexible, and has the potential to produce higher and more consistent product quality. At the same time, it faces some challenges, especially in cell culture. As a steady state has to be maintained over a prolonged time, it is unavoidable to implement advanced process analytical technologies to control the relevant process parameters in a fast and precise manner. One such analytical technology is Raman spectroscopy, which has proven its advantages for process monitoring and control mostly in (fed-) batch cultivations. In this study, an in-line flow cell for Raman spectroscopy is included in the cell-free harvest stream of a perfusion process. Quantitative models for glucose and lactate were generated based on five cultivations originating from varying bioreactor scales. After successfully validating the glucose model (Root Mean Square Error of Prediction (RMSEP) of ∼0.2 g/L), it was employed for control of an external glucose feed in cultivation with a glucose-free perfusion medium. The generated model was successfully applied to perform process control at 4 g/L and 1.5 g/L glucose over several days, respectively, with variability of ±0.4 g/L. The results demonstrate the high potential of Raman spectroscopy for advanced process monitoring and control of a perfusion process with a bioreactor and scale-independent measurement method.
The early detection of head and neck cancer is a prolonged challenging task. It requires a precise and accurate identification of tissue alterations as well as a distinct discrimination of cancerous from healthy tissue areas. A novel approach for this purpose uses microspectroscopic techniques with special focus on hyperspectral imaging (HSI) methods. Our proof-of-principle study presents the implementation and application of darkfield elastic light scattering spectroscopy (DF ELSS) as a non-destructive, high-resolution, and fast imaging modality to distinguish lingual healthy from altered tissue regions in a mouse model. The main aspect of our study deals with the comparison of two varying HSI detection principles, which are a point-by-point and line scanning imaging, and whether one might be more appropriate in differentiating several tissue types. Statistical models are formed by deploying a principal component analysis (PCA) with the Bayesian discriminant analysis (DA) on the elastic light scattering (ELS) spectra. Overall accuracy, sensitivity, and precision values of 98% are achieved for both models whereas the overall specificity results in 99%. An additional classification of model-unknown ELS spectra is performed. The predictions are verified with histopathological evaluations of identical HE-stained tissue areas to prove the model’s capability of tissue distinction. In the context of our proof-of-principle study, we assess the Pushbroom PCA-DA model to be more suitable for tissue type differentiations and thus tissue classification. In addition to the HE-examination in head and neck cancer diagnosis, the usage of HSI-based statistical models might be conceivable in a daily clinical routine.
The detection and characterisation of oxide layers on metallic copper samples plays an important role for power electronic modules in the automotive industry. However, since precise identification of oxide layers by visual inspection is difficult and time consuming due to inhomogeneous colour distribution, a reliable and efficient method for estimating their thickness is needed. In this study, hyperspectral imaging in the visible wavelength range (425–725 nm) is proposed as an in-line inspection method for analysing oxide layers in real-time during processing of copper components such as printed circuit boards in the automotive industry. For implementation in the production line a partial least square regression (PLSR) model was developed with a calibration set of n = 12 with about 13,000 spectra per sample to determine the oxide layer thickness on top of the technical copper surfaces. The model shows a good prediction performance in the range of 0–30 nm compared to Auger electron spectroscopy depth profiles as a reference method. The root mean square error (RMSE) is 1.75 nm for calibration and 2.70 nm for full cross validation. Applied to an external dataset of four new samples with about 13,000 spectra per sample the model provides an RMSE of 1.84 nm for prediction and demonstrates the robustness of the model during real-time processing. The results of this study prove the ability and usefulness of the proposed method to estimate the thickness of oxide layers on technical copper. Hence, the application of hyperspectral imaging for the industrial process control of electronic devices is very promising.