NIR spectroscopy-CNN-enabled chemometrics for multianalyte monitoring in microbial fermentation.

As the biopharmaceutical industry looks to implement Industry 4.0, the need for rapid and robust analytical characterization of analytes has become a pressing priority. Spectroscopic tools, like near-infrared (NIR) spectroscopy, are finding increasing use for real-time quantitative analysis. Yet detection of multiple low-concentration analytes in microbial and mammalian cell cultures remains an ongoing challenge, requiring the selection of carefully calibrated, resilient chemometrics for each analyte. The convolutional neural network (CNN) is a puissant tool for processing complex data and making it a potential approach for automatic multivariate spectral processing. This work proposes an inception module-based two-dimensional (2D) CNN approach (I-CNN) for calibrating multiple analytes using NIR spectral data. The I-CNN model, coupled with orthogonal partial least squares (PLS) preprocessing, converts the NIR spectral data into a 2D data matrix, after which the critical features are extracted, leading to model development for multiple analytes. Escherichia coli fermentation broth was taken as a case study, where calibration models were developed for 23 analytes, including 20 amino acids, glucose, lactose, and acetate. The I-CNN model result statistics depicted an average R2 values of prediction 0.90, external validation data set 0.86 and significantly lower root mean square error of prediction values ∼0.52 compared to conventional regression models like PLS. Preprocessing steps were applied to I-CNN models to evaluate any augmentation in prediction performance. Finally, the model reliability was assessed via real-time process monitoring and comparison with offline analytics. The proposed I-CNN method is systematic and novel in extracting distinctive spectral features from a multianalyte bioprocess data set and could be adapted to other complex cell culture systems requiring rapid quantification using spectroscopy.

Soft sensor based rapid detection of trace chlorine dioxide (ClO2) concentration in water.

Chlorine dioxide (ClO2) is a widely used sterilizer and a disinfectant across a multitude of industries. When using ClO2, it is imperative to measure the ClO2 concentration to abide by the safety regulations. This study presents a novel, soft sensor method based on Fourier transform infrared spectroscopy (FTIR) spectroscopy for measurement of ClO2 concentration in different water samples varying from milli Q to wastewater. Six distinct artificial neural network models were constructed and evaluated based on three overarching statistical standards to select the optimal model. The OPLS-RF model outperformed all other models with R2, RMSE, and NRMSE values of 0.945, 0.24, and 0.063, respectively. The developed model demonstrated limit of detection and limit of quantification values of 0.1 and 0.25 ppm, respectively, for water. Furthermore, the model also exhibited good reproducibility and precision as measured by the BCMSEP (0.064). The soft sensor-based method presented in the study offers significant advantages in terms of simplicity and speedy detection. In summary, the study presents development of a soft sensor that is capable of predicting the trace content of chlorine dioxide ranging between 0.1 to 5 ppm in a water sample by connecting FTIR with an OPLS-RF model.