To address these limitations, the research team combined NIR and Raman spectroscopy—two complementary, non-invasive optical techniques—to track substrate and product concentrations in real-time. While NIR spectroscopy excels at monitoring bulk chemical features, Raman spectroscopy can detect specific molecular signatures, even at low concentrations (1–3).
Smarter Sensing Through Integration
Using machine learning (ML) algorithms, the researchers fused NIR and Raman datasets to overcome the shortcomings of single-sensor systems. Their hybrid model dramatically improved the predictive accuracy for key bioprocess parameters, with model performance increasing by up to 100.4% in terms of the coefficient of determination (R²). External validations showed R² values above 0.99, a clear indicator of the system’s robustness under varying fermentation conditions (1).
The team tested 13 different ML algorithms—including ridge regression, gradient boosting, and multilayer perceptron—to refine the prediction framework. Ultimately, the model was capable of generating accurate results within one minute, compared to over two hours required for conventional lab-based methods (1).
Autonomous Fermentation in Action
To put the system to the test, the researchers implemented it in a fed-batch fermentation process for producing gentamicin C1a using the Micromonospora echinospora 49-92S KL01 strain. Their AI-powered platform dynamically adjusted glucose feeding in response to real-time sensor data, keeping the glucose level stable at 5 g/L with less than 2% variation (1).
This precise control significantly enhanced the overall fermentation output. The final concentration of gentamicin C1a reached 346.5 mg/L—a 33% increase compared to traditional intermittent feeding strategies. Importantly, this improvement came with greater sustainability and reduced waste (1).
Implications for the Biotech Industry
The success of this dual-sensor, AI-driven approach demonstrates its potential for broader application in biomanufacturing. By enabling near-instantaneous feedback and control, this technology aligns well with the principles of Process Analytical Technology (PAT) and Quality by Design (QbD), which are increasingly favored in pharmaceutical production (1).
Furthermore, this method addresses a long-standing challenge in industrial biotechnology: how to maintain efficiency, scalability, and precision in the face of complex and variable biological systems. The study highlights the power of combining spectroscopy and AI, pushing industrial fermentation into a new era of precision and productivity (1–3).
References
(1) Xu, F.; Su, L.; Gao, H.; Wang, Y.; Ben, R.; Hu, K.; Mohsin, A.; Li, C.; Chu, J.; Tian, X. Harnessing Near-Infrared and Raman Spectral Sensing and Artificial Intelligence for Real-Time Monitoring and Precision Control of Bioprocess. Bioresour. Technol. 2025, 132204. DOI: 10.1016/j.biortech.2025.132204
(2) Rozov, S. Machine Learning and Deep Learning Methods for Predictive Modelling from Raman Spectra in Bioprocessing. arXiv 2020, arXiv:2005.02935. DOI: 10.48550/arXiv.2005.02935
(3) Esmonde-White, K. A.; Cuellar, M.; Lewis, I. R. The Role of Raman Spectroscopy in Biopharmaceuticals from Development to Manufacturing. Anal. Bioanal. Chem. 2022, 414, 969–991. DOI: 10.1007/s00216-021-03727-4