Glucose and Lactate Monitoring with PTRam

Importance of the topic

Raman spectroscopy enables non invasive real time monitoring of critical analytes in biopharmaceutical production. Its inline and online compatibility addresses the need for rapid quality control and process analytical technology in cell culture and fermentation workflows.

Objectives and study overview

This application study evaluates the capability of a PTRam process development Raman analyzer to quantify glucose and lactate in aqueous solutions under static calibration and dynamic simulation of cell culture conditions.

Methodology

Static calibration was performed on 25 aqueous standards spanning glucose concentrations from 0 to 4.5 g/L and lactate from 0 to 4.4 g/L. Each sample was measured with a fiber optic immersion probe at full laser power and 18 s integration. Preprocessing for calibration models employed Savitzky Galley derivatives and standard normal variate corrections over defined spectral regions, followed by partial least squares regression with cross validation.

A dynamic experiment simulated glucose consumption and lactate production by successively spiking and replenishing a starting solution, tracking concentrations over 6.5 hours with real time prediction via Vision software.

Used instrumentation

• PTRam process development Raman analyzer model BWS476 785H with 785 nm laser at up to 340 mW and spectral range 150–2800 cm-1
• Fiber optic immersion probe with fused silica shaft
• Vision software for data acquisition, calibration model building and routine analysis
• ASTM polystyrene validation standard and safety accessories

Main results and discussion

The calibration models achieved linear quantification of glucose and lactate with three latent factors and low prediction errors. In dynamic mode, real time concentration trends closely followed theoretical profiles. Routine prediction statistics showed sub 0.2 g/L standard error for glucose and sub 0.12 g/L for lactate, with minimal bias.

Benefits and practical applications

• Rapid non destructive monitoring of key metabolites supports process control in pharmaceutical and biotech manufacturing
• Inline implementation reduces sampling delays and contamination risk
• Robust calibration workflow enables transferable models from lab scale to pilot plant

Future trends and possibilities of use

Advances may include integration with automated reactors, expansion to additional analytes via multivariate techniques, and deployment of compact Raman hardware in manufacturing environments for continuous process verification.

Conclusion

The PTRam analyzer paired with Vision software demonstrates reliable real time monitoring of glucose and lactate in static and dynamic settings, offering a valuable PAT tool for bioprocess development and production quality assurance.

Reference

Metrohm AG application note 8410000058 AGlucose and Lactate Monitoring with PTRam