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Time-Gated Raman spectroscopy to improve chemical sensitivity for in-situ bioreactor monitoring

This project proposes to demonstrate the capabilities of timegated Raman spectroscopy (TG-RS) to improve the SNR ratio of Raman data using a traditional chemometrics approach (PLS) and a calibration free approach (iterative optimization technology, IOT).
Categories
Process control
Data
Project status
82% Completed

Industry Need

  • Raman spectroscopy has seen widespread application as a process analytical technology for bioreaction monitoring. 
  • Traditional Raman spectroscopy (TRS) struggles with fluorescence emission (common to many components in bioreactions). 
  • Fluorescence interference decreases the signal-to-noise ratio (SNR) of the acquired spectra, reducing interpretability. 
  • Time-gated Raman spectroscopy (TG-RS) overcomes fluorescence interference by taking advantage of the delay between Raman signal and fluorescence emission. 


Solution

  • Interpretation of Raman spectra is accomplished by employing chemometric models, namely partial least squares (PLS).  
  • Developing and calibrating these models can be demanding, particularly in complex bioreaction systems. Calibration-free models based on linearly additive pure component spectra offer a favorable alternative, but non-linear interferences (e.g., fluorescence) reduces model performance.  
  • Mitigating interference via TG-RS enables pure component model approaches. 

NIPTE and Pfizer have teamed up to demonstrate the ability of TG-RS to reduce fluorescence and improve SNR of key metabolites in bioreactions. The superior SNR will enable the development and comparison of PLS and pure component models for the quantification of these metabolites during bioreactions of industrially relevant organisms.  

Outcomes and Impacts

Demonstrate that combining TG-RS and pure component modeling improves bioreaction monitoring capability while reducing calibration resource burden in a system ready for industrial deployment

Use the real-time data collected during reactor monitoring as an input in a control strategy to maximize product yield and quality while minimizing inefficiencies that lead to product failure and loss of profit

Demonstrate the suitability of TG-RS for regulators as an appropriate process analytical technology (PAT) system

Create broad acceptance and implementation of TG-RS as an industry standard technology for bioreaction monitoring

Updates, Related Publications, and Deliverables

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Project Lead

National Institute for Pharmaceutical Technology and Education, Inc (NIPTE)

National Institute for Pharmaceutical Technology and Education, Inc (NIPTE)

Participating Organizations

Pfizer, Inc.

Pfizer, Inc.