Real-Time Process Monitoring with Raman Spectroscopy
This interactive report explores the use of Raman spectroscopy as a key Process Analytical Technology (PAT) in biomanufacturing. Discover what it is, why it's a game-changer for process control, and how it's being applied to monitor bioreactors in real-time.
What & Why
Raman spectroscopy provides a non-invasive "molecular window" into bioprocesses. This section breaks down what the technology is and contrasts it with traditional methods to explain why it has become a critical tool for modern biopharma manufacturing.
What is Raman Spectroscopy?
It's a non-destructive analytical technique that uses a laser to measure the molecular vibrations of a sample. When the laser hits the molecules, it scatters, and a tiny fraction of that scattered light (the "Raman scatter") shifts in energy.
This energy shift is unique for each molecule, creating a chemical "fingerprint" that allows for the identification and quantification of multiple components in a complex mixture, like a bioreactor broth.
- ✔Non-invasive & Non-destructive
- ✔Provides real-time, in-situ data
- ✔Monitors multiple analytes simultaneously
The PAT Game-Changer
Raman addresses the major drawbacks of traditional process monitoring, which creates critical time-lags in decision making.
Traditional Methods
- ✖ Offline (manual sampling)
- ✖ Slow (hours to days for results)
- ✖ Destructive to sample
- ✖ Retrospective control
Raman (PAT)
- ✔ Online / In-situ (no sampling)
- ✔ Fast (seconds to minutes)
- ✔ Non-destructive
- ✔ Proactive, real-time control
Core Applications
Raman technology is applied across the biomanufacturing workflow, but its primary impact is in upstream cell culture. Use the buttons below to explore the different application areas and the key data it provides.
In upstream processing, Raman probes are inserted directly into bioreactors to continuously monitor the health of the cell culture and the consumption of nutrients. This allows for precise control over feeding strategies to maximize yield and ensure product quality.
Key Analytes Monitored (Upstream)
Primary Use Case: Upstream vs. Downstream
In downstream processing, Raman is used to monitor purification steps like chromatography. It can measure protein concentration, buffer composition, and detect aggregation in real-time, ensuring the final product meets purity specifications. While less common than upstream use, its adoption is growing.
Key Measurements (Downstream)
- ●Total Protein Concentration
- ●Buffer Component Analysis
- ●Product Aggregation Monitoring
- ●Glycosylation Patterns
How it Works: A Simplified View
The process involves four key stages, from sending light into the reactor to translating the complex spectral data into actionable insights. The real "magic" happens in the final chemometrics step.
Probe & Laser
A fiber-optic probe sends a stable laser light directly into the bioreactor broth.
Raman Scatter
Molecules (glucose, lactate, etc.) scatter the light, creating a unique "Raman shift."
Spectrometer
The probe collects the scattered light and sends it to a spectrometer, which generates a spectrum (a complex graph).
Chemometrics
A software model analyzes the spectrum to isolate and quantify each specific analyte in real-time.
The Power of Chemometrics
This is the most critical component. The raw Raman spectrum is complex, with signals from all molecules overlapping. Chemometric models (like Partial Least Squares, or PLS) are statistical models that are "trained" to find the specific patterns for glucose, lactate, etc., within the noisy data. Building and validating these models is the biggest challenge and the key to a successful implementation.
Industry Outlook: Benefits & Challenges
While powerful, Raman technology is not without hurdles. This dashboard shows the primary benefits and challenges cited by industry professionals, illustrating the trade-offs involved in its adoption.