Multi-Wavelength Spectrophotometer for Biomanufacturing Concentration Monitoring
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Solution Overview
Problem
Current biomanufacturing processes face challenges in continuously monitoring protein concentration due to UV absorbance sensor saturation, requiring frequent sampling and costly process development, which limits the ability for real-time process control and continuous processing.
Innovation Solution
A method involving a flow-through mechanism with a variable path length spectrophotometer that continuously monitors the ultraviolet spectrum of substances, allowing for real-time concentration measurement and process control without the need for sample dilution or purification, enabling continuous biomanufacturing processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If UV absorbance sensor is used to monitor protein concentration, then real-time monitoring capability is provided, but sensor saturation occurs at high concentrations limiting measurement range
Solution Approach 1:
The patent transitions from single-wavelength UV absorbance measurement to multi-wavelength spectroscopic measurement. By measuring absorbance across multiple wavelengths (200-400 nm) rather than a single wavelength, the system creates a spectral fingerprint that provides both concentration information and substance identification, effectively adding a dimensional aspect to the measurement that expands the usable dynamic range and eliminates saturation limitations.
Solution Approach 2:
The patent changes the measurement parameter from single-wavelength absorbance to multi-wavelength spectral absorbance. By collecting absorbance data across the entire UV spectrum (200-400 nm) and analyzing the spectral shape rather than relying on a single absorbance value, the system can accurately measure concentrations across a much broader range without sensor saturation, as different wavelengths provide complementary information about the substance composition.
2Adaptability or versatility
If surrogate wavelength (300 nm) is used to avoid sensor saturation, then extended measurement range is achieved, but measurement accuracy decreases and process reliability is compromised
Solution Approach 1:
The patent changes from using a single surrogate wavelength (300 nm) to analyzing the complete spectral profile across 200-400 nm. By examining the shape and characteristics of the entire spectrum rather than relying on absorbance at a single wavelength, the system maintains high measurement accuracy across the full dynamic range. The spectral fingerprint approach allows differentiation between substances and accurate quantification without the limitations of surrogate wavelength measurements.
Solution Approach 2:
The patent makes the measurement system universal by enabling it to identify and quantify multiple different substances (proteins, peptides, nucleic acids, etc.) across a broad concentration range using a single multi-wavelength spectrophotometer. The spectral fingerprinting capability provides both identification and quantification functions simultaneously, eliminating the need for substance-specific calibration at surrogate wavelengths and providing reliable measurements for diverse biopharmaceutical formulations.
3Loss of information
If frequent sampling is performed to monitor process parameters, then process control information is obtained, but time consumption and operational complexity increase
Solution Approach 1:
The patent implements continuous in-line spectroscopic monitoring rather than discrete offline sampling. The multi-wavelength spectrophotometer is positioned in the process flow to continuously measure the spectral properties of the flowing stream, providing uninterrupted real-time information about concentration and substance identity. This eliminates the need for repeated sampling, manual analysis, and data compilation, while maintaining continuous process oversight.
Solution Approach 2:
The patent replaces the mechanical sampling and analysis system with an automated in-line spectroscopic measurement system. Instead of physically withdrawing samples, transporting them to analysis equipment, and performing manual or batch analysis, the system uses optical detection directly in the process stream. This substitution eliminates the time-consuming mechanical steps of sampling and sample preparation while providing continuous measurement capability.
4Adaptability or versatility
If path length is reduced to prevent sensor saturation, then high concentration measurements become possible, but measurement sensitivity decreases
Solution Approach 1:
The patent compensates for reduced path length sensitivity by utilizing the multi-wavelength spectral dimension. Instead of relying on a single absorbance value that diminishes with shorter path lengths, the system measures absorbance across 200-400 nm and analyzes the spectral profile. The characteristic spectral shape and relative absorbance ratios at different wavelengths remain detectable even at short path lengths, maintaining sensitivity while enabling high concentration measurements.
Solution Approach 2:
The patent changes the measurement approach from single-wavelength absorbance magnitude to multi-wavelength spectral pattern recognition. By analyzing the shape and relative features of the spectrum rather than absolute absorbance values, the system maintains detection sensitivity at short path lengths. The spectral fingerprint characteristics (peaks, valleys, slope patterns) provide robust concentration information even when absolute absorbance is reduced due to shorter optical path.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for real-time monitoring of protein concentration and process control, reducing sampling time and costs, and enabling continuous biomanufacturing by expanding the dynamic range of spectrophotometers to measure substances of varying concentrations without dilution, thereby improving process efficiency and reducing the risk of lost batches.
Implementation Method 1
the UV absorbance sensor (at 280 nm)... the ultraviolet spectrum of the substance by detecting the spectrum in a flow through mechanism having a light source, a path length and a detector
Data Source
AI summary
The present invention relates to methods for determining the change in concentration of a substance in solution over time by continuously monitoring in real time. In particular, the present invention relates to methods for continuously monitoring the concentration of compounds during the manufacturing process of biomolecules.