Dual-Location Analyte Measurement for Purification Referencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for analyte measurement in purification systems, particularly in downstream biopharmaceutical processes, fail to provide an optimal reference for absorbance measurements due to the inability of single or autonomous measurement systems to account for changes in the matrix when the analyte is added or removed, leading to inaccurate quantitative predictions.
Innovation Solution
A method involving two measurements, one upstream and one downstream of the purification unit, where the measurement at one location is referenced to the other to establish a relative measurement based on the matrix without the analyte, ensuring accurate referencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a single measurement system is used downstream of the purification unit, then the measurement setup is simple, but accurate referencing is impossible because the reference matrix changes when analyte is added or removed
Solution Approach 1:
The measurement system is segmented into two separate measurement locations: one upstream of the purification unit and one downstream. Each measurement system independently measures the analyte concentration in its respective location, allowing for accurate referencing without requiring a single complex system to handle all measurement scenarios.
Solution Approach 2:
The upstream measurement system acts as an intermediary reference source for the downstream measurement system. By measuring the analyte concentration upstream (where the matrix is known and stable) and using this as a reference for the downstream measurement, accurate quantification is achieved even when the downstream matrix changes.
2Reliability
If the measurement location is fixed downstream of the purification unit, then the setup is simple, but the reference matrix is not available when analyte is completely removed or added
Solution Approach 1:
The measurement function is segmented across two locations: upstream measurement provides reliable reference data when analyte is present in the feed, while downstream measurement monitors the purification effect. This segmentation ensures that at least one measurement system always has a valid reference matrix available.
Solution Approach 2:
The upstream measurement system performs preliminary measurement of the analyte concentration in the feed stream before purification. This preliminary measurement establishes a reference value that can be used to interpret downstream measurements, ensuring reliable quantification throughout the process.
3Measurement precision
If separate reference measurements are taken for different detection cases, then optimal absorbance measurement is achieved, but the measurement process becomes complex and time-consuming
Solution Approach 1:
The upstream and downstream measurement systems are merged into an integrated purification monitoring system. Both measurements are taken simultaneously during the same process step, and the upstream measurement automatically serves as the reference for the downstream measurement, eliminating the need for separate reference measurement procedures.
Solution Approach 2:
The dual measurement system operates continuously during the purification process, with both upstream and downstream measurements being taken throughout. This continuous measurement approach maintains accurate referencing without interrupting the process or requiring separate reference measurement steps, thus maintaining high productivity.
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
Enables precise and accurate analyte quantification by correcting measurements using the matrix without the analyte, improving the reliability of quantitative predictions in purification processes.
Implementation Method 1
UV/Vis spectrophotometers that detect a certain wavelength, typically somewhere between 220 and 390 nm... The spectral data is recorded in absorbance units (AU, a dimensionless quantity), which is defined as A=log10 (Φ0/Φ)
Data Source
AI summary
In a method of referencing an analyte measurement in a purification system during a process step in a biopharmaceutical process, the following sub-steps are performed during the same process step: guiding a medium through a purification unit where the analyte is either removed from or added to the medium; measuring at least one parameter related to the presence and/or quantity of the analyte with a first measurement system at a first measurement location upstream of the purification unit; measuring the at least one parameter with a second measurement system at a second measurement location downstream of the purification unit; and referencing the upstream measurement to the downstream measurement, or referencing the downstream measurement to the upstream measurement.