Supercritical Fluid Chromatography Method Transfer via Density Matching
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Solution Overview
Problem
Current methodologies for transferring supercritical fluid chromatography and carbon dioxide-based chromatography methods between different system and column configurations are time-consuming and costly, as they require extensive re-optimization due to changes in mobile phase density and pressure profiles, which affect analyte retention and selectivity.
Innovation Solution
The method involves determining and maintaining the average mobile phase density or average pressure across different chromatographic systems, using sensors and controllers to ensure similar operating conditions, thereby minimizing the need for re-optimization and maintaining chromatographic integrity during scale-up or configuration changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If chromatographic methods are transferred between different system and column configurations, then the separation can be performed on different scales, but extensive re-optimization is required due to changes in mobile phase density and pressure profiles
Solution Approach 1:
The patent applies parameter changes by systematically adjusting operating parameters (flow rate, pressure, temperature) when transferring chromatographic methods between different system configurations. The methodology involves calculating and matching the average mobile phase density in the original system, then adjusting parameters in the new system to achieve equivalent density conditions, thereby maintaining consistent analyte retention and selectivity without extensive re-optimization
Solution Approach 2:
The patent implements feedback by using density calculations and comparisons between original and transferred systems. The methodology continuously monitors and adjusts operating parameters based on the calculated average mobile phase density to ensure it matches the original separation conditions, providing a closed-loop approach that maintains separation integrity during method transfer
2Adaptability or versatility
If chromatographic methods are transferred between different system and column configurations, then the separation can be performed on different scales, but extensive re-optimization is required
Solution Approach 1:
The patent applies parameter changes by systematically adjusting operating parameters (flow rate, pressure, temperature) when transferring chromatographic methods between different system configurations. The methodology involves calculating and matching the average mobile phase density in the original system, then adjusting parameters in the new system to achieve equivalent density conditions, thereby maintaining consistent analyte retention and selectivity without extensive re-optimization
Solution Approach 2:
The patent applies preliminary action by performing density calculations and parameter adjustments before actually executing the method transfer. The methodology calculates the average mobile phase density under original conditions in advance, then uses this pre-calculated value to guide parameter selection in the new system, eliminating the need for time-consuming trial-and-error optimization during the transfer process
3Adaptability or versatility
If column length or stationary phase particle size is changed, then the system configuration is adapted, but the pressure profile changes affecting retention factors and selectivity
Solution Approach 1:
The patent applies parameter changes by adjusting operating parameters (particularly flow rate and pressure) to compensate for changes in column configuration. When column length or particle size is changed, the methodology calculates the resulting impact on average mobile phase density and adjusts parameters to restore the original density conditions, thereby maintaining consistent retention factors and selectivity despite configuration changes
Solution Approach 2:
The patent applies preliminary anti-action by calculating and compensating for the expected changes in pressure profile and mobile phase density before they adversely affect the separation. The methodology anticipates the impact of column configuration changes on chromatographic performance and pre-adjusts operating parameters to counteract these effects, preventing deviations in retention and selectivity
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 efficient transfer of chromatographic methods between different systems and configurations, preserving retention factors and selectivity, thus reducing time and resources required for re-optimization and ensuring consistent separation results.
Implementation Method 1
Because of the high compressibility of CO2 under standard operating conditions, the density can change significantly with changes in pressure (under isothermal conditions), with retention factors decreasing with increasing mobile phase density (pressure).
Implementation Method 2
determining at least one of an average mobile phase density or average pressure on column for a first carbon dioxide based separation
Data Source
AI summary
A methodology scales supercritical fluid chromatography (SFC) and/or carbon dioxide based chromatography methods between different system and/or column configurations. The methodology includes measuring an average mobile phase density during a first separation utilizing C02 as a mobile phase component and substantially duplicating the average density profile for a second separation. Substantial duplication of the average mobile phase density (e.g., within about 10%, 5%, 2.5%, 1%, 0.5%, 0.1 %, 0.05%) results in chromatography for both system and/or column configurations having similar selectivity and retention factors. Average mobile phase density may be, either measured directly, calculated, or approximated using average pressure or density measurements. The average pressure profile may be used as a close approximation to duplicate average density profiles between separations.