In-line Buffer Conditioning for Chromatography Optimization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for optimizing chromatography conditions in bioprocessing require a large number of experiments, consuming time and resources, and lack efficient ways to separate biomolecules from complex solutions, such as antibodies, directly from liquid cell cultures.
Innovation Solution
A method using Design of Experiments (DoE) with in-line conditioning of orthogonal gradients to determine efficient chromatography conditions for biomolecule separation, reducing the number of experiments needed by selecting experiments that utilize orthogonal quality measures like pH and conductivity, and predicting optimal conditions based on few chromatographic runs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If traditional Design of Experiments (DoE) is used to optimize chromatography conditions, then comprehensive information about process variables can be obtained, but a relatively large number of experiments are required, consuming time and resources
Solution Approach 1:
The patent applies preliminary action by using in-line buffer preparation and conditioning before chromatography experiments. Buffer solutions are prepared and conditioned online immediately before use, ensuring optimal pH and ionic strength without requiring separate pre-preparation steps. This preliminary conditioning of buffers allows experiments to proceed directly with optimized conditions, reducing the number of iterative experiments needed while still gathering comprehensive process variable information.
Solution Approach 2:
The patent employs parameter changes by systematically varying buffer composition parameters (pH, ionic strength) and chromatography conditions (flow rate, column type, mobile phase composition) to find optimal separation conditions. By changing these parameters in a controlled manner with in-line buffer preparation, the method achieves comprehensive process optimization with fewer experiments compared to traditional DoE approaches.
2Manufacturing precision
If in-line conditioning of buffers is implemented, then precise control of pH and ionic strength is achieved, but system complexity increases
Solution Approach 1:
The in-line buffer preparation system performs multiple functions within a single integrated platform: buffer mixing, pH adjustment, ionic strength control, and direct delivery to the chromatography system. This multi-functional approach consolidates what would otherwise require separate equipment for each function, achieving precise control of buffer parameters without proportionally increasing overall system complexity.
Solution Approach 2:
The patent uses an intermediary in-line buffer preparation system that acts as a mediator between stock buffer solutions and the chromatography column. This intermediary device automatically conditions buffers by adjusting pH and ionic strength based on pre-calculated requirements, eliminating the need for manual buffer preparation and ensuring precise control without requiring complex manual intervention systems.
3Productivity
If orthogonal gradients of multiple quality measures are used, then efficient chromatography conditions are determined faster, but experimental design complexity increases
Solution Approach 1:
The patent applies dimensionality change by using orthogonal gradients that simultaneously vary multiple quality measures (pH, ionic strength, flow rate) in independent dimensions. Instead of optimizing one parameter at a time through sequential experiments, the method explores the parameter space in multiple dimensions concurrently through carefully designed gradient experiments, achieving faster optimization despite the increased design complexity.
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 significantly reduces the time and resources required for optimizing chromatography conditions, allowing for faster and more efficient separation of biomolecules by determining optimal chromatography conditions using fewer experiments and providing higher purity biomolecule outputs.
Implementation Method 1
chromatography is still used as at least one step in almost all processes approved by the authorities for the manufacture of a biomolecule
Implementation Method 2
EP 2 269 055 relates to a method of generating a liquid mixture of controlled pH and ionic strength
Implementation Method 3
EP 2 269 055 relates to a method of generating a liquid mixture of controlled pH and ionic strength
Data Source
AI summary
The present invention relates to a method for the determination of chromatography conditions for the separation of a biomolecule from a liquid sample, which method comprises selecting a number of experiments using design of experiments (DoE); performing said experiments with in-line conditioning of orthogonal quality measures; and based on the results from the experiments, determining efficient chromatography conditions for said biomolecule.The invention also relates to a system for performing the method as well as a computer program and an instrument comprising such a computer program.