Disposable Expanded Bed Chromatography Column
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Solution Overview
Problem
Current methods for purifying monoclonal antibodies using packed-bed chromatography are time-consuming, produce low-purity antibodies, and require expensive, reusable columns that need extensive cleaning and maintenance, while also generating waste disposal issues due to the use of lyotropic salts and Protein A ligands.
Innovation Solution
The implementation of an expanded bed adsorption system with a disposable column design that uses a stationary phase medium with controlled density and particle size, and a dual-pump system to regulate flow rates, minimizing back-pressure and eliminating the need for pressurized equipment, allowing for efficient and sterile separation with minimal downtime.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If packed-bed chromatography is used with reusable columns, then the stationary phase can be cleaned and reused multiple times, but the cleaning process is time-consuming and requires significant downtime
Solution Approach 1:
The patent employs disposable single-use columns made from inexpensive materials that are discarded after one use, eliminating the time-consuming cleaning and validation processes required for reusable columns. This approach trades the reusability of columns for significant time savings in the purification process.
2Ease of manufacture
If Protein A chromatography is used with reusable columns, then the columns must be cleaned with sodium hydroxide solution, but this cleaning process shortens the operational lifetime of the adsorbent due to Protein A instability at high pH
Solution Approach 1:
The disposable column design eliminates the need for harsh chemical cleaning with sodium hydroxide that degrades Protein A ligands. Each column is used once and discarded, avoiding the cumulative damage to the adsorbent that occurs with repeated cleaning cycles in reusable columns.
3Productivity
If packed-bed chromatography is used, then the apparatus must withstand high back pressure to force mobile phase through the column, but this requires permanent installation with heavy-duty construction
Solution Approach 1:
The disposable columns are designed to be used in simpler apparatus that do not require heavy-duty pressure-containing construction. Each single-use column operates at lower pressures, allowing the use of lighter materials and simpler installation while maintaining purification effectiveness.
4Manufacturing precision
If Protein A ligand is used in chromatography columns, then selective purification of antibodies is achieved, but the ligand itself is expensive
Solution Approach 1:
The disposable columns use alternative, less expensive stationary phase materials that achieve adequate purification without requiring costly Protein A ligands. The single-use nature of the columns makes the lower selectivity of alternative materials acceptable while significantly reducing ligand costs.
5Reliability
If clarification procedures such as filtration and centrifugation are used before chromatography, then particulates are removed to avoid clogging, but these procedures are expensive, time-consuming and lead to significant product loss
Solution Approach 1:
The disposable columns are designed with features that allow them to tolerate particulate matter better than reusable columns. The single-use nature eliminates the risk of permanent clogging, allowing direct injection of crude fermentation broth without expensive and time-consuming clarification steps.
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 enables high-separation efficiency at high flow rates, reducing production costs and waste, and allows for the use of disposable, lightweight columns made from low-cost materials, improving the productivity and efficiency of monoclonal antibody purification.
Implementation Method 1
the density of the stationary phase is selected to create a stable fluidised bed in a certain range of flow rate of the mobile phase
Implementation Method 2
expanded bed adsorption, in which the pressure applied to the mobile phase is at least much reduced
Data Source
Figure 1
Figure 2A~2C
Figure 3A~3C
AI summary
In the field of expanded bed adsorption chromatography, with particular but not exclusive relevance to disposable expanded bed chromatography columns, a method of conducting upward flow expanded bed chromatography comprising: supplying a liquid via an inlet to a stationary phase medium contained in a column, allowing adsorption of at least one component from the liquid by the stationary phase medium, withdrawing the liquid from the column via an outlet, regulating the expansion of the stationary phase medium by regulation of the flow rate of the liquid through at least the inlet, and restricting any overpressure in the headspace of the column to not more than the outside pressure plus 0.1 bar, is provided. In addition, apparatus for use in said method, in particular columns for use in expanded bed chromatography, are provided.