Bioprocess Installation Synchronization Eliminates Filter Blocking
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Solution Overview
Problem
Bioprocesses face inefficiencies due to filter blocking and pressure drops in chromatography units, leading to compromised purification results, increased process times, and reduced reproducibility, as well as energy inefficiencies in dynamic filtration methods.
Innovation Solution
Eliminating solid/liquid separation units between the clarification and chromatography units and implementing synchronization strategies to control particle depletion, allowing direct connection and synchronized operation of these units, thereby maintaining constant fluid flow and pressure, and using electronic process control to manage the bioprocess.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a filter is interposed upstream of a chromatograph to prevent blocking, then the chromatograph is protected from solid particles, but the filter causes pressure drop and damping effect that delays fluid flow and pressure transmission
Solution Approach 1:
The patent removes the filter component from the system entirely. Instead of filtering the cell broth before chromatography, the invention uses the chromatography unit itself to handle the unfiltered stream, allowing solid particles to pass through without causing blocking. This eliminates the filter resistance and associated time delays while maintaining chromatograph functionality.
Solution Approach 2:
The conventional approach filters first then chromatographs. This patent inverts the sequence by allowing unfiltered material to enter the chromatograph directly, relying on the chromatography process to separate and retain particles while passing the liquid phase. This reversal eliminates the bottleneck created by pre-filtration.
2Quantity of substance
If static filtration is used to remove particles, then solid particles are removed from the fluid, but filter resistance increases continuously over time leading to compromised process times and chromatograph performance
Solution Approach 1:
The patent implements continuous chromatography operation without interruption for filter changes or cleaning. By eliminating the filter entirely and using the chromatography column to handle particle-laden streams continuously, the system maintains steady-state operation without the periodic disruptions caused by increasing filter resistance.
Solution Approach 2:
The filter component is completely removed from the system. The chromatography unit is designed to process unfiltered cell broth directly, eliminating the source of increasing resistance that plagues static filtration systems.
3Reliability
If dynamic filtration is used to prevent filter cake formation, then filtrate viscosity increases due to continuous concentration, causing transmembrane pressure to decrease and filtration efficiency to drop
Solution Approach 1:
The patent eliminates the dynamic filtration system entirely. Instead of using energy-intensive cross-flow or tangential flow filtration to prevent filter cake formation, the invention allows particles to pass through the chromatography column without pre-filtration, removing the source of energy inefficiency.
Solution Approach 2:
The mechanical filtration system is replaced with a chromatographic separation system that handles particles differently. Rather than using mechanical forces to prevent particle accumulation on a filter surface, the system uses chromatographic mechanisms to separate and retain particles within the column matrix.
4Quantity of substance
If filters are used to clarify cell broth before chromatography, then solid particles are removed, but the pressure drop and non-uniform pressure lead to non-uniform separation results with limited reproducibility
Solution Approach 1:
The patent changes the operational parameters of the chromatography system to accommodate unfiltered streams. By adjusting flow rates, pressure settings, and column conditions, the system maintains uniform pressure distribution and separation performance even when processing particle-laden cell broth directly, thereby improving reproducibility.
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 enhances bioprocess efficiency, reduces process times, improves controllability, and minimizes the risk of chromatography column blocking, resulting in cost-effective and time-effective bioproduct production with increased reproducibility.
Implementation Method 1
a clarification unit with a centrifuge wherein cell broth obtained from the bioprocess unit is being lead through the clarification unit
Data Source
AI summary
Various embodiments provide a method for producing a bioproduct using a bioprocess installation. The bioprocess installation comprises an process control and a bioprocess unit. The bioprocess unit comprises a receptacle, a clarification unit with a centrifuge and a chromatography unit with a chromatograph. Cell broth obtained from the receptacle is lead through the clarification unit and the chromatography unit in a liquid stream. The clarification unit with its centrifuge is being operated in a centrifugation cycle comprising centrifugation steps. The chromatography unit with its chromatograph is being operated in a chromatography cycle comprising chromatography steps. The particle depletion can be less than 10% in particle concentration and that the execution of the steps assigned to the centrifugation cycle and the execution of the steps assigned to the chromatography cycle are at least partly being synchronized with each other by the process control in synchronization routines based on assigned synchronization strategies.