Biomolecule Isolation Through Centrifugation and Affinity Chromatography
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Solution Overview
Problem
Existing biomolecule production systems face inefficiencies due to the need for multiple filtration steps, which increase costs and time, and the removal of depth filtration leads to chromatography unit clogging and pressure issues.
Innovation Solution
A system and method that combines centrifugation with a chromatography unit, eliminating filtration steps by using beads with specific diameters and capture ligands to directly process unclarified samples, allowing for continuous or semi-continuous processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If multiple depth filtration steps are used to clarify samples before chromatography, then biomolecule purity is improved, but processing time and operational complexity increase significantly
Solution Approach 1:
The invention extracts and eliminates the depth filtration step from the traditional biomolecule purification process. By using centrifugation alone followed directly by chromatography, the patent removes the time-consuming filtration bottleneck while maintaining purification effectiveness through the chromatography column's ability to handle unclarified samples.
Solution Approach 2:
The invention enables continuous processing by eliminating batch filtration steps that require stopping and restarting. The system allows continuous flow of unclarified sample through centrifugation directly into the chromatography column, maintaining uninterrupted useful action throughout the purification process.
2Productivity
If depth filtration is removed to reduce processing steps, then productivity improves, but chromatography unit clogging and pressure issues worsen
Solution Approach 1:
The invention replaces the mechanical depth filtration system with a centrifugation-based clarification approach. The centrifuge uses centrifugal force to separate particulates from the sample, and the resulting clarified supernatant can be directly applied to the chromatography column without causing clogging or pressure issues.
Solution Approach 2:
The invention changes the physical parameters of sample clarification by using centrifugation (centrifugal force, rotation speed) instead of pressure-driven filtration. This parameter change allows the sample to be clarified in a way that preserves flowability and prevents chromatography column clogging while maintaining high throughput.
3Reliability
If batch processing is used to allow filter replacement, then chromatography column clogging is prevented, but operational complexity and cost increase
Solution Approach 1:
The invention extracts and eliminates the need for batch processing and filter replacement operations. By using centrifugation to clarify samples before chromatography, the system continuously produces clarified supernatant that can be directly applied to the chromatography column, removing the complexity of batch operations and filter management.
4Productivity
If pressure is increased to maintain flow rate through depth filters, then productivity is maintained, but contaminant breakthrough increases rapidly
Solution Approach 1:
The invention replaces the pressure-driven depth filtration system with centrifugation-based clarification. This substitution eliminates the trade-off between pressure and purity because centrifugation separates particulates through centrifugal force rather than pressure, producing clarified samples that can be applied to chromatography at optimal flow rates without contaminant breakthrough.
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 reduces time and cost by maintaining efficient biomolecule capture and purification without filtration, achieving high yield and purity with reduced contamination risk.
Implementation Method 1
a centrifuge unit; and a chromatography unit configured to receive an unfiltered supernatant comprising the substance of interest from the centrifuge unit
Implementation Method 2
a chromatography unit comprising a plurality of beads, each of the plurality of beads comprising a capture ligand
Data Source
AI summary
Systems and methods for enriching or isolating one or more biomolecules are disclosed herein. Existing biomolecule collection and isolation systems and methods require multiple, sequential processes for pre-processing biomolecules after in vitro production and before final isolation (e.g., using affinity chromatography). Failure to sufficiently pre-process (e.g., purify) biomolecules prior to isolation using affinity chromatography frequently results in failure of chromatography equipment, unacceptable decreases in contaminant breakthrough, process throughput, and reagent usage, and increased likelihood of sample contamination or degradation. Systems and methods are disclosed herein that eliminate one or more steps of existing biomolecule isolation systems and protocols, which can decrease time and cost of purification or isolation of biomolecules of interest while maintaining acceptable yield and purity parameters.