Semi-Continuous Chromatography Protein Purification

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Solution Overview

Problem

Current protein purification methods, particularly in the biotechnology industry, face challenges such as high costs and inefficiencies in using chromatography matrices, as well as the need for multiple purification cycles to achieve sufficient protein purity, which can lead to protein loss and reduced operational speed due to complex setups and high maintenance requirements.

Innovation Solution

A semi-continuous chromatography process that involves loading a mixture onto a chromatography matrix until a significant portion of its binding capacity is reached, collecting flow-through, and re-loading it in subsequent cycles to maximize matrix utilization, thereby optimizing protein binding and recovery while minimizing protein loss and operational complexity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional batch chromatography is used to purify proteins, then protein purity can be achieved through multiple cycles, but the number of purification cycles increases and productivity decreases

Engineering Contradiction:
Improveprotein purityVSAvoidproductivity
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent implements continuous chromatography where the chromatography matrix is continuously loaded with protein mixture and flow-through is continuously collected and re-loaded in a seamless cycle, eliminating the interruptions and multiple discrete batches required in traditional methods to achieve sufficient purity

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent pre-establishes a feedback loop where flow-through from each cycle is automatically collected and prepared for re-loading in the next cycle, allowing the system to maintain optimal binding capacity continuously without requiring multiple separate purification steps

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If chromatography matrix is loaded to maximum binding capacity in each cycle, then protein recovery increases, but protein loss occurs due to breakthrough and operational complexity increases

Engineering Contradiction:
Improveprotein recoveryVSAvoidprotein loss
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent dynamically adjusts the loading capacity parameter of the chromatography matrix based on real-time monitoring of binding capacity, allowing the system to operate at optimal levels that prevent protein loss through breakthrough while maximizing recovery

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent incorporates feedback mechanisms to monitor the binding capacity of the chromatography matrix in real-time and adjust the loading parameters accordingly, ensuring that the matrix is loaded to the optimal capacity without exceeding it and causing protein loss

Inventive Principle:
Principle #23Feedback

3Manufacturing precision

If multiple purification cycles are performed to achieve sufficient purity, then protein purity improves, but operational speed decreases and time is lost

Engineering Contradiction:
Improveprotein purityVSAvoidoperational time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent establishes a continuous operation mode where the chromatography matrix is continuously loaded, washed, and re-loaded without interruption, eliminating the time losses associated with multiple discrete purification cycles while maintaining high protein purity through consistent feedback-controlled operation

Inventive Principle:
Principle #20Continuity of useful action

4Manufacturing precision

If conventional chromatography setup is used, then protein purification can be achieved, but device complexity and maintenance requirements increase

Engineering Contradiction:
Improveprotein purificationVSAvoidoperational complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent implements a self-regulating chromatography system where feedback mechanisms automatically monitor and adjust operating parameters, reducing the need for complex external control systems and manual intervention while maintaining high purification standards

Inventive Principle:
Principle #25Self-service

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 the yield and purity of purified proteins by efficiently utilizing chromatography matrices, reducing the number of purification cycles, and simplifying the operational process, leading to improved productivity and cost-effectiveness.

Implementation Method 1

loading a first volume of a mixture containing the protein of interest from a first container to a chromatography matrix operated such that the protein binds to the chromatography matrix

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS11905310B2Protein purification
Publication Date: 2024.02.20 UCB BIOPHARMA SPRL
  • US11905310B2 patent drawing
  • US11905310B2 patent drawing
  • US11905310B2 patent drawing

AI summary

The present invention relates to a process for purification a protein comprising a semi-continuous chromatography step whereby the flow-through is collected and re-loaded onto the chromatography matrix.