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    Membrane chromatography

    A powerful approach for purification challenges

    Chromatography is a critical purification technique used to separate biomolecules such as proteins, nucleic acids, and other biologics. Resin-based column chromatography has long been a gold standard, but membrane chromatography is transforming separation and purification strategies. With its ability to handle higher flow rates, reduce process times, and maintain product quality, membrane chromatography offers distinct advantages, especially in the field of biomanufacturing. This article compares resin column chromatography and membrane chromatography, highlighting why membrane chromatography is becoming a preferred choice for many bioprocessing applications.

    • What is membrane chromatography?
    • Why use membrane chromatography?
    • Applications
    • The future
    Man with beard, safety goggles and white shirt working in a biotech environment

    What is membrane chromatography?

    Membrane chromatography integrates the principles of chromatography with the benefits of porous membranes. Unlike resin columns that rely on beads for separation, membrane chromatography uses a flat or pleated membrane matrix functionalized with ligands to bind target molecules. This approach significantly reduces diffusion limitations and allows for high binding capacity with very short resident times, resulting in more efficient processing.
    Membrane chromatography operates through convective flow rather than diffusion, significantly reducing processing time. For example, during virus clearance, membrane chromatography enables rapid and efficient purification in a fraction of the time required by other methods.

    Why use membrane chromatography?

    1. Reduced buffer consumption

    Membranes require lower buffer volumes due to their smaller column volume and higher flow-through rates. This reduction lowers costs and simplifies downstream operations, particularly in polishing steps.

    2. High efficiency for large biomolecules

    Membrane chromatography excels in purifying large biomolecules, such as viral vectors, plasmids, and mRNA. Its convective flow ensures consistent performance, even for high molecular weight molecules.

    3. Minimal fouling and maintenance

    Membranes are less prone to fouling and are often designed for single-use applications. This eliminates the need for cleaning and regeneration, reducing downtime and cross-contamination risks. For instance, single-use membranes are ideal for multi-product facilities, where minimising cross-contamination is essential.

    4. Compact footprint

    Membranes are much smaller than traditional purification systems, making them ideal for facilities with space constraints. Their smaller footprint reduces infrastructure requirements and supports flexible production layouts. This is especially beneficial for biopharma start-ups and small-scale facilities aiming to maximize productivity in limited spaces.

    5. Scalability and flexibility

    Scaling membrane chromatography is straightforward due to its modular design. Membranes can be easily adjusted to accommodate different production volumes without extensive system redesigns. For instance, during clinical trial phases, membrane chromatography systems can quickly scale to meet changing batch sizes as production requirements evolve.

    Applications of membrane chromatography

    Membrane chromatography is widely used in the biotechnology field for various applications, including:

    • Biomanufacturing: Rapid polishing steps for removing host cell proteins, DNA, and endotoxins from therapeutic proteins.
    • Analytical applications: High-throughput screening and quality control, ensuring biomolecule purity and monitoring critical quality attributes during bioprocessing. Membrane chromatography is also used in detecting contaminants like endotoxins and aggregated proteins in therapeutic formulations.
    • Vaccine production: Streamlining viral clearance processes to remove viral contaminants effectively. For instance, membrane chromatography has been employed in the purification of influenza vaccines, ensuring the removal of residual impurities while maintaining high yields.
    • Gene therapy and mRNA vaccines: Purification of viral vectors, plasmids, and mRNA to produce clinical-grade therapeutic agents. This method is particularly effective for purifying viral vectors used in CAR-T cell therapies, which are highly sensitive to residual impurities.
    Advantages of membrane chromatography

    The future of membrane chromatography

    Membrane chromatography represents a significant advancement in downstream processing. Its rapid processing, flexibility, and scalability make it indispensable in biomanufacturing. For instance, in vaccine production, membrane chromatography streamlines the removal of viruses and impurities, ensuring faster production cycles without compromising quality.
    Beyond biomanufacturing, membrane chromatography also plays an important role in analytical applications. It enables high-throughput purification and screening, supporting quality control and biomolecule characterisation processes essential for drug development and manufacturing. Another field where membrane chromatography plays a growing role is the development of personalised medicine. For example, it is being used in small-scale purification systems tailored to individual patient therapies, such as autologous CAR-T cell treatments. These therapies require rigorous purification to ensure patient safety and efficacy.
    As industries continue to evolve, producing more complex and diverse therapies, the demand for efficient, flexible, and scalable purification technologies will continue to grow. Membrane chromatography’s ability to deliver faster processing, reduced costs, and enhanced performance positions it as a cornerstone of future purification strategies.

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