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Membrane Filtration Technology

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Membrane filtration technology is a physical separation method that can separate molecules of different sizes and properties. It has been widely used in downstream bio-purification processes to reduce production costs and increase batch processing volume. CD Formulation integrates cutting-edge membrane filtration technology into our protein characterization technology platform to provide reliable support for the downstream process development of your protein/peptide drugs.

What is Membrane Filtration Technology?

Membrane filtration, a high-throughput technology that separates substances according to size specifications, can be used for microfiltration clarification and sterilization, as well as ultrafiltration protein concentration and liquid exchange. Its driving force is the pressure difference on both sides of a special membrane. Membrane filtration can be dead-end filtration or cross-flow filtration.

  • Dead-End Filtration: The filtration of liquid on the membrane surface, all liquid passes from one side of the membrane, and the filtered liquid (permeate) is collected from the other side of the membrane. This method is simple and easy to operate, but during operation, the membrane surface is prone to the deposition of solid particles, resulting in a decrease in filtration rate, and frequent cleaning or replacement of the membrane is required.
  • Cross-Flow Filtration: The liquid flows parallel to the surface of the membrane at a certain flow rate, which allows a portion of the liquid to be collected through the membrane while keeping most of the liquid flowing on the membrane surface.

Compared with dead-end filtration, cross-flow filtration has significant inherent advantages. Because the treated liquid flows continuously through the membrane, there is no filter cake that can cause scaling and uneven flow. In addition, dead-end filtration does not require filter aids and the membrane has a longer service life, which makes continuous and automated filtration processes possible, thereby achieving consistent and controllable product quality.

Fig. 1 Dead-end filtration and cross-flow filtration.Fig.1 Comparison between: (a) dead-end, (b) cross-flow configuration. (Saxena A, et al., 2009)

Our Services Related to Membrane Filtration Technology

Thanks to decades of experience supporting protein/peptide biopharmaceutical development and manufacturing using membrane filtration technology, our team of highly qualified experts offers a range of membrane filtration-related services to accelerate the implementation and success of your project.

Our experienced team of experts has completed hundreds of membrane filtration separation and purification projects for protein and peptide, supporting all stages of your protein/peptide drug development and manufacturing - from early studies to downstream process monitoring and GMP batch release testing.

Utilizing cutting-edge membrane filtration technology, we support the following protein/peptide development and characterization plans, including but not limited to:

  • Purify proteins from complex mixtures (e.g., cell lysates, fermentation broths).
  • Concentrate proteins and remove contaminants such as salts, nucleic acids, and other biomolecules prior to characterization techniques such as chromatography or electrophoresis.
  • Concentrate proteins in biopharmaceutical production and improve downstream processing efficiency.
  • Separate isomers and glycosylation variants of proteins based on size and molecular weight.
  • Effectively remove contaminants such as nucleic acids, endotoxins, and other impurities that may interfere with protein characterization.
  • In process development, integrate membrane filtration into bioreactors to monitor protein properties in real time as cells express proteins.
  • Combined with online characterization methods to continuously assess protein quality to address and solve any emerging issues related to protein stability, aggregation, or degradation.

Available Types for Membrane Filtration

In our downstream purification process development for protein pharmaceuticals, four commonly used membrane filtration technologies include reverse osmosis (RO), microfiltration (MF), ultrafiltration (UF), and nanofiltration (NF). These technologies are selected based on the size of the species they need to separate from the feed liquid.

Fig. 2 Various membrane filtration technologies.Fig.2 Membrane filtration types. (CD Formulation)

Microfiltration (MF)

MF involves capturing particles larger than ~0.1 µm with porous membranes, allowing the separation of larger particles, cell debris, and microorganisms from protein solutions.

Ultrafiltration (UF)

UF is used to concentrate proteins and remove low molecular weight impurities. It is typically operated using membranes with pore sizes typically in the 1-100 kDa range, allowing water and small solutes to pass through while retaining larger proteins.

Nanofiltration (NF)

NF is used to selectively separate molecules based on size and charge. Small molecules can be concentrated while larger organic compounds are retained. Pore sizes are typically in the 1-10 kDa range.

Reverse Osmosis (RO)

RO is designed to deionize solutions and achieve higher purity in protein applications by removing salts and other small molecules. It is typically operated at high pressure, forcing the solvent through a semipermeable membrane. In principle, water is the only substance that can permeate the membrane. All other substances, such as bacteria, proteins, colloids, salts, sugars, minerals, etc., can't pass.

Advantages of Membrane Filtration Technology

  • Membrane filtration generally requires lower energy input compared to traditional separation processes, especially in processes such as microfiltration and ultrafiltration.
  • Membrane filtration involves fewer processing steps, allowing for higher purity and higher overall yields.
  • Membrane filtration is a clean technology. The separation process is based solely on molecular size, without the use of additives.
  • Membrane filtration systems can be easily scaled up or down, providing flexibility for production processes from laboratory scale to industrial scale applications.
  • Membrane filtration can be operated continuously, increasing yield and productivity while reducing the time required for batch processing.
  • Membrane filtration processes are generally gentle, helping to maintain the structural integrity and biological activity of proteins.
  • Membrane filtration can be tailored to different protein types and applications, including MF, UF, NF, and RO.

Cutom Membrane Filtration Services

Downstream Purification Process Development

Downstream purification process development involves purification, isolation, and characterization of target products from complex biological matrices to ensure that the final product is safe, effective, and of high quality. Our team of process experts will perform many unit operations, providing you with high-quality downstream process development services by adopting various protein purification and preparation technologies.

Why Choose Our Membrane Filtration Technology?

  • Our team comprises highly qualified experts with extensive experience in the development and validation of membrane filtration analytical methods.
  • We have accumulated decades of expertise and successful project experience using membrane filtration technology to support protein/peptide biopharmaceutical development.
  • Our laboratories are equipped with the latest membrane filtration equipment, enabling innovative methods and high-quality data generation.
  • From initial consultation to ongoing maintenance, our dedicated support team is here to assist you at every stage, ensuring seamless integration and operation of our filtration solutions.
  • We adhere to strict quality control and regulatory standards to ensure the integrity and compliance of your data.
  • We provide flexible experimental design and customized solutions.

Publication

Published Data

Technology: Ultrafiltration (UF)

Journal: Separation and Purification Technology.

IF: 8.1

Published: 2016

Results:

The authors investigated the ability of ultrafiltration (UF) membranes to remove proteins (bovine serum albumin (BSA) or lysozyme (LYS)) from silica nanoparticles in dispersed mixtures. RC and PES UF membranes with different nominal molecular weight cutoffs (NMWCO) were used. The molecular weight cutoff was experimentally determined to be 180 kDa. Membrane characteristics and filtration conditions, particularly pH and flux, were selected or adjusted based on single-component feed data to achieve maximum protein transport with complete silica retention. Batch dead-end and continuous diafiltration processes were used for fractionation and purification. Results showed that both RC and PES UF membranes could achieve quantitative retention of silica and the retained silica nanoparticles remained stable in the dispersion without any signs of aggregation.

Fig. 3 Removal of proteins through the membrane.Fig. 3 Schematic concept for the purification of metal oxide nanoparticle dispersion by removal of proteins through the membrane. (Alele N, et al., 2016)

CD Formulation aims to provide a powerful analytical tool for the separation, purification, and characterization of proteins and peptides. Please feel free to contact us if you are interested in our services. Learn how our membrane filtration technology can support the smooth implementation of your protein/peptide biopharmaceutical program.

References

  1. Saxena A, Tripathi BP, Kumar M, et al. Membrane-based techniques for the separation and purification of proteins: an overview. Adv Colloid Interface Sci. 2009 Jan 30;145(1-2):1-22.
  2. Alele N, Ulbricht M. Membrane-based purification of proteins from nanoparticle dispersions: Influences of membrane type and ultrafiltration conditions. Separation and Purification Technology. 2016;158: 171-182.
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