Membrane Filtration Technology

Drug separation membrane is a new type of membrane technology product combining functional fibre materials and membrane filtration technology, which has the advantages of high filling density, large filtration membrane area, high volume share per unit space and relatively low cost. Biomedicine is an important application market for drug separation membrane. The membrane can retain bacteria and viruses and is not easy to block, thus effectively filtering bacteria and viruses and ensuring their integrity, and has been widely used in vaccine research and development, haemodialysis, pharmaceutical purification, artificial lungs and other fields.

Overview of Truking's Membrane Technology and Products

Truking shoulders the mission of leading the membrane separation technology in the global biopharmaceutical field, committing to deepening fundamental scientific research and establishing a forefront position in the realm of membrane separation for the biopharmaceutical industry worldwide. In this context, Truking?Technology?has developed a full range of customised hollow fibre ultrafiltration membranes, microfiltration membranes and ultrafiltration membrane packages, which are being researched and applied in major domestic biomedical enterprises.

Truking?Technology has independently built the Membrane and Membrane Processes Innovation Platform Center based on the Biomacromolecule Materials Research Department II of the Central R&D Institute.Our product range includes:?2KDa, 5KDa, 10KDa, 20KDa, 50KDa, 100KDa, 300KDa, 500KDa, and 750KDa Ultra Filtration Membrane products for?the?concentration and separation of drugs, proteins, viruses, etc., and 0.1μm, 0.2μm, 0.45μm, 0.65μm microfiltration membranes for?filtration and clarification, cell culture, protein purification, ATF, TFF, CFF, and customized pore sizes for?special application scenarios.?Meanwhile, our laboratory has a series of precise experimental instruments for membrane preparation and testing and evaluation, such as scanning electron microscope?(SEM), pore size analyser, gel permeation chromatography (GPC), biochemical analyser, UV spectrophotometer, Optical Image Analyzer and mechanical property tester, which form a strong and innovative R&D?team and production team, as?well as?preparation capability.

I. Tangential Flow Filtration (TFF) Systems

Tangential Flow Filtration (TFF), also known as Staggered Flow Filtration, is a process where the feed solution flows tangentially (parallel) to the filter medium surface during operation. A small portion of the fluid passes through the filtration medium, while particles retained or deposited on the filter medium surface are swept away by the liquid flow parallel to the medium, thereby delaying membrane fouling.?TFF technology?is a membrane separation technology that is widely used for sample concentration, dialysis, separation and filtration. The retention range is from 1－1000 KDa.

Membrane filtration technology can be mainly categorized into: microfiltration, ultrafiltration, nanofiltration, reverse osmosis. Ultrafiltration (UF) is a method of separating particles such as viruses, proteins, tiny suspended matter, microorganisms, and other soluble molecules of 2 nm-100 nm from a solution. Ultrafiltration is usually used to separate molecules that differ by more than a factor of 3 to 5 and is not applicable to molecules of similar size. Microfiltration (MF) is the process of filtering large particulate matter (cellular debris, suspended matter, etc.) out of solution, which significantly improves clarity and reduces turbidity of the solution, thereby facilitating subsequent processing.

Main Applications?of?Tangential Flow Filtration:

· Clarification: such?as?separation of cells or cellular debris

· Concentration: protein concentration

· Desalination: desalting of nucleic acid,?nano microspheres and peptides

· Buffer exchange：buffer system changes before and after chromatography

· Depyrogenation：pyrogen removal of culture medium and TCM injection

II. Hollow Fiber Membrane

Hollow Fibre Membrane (HFM) is a thin structure with a porous structure. It is ideal for filtration applications as it can separate various substances according to their size and chemical properties.

Truking?Technology's HFMs are prepared using modified polyethersulfone (mPES) as the substrate. Compared to the polyvinylidene fluoride (PVDF) HFMs?available in the market, these HFMs?offers?exceptionally high processing capacity and flux. Furthermore, polyethersulfone is chemically compatible,?allowing its use in strongly acidic and alkaline working environments. Polyethersulfone also demonstrates superior biocompatibility with virtually no toxicity. Its low protein adsorption characteristic ensures maximum retention of target active ingredients.

Structure of products

The?outer diameter?of Truking?Technology's hollow fiber membrane filament ?ranges from?0.5?to 1.0mm.?The fiber wall is covered with microporous, and substance?filtration is mainly achieved through the difference in pore size.

Advantages and features of the product

Using modified polyethersulfone as the substrate and advanced membrane processing technology, Truking?Technology has manufactured a rich and comprehensive?series of hollow fibre membrane products. The products are characterised by mild and low shear, open flow channel structure, high dust holding capacity, homogeneous membrane pore size, good physical and chemical resistance and excellent biocompatibility.

1. Low shear

Truking?Technology's hollow fibre membrane has the advantage of low shear, avoiding the irregular and violent turbulence in the process of biological material circulation. This?effectively prevents?the aggregation and conformational change of proteins and other biological macromolecules, which?is beneficial for preserving?the integrity of?viral proteins and other macromolecules, thereby improving?the activity yield of the target samples.

2. Open flow channel design structure

Truking?hollow fibre membrane is designed with open flow path, which can directly deal with complex materials containing solids such as bacterial fermentation solution or high-density cell culture solution without blocking the flow path.?This eliminates?the need for centrifugation,?pre-filtration and other cumbersome pre-treatment steps. It?is widely used in applications such as one-step clarification of cell culture solution, collection and washing of bacterial organisms, collection of ammonium sulphate precipitation and protein crystals, and clarification of plant extracts.

3. Rich and comprehensive?products

Truking?technology's hollow fiber membrane product series is rich and comprehensive.?The?ultrafiltration hollow fibre membrane includes: 1 kDa, 3 kDa, 5 kDa, 10 kDa, 30 kDa, 50 kDa, 100 kDa NMWC (molecular weight cut-off), used for a variety of biological samples concentration and separation.?Through gel permeation chromatography determination, Truking has also introduced ultrafiltration hollow fiber membranes with market-rare specifications of 300 kDa, 500 kDa, and 750 kDa.?The microfiltration hollow fibre membranes include: 0.1 μm, 0.2 μm, 0.45 μm, 0.65 μm, used for biological samples filtration and clarification and solid-liquid separation and other applications.

4. Homogeneous membrane pore size

Truking's hollow fiber membranes are manufactured with strict control over processing technology and product quality, resulting in homogeneous membrane pore sizes. This uniformity allows for the selection of membranes with pore sizes closely matching the target molecular weight during concentration processes. Such precision ensures high retention yields while achieving faster transmission rates. This characteristic facilitates the removal of impurities through the membrane, thereby improving production efficiency and enhancing product quality.

5. Excellent physical and chemical resistance

Truking?hollow fiber membrane using advanced membrane processing and manufacturing technology?to avoid the generation of large pores of the membrane (No Macrovoids), thereby improving?its?pressure resistance.?These hollow fiber ultrafiltration membranes?can withstand inlet pressures of up to 4 bar and have passed strict membrane integrity tests.?Truking?hollow fiber membrane is processed and manufactured with biocompatible material modified polyethersulfone (mPES), which is stable in nature and can withstand 1M NaOH and 500 ppm sodium hypochlorite heating at 50 ℃ for?thorough CIP cleaning.?The membranes exhibit complete recovery of water flux, ensuring a long service life and low costs.

6. Excellent biocompatibility

Truking?hollow fibre membrane has been approved by CNAS and international mutual recognition for?biological evaluation. The polyethersulfone hollow fibre columns have been subjected to a series of biological tests and animal experiments, such as acute systemic toxicity test, endotoxin test, skin sensitization test, intradermal reactivity test, pyrogen test, in vitro cytotoxicity test, haemolysis tests, among others.?The results of the tests have been favorable, demonstrating that?Truking’s?hollow fibre membranes exhibit excellent biocompatibility.

Product specifications and application scenarios

III. Application Scenarios of Hollow Fiber Technology

1. In the field of biopharmaceuticals，what drug manufacturing processes can use hollow fibers?

Hollow fiber can be used in many drug manufacturing processes in the field of biopharmaceuticals, such as cell culture, separation and purification, protein purification, and depth filtration. Hollow fibers are commonly employed as a means to remove impurities, reduce contamination, enhance production efficiency, and lower costs.

2. What steps can be taken to use hollow fibres in gene therapy and cell therapy?

In gene therapy and cell therapy, hollow fibers can be used in these process, such as cell culture, cell separation, washing, concentration, purification, etc. Specific applications include:

Cell culture: hollow fibers can be used as support materials for cell culture, providing greater cell density and surface area.

Cell separation: hollow fibers can be used for cell isolation and collection, increasing the purity and productivity of individual cells.

Washing and concentration: hollow fibers can be used for washing, protein concentration and cell preparation.

Purification: hollow fibers can be used in the Purification steps of biological agents such as proteins, viruses, and plasmids to improve product purity and productivity.

Case applications include:

When preparing cell preparations related to CAR-T therapy, use hollow fibers to concentrate, collect and purify T cells.

Screen and purify the gene sequences through hollow fiber to prepare plasmids for gene therapy.

Use hollow fiber filtration to purify and concentrate recombinant collagen for the preparation of biopharmaceuticals.

3. Case study of hollow fiber used in the collection of bacteria

Hollow fibers are widely used in the collection of bacteria, the following is one of the case studies

Cultivate and collect Rhodotorula strains, which grow slowly in culture medium and are difficult to collect by traditional methods such as centrifugation. The use of hollow fiber will quickly and conveniently collect the bacteria and replace them with the buffer we needed.

A liquid medium containing Rhodotorula is added to the membrane module. Bacteria enter the hollow fiber through the holes inside the fiber and precipitate in it. Wash the hollow fiber with a buffer such as PBS to remove non-specifically bound substances.

At last, the bacteria are extracted with methanol and chloroform for subsequent analysis.?Advantages of using hollow fibers for collection include high collection efficiency, easy?of operation, and the ability to prevent sample damage or inactivation, and multiple samples can be processed at the same time.

4. Hollow fiber are used for the process steps of polysaccharide concentration

Hollow fiber is a kind of material usually used for polysaccharide concentration, the following are the process steps for polysaccharide concentration using hollow fibers:

Preparation of hollow fibers: Immerse the hollow fibers in deionized water to ensure thorough wetting.

Sample loading: Pour the polysaccharide-containing solution into the hollow fibers, utilizing pressure differential to facilitate the flow of the solution into the fibers.

Sample processing: Treat the polysaccharide solution within the hollow fibers, such as removing excess water and increasing?the concentration of polysaccharide by heating, evaporating, etc.

Collection of concentrate: Collect the concentrated polysaccharide solution?from the hollow fibers, employing backwashing or applying a small pressure differential to eliminate unnecessary water and other impurities.

Verification of concentration effectiveness: Use appropriate methods (e.g. UV absorption spectroscopy, HPIC, GPC, etc.) to verify?whether the polysaccharide concentration after concentration meets the expected levels.

Storage of concentrate: For qualified?polysaccharide concentrates, store under suitable conditions for subsequent application research and other purposes.

Quality Assurance

l High quality, high stability and high reliability.

l Pyrogen: Production and assembly are performed under strict conditions to ensure minimal endotoxin levels.

l Tested and certified by USP87 and USP88,?meeting the corresponding biocompatibility standards.

l The production is completed under ISO9001 quality management system.

l Animal-free: The materials used in the production of membrane modules do not contain any?animal-derived substances?or derivatives.

Product Application

l E.coli,?yeast, cell lysate clarification

l Diafiltration and separation of nanoparticles

l Concentration of target proteins

l Virus purification

l Upstream cell perfusion culture

IV. Truking Membrane Technology and Product Development Platform

Truking?Technology has independently built the Membrane and Membrane Processes Innovation Platform Center based on the Biomacromolecule Materials Research Department II of the Central R&D Institute.Our product range includes:?2KDa, 5KDa, 10KDa, 20KDa, 50KDa, 100KDa, 300KDa, 500KDa, and 750KDa Ultra Filtration Membrane products for the?concentration and separation of drugs, proteins, viruses, etc., and 0.1μm, 0.2μm, 0.45μm, 0.65μm microfiltration membranes for?filtration and clarification, cell culture, protein purification, ATF, TFF, CFF, and customized pore sizes for?special application scenarios.?Meanwhile, our laboratory has a series of precise experimental instruments for membrane preparation and testing and evaluation, such as scanning electron microscope?(SEM), pore size analyser, gel permeation chromatography (GPC), biochemical analyser, UV spectrophotometer, Optical Image Analyzer and mechanical property tester, which form a strong and innovative R&D team and production team, as well as?preparation capability.?Truking?Technology has developed a full range of customised hollow fibre ultrafiltration membranes, microfiltration membranes and ultrafiltration membrane packages, which are being researched and applied in major domestic biomedical enterprises.