Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids Concentration, Improved Process Throughput, Capacity and Cost in Microfiltration, Ultrafiltration, Nanofiltration, and Reverse Osmosis
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Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids Concentration, Improved Process Throughput, Capacity and Cost in Microfiltration, Ultrafiltration, Nanofiltration, and Reverse Osmosis



Cross Flow or Tangential Flow Filtration (TFF) Membrane Plants are used in Desalination, Brackish Groundwater Treatment, High Chloride Surface Water Treatment, Waste Water Treatment Plant Effluent ...

Cross Flow or Tangential Flow Filtration (TFF) Membrane Plants are used in Desalination, Brackish Groundwater Treatment, High Chloride Surface Water Treatment, Waste Water Treatment Plant Effluent Reuse, Biopharmaceutical, Food & Protein Applications for removal of undesired constituents and harvesting of desireable products. Cross flow membrane filtration technology has been used widely in industry globally. Filtration membranes can be polymeric or ceramic, depending upon the application. The principles of cross-flow filtration are used in reverse osmosis, nanofiltration, ultrafiltration and microfiltration. When purifying water, it can be very cost effective in comparison to the traditional evaporation methods. Techniques to improve performance of cross flow filtration include:

Backwashing: In backwashing, the transmembrane pressure is periodically inverted by the use of a secondary pump, so that permeate flows back into the feed, lifting the fouling layer.

Clean-in-place: Clean-in-place systems are typically used to remove fouling from membranes after extensive use. The CIP process may use detergents, reactive agents such as sodium hypochlorite and acids and alkalis such as citric acid and sodium hydroxide.

Concentration: The volume of the fluid is reduced by allowing permeate flow to occur. Solvent, solutes, and particles smaller than the membrane pore size pass through the membrane, while particles larger than the pore size are retained, and thereby concentrated. In bioprocessing applications, concentration may be followed by diafiltration.

Diafiltration: In order to effectively remove permeate components from the slurry, fresh solvent may be added to the feed to replace the permeate volume, at the same rate as the permeate flow rate, such that the volume in the system remains constant. This is analogous to the washing of filter cake to remove soluble components. Dilution and re-concentration is sometimes also referred to as "diafiltration."



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    Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids Concentration, Improved Process Throughput, Capacity and Cost in Microfiltration, Ultrafiltration, Nanofiltration, and Reverse Osmosis Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids Concentration, Improved Process Throughput, Capacity and Cost in Microfiltration, Ultrafiltration, Nanofiltration, and Reverse Osmosis Presentation Transcript

    • Tangential Flow Filtration to Enable High Solids Concentration, Improved Process Throughput, Capacity, and Cost Daniel Christodoss, Ph.D., P.E. Principal Municipal Engineer Urs i&e (817) 894-1357 2013 23rd Annual Practical Membrane / Filtration & Separations Technologies Short Course Sponsored by: Food Protein R&D Center at Texas A&M University
    • Outline What is filtration? Types of Filtration? Filtration Classification Introduction to TFF and Applications Configurations & Operational Concerns Quality Control and Filtrate Monitoring Increasing Filtration Rate and Filtration Theory Advantages of TFF TFF Design Principles and Example
    • Filtration Filtration is the use of a medium to separate solids from liquid. The solids can be from the size of particles down to cells or cellular tissue down to individual molecules. Depending on the filtration medium chosen as the filter material, selective cut-off of particle sizes are achieved in the filtration process.
    • Selectivity Filtration is usually utilized to concentrate the material for mineral extraction or purification. Filtration can provide selectivity based on size, but not on charge.
    • Types of filtration Filtration is usually broken down into two primary techniques: – deadend – cross-flow filtration
    • Deadend Filtration (Through flow) Deadend filtration is when the feed material is forced through the membrane. The flow is only in the direction perpendicular to the membrane. All the suspended solids in the feed end up on the membrane in a filter cake
    • Cross-Flow Filtration (Tangential Flow Filtration TFF) In cross-flow filtration the feed material is allowed to flow parallel to the membrane, while the pressure gradient is across the membrane. The primary advantage of cross-flow filtration is that it allows the solids to be kept in suspension and minimizes the build up of a filter cake to plug or foul the membrane
    • Filtration Classification Classification of filtration falls into several categorizes depending on the size of the substance being excluded by the membrane
    • MF, UF and RF Microfiltration generally refers to the filtration of suspension particle such as cells and cellular fragments Ultrafiltration is the filtration of macromolecules Reverse Osmosis is the filtration of molecules such as salts and sugars
    • MF, UF and RF
    • 1 micron is 1×10−6 of a meter
    • TFF Applications Microfiltration and ultrafiltration processes incorporating tangential flow or cross flow filtration is utilized in a wide range of biopharmaceutical applications. Examples of a few typical applications are listed below: 1. Water Desalination and Brackish Water Treatment + Concentration and desalting of protein, peptide, and oligonucleotide solutions 2. Purification and recovery of antibodies or recombinant proteins 3. Vaccine and conjugate concentration and diafiltration. 4. Fractionation of protein mixtures 5. Blood plasma fractionation and purification 6. Cell broth clarification, concentration 7. Cell culture perfusion such as in monoclonal antibody (Mab) production 8. Clarification of Fermentation broths 9. Concentration and washing of bacterial cells 10. Water and buffer purification (endotoxin removal)
    • Cross-Flow or Tangential Flow In cross-flow filtration (TFF) the membrane does the primary work compared to the combination of cake and membrane in deadend cake filtration. The cross-flow allows the membrane to be swept free of solids allowing for a lower resistance to fluid flow through the membrane
    • Membrane Configurations Spiral wound Hollow fiber
    • Quality Control Inline real time photometers are an extremely effective way of monitoring filtration performance to achieve the most efficient and cost effective means of clarifying product as it passes from filtration step to filtration step. Sensors can determine the point at which acceptable purity is achieved or detect filter upset or breakthrough.
    • Quality Control Inline photometric control guarantees the clarification of final product. Any deviation can be instantly detected, allowing process changes to be initiated immediately. The photometric system becomes an unsurpassed tool for quality assurance and quality control; thereby, reducing lab analysis, visual inspection and increasing filter system automation.
    • Quality Control sensor sensor
    • Theory of Filtration In filtration, solid particles are separated from solidliquid mixtures by forcing the fluid through a filter medium or filter cloth that retains the particles. The Filtration rate can be improved either by using a vacuum or pressure. Filter aides such as Diatomaceous Earth which are highly porous also improve the filtration rate. Filtration theory is used to estimate the rate of filtration.
    • Ultrafiltration and Microfiltration Theory Microfiltration 0.1 to 10 µm filter sizes Used to separate cells Ultrafiltration MW range 2000 to 500,000 (2 to 500 kilo Daltons (kD)) Used to concentrate or sieve proteins based on size A thin membrane with small pores supported by a thicker membrane with larger pores Low MW solutes pass through the filter and high MW solutes are retained Pressure driven process Can result in concentration polarization and gel formation at membrane surface
    • Theory of Filtration The rate of filtration is usually measured as the rate at which liquid filtrate is collected. Filtration rate depends upon: 1. Area of the filter cloth or membrane 2. Viscosity of the fluid 3. The pressure difference across the filter 4. The resistance to filtration offered by the cloth or membrane and deposited filter cake.
    • Increasing filtration rate 1. increase the filtration area (A) 2. reduce the filtration pressure drop (membrane cleaning) ∆P decreases α, which causes filtration rate to increase. 3. reduce the cake mass 4. reduce the liquid viscosity (by dilution) 5. reduce specific cake resistance (α) 1. Increase porosity 2. Reduce particle size
    • UF Cross-Flow Filtration (TFF)
    • Cross-Flow or Tangential Flow The term cross-flow or TF refers to the fact that the flow direction of the retentate is perpendicular to the flow direction of permeate. The pressure gradient for the flow is still across the membrane, while the retentate is allowed to flow through the system
    • Cross-flow also allows the concentration of the retentate without the contamination with filter aids. Therefore TFF can be used to collect either the permeate or the retentate
    • Advantages of Cross-flow Filtration Process Goal Crossflow Filtration Deadend Filtration Ability to handle wide variation in particle size Ability to handle wide variations in solids concentration Continuous concentration with recycle Waste minimization Excellent Generally poor Excellent Poor or unacceptable Excellent Poor or unacceptable Superior Can minimize waste if handling low solids feed where cartridge disposal is infrequent High product purity or yield Excellent Performance is generally acceptable except in situations involving high solids or adsorptive fouling
    • Cross-flow Filtration Systems
    • Concentration Factors Many products start out in very low concentrations in the original broth This requires very high concentration or removal of most of the water from the system
    • Solids effects
    • TFF System Design Define the purpose of the TFF process – The biomolecule of interest in your sample is called a product. Separation can occur by choosing a membrane that retains the product while passing any low molecular weight contaminants. – Alternatively, a membrane can be chosen that passes the product while retaining higher molecular weight components in the sample. – It is important to know the concentration factor or the level of salt reduction required in order to choose the most appropriate membrane and system for the process.
    • TFF System Design Choose the membrane molecular weight cutoff – The molecular weight cutoff (MWCO) of a membrane is defined by its ability to retain a given percent of a molecule in solution (typically 90% retention). To retain a product, select a membrane with a MWCO that is 3 to 6 times lower than the molecular weight of the target protein. For fractionation, select a membrane MWCO that is lower than the molecular weight of the molecule to be retained but higher than the molecular weight of the molecule you are trying to pass.
    • TFF System Design Determine the required membrane area for the application – Choosing an appropriate TFF system depends on the total sample volume, required process time, and desired final sample volume. – Use the following equation to calculate the membrane area required for processing a sample in a specified time:
    • Example 1: What TFF system should I use to concentrate 10 liters to 200 mL in 2.5 hours? Assume the average filtrate flux rate of 50 liters/m2/hour (L/m2/h, LMH).
    • Transmembrane Pressure (TMP) driving force for liquid transport through the ultrafiltration membrane, calculated as the average pressure applied to the membrane minus any filtrate pressure. In most cases, pressure at filtrate port equals zero. PRESSURE DROP DP = (30 - 20) = 10 PSI Inlet Pressure minus Retentate Pressure
    • BASIC TFF APPLICATIONS Clarification - Product Passes Through Membrane, Large Particles Retained Concentration - Product Retained, Solvent Passes Through Membrane Diafiltration or Buffer Exchange - Product Retained, Solvent Passes Through Membrane with unwanted salts (50%) and New Solvent Added to Product to ultrafilter remaining 50%
    • FILTER RATINGS Microfiltration – Rated by pore size 0.1 - 0.65 Micron Ultrafiltration – Rated by size of molecule retained 1,000 - 1,000,000 NMWL Reverse Osmosis – Rated by retention of marker ions NaCl
    • MEMBRANE CHEMISTY Microfiltration – PVDF (Durapore™) – Polyethersulfone Ultrafiltration – Polyethersulfone (Biomax™) – Regenerated Cellulose (Ultracell™) Reverse Osmosis – Thin Film Composite (TFC) – Polyamide on Polysulfone UF Membranes – – – – Conventional with subsurface voids New void-free composite structure (Ultracell™)
    • Successful Scaleup of a TFF Process Understanding of the process objectives purity, yield, times, volumes, concentrations, etc. Select Correct Membrane Select Correct Device Collect Adequate Data to Select Proper Operating Conditions Flux vs. Crossflow Flux vs. TMP Flux vs. Concentration Collect Data for Multiple Runs to Prove Robustness