Cross-flow filtration
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In
chemical engineering Chemical engineering is an engineering field which deals with the study of operation and design of chemical plants as well as methods of improving production. Chemical engineers develop economical commercial processes to convert raw materials in ...
,
biochemical engineering Biochemical engineering, also known as bioprocess engineering, is a field of study with roots stemming from chemical engineering and biological engineering. It mainly deals with the design, construction, and advancement of unit processes that inv ...
and
protein purification Protein purification is a series of processes intended to isolate one or a few proteins from a complex mixture, usually cells, tissues or whole organisms. Protein purification is vital for the specification of the function, structure and interact ...
, crossflow filtration (also known as tangential flow filtrationMillipore Technical Library: Protein Concentration and Diafiltration by Tangential Flow Filtration
/ref>) is a type of
filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter ...
(a particular unit operation). Crossflow filtration is different from dead-end filtration in which the feed is passed through a
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
or bed, the solids being trapped in the
filter Filter, filtering or filters may refer to: Science and technology Computing * Filter (higher-order function), in functional programming * Filter (software), a computer program to process a data stream * Filter (video), a software component tha ...
and the
filtrate Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter m ...
being released at the other end. Cross-flow filtration gets its name because the majority of the feed flow travels tangentially ''across'' the surface of the filter, rather than into the filter. The principal advantage of this is that the
filter cake A filter cake is formed by the substances that are retained on a filter. Filter aids, such as diatomaceous earth or activated carbon are usually used to form the filter cake. The purpose is to increase flow rate or achieve a smaller micron filtr ...
(which can blind the filter) is substantially washed away during the filtration process, increasing the length of time that a filter unit can be operational. It can be a continuous process, unlike batch-wise dead-end filtration. This type of
filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter ...
is typically selected for feeds containing a high proportion of small particle size solids (where the permeate is of most value) because solid material can quickly block (blind) the filter surface with dead-end filtration. Industrial examples of this include the extraction of soluble
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s from
fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
liquors. The main driving force of cross-flow filtration process is transmembrane pressure. Transmembrane pressure is a measure of pressure difference between two sides of the membrane. During the process, the transmembrane pressure might decrease due to an increase of permeate viscosity, therefore filtration efficiency decreases and can be time-consuming for large-scale processes. This can be prevented by diluting permeate or increasing flow rate of the system.


Operation

In crossflow filtration, the feed is passed across the filter membrane (tangentially) at positive
pressure Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country a ...
relative to the permeate side. A proportion of the material which is smaller than the membrane pore size passes through the membrane as
permeate In physics and engineering, permeation (also called imbuing) is the penetration of a permeate (a fluid such as a liquid, gas, or vapor) through a solid. It is directly related to the concentration gradient of the permeate, a material's intrins ...
or
filtrate Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter m ...
; everything else is retained on the feed side of the membrane as retentate. With crossflow filtration the
tangent In geometry, the tangent line (or simply tangent) to a plane curve at a given point is the straight line that "just touches" the curve at that point. Leibniz defined it as the line through a pair of infinitely close points on the curve. Mo ...
ial motion of the bulk of the fluid across the membrane causes trapped
particle In the physical sciences, a particle (or corpuscule in older texts) is a small localized object which can be described by several physical or chemical properties, such as volume, density, or mass. They vary greatly in size or quantity, from ...
s on the filter surface to be rubbed off. This means that a crossflow filter can operate continuously at relatively high solids loads without blinding.


Benefits over conventional filtration

* A higher overall liquid removal rate is achieved by the prevention of filter cake formation * Process feed remains in the form of a mobile slurry, suitable for further processing * Solids content of the product slurry may be varied over a wide range * It is possible to fractionate particles by size * Tubular pinch effect


Industrial applications

Cross-flow membrane filtration technology has been used widely in industry around the globe. Filtration membranes can be polymeric or ceramic, depending upon the application. The principles of cross-flow filtration are used in
reverse osmosis Reverse osmosis (RO) is a water purification process that uses a partially permeable membrane to separate ions, unwanted molecules and larger particles from drinking water. In reverse osmosis, an applied pressure is used to overcome osmotic ...
,
nanofiltration Nanofiltration is a membrane filtration process used most often to soften and disinfect water. Overview Nanofiltration is a membrane filtration-based method that uses nanometer sized pores through which particles smaller than 10 nanometers pa ...
,
ultrafiltration Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in the ...
and
microfiltration Microfiltration is a type of physical filtration process where a contaminated fluid is passed through a special pore-sized membrane filter to separate microorganisms and suspended particles from process liquid. It is commonly used in conjunction ...
. When purifying water, it can be very cost-effective in comparison to the traditional evaporation methods. In
protein purification Protein purification is a series of processes intended to isolate one or a few proteins from a complex mixture, usually cells, tissues or whole organisms. Protein purification is vital for the specification of the function, structure and interact ...
, the term tangential flow filtration (TFF) is used to describe cross-flow filtration with membranes. The process can be used at different stages during purification, depending on the type of membrane selected. In the photograph of an industrial filtration unit (right), it is possible to see that the recycle pipework is considerably larger than either the feed pipework (vertical pipe on the right hand side) or the permeate pipework (small manifolds near to the rows of white clamps). These pipe sizes are directly related to the proportion of liquid that flows through the unit. A dedicated pump is used to recycle the feed several times around the unit before the solids-rich retentate is transferred to the next part of the process.


Techniques to improve performance


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 from the surface of the membrane. Backwashing is not applicable to spirally wound membranes and is not a general practice in most applications. (See
Clean-in-place Clean-in-place (CIP) is an automated method of cleaning the interior surfaces of pipes, vessels, equipment, filters and associated fittings, without major disassembly. CIP is commonly used for equipment such as piping, tanks, and fillers. CIP emp ...
)


Alternating tangential flow (ATF)

A
diaphragm pump A diaphragm pump (also known as a Membrane pump) is a positive displacement pump that uses a combination of the reciprocating action of a rubber, thermoplastic or teflon diaphragm and suitable valves on either side of the diaphragm (check valve, ...
is used to produce an alternating tangential flow, helping to dislodge retained particles and prevent membrane fouling.
Repligen Repligen is an American company devoted to the development and production of materials used in the manufacture of biological drugs. The company is based in Waltham, Massachusetts, and incorporated in Delaware in 1981. A public company, Repli ...
is the largest producer of ATF systems.


Clean-in-place (CIP)

Clean-in-place Clean-in-place (CIP) is an automated method of cleaning the interior surfaces of pipes, vessels, equipment, filters and associated fittings, without major disassembly. CIP is commonly used for equipment such as piping, tanks, and fillers. CIP emp ...
systems are typically used to remove fouling from membranes after extensive use. The CIP process may use detergents, reactive agents such as
sodium hypochlorite Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
and acids and alkalis such as
citric acid Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in ...
and
sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and al ...
(NaOH). Sodium hypochlorite (bleach) must be removed from the feed in some membrane plants. Bleach oxidizes thin-film membranes. Oxidation will degrade the membranes to a point where they will no longer perform at rated rejection levels and have to be replaced. Bleach can be added to a sodium hydroxide CIP during an initial system start-up before spirally-wound membranes are loaded into the plant to help disinfect the system. Bleach is also used to CIP perforated stainless steel (Graver) membranes, as their tolerance for sodium hypochlorite is much higher than a spirally-wound membrane. Caustics and acids are most often used as primary CIP chemicals. Caustic removes organic fouling and acid removes minerals. Enzyme solutions are also used in some systems for helping remove organic fouling material from the membrane plant. The pH and temperature are important to a CIP program. If pH and temperature are too high the membrane will degrade and flux performance will suffer. If pH and temperature are too low, the system simply will not be cleaned properly. Every application has different CIP requirements. e.g. a dairy
reverse osmosis Reverse osmosis (RO) is a water purification process that uses a partially permeable membrane to separate ions, unwanted molecules and larger particles from drinking water. In reverse osmosis, an applied pressure is used to overcome osmotic ...
(RO) plant most likely will require a more rigorous CIP program than a water purification RO plant. Each membrane manufacturer has their own guidelines for CIP procedures for their product.


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".


Process flow disruption (PFD)

A technically simpler approach than backwashing is to set the transmembrane pressure to zero by temporarily closing off the permeate outlet, which increases the attrition of the fouling layer without the need for a second pump. PFD is not as effective as backwashing in removing fouling, but can be advantageous.


Flow rate calculation

The flux or flow rate in cross-flow filtration systems is given by the equation: J = \frac in which: * J: liquid flux * \Delta P: transmembrane pressure (should also include effects of
osmotic pressure Osmotic pressure is the minimum pressure which needs to be applied to a solution to prevent the inward flow of its pure solvent across a semipermeable membrane. It is also defined as the measure of the tendency of a solution to take in a pure ...
for reverse osmosis membranes) * R_: Resistance of the membrane (related to overall
porosity Porosity or void fraction is a measure of the void (i.e. "empty") spaces in a material, and is a fraction of the volume of voids over the total volume, between 0 and 1, or as a percentage between 0% and 100%. Strictly speaking, some tests measur ...
) * R_: Resistance of the cake (variable; related to membrane fouling) * \mu: liquid
viscosity The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inte ...
Note: R_ and R_ include the inverse of the membrane surface area in their derivation; thus, flux increases with increasing membrane area.


See also

* Dead-end filtration *
Membrane fouling Membrane fouling is a process whereby a solution or a particle is deposited on a membrane surface or in membrane pores in a processes such as in a membrane bioreactor, reverse osmosis, forward osmosis, membrane distillation, ultrafiltration, microf ...


References


External links


IUPAC Terminology for membranes and membrane processes (1996)

Ultrafiltration Learning Center

Cross Flow Filtration Method Handbook for protein purification
{{DEFAULTSORT:Cross-Flow Filtration Biochemical separation processes Filtration Water filters Membrane technology