Teknologi Bioproses
Filtration
Pertemuan ke-12
Marcelinus Christwardana, PhD
Downstream Process
• Typically in the field of bioprocess technology, the
highest equipment and operating cost exist in the
downstream processing of fermentation products.
• Manufacturing costs, including capital and
operational expenses, of downstream processing
part can be up to 50 % of the overall costs.
Filtration
Filtration is one of the most common methods for the
downstream processing of fermentation products and it
is used at all production scales.
Basic principle in filtration is to separate the
suspended particles or larger molecular mass
components from bulk liquid with porous medium.
• Filtration is applicable as a separation method
when molecular sizes of substances in
process stream differ significantly.
• Driving force can be pressure difference,
vacuum, concentration gradient, valence or
electrochemical affinity
Several parameters affect effectivity of filtration processes,
such as
• pore size
• pressure
• Temperature
Filtration processes and equipment are often classified by:
• pore size
• direction of flow in relation to filter
• type of filter
• geometry of filters.
filtration and membrane separation technologies can be used four
different ways:
1. clarifying the cells from the fermentation broth and
conditioning the cells for mechanical or chemical disruption
2. clarifying the products from homogenate of cellular debris
after the disruption process
3. clarifying extracellular product from the culture after
fermentation
4. concentration and diafiltration of a clarified product for
chromatography
• Filtration materials can be classified in:
1. depth filters
2. screen filter
3. membranes.
• Depth filters and screen filter are commonly
used in dead-end filtration, while membranes
are used in tangential flow filtration.
Depth Filter
• Depth filters do not have a precise pore size or
structure and thus they are not absolute.
• This means that particles with wider range in
size will permeate through the filter.
• Components that are larger than the apertures
of the filter will be trapped on the surface of
the filter.
Depth Filter
• In the case of smaller particles, random entrapment
and adsorption of matter occurs within the structure
of the media.
• Depth filter may also have an electric charge which
aids in the entrapment of smaller particles.
• Depth filters have thicker construction and higher
porosity.
Depth Filter
This leads to some advantages, such as:
• higher flow rate and dirt loading capacity
• Cheaper
Depth filters are manufactured from fibrous materials,
woven or nonwoven polymeric material or inorganic
materials
Screen Filter
• In the case of screen filters (or mesh filters), particles are
retained directly on the surface of the screen.
• Their pore size is precisely defined, so that only particles with
diameter below pore size of the filter will permeate the filter.
• Screens are used when there is need for low nonspecific
binding or low adsorption or absorption of the filtrate.
Membrane
• Membrane filters are thin membranes often manufactured
from polymeric material but also other materials can be used.
• Due to manufacturing techniques, they relatively well defined
flow rate, pore size, pore structure, pore density, bubble
point and tensile strength.
• Membrane filter mainly function by trapping the particles on
its surface, but some entrapment into the membrane also
occurs
Membrane
• Typical housings for membrane filters are:
1. Tubular
2. flat sheet
3. hollow fibre
4. spiral wound
5. vibrating membrane systems
Temperature
• Temperature is one important parameter affecting filtration.
• Increasing temperature increases the disruption rate which
is beneficial if the product is intracellular product.
• High temperature can cause deactivation or degradation of
proteins which can be the desired product.
• Temperature also reduces the viscosity of the fermentation
broth which leads to reduced filtration time.
• Viscosity can also be reduced by chemical additives
Cake Resistance
• Different types of cells disrupt differently.
• Other are weaker than others and disrupted cell can
block the pores.
• Some filter aids can be used to reduce the cake
resistance.
• These filter aids increase the porosity of the cake and
thus increase the flow rate through the cake.
Filtration Time
Filtration Volume
Where:
• V is the volume of filtrate
• A is the surface area of the filter
• Dp is the pressure drop through the cake and filter
medium
• m is the viscosity of the filtrate
• rm is the resistance of the filter medium
• rc is the resistance of the cake
Cake Resistance
Where:
• W is the total weight of the cake on filter
• C is the weight of the cake deposited per unit volume of
filtrate
• is the average specific resistance of the cake
Ruth equation for constant-pressure filtration
A plot of t/V versus V yields a straight line with a slope of
1/K and intercept of 2V0/K
Microfiltration
Microfiltration (MF) is a well-known separation process,
which is capable of removing particle sizes of micro-
scale (from 0,02μm up to 10μm) in contaminated liquid
or gas streams by a semi-permeable membrane of
certain pore size.
Microfiltration
• The most prominent process designs for MF include in-line
(dead-end) filtration and cross-flow (tangential) filtration.
• In in-line filtration the feed stream is forced completely
through the membrane which results in particle
accumulation on membrane surface and a particle free
permeate.
• In cross-flow filtration the feed is circulated across the
membrane surface which results in particle free permeate
and in retentate concentrated in particles
Microfiltration
• The membranes utilized in MF can be divided in two classes:
1. In depth
2. Membranes
• The difference between them is the pore size and particle
capture site
• In depth membranes have small pores that capture the
particles on the surface on the membrane and screen
membranes have larger pores which capture the particles in
the membrane interior.
Microfiltration
Microfiltration
• MF processes in industry usually consist of two cartridge
filters (pre filter and final filter) consisting of two or more
membranes, a feed-pump and pressure difference
measuring and control equipment.
• The prefilter is the main filtering unit, which captures the
largest of particles and the final filter is used to capture the
residual fine particles.
• The main purpose of prefilter is to prevent plugging of the
fine filter and thus extend its operation time.
Nanofiltration
• Ultrafiltration (UF) is a separation process that makes use
of filters with pore size between 1 and 20 nanometers
• Membrane permeability in UF is however often specified
by molecular weight cut-off (MWCO) rather than by pore
diameter.
• The separation is often done using hydraulic pressure of
2 to 10 atmospheres to force low molecular weight
solutes through membrane.
Nanofiltration
• UF membranes are designed to provide high retention of
proteins and other macromolecules by small pore size
and sometimes by electrostatic interactions.
• Amino acids generally pass through UF membranes,
while proteins are too large to pass through
Nanofiltration
• UF is typically used for protein concentration and buffer
exchange, processes which were earlier performed using
size exclusion chromatography.
• However, UF is practical only when separating molecules
whose molecular weights differ by at least a factor of ten
as the membranes often have significant variance in pore
size.
Nanofiltration
• At industrial scale, UF processes are generally carried out
as fed batch operations followed by batch operation.
• Membrane material is typically composite regenerated
cellulose in industrial scale, but also regenerated
cellulose, polysulfone and polyethersulfone can be used.
Nanofiltration
• Membranes can be either anisotropic or isotropic.
• Anisotropic filters have a thin skin with small pores on top
of a thicker, highly porous layer that provides mechanical
strength.
• Isotropic, self-supporting filters have homogenous
structure that allows them to be cleaned by backflushing.
• Anisotropic filters are geometrically generally flat sheets
while isotropic filters are hollow fibers.
Nanofiltration
Thanks for your attention…