CSB 30103

Downstream processing of
bio-product
(Chapter 3: Filtration)
Contact:
Mrs. Rozyanti Mohamad
06-551 2077 / 012-652 0389
rozyanti@unikl.edu.my

Learning outcomes
1. Describe and apply the principle of filtration
2. Explain membrane fouling
3. Identify and explain various type of filtration
equipment and process
4. Perform experiment using filtration unit

Introduction

Filtration is a
technique to separates solid and liquid through a solid
support or filter medium

Process description
The liquid to be clarified
is passed through a
porous barrier

Large particles are

retained while some
small particles pass
through the filter

Pressure-driven process
Usually involves in early
stages of product
purification

Filtration rate
Area of
filter cloth

Volume of
filtrate

Time

Viscosity of
filtrate

Pressure drop
across the filter

Resistance between
cloth and cake

How to increase filtration rate?

Increase
filter area

Reduce liquid
viscosity

Increase filtration
pressure drop

Reduce the cake

mass / thickness

Principle of filtration
Two broad categories based on the direction of the fluid
feed in relation to the filter medium.

Fluid flows perpendicular

to the medium

Fluids flows parallel to the

medium

Conventional vs cross-flow filtration

Conventional

Cross flow

Feed is directed into the

membrane

Feed flows along the surface as

well as through the membrane.

Larger molecules than the pores

accumulate and fouls the surface

Prevents build up of molecules at

the surface that can cause fouling.

As the volume filtered increases,

fouling increases.

Allowing a greater volume to be

processed per unit area of
membrane surface.

Conventional filtration:
Darcys law
Darcys law describe the flow of liquid through a
porous bed of solids:
1 dV
p
=
......Eq(3.1)
A dt o R

R = Rm + Rc ......Eq(3.2)
V
Rc = c ......Eq(3.3)
A

Where,
V
t
A
p

R
Rm
Rc

: volume of filtrate
: time
: cross-sectional area of filter medium
: pressure drop through the filter
medium
: viscosity of filtrate
: resistance (filter medium + solid cake)
: filter medium
: solid cake
: specific cake resistance
: mass of dry cake solid per volume of
filtrate

Conventional filtration:
Darcys law
Combining previous equation will obtain:
p
1 dV
=
......Eq(3.4)
A dt o [ c (V / A) + Rm ]

For the case of zero filtrate at zero time, integration the

equation will obtain:
t
o c V o Rm
V/A

......Eq(3.5)
+
2p A p

t
V
Plot of V / A vs A

should give a straight line

Conventional filtration:
Specific cake resistance
Specific resistance of the cake is directly affected by the
pressure drop across the cake:
= (pc)s Eq(3.6)
where and s are empirical constants
The power s has been called the cake compressibility
factor, range from zero for incompressible cakes such as
sand and diatomite to near unity for highly compressible
cakes.

Conventional filtration:
Washing rate
For products that are recovered in the filtrate, it is
often necessary to wash the filter cake with water or a
salt solution to maximize the recovery yield as
correlated by Choudhury & Dahlstrom:
n

R ' = 1
......Eq(3.7)
100
Where:
R : weight fraction of solute remaining in the cake after washing (R=1.0
prior to washing)
E : percentage wash efficiency (usually between 35-86%)
n : volume of wash liquid per volume of liquid in unwashed cake (n=1.0)

Conventional filtration:
Washing rate
Assume P and during washing and filtration are the
same, washing rate per cross-sectional area is
represented as:
p
1 dV
=
......Eq(3.8)

A dt V =V f o c (V f / A)

If Vw is the volume of wash liquid at time tw:

dV
Vw = t w
......Eq (3.9)

dt V =V f

Conventional filtration:
Washing rate
From (3.9) we obtain:

Vw
t w p
1 dV
= tw
......Eq (3.10)
=

A
A dt V =V f o c (V f / A)
At the end of filtration process, the equation (3.5),
with neglecting Rm can be written as:
1

2pt f
......Eq (3.11)
=
A o c

Vf

Conventional filtration:
Washing rate
Subtitute (Vf / A) from equation 3.11 into 3.10:

p
Vw
=
A 2 o c t f

t w ......Eq (3.12)

From equation 3.11 and 3.12, the ratio of tw to tf is:

t w 2Vw
=
......Eq(3.13)
tf
Vf

Conventional filtration:
Washing rate
Write tw / tf in terms of (n), the ratio of the volume Vw
of wash liquid to the volume Vr of residual liquid in
cake:
tw
Vw Vr
=2
= 2nf ......Eq (3.14)
tf
Vr V f

where f is the ratio of Vr to Vf (filtrate at the end).

The ratio f can be determine by material balance.
Thus, for a given cake formation time tf, a plot of wash
time tw versus wash ratio, n will be a straight line.

Crossflow filtration:
Introduction
Divided into two categories depending on whether the
component being filtered is soluble or insoluble.

Crossflow filtration:
Dissolved species
A solution under pressure flows across the surface of
a membrane fluid is forced through the
membrane.
For a solute that is rejected by the membrane, there
will be a concentration gradient of this solute across
a stagnant boundary layer next to the surface of the
membrane.
Concentration polarization: elevation of the solute
concentration at the membrane surface (cw)
compared to that in the bulk solution (cb).

Crossflow filtration:
Dissolved species
At steady state, the rate of convective mass transfer of solute toward
the membrane surface must be equal to the rate of mass transfer of
solute diffusion away from the membrane surface:

dc
Jc = D ......Eq(3.15)
dx
For boundary layer thickness :

cw
J = ln ......Eq (3.16)
cb
D

Or

cw
J
= exp
......Eq(3.17)
cb
D

where;:
J = transmembrane fluid flux
c = solute concentration
D = diffusion coefficient of solute
= boundry layer thickness
k = mass transfer coefficient
cw/cb = polarization modulus

Crossflow filtration:
Dissolved species
For high Mw solutes (small D) and membrane with
high solvent permeability (high J), concentration
polarization can become severe, with cw/cb >10.
At high cw/cb, the solubility of the solute can be
exceeded, resulting in the precipitation of the solute
and the formation of a solid or gel layer on the
membrane surface.

Crossflow filtration:
Dissolved species
Mass transfer coefficient, k for laminar flow (Re < 1,000 or
2,000):
D

k = 0.816 w
L

For a rectangular slit:

3ub
w =
h
For a circular tube
8ub
w =
D

Where:
w : fluid shear rate at the membrane surface
L : length of flow channel over membrane
ub : bulk stream velocity

Crossflow filtration:
Dissolved species
Mass transfer coefficient, k for turbulent flow (Re >2,000 or
4,000):
Dh b

kDh
Where
:
Re
=
and
=
Sc
Sh =
= f (Re, Sc, L Dh )

D
D
Typical correlation for Sherwood number:

Sh = 0.082 Re 0.69 Sc 0.33

Note:
Dh

= equivalent diameter of the channel

= 4(cross section area/wetted perimeter)

Crossflow filtration:
Insoluble species
o Suspended particles form a cake layer (a.k.a gel layer in
ultrafiltration) at the surface of membrane.
o Microfiltration membranes are generally utilized
membranes having pores 0.1m and larger.
o Allow dissolved components pass through but retain
particles above a certain size.

Crossflow filtration:
Insoluble species
Cake layer initially grows with time, thus reducing the permeate
flux.
At steady state conditions, the layer reaches a constant
thickness, which is relatively thin if the shear exerted by the
fluid flowing tangentially to the membrane surface is high
enough.

Crossflow filtration:
Insoluble species
Two different theories developed for particles larger than
1m.
1. Shear-induced diffusion theory for small particle
Particles are randomly displaced from the streamlines in a
shear flow and collide with other particles.
Dominate for particles up to 30 to 40 m in size
The shear induce for 0.2 <<0.45, ( is particle volume
fraction in the bulk suspension):

Ds = 0.3 w 2 Where

yw

: particle radius
: fluid shear rate at membrane surface

Crossflow filtration:
Insoluble species
For laminar flow mass transfer coefficient in concentration
polarization model

k = 0.366 w
L

Where L : tube/channel length

k much more dependent on the shear rate at the wall than

k for dissolved species in laminar flow.

Crossflow filtration:
Insoluble species
2. Inertial lift for larger particle
Arises when the Re based on the particle size is not negligible.
Produces a velocity that carries particles away from the
membrane surface.
For fast laminar flow of dilute suspensions with thin fouling
layers, the steady state transmembrane flux, J :
J=

0.036 o 3 w2

The flux strongly dependent on the

particle size & shear rate at the
membrane surface.
Flux also not dependent at all on the
length of the filter (L) or on the
concentration of particles in the bulk
suspension.

where
: density of permeate
: viscosity of permeate
: particle radius
w : fluid shear rate at membrane surface

Crossflow filtration:
Insoluble species
The flux strongly dependent on the particle size &
shear rate at the membrane surface.
Flux also not dependent at all on the length of the
filter (L) or on the concentration of particles in the
bulk suspension.

Membrane fouling

Process whereby a solution or a particle is deposited on

a membrane surface or in membrane pores.

Membrane fouling
Fouling results from physical or chemical interactions
between the membrane and various components that
are present in the process stream.

Leads to a decline in the permeate flux and a change

in the membrane selectivity.

Membrane fouling
It can be divided into reversible and irreversible fouling based on the
attachment strength of particles to the membrane surface.
Reversible fouling can be
removed by a strong shear
force or backwashing.

Irreversible fouling is the

strong attachment of
particles which cannot be
removed by physical
cleaning.

Formation of a strong matrix of fouling layer with the solute during a

continuous filtration process will result in reversible fouling being
transformed into an irreversible fouling layer.

Membrane fouling :
Mechanisms
Filtration process starts (based on the
diameter of the particles)
1. Pore become narrowing &
constriction

2. Pore plugging

3. Solute deposition and formation of a

gel or cake layer

Membrane fouling :
Mechanisms (example)
Flux decrease caused by proteins can be attributed to the
following processes:
Protein adsorption :
Interaction of proteins and
membrane, which occurs without
convective flow through the
membrane

Use
hydrophylic
membrane

Protein accumulation :
Membrane surface exposed to the
flowing process stream as a result of
concentration polarization, which can
lead to formation of a gel layer.

Protein deposition :
Addition of more protein that
is associated with membrane,
over and above the protein
that would be adsorbed in a
non-flowing system.

Increase fluid
shear rate at
filtering surface

Membrane fouling :
Mechanism
The three process can lead to pore narrowing:
o constriction, plugging and solute deposition

Protein fouling within the membrane can be

completely eliminated by making the pore size small
enough.

Membrane fouling :
Control measures
1) Cleaning

Physically

Biologically

Uses sponges, water

jets, backflushing
with permeates

Uses biocides to
remove all viable
microorganisms.

Chemically
Use of acids and
bases to remove
foulants and
impurities.

Membrane fouling :
Control measures
2) Appropriate membrane selection
The nature of the feed water must first be known; then a
membrane that is less prone to fouling with that solution is
chosen. For aqueous filtration, a hydrophilic membrane is
preferred.
3) Choice of operating conditions
For instance, crossflow filtration is always preferred to dead-end
filtration, because turbulence generated during the filtration
entails a thinner deposit layer and therefore minimizes fouling.

Filter media & equipment:

Conventional filtration (filter media)
Most commonly filter media used:
Woven fabric

Metal fabric

Chemical resistance of
the fabric is a primary
consideration.
Minimal or no
leaching of
components from the
fabric during filtration
Withstand any
chemicals used during
cleaning.
Minimum size of
particles trapped in
woven fabrics is 10
m.

Available in several
types of weave in nickel,
copper, brass,
aluminum, steel,
stainless steel.
Desirable when good
resistance to leaching
and corrosion is
required & at high
temperature operation.
Minimum size of
particles trapped in
woven wire media is 5
m.

Rigid porous
medium
Available in sheets &
tubes.
A wide variety of
materials are available
for rigid porous media,
including sintered
stainless steel and other
metals, silica, porcelain,
and some plastics.

Filter media & equipment:

Conventional filtration (filter media)
Sterile filtration in biopharmaceutical production is
usually carried out in the conventional mode.
Asymmetric membrane filter is used in cartridge style.
Made of cellulose esters or other polymers
Pore sizes of 0.22 or 0.45 m.

Filter media & equipment:

Conventional filtration (filter media)
Two types of filter for sterile filtration of air:
1.

Vent filter
Installed on all equipment that need to be filled or drained such as
product tank.
Hydrophobic asymmetric membrane filters
Rated at 0.22m.

2.

HEPA (high efficiency particulate air) filter

Large & high throughput ventilation filters.
Depth type filter: can collect microbes and other airborne particulates at
high flow rates.
Consist of compacted beds of pads of fibrous material such as glass wool.
Minimum particle collection efficiency: 99.97% for 0.3m diameter
particles.
Filter made of pleated borosilicate glass.

Filter media & equipment:

Conventional filtration (filter aids)
Filter aids:
Significantly improve the filtration operation by adding a
powdered solid to a feed that is to be filtered.

Added
directly to the
feed

Applied to the
filtration
equipment

Filter media & equipment:

Conventional filtration (filter aids)
Properties of the filter aids:
Inert materials, incompressible, insoluble, and irregularly shaped
Highly permeable, chemical resistance, compatibility with the
product.
Examples: diatomite, asbestos, cellulose and perlite.

Filter media & equipment:

Conventional filtration (filter aids)
Filter aids (examples)
Diatomite
Skeletal remain of diatoms,
which are type of algae
Skeletal structure give high
intrinsic permeability
Consists mostly of silica and thus
is insoluble in both strong acids
and alkalies

Perlite
Glassy volcanic material
consisting mainly of aluminum
silicate with some combined
water
Expands on heating during
processing to give highly porous
particles
Used for rough filtration: high
flowrate and less significance is
given to filtrate clarity.

Filter media & equipment:

Conventional filtration
Equipment for filtration is classified according to:
Driving
force
Pressure

Vacuum

The equipment is designed for:

Batch
Semicontinuous
continuous

Gravity

Filter media & equipment:

Conventional filtration
Batch filter
Most common type: plateand-frame filter press.
Consists of a varying
number of filter chambers
with either mediumcovered recessed filter
plates, or medium-covered
plates alternated with
frames that provide space
for the cake.

Filter media & equipment:

Conventional filtration
Batch filter operation (plate and frame)
The chambers are closed
and tightened by a
hydraulic ram or screw
that pushes the plates
and frames together.

The feed enters the

filter press under
pressure and fills each
chamber
simultaneously.

The clear filtrates is

taken off at a discharge
outlet.

Mechanized system to
open and close the
filter press.

The liquid passes

through the filter
medium and the solids
are retained on the
filter medium.

Filter media & equipment:

Conventional filtration
Batch filter
Other type : horizontal or vertical leaf filter,
plate filter, tray filer, tube or candle filter, and
Nutsch filter.
Example : vertical leaf filter operation
Filter leaves are covered with the
filter medium on either side.
The filtrate passing into the inside of
each filter leaf flows into a filtrate
manifold.

Filter media & equipment:

Conventional filtration
Semicontinuous or continuous filter
Most common type Rotary vacuum filter

Operation:
Drum rotates slowly and is partially
submerged in a slurry reservoir.
Surface of the drum is covered with the
filter medium and a vacuum is maintained
below the medium on the inside of the
drum.
Liquid is sucked through the filter medium
and solids are retained on the filter
medium.
Filtration is followed by cake washing and
dewatering.

Filter media & equipment:

Crossflow filtration
Filter media for crossflow filtration are generally
referred to as membrane.
General categories of membranes:

Microfiltration

Nanofiltration

Ultrafiltration

Hyperfiltration /
Reverse osmosis

Filter media & equipment:

Crossflow filtration
1) Microfiltration (MF) membrane

Bacteria & cell level

Membranes having pores 0.1 m and larger

2) Ultrafiltration (UF) membrane

Virus & protein level
Pore size in the range of 0.001 to 0.1 m
Usually classified by their molecular weight cutoff (MWCO),
which is the Mw of a globular solute at which the solute is
rejected by the membrane.
Typically 90% rejection level is used for establishing the MWCO.

Filter media & equipment:

Crossflow filtration
3) Nanofiltration
Pore sizes : RO < ranged from 1-10 nm < MF & UF
Often used with low total dissolved solids water such as
surface water and fresh groundwater
Range of applications: water treatment, food processing,
pharmaceuticals

4) Reverse osmosis (RO) or hyperfiltration membrane

Soluble salts & metal ion level (<0.001m).
Pass only water & a very low flux of solutes.
Very good RO membranes rejects 99.7% or more of NaCl.

Filter media & equipment:

Crossflow filtration (reverse osmosis)
OSMOSIS
When two liquids with different concentrations of
a solute are separated by a semipermeable
membrane, the fluid has a tendency to move from
low to high solute concentrations for chemical
potential equilibrium.

REVERSE OSMOSIS
Process of forcing a solvent from a region of high
solute concentration through a semipermeable
membrane to a region of low solute concentration by
applying a pressure in excess of the osmotic pressure.

Filter media & equipment:

Crossflow filtration (reverse osmosis)

Filter media & equipment:

Crossflow filtration (reverse osmosis)
Reverse osmosis a.k.a hyperfiltration, is the finest
filtration known which allow the removal of particles
as small as ions from a solution.
Reverse osmosis is used to purify water and remove
salts and other impurities in order to improve the
color, taste or properties of the fluid.

Filter media & equipment:

Crossflow filtration (reverse osmosis)
Reverse osmosis uses a membrane that is semipermeable, allowing the fluid that is being purified to
pass through it, while rejecting the contaminants that
remain.
The process of reverse osmosis requires a driving force
to push the fluid through the membrane, and the most
common force is pressure from a pump.
The higher the pressure, the larger the driving force.

Filter media & equipment:

Crossflow filtration (reverse osmosis)
As the concentration of the fluid being rejected
increases, the driving force required to continue
concentrating the fluid increases.
The separation of ions is aided by charged particles.
This means that dissolved ions that carry a charge, such
as salts, are more likely to be rejected by the
membrane than those that are not charged, such as
organics.
The larger the charge and the larger the particle, the
more likely it will be rejected.

Filter media & equipment:

Crossflow filtration
Basic structures for membranes
Homogeneous:
No significant variation in
pore diameter from the
filtering surface to the
other side.

Assymetric:
Consist of a number of
layers, each with different
structures and permeability

Composites:
Similar to the asymmetric membrane
but layers of the membrane are made
of different types of material.

Filter media & equipment:

Crossflow filtration
Filtration membranes materials:
Made from a wide variety of polymers and inorganic
materials.
Polymers: cellulose acetate, polyamide, polyether,
polycarbonate, polyester, polypropylene, polyethylene,
regenerated cellulose, poly(vinyl chloride) poly(vinylidene
fluoride) (PVDF), poly(tetrafluoroethylene) (PTFE),
acrylonitrile copolymers, polysulfones.
Inorganic materials: ceramics, zirconium oxide, borosilicate
glass, stainless steel, silver

Filter media & equipment:

Crossflow filtration
Equipment
The membranes are housed in a physical unit call a module.
Five types of module configuration for crossflow filtration:
Hollow
fiber

Rotating

Tubular

Flat plate

Spiral
wound

Filter media & equipment:

Crossflow filtration (Hollow fiber)
Consists of an array of narrow-bore,
self-supporting fibers (generally
have an asymmetric membrane
structure)
Typically involves laminar flow.
Cleaned by backflushing
Disadvantage:
Rupture of even a single fiber entire
module need to be replaced.
Feed streams generally need to be
prefiltered to avoid flugging of the
small-diameter fibers

Filter media & equipment:

Crossflow filtration (Tubular module)
Feed flows through the inside of the tubes, while the permeate
flows radially outward across the membrane and support tube.
Typically operated in the turbulent flow regime.
Large diameter of the tube relatively high pumping cost.
Highly resistant to plugging by particulate, cleaned by
backflushing and no prefiltration.

Filter media & equipment:

Crossflow filtration (Flat plate)
Most are in a rectangular
Plate module
configuration.
Flow channel can be open or have
separator screen to improve mass
transfer.
Unit with open channel usually
operated in laminar flow.
Backflushing is often impractical
because the membrane are
effectively supported only on one
side.

Filter media & equipment:

Crossflow filtration (Spiral-wound)
Constructed from flat sheet membranes separated by spacer
screens.
Feed solution is fed into one end of the module and flows
through the separator screens along the surface of the
membrane.
Retentate is then collected on the other end of the module.
Permeate spirals radially inward,
eventually to be collected through a
central tube.
Flow tend to be turbulent.
Main disadvantage susceptible to
fouling by particulates because of the
narrow and irregular flow through the
spacers.

Filter media & equipment:

Crossflow filtration (Rotating type module)
Feed flows into a thin annular region
between two concentric cylinders.
Either cylinder or both can be porous and
can have a membrane bound to the
surface.
With the membrane on the inner cylinder,
permeate is collected in the central
chamber. When the membrane is on the
outer cylinder, permeate is collected in a
separate annular permeate region adjacent
to the outer porous cylinder.

Filter media & equipment:

Crossflow filtration (Rotating type module)
Inner cylinder rotate at high speed (>3000rpm): create vortices
to increase mass transfer and reduce thickness of cake/gel.
One advantage: rate of mass transfer is determined almost by
the rate of rotation of the inner cylinder which decoupled the
mass transfer from the feed flowrates (can be operate at low
feed flowrate and minimum pumping cost)
High energy requirements for rotating the device is very high,
capital cost also high and difficult to scale up.
Limited to small-scale operation.

Filter media & equipment:

Crossflow filtration

Filter media & equipment:

Crossflow filtration
Requirements for membrane module
1. Mechanical
Effective (physical) separation of the feed and permeate
streams.
Provide necessary physical support for the membrane (the
ability of the module to endure the required pressure drops
and backflushing).

Filter media & equipment:

Crossflow filtration
2. Hydrodynamic
Minimize pressure drops through the module (reduce
pumping cost).
Optimize solute mass transfer (reduce concentration
polarization).
Minimize particulate plugging or fouling.
Avoid dead spots (for sanitary design)

Filter media & equipment:

Crossflow filtration
3. Economic
Maximize membrane packing density (ratio of membrane
area to module volume).
Minimize manufacturing costs.
Permit easy access for cleaning and/or membrane
replacement.
Provide sufficient chemical resistance and operational
lifetime.
Incorporate modularity of design for easy scale up, staging,
or cascading

Filtration Principles
Direction of feed
flows to the
medium
Conventional
Darcys Law

Crossflow
Dissolves species
(soluble)
Suspended particles
(insoluble)

Filter Media and Equipment

Conventional
Media

Woven
fabrics
Metal
fabrics /
screens

Rigid
porous
media

Aid
Sterile
filtration
of
solution
HEPA
Vent
filter

Equipment

Diatomite

Batch

Perlite

Semicontinuous/
continuous

Crossflow

Media /
membrane

Types

Equipment / Module
configuration
Basic structure

Materials

Hollow fiber
Tubular membrane

Ultrafiltration

Homogenous

Polymer
Flat plate

Microfiltration
Nanofiltration
Hyperfiltration /
RO

Asymmetric
Composite

Organic
material

Spiral wound
Rotating type