ERT 313 :

BIOSEPARATION ENGINEERING

Mechanical - Physical Separation Process

Students should be able to;

APPLY and CALCULATE based on

filtration principles; ANALYZE cake
filtration, Constant Pressure Filtration,
Continuous Filtration and Constant Rate
Filtration.
Introduction
• Filtration is a solid-liquid separation where the
liquid passes through a porous medium to remove
fine suspended solids according to the size by
flowing under a pressure differential.

• The main objective of filtration is to produce high-

quality drinking water (surface water) or high-
quality effluent (wastewater)
2 categories of filtration, which differ according to the
direction of the fluid feed in relation to the filter
medium.

Minimize buildup of solids on the

Results in a cake of solids filter medium
depositing on the filter medium
 Application of Filtration in
Bio-industry
Recovery of crystalline solids
Recovery of cells from fermentation
medium
Clarification of liquid and gasses
Sterilization of liquid for heat sensitive
compound
 Filtration Equipment
Filtration for biological materials is generally completed using batch
filtration, rotary drum filtration, or ultrafiltration methods.

1. Batch Filtration
• Usually performed under constant pressure with a pump that
moves the broth or liquor through the filter
• Filter cake will build-up as filtration proceeds and resistance
to broth flow will increase
• The filter press is the typical industrial version of a batch
vacuum filter, using a plate and frame arrangement
• Can be used to remove cells, but does not work particularly
well for animal cell debris or plant seed debris
 Cont….Filtration Equipment
2. Rotary Drum Filtration
• Rotary vacuum filters can be used to efficiently remove
mycelia, cells, proteins, and enzymes, though a filter aid or
precoat of the septum may be necessary

3. Ultrafiltration
• Utilizes a membrane to separate particles that are much larger
than the solvent used
• Successful removal occurs in the partical size range of 10
solvent molecular diameters to 0.5 μ
 Filter Media
• To act as an impermeable barrier for particulate matter.
• Filtration media for cross-flow filtration are generally referred
as “MEMBRANE”
• First and foremost, it must remove the solids to be filtered
from the slurry and give a clear filtrate
• Also, the pores should not become plugged so that the rate of
filtration becomes too slow
• The filter medium must allow the filter cake to be removed
easily and cleanly
• Some widely used filter media (for conventional filtration) like
filter paper, ceramics, synthetic membrane, sinterd &
perforated glass, woven materials (woven polymer fiber).
 Filter Aids
• Substance (solid powder)that are mixed with the feed for
creating very porous cakes ( increase filtration rate very
significantly)
• Can be added to the cake during filtration to increases
the porosity of the cake and reduces resistance of the
cake during filtration
• Can also be added directly to the feed to:
i) maintain the pores in the filter cake open
ii) Make the cake less compressible
iii)Provide faster filtration
• Common types of filter aid is diatomite (types of algae)
and perlite. The structure of diatomite
particles gives them a high
intrinsic permeability
 Filtration Principles
• When a slurry containing suspended solids flow against a filter medium by the application of a
pressure gradient across the medium, solids begin to build up on the filter medium
• The buildup of solids on the filter medium is called a cake
• This type of filtration is sometimes referred to as “dead-end” filtration
• Darcy’s law describes the flow of liquid through a porous bed of solids and can be written as follows:
(1)

• where V is the volume of filtrate, t is time, A is the cross-sectional area of exposed lilter medium, Δp is
the pressure drop through the bed of solids (medium plus cake), µ0 is the viscosity of the filtrate, and R is
the resistance of the porous bed. In this case, R is a combination of the resistance Rm of the filter
medium and the resistance Rc of the cake solids:
(2)

• It is convenient to write the cake resistance Rc in terms of specific cake resistance α as follows:

(3)
• where ρc is the mass of dry cake solids per volume of filtrate.
• Thus, the resistance increases with the volume filtered
• Combining Eq. (1), (2) and (3), we obtain

(4)
 Incompressible Cake
• For the case of zero filtrate at time zero (before start an exp),
integration of this equation yields

(5)

At V   o Rm
 K   B K
•  A where 2P and B 
V P

Y  mX  C (can determine specific cake resistance,α and

medium resistance, Rm by plotting the graph)

In a cake filtration process where a significant amount of cake is allowed to

accumulate, the medium resistance, Rm become neglegible compare witn the cake
 o  V 
2
resistance. (Rm=0). So,
t  
2P  A 
Example 1
Batch Filtration
A Buchner funnel 8 cm in diameter is available for testing the filtration of a cell
culture suspension, which has a viscosity of 3.0 cp. The data in Table E1 were
obtained with a vacuum pressure of 600 mm Hg applied to the Buchner funnel.
The cell solids on the filter at the end of filtration were dried and found to weigh
14.0 g.
Determine the specific cake resistance α and the medium resistance
Rm. Then estimate how long it would take to obtain 10,000 liters of filtrate from
this cell broth on a filter with a surface area of 10 m2 and vacuum pressure of
500 mm Hg.

TABLE E1
 Example 1
Solution
According to Equation (5), we can plot t/(V/A) versus V/A and obtain α from the slope
and Rm from the intercept. We see that the data are reasonably close to a straight line.

(5)
Figure E1
Plot of batch
filtration data
At V 
 K   B for the
V  A determination
of α and Rm.

Y  mX  C

A linear regression of the data in this plot gives the following results (Figure E1):
 Example 1
From these values, we can calculate α and Rm:

This is a typical value of Rm for a large-pore (micrometer-sized) filter .

To determine the time required to obtain 10,000 liters of filtrate using a filter
with an area of 10 m2, we must make the assumption that α does not change at
the new pressure drop of 500 mm Hg. We use Equation (5) and solve for time:
(5)
 Example 1
(5)

We calculate the two components of this equation as follows:

and finally

Thus, this filter is probably undersized for the volume to be filtered. In addition, from this
calculation we see that at the end of the filtration,

Therefore, the filter medium is contributing very little of the resistance to

filtration, a typical situation in a lengthy dead-end filtration.
 Compressible Cake
• Almost all cakes formed for biological material are compressible.
• As these cake compressed, filtration rate drop (flow become relatively more
difficult as pressure increase)
• The pressure drop is influence by α, the specific cake resistance
• α can be increased if the cake is compressed
• The specific resistance of the cake is directly affected by Δpc, the pressure drops
across the cake
• Studies have shown that the relationship between specific resistance and pressure
drop commonly takes the form:

(6)

• where α’ and s are empirical constants.

• The power s has been called the “cake compressibility factor”. (for incompressible
cake, s=0 and for compressible cake, s=0.1-0.8)
 Cake Washing
• After filtration, the cake contains a significant amount of
solute-rich liquid broth that usually removed by washing
the cake
• 2 function of washing:
A) displaces the solute-rich broth trapped in pores in
the cake
B) allows diffusion of solute out of the biomass in
the cake(enhance recovery if the desired
product is in the biomass)
• It is often necessary to wash the filter cake with water or a salt solution to maximize the
removal of dissolved product from the cake.
• Frequently, the wash must be done with more than the volume of the liquid in the cake
because some of the product is in stagnant zones of the cake, and transfer into the wash
liquid from these zones occurs by diffusion, which takes place at a slower rate than the
convective flow of wash through the cake
• Data for the washing of the filter cakes has been correlated by Choudhary and Dahlstrom
using the following equation:
(7)

• where R’ is the weight fraction of solute remaining in the cake after washing (on the basis
that R’ = 1.0 prior to washing), E is the percentage wash efficiency, and n is the volume of
wash liquid per volume of liquid in the unwashed cake.
• Assuming that the liquid viscosity and the pressure drop through the bed solids are the same
during the filtration of the solids, the washing rate per cross-sectional area can be found
from the filtrate flow rate per unit area given in Equation (4) at the end of the filtration
• Thus, for negligible filter medium resistance for filtrate volume Vf at the end of time tf to
form the cake, this yields
(8)
 Filtration Principles
• If Vw is the volume of wash liquid applied in time tw, then
(9)

• Using the definition of (dv/dt)V=Vf from Eq. (8), we obtain

(10)

• At the end of filtration, the integrated form of the filtration equation (Eq. 5), with Rm
neglected, can be written

(11)
• Substituting this expression for Vf/A in Eq. (10) and simplifying gives

(12)
 Filtration Principles
• From Eq. (11) and (12), the ration of tw to tf is

(13)
• It is helpful to write tw/tf in terms of n, the ration of the volume Vw of wash liquid to the
volume Vr of residual liquid in the cake:

(14)

• where f is the ratio of Vr to the volume Vf of filtrate at the end of filtration.

• The ratio f can be determined by a 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
 Example 2
Rotary Vacuum Filtration
It is desired to filter a cell broth at a rate of 2000 liters/h on a rotary vacuum filter at a
vacuum pressure of 70 kPa. The cycle time for the drum will be 60 s, and the cake
formation time (filtering time) will be 15 s. The broth to be filtered has a viscosity of 2.0
cp and a cake solids (dry basis) per volume of filtrate of 10 g/liter. From laboratory tests,
the specific cake resistance has been determined to be 9 x 10 cm/g.
Determine the area of the filter that is required. The resistance of the filter medium can be
neglected.

Solution:
We can use the integrated form of the filtration equation, Equation (5), with Rm = 0:

We solve for A2 to obtain

In applying this equation, it is helpful to focus on the area of the drum, which is where the cake
is being formed and where filtrate is being obtained.
Thus, A is the area of that part of the drum. We can calculate the
volume of filtrate that needs to be collected during the cake
formation time of 15 s:

We use this volume of filtrate with t = 15 s in the equation for A2 to

obtain

The area A’ of the entire rotary vacuum filter can be calculated from
the cake formation time (15s) and the total cycle time (60s) as

This is a medium-sized rotary vacuum filter, with possible dimensions of

1.0 m diameter by 1.0 m long.
 Example 3
Washing of a Rotary Vacuum Filter Cake
For the filtration in Example 2, it is desired to wash a product antibiotic out of the cake so
that only 5% of the antibiotic in the cake is left after washing. We expect the washing
efficiency to be 50%. Estimate the washing time per cycle that would be required.

Solution;
From Equation (7) for the washing efficiency of a filter cake

where R’ is the weight fraction of solute remaining in the cake after washing (on the
basis of R’ = 1.0 before washing), E is the percentage wash efficiency, and n is the
volume of wash liquid per volume of liquid in the unwashed cake. Substituting R’ = 0.05
and E = 50% into this equation gives

From Equation (14), the relationship between the washing time tw, and the cake
formation time tf is given by
where f is the ratio of volume Vr of residual liquid in the cake to the
volume of filtrate Vf
after time tf. Thus, we need to estimate the volume of residual liquid in
the filter cake to determine tw. At the end of the 15 s cake formation
time,

Volume of filtrate need to be

Cake solids per volume
collected during the cake formation
of filtrate
time of 15s
Assuming the cake is 70 wt% water, which is typical for filter cakes, we
find m
 , so
V
Thus, m 194 g
V    0.194l
 1000 g / l
 Crossflow filtration

 as for conventional filtration, scale up of crossflow

requires data from laboratory or pilot-scale units
 the determination of the size of a plant unit can be
done by a direct scaleup of the filtration area based on
the feed or output flow rate
 continued

 for this scaleup, however, it is important that the

following variables be kept constant:
inlet and outlet pressures
crossflow (or tangential) velocity
flow channel sizes (height and width)
Feed stream properties – test slurries should be
representative of the actual process streams
Membrane type and configuration – test data from one
design cannot directly be used to design another
geometry
 four basic modes of operation of CFF: batch
concentration, diafiltration, purification and complete
recycle (figure 3.11)
Figure 3.11: The four basic modes of operation of C/flow
filtration (CF=crossflow filter)
 continued

Mode Description
Batch The retained stream containing the product suspended
concentration particles or dissolved macromolecules is reduced in vol.
Diafiltration The vol. of the retained stream is maintained constant by the
continuous addition of water or buffer which results in the
removal of low MW solutes into the permeate
Commonly used when salt removal or exchange is desired
Purification A low MW product passes into the permeate and is thus
separated from higher MW impurities or
The product can be retained and impurities removed in the
filtrate
Complete Both the retained stream and the permeate are returned to the
recycle feed tank
Systems may be operated in complete recycle at start-up to
reach steady state, saturate the membranes, test for leaks and
blockage and adjust the feed rate
 continued

 in designing a diafiltration process, a decision must be

made about the concentration of retained product at
which to operate
 as this concentration is increased, the filtration flux will
decrease according to eqn. (3.16), and
 the total vol. of filtrate will decrease for the removal of
a given percentage of a low MW solute
 this leads to an optimum concentration to minimize the
time required which can be determined mathematically
if the relation between filtrate flux and concentration in
the bulk fluid (cb) is known
 continued

 the basic components in the design of a c/flow filtration

sys. are shown in figure 3.12
 a pump flows the feed through the filtration module to
give a permeate and a retentate or retained stream
 the pump needs to be sized to provide the desired flow
velocity and pressure
 the TMP is controlled by a back-pressure valve on the
retentate stream exiting from the filtration module
 thus the TMP drop is estimated by

PTM   pi  p0   p p
1 (3.28)
2
 continued

 where pi and po are the retentate pressures in and out

of the module respectively and
pp = the pressure of the outlet permeate

 in designing a CFF system – important to minimize

the occurrence of gas-liquid interfaces, since bioproduct
denaturation, especially of proteins, can occur at these
interfaces in the presence of mechanical shear and
turbulent flow
 continued

Figure 3.13: Comparison of (a) batch

and (b) single-stage continuous (feed-
and-bleed) crossflow
filtration systems

Figure 3.12:Basic components

of a crossflow filtration system.
 continued

 CFF systems : operate in batch or the continuous mode

(Figure 3.13)
 batch system : feed is pumped through the filtration
module and then back to the feed tank
 variation mode (semibatch) for diafiltration: fluid is
continuously added to the feed tank to keep the feed
volume constant (3.11b)
 continuous mode of operation (“feed-and-bleed” or
“retentate bleed”): feed is added to a recirculation loop
by the feed pump, and concentrate exiting in the retained
stream is withdrawn from the system so that the
concentration factor is at the desired value
 continued

 * concentration factor : i.e. conc. in the retentate

divided by the conc. in the feed)
 when steady state – achieved, the concentrate will be at
its max. conc.- means that the filtration flux will be at a
min. throughout the run
 generally, more economical to use a multistage system
in a continuous process (Figure 5.14)
 continued

 Figure 5.14: Multistage CFF system using the retentate

bleed mode
 continued

 as more stages are added, the ave. filtration flux

approaches that for a batch sys., thus the total filtration
area decreases
 refer to table 3.2 – batch UF operation is compared
with continuous operation using one, two, three and five
stages
 continuous operation : economical – reduced tankage –
preferable to batch operation for most large –scale UF
operations
 another advantage: it permits the minimization of the
residence time of the product in the CFF unit (important
for products that are sensitive to heat or shear)
 Table 3.2: Comparison of Batch and Continuous UF System

System b Flux (litersm-2h-1) Total area (m2)

Batch 33.1 (average) 136
Continuous
One-stage 8.1 555
Two-stage 31.1 243
8.1
Three-stage 38.7 194
23.4
8.1
Five-stage 44.7 165
35.6
26.4
17.3
8.1
 b System design for 10x conc. factor and feed rate of 5000liters/h .Flux from J = 20ln(30/cb)
Cell disruption / lysis is a method or process for
releasing biological molecules from inside a cell
(breaking / lysing cells and tissues)

Biotechnological products produced by different

types of cells can be intracellular or extracellular.

If these are intracellular (inside the cell), the cells

have to be disrupted to release these products
before further separation can take place.
 Types of Cell Need to Disruption
Ease  Bacteria ( gram +ve @ gram –ve)
of cell  Yeast
breaks
 Culture (plant culture @ animal culture)

Gram-positive Gram-negative
Thick wall No wall (got multilayer
enveloped)
 Some Elements of Cell Structure
Prokaryotic Cells
• Cells that do not contain a membrane-enclosed
nucleus.
• The bacteria cell envelope consists of an inner plasma
membrane that separates all contents of the cell from
the outside world, a peptidoglycan cell wall, and outer
membrane
• Bacteria cells with a very thick cell wall stain with
crystal violet (Gram stain) and are called “Gram
positive”, while those with thin cell wall stain very
weakly – “Gram negative”
 Some Elements of Cell Structure
Eukaryotic cells
• Eukaryotic cells (cells with nuclei and internal
organelles) are considerably more complicated than
prokaryotic cells, and bioproducts may have to
released from intracellular particles that are
themselves coated with membranes and/or consist
of large macromolecular aggregates
• The eukraryotes includes fungi, and, of course, the
higher plants and animals
• The cell membrane of animal cells is easily broken,
whereas the cell wall of plants is strong and
relatively difficult to break
Figure : Eukaryotic cells. Simplified diagrammatic representation of
an animal cell and a plant cell.
Different cell disruption techniques are used. These
include:

Physical methods
•Disruption in ball mill or pebble mill
•Disruption using a colloid mill
•Disruption using French press
•Disruption using ultrasonic vibrations

Chemical methods
•Disruption using detergents
•Disruption using enzymes e.g. lysozyme
•Combination of detergent and enzyme
•Disruption using solvents
 Mechanical Methods for Cell Lysis

• Sonication
• Ball milling
• Pestle homogenization
• Shearing devices
(blender)
• High pressure
homogenizers
• Bead mills
 Bead mill

Cascading
beads
Rolling
beads Cells being
disrupted

• Disruption takes place due to the grinding action of the

rolling beads and the impact resulting from the cascading ones
• Bead milling can generate substantial heat
• Application: Yeast, animal and plant tissue
• Small scale: Few kilograms of yeast cells per hour
• Large scale: Hundreds of kilograms per hour.
Colloid mill
Rotor
Disrupted
cells

Cell Stator
suspension

• Typical rotation speeds: 10,000 to 50,000 rpm

• Mechanism of cell disruption: High shear and turbulence
• Application: Tissue based material
• Single or multi-pass operation
ERT 313/4 BIOSEPARATION ENGINEERING
SEM 2 (2010/2011)
 Separation of cells and medium
• Recovery of cells and/or medium
(clarification)
– For intracellular enzyme, the cell
fraction is required
– For extracellular enzymes, the culture
medium is required
• On an industrial scale, cell/medium
separation is almost always
performed by centrifugation
– Industrial scale centrifuges may be
batch, continuous, or continuous with
desludging
CENTRIF UGATION
A centrifuge is used for separating particles from a
solution according to their size, shape, density and
viscosity of the medium by the application of an
artificially induced gravitational field.

In bioprocesses, these particles could be cells, sub

cellular components, viruses and precipitated forms
of proteins and nucleic acids.

Centrifugation can be used to separate cells

from a culture liquid, cell debris from a broth, and a
group of precipitates.

Centrifugation may be classified into two types:

•Analytical centrifugation
•Preparative Centrifugation
 Industrial centrifuges
Tubular Bowl Centrifuge
• Most useful for solid-liquid separation with
enzymatic isolation
• Can achieve excellent separation of
microbial cells and animal, plant, and most
microbial cell debris in solution

Disc Bowl Centrifuge

• Widely used for removing cells and animal
debris
• Can partially recover microbial cell debris
and protein precipitates
Perforate Bowl Basket Centrifuge
• Exception at separation of adsorbents,
such as cellulose and agarose

Zonal Ultracentrifuge
• Applied in the vaccine industry
because it can easily remove cell debris
from viruses
• Can collect fine protein precipitates
• Has been used experimentally to purify
RNA polymerase and very fine debris
in enzymes
Properties of industrial centrifuges
• Tube
– High centrifugal force – Limited solids capacity
– Good dewatering – Difficult to recover protein
– Easy to clean
• Chamber
– Large solids capacity – No solids discharge
– Good dewatering – Cleaning difficult
– Bowl cooling possible – Solids recovery difficult
• Disc type
– Solids discharge – Poor dewatering
– Difficult to clean
– No foaming
– Bowl cooling possible
Centrifugation properties of different cell types

• Bacteria
– Small cell size – High speed required
– Resilient – Low cell damage
• Yeast cells
– Large cells – Lower speed required
– Resilient – Low cell damage
• Filamentous fungi
– Mycelial – Lower speed required
– Resilient – High water retention in pellet
• Cultured animal cells
– Large cells – Very susceptible to damage
– Very fragile
 Forced Developed in Centrifugal Separation
1. Introductions
• Centrifugal separators use the common principal
that an object whirled about an axis or center
point a constant radial distance from the point is
acted on by a force

• The object is constantly changing direction and is

thus accelerating, even though the rotational
speed is constant

• This centripetal force acts in a direction toward

the center of rotation
3.2. Sedimentation in a centrifugal field

3.2.1.1 Centrifugal settling or sedimentation

Use of centrifuges increases the forces on particles manyfold.

Hence, particles that will not settle readily or at all in gravity

settlers can often be separated from fluids by centrifugal force.

These high centrifugal forces do not change the relative settling

velocities of small particles, but these forces do overcome the
disturbing effects of Brownian motion and free convection currents.

Sometimes gravity separation may be too slow because of the

closeness of the densities of the particles and the fluid, or because of
association forces holding the components together as in emulsions.
 continued

 gravity and centrifugal sedimentation of a single particle are

illustrated in Figure 3.9

Figure 3.9: Gravity

and centrifuge
sedimentation of a
single particle.
Angular speed
(ω); distance of
particle to axis of
rotation (r), m =
mass, g = gravity
 continued

 An example in the dairy industry is the separation of cream

from whole milk, giving skim milk.
 Gravity separation takes hours, while centrifugal separation is
accomplished in minutes in a cream separator.
 Centrifugal settling or separation is employed in many food
industries, such as breweries, vegetable-oil processing, fish-
protein-concentrate processing, fruit juice processing to remove
cellular materials, and so on.
Centrifugal separation is also used in drying crystals and for
separating emulsions into their constituent liquids or solid—liquid
 continued

3.2.1.2 Centrifugal filtration

 Centrifuges are also used in centrifugal filtration, where a

centrifugal force is used instead of a pressure difference to cause the
flow of slurry in a filter where a cake of solids builds up on a screen.

 The cake of granular solids from the slurry is deposited on a filter

medium held in a rotating basket, washed, and then spun ‘dry.’
Centrifuges and ordinary filters are competitive in most solid—liquid
separation problems.
3.2.2 Forces developed in centrifugal separation

If the object being rotated is a cylindrical container, the contents of

fluid and solids exert an equal and opposite force, called centrifugal
force, outward to the walls of the container.

This is the force that causes settling or sedimentation of particles

through a layer of liquid or filtration of a liquid through a bed of filter
cake held inside a perforated rotating chamber

 In Fig. 3.10a cylindrical bowl is shown rotating, with a slurry feed of

solid particles and liquid being admitted at the center
Figure 3.10: Sketch of centrifugal separation: (a) initial slurry feed
entering. (b) settling of solids from a liquid, (c) separation of two
liquid fraction.
 continued

The feed enters and is immediately thrown outward to the walls of

the container, as in Fig. 3.10b.

 The liquid and solids are now acted upon by the vertical
gravitational force and the horizontal centrifugal force. The centrifugal
force is usually so large that the force of gravity may he neglected.

 The liquid layer then assumes the equilibrium position, with the
surface almost vertical. The particles settle horizontally out ward and
press against the vertical bowl wall.

 in Fig. 3.10c two liquids having different densities are being

separated by the centrifuge. The denser fluid will occupy the outer
periphery since the centrifugal force on it is greater.
 3.2.2.1 Equations for centrifugal force

In Fig 3.11 a schematic of a tubular-bowl centrifuge is shown.

The feed enters at the bottom, and it is assumed that all the liquid
moves upward at a uniform velocity carrying solid particles with it.
 The particle is assumed to be moving radially at its terminal
settling velocity υt.
 The trajectory or path of the particle is shown in Fig. 3.10.
 A particle of a given size is removed from the liquid if sufficient
residence time is available for the particle to reach the wall of the
bowl where it is held. The length of the bowl is b m.
 At the end of the residence time of the particle in the fluid, the
particle is at a distance rB m from the axis of rotation. If rB < r2, then
the particle leaves the bowl with the fluid.
Figure 3.11: Particle settling in sedimenting tubular-
bowl centrifuge.
 continued

If rB = r2 , it is deposited on the wall of the bowl and effectively

removed from the liquid.

In circular motion the acceleration due to the centrifugal force is

ae  r 2 E3.19
where ae is the acceleration from a centrifugal force in m/s2 (ft/s2),
r is radial distance from the center of rotation in m (ft), and ω is
angular velocity in rad/s

 The centrifugal force Fc in N (lbf ) acting on the particle is given

by
Fc  mae  mr 2
(SI) mr 2 E3.20
Fc  (English)
gc
 Where gc= 32.174lbm.ft/lbf.s2
 continued

Since ω = υ/r, where υ = the tangential velocity of the particle in m/s

 m 2
2
E3.21
Fc  mr  
r r
Often rotational speeds are given as N rev/min and
2N 60
 N E3.22
60 2r
 continued

For settling in the Stokes’ law range, the terminal settling velocity
at a radius r is obtained by substituting eqn. (3.19) for the
acceleration g into eqn. (3.8):
 2 rDp2  p    E3.23
t 
18

where υt = settling velocity in the radial direction (m/s)

Dp = particle diameter (m)
ρp = particle density kg/m3
ρ = liquid density in kg/m3 and
μ = liquid viscosity in Pa s,
 continued

If hindered settling occurs,

gD p2  p   
t 
18
  
2
p E3.24

Since υt = dr/dt, Eqn. (3.23) becomes

18 dr
dt  2 E3.25
  p   D p2 r

Integrating between the limits r = r1 at t = 0 and r = r2 at t = tT

18 r2
tT  E3.26
 2  p   D p2 r1
ln
 continued

V = πb (r22 – r12) , thus, the feed volumetric flow rate Q in m3/s is

 2  p   D p2  2  p   D p2
Q V   br2
 r12  E3.27
18 ln  r2  18 ln  r2 
2

 r1   r1 

Particles having diameters smaller than that calculated from

eqn. ( 3.27) will not reach the wall of the bowl and will go out with the
exit liquid.
Larger particles will reach the wall and be removed from the liquid.
 Notes:

centrifugation is most effective when the particles to be

separated are large, the liquid viscosity is low and the
density difference between particles and fluid is great
 it is also assisted by large centrifuge radius and high
rotational speed
 in centrifugation of biological solids such as cells, the
particles are very small, the viscosity of the medium can
be relatively high and the particle density is very similar
to the suspending fluid. These disadvantages – easily
overcome in the lab with small centrifuges operated at
high speed
 continued

 however, problems arise in industrial centrifugation

when large quantities of material must be treated
 centrifuge capacity cannot be increased by simply
increasing the size of equipment without limit;
mechanical stress in centrifuges increases in proportion
to (radius)2 so that safe operating speeds are
substantially lower in large equipment
 the need for continuous throughput of material in
industrial applications also restricts practical operating
speeds
 to overcome these difficulties, a range of centrifuges
has been developed for bioprocessing industry
 3.2.2.2 Sigma Analysis & Scale up

 commonly used analysis in industry is “sigma analysis” which

uses the operation constant Σ to characterize a centrifuge into which
feed flows at volumetric flow rate Q
 Estimation of Q the followed equation can be used:

Q = {υg} [Σ] E3.28

 where υt = the sedimentation velocity at 1 x g, namely

gD p2  p   
t  E3.29
18
 and Σ represents the geometry and speed of centrifuge and as the
cross-sectional area equivalent of the centrifuge with units of length
squared
 continued

 therefore, in eqn. (3.28) the accolades { } indicate properties of the

particle to be separated and of the fluid in which separation is
occurring and the brackets [ ] indicate properties of the centrifuge
 if two centrifuges perform with equal effectiveness:

Q1 Q2

1  2
where subscripts 1 and 2 denote the two centrifuges
 the above equation can be used to scale-up centrifuge equipment

 equations for evaluating Σ depend on the centrifuge design

 continued

 the above equations for Σ are based on ideal operating conditions

Because different types of centrifuge deviate to varying degrees
from ideal operation that equation cannot generally be used to
compare different centrifuge configurations
 performance of any centrifuge can deviate from theoretical
production due to factors such as
Particle shape and size distribution

Aggregation of particles

Non-uniform flow distribution in the centrifuge and

Interaction between particles during sedimentation

Experimental tests must be performed to account for these factors

3.2.3 Centrifuge Equipment

Figure 3.12:
Common types of
production
centrifuge:
(a) tubular bowl
(b) Multichamber,
(c) disk, nozzle (d)
disk, intermittent
discharge, (e) scroll
and
(f) basket. Arrows
indicate the path of
the liquid phase;
dashed lines show
where
the solids
accumulate
 The Operation Steps of Centrifuge Equipment
Centrifuge equipment is classified according to internal structure

Tubular-  the simplest configuration

bowl  widely employed in the food and pharmaceutical industries
centrifuge Feed enters under pressure through a nozzle at the bottom,
is accelerated to rotor speed and moves upwards through the
cylindrical bowl
As the bowl rotates, particles are traveling upward are spun
out and collide with the walls of the bowl as illustrated
schematically in Figure 3.13
Solids are removed from the liquid if they move with
sufficient velocity to reach the wall of the bowl within the
residence time of liquid in the machine
As the feed rate is increased the liquid layer moving up the
wall of the centrifuge becomes thicker;
this reduces performance of the centrifuge by increasing the
distance a particle must travel to reach the wall
 continued

= R1
= R0

Figure 3.13: Separation of solids in a tubular-bowl centrifuge

 continued

liquid from the feed spills over a weir at the top of the bowl;
solids which have collided with the walls are collected
separately
when the thickness of sediment collecting in the bowl reaches
the position of the liquid-overflow weir, separation efficiency
declines rapidly.This limits the capacity of the centrifuge
applied mainly for difficult separations requiring high
centrifugal forces
solids in tubular centrifuges are accelerated by forces between
13 000 and 16 000 times the force of gravity
 continued

 The equations of motion that give the trajectory of sedimented

particles - in the radial direction from equation (E3.23)
dR  rDp  p    (E3.30)
2 2

t  
dt 18
 then in the axial direction, due only to pumped flow, Q
dz Q Q
  (E3.31)
dt A  R0  R1 
2 2

 where A = the cross-sectional area for liquid flow in the

centrifuge. These equations of motion are combined to give the
trajectory equation dR
dt dR (E3.32)

dz dz
dt
 continued

 substituting equation (E3.30) and (E3.31) into this ratio

(E3.32), integrating dR between r1 and r2 and integrating dz
between 0 and b and solving for Q gives
 
  p   D  br22  r12  2 
2 (E3.33)
Q
p
 
 18  ln  2  
r
  r1  
 the first factor in equation (3.33) can be multiplied by g
while the second is divided by g to give, again, equation
(E3.28) for Σ analysis:
Q ={υg}[Σ] (E3.28)
 continued

 where for a tubular bowl centrifuge,

br22  r12  2
 (E3.34)
 r2 
g ln  
 r1 
 Example 3.5: Complete recovery of bacterial cells in a
tubular bowl centrifuge

It is desired to achieve complete recovery of bacterial cells

from a fermentation broth with a pilot plant scale tubular
centrifuge. It has been already determined that the cells are
approximately spherical with a radius of 0.5μm and have a
density of 1.10g/cm3. The speed of the centrifuge is 5000rpm,
the bowl diameter is 10cm, the bowl length is 100cm and the
outlet opening of the bowl has a diameter of 4cm. Estimate the
maximum flow rate of the fermentation broth that can be
attained.
Solution
 continued

Ultracentrifuge Used for

(A type of recovery of fine precipitates from high-density solutions,
narrow tubular- breaking down emulsions
bowl centrifuge) separation of colloidal particles such as ribosomes and
mitochondria
produces centrifugal forces 105-106 times the force of gravity
the bowl is usually air-driven and operated at low pressure or in
an atmosphere of nitrogen to reduce generation of frictional heat
a typical ultracentrifuge operates discontinuously so its
processing capacity is restricted by the need to empty the bowl
manually
continuous ultracentrifuge are available commercially
 continued

Disc-stack  many types of disc centrifuge; the principal difference between them
bowl is the method used to discharge the accumulated solid
centrifuge In simple disc centrifuges, solids must be removed periodically by
hand
Continuous or intermittent discharge of solids is possible in a variety
of disc centrifuges without reducing the bowl speed
Some centrifuges are equipped with peripheral nozzles for continuous
solids removal; others have valves for intermittent discharge
Another method is to concentrate the solids in the periphery of the
bowl and then discharge them at the top of the centrifuge using a paring
device; figure (3.14)
A disadvantage of centrifuge with automatic discharge of solids is that
the solids must remain sufficiently wet to flow through the machine
Extra nozzles may be provided for cleaning the bowl should blockages
of the system occur
 continued

Figure 3.14: Disc-stack bowl centrifuge with continuous discharge of

solids
 continued

Contain conical sheets of metal called discs - stacked one on

top of the other with clearances as small as 0.3 mm
The discs rotate with the bowl and their function is to split the
liquid into thin layers
As shown in figure (3.15), the feed is released near the bottom
of the centrifuge and travels upward through matching holes in
the discs
Between the disc, heavy components of the feed are thrown
outward under the influence of centrifugal forces as lighter liquid
is displaced towards the center of the bowl
As they are flung out, the solids strike the undersides of the
discs and slide down to the bottom edge of the bowl
At the same time, the lighter liquid flows in and over the upper
surfaces of the discs to be discharged from the top of the bowl
Heavier liquid containing solids can be discharged either at the
top of the centrifuge or through nozzles around the periphery of
the bowl
 continued

Figure 3.15: Mechanism of solids separations in a disc-

stack bowl centrifuge
 continued

 2a 2   0 g  2n 2 ( R03  R13 ) cot  

Q   (E3.35)
 9   3 g 

Q ={υg}[Σ]

 therefore, in a sensitivity analysis, ∑ factor depends on

the cube of the bowl radius,
the cotangent of the disk acute angle,

the number of disks in the stack and

as in the tubular centrifuge, the square of the rotor speed

 the disk acute angle θ made by the conical disks is typically

between 35 and 45 degrees
 A comparison of the advantages and disadvantages of
the different centrifuge designs is given in table (3.2.1)

System Advantages Disadvantages

Tubular bowl a)High centrifugal force a)Limited solids capacity
b)Good dewatering b)Foaming unless special
c)Easy to clean skimming or centrifugal pump
d)Simple dismantling of bowl used
c)Recovery of solids difficult
Chamber a)Clarification efficiency remains a)No solids discharge
bowl constant until sludge space full b)Cleaning more difficult than
b)Large solids holding capacity tubular bowl
c)Good dewatering c)Solids recovery difficult
d)Bowl cooling possible
Disk a)Solids discharge possible a)Poor dewatering
centrifuge b)Liquid discharge under pressure b)Difficult to clean
eliminates foaming
c)Bowl cooling possible
 continued

System Advantages Disadvantages

Scroll or a)Continuous solids discharge a)Low centrifugal force
decanter b)High feed solids concentration b)Turbulence created by scroll
centrifuge
Basket a)Solids can be washed well a)Not suitable for soft biological
centrifuge b)Good dewatering solids
c)Large solids holding capacity b)No solids discharge
c)Recovery of solids difficult
 Table 3.2.2: Capabilities of tubular and disk centrifuges

Type Bowl Speed Max. dimensionless Throughput

dia.(mm) (rpm) acceleration G, ω2R/g (liters/min)
Tubular 44 50,000 61,400 0.2-1.0
bowl 105 15,000 13,200 0.4-38
127 15,000 16,000 0.8-75
Disk with 254 10,000 14,200 40-150
nozzle 406 6,250 8,850 100-570
discharge 686 4,200 6,760 150-1500
762 3,300 4,630 150-1500