BT 5041: Downstream Processing in Biotechnology

Lecture 5-9: Solid-Liquid Separation Processes

Filtration Processes
Solid-Liquid Separation Processes in Biotech Industries
n Filtration

n Centrifugation

n Applications
q Removal of cells from fermentation broth;

q Cell recycle to fermenter

q Removal of cell debris after cell disruption (intracellular products)

q Separation of insoluble aggregates from liquid broth

n (e.g. precipitates, inclusion bodies)

q Separation of crystals (after crystallization operations)

q Removal of fine particulates and viral contaminants

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 Types of Filtration Processes
n Depth (or deep-bed) filtration
q Removal of fine particles from very dilute suspensions (e.g. Water-treatment,
air-filtration)
q Recovery of particulate material is not important
q Resistance to filtration increases gradually
n Cake filtration
q Slurry or suspension has high proportion of solids (e.g. fermentation broth)
q Filter bed (or cake) is formed by the solids in the slurry, which are separated
from the liquid by a filter medium
q Resistance to filtration increases with increased thickness of the cake being
formed
n Cross-flow (or tangential-flow) filtration
q The feed material flows (tangentially) across the surface of the filter medium
(usually a semi-permeable membrane) while filtrate flows through the filter
medium, perpendicular to the feed
q Used to recycle or concentrate particulate matter (cells) or proteins

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process RO NF UF MF
reverse nano- ultra- micro-
osmosis filtration filtration filtration

Dp

'pore' size 0.3 1 nm 3 300

nm nm nm
retains salts sugars proteins micro-
organisms
>30 >100 >3000
Da Da Da
larger flux
larger pressure
drop
 Equations for flow through a packed bed
Darcy’s law relates flow rate through a porous bed of solids to the pressure drop
causing the flow (for Rep < 5)
" ∆$ ∆'
𝑢! = %&
= %( (2.1)

𝑢! is the superficial velocity of the liquid (flow rate div. by cross-sectional area);
k is the permeability of the bed (cake); DP is the pressure drop across the bed; l is
bed thickness; µ is viscosity of the liquid;
R (= l / k) is the total resistance of the cake and filter medium
Kozeny-Carman equation for flow through packed beds:
) ,! ∆$
𝑢! = *+ -" )., "%& (2.2)
Where: e is the bed porosity or the void fraction, S is the specific surface area of
the particles, 𝐾′ is a constant (~ 5) which depends on particle shape etc.
,! /# " ∆$
𝑢! = 0.0055 )., " %&
(spherical particles of diameter dp) (2.3)
Applications of flow through packed beds
n Packed-bed reactors (heterogeneous catalysis)

n Adsorption-based separations (chromatography)

n Solid-liquid extraction processes

n Filtration processes

n Biomass pretreatment; cellulose hydrolysis

n Waste-treatment processes (sludge reactors)

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Factors to be considered for selection of filtration process or
equipment during cake filtration

n The properties of the fluid (viscosity, density, corrosive props etc.)

n Nature of solids in the slurry – particle size, shape, size-distribution,

packing characteristics

n Concentration of solids in the slurry

n Quantity of broth to be filtered and time taken for filtration

n Whether product of interest is in the solid or liquid

n Whether it is necessary to wash the cake

n Whether addition of filter aids or any pre-treatment would be helpful

Factors affecting rate of filtration

n Pressure drop across the bed (cake)

n Filter surface area

n Viscosity of the filtrate

n Resistance of the filter-medium and filter-cake

Plate and Frame Filters
Rotary Drum Filter
Operation
General equation for cake filtration (dead-end filtration)
For batch filtration, superficial velocity (or flux) can be re-written as
! #$ ∆&
𝑢$ = = (2.4)
" #% '(
where V is the total volume of filtrate collected in time t

The total resistance (offered by cake + filter medium) is:

R = RM + Rc (2.5)
where RM is filter medium resistance (constant) and Rc is cake resistance

Combining equations 2.4 and 2.5, we get

! #$ ∆'
= (2.6)
" #% ( (*0 + *1 )
Modes of operation for filtration processes
n Constant Pressure Filtration
q Involves build-up of cake (resistance);
q decrease in filtration rate with time

n Constant Rate Filtration

q Involves increased build-up of cake-resistance as well as
pressure-drop across the cake
q Both the above are batch processes

n Continuous Filtration Processes

q Involves constant rate, constant pressure
q continuous removal of cake (constant thickness)

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Cake Resistance
Incompressible Cakes:
"
The cake resistance can be written as: R c = α𝜌! (2.7)
#
where α is specific cake resistance; 𝜌! is the mass of dry cake solids per volume of filtrate

) /5 ∆'
4 /6
= % 78 5⁄4 :(%
(2.8)
$

/6
Eqn. (2.6) can be re-written as
/5
= 𝐾' 𝑉 + 𝐵 (2.9)
%78$ % (%
where 𝐾' = 4" ∆'
𝐵= 4 ∆'
(2.10)

Integrating (2.7) subject to condition that V= 0 at t =0 and re-arranging, we get

6 *& 5
5
= ;
+𝐵 (2.11)
Plot of t/V vs. V should give a straight line for incompressible cakes
Calculation of cake resistance and filtration time
Specific cake and medium resistances can be calculated from the slope and
intercept obtained from plot of t/V vs. V (eq. 2.9)

*& %78$ %(%

Slope = ;
= ;4" ∆'
; Intercept = 4 ∆'
(2.12)

Filtration time for constant pressure filtration (incompressible cakes) is given by:
5" %78$ 5 ; %(% 5
𝑡 = 𝐾' ; + 𝐵𝑉 = ;∆' 4
+ ∆' 4
(2.13)

If the medium resistance is insignificant compared to cake resistance (typical

situation in lengthy filtrations), then filtration time is given by:
5" %78$ 5 ;
𝑡= 𝐾' = (2.14)
; ;∆' 4
Constant Rate Filtration
If filtration occurs under conditions of constant rate rather than constant
pressure (for e.g. if the slurry is fed by a positive-displacement pump), then by
re-arranging the eqn. (2.6), we get
) /5 ∆'
= (2.15)
4 /6 % 78$ 5⁄4 :(%

%78$ /5 %(% /5
∆𝑃 = 𝑉+ = 𝐾5 𝑉 + 𝐶 (2.16)
4" /6 4 /6

In terms of filtration time (since dV/dt = V/t ), eqn 2.16 is re-written as

%78$ /5 ; %(% /5
∆𝑃 = 4" /6
𝑡+ 4 /6
(2.17)

Thus, pressure across the filter cake increases with time (or volume of filtrate)
and the rate of increase in pressure is proportional to square of filtration rate

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Compressible cakes
In case compressible cakes (where bed porosity changes during
course of filtration), the specific cake resistance is function of the
pressure drop across the cake and takes the form:

𝛼 = 𝛼 ! ∆𝑃" #
(2.18)

where ∆𝑃! is pressure drop across the cake (~ DP);

𝛼 ! is a constant related to shape and size of particles forming the
cake
s is the cake compressibility factor; it varies from 0 for rigid,
incompressible cake to ~ 1 for a highly compressible cake.
In practice, s ranges from 0.1 – 0.8
Pretreatment of slurries
Particles forming the filter cake should have as large a size as
possible and cake should have high porosity and low
compressibility
Since fermentation biomass often forms a highly compressible
and impermeable mat, it is often subjected to pretreatment.
Following forms of pretreatment can be used
n Heating

n Changing the pH

n Coagulation
q Addition of electrolytes promotes coagulation and flocculation
n Adsorption on filter aids

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Filter Aids
n Filter aids are used when the filter cake is relatively impermeable to the
flow of the filtrate

n The flocculated suspension gives rise to a more porous cake and reduces
specific resistance although compressibility increases

n Use of filter-aids is restricted to operations where product is in the filtrate

n Sometimes the filter medium is pre-coated with the filter aid

n Two types of (siliceous) filter aids commonly used are

q Diatomaceous earths or Kieselguhr (fossilized remains of diatoms)

q Perlite (amorphous volcanic material)

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 Filter washing and total cycle time
n To calculate washing rates, it is assumed that conditions during washing are
same as conditions at the end of filtration.
n It is assumed that cake structure (resistance) is not affected and wash liquid
replaces the slurry liquid in the cake
n The washing rate is given by the final filtration rate
!" %
!# $
= & " '( (2.19)
& '
Where 𝑑𝑉 ⁄𝑑𝑡 " is the final filtration rate and Vf is the total volume of filtrate
collected at the end of the filtration period

Neglecting the filter-medium resistance, the final filtration rate is given by

!" -" ∆/ %
!# $
= 012$ "'
= && "'
(2.20)
The washing rate (final filtration rate) per unit cross-sectional area is
% !" ∆/
- !# $
= 012$ "' ⁄-
(2.21)
If Vw is the volume of wash liquid flowing through the cake in time tw, then
!"
𝑉3 = 𝑡3 !# $
(2.22)

The wash volume per unit cross-sectional area is given by

"( % !" #( ∆/
= 𝑡3 = (2.23)
- - !# $ 012$ "' ⁄-
$%&! " '
Re-arranging Eqn. (2.14), i.e. 𝑡 = , we get
'∆) #
)⁄
"' 4∆/#' "

-
= 012$
(2.24)

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Substituting the expression for 𝑉* ⁄𝐴 from (2.24) in eqn. (2.23) and
simplifying,
)⁄
"( ∆/ "

-
= 𝑡3 4012$ #'
(2.25)

Dividing eqn. (2.24) by eqn. (2.25), we get

"' 4#' #( 4"(
"(
= #(
or
#'
= "'
(2.26)

The above ratio can be re-written as

#( " "
#'
= 2 "( "* = 2𝑛𝑓 (2.27)
* '
Where n is the ratio of the wash liquid volume (𝑉+ ) to residual liquid volume
(𝑉, ) in the cake; and f is the ratio of 𝑉, to 𝑉* and can be determined by a
material balance

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Recovery of filtrate solute during cake washing

n The fraction of filtrate-solute remaining in the cake after washing is

related to volume wash liquid by the eqn.
𝑅 = 1−𝐸 - (2.28)
Where R is the weight fraction of the solute remaining in the cake after
washing to that present in the cake prior to wash (when R = 1);
E is the wash efficiency of the cake (varies from around 0.35 to 0.85);
n is the ratio of the wash liquid volume (𝑉+ ) to volume of residual liquid (𝑉, )
retained in the unwashed cake

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Rotary-Drum Vacuum Filter (continuous filtration)

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Rotary Drum Filter
Continuous filtration in Rotary-Drum Vacuum Filter

n For a continuous filtration such as the rotary drum filter, the feed, filtrate
and cake move at steady, continuous rates

n The pressure drop (difference between atmospheric pressure and vacuum

applied) is held constant during filtration since there is no cake build-up.

n The time period for cake formation is given by the residence time of drum
fraction immersed in the slurry
𝑡 = 𝑓𝑡! (2.29)

Where tc is the total cycle time for the drum to complete one rotation and f is
the fraction of drum surface submerged in the slurry (equal to fraction of the
cycle time used for cake formation)
Equations for continuous filtration
Assuming negligible filter-medium resistance (compared to cake
resistance),
"" 012$ " "
𝑡 = 𝑓𝑡5 = 𝐾/ 4 = -" ∆/ 4
(2.30)
" 4 4$#$ ∆/
= (2.31)
- 012$

)⁄
" 4$∆/ "
𝐹𝑙𝑢𝑥 = -#$
= #$ 012$
(2.32)

Flow rate (or flux) varies inversely with square root of cycle time
and directly as square root of pressure and fractional submergence

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 Dp

permeate

membrane

feed
Industrial Applications of Membrane Separation Processes

n Reverse Osmosis
q Desalination; Wastewater treatment
n Dialysis / Electrodialysis
q Hemodialysis of human blood; Production of ultrapure water for biotech and
semiconductor industry
n Microfiltration
q Cell separation; Media sterilization; Clarification of beverages
n Ultrafilatration
q Concentration and separation of proteins and other biopolymers
n Pervaporation
q Removal of water from organic solvents; Ethanol separation from fermentation broths
n Gas Permeation
q Separation of CO2 or H2 from methane and other hydrocarbons
q Enrichment of O2 or N2 from air
q Recovery of methane from biogas

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