RADIAL FLOW

CHROMATOGRAPHY
DEVELOPMENT & APPLICATION
SUBJECT:-FUNDAMENTAL OF BIOPROCESS
ENGINEERING
VIKAS KUMAR
MAYUR SOLANKI

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INTRODUCTION
The RFC itself was actually invented in the 1950s. Radial
Flow Chromatography (RFC) is an efficient, low pressure
technology for bio-molecule fractionation &
purification. RFC is very suitable for high throughput
adsorptive separations in process.The short bed height,
packed bed, allows robust adsorptive separations from
crude feed (large dirt tolerance)
In an RFC column , the mobile phase flows in the radial
direction, not in the axial direction. The mobile enters from
the outside tube and merges into the center tube .
The radial flow chromatography column consist of two
concentric porous cylindrical frits between which the
stationary phase is packed.

DVANTAGE OF RFC OVER AFC

Radial flow chromatography offers

several potential advantages over
conventional axial flow column systems.
It has a short bed depth and large area
available for flow, allowing fast
separations and low pressure drops
(Saxena and Dunn, 1989; Levison, 2003),
and has been used for a wide range of
separations (e.g., Lapidus and Amundson,

RADIAL

AXIAL

COLUMN CONFIGURATIONS

DEVELOPMEN
In 1947, Hopf (2) described a radial
T device. The device
chromatography
1ST RADIAL FLOW

had a feed pipe in the center. The

outward liquid flow in the radial
direction was driven by the centrifugal
force when the device was rotated.
Because of this, he called this device a
chromatofuge. Such a device was
obviously too complex and expensive
for large-scale industrial application

Radial Flow Chromatography (RFC)

columns.
RFC columns offer increased throughput
and reduced pressure drop, while the
systems weight and footprint can be onequarter that of an axial-flow column.
Existing RFC-column technology performed
only moderately well and Raedts
determined that the columns should be able
to perform much better, if they were
properly designed.
Differences in favour of Radial processing

(optimizing to lower bed height)

1.Pressure drop 20-50% reduced
2.Loading efficacy improved

COLUMN

2ND DIAPHRAGM PUMP FOR PROCESS

There had to be a better pump for critical producthandling applications in the pharmaceutical and biotech
industries. They developed a positive displacement
quaternary pump that features four pistons and four
smooth-operating diaphragms, a design similar in concept
to that of the human heart.
The Quattroflow pump performed much better than
we expected and
showed highly reduced resin
damage,. Since it has four diaphragms and five
valves we expected some additional shear, but there
was none at all, even at elevated flow rates.
There was truly a strong similarity to the human heart
in its operation and that provided proof of its suitability
for demanding applications like human blood plasma
fractionation. Additionally, we found an excellent

3RD PRESSURE DROP

The average velocity in the columns was set
equal. No difference in performance between
the two columns could be observed.
Using mathematical models we found that
the breakthrough performance of radial flow
chromatography is very similar to axial flow
when the ratio between outer and inner radius
of the radial flow column is around 2.
When this ratio is increased, differences
become more apparent, but remain small.
However, the ratio does have a significant
influence on the velocity profile inside the

If the pressure drop per unit radial length

progressively increases toward the center in
inward flow, , gel density increases. This helps
balance the gradual reduction of gel volume toward
the center.
(Graph: TINGYUE GU Department of Chemical and Biomolecular Engineering,
Ohio University, Athens, Ohio

4th Radial Compressed packing

( results in homogenous packing)
Annular port Radial Compressedpackingpacks
the radial columns with unique precision and
reproducibility. This packing technique allows
accurate and reproducible packing of
extremely short bed heights (<3cm !!) and tall
columns (130 cm !!). Flow rate during packing is
optimized for each resin.

Recycling packing is the most flexible packing

mode, suitable for medium- to rigid resins
(sepharose, polymeric). Recycling packing
procedure allows a starting slurry concentrations
between 50% and 80% therewith reducing the
packing vessel volume to a suitable size.

During the recycling packing procedure the

packing liquid is fed back into the packing
vessel.
The main recycling packing control parameters
are

a.Slurry concentration
b.Packing velocity
c.Amount of settleled resin: suplus or
insufficient
d,D.Viscosity (density) of the packing
buffer

5th Effect of resin quantity

and packing velocity
Graphs below show the mechanism behind recycling packing. Diluted starting
slurry will increase the durstion of packing, hence allowing the resin to
compact stronger. A number of protocol variants are available to make a
robust reproducible S.O.P. for the packing of any column.

The Picture shows a column being packed. ~85% of the resin is packed

APPLICAT
ION

Three types of membrane adsorbers are used for

Protein Bioseparation
flat sheet
hollow fibre

radial flow

Radial flow adsorbers are prepared byspirally winding a flat

sheet membrane over a porouscylindrical core. The liquid
flowpattern in a radial flow device is shown in Fig.

Radial flow adsorbers are claimed to be

suitable for large-scale applications. However,
flow distribution in these devices is expected
to be quite challenging. The membrane area
also increases in a radially outward direction..
The radial flow adsorber is clearly not suitable
for pulse chromatography. It is likely to be
more suitable for use in the bind and elute
modeHowever, the binding and elution
processes might be difficult to model and
predict. In spite of such perceived
disadvantages, radial flow adsorbers are
popular with users in the industry.

R. Ghosh / J. Chromatogr. A 952 (2002) 1327

Thanks