Note: Descriptions are shown in the official language in which they were submitted.
CA 02597448 2007-08-16
PU0757-1
Chromatography Column and Method of Maintenance
Field of the Invention
The present invention relates to chromatography columns and methods for
operating columns in industrial-scale chromatography. In particular, the
invention is
concerned with chromatography columns and safer methods for performing
maintenance
on such columns, such as cleaning and replacing bed supports, distributors and
0-rings,
without the need for heavy lifting equipment such as hoists or cranes to
dismantle the
columns.
Background of the Invention
Chromatography columns may be used in industrial processes to purify process
liquids and separate substances of interest from process liquids; typical
examples
include large-scale preparative purification of fine chemicals and
pharmaceuticals,
together with biological products.
Industrial-scale chromatography columns typically comprise a hollow, axially
vertical tubular housing including a liquid inlet at the upper end and through
which the
buffer and substances to be separated are dispensed to the media bed located
within the
cavity of the tube, and a liquid collecting system at the lower end for
collecting
substances and buffer. The particulate chromatographic media or bed through
which the
buffer fluid and/or substances to be separated and purified percolates is
located between
the liquid inlet and collecting system.
An adapter assembly is typically affixed to the upper end of the tubular
housing
and a base assembly to the lower end where it is bolted to the bottom flanges.
Each of
these assemblies typically comprises a strong backing plate and a distributor
which
further supports a bed support: a bed support is a layer of mesh, filter,
sinter, screen or
other fluid-permeable media-retaining material which permits process liquid
flow into and
out of the chromatography bed space or cavity while retaining the bed of
particulate
1
CA 02597448 2007-08-16
PU0757-1
medium. To provide adjustability and control of the bed height and bed
compression, the
adapter assembly is typically made in the form of a piston or sliding adapter
in the
column tube interior. After the column is charged with bed media, typically.
through a
nozzle, the adapter may be forced toward the bottom of the tube to compress or
pressurize the media bed. Generally the base assembly is a fixed structure
which is
bolted against the bottom flange of the column tube but, in some instances,
may also be
in the form of a movably slidable piston or adapter.
The backing plate of the base assembly generally acts as a support for the
column, being itself supported on legs or some other stand arrangement which
allows
clearance for outlet pipework projecting beneath the base assembly.
When such a column requires maintenance to, or cleaning of, internal
components, such as the valves, seals, meshes/screens, distribution systems
etc.,
heavy lifting gear such as a crane or hoist is necessary to lift the upper
end/adapter
assembly away from the column tube and the column tube away from the lower end
/base assembly as these assemblies can weigh in excess of three tons. The use
of
heavy overhead lifting equipment to disassemble the column in order to carry
out internal
maintenance is not desirable. Operator safety is obviously a concern when
heavy
equipment is lifted overhead and technicians exposed below. Furthermore,
alignment
structures are required to keep the column and its base/adapter assemblies
axially
aligned as they are separated from each other, to avoid damage to the
precision
components.
The presence of such alignment and lifting structures imposes significant
obstructions around the tube and need to be carefully laid out to provide
sufficient
clearance at some point of the circumference for insertion/removal of the
internal
components. Furthermore, the requirement to use heavy lifting equipment
imposes
constraints on housing such columns, sufficient overhead space and support
being
required to accommodate hoists or cranes. As many chromatography columns are
now
run in "clean" environments under GMP, to avoid microbiological contamination,
where it
2
CA 02597448 2007-08-16
PU0757-1
is extremely difficult to accommodate overhead equipment, the requirement of
moving
the column to another room for disassembly and maintenance is problematic.
This
problem is exacerbated by the need to clean and verify the column before
returning it for
use to the clean environment. The presence of hoists or cranes in GMP
facilities used
for biopharmaceutical manufacturing is thus highly undesirable for the above
mentioned
reasons, together with the fact that these machines shed particulate matter,
in the form
of dirt, during their operation and maintenance.
U.S. 6,736,974 addresses some of the above problems by providing a column
which is capable of lifting the adapter assembly above the column tube and/or
raising the
column tube above the base assembly by means of an hydraulic system which is
integral
to the column.
However, the system described in U.S. 6,736,974 has significant disadvantages
associated with it by virtue of its design. As can be seen from FIGS. 4 and 5
of U.S.
6,736,974 and described in column 4, lines 63-66 of that document, in order to
remove
the distributor plate (31) and/or mesh (28/60) from the interior of the
column, the operator
must work within the centre of the drum (18) to access and remove the fixing
nut (30)
which secures these component parts. As industrial columns typically have
diameters
ranging from about 200 mm to 2000 millimetres, this means that the operator
must work
below a suspended or supported load to unscrew the nut. This clearly poses a
significant safety risk to the operator, particularly where the operator's arm
or head is
exposed below the suspended or supported load.
Furthermore, once the column tube/cylinder or adapter assembly has been raised
from the base assembly or tube, respectively, removal of the heavy bed support
and/or
distributor from the column can only be accomplished by tilting the bed
support or ,
distributor at an angle to negotiate the hydraulic drive pistons or safety
rods. This can
clearly be seen from, for example, FIGS. 3, 4 and 5 in which the distance
between any
two safety rods (69) or between any two hydraulic pistons (36) is less than
the diameter
of the mesh (28/60) or distributor plate (31). The same problem would exist
for the base
3
CA 02597448 2007-08-16
PU0757-1
or adapter bed support (not shown). Removal of these internal components,
which could
weigh in excess of 100 kg, requires considerable manhandling by the operator
and
necessitates their being exposed below the suspended column or adapter
assembly.
Once again, this represents a significant safety risk for the operator.
The task of physically removing the heavy bed support or distributor, as
described in U.S. 6,736,974, must be carried out by an operator, there being
no
disclosure of the use of any lifting aid to assist in this task. The
configuration of the
hydraulic pistons and the safety rods, and the need to tilt the bed support
and/or
distributor in order to avoid hitting these supporting structures in
withdrawing these
components from the column, would require the design of a bespoke lifting
device:
WO 2005/056156 (Euroflow (UK) Limited) also discloses a column which can be
accessed for maintenance without the need for a crane or hoist. The column is
designed
such that the tube and the base assembly can be separated by means of
hydraulic drive
cylinders to provide an access space between them to conduct maintenance or
service
on the base assembly. The piston of the adapter assembly can be advanced
through
the column tube to expose it at the open end of the column tube, i.e. in the
space
between the tube and the base assembly, for maintenance.
However, as is evident from this document (for example, FIGS. 19 and 20 and
related description on page 23) access to release the fastening screws
retaining the bed
support or mesh in place is provided by the space between the tube and the
base
assembly. Removal of the bed support necessitates the operator being exposed
to a
suspended load while retaining screws are removed. Furthermore, the distance
between
any two drive cylinders for maintenance access is less than the diameter of
the bed
support (see, for example, FIG. 7), which requires the operator to manhandle
and tilt the
bed support when removing or replacing it. Maintenance of the column thus
imposes a
significant safety risk for the operator.
Accordingly, a need exists to improve the maintenance methods available for
chromatography columns by providing columns which are safer and easier for
operators
4
CA 02597448 2007-08-16
PU0757-1
to use and which do not expose them to a suspended or supported load, thereby
reducing the risk of operator error and injury.
Summary of the Invention
The present invention recognises and addresses these needs and others.
In a first aspect of the present invention, there is provided a method for
conducting maintenance on a chromatography column comprising the steps of:
a) providing a chromatography column comprising;
a dispersion system comprising a nozzle including a mobile phase
pathway connected to a liquid inlet;
a tube with an adapter assembly connected to a drive system, said
adapter assembly moveable within a cavity of said tube in an operational
mode;
the adapter assembly comprising a distributor and a bed support
fastened to each other by releasable fixing means,
said drive system comprising one or more cylinders;
a collection system opposing the dispersion system; and
one or more seals;
b) disconnecting the adapter assembly from the tube;
c) lifting the adapter assembly above the tube with the drive system to
provide a gap for access therebetween;
d) unfastening the bed support from the distributor by releasing the fixing
means without accessing said gap;
e) removing the bed support from the column;
f) conducting maintenance on the column and /or the bed support and/or
said one or more seals;
g) returning the bed support to the column and fastening the bed support to
the distributor; and
5
CA 02597448 2007-08-16
PU0757-1
h) lowering the adapter assembly with the drive system to an operational
position
within the tube and reconnecting the adapter assembly to the tube.
The gap provided for access between the adapter assembly and the tube is at
least three inches in height in order to permit removal of the bed support
from the column
or return thereto. Preferably the gap is at least six inches in height to
allow for greater
access to the column. More preferably the gap is at least nine inches in
height. More
preferably the gap is at least twelve inches in height. More preferably the
gap is at least
fifteen inches in height. Most preferably the gap is at least eighteen inches
in height.
In a preferred aspect, the fixing means are releasable from the exterior face
of
the distributor. This reduces the exposure of the operator to a suspended or
supported
load as they do not need to enter the gap.
In a particularly preferred aspect, the drive system comprises at least two
cylinders and the distance between any two said cylinders for maintenance
access is
greater than the diameter of the bed support. This permits the use of a
handling device
to support and remove or replace the bed support and/or distributor from/to
the column.
Preferably cylinders are externally mounted to the column. This facilitates
greater
spacing between the cylinders. More preferably, each said cylinder is
independently
removable from the column.
Preferably, the step of removing the bed support is carried out without
substantially tilting the bed support. This reduces operator exposure beneath
the
suspended load and facilitates manhandling and/or mechanical handling of the
bed
support. The term `without substantially tilting' as used herein means
`tilting at an angle
of no more than 5 to the horizontal'.
More preferably, the step of removing the bed support without substantially
tilting
the bed support involves use of a handling device. More preferably, the
handling device
comprises at least one arm and the method comprises supporting the bed support
on at
least one arm of the handling device.
6
CA 02597448 2007-08-16
PU0757-1
Optionally, the step of conducting maintenance on the column further comprises
removing the distributor without substantially tilting said distributor. The
term 'without
substantially tilting' as used herein means 'tilting at an angle of no more
than 5 to the
horizontal'. It will be understood that the distributor and the bed support
could be
removed together and at the same time.
Preferably, the column further comprises a locking system, the method further
comprising the step of locking the adapter assembly with said locking system
after lifting
the adapter assembly above the tube with the drive means. This provides for
greater
operator safety.
According to a second aspect of the present invention, there is provided a
method for conducting maintenance on a chromatography column comprising the
steps
of:
a) providing a chromatography column comprising
a dispersion system comprising a nozzle including a mobile phase
pathway connected to a liquid inlet;
a tube with an adapter assembly and a base assembly connected to a
drive system, said adapter assembly moveable within a cavity of said tube in
an
operational mode;
the base assembly comprising a distributor and a bed support fastened to
each other by releasable fixing means,
said drive system comprising one or more cylinders;
a collection system opposing the dispersion system; and
one or more seals;
b) releasing the tube from the base assembly;
c) lifting the tube and the adapter assembly above the base assembly with
the drive system to provide a gap for access therebetween;
d) unfastening the bed support from the distributor by releasing the fixing
means without accessing said gap;
7
CA 02597448 2007-08-16
PU0757-1
e) removing the bed support from the column;
f) conducting maintenance on the column and /or the bed support
and/or said one or more seals;
g) returning the bed support to the column and fastening the bed support to
the distributor; and
h) lowering the tube and the adapter assembly with the drive system and
reconnecting the tube to the base assembly.
The gap provided for access between the tube and adapter assembly and the
base assembly is at least three inches in height in order to permit removal of
the bed
support from the column or return thereto. Preferably the gap is at least six
inches in
height to allow for greater access to the column. More preferably the gap is
at least nine
inches in height. More preferably the gap is at least twelve inches in height.
More
preferably the gap is at least fifteen inches in height. Most preferably the
gap is at least
eighteen inches in height.
Preferably, the fixing means are releasable from the exterior face of the
distributor. This reduces the exposure of the operator to a suspended load as
they do
not need to enter the gap.
Preferably, the cylinders are externally mounted to the column. This
facilitates
greater spacing between the cylinders. More preferably, each said cylinder is
independently removable from the column.
Preferably, the distance between any two said cylinders for maintenance access
is greater than the diameter of the bed support. This permits the use of a
handling
device to support and remove or replace the bed support and/or distributor
from/to the
column. Maintenance access is the access to the column and its component parts
such
as the bed support and/or distributor which is required in order to carry
out.maintenance
or service.
Preferably, the step of removing the bed support is carried out without
8
CA 02597448 2007-08-16
PU0757-1
substantially tilting the bed support. This reduces operator exposure beneath
the
suspended load and facilitates manhandling and/or mechanical handling of the
bed
support. The term 'without substantially tilting' as used herein means
'tilting at an angle
of no more than 5 to the horizontal'.
Preferably, the step of removing the bed support involves use of a handling
device. More preferably, the handling device comprises at least one arm and
the
method comprises supporting the bed support on at least one arm of the
handling device.
More preferably, the method comprises releasably affixing the outer rim of the
bed
support to at least one arm of said handling device.
Optionally the step of conducting maintenance on the column further comprises
removing the distributor without substantially tilting said distributor. The
term 'without
substantially tilting' as used herein means 'tilting at an angle of no more
than 5 tothe
horizontal'. It will be understood that the distributor and the bed support
could be
removed together and at the same time.
Preferably, the column further comprises a locking system, the method further
comprising the step of locking the adapter assembly and the tube above the
base
assembly with said locking system after lifting said adapter assembly and the
tube with
the drive means. This provides for greater operator safety.
According to a third aspect of the invention, there is provided a
chromatography
column comprising:
a dispersion system and a nozzle including a mobile phase pathway connected
to a liquid inlet;
a tube with an adapter assembly and a base assembly connected to a drive
system having at least one cylinder,
said adapter assembly moveable within a cavity of said tube in an operational
mode;
the adapter assembly comprising a distributor and a bed support fastened to
each other by releasable fixing means;
9
CA 02597448 2007-08-16
PU0757-1
the base assembly comprising a distributor and a bed support fastened to each
other by releasable fixing means;
a collection system opposing the dispersion system; and
one or more seals;
wherein the fixing means fastening the distributor and bed support of the
adapter
assembly or the base assembly to each other are releasable from the exterior
face of the
distributor.
Preferably, the drive system comprises at least two cylinders and the distance
between any two said cylinders for maintenance access is greater than the
diameter of
the bed support. This permits the use of a handling device to support and
remove or
replace the bed support and/or distributor from/to the column. Maintenance
access is
the access to the column and its component parts such as the bed support
and/or
distributor which is required in order to carry out maintenance or service.
Preferably, the adapter assembly is disconnectable from the tube and the drive
system is capable of lifting the adapter assembly above the tube to provide a
gap for
maintenance access. The gap provided for access between the adapter assembly
and
the tube is at least three inches in height in order to permit removal of the
bed support
and/or the distributor from the column or return thereto. Preferably the gap
is at least six
inches in height to allow for greater access to the column. More preferably
the gap is at
least nine inches in height. More preferably the gap is at least twelve inches
in height.
More preferably the gap is at least fifteen inches in height. Most preferably
the gap is at
least eighteen inches in height.
Preferably, the tube and the adapter assembly are disconnectable from the base
assembly and the drive system is capable of lifting the tube and the adapter
assembly
above the base assembly to provide a gap for maintenance access. The gap
provided
for access between the tube and the adapter assembly and the base assembly is
at least
three inches in height in order to permit removal of the bed support and/or
the distributor
from the column or return thereto. Preferably the gap is at least six inches
in height to
CA 02597448 2007-08-16
PU0757-1
allow for greater access to the column. More preferably the gap is at least
nine inches in
height. More preferably the gap is at least twelve inches in height. More
preferably the
gap is at least fifteen inches in height. Most preferably the gap is at least
eighteen
inches in height.
Preferably, the drive means comprises at least two hydraulic cylinders and
most
preferably three hydraulic cylinders. Other drive means include, for example,
electrical
or pneumatically powered cylinders.
Preferably, the drive means is external to the column.
Preferably, the column additionally comprises a locking system for securing
the
raised adapter assembly above the tube. This improves operator safety.
Preferably, the column additionally comprises a locking system for securing
the
raised tube and adapter assembly above the base assembly.
Brief Description of the Drawings
The features and advantages of the invention will become apparent from the
following description taken in connection with the accompanying drawings in
which:
FIG. 1 shows an embodiment of a column known in the art in a first maintenance
position
in cross sectional view.
FIG. 2 is a cross sectional view showing the same embodiment of the column of
FIG. 1
in a second maintenance position.
FIG. 3 is a schematic exploded front view of an embodiment of the present
invention.
FIG. 4a is a schematic front view of a column in accordance with the
invention; FIG. 4b is
a side sectional view of the column of FIG. 4a; and FIG. 4c is a top plan view
of the
column of FIG. 4a.
11
CA 02597448 2007-08-16
PU0757-1
FIG. 5a is a front perspective view showing the adapter assembly raised and
secured
into position to provide a gap for access; FIG. 5b shows removal of the
fastening means
securing the distributor and bed support.
FIG. 6 is a perspective view of a handling device used to remove/insert a
distributor or a
bed support from/into a column in accordance with the invention.
FIG. 7a and FIG. 7b are perspective views of the column of FIG. 5 showing the
removal
of securing rods which fasten the bed support to the distributor.
FIG. 8a and FIG. 8b are perspective views showing the removal of the bed
support from
the column.
FIG. 9a is a perspective view of a column with an inset showing a locking
system in
accordance with the invention; FIG. 9b shows the column tube raised above the
base
and in the process of being locked into position.
FIG. 10 is a perspective view of a column with the column tube raised and
locked into
position in readiness for maintenance.
FIG. 11 a and FIG. 11 b illustrate the process of removing the bed support
from the
column using a handling device.
FIG. 12 shows the bed support having been removed from the column in readiness
for
maintenance.
FIG. 13 is a perspective view of the column of FIGS. 10 and 11 with the column
tube
12
CA 02597448 2007-08-16
PU0757-1
lowered awaiting bolting to the base.
Detailed Description of the Preferred Embodiments
The present invention is concerned with a method and apparatus for enabling
maintenance within a chromatography column. FIG. 1 shows a column 10 known in
the
art and described in U.S. 6,736,974 which permits maintenance within a
chromatography
column without the need for a hoist or crane. The column 10 comprises an
elongated
hollow cylindrical housing 12, or tube, having a dispersion system 14 at the
top and a
collection system 16 at the bottom. The dispersion system 14 includes a
cylindrical drum
18 having an upper cylindrical plunger head or adapter 20 formed at the lower
or interior
end (i.e. interior to the column). The adapter 20 is normally disposed within
the upper
portion of tube 12 such as is illustrated in the first operational position of
FIG. 1. The
adapter 20 may be moved by a drive system 34 such as the hydraulic arrangement
shown in FIG. 1. The movement of the adapter 20 allows for the compression of
chromatography media in order to produce a packed media bed of the optimum
height
within the column; a cavity 22 is formed between the dispersion and collection
systems
14, 16 and/or between the adapter 20 and the base 64.
The dispersion system 14 may include a mobile phase pathway connected to a
liquid inlet 24 together with an inlet manifold 26 to distribute incoming
liquid throughout a
top portion of a media bed contained within the cavity 22. A bed support (or
inlet screen)
28 or filter is attached to the adapter 20 by connectors and/or by an inner
clamp nut 30
which is accessible from the cavity 22. The bed support 28 may be removed for
maintenance purposes by release of the clamp nut 30; the distributor plate 31
may also
be removable (see U.S. 6,190,560 for a description of a distributor plate
design).
A drive system is used to move the adapter 20 in an operational mode. The
drive
system is comprised of at least one and preferably three or more, drive
cylinders 34.
The drive cylinders 34 move drive pistons 36 which are coupled to the drum 18.
A
portion of the drive pistons 36 may by threaded 38 to allow for the drive
piston 36 to
13
CA 02597448 2007-08-16
PU0757-1
connect or couple to connection arms 40 at specific locations relative to the
drive piston
36 such as with nuts 42, 44.
FIG. 1 shows a first maintenance position of the adapter 20 wherein the
adapter
20 is raised a predetermined distance from a top 54 of the cavity 22 within
the cylinder
by means of the drive system 34 and piston 36. The operator is thereby
provided access
with a hand to the centre of the drum 18 to release or affix nut 30 which
retains the
distributor plate 31 and bed support 28 to the adapter 20. The distributor
plate 31 and
or/bed support 28 may then be removed for maintenance. These are then replaced
by
affixing them to the adapter 20 and the adapter 20 may be lowered to return to
an
operational mode, nuts 42, 44 being reset to a proper operational
configuration, if
necessary.
In order to perform a second maintenance operation, such as removal of the
lower bed support (or screen) 160 which is typically positioned so that its
outer edge 162
is between the tube 112 and the collection system 116, the tube 112 may be
raised by
the drive system as illustrated in FIG. 2. The bolts which normally secure the
tube:112 to
the base 164 are removed, and the nuts 142, 144 may be coupled to the piston
136 to
drive the tube 112 along with the drum 118 upwards as shown. A gap is thus
provided
which allows access for an operator to loosen nut 132, which affixes the bed
support 160
to the base 164, and remove the bed support 160 for maintenance. Once
maintenance
has been completed, the bed support 160 is replaced, affixed by nut 132 to the
base 164
by the operator, and the process reversed to lower tube 112 and the drum 118
into an
operational position.
The present invention will now be described with reference to FIGS. 3 to 13;
FIGS. 3 to 8 relate to providing access to the upper adapter assembly and
FIGS. 9 to 13
to providing access to the base assembly for maintenance.
FIG. 3 is a schematic exploded front view of a column in accordance with the
invention. The column is made of strong, inert materials such as stainless
steel and
other materials which are suitable for use in a GMP environment typical of the
14
CA 02597448 2007-08-16
PU0757-1
pharmaceutical industry. The column 210 is supported on legs 204 having feet
206
which are adjustable in order to modify the height and/or the level of the
column. The
legs 204 support the column 210 which comprises a cylindrical housing or tube
212
separating a base assembly 263 at one end from an adapter assembly 215 at the
other.
The tube 212 may typically be made from stainless steel, or other strong,
inert materials.
Adjacent to the adapter assembly 215 is a dispersion system comprising a
nozzle 211
which includes a mobile phase pathway, for the introduction of buffer or other
suitable
mobile phase liquids or chemicals/materials to be separated, and a liquid
inlet 209. The
tube 212 may be connected to the adapter assembly 215 and base assembly 263 by
a
] 0 drive system having one or more cylinders 234. The drive system may be a
hydraulic
system, as shown, or may be powered by other suitable means, such as pneumatic
or
electrical means. The adapter assembly 215 is moveable within a cavity 222 of
the tube
212 in an operational mode, for example, to pack or compress the bed of
chromatographic media used to effect chromatographic separation of chemicals
within
the column. The adapter assembly 215 comprises an adapter flange 217, one or
more
distance pillars 219, a backing plate 220 made typically of stainless steel, a
distributor
231 which may take the form of a plate having many channels to effect the even
distribution of liquids, and a bed support 228 comprising a screen or mesh or
filter and
optionally a sealing ring (e.g. 229). The bed support may be made of an inert
plastic or
metal material such as stainless steel. The distributor 231 and bed support
228 are
fastened to each other by releasable fixing means (not shown). Typical
releasable fixing
means include, but are not limited to, a screw, a nut or a clamp. The fixing
means 230
may only be accessed and thus released from the exterior face of the
distributor 231 or
backing plate 220, that is the face of the plate furthest away from the cavity
222. In the
present example, the nozzle 211 must first be removed to provide access to the
fixing
means 230. Additional releasable fixing means, accessible from the exterior
face of the
backing plate, may optionally be employed to fasten the backing plate,
distributor and
bed support together. These fixing means can take the form of bolts inserted
through
CA 02597448 2007-08-16
PU0757-1
corresponding holes around the perimeter of the components. Access from the
exterior
face of the backing plate or distributor avoids unnecessary exposure of the
operator to a
suspended or supported load within the column.
The base assembly 263 comprises a distributor 266 and a bed support 268 and
optionally a backing plate 264 fastened to each other by releasable fixing
means 269.
The bed support 268 comprises a screen or mesh or filter and optionally a
sealing ring
(e.g. 274). The bed support may be made of an inert plastic or metal material
such as
stainless steel. Releasable fixing means 269 are, for example, a screw, a nut,
a bolt or a
clamp; it will be appreciated that other releasable fixing means are also
possible. As can
be seen from the figure, the fixing means 269 secures bed support 268 and the
distributor 266 through a central hole in each component. The fixing means 269
is only
accessible and may therefore only be released from the exterior face of the
distributor
266. In FIG. 3, nozzle 272 must first be removed to provide access to release
fixing
means 269. Additional releasable fixing means, accessible from the exterior
face of the
backing plate, may optionally be employed to fasten the backing plate,
distributor and
bed support together. These fixing means can take the form of bolts inserted
through
corresponding holes around the perimeter of the components. Access from the
exterior
face of the backing plate 264 avoids operator exposure beneath a suspended
load, were
access only to be available from within the interior of the column.
It will be understood that separation of chemical or biological materials on
the
column, when the tube 212 is full of chromatographic media, can be carried out
in either
a downward or upward flow. Thus, in a downward flow, liquid containing
chemical or
biological materials to be separated, is introduced through nozzle 211 and
moves in a
downward direction through the bed of media, to be collected in the collection
system at
the base of the column via an outlet port (not shown). In upward flow mode,
liquid
containing materials to be separated is introduced via the bottom nozzle 272
and flows
upwards through the media bed to be collected at the top of the column via an
outlet port
(not shown). In the interests of clarity, the maintenance or servicing of the
column will be
16
CA 02597448 2007-08-16
PU0757-1
described in downward flow mode.
In order to conduct maintenance on the adapter assembly 215 or distributor
231,
the adapter assembly 215 is disconnected from the column tube 212 by
unscrewing the
nuts which join the adapter flange 217 to the upper column flange 213a. The
drive
system then raises the adapter assembly 215 by means of cylinders 234 to allow
for
access to the interior of the column for maintenance or service. The adapter
assembly
215 is locked into position by means of locking rods 225 which are aligned
with and
screwed into threaded holes in the locking system 270. In this secured
position, the
adapter bed support and/or the distributor may be removed from the column for
maintenance once the fixing means are released, release being effected by
removal
from the exterior face of the column following removal of the nozzle 211 as
described
above. Once maintenance has been carried out on the column (e.g. the bed
support 228
has been replaced), the column 210 is made operational again by reversing the
above
procedure: the adapter assembly 215 is released from the locking rod 225 and
lowered
by use of cylinders 234, and then reconnected to the column tube 212 by
replacing the
nuts which join the adapter flange 217 to the upper column flange 213a.
Maintenance or service is carried out on the bottom distributor 266 or base
assembly 263 by releasing the tube 212 from the base assembly 263 and lifting
the tube
212 and adapter assembly 215 with the aid of the drive system. The bolts on
the lower
flange 213b of the column tube 212 which join it to the bottom backing plate
264 are
removed. The column tube 212 and adapter assembly 215 are then lifted by means
of
the drive cylinders 234. The tube 212 and upper adapter assembly is secured in
position
above the base with the cylinder brackets 236 by screwing locking bolts
through holes
aligned in the locking pin 270, bracket 236 and cylinder 234.
The bottom nozzle 270 is then disconnected from the back plate 264 and
distributor 266. The nozzle 270 is removed together with the distance ring
235, to allow
access to release the fixing means 269 which may be in the form of a nut. The
nut 269
is removed from the exterior face of the distributor 266, i.e. the face
distant.from the
17
CA 02597448 2007-08-16
PU0757-1
cavity 222, and thus eliminates operator exposure to a suspended or supported
load. If
additional releasable fixing means, such as bolts inserted through the backing
plate,
distributor and bed support as described above are present, these must be
removed
from the exterior face of the backing plate. The interior of the column may
now be
accessed for maintenance or service, such as the replacement or cleaning of
the bed
support 268 and/or 0-rings. To return the column to an operational mode, the
above
procedure is reversed.
FIG. 4a is a schematic front view of a column in accordance with the
invention.
The column 310 is supported on legs 304 and has a base assembly 363 separated
from
an adapter assembly 315 by a tube 312. These components are made of strong,
inert
materials which are approved for GMP within the pharmaceutical industries,
such as
stainless steel. In the figure, the base assembly 363 and adapter assembly are
connected to a drive system which takes the form of three hydraulic cylinders
334. It will
be understood that in other embodiments, different drive systems may be used
to raise
and lower the column, such as those powered by compressed air or electricity.
Furthermore, it is not essential that three cylinders are used, in some cases
one being
sufficient. The column 310 has a top nozzle 311 and a bottom nozzle for the
introduction
of liquids into the column. An electrical unit 378 for controlling the drive
system is also
shown.
FIG. 4b is a side sectional view of the column of FIG. 4a showing one of the
hydraulic cylinders 334 in cross section. The cavity 322 for containing the
bed of
chromatographic media can be seen in cross section. The liquid inlet 305, 375
and
outlet 306, 376 of the top 311 and bottom 372 nozzle are shown, for the
introduction and
removal of liquids from the column 310. The cylinder 334 is connected to the
base
assembly (seen here comprising backing plate 364, distributor 366 and bed
support 368)
and the adapter assembly 315 (seen here comprising backing plate 320,
distributor
331 and bed support 328).
FIG. 4c is a top plan view of the column of FIG. 4a which shows the three
18
CA 02597448 2007-08-16
PU0757-1
hydraulic cylinders 334 and nozzle 311 with liquid inlet 305 and outlet 306.
To raise the adapter assembly 315 for maintenance purposes, the nuts under the
upper column flange, which join the adapter 315 and column flange 313a, are
loosened
and removed. The drive system then lifts the adapter assembly 315 by means of
the
hydraulic cylinders 334. The adapter assembly 315 is raised until the locking
bolts are
opposite the threaded holes in the hydraulic cylinders 334 and the bolts
screwed in to
secure the assembly in the service or maintenance position (see FIG. 3).
FIG. 5a is a front perspective view showing the adapter assembly 415 raised
and
secured into position to provide a gap 427 for access to the interior of the
column for
service or maintenance. The column 410 has a drive system comprising three
hydraulic
cylinders 434. The adapter bed support 428 of the bed support, the distributor
431 and
the backing plate 420 are now visible; the bed support 428 can be unfastened
from the
distributor 431 by releasing the fixing means (not shown) without accessing
the gap 427.
In order to describe this process, reference is made to FIG. 4 in that the
nozzle 311 is
first removed to provide access to remove the retaining nut (not shown) which
secures
the bed support 328 to the distributor 331 without accessing the gap 427. The
fixing nut
is removed from the exterior face of the distributor 331.
FIG. 5 b shows release of the fixing means from the backing plate 420 side of
the
adapter assembly using a spanner 446. The fixing means (in the form of a
retaining nut,
obscured by the spanner) secures the adapter bed support to the distributor.
The bed support 428 is heavy and requires the use of a special handling device
to lift it once it has been separated from the adapter assembly.
An embodiment of the handling device 580 is shown in FIG. 6. The device 580 is
in the form of a trolley or cart with a central pillar 581 supported on frame
582 having
legs 583. The device 580 is made of strong, inert materials; such materials
include, but
are not limited to, stainless steel and other materials which are suitable for
use in a GMP
environment typical of the pharmaceutical industry. Extendable arms 585 a, b,
c project
from the pillar 581 and can be raised or lowered relative to the pillar 581 by
mechanical
19
CA 02597448 2007-08-16
PU0757-1
or other means. In the embodiment shown, the arms 585 a, b, c are raised or
lowered
by a manual jacking mechanism (not shown) adjacent to the handle 584 which
provides
the means to steer or control the device. The arms 585 a, b, c are designed to
bear the
weight of the distributor or bed support and are extendable to the diameter of
these
components. While the embodiment shown has three arms 585 a, b, c, it will be
understood that the device is not so limited and that other embodiments may
have less
than or more than three arms (e.g. one, two, four, five) depending on the
individual
design. Holes 587 a, b, c at the extremities of the arms 585 a, b, c are
provided for
bolting or securing of the distributor and/or bed support to the arms for
safety, particularly
during transport. Pads (not shown) may be fitted to the arms 585 a, b, c to
minimise any
risk of damage to the bed support/distributor when these components come into
contact
with the arms. A raised, central element, 588 (typically of conical shape) for
receipt of
the central hole in the bed support or distributor provides a means for
centralising these
components on the arms 585 a, b, c of the device 580. This element 588 may be
fitted
on either, or both, the upper or under side of the point where the arms 585 a,
b, c
intersect. In operation, the distributor and/or bed support is either
suspended from the
arms 585 a, b, c or supported on the arms. Pivotal wheels 586 allow easy
movement
and manoeuvrability of the handling device 580. In the embodiment shown, the
movement of the device 580 and the raising/extension of the arms 585 a, b,c
are by
manual means, but it will be understood that other embodiments are possible
which
incorporate powered systems (e.g. electrical, pneumatic or hydraulic systems)
to drive
the device 580 and lift/lower the arm 585. It will also be understood that in
other
embodiments of the handling device (not shown), arm 585a is capable of
pivoting or
rotation around pillar 581 to enable the arms 585 b and c to access a narrow
gap
between any two cylinders (e.g. 434 of FIG. 5a) and remove/insert a bed
support and/or
distributor which have a diameter which is greater than the distance between
any two
cylinders in the column (e.g. 434 of FIG. 5a).
The operation of the device 580 in removing the bed support is shown in FIG. 7
CA 02597448 2007-08-16
PU0757-1
to 9.
FIG. 7a and FIG. 7b are perspective views of the column of FIG. 5 showing the
handling device of FIG. 6 supporting the bed support 628 on one or more arms
685. The
arms 685 are raised into position below the bed support 628, care being taken
not to
damage the bed support by positioning the pads (not shown) on the arms 685 of
the
handling device 680 under the outer rim of the bed support and then gently
raising the
arms 685 up to the bed support. Once the arms 685 are in position, the nuts on
the
threaded rods 633 that go through the back plate 620 and distributor 631 into
the outer
perimeter of the bed support 628 are loosened and the bed support can be
removed on
the handling device. The rods 633 are initially loosened with a spanner and
finally
removed by hand. As can be seen from the figures, the removal of the rods 633
is
carried out from the exterior face of the backing plate 620 without accessing
the gap and
thus without exposing the operator to a suspended or supported overhead
weight.
FIG. 8a and FIG. 8b are perspective views showing the removal of the bed
support 728 on the handling device 780 from the column 710. In FIG. 7a the bed
support 728, supported on the arms 785 of the device 780, is removed from the
column
710 without substantially tilting the support 728. The device 780 can then be
moved
away from the column (FIG. 8b) and the arms 785 lowered in order that the bed
support
728 can be cleaned or replaced. Maintenance or servicing the column may now be
carried out as required. For example, the bed support 728 may be cleaned or
replaced,
0-rings replaced and/or the distributor 731 may also be removed for cleaning.
To return to an operational mode, the above procedure is simply reversed. The
bed support and/or distributor is returned to the column and affixed to each
other and to
the backing plate, the nozzle reattached, the adapter assembly lowered and
bolted to the
column tube.
Access to the bottom bed support and interior of the column will now be
described with reference to FIGS. 9 to 13. To access the bottom bed support,
the tube is
released from the base assembly by unscrewing the bolts that join it to the
base and
21
CA 02597448 2007-08-16
PU0757-1
then lifting the tube and upper adapter assembly with the hydraulic cylinders.
FIG. 9a shows a column 810 as previously described in FIGS. 3 to 5 and FIGS. 7
and 8. The bolts on the lower flange 813b of the column tube which fasten the
tube 812
to the bottom backing plate 864 are loosened and unscrewed. The column tube
812 and
adapter assembly 815 are lifted by the hydraulic cylinders 834 of the drive
system until
the hole indicated by 'A' is opposite the hole indicated by 'B' in the inset
of FIG. 9a.
Locking bolts 837 are then introduced into the aligned holes in the locking
pin 870,
bracket 836 and cylinder 834 to secure the tube and adapter assembly in
position (FIG.
9b). After removal of the bolts securing the tube 812 to the bottom backing
plate 864,
maintenance can now be carried out on the column in the gap 827 created by
raising the
tube and adapter assembly.
FIG. 10 shows the column 910 with the tube 912 raised and mechanically locked
to the cylinders 934 in readiness for maintenance. The bottom nozzle (not
shown - see
272 in FIG. 3) is first removed from the back plate 964 by unscrewing the
retaining bolts.
The retaining nut (or fixing means) which fastens the bed support 968 to the
distributor
966 is released from the backing plate 964 side of the column 910. If
additional fixing
means are present, such as bolts (not shown) which fasten the bed support to
the
distributor and the backing plate, and are located on the perimeter of the
backing plate,
these are released from the backing plate face of the column.
The bed support 1068 can now be removed from the column by use of the
handling device as shown in FIG. 11a and FIG. 11b. The handling device (as
described
in FIG. 6 above) 1080 is wheeled into position where the arms 1085 are a few
centimetres or inches above the bed support 1068. The bed support 1068 has a
number
of threaded holes that correspond to the holes used to bolt the bed support to
the
backing plate 1064. The arms 1085 of the handling device 1080 have holes
through
which bolts are screwed into the bottom bed support 1068; these holes are
aligned to
those of the bed support 1068 and bolts affixed to secure the bed support to
the arms
1085. Once attached, the bed support 1068 can be removed from the column by
raising
22
CA 02597448 2007-08-16
PU0757-1
the arms 1085 a few centimetres and wheeling the handling device 1080 away
from the
column 1010. The bed support 1068 can now be cleaned or new 0-rings replaced
as
necessary. Generally the bed support will be moved away from the column, as
shown
in FIG. 12, lowered onto a surface (such as a trolley or workbench) and
released from
the arms 1185 of the handling device 1180 to facilitate cleaning and
servicing. The
distributor (1066 in FIG. 11) can also be removed and serviced in a similar
manner using
the lifting device.
Once maintenance or servicing has been completed, the column is returned to an
operational mode by simply reversing the process as described above. This
involves
replacing the bed support/and or distributor in the column, affixing the
components to the
backing plate, reattaching the nozzle, lowering the tube and adapter assembly.
FIG. 13
shows the column 1210 of FIG. 11 connected to the hydraulic control unit 1290
with the
tube 1212 lowered and ready to be bolted to the backing plate 1264.
All patents, patent publications, and other published references mentioned
herein
are hereby incorporated by reference in their entireties as if each had been
individually
and specifically incorporated by reference herein. While preferred
illustrative
embodiments of the present invention are described, one skilled in the art
will appreciate
that the present invention can be practiced by other than the described
embodiments,
which are presented for purposes of illustration only and not by way of
limitation. The
present invention is limited only by the claims that follow.
23
