Note: Descriptions are shown in the official language in which they were submitted.
78S
Background of the Invention
Liquid chromatography is a process utilized in
both preparative and analytical chemistry. Essentially,
the process comprises a stationary phase interacting with
a mobile phase. Typically, the stationary phase is a surface-
active powder suchas silica, alumina, or an inert size-
separating material like a gel-permeation chromatography
packing, or the like. This powder is contained in a chromato-
graphic column. A mobile phase, generally consisting of
a carrier fluid and a sample of a chemical to be identified,
analyzed, or purified, is passed through the column. A
typical utility of the process is to identify various chemical
components in an unknown sample. This identification is
made by (1) using an immobile phase which differentially
retards the progress of different components of the sample
through the column so that the components are separated
and leave the column at different times and (2) continuously
analyzing the effluent of the column over a period of time.
The separation ls achieved when one component of the sample
has more affinity for the stationary phase than does another
component. Also, the separation may be achieved by an exclusion
process based on the difference in sizes between molecules,
e.g., by gel-permeation chromatography processes. The invention
to be described below is related to achieving better and
more dependable identity of the sample components by improving
the efficiency of the process in such a way as to provide
better resolution of the sample.
In order to achieve separation of sample components
which are very close to each other in chemical and physical
.'
7~5
properties, highly sophisticated procedures have been developed
in the many processing techniques associated with liquid
chromatography. Special pumps and valves have been developed
for presenting sample to the inlet of the chromatographic
columns with as much integrity as is possible to avoid building
into the process an initial and inherent dispersal of the
sample which dispersal would tend to reduce the resolution
capabilities of the chromatographic packing within the column.
Moreover, much work has been done to provide flow-distributing
devices at the inlet of the column to assure the even place-
ment of the sample across the column's cross-sectional area.
Also, a great deal of technical effort has provided improved
chromatographic packings and highly-sophisticated analytical
apparatus for measuring various properties of the liquid
effluent leaving the column.
Despite such work as has been described above,
it has remained a problem to achieve a unifo~m packing of
the chromatographic material into a column. Many techniques
have been suggested including vibration (See U.S. Patent
20 3,300,849): All of these techniques require careful control
if segregation of particles by size is to be avoided and -
uniformly packed columns are to be obtained. Even after
the column is filled, problems exist in maintaining the
filling in proper condition during transportation and operation
of the packed columns. (See patent 3,349,920 to Waters)
In general, the most commonly used practice of
filling a high-performance column has been a costly method
including slurrying the packing and passing the slurry into
the column; thereby, in effect, using the column itself
as a form for placing a "filter cake" of chromatographic
-- 3 --
X'
packing therein. Even this costly, time-consuming method
of column manufacture is not without problems caused by
shifting of the packing during shipment when it can be subjected
to various vibration and other transient, non-predictable
physical abuse. This tends to cause voids in the column
and such voids can wholly destroy a column's operating character-
istics for many separations. Such defects in stainless
steel columns are not usually detectable until a standard
sample is measured as a control. Indeed, suppliers of
quality chromatographic columns, until this day, have pre-
tested individually each column before shipment to the customer
to assure that the packing is properly placed in the column.
Of course, this "certifying procedure" provides no protection
against the hazards encountered during shipment or during
use by the customer. -~
A number of solutions have been suggested for
holding the packing "in-place". Some of these, like the
aforementioned vibration technique and slurrying technique,
emphasize a maximum effort to put a conventional packing
into the column in such a way as to have it assume a stable
position. Other techniques such as those described in U.S.
patent 3,808,125 to Good use rather complex or expensive
procedures for fastenin~ the packing to the column wall.
None of these attempts by the prior art have been
dependably successful in achieving any of an excellent perform-
ance, a column-to-column consistency in separating character- -
istics, or a desired degree of stability of performance
over a period of time for a single column, at a cost which
can make the apparatus available to the broadest spectrum
of chromatographers.
-- 4
s
Although the foregoing description of problems
relating to chromatographic columns has been largely devoted
to liquid chromatographic columns, it is emphasized that
many of the problems described above also relate to gas
chromatography, i.e. chromatography wherein the sample and
mobile phase are in gaseous, rather than liquid, form.
Indeed, in many respects, the prohlems relate to all packed-
bed apparatus comprising a porous mass of particles intended
to be intimately and uniformly contacted by a fluid. Such
apparatus includes catalytic beds for the treating of gas
and liquid, packed beds used in ion exchange processes,
in electrophoresis applications, and the like. It is intended
that the invention described below be viewed as an improvement
in packed-column preparation for all such processes; albeit,
the invention will be seen to have particular advantage
in the field of liquid chromatography.
In discussing packed-column processes, it is helpful
to recognize four kinds of space, all of which can be referred
to as "void volume". These include (1) void volume inside
a porous particle; (2) theoretical void volume between particles,
i~e,the type of unavoidable volume which would result from
a perfectly packed bed of spheres of the same size; (3)
void volume which is attributable to imperfect packing of
particles, usually present to some extent in any actual
system utili~ing a particulate packing system; and (4) void
volume which represents relatively large voids resulting
from the consolidation of those voids described in (3).
Voids (4) substantially reduce resolution of a sample being
subjected to chromatographic analysis.
-- 5
7g5
The invention to be disclosed below is believed
to be most useful in avoiding the occurrence of such void
volume as described in (4). The present invention also
tends to reduce void volume as described in (3); moreover,
it makes such void volume more nearly uniform, and closer
to a theoretical idea. Void volume, as generally used
herein relates to a composite of void volumes (3)and (4).
Some workers have suggested compression of the
packing of a chromatographic column by force directed longi-
tudinally, i.e. parallel to the direction of liquid flow.However, such a proeedure is relatively ineffective probably
because the packing tends to bridge the column and interfere
with propogation of the compression force downwardly throughout
the length of the column. An example of such work is described
in the Journal of Chromatoaraphie Seience of Oetober, 1974,
in an artiele entitled "Deseription and Performance of an
8 em. i.d. Column For Preparative Scale High Pressure Liquid-
Solid Chromatography" by Godbille and Devaux.
The above discussion of the sac~ground of the
Invention is made, neeessarily, in view of the Applieants'
invention to be deseribed below. It should be understood
that the eollection, interpretation and discussion of this
baekground is not intended to disclose the background from
the point of view of one being ordinarily skilled in the
art and having no preliminary knowledge of Applicant's invention.
Summary of the Invention
Therefore, it is an object of the present invention
to provide a novel column structure for use in chromatographic
applications wherein the column will exhibit improved uniformity
of separating eharacteristics over its product life.
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78$
Another object of the invention is to provide
a package for shipment of chromatographic packing which
package is readily converted into a dependable chromatographic
column free of any undesirable voids.
Another object of the invention is to provide
improved processes for making and operating chromatographic
columns.
Still another and broader object of the invention
is to provide improved packed columns for use in fluid- --
contacting processes whatever the chemical nature of the
packing or the physical form of the fluid passed therethrough.
Another object of the invention is to provide
a novel means for preparing chromatographic columns which
provides an improved column-to-column uniformity of separating
characteristics.
Still another object of the invention is to provide
a column which may tolerate transportation stresses without
substantial reduction in the column's eventual performance.
A further object of the invention is to provide
a process for making a chromatographic column with such
a high degree of reliability that pre-testing of performance
characteristics become unnecessary.
A further object of the invention is to provide
an inexpensive r high-quality chromatographic column which
can be a disposable item in many, perhaps most, commercial
processing situations.
Another object of the invention is to provide
apparatus and process means for reestablishing excellent
sample resolution in a chromatographic column after the
packing therein has been disturbed.
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78~i
Another object of the invention is to prepare
liquid chromatography apparatus which is easily packed and
which can be easily repaired, e.g., by adding new packing
or changing the packing.
Still another object of the invention is to provide
a column which can be readily "healed" if, somehow, excessive
voids appear in the packing as might occur, for example,
if packing beads break.
Another object of the invention is the achievement
of a column having superior resolution characteristics compared
to previously-known columns of like diameter and packing, -
e.g. a smaller time-concentration profiles of sample components
as they emerge from the column.
Other objects of the invention will be obvious
to those skilled in the art on reading the objects of this
invention.
The above objects have been achieved as a consequence
of the discovery that radial compression of the packing
within a chromatographic column during the use thereof greatly
improves the quality and uniformity of the performance character-
istics of the chromatographic column so compressed.
In the most simple case, the column can be filled
with packing and compressed just before its use by external
pressure acting on the cylindrical wall of the column, e.g.
a wall formed of material such as a thin polyethylene, a
polytetrafluoroethylene polymer, or like sheet material.
The wall is surrounded by a pressure chamber and pressed
inwardly about the entire cylindrical bed, thereby compressing
the particles slightly and achieving better uniformity through-
out the bed. The pressure applied to the bed, preferably
L78S
should not exceed the lateral, radial, yield point of anyportion of the bed, should not cause substantial breaking
of particles, and should not exceed the pressure at which
the mechanical stability of the wall is maintained. If
this happens, there will tend to be a distortion in the
uniformity of the cross-sectional size or shape of the bed
which is, generally, undesirable and tends to make the desired
consistency of the properties of the bed more difficult
to achieve. Usually, excellent results can be obtained
well below this yield point and the determination thereof
is only of academic interest. The yield point, in some
case, might result from breaking or gross displacement of
particles.
As will be indicated below, it is often preferred
to pre-pressurize some of the column packages before they
are shipped. This guarantees a predictable uniformity of
the commercial product. It is emphasized that such pre-
pressurizing, or the filling of a pre-expanded column structure,
is not necessary to the practice of this invention.
There are a number of alternate ways the radial
pressure can be applied: It can be applied by use of mechanical
as well as fluid means. It can be applied from the interior
of the column as well as the exterior of the column. Pressure
from the exterior of the column is believed to be more desirable
because it does not increase the complexity of construction
of the column. However, since one of the substantial advantages
of the invention is the improved performance and consistency
of relatively large diameter columns used in preparative
(as opposed to merely analytical) work, internal radial
compression is sometimes desirable to maximize the distribution
.. .. , ~
of vectors contributing to the radial compression for particu- :
late packing materials. This is believed to be especially
so in columns of up to a foot, or even 10 feet, in diameter.
~If gas is used as a pressurizing medium, consideration
should be given to the permeability of the wall material to
the gas being used. Coatings of less gas permeable materials
may be indicated in some circumstances.)
In this connection, it can be noted that in
most particulate systems any force imposed upon one site
will, at some distance from the site, be attenuated to
a relatively small and ineffectual force. This invention,
in its most advantageous mode, will have every part of
the column packing within the a-foresaid distance (which
may be called a "radius of fluidity") from the portion
of the column.wherein a force-manifesting strain is imposed.
As indicated above, the pressure applied to
a given column should be below the radial yield point
of the particular packing mass utilized. The yield point
itself.will depend on such factors as (1) the nature
of the packing and (2) the way the column is packed.
Thus, a column which has been packed:using a special
procedure such as.slurry or other techniques adapted
to achieve a more densely-packed column, will often be
able to withstand a.somewhat higher pressure than will
a column containing the.same column packing w~ich has
been compacted to a lesser degree. Ne~ertheless, in
many circumstances, the above considerations become moot,
because there simply is no reason to use the more expensive
column-filling techniques when the column is to be operated
in such a way as to achieve the processing benefits achieved
by practice of the process of the invention. A light
-- 10 --
.
tapping technique is entirely suitable for filling columns
to be operated according to the invention.
In general, satisfactory exterior pressures
also depend upon the ease of deformability of the wall,
i.e. the force required to push the wall inwardly towards
the particles. In a column of 2.25-inch inside diameter
and about one foot in length, the following pressure
differ~ntials were found to be useful.
Wall Material External Jacket Pressure
less Internal Column
Pressure
low density polyethylene about 75 psig
0.006-inch wall
polytetrafluoroethylene about 200 psig
0.030-inch wall
These parameters were measured in tests wherein the interior
operating pressures of the chromatographic columns ranged
from 50 to about 500 psig in this series of experiments.
The invention is a much improved way to avoid
packing bed voids. The invention is also believed to
be an excellent way of reducing~ indeed virtually overcoming,
wall channeling effects whereby liquid preferentially
flows through space at the interface of the column wall
and the packing. This is particularly true when a distensible
wall (such as organic resin walls formed of polyethylene
of halogenated hydrocarbon polymers such as that sold
under the trade designation "Teflon" by E.I duPont ~eNemours)
is utilized. Notwithstanding the special advantage achievable ~ -
by reducing wall channeling, the "radial-compression"
process described herein allows a column to be repressurized
time and again to what is substantially the same condition
throughout its volume. The result of this is that a
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X
7~
column produced and operated according to the invention
is more dependable for a series of comparative experiments
than any comparable liquid chromatographic columns known
to the art. How~ver, this effect is of major importance
even if the column is used only once, because its packing
characteristics will be much more dependable when the
column is subject to radial compression. Indeed~ in
columns of larger diameter, e.g. those of over about
one inch in diameter, the primary improvements are largely
due to the uniform packing achieved by the radial compression.
For a given particle size, the undesirable effect of
wall channeling in such large columns has beenl usually,
small in comparison to other imperfections in the packing
arrangement.
Distensible polymers include elastomers and
rubbers of various types. However, it is important to
remember that a chemically inert surface is required
for most chemical operations land especially for liquid
chromatographic analysis). Consequent polyolefins
and halo~enated hydrocarbon polymers like~Teflon
are preferred. Another highly desirable characteristic
of the distensible polymer is a "memory" characteristic
well-known to the art and possessed by many plastics
like polyethylene and Teflon. This characteristic might
be more aptly expressed~ in the present situation, as
an ability to "forget" the shape assumed during a first
pressurization against the packing material and an ability to
assume a new shape if later pressed and molded against
the packing material after it has been disturbed by movement
and shifted relative to the polymeric wall surface.
~ 12 -
Another aspect of the present invention is the
fact that high performance liquid chromatography columns,
even those o~ the type used in high-pressure liquid chroma-
tography (HPLCl can now be manufactured in a large variety
of configurations. The best-known prior art techniques
of column-filling utilized special-frequency vibrations
or settling of particles from a slurry pumped through
the tube. Each of these techniques was basically a s~ttling
technique utilizing gravitational force and best-suited
for use with a elongate 'cylinder. The present invention
can be used in any conEiguration including tubes, coils,
U-shapes or the like~ However, it should be realized
that, in many such configurations~ the present invention ~'
will merely minimize the effect of inherent disadvantages
caused by such disadvantages as the lack of equidistant
fluid paths through the configuration. These shapes
can be oriented vertically or horizontally, the only
limitation being that they be so shaped that each segment
thereof may be subjected to force vectors generally directed
2~ from the outer walls thereof towards the center of the
configuration - a condition described as "radial compression"
in this application
Another means for obtaining the desirable radial
compression is to form a rigid column, say a steel tube,
which has a coating of a deformable material, say a coating
of a plastic such as poly (tetrafluoroethylene), polyethylene,
or the like on inside thereof~ The coating is preferably
chemically inert and among current commercial materials,
poly (tetrafluoroethylene) is a preferred coating. The
- 13 -
coated tube is expanded, e.g. by heat or pressure or
both, filled with a packing material and then allowed
to contract. This contracting resuIts in a radial compression
of the packing particles, with the steel wall acting
as a diaphragm. The particles are pushed into the plastic
coating to the extent that wall-channeling is virtually
eliminated. Residual compression is sufficient to achieve
the uniformity of packing compaction that has been described
for the externally-applied pressure aspect of this invention.
There is some advantage to use of a prestressed
column where in the chamber wall structure is formed
of a relatively non-flexible material like steel~ Such
a column avoids any marked gradient in-differential pressure
between the entrance of a column and the exterior of -
a column. Thus, at higher column operating pressures,
there can be no tendency for a packing to be moved from
the bottom of the column (where a relatively high pressure
differential would be experienced using a flimsy, otherwise
non-structured, retaining package) towards the top of
the column (where the high internal pressure in the column
itself would be much closer to the pressure exerted on
the exterior of a relatively flimsy, otherwise non-structured,
retaining package).
Also, the prestressed columns have advantage
in many low pressure operations wherein the particles
are soft, or spongy, or have internal porosity which
must be prestress and, consequently, where very close
control of the strain on the particles must be exerted
all along the length of the column.
- 14 -
AS may be deduced from the above, in largerdiameter columns, where wall channeling is not a substantial
factor, the above-described pre-compressed metal columns
can be used advantageously without a distensible material
adapted for conforming to the surface of the packing
particles in response to the opposite force exerted by
the particles on the surface. This distension reduces
the void volume at the interface of said mass of particles
with the metal wall of column. "Distensible" in the
sense used here means ability to conform to the irregularities
of diverse particles in the surface of the mass of packing
and to subs~ntially reduce the channeling volume between
the packing and the wall.
It is also possible to expand polymeric columns,
fill them with packing, and allow them to contract to
exert the proper radial pressure on the packing without
the need of maintaining an external pressure~ However,
it is believed that this procedure is best avoided because
of the unpredictable nature of conditions to be encountered
in transportation of such columns. Nevertheless, it
should be noted that such columns can be prepared. Indeed,
a small amount of expansion is also advantageously utilized
before packing thin-wall plastic columns, but this is
done to eliminate ripples and bulges in the compressed
wall, a cosmetic advantage to facilitate the filling
operations and assure a proper initial packing procedure
rather than permanently prestress a diaphragm wall.
It has been found that those advantages of
the instant invention relating to a) reduction or elimination
of wall channeling and b) a more uniform packing also
- 15 -
: -
s
allow optimization of the effects of flow-distributing
techniques at the head of a column. That is, the flow-
distributing techniques-known to the prior art tend to
work better when utilized in columns constructed and
operated according to the instant invention. Moreover,
the instant invention makes the further optimization
of flow-distribution apparatus practical and desirable
because the packed column is, in many cases, no longer
the limiting factor in achieving good uniform flow distri-
bution.
"Bridging" is a phenomena wherein packing arrangesitself in such a mechanical relationship with the walls
of a column that an arch-like resistance is formed to
compression of the packing in directions generally parallel
to the walIs.
One of the advantages of the instant invention
is to avoid bridging interference resistance to effective
compression of the columns. However, it should be realized,
that by radial compression, it is also possible to effect
an improved bridging phenomena ~7herein vertical incremen's
of packing are isolated by bridges which are relatively
close to another. As the bridges become very close to
one another, an improved chromatographic column is produced
which can be successfully operated at higher pressures
than a column containing the same packing which has been
operated with prior art techniques. This is so because
each bridge protects those particles below it from the
pressure exerted above that bridge.
The most advantageous use of this increased
0 bridge frequency is in using relatively soft compressible
- 16 -
packing materials such as a relatively large-pore, lightly-
crosslinked polymeric packing material sold under the
trade designation Sephadex~ Advantage is also achieved
with somewhat smaller-pore, more crosslinked materials
sold under the same trade designation. Such materials
are very well known in the art. Somewhat less advantage
is achieved with less compressible materials, and the
increased bridging is not believed to make a major contribution
to the improved performance of alumina and silica-type
packing materials, the improved performance of such packing
materials in the practice of the instant invention is
believed to be primarily due to factors discussed elsewhere
in this disclosure.
When gas is used to pressuri2e the column,
it may be desirable to use a wall-material which has
a gas-impermeable barrier layer. Various polymeric coating
materials are known to be particularly resistant to passage
of particular gases and may be used. Also, thin metallic
foils may be incorporated between or used in conjunction
with or in place of polymeric films to form suitable
column wall structures.
Illustrative Examples of the Invention
In this application and accompanying drawings
there is shown and described a preferred embodiment of
the invention and suggested various alternatives and :
modifications thereof, but it is to be understood that
these are not intended to be exhaustive and that other --
changes and modifications can be made within the scope -
of the invention. These suggestions herein are selected
- 17 -
and included for purposes of illustration in order that
others skilled in the art will more fuIly understand
the invention and the principles thereof and will be
able to modify it and embody it in a variety of forms,
each as may be best suited in the condition of a particular
case.
Figures one through nine are sections of a
column illustrating steps used to form an externally
pressurized column, and the novel compression columns
formed by said steps.
Figures 10-13 illustrate schematically those
steps used to form a column having an exterior compression
cylinder lined with a deformable polymeric coating according
to the invention and the novel compression column formed
by said steps.
Figures 14a and 14b illustrate schematically
various configurations of chromatographic tubes which
can be advantageously filled according to the invention:
These are set out to illustrate one novel aspect of column
construction made possible by practice of the invention,
i.e. the construction of packed beds which are suitably
packed although shaped with conical (Figure 14a) sinusoidal
(Figure 14B), or other elongate passages which are not
reliably packed using the packing techniques of the prior
art.
Figure 15 is a schematic showing the cross
section of a cylindrical column about which are mounted
mechanically actuated compressing means.
Figure 1 ill-ustrates a polytetrafluoroethylene
tubing 30 of about 0.030 inch wall thickness, 12 inches
long and about 2 inches in tubing diameter. Figure 2
- 18 -
: , . :
~3~8~i
illustrates the placement of the tube in a packing chamber
32. Figure 3 shows a porous glass-frit plug 38 inserted
into the bottom end of the tube to hold it snugly in
the packing chamber. A plug 34 is inserted in the top.
Gas is admitted into the tube 30 through conduit 36 and
plug 34 to obtain an expansion thereof as seen in Figure
4. Air pressure is used to achieve an expansion of about
15% in volume.
Plug 34 is removed. (Fig. 5) Then the tube
is filled with a chromatographic packing material, 60-
200 mesh silica-based packing. Only a slight tapping
or shaking action need be used in filling the column.
A glass frit 38 (Fig. 6) is inserted at the top of the
column and end caps 39 are bolted on to form a pressure
chamber.
Figure 7 illustrates the radial compression
as gas at 250 psig is admitted into chamber 32 through
valve 40 to achieve an initial radial compression of
the tube. End caps 42 ~Fig. 8l are snapped over the
column after it is removed from the packing chamber 32,
for protection of the column during shipment.
The column is then ready for shipment. When
received, end caps are removed, and it is placed into
a pressure vessel ~Fig. 9) such as 50. Gasketed end
plates 51 are bolted down with bolts 52, and in general
such good practice as is known in the art is followed
in manufacture and use of such pressure vessels. In
use, the tube is externally pressurized to about 200
psig above the operating pressure of a li~uid chromatographic
process as measured at the head of the column.
-- 19 -- :
7~
The same procedure is repeated using a medium
density polyethylene film. The film was heated to about
110C to facilitate its pre-fill expansion to 15~. Such
heating resulted in a snug, superior fit of the film
over the packing when after compression the film was
cooled and allowed to shrink to form a taut package~
Indeed, the fit would allow the column to be utilized
advantageous at low pressures, say below about 100 psi~
However, the column tends to "loosen up" a bit on storage
and repressurization is required for the illustrated
construction.
Figure 10 illustrates a steel tube 60 (316
stainless steel) of a wall thickness of 0.080 inch and
an inside diameter dl of about 0.25 inch. The tube is
placed in a heat exchanger schematically shown at 61
and heated from 25C to 85C. Simultaneously a slurry
of 10-micron silica-based chromatography packing is run
through the column in order to deposit the packing according
to the well-known slurry techniques. The combination
of the pressurized slurry and the heated tube expands
the tube during the filling operation substantially
to a diameter d2 as seen in Figure 11.
When the tube is allowed to return to room
temperature as seen in Figure 12, it radially compresses
the packing according to the invention. If a wall channel
effect is to be avoided or minimized, it is most desirable
to utilize a metal tube 62 (Fig. 13~ with its wall 64
coated with about 0~001 inch of a polytetrafluoroethylene
polymer 66 which is distensible under the radial compression
to conform substantially to the shape of the packing
material 69 at interface 68, thereby avoiding highly
- 20 -
:~0~78S
undesirable wall channeling.
The columns described in Figure 10-13 are fitted
with and include end fittings, as are other columns sold
in the chromatographic art, and are shipped pre-compressed
for direct use. Their radial compression is permanent:
they do not usually require any further compression steps
as long as the same packing remains in the column~
A number of simple mechanical means can be
used to achieve the required radial compression. These
are advantageously constructed so that they reduce the
cross-section of the column all the way along its length,
i.e. inlet end fitting to outlet fitting~ The shrinking
of a heat expande~ tube is a species of such mechanical
means wherein the tube itself is the radial compressing
means. In other embodiments of the invention, flexible
wall tubes formed of foil, plastic film, or the like
are distorted, as from a circular to non-circular cross
section, by an external means such as a cam or like device
which is forced against the wall to change its shape
in such a way as to reduce its cross-sectional area.
A decrease in cross-sectional areaJ typically as little
as a 2 to 5 change, is effective in well-packed columns,
decreases of over about 10% are seldom required,
Figure 15 is illustrative of a column equipped
with such mechanical pressurizing means. Column 80 comprises
a tube formed of 0.030-mil thick polytetrafluoroethylene.
It is mounted with 4 cams 82 mounted thereabout in a normal
position indicated in solid lines where they do not press
into the wall 84. These cams extend along the entire length
7~35
of flexible column wall ~l. When it is desired to anply
radial compression, the cams are turned to the position
defined by the dotted lines and they so compress packing
86 that the desired amount of radial compression is achieved.
As in other aspects of the invention, a distensible polymer
surface is advantageous at the interface between column
wall and packing.
It is no part of this invention to discuss in
detail those well-known aspects of the mechanical arts which
can be utilized in devising various means to assure proper
compression. Those skilled in the art will be able to devise
many such quick-actuating devices capable of performing
according to the teaching of this invention. In general,
however, it is desirable to have at least two or three different ~ -
pressure sites on a given column; although in shorter columns,
one pressure site can be very effective.
Figure 15 is also illustrative of the broad scope - ~-
radial compression is intended to have. Obviously the vectors
emanating from the pressure points caused by the cams (des-
cribed hereinafter) are not strictly radial nonetheless,
they have a substantial, effective, net effect which is
radial and act well within the term "radial compression"
as it is used in this specification.
There are numerous other means to provide for
a source of strain-inducing pressure on the packed bed.
For example, the bed could be surrounded by a jacket into
which a low-melting alloy such as Woods Metal could be poured,
pressurized, and allowed to cool and solidify under pressure.
Metals which expand on cooling are preferred. Whenever,
repressurization is required to heal, or repack, or repair
the packing, the alloy could be melted and repressurized
and once again frozen.
Another approach would be to wind a helical wire
or tubing or series of circuIar rings about the column and
use thermal or pneumatic or mechanical means to change the
dimensions of the tubing or rings and produce a strain,
that is a reduction of cross-sectional area on the column.
As has been indicated above, an improved flow
distribution is achieved whenever a good flow distribution
means is employed at the column inlet, and this distribution
is maintained with remarkable fidelity throughout the length
of a novel radially compressed column of the type disclosed.
It has been found that it is usually most desirable
to apply the strain to a packed column before the column
is wetted, i.e., before the liquid chromatographic procedure
is started. When the prepacked columns such as those formed
of polymeric walls are to be used, they will often have
"relaxed" somewhat over a period of time after the initial
packing. Thus, if they are advantageously repressurized before
being wetted, the resulting force is maintained on the column
during use.
The term "diaphragm" as used herein means a column
wall section that can be moved to impart strain to the packing
within the column. Many complex structures can be used
to achieve this result. As will be suggested by example
below, all of the column wall need not be moved, it is often
sufficient to impart strain along a single linear situs
along the column wall. Also, it is possible to exert such
strain by pushing on a substantial number of sites distributed
over the column surface. Walls using all such techniques
are "diaphragms" according to this ~eneral use of the term
in this disclosure. Such walls may be internal, e.g. in
;~
the center of the column and adapted for movement towards
the exterior wall of the column. Nevertheless, it is usually
desirable to use one of the relatively simple structures
disclosed herein.
There are other ways to place the packing under
a suitable,repetitive compressing force. One, is to make ~ -
a dynamically balanced column spun at high speed about its
axis pushing the packing particles outwardly toward the
outer wall of the column. It might well be necessary to
have an axially-positioned follower device ~mechanical or
hydraulic) which would expand to the extent necessary to
fill any space that outwardly-moving particles left. It
is the applicants' position that such a device is a mechanical
equivalent to the present invention because it would use
radial compression and a reduction in effective cross-sectional
area of the packing. The primary forces would be outwardly
directed in this situation, but the centrifugal device would
only be a means for achieving the radial compression. In
such a situation, the one operation achievement of compression
and taking-up of void volume created by the compression
is not achieved, and it is necessary to use the axial follower
to take up the void volume. The follower would be means
made necessary to avoid a central void from forming, by
movement of packing towards the outer wall of the column.
Moreover, a doughnut-shaped column, i.e. one with
a hollow axial bore, could be constructed. Not only could
pressure be exerted from both internal and external cylindrical
walls, but the walls could be used to improve heat transfer
properties of the apparatus.
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s
In general, the term "radial compression" is meant
to describe a compression wherein the compression f~rces
are predominantly aligned in a direction which is normal
to flow of liquid through the column, i.e. in the classical
situation of a cylindrical column, the forces would be directed
toward the center of the cylinder.
It is to be understood that the following claims
are intended to cover all of the generic and specific features
of the invention herein described and all statements of
the scope of the invention which might be said to fall there-
between.
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