U.S. patent number 3,856,681 [Application Number 05/281,511] was granted by the patent office on 1974-12-24 for chromatography apparatus and method.
Invention is credited to Charles N. Huber.
United States Patent |
3,856,681 |
Huber |
December 24, 1974 |
CHROMATOGRAPHY APPARATUS AND METHOD
Abstract
A preparative and production chromatography column includes a
relatively inert core onto which is wound in a spiral pattern a
relatively inert sheet of material such as a synthetic polymeric
film. Prior to winding the film is coated with a chromatographic
media. The completed column contains alternating layers of
relatively inert material and layers of chromatographic media. The
thickness dimension of the chromatographic media is arranged
substantially perpendicularly to the primary direction of fluid
flow through the column.
Inventors: |
Huber; Charles N. (Sequim,
WA) |
Family
ID: |
23077605 |
Appl.
No.: |
05/281,511 |
Filed: |
August 17, 1972 |
Current U.S.
Class: |
210/198.2;
96/107 |
Current CPC
Class: |
B01D
53/025 (20130101); B01J 20/28052 (20130101); B01J
20/282 (20130101); B01J 20/28033 (20130101); B01J
20/283 (20130101); B01J 2220/52 (20130101) |
Current International
Class: |
B01D
53/02 (20060101); B01d 015/08 () |
Field of
Search: |
;210/31C,198C
;55/67,386,191 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Adee; John
Attorney, Agent or Firm: Christensen, O'Connor, Garrison
& Havelka
Claims
What is claimed is:
1. In a chromatography column in which flow of a fluid to be
separated occurs primarily along a predetermined axis, said column
having a height dimension, a packing for said column
comprising:
a plurality of layers of chromatographic media arranged contiguous
to each other, said layers having a thickness dimension and a
height dimension, said thickness dimension of said layers extending
substantially perpendicularly to said predetermined axis, said
height dimension of said layers extending substantially parallel to
said predetermined axis, said layers being substantially continuous
and homogeneous to form a uniformly dense layer in both the
thickness and height dimensions of said layers, said height
dimension of said layers being substantially equal to the height
dimension of said column.
2. The column of claim 1 wherein said layers are composed of sheets
of chromatographic media, said sheets having surfaces arranged
contiguous to the surface of a next adjacent sheet.
3. The column of claim 1 wherein said sheets are serially
interconnected to form an integral, continuous roll of
chromatographic media.
4. In a chromatography column in which the flow of fluid to be
separated occurs primarily along a predetermined axis, packing
means for said column comprising:
a plurality of layers of chromatographic media being arranged
adjacent each other having the surfaces thereof extending
substantially along said axis, said surfaces being arranged
adjacent each other, said layers having a thickness dimension
extending in a direction substantially perpendicular to said
axis,
partitioning means interposed between adjacent ones of said
plurality of layers for separating said layers and maintaining said
layers at a substantially uniform thickness, said partitioning
means being substantially impervious to fluid, said partitioning
means contacting said surfaces to prevent substantial fluid flow
between said surfaces and said partitioning means.
5. The column of claim 4 wherein said layers of chromatographic
media are of substantially uniform thickness and density.
6. The column of claim 4 wherein said partitioning means comprises
at least one sheet of relatively inert material, said layers being
adhered to said partitioning means.
7. The column of claim 4 wherein said partitioning means is a
structural component of said packing.
8. The column of claim 7 wherein said partitioning means has a
thickness less than the thickness of said layer.
9. The column of claim 4 wherein said column has a substantially
cylindrical shape, said partitioning means comprising a continuous
sheet of partitioning material arranged in a spiral pattern to form
said cylinder, said chromatographic media forming a continuous
spiral layer adjacent said partitioning means.
10. The column of claim 4 wherein said column is composed of
separate layers of media alternating with separate layers of said
partitioning means to form a laminated structure.
11. The column of claim 10 wherein said column is substantially
cylindrical, said layers of chromatographic media comprising
coaxial substantially cylindrical shells and wherein said
partitioning means comprises separate substantially cylindrical
coaxial shells interposed between said layers of chromatographic
media.
12. The column of claim 10 wherein said column is a parallelepiped
of separate layers of chromatographic media alternating with
separate layers comprising said partitioning means to form a
sandwich structure.
13. The column of claim 4 wherein said partitioning means comprises
a sheet of relatively inert material.
14. The column of claim 13 wherein said sheet comprises a material
of relatively high thermal conductivity.
15. The column of claim 14 wherein said thermally conductive
material comprises a metal.
16. The column of claim 13 wherein said sheet comprises a synthetic
polymer.
17. The column of claim 4 further comprising:
means in said column for thermally conditioning selected locations
within said column.
18. The column of claim 17 wherein said means for thermally
conditioning comprises means for heating selected portions of said
column.
19. The column of claim 17 wherein said means for thermally
conditioning comprises means for cooling selected portions of said
column.
20. The column of claim 17 wherein said means for thermally
conditioning selected portions of said column further comprises
means for transmitting heat from a first portion of said column to
a second portion of said column.
21. The column of claim 4 further comprising:
heat transfer conduit means interposed between said layers of
chromatographic media.
22. The column of claim 21 wherein said heat transfer conduit means
comprise channels formed in said partitioning means.
23. The column of claim 4 wherein the thickness of said individual
layer of chromatographic media does not exceed a thickness at which
a substantial temperature gradient will occur across said multiple
layers of chromatographic media.
24. The column of claim 23 wherein said thickness is less than
about one centimeter.
25. The column of claim 4 wherein said column has substantially a
cylindrical shape, said column further comprising a core composed
of a relatively inert material.
26. The column of claim 25, said core having a channel means
therein for circulating a heat transfer fluid therethrough.
27. The column of claim 4 further comprising:
means in said column contacting said layers of chromatographic
media for sensing the temperature at selected locations in said
column.
28. The column of claim 4 further comprising an outer shell
surrounding said column, said shell providing structural support
for said column.
29. The column of claim 28 wherein said outer shell comprises the
same material as said partitioning means.
Description
BACKGROUND OF THE INVENTION
The invention relates to chromatography, and more particularly to
apparatus and method for effectively conducting preparative and
production chromatography. In a chromatographic process, it is
customary to pass a mixture of the components to be resolved in a
carrier fluid through a chromatographic apparatus or separative
zone. The separative or resolving zone generally consists of a
material referred to as a chromatographic media, which has an
active chromatographic sorptive function for separating or
isolating the components in the carrier fluid. The separative zone
usually takes the form of a column through which the carrier fluid
passes.
A major problem in the art of chromatography is to obtain uniform
fluid flow across a column. It is recognized that the solution to
this problem resides in an ability to obtain uniform distribution
and density of the chromatographic media within a column.
To a large degree the packing problem is surmounted in the
laboratory chromatography columns by using columns having a small
internal diameter, generally on the order of one-eighth inch to
one-half inch. In such columns uneven chromatographic fluid flow
resulting from nonuniform packing of the chromatographic media is
quickly relaxed across the column diameter and does not
significantly affect analytical results. Relaxation of the uneven
fluid flow is caused by radial fluid mixing across the column.
Radial mixing occurs between the particles in the column, but loses
its ability to compensate for nonhomogeneous media distribution
when the thickness of the bed exceeds about 75 particle diameters.
Optimum chromatographic bed thickness has been treated in Journal
of Gas Chromatography, 4, 401, 1966 by Willmott and Littlewood.
To provide an economically feasible preparative chromatography
column, the column diameter must be larger than one inch and
preferably on the order of one foot or more. Attempts to scale up
analytical chromatography columns to a size feasible for
preparative and/or production chromatography have met with
substantial losses in column efficiency. It has been found that as
the column diameter or cross-sectional area is increased, the
separation or resolving power of the chromatography column
decreases. The resolution loss can be attributed primarily to the
fluid flow distribution in the column.
It has also been found that uneven chromatographic fluid flow
occurs at or near the interface between the bed of chromatographic
media and the internal surface of the column wall or support. Fluid
flow at or near this interface occurs at a different rate than
throughout the bed. The particular type of chromatographic media
and the column packing procedure introduce variables which affect
fluid flow at or near this interface. This problem has been treated
in Journal of Chromatography Science, 7,7 (1969) and Modern
Practice of Liquid Chromatography, Chap. 1, 1970. These references
teach that uneven flow at or near the bed-column interface can be
minimized by proper column packing procedure to achieve more
uniform chromatographic media density across column diameter and by
increasing the density of the chromatographic media to eliminate a
free fluid flow path at the interface. Increasing the diameter of
the chromatography column will also minimize the overall effect of
uneven fluid flow at or near the interface. However, an increase of
the column diameter over five millimeters will not allow uneven
fluid flow to be relaxed across the column diameter because the
effect of radial mixing is significantly decreased.
Still another problem which has been encountered with larger
diameter chromatography columns is the occurrence of temperature
gradients through the column. These temperature gradients are
caused by increased sample loading. For a discussion of this
subject see Gas Chromatography, A. B. Littlewood, pp. 219, Academic
Press (1970). Small diameter analytical columns have a favorable
column surface area to volume ratio, which allows rapid
equilibration of column temperature. In larger diameter columns,
the migration of a sample peak through the column is accompanied by
thermal gradients. These thermal gradients cause an enlargement of
the sample peak and a resulting loss in chromatographic resolution.
In larger columns the dissipation of heat required to eliminate the
thermal gradients cannot be accomplished through the column wall
because of the decrease in the column surface to column volume
ratio, i.e., the increase in column diameter.
Various internal column devices have been proposed to overcome the
difficulties of producing large diameter preparative and production
chromatography columns which will yield a sharp sample separation.
Such devices have been described in U.S. Pat. No. 3,250,058, South
African application 66/3,204, U.S. Pat. No. 3,310,932, U.S. Pat.
No. 3,436,897 and U.S. Pat. No. 3,492,794. Several of these
references disclose partition elements which are placed
perpendicularly to the primary flow axis of the chromatography
column. Such partition elements are introduced into the column in
an attempt to correct the uneven fluid flow by inducing lateral
flow and radial mixing of the normally axially flowing fluid
streams. These partition elements must also subsequently redirect
the lateral fluid flow in an axial direction. These attempts at
solving the uneven fluid flow problems still result in reduced
efficiency for large scale applications when compared to analytical
results.
Another approach to resolve the problems encountered in large scale
preparative and production chromatography has been to limit the bed
diameter or thickness over which radial mixing can function, while
increasing the overall cross-sectional area of the chromatography
column. U.S. Pat. No. 3,386,035 describes a technique whereby
elongated rod-like elements are arranged parallel to the axis of
the column. These rod-like elements produce unsymmetrical column
cross sections causing difficult column packing and uneven fluid
flow. The elements also limit overall productive output of the
column.
To build an effective preparative or production chromatography
column, a homogeneous distribution of chromatographic media and
maintenance of uniform media density across the column must be
achieved. This thesis has been set forth in several published
articles, among which are those appearing in "Journal of
Chromatography Science," 7,1 (1969), "Journal of Chromatography
Science," 7,257 (1969) and "Journal of Chromatography Science,"
8,434 (1970).
The present invention provides a chromatography column which
achieves results on a scale which have heretofore eluded others'
attempts. An object of the present invention, therefore, is to
provide an efficient, large diameter, preparative or production
chromatography column for use with both gas and liquid
chromatographic techniques. Other objects of the present invention
are to provide: a relatively simply constructed, inexpensive, and
effective preparative and production chromatography column which
embodies a homogeneous chromatographic media distribution and
uniform chromatographic media density; means of determining
temperature at any preselected point within the column; means for
controlling temperature and minimizing temperature gradients
throughout a chromatography column; a chromatography column having
essentially no diametric size limitation; a column which can be
produced in many desired cross-sectional shapes; a chromatography
column which can be quickly and relatively inexpensively
manufactured; a chromatography column which resolves the uneven
fluid flow problems encountered when attempting to scale up
analytical columns to preparative and production columns; and a
chromatography column which can also be utilized for analytical
procedures.
SUMMARY OF THE INVENTION
The present invention invention therefore provides a chromatography
column in which primary fluid flow occurs along a predetermined
axis comprising a plurality of layers of chromatographic media
arranged adjacent each other, the thickness dimension of said
layers extending substantially perpendicularly to said axis.
Preferably the chromatography column comprises a plurality of
layers of chromatographic media spaced laterally from each other by
relatively inert partitioning means interposed between the
layers.
BRIEF DESCRIPTION OF THE DRAWINGS
A better understanding of the present invention can be acquired by
reading the ensuing specification in conjunction with the
accompanying drawings wherein:
FIG. 1 is a pictorial isometric view of a preferred embodiment of
the chromatography column of the present invention;
FIG. 2 is an enlarged cross-sectional view of a portion of the
preferred chromatography column taken along section line 2--2 of
FIG. 1;
FIG. 3 is an enlarged cross-sectional view of a portion of the
preferred chromatography column taken along section line 3--3 of
FIG. 1;
FIG. 4 is an enlarged cross-sectional view similar to that of FIG.
3 of a second embodiment of the chromatography column of the
present invention;
FIG. 5 is a cross-sectional view of a portion of a third embodiment
of the present invention;
FIG. 6 is a pictorial isometric view of one type of partitioning
layer which can be utilized with the present invention;
FIG. 7 is a pictorial isometric view of one type of core which can
be utilized with the present invention;
FIG. 8 is a pictorial isometric view of a temperature sensing and
heating means positioned within a portion of the preferred
chromatography column of the present invention; and
FIG. 9 is a pictorial isometric view of a fourth embodiment of the
present invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention broadly relates to preparative and production
chromatography columns. A chromatography column in accord with the
present invention is made by arranging a plurality of layers of
chromatographic media adjacent and/or contiguous each other. The
layers of chromatographic media are preferably preconstructed in
relatively thin lamina so that the length and width dimensions of
each layer are relatively large in comparison to the thickness of
the layer. The thin layers are then formed into a column of desired
shape and dimension to provide a usable preparative chromatography
column having overall dimensions dependent upon the length and
width of the original preconstructed layers and a total thickness
dependent upon the number of preconstructed layers employed.
Depending on whether a continuous preconstructed layer or whether
individual preconstructed layers of equal size are initially
prepared, a chromatography column can be constructed in accord with
the present invention which has a circular cross section or which
has a rectangular cross section. Other cross-sectional
configurations can be constructed as desired.
To form a rectangular chromatography column, the thin layers of
chromatographic media are stacked on each other with the surfaces
of the layers adjacent each other. A sufficient number of layers
are superposed on each other until a chromatography column of
desired overall thickness is produced. The thickness (T) of the
chromatography column is directly proportional to the number of
thin layers of thickness (t) used in the column. The width (W) of
the column is substantially equal to the width (w) of the original
layer of chromatographic media utilized to build the column. The
height (H) of the column corresponds to the length (l) of the
original layers.
Likewise a chromatography column of substantially circular cross
section can be formed from a single, elongate, preconstructed layer
of chromatographic media of width (w), length (l) and thickness
(t). A core rod of height (h) is placed along one end of an
elongated, preconstructed layer of chromatographic media. The layer
of chromatographic media is then rolled in a spiral pattern about
the core rod to build up successive layers of material of
chromatographic media to form a chromatography column of height (H)
corresponding to the original width (w) of the elongate layer of
chromatographic media, and having a diameter (D) which is a
function of both the original thickness (t) and the length (l) of
the elongate layer of chromatographic media.
It is important when constructing a chromatography column in accord
with the present invention that the preconstructed layer of
chromatographic media be of uniform thickness throughout its length
and width and that the media in the thin layer have a uniform
density throughout. It is preferred that the layer of media be
substantially homogeneous with respect to itself; however, for
certain applications and materials it is to be understood that
nonhomogeneous construction can be employed.
A chromatography column prepared in accord with the present
invention, whether rectangular, circular, or other desired cross
section, can be formed from a continuous layer or successive
discrete layers of chromatographic media. For example, a
substantially cylindrical column can be formed from successive
cylindrical shells of chromatographic media, each of which increase
in diameter approximately 2(t) for each successive shell. Likewise
a column of rectangular cross section can be prepared in an
accordion-like manner or can be prepared by stacking individual
sheets or layers of media contiguous with or adjacent with the
immediately preceding layer to form a stack.
The present invention is adaptable to use with both gas and liquid
chromatography. As those of ordinary skill in the art are aware,
the chromatographic media may change when utilizing gas and liquid
chromatography. In addition, of course, the chromatographic media
will change depending upon the particular liquid or gas system
encountered as a starting material or carrier, and will vary with
the particular separation to be effected or particular application
of the individual column.
As stated, it is important that the process conditions, primarily
formation of homogeneous, uniformly dense, and thick individual
layers of chromatographic media, be maintained with care. If
reproducibility of results among columns of dissimilar or similar
cross-sectional structure is desired, then uniformity in density
and thickness should be maintained for the layers utilized in
building each of the different columns. An additional criteria of
the present invention is homogeneity or perfect distribution of the
chromatographic media within the individual media layers. This is
much easier to achieve when forming thin layers of chromatographic
media. Thus it is much easier to maintain homogeneity in a layer
having a 2 millimeter thickness than one having a 25 millimeter
thickness.
Additionally, it is preferred that the thickness (t) of an
individual layer of chromatographic media does not exceed a
thickness at which a substantial temperature gradient appears
across that dimension. Resultantly, there will be substantially no
temperature gradient appearing through the multiplicity of layers
in the column. In most instances, the thickness of a single layer
of chromatographic media should not exceed about 15 percent of the
total chromatographic column diameter or thickness. Most preferably
the thickness of an individual layer is about 1 percent or less of
the column thickness or diameter. For example, for a column having
a diameter of 500 millimeters it is preferred that the average
thickness of an individual layer be less than above 5 millimeters.
A preferred chromatographic media layer thickness is on the order
of less than 1 centimeter.
In a preferred form of the chromatography column of the present
invention, a layer of partitioning material can be interposed
between the successive layers of chromatographic media. The
partitioning layer functions to maintain uniform temperature within
the layer of chromatographic media and functions to relax fluid
flow unevenness across the thin media layer. A layer of
partitioning material also maintains uniform thickness and density
in the layer of chromatographic media prior to and during use. In
addition the layer of partitioning layer can serve as a backing or
support for the layer of chromatographic media. It is preferred
that the thickness of the partitioning layer be less than the
thickness of the media layer. In this manner the overall width of
the column does not greatly exceed the effective width of the
column, i.e., the additive width of the individual layers of
chromatographic media. Moreover, when using a partitioning
material, it is important that the portion of the layer of
chromatographic media next to the partitioning material be
maintained at the same uniform density as the interior of the media
layer. Good physical contact must also be present between the media
layer and the surface of the partitioning material.
The partitioning layer can be constructed from a variety of
materials as pointed out hereinafter. It is preferred that the
partitioning layer is composed of a material which is relatively
inert with respect to the chromatographic process. By relatively
inert it is meant the material does not adversely affect the
chromatographic process. Depending upon, among other things, the
particular application of a column, the type of materials being
separated, the composition of the carrier, and whether gas or
liquid chromatography is being used, the partitioning layer can
have a smooth or rough surface texture, can be pervious or
substantially impervious to chromatographic fluid, and need not be
uniformly dense.
Referring now to FIGS. 1, 2 and 3 a preferred embodiment of the
present invention is illustrated. A pictorial isometric view of a
chromatography column 10 in accord with the present invention is
shown in FIG. 1. Column 10 is formed by initially positioning a
central core 12, preferably composed of relatively inert material,
horizontally on a temporary support structure. Although it is not
preferred, a core prepared from chromatographic media could be
utilized. Exemplary preferred materials for the central core 12
include a dowel composed of a nonporous, rigid synthetic polymeric
material, such as polytetrafluoroethylene, or a dowel composed of
stainless steel.
A long sheet of material which will form a partition layer 14 is
then attached to the central core 12 by heat sealing or affixation
with adhesive. The width (w) of the sheet of material forming the
layer 14 will correspond to the height (H) of the column 10. A
uniformly dense and constant thickness layer 16 of chromatographic
media is then contacted with or applied to the partitioning layer
14. The central core 12 is then rotated so as to roll the
superposed layer 16 of chromatographic media and partitioning layer
14 onto the core. The rolling process is continued until a column
of desired diameter (D) has been constructed. The diameter (D) will
correspond to the diameter of the core 12 and the multiple
thicknesses of the layers 16 and 14 of chromatographic media and
partitioning material, respectively.
As shown in FIGS. 2 and 3 the resultant chromatography column will
thus be composed of the central core 12 and, viewing in a lateral
direction with respect to the column 10, a plurality of adjacent
layers 16 of chromatographic media which have a uniform thickness
and packing density. The composition of chromatographic material
from which the layers 16 are constructed will be dependent upon the
particular chromatographic application. Factors to be considered
are whether gas or liquid chromatography will be utilized, in
addition to the components of the mixture of fluid which will be
separated. Herein when the word fluid or chromatography fluid is
utilized it is to be understood that reference is being made to
carrier gas or liquid and the components in the carrier gas or
liquid which are transported through the column for purposes of
separation. Exemplary chromatographic media used in liquid
chromatography can be cellulose, silica, alumina, kieselguhr,
silicone grease, glass fibers, carbon and several others. Gas
chromatography can use these media in addition to certain others,
such as crushed firebrick, squalane and apiezone grease.
The chromatographic media layer 16 can be applied to the
partitioning layer in a variety of ways. If the chromatographic
media is in particulate or powder form, a layer of uniform
thickness can be distributed over the sheet of partitioning
material prior to the time it is rolled onto the core. The
chromatographic media may be put into a liquid suspension and then
applied to the partitioning layer. An adhesive or binder can be
used to coalesce particulate media into a uniformly dense and
mechanically stable layer. A suitable adhesive or binder is calcium
sulfate or polymerizable ethylene monomer. The chromatographic
media itself may also act as a binder to the partitioning layer.
Additionally, the chromatographic media can be a liquid alone, such
as silicone oil, and can be applied in a uniform layer to the
support film or partitioning layer. If desired, relatively large
particles, composed of media or relatively inert material, can be
uniformly distributed throughout the media layer. Such particles
can function to reduce the overall pressure drop through the final
column.
In the embodiment of FIGS. 1 through 3, the partition layer can be
composed of a relatively inert, support film of a synthetic
polymeric material, such as polytetrafluoroethylene, having a
thickness on the order of 0.004 inches. For other applications, a
metallic sheet or film of aluminum or other material compatible
with the chromatographic solvents, pressures and temperatures can
be used. As stated above, it is preferred that the materials
utilized for the partition layer be composed of a material
relatively inert with respect to the chromatography process. Other
support films, such as nonwoven fibrous mats or woven cloth of
either synthetic polymeric or metallic filaments, or glass fiber
mats can be effectively employed.
As shown in FIG. 1 column 10 also contains an outer shell 18 which
is present primarily for structural purposes. The exterior shell 18
is formed by continuing to wrap the partitioning layer 14 about the
column 10, while omitting the step of coating the partitioning
material 14 with a layer 16 of chromatographic media. Thus a
plurality of wraps around the exterior of the column can consist
solely of the partitioning material. The structural integrity can
thus be enhanced. As an alternate, different structural material
can be interposed between or substituted for the layers of material
composing the outer shell 18 to provide enhanced structural
integrity. For example, if a polymeric film is utilized for layers
14, a metal sheet can be placed on the film as it is being wrapped
about the column 10 to form the outer shell 18. In addition, an
adhesive or other suitable fastening means can be applied to the
last wraps of the material which form the outer shell 18 to provide
a secured outer shell.
If desired a suitable casing can be employed to surround the column
10. For example, column 10 can be inserted into a glass, metal or
polymeric tube having an internal diameter corresponding to the
external diameter of the column 10. Suitable fluid admission,
collection and monitoring systems can also be employed with the
present column as in conventional analytical columns.
Referring now to FIGS. 4 and 5 an alternate embodiment of the
present invention is illustrated. In this embodiment a plurality of
layers 20 of chromatographic media are built up in the form of
successively larger diameter, coaxial cylindrical shells. These
shells are applied to a central structural core 22. Referring to
the enlarged cross section of FIG. 5, cylindrical shells can be
formed by suspending chromatographic media in a carrier and
incorporating an adhesive. The suspension can then be sprayed onto
the cylindrical core 22 as it is being axially rotated to provide
uniform layers 20. Thus, a plurality of uniformly dense and thick
layers can be achieved as long as the producton conditions are well
regulated. This coaxial layer configuration can be formed with or
without partitioning layers alternating and coaxial with media
layers.
Referring now to FIG. 6 an alternate embodiment for a layer 24 of
partitioning material is illustrated. The partitioning layer 24
includes a plurality of heat transfer fluid flow channels 26. Flow
channels 26 as shown are formed integrally with the partitioning
sheet 24. As will be noted, the partitioning sheet 24 has a uniform
thickness (t) between which the flow channels are situated in a
corrugated pattern. A preferable material for this embodiment of
the partitioning layer 24 is a material of relatively high thermal
conductivity such as aluminum or some other metallic substance. It
should be understood that if such heat transfer channels are to be
utilized with a column such as shown in FIGS. 1 through 3, a
suitable manifold system must be utilized to introduce the heat
transfer fluid, such as water, into channels 26 and to exhaust the
fluid from channels 26 in the direction exemplified by the
arrows.
FIG. 7 shows an alternate core 28 which can be utilized for the
purpose of transmitting heat to or from the interior of a
chromatography column constructed in accord with the invention.
Hollow core 28 can be utilized to construct a column similar to
that of FIGS. 1 through 3. Core 28 contains a channel 30 formed in
the interior of the core 28. Again suitable inlet and outlet
connections are required for ingress and egress of a heat transfer
fluid. Core 28 can be composed of a material of relatively high
thermal conductivity such as a metal, for example, aluminum.
As shown in FIG. 8, the heating function can alternatively be
performed by an electric resistance heater 32, shown schematically.
Heater 32 can be interposed between a layer 34 of chromatographic
media and a partitioning layer 36. Electric resistance heater 32 is
powered through leads 38 which extend outside the column to a
suitable source of electrical energy. One or more resistance
heaters can be energized at selected locations within the column as
required.
For conjunctive use with heat transfer means such as that shown in
FIGS. 6 through 8, a temperature monitoring system is also of great
value. One means by which the temperature can be monitored within
the column is by interposing a thermocouple 40 adjacent layer 34 of
chromatographic media. This can be accomplished by positioning the
thermocouple 40 on a layer of chromatographic media 34 as the
column is being rolled up in accord with the embodiment of FIG. 1.
Leads 42 associated with the thermocouple 40 will run away from the
thermocouple to the exterior of the column and will be connected to
a suitable monitoring instrumentation system. Thus, for
appropriately placing suitable thermocouples 40 throughout the
column the appearance of a thermal gradient across the column can
be detected. In response to the detection of a thermal gradient a
heat transfer fluid can be pumped through the flow channel such as
26 in FIG. 6 to either add or remove heat as required. Similarly,
an electric resistance heater 32 can be energized to add heat to
the appropriate location in the system. It is to be understood that
resistance heaters 32 can be more strategically located than heat
transfer channels such as 26 to provide a more localized control of
the thermal conditions within the column. It should also be
realized that for many applications sole use of a thermally
conductive partitioning layer 36 can provide adequate heat transfer
to equalize a thermal gradient throughout the column.
FIG. 9 shows another embodiment of the chromatography column of the
present invention. In this embodiment a central core or dike 44 is
formed from any suitable relative inert composition, such as a
polytetrafluoroethylene block. Sheets or layers 46 of partitioning
material are prepared and coated with a layer 48 of appropriate
chromatographic media. Layers 46 and 48 are then alternately
superposed until a column 50 of desired thickness (T) is completed.
The length dimension of the individual sheets or layers 46 of
partitioning material will determine the overall height (H) of the
column while the total combined thickness of the partitioning
layers 46 and media layers 48 will determine the overall thickness
(T). The width (w) of the layers 46 of partitioning material will
determine the final width (W) of the column. Although not
necessary, dike 44 can be incorporated into column 50 as an aid to
the separation process. Dike 44 is formed of a relatively inert
material and can be recessed into the top of the column to a depth
on the order of one-eighth inch. Dike 44 is used to hold the
carrier fluid and sample at the top of the column when a separation
is begun. If desired, structural side plates can be placed on all
four sides of the column 50.
At this point it should be noted that all chromatography columns
have a primary direction of fluid flow. Generally chromatography
columns are arranged in a vertical direction with the
chromatographic fluid either flowing upwardly or downwardly through
the column. According to the embodiments of the present invention
as illustrated, the thickness dimension of the successive adjacent
layers of chromatographic media are arranged so that the thickness
dimension is substantially perpendicular to the column axis, i.e.,
the primary direction of fluid flow.
The present invention provides variety and flexibility in
constructing different types of chromatography columns. For
example, materials which can be utilized in the chromatographic
layer include glass beads, porous layer beads, molecular sieves,
gels for gel filtration, alumina, carbon, fibers or filaments,
woven cloth, mesh, porous films and the like. Whenever the term
chromatographic media is utilized herein it is intended to refer
primarily to the active chromatographic composition. When layer of
chromatographic media or similar phrase is used, the layer can
include not only the chromatographic media itself, but also
materials for reducing pressure drop, materials to assist in
homogeneous distribution of the chromatographic media, adhesive
compositions and the like. Any conventional treatment utilized for
the chromatographic media can be applied to the chromatographic
layer of the present invention. The present invention as conceived
utilizes conventional media and conventional media preparation
techniques. The invention as conceived relates to the method and
manner of forming a chromatography column and to the column
itself.
EXAMPLE
An example of a chromatography column prepared in accord with the
present invention follows. A porous chromatographic media composed
of silica powder with a particle diameter on the average of 10
microns is conventionally prepared as normal. One end of a sheet of
aluminum film, 0.004 inches thick, 12 inches wide and 50 feet long,
is connected to a stainless steel core rod, 12 inches long by 0.75
inches in diameter. The prepared chromatographic media is then laid
down on one surface of the aluminum sheet by spreading it onto the
surface to a uniformly packed thickness of 1.0 millimeter. As the
silica powder is spread onto the aluminum sheet, the sheet and
layer of chromatographic media are carefully rolled onto the steel
core rod. This construction provides a cylindrical column with
alternating adjacent layers of aluminum film and silica.
The foregoing example illustrates the basic technique of forming a
chromatography column in accord with the present invention. The
diameter of the column has been limited to a plurality of thin
layers of chromatographic media. The column thus produced is 12
inches high in the direction of longitudinal solvent flow, which
height is dictated by the width of the original aluminum film. The
dimension of the individual layers of chromatographic media are
limited to a finite value, taking into consideration such variables
as type of chromatographic media, activity of chromatographic
media, column diameter, column operating pressure and temperature,
solvent flow rate, separation time, longitudinal diffusion of
samples in the moving solvent phase, and the mass transfer rates of
a sample between the moving and stationary phases of the
chromatographic solvent or carrier.
The overall width of the column in accord with the present
invention can be infinite, the actual diameter being limited only
by practical considerations such as space requirements. Since the
diameter or width of the overall column can be increased without
theoretical limitation, the sample size or amount of substance to
be separated in the bed is not limited. Thus the diameter can be
increased to separate the desired amount of the sample substance to
be produced.
To reiterate, the present invention is applicable to both liquid
and gas chromatography, various porous chromatographic media in
most physical states, for example, powders, pastes, liquids, gels,
beads, fibers etc., can be utilized to produce a column in accord
with the present invention. The partitioning layers and core rods
utilized in the preferred embodiment to partition the adjacent
layers of chromatographic media can be of any material that is
compatible with the physical requirements and chemical reactivity
of the chromatographic system. The partitioning material is
preferably relatively inert. By appropriate selection of core rod
material and partitioning material, a reinforced chromatography
column can be constructed to allow the use of higher pressures
during the chromatography process.
It should also be understood that the present invention is
applicable not only to preparative and production chromatography,
but is equally applicable to analytical techniques. The main thrust
of the invention has been directed toward the former since these
are the areas in which larger chromatography columns are normally
required.
The present invention has been described in relation to several
embodiments. Upon reading the specification one of ordinary skill
in the art will be able to effect various alterations, changes and
substitutions of equivalents to the present invention as disclosed.
It is intended that the invention as conceived be limited only by
the definition of the invention contained in the appended
claims.
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