U.S. patent application number 10/914341 was filed with the patent office on 2005-01-13 for composite chromatography column.
This patent application is currently assigned to Biotage, Inc., a Delaware corporation. Invention is credited to Horsman, Jeffrey A., Van Davelaar, Peter C..
Application Number | 20050006292 10/914341 |
Document ID | / |
Family ID | 31887258 |
Filed Date | 2005-01-13 |
United States Patent
Application |
20050006292 |
Kind Code |
A1 |
Horsman, Jeffrey A. ; et
al. |
January 13, 2005 |
Composite chromatography column
Abstract
Apparatus for chromatography, featuring a composite
chromatography column including a tubular member having an inlet
end and an outlet end, where the tubular member includes an
innermost first layer comprised of a first material and asecond
layer comprised of a second material. The chromatography apparatus
can also include a first intermediate layer formed from a third
material, where at least a portion of the first intermediate layer
is disposed between the innermost first layer and the second layer.
A second intermediate layer formed from a fourth material, can
further be included in the chromatography apparatus, where at least
a portion of the second intermediate layer is disposed between the
innermost first layer and the second layer. A portion of the second
intermediate layer can be disposed between the second layer and the
first intermediate layer.
Inventors: |
Horsman, Jeffrey A.;
(Charlottesville, VA) ; Van Davelaar, Peter C.;
(Charlottesville, VA) |
Correspondence
Address: |
FISH & RICHARDSON PC
225 FRANKLIN ST
BOSTON
MA
02110
US
|
Assignee: |
Biotage, Inc., a Delaware
corporation
|
Family ID: |
31887258 |
Appl. No.: |
10/914341 |
Filed: |
August 9, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10914341 |
Aug 9, 2004 |
|
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10226530 |
Aug 23, 2002 |
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6783673 |
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Current U.S.
Class: |
210/198.2 ;
422/70; 73/61.52 |
Current CPC
Class: |
G01N 30/6073 20130101;
B01D 15/22 20130101; G01N 30/6026 20130101 |
Class at
Publication: |
210/198.2 ;
422/070; 073/061.52 |
International
Class: |
B01D 015/08 |
Claims
1. A chromatography apparatus comprising: a tubular member having
an inlet end and an outlet end, said tubular member having a
plurality of layers, said layers including at least an innermost
first layer comprising a first material and a second layer
comprising a second material.
2. The chromatography apparatus of claim 1, further comprising: a
first intermediate layer comprising a third material, at least a
portion of said first intermediate layer being disposed between
said innermost first layer and said second layer.
3. The chromatography apparatus of claim 2, further comprising: a
second intermediate layer comprising a fourth material, at least a
portion of said second intermediate layer being disposed between
said innermost first layer and said second layer.
4. The chromatography apparatus of claim 3, wherein at least a
portion of said second intermediate layer is disposed between said
second layer and said first intermediate layer.
5. The chromatography apparatus of claim 2, wherein said first
intermediate layer comprises an adhesive material.
6. The chromatography apparatus of claim 1, wherein at least one of
said plurality of layers comprises an adhesive material.
7. The chromatography apparatus of claim 1, wherein the second
layer is an intermediate layer and an outermost layer is comprised
of the first material.
8. The chromatography apparatus of claim 1, wherein said second
layer has an outer surface having a cross-sectional shape having at
least one substantially flat side.
9. The chromatography apparatus of claim 8, wherein said outer
surface has a substantially rectangular cross-sectional shape.
10. The chromatography apparatus of claim 9, wherein said outer
surface has a substantially square cross-sectional shape.
11. The chromatography apparatus of claim 1, wherein said second
layer has an outer surface having a substantially circular
cross-sectional shape.
12. The chromatography apparatus of claim 1, wherein said second
layer has an outer surface having a substantially triangular
cross-sectional shape.
13. The chromatography apparatus of claim 1, wherein said second
layer has an outer surface having a substantially hexagonal
cross-sectional shape.
14. The chromatography apparatus of claim 1, wherein said second
layer has an outer surface having a substantially octagonal
cross-sectional shape.
15. The chromatography apparatus of claim 1, wherein said second
layer comprises a rigid material.
16. The chromatography apparatus of claim 1, wherein said second
layer comprises a deformable material.
17. The chromatography apparatus of claim 1, wherein said second
layer comprises polypropylene.
18. The chromatography apparatus of claim 1, wherein said second
layer comprises polyethylene.
19. The chromatography apparatus of claim 1, wherein said second
layer comprises stainless steel.
20. The chromatography apparatus of claim 1, wherein said second
layer comprises aluminum.
21. The chromatography apparatus of claim 1, wherein said second
layer comprises anodized aluminum.
22. The chromatography apparatus of claim 1, wherein said second
layer comprises acetal.
23. The chromatography apparatus of claim 1, wherein said second
layer comprises polycarbonate.
24. The chromatography apparatus of claim 1, wherein said second
layer comprises glass.
25. The chromatography apparatus of claim 1, wherein said innermost
first layer comprises a chemically inert material.
26. The chromatography apparatus of claim 25, wherein said inner
layer comprises a fluoropolymer.
27. The chromatography apparatus of claim 26, wherein said
fluoropolymer is TEFLON.
28. The chromatography apparatus of claim 26, wherein said
fluoropolymer is TEFZEL.
29. The chromatography apparatus of claim 26, wherein said
fluoropolymer is PTFE.
30. The chromatography apparatus of claim 26, wherein the
fluoropolymer is EFEP.
31. The chromatography apparatus of claim 1, wherein said innermost
first layer is a lining.
32. The chromatography apparatus of claim 11, wherein said
innermost first layer is a sleeve.
33. The chromatography apparatus of claim 1, wherein said first
material encapsulates said second layer, thereby forming an
outermost layer comprised of the first material.
34. The chromatography apparatus of claim 1, wherein said second
layer comprises polypropylene and said innermost first layer
comprises TEFLON.
35. The chromatography apparatus of claim 1, wherein said second
layer comprises polyethylene and said innermost first layer
comprises TEFLON.
36. The chromatography apparatus of claim 1, further comprising
first and second porous members and a chromatography media disposed
within said tubular member, said chromatography media being bounded
between said first and second porous members.
37. The chromatography apparatus of claim 36, wherein said first
porous member is spaced from said inlet end, so as to define an
inflow region.
38. The chromatography apparatus of claim 37, wherein said second
porous member is spaced from said outlet end, so as to define an
outflow region.
39. The chromatography apparatus of claim 38, wherein said second
porous member is in slidable contact with said tubular member.
40. The chromatography apparatus of claim 37, wherein said first
porous member is in slidable contact with said tubular member.
41. The chromatography apparatus of claim 40, wherein said second
porous member is in slidable contact with said tubular member.
42. The chromatography apparatus of claim 38, wherein said inflow
region is longer than said outflow region.
43. The chromatography apparatus of claim 38, wherein said inflow
region is substantially longer than said outflow region.
44. The chromatography apparatus of claim 37, further comprising a
sample carried on said chromatography media, so that the apparatus
may be employed as a chromatography sample module.
45-65. (Cancelled)
66. A chromatography column comprising: a tubular member having an
inlet and outlet end, said tubular member including an innermost
first layer comprising a chemically inert material and a rigid,
deformable second layer; first and second porous members disposed
within said tubular member; and a chromatography or separating
media disposed within said tubular member and bounded by said first
and second porous members; wherein said second porous member abuts
said media and said second porous member is held firmly by crimping
a first portion of said tubular member against said second porous
member.
67. The chromatography column of claim 66, wherein said tubular
member includes a plurality of layers, including at least the
innermost first layer comprised of the chemically inert material
and the rigid, deformable second layer.
68. The chromatography column of claim 67, wherein the second layer
is an intermediate layer and an outermost layer is comprised of the
chemically inert material.
69. The chromatography column of claim 67, wherein said chemically
inert material encapsulates said second layer, thereby forming an
outermost layer comprised of the chemically inert material.
70. The chromatography column of claim 66, wherein said first
porous member is in slidable contact with said innermost first
layer and is spaced sufficiently from said inlet end to form a
module receiving region deep enough for a sample module to be
inserted completely into said receiving region.
71. The chromatography column of claim 66, wherein said first
porous member is held firmly by crimping a second portion of said
tubular member against said first porous member.
72. The chromatography column of claim 71, wherein said crimped
first porous member is spaced sufficiently from said inlet end to
form a module receiving region deep enough for a sample module to
be inserted completely into said receiving region.
73. The chromatography column of claim 66, wherein said tubular
member further comprises a sealing region between said inlet end
and said module receiving region, said sealing region being
sufficiently long to receive a sealing head for making a seal with
said innermost first surface of said tubular member.
74. The chromatography column of claim 66, wherein said tubular
member further comprises a chamfered region near said inlet
end.
75. The chromatography column of claim 66, wherein said second
layer comprises polypropylene.
76. The chromatography column of claim 66, wherein said second
layer comprises polyethylene.
77. The chromatography column of claim 66, wherein said second
layer comprises stainless steel.
78. The chromatography column of claim 66, wherein said second
layer comprises aluminum.
79. The chromatography column of claim 66, wherein said second
layer comprises anodized aluminum.
80. The chromatography column of claim 66, wherein said second
layer comprises acetal.
81. The chromatography column of claim 66, wherein said second
layer comprises polycarbonate.
82. The chromatography column of claim 66, wherein said second
layer comprises glass.
83. The chromatography column of claim 66, wherein said innermost
first layer comprises a fluoropolymer.
84. The chromatography column of claim 83, wherein said
fluoropolymer is TEFLON.
85. The chromatography column of claim 83, wherein said
fluoropolymer is TEFZEL.
86. The chromatography column of claim 83, wherein said
fluoropolymer is PTFE.
87. The chromatography column of claim 83, wherein said
fluoropolymer is EFEP.
88. The chromatography column of claim 66, wherein said second
layer comprises polypropylene and said innermost first layer
comprises TEFLON.
89. The chromatography column of claim 66, wherein the inlet end of
the tubular member includes an inlet tube abutting an upper surface
of the first porous member, the inlet tube having an inner layer
comprising a chemically inert material.
90. The chromatography column of claim 89, wherein the chemically
inert material is a fluoropolymer.
91. The chromatography column of claim 90, wherein the
fluoropolymer is TEFLON.
92. The chromatography column of claim 90, wherein said
fluoropolymer is TEFZEL.
93. The chromatography column of claim 90, wherein said
fluoropolymer is PTFE.
94. The chromatography column of claim 90, wherein said
fluoropolymer is EFEP.
95. The chromatography column of claim 66, wherein the outlet end
of the tubular member includes an outlet tube abutting a lower
surface of the second porous member, the outlet tube having an
inner layer comprising a chemically inert material.
96. The chromatography column of claim 95, wherein the chemically
inert material is a fluoropolymer.
97. The chromatography column of claim 96, wherein the
fluoropolymer is TEFLON.
98. The chromatography column of claim 96, wherein said
fluoropolymer is TEFZEL.
99. The chromatography column of claim 96, wherein said
fluoropolymer is PTFE.
100. The chromatography column of claim 96, wherein said
fluoropolymer is EFEP.
101. A chromatography column comprising: a tubular member having an
inlet and outlet end; first and second porous members disposed
within said tubular member; and a chromatography or separating
media disposed within said tubular member and bounded by said first
and second porous members; wherein said second porous member abuts
said media and said second porous member is held firmly by crimping
a portion of said tubular member against said second porous
member.
102. The chromatography column of claim 101, wherein said first
porous member is in slidable contact with an inner surface of said
tubular member and is spaced sufficiently from said inlet end to
form a module receiving region deep enough for a sample module to
be inserted completely into said receiving region.
103. The chromatography column of claim 101, wherein said tubular
member is crimped near the inlet end and above said first porous
member, such that said first porous member is restrained from
sliding above the crimped portion of said tubular member.
104. The chromatography column of claim 103, wherein the crimped
portion of said tubular member is spaced sufficiently from said
inlet end to form a module receiving region deep enough for a
sample module to be inserted into said receiving region.
105. The chromatography column of claim 101, wherein said first
porous member is held firmly by crimping a portion of said tubular
member against said first porous member.
106. The chromatography column of claim 105, wherein said crimped
first porous member is spaced sufficiently from said inlet end to
form a module receiving region deep enough for a sample module to
be inserted completely into said receiving region.
107. The chromatography column of claim 101, wherein said tubular
member further comprises a sealing region between said inlet end
and said module receiving region, said sealing region being
sufficiently long to receive a sealing head for making a seal with
said inner surface of said tubular member.
108. The chromatography column of claim 101, wherein said tubular
member further comprises a chamfered region near said inlet
end.
109. A chromatography column comprising: a tubular member having an
inlet end and an outlet end; first and second porous members
disposed within said tubular member and in slidable contact with an
inner surface of said tubular member; and a chromatography or
separating media disposed within said tubular member and bounded by
said first and second porous members; wherein said tubular member
is first crimped near the inlet end above the first porous member,
such that the first porous member is restrained from sliding above
said first crimping, and wherein said tubular member is second
crimped near the outlet end below the second porous member, such
that the second porous member is restrained from sliding below said
second crimping.
110. The chromatography column of claim 109, wherein: said first
crimping of said tubular member is spaced sufficiently from said
inlet end to form a module receiving region deep enough for a
sample module to be inserted into said receiving region.
Description
BACKGROUND OF THE INVENTION
[0001] The invention relates to columns used in liquid
chromatography.
[0002] Liquid chromatography is a technique for separating the
individual compounds that exist in a subject sample. In employing
the technique, the subject sample is carried in a liquid, called a
mobile phase. The mobile phase carrying the subject sample is
caused to migrate through a media, sometimes called a stationary
phase. Different compounds will have differing rates of migration
through the media, which effects the separation of the components
in the subject sample. Liquid chromatography is commonly performed
with reusable columns or with disposable cartridges, both of which
are usually cylindrical, in which the media bed is bounded axially
by porous plates, or plates containing defined flow paths, through
which the mobile phase will flow. (See U.S. Pat. No. 4,250,035 to
McDonald et al.)
SUMMARY OF THE INVENTION
[0003] The present invention provides apparatus for chromatography.
In general, in one aspect, the invention features a chromatography
apparatus including a tubular member having an inlet end and an
outlet end. The tubular member includes an innermost first layer
comprised of a first material and a second layer comprised of a
second material.
[0004] Embodiments of the invention may include one or more of the
following. The chromatography apparatus can further include a first
intermediate layer formed from a third material, where at least a
portion of the first intermediate layer is disposed between the
innermost first layer and the second layer. The first intermediate
layer can be formed from an adhesive material. The chromatography
apparatus can further include a second intermediate layer formed
from a fourth material, where at least a portion of the second
intermediate layer is disposed between the innermost first layer
and the second layer. A portion of the second intermediate layer
can be disposed between the second layer and the first intermediate
layer.
[0005] The tubular member of the chromatography apparatus can
include a plurality of layers, including at least the innermost
first layer formed of the first material and a second layer formed
of the second material. The second layer can be an intermediate
layer and an outermost layer can be included, formed also of the
first material. In one embodiment, the first material can
encapsulate the second layer, thereby forming an outermost layer of
the first material.
[0006] The outer surface of the second layer can have a
cross-sectional shape having at least one flat side. For example,
the outer surface can have a rectangular cross-sectional shape, or
a square cross-sectional shape. In other embodiments, the outer
surface can have a circular cross-sectional shape, a triangular
cross-sectional shape, hexagonal cross-sectional shape or an
octagonal cross-sectional shape.
[0007] The second layer can be formed from a deformable material
and/or a rigid material. For example, the second layer can be
formed from a polyolefin (e.g., polypropylene or polyethylene),
stainless steel, aluminum, anodized aluminum, acetal, polycarbonate
or glass. The innermost first layer can be formed from a chemically
inert material. For example, the innermost first layer can be
formed from a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE,
and can be a lining, sleeve, or cladding. The innermost first layer
may be impregnated in the second layer or may be formed by,
coating, encapsulating, co-extrusion, anodizing, or bonding.
Innermost first layers of TEFLON or like materials may be formed by
TEFLON hardcoating or a similar technique. Forming an innermost
first layer of TEFLON on an aluminum outer layer or intermediate
layer surface through TEFLON hardcoating is an exemplary technique.
The innermost first layer can also be formed from a deformable
material and/or a rigid material. In one embodiment, the second
layer can be formed from polypropylene and the innermost first
layer formed from TEFLON. In another embodiment, the second layer
can be formed from polyethylene and the innermost first layer
formed from TEFLON.
[0008] In general, in another aspect, the invention features a
chromatography column including a tubular member having an inlet
and outlet end, first and second porous members disposed within the
tubular member, and a chromatography or separation media disposed
within the tubular member and bounded by the first and second
porous members. The tubular member includes an innermost first
layer formed from a chemically inert material and a second layer.
The first porous member abuts the media and the first member is
also in slidable contact with the inner layer of the tubular
member, and is spaced sufficiently from the inlet end to define a
module receiving region for receiving a sample module entirely
within the tubular member.
[0009] Embodiments of the invention may include one or more of the
following. The tubular member of the chromatography column can
include a plurality of layers, including at least the innermost
first layer (formed from the chemically inert material) and the
second layer. The second layer can be an intermediate layer, and an
outermost layer can be formed from the chemically inert material.
In one embodiment the chemically inert material encapsulates the
second layer, thereby forming both an innermost first layer and an
outermost layer comprised of the chemically inert material.
[0010] The tubular member can further include a sealing region
between the inlet end and the module receiving region. The sealing
region is sufficiently long to receive a sealing head for making a
seal with the innermost first surface of the tubular member. The
tubular member can include a chamfered region near the inlet
end.
[0011] The second layer of the chromatography column can be formed
from polypropylene, polyethylene, stainless steel, aluminum,
anodized aluminum, acetal, polycarbonate or glass. The innermost
first layer of the chromatography column can be formed from a
fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE. In one
embodiment, the second layer can be formed from either
polypropylene or polyethylene and the innermost first layer formed
from TEFLON.
[0012] In general, in another aspect, the invention features a
chromatography column including a tubular member having an inlet
and outlet end, first and second porous members disposed within the
tubular member, and a chromatography or separating media disposed
within the tubular member and bounded by the first and second
porous members. The tubular member includes an innermost first
layer formed from a chemically inert material and a rigid and/or
deformable second layer. The second porous member abuts the media
and is held firmly by crimping a portion of the tubular member
against the second porous member.
[0013] Embodiments of the invention may include one or more of the
following. The tubular member included in the chromatography column
can include a plurality of layers, including at least the innermost
first layer formed from the chemically inert material and the
rigid, deformable second layer. The second layer can be an
intermediate layer and an outermost layer can be formed from the
chemically inert material. In one embodiment, the chemically inert
material encapsulates the second layer, thereby forming both an
innermost first layer and an outermost layer of the chemically
inert material.
[0014] The first porous member can be in slidable contact with the
innermost first layer, and spaced sufficiently from the inlet end
to form a module receiving region deep enough for a sample module
to be inserted completely into the receiving region.
[0015] The first porous member can be held firmly by crimping the
column wall against or above the first porous member. The crimped
first porous member can be spaced sufficiently from the inlet end
to form a module receiving region deep enough for a sample module
to be inserted completely into the receiving region. The column
wall may be crimped into a grooved region of the first porous
member.
[0016] The tubular member can further include a sealing region
between the inlet end and the module receiving region, the sealing
region being sufficiently long to receive a sealing head for making
a seal with the inner surface of the tubular member. The tubular
member can include a chamfered region near the inlet end.
[0017] The second layer can be formed from polypropylene,
polyethylene, stainless steel, aluminum, anodized aluminum, acetal,
polycarbonate or glass. The innermost first layer can be formed
from a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE. In one
embodiment the outer layer can be formed from either polypropylene
or polyethylene and the innermost first layer formed from
TEFLON.
[0018] The inlet end of the tubular member can include an inlet
tube abutting an upper surface of the first porous member. The
inlet tube can have an inner layer formed from a chemically inert
material. The chemically inert material can be a fluoropolymer,
such as TEFLON, TEFZEL, EFEP or PTFE. The outlet end of the tubular
member can include an outlet tube abutting a lower surface of the
second porous member. The outlet tube can have an inner layer
comprising a chemically inert material. The chemically inert
material can be a fluoropolymer, such as TEFLON, TEFZEL, EFEP or
PTFE.
[0019] In general, in another aspect, the invention features a
chromatography column including a tubular member having an inlet
and outlet end and first and second porous members disposed within
the tubular member. A chromatography or separating media is
disposed within the tubular member and bounded by the first and
second porous members. The second porous member abuts the media and
is held firmly by crimping a portion of the tubular member against
the second porous member or into a grooved region of the second
porous member.
[0020] Embodiments of the invention may include one or more of the
following. The first porous member can be in slidable contact with
an inner surface of the tubular member, and spaced sufficiently
from the inlet end to form a module receiving region. The module
receiving region is deep enough for a sample module to be inserted
completely into the receiving region.
[0021] In another embodiment, the tubular member can be crimped
near the inlet end and above the first porous member, such that the
first porous member is restrained from sliding above the crimped
portion of the tubular member. The crimped portion of the tubular
member can be spaced sufficiently from the inlet end to form a
module receiving region deep enough for a sample module to be
inserted into the receiving region. Alternatively, the first porous
member can be held firmly by crimping the tubular member against
the porous member or into a grooved region of the first porous
member. The crimped first porous member can be spaced sufficiently
from the inlet end to form a module receiving region deep enough
for a sample module to be inserted completely into the receiving
region.
[0022] The tubular member can further include a sealing region
between the inlet end and the module receiving region, the sealing
region being sufficiently long to receive a sealing head for making
a seal with the inner surface of the tubular member. The tubular
member can further include a chamfered region near the inlet
end.
[0023] In general, in another aspect, the invention features a
chromatography column including a tubular member having an inlet
end and an outlet end and first and second porous members disposed
within the tubular member and in slidable contact with an inner
surface of the tubular member. A chromatography or separating media
is disposed within the tubular member and bounded by the first and
second porous members. The tubular member is first crimped near the
inlet end above the first porous member, such that the first porous
member is restrained from sliding above the first crimping. The
tubular member is also crimped near the outlet end below the second
porous member, such that the second porous member is restrained
from sliding below the second crimping. In one embodiment, the
first crimping of the tubular member is spaced sufficiently from
the inlet end to form a module receiving region deep enough for a
sample module to be inserted into the receiving region.
[0024] The invention can be implemented to realize one or more of
the following advantages. Using two or more layers of materials to
form a composite column, the mechanical characteristics of the
outer layer, and optionally intermediate layers, can provide
structural benefits, such as rigidity, flexibility, deformability
and hoop strength, while the properties of the inner layer, such as
chemical inertness, can improve chromatographic performance. For
example, a composite column having an outer layer formed from
polypropylene or polyethylene, and an inner layer formed from a
fluoropolymer, is cost-effective and able to achieve high levels of
chromatographic performance relative to theoretical maximums, while
achieving the necessary structural characteristics.
[0025] An inner layer formed from a fluoropolymer increases
performance of the chromatography column, because, for example, the
fluoropolymer does not interact with a solvent or compound being
purified. Due to the higher performance, more concentrated
fractions of purified components can be achieved, hence decreasing
solvent consumption during the chromatography process.
[0026] The physical aspects of the column wall may be determined by
the materials used in the outer or intermediate layers of the
column wall. Flexible column walls may be used in a pressure vessel
to radially compress the column and the chromatographic media
within, thereby improving column performance. The combination of
the outer, inner, and any intermediate layers may be chosen so that
the column wall is deformable, so that it may be crimped, in order
to fix a porous member in place, for example. The material for the
outer layer may be chosen for its ability to be engraved, embossed,
written upon, or otherwise inscribed. The thickness and
cross-sectional shape of intermediate layers or the outer layer may
be selected for particular physical characteristics, such as
strength, flexibility, and durability. The cross-sectional shape of
the outer layer may be selected for improved packaging and storage.
For example, the cross-sectional shape of the outer layer may be
selected to increase the number of columns that can be packed into
a minimum space during use or storage. The cross-sectional shape of
the outer layer may also be selected in order to include flat
surfaces, protrusions, oblong surface(s), or other shapes that will
prevent the column from rolling.
[0027] Use of beveled or chamfered edges at the inlet end of a
composite chromatography column eases insertion of a sealing
device, precolumn or sample module into the column. Additionally,
beveled or chamfered edges can be advantageous in the manufacturing
process, particularly if the composite columns are formed from
molding.
[0028] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features and advantages of the invention will be apparent
from the description, the drawings, and the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 is a longitudinal cross-sectional view of a
chromatography column according to the invention.
[0030] FIG. 2A is a cross-sectional view of a chromatography
column.
[0031] FIG. 2B is a longitudinal cross-sectional view of a portion
of the chromatography column of FIG. 2A.
[0032] FIG. 3 is a longitudinal cross-sectional view of a portion
of a chromatography column.
[0033] FIG. 4 is a longitudinal cross-sectional view of a portion
of a chromatography column.
[0034] FIG. 5 is a longitudinal cross-sectional view of a portion
of a chromatography column.
[0035] FIG. 6 is a longitudinal cross-sectional view of a
chromatography column.
[0036] FIG. 7 is a longitudinal cross-sectional view of a
chromatography column.
[0037] FIG. 8 is a cross-sectional view of a chromatography column
having a rectangular outer cross-section and a circular inner
cross-section.
[0038] FIG. 9 is a cross-sectional view of a chromatography column
having a semi-curved shaped outer cross-section and a circular
inner cross-section.
[0039] FIG. 10A is a cross-sectional view of a chromatography
column having an octagonal outer cross-section and a circular inner
cross-section.
[0040] FIG. 10B is a cross-sectional view of a chromatography
column having a hexagonal outer cross-section and a circular inner
cross-section.
[0041] FIG. 11 is a cross-sectional view of a chromatography column
having a triangular outer cross-section and a circular inner
cross-section.
[0042] FIG. 12 is a cross-sectional view of a chromatography column
having a diamond-shaped outer cross-section and a circular inner
cross-section.
[0043] FIG. 13 is a cross-sectional view of a chromatography column
having three composite layers.
[0044] FIG. 14A is a longitudinal cross-sectional view of a
composite chromatography column having a slidable upper porous
plate.
[0045] FIG. 14B is a longitudinal cross-sectional view of a
composite chromatography column having a slidable upper porous
plate and a crimped lower porous plate.
[0046] FIG. 14C is a longitudinal cross-sectional view of a
composite chromatography column having crimped upper and lower
porous plates.
[0047] FIG. 14D is a longitudinal cross-sectional view of a
composite chromatography column having a crimp in the column above
the upper porous plate and below the lower porous plate.
[0048] FIG. 15 is a longitudinal cross-sectional view of a
composite chromatography column having an inlet tube and an outlet
tube.
[0049] FIG. 16 is a longitudinal cross-sectional view of a sealing
apparatus and a chromatography column.
[0050] FIG. 17 is a longitudinal cross-sectional view of a sealing
apparatus.
[0051] FIG. 18 is a longitudinal cross-sectional view of a sealing
apparatus showing the formation of a seal with a chromatography
column.
[0052] FIG. 19A is a longitudinal cross-sectional view of a sealing
apparatus.
[0053] FIG. 19B is a longitudinal cross-sectional view of a sealing
apparatus and a chromatography column.
[0054] FIG. 19C is a longitudinal cross-sectional view of a sealing
apparatus showing the formation of seals with a chromatography
column.
[0055] FIG. 20 is a schematic diagram of a chromatography
system.
[0056] FIG. 21 is a longitudinal sectional view of a chromatography
sample module used in the FIG. 20 system.
[0057] FIG. 22 is a plan view of a rack containing a plurality of
the FIG. 21 sample modules in an array.
[0058] FIG. 23 is an elevation of the FIG. 22 rack and modules.
[0059] FIG. 24A shows an exploded longitudinal cross-sectional view
of an alternate sealing apparatus with a sample module and
chromatography column.
[0060] FIG. 24B shows a longitudinal cross-sectional view of an
alternate sealing apparatus with a sample module and chromatography
column.
DETAILED DESCRIPTION
[0061] Referring to FIG. 1, a chromatography column 100 having
layers 102, 104, each terminating at either end of the column 100
with beveled edges 106 is shown. A chromatography media 108 is
bounded axially by porous plates 110, which form a stop within the
column 100.
[0062] The column 100 can be formed from two or more layers, for
example, an outer layer 102 and an inner layer 104. Optionally, one
or more intermediate layers can be included between the outer layer
102 and the inner layer 104.
[0063] The outer layer 102 is a rigid, tubular member. Material for
the outer layer 102 is selected for properties desirable to the
chromatography column application, for example, hardness, hoop
strength, flexibility, deformability and inexpensiveness. Suitable
materials for forming the outer layer 102 include plastic, metal,
glass or a suitable composite material. Plastic materials
exhibiting some or all of the desired properties referred to above
include polypropylene, polyethylene, acetal (also known as DELRIN)
and polycarbonate. Polypropylene and polyethylene are particularly
well suited materials to form the outer layer, since they are able
to achieve the required hoop-strength to contain low to medium
pressure during the chromatographic process. Suitable metals
include stainless steel, steel alloys, aluminum and anodized
aluminum.
[0064] The material for the inner layer 104 is selected for its
superior chromatographic column properties, such as the material's
chemical inertness, in that the material does not interact with
solvents or compounds being purified. Suitable materials for the
inner layer 104 include fluoropolymers such as PTFE, EFEP and
materials sold under the trade names TEFLON and TEFZEL.
[0065] A column formed of a single layer of pure TEFLON tubing, or
another fluoropolymer, may be considered too expensive,
particularly for disposable chromatography columns, and would be
relatively thick, because thinner layers of fluoropolymers lack the
hoop-strength that is necessary to maintain the rigidity of the
column. Polypropylene and polyethylene, as discussed above, have
the required hoop-strength to form a single layer column, but lack
the chemical inertness of a fluoropolymer. As such, polypropylene
and polyethylene columns are able to achieve high levels of
chromatographic performance, for example, in relation to plate
count and asymmetry of peaks, but fall short of the theoretical
maximums. By contrast, fluoropolymer columns can attain performance
closer to the theoretical maximums.
[0066] By using two or more layers of materials to form a column,
the mechanical characteristics of the outer layer, and optionally
intermediate layers, can provide structural benefits, such as
rigidity, flexibility, deformability and hoop strength, while the
chemical properties of the inner layer, such as chemical inertness,
can improve chromatographic performance. For example, a column 100
having an outer layer 102 formed from polypropylene or
polyethylene, and an inner layer 104 formed from a fluoropolymer,
is cost-effective and able to achieve high levels of
chromatographic performance relative to theoretical maximums, while
achieving the necessary structural characteristics.
[0067] Referring to FIG. 2A and FIG. 2B, a cross-sectional view and
partial longitudinal cross-sectional view of column 100 are shown.
The inner and outer layers 104, 102 can have any suitable
thickness. The outer layer 102 should be at least thick enough to
achieve the required hoop-strength. It is often desirable for a
chromatography column to have beveled or chamfered edges, so as to
ease the insertion of a sealing device, precolumn or sample module
into the column. For a composite column having two or more layers
all layers may be beveled. For example, the inner and outers layers
104, 102 of column 100 can each run the entire length of the column
100, and terminate on either end with a beveled edge 106, as shown
in FIG. 2B.
[0068] Referring to FIG. 3, in another embodiment, a column 120 is
formed from an outer layer 122 and an inner layer 124. The inner
layer 124 terminates at one or both ends (only one end is shown)
with a substantially flat surface region 128. The outer layer 122
extends beyond the inner layer 124 and terminates with a beveled
edge 126 slanting inwardly until meeting the innermost surface 130
of the inner layer 124, thus forming a lip 132 over the
substantially flat surface region 128 of the inner layer 124. This
design can be especially advantageous in the manufacturing process,
particularly if the column 120 is formed from molding.
[0069] Referring to FIG. 4, in yet another embodiment, a column 140
is formed from an outer layer 142 and an inner layer 144. The outer
layer terminates at one or both ends (only one end is shown) with a
substantially flat edge 146. The inner layer 144 extends beyond the
outer layer 142 and terminates with a beveled edge 148 slanting
outwardly until flush with the outermost surface 150 of the outer
layer 142, thus forming a lip 152 over the substantially flat edge
146 of the outer layer 142. As mentioned above in reference to FIG.
3, this design can also be especially advantageous in the
manufacturing process, particularly if the column 120 is formed
from molding.
[0070] In another embodiment, as shown in FIG. 5, a column 160 is
formed from an outer layer 162 and an inner layer 164, each layer
running the entire length of the column 160 and terminating on
either end with a substantially flat edge 166.
[0071] Alternatively, a column can be formed from two or more
layers terminating in any other combination of ends, for example
the beveled edge described with reference of FIG. 3 above, can be
combined with the flat edge described with reference to FIG. 5
above, wherein one end of the column terminates in a beveled edge
and one end terminates in a flat edge. Similarly, the beveled edge
of FIG. 4, can be combined with the beveled edge of FIG. 3 or the
flat edge of FIG. 5.
[0072] In another embodiment, any of the column layers can be
situated at only desired portions of the column, such as a sealing
region or a region that contacts the chromatographic media. For
example, referring to FIG. 6, a column 170 is shown employing an
outer layer 172 that extends the entire length of the column 170
and an inner layer 174 at only the upper and lower sealing regions
176 of the column 170. Alternatively, referring to FIG. 7, a column
180 is shown having an outer layer 182 extending the entire length
of the column 180, and an inner layer 184 employed only in the
central region 186 of the column 180.
[0073] The outer layer and any intermediate layers of a column can
have any desired shape. For example, the outer layer 102 of column
100 shown in FIGS. 1, 2A and 2B, is cylindrical, having a
substantially circular horizontal cross-section, as shown in FIG.
2A.
[0074] In other embodiments, the outer and any optional
intermediate layers can have differing horizontal cross-sectional
shapes. For example, referring to FIG. 8, the cross-sectional view
of a column 190 is shown, having an outer layer 192 and an inner
layer 194. The cross-section of the outer layer 192 has a square
outer shape and a substantially circular inner shape, while the
cross-section of the inner layer 194 is substantially circular.
Thus, column 190 has a rectangular, tubular exterior shape and a
circular, cylindrical inner shape.
[0075] Referring to FIG. 9, a cross-sectional view of a column 200
is shown, having an outer layer 202 and an inner layer 204. The
cross-section of the outer layer 202 has a curved outer shape 206
on three exterior sides, at least one flat exterior side 208, and a
substantially circular inner shape. The cross-section of the inner
layer 204 is substantially circular, thus forming a column 200 with
a circular, cylindrical inner shape.
[0076] FIG. 10A depicts a cross-sectional view of a column 210
having an outer layer 212 with an octagonal exterior
cross-sectional shape, and a substantially circular interior
cross-sectional shape. The column 210 also includes an inner layer
214, having a substantially circular cross-sectional shape. Thus,
the column 210 formed from the outer and inner layers 212, 214, has
an octagonal, tubular exterior shape and a circular, cylindrical
interior shape.
[0077] FIG. 10B depicts a cross-sectional view of a column 216
similar to that shown in FIG. 10A, but having an outer layer 218
with a hexagonal exterior cross-sectional shape. The interior
cross-sectional shape is substantially circular. The column
includes an inner layer 219, also having a substantially circular
cross-sectional shape. The column formed from the outer and inner
layers 218, 219 has a hexagonal, tubular exterior shape and a
circular, cylindrical interior shape.
[0078] As shown in FIG. 11, a column 220 can be formed from an
outer layer 222 having a triangular exterior cross-sectional shape
and a substantially circular interior cross-sectional shape, and an
inner layer 224 having a substantially circular interior
cross-sectional shape. The column 220 thus has a three-sided,
tubular exterior surface and a cylindrical inner surface.
[0079] Referring to FIG. 12, a column 230 can be formed from an
outer layer 232 having a diamond-shaped exterior cross-section and
a substantially circular interior cross-section, and an inner layer
234 having a substantially circular interior cross-section. The
column 230 thus has a four-sided, tubular exterior surface and a
cylindrical inner surface.
[0080] In another embodiment, the inner layer can have an exterior
cross-sectional shape differing from the inner cross-sectional
shape of the inner layer. Any number of other embodiments are also
possible, having any number of combinations of inner, outer and
intermediate cross-sectional shapes. An outer layer shape can be
selected to advantageously allow for a maximum number of columns to
be packed into a minimum space during use or for storage or to
prevent a column from rolling, when set on a surface.
[0081] A composite column can be formed with one or more
intermediate layers in between an outer layer and an inner layer.
For example, referring to FIG. 13, a cross-sectional view of a
column 240 is shown, the column 240 including an outer layer 242,
an intermediate layer 244 and an inner layer 246. Material for an
intermediate layer can be selected to exhibit desirable properties
similar to those discussed above in reference to the outer layer,
i.e. hardness, hoop-strength, flexibility and deformability.
Alternatively, an intermediate layer can be used to form a bond
between two layers, for example, the outer layer and the inner
layer. In this instance, the intermediate layer could be an
adhesive material used to bind the inner and outer layers
together.
[0082] The porous plates positioned within a chromatography column
can be held firmly in place by convenient means, or can be slidable
along the interior of the inner layer of a composite column.
Referring to FIG. 14A, a composite column 250 is shown, including
an outer layer 252 and an inner layer 254, and can optionally
include one or more intermediate layers. An upper porous plate 256
is situated near an inlet end 258 of the column 250, and a lower
porous plate 260 is situated near an outlet end 262 of the column
250. A chromatography or a separation media 264 is bounded between
the upper and lower porous plates 256, 260.
[0083] In this embodiment, the upper porous plate 256 is in
slidable contact with the inner layer 254. The upper porous plate
256 is spaced sufficiently from the inlet end 258 to define a
module receiving region 266 for receiving a sample module entirely
within the column 250. The lower porous plate 260 may be in
slidable contact with the inner layer 254. As shown in FIG. 14B, in
another embodiment 250', the lower porous plate 260' may
alternatively be held firmly in place near the outlet end 262, for
example, by crimping the outer layer 252 so that the inner layer
254 presses against the lower porous plate 260'. The lower porous
plate 260' may have a grooved region 261 for receiving the crimped
portion 259 of the composite column 250'. In another embodiment
250", shown in FIG. 14C, the upper porous plate 256' and lower
porous plate 260' can both be held firmly in place, for example, by
crimping the outer layer 252 so that the inner layer 254 presses
against the upper and lower porous plates 256', 260'.
[0084] Another embodiment 250'" is shown in FIG. 14D, with the
column crimped above upper porous plate 256'" and below lower
porous plate 260'". The upper and lower porous plates 256'", 260'"
remain slidable relative to the inner layer of the column wall 278,
but are retained by the crimped portion of column 250'" at a
maximum upper and lower position, respectively. In this way, column
250'" may be filled with media 264, crimped above and below upper
and lower porous plates 256'", 260'" respectively, and the media
264 may be further compressed as needed if media 264 settles (e.g.,
during shipping or use). By positioning the crimping sufficiently
below the inlet end 258, a module receiving region 266 can be
defined for receiving a sample module entirely within the column
250'".
[0085] The crimping feature shown in FIGS. 14B-14D can also be used
with a chromatography column formed of a single layer, rather than
a composite column. Crimping a column on or above a porous member
or plate may reduce the exactness of the tolerances required in
order to achieve the desired fit between the porous member and the
column wall. Crimping is an effective way to fix or retain a porous
member within a column and may prove more efficient and less
expensive that techniques such as milling or molding a column with
an internal rim, projection, or stop.
[0086] The crimping feature may be employed with a deformable metal
column, such as aluminum, anodized aluminum, stainless steel, or
any other metal, or crimping may also be performed with a plastic
column and may be accomplished by deforming a tube with or without
the use of heat, as well as pressure. For example, a cylindrical
plastic tube may be formed by extrusion and then heat-molded, in
order to form a crimped region.
[0087] Referring to FIG. 15, in another embodiment, a composite
chromatography column 270 can include an inlet member 272 and an
outlet member 274 at either end of the column 270. The column 270
includes an outer layer 276 and an inner layer 278, and can
optionally include one or more intermediate layers. The inlet
member 272 includes an inner layer 280 formed from a chemically
inert material, for example, a material such as was described above
in reference to an inner layer of a composite column. The outlet
member 274 also includes an inner layer 282 formed from such a
chemically inert material. Alternatively, the inlet and outlet
tubes 272, 274 can be a single layer formed entirely from a
chemically inert material (for example, a fluoropolymer, such as
TEFLON, TEFZEL, EFEP or PTFE), or from any other suitable material
such as, for example, polypropylene, polyethylene, stainless steel,
aluminum, anodized aluminum, acetal, polycarbonate or glass.
[0088] The inlet member 272 abuts an upper porous plate 284, and
the outlet tube 274 abuts a lower porous plate 286. The inlet
member 272 forms a flow distribution region 281 adjacent to the
upper porous plate 284. Similarly, the outlet member 274 forms a
flow collection region 283 adjacent to the lower porous plate 286.
Flow can be introduced into the column 270 through the narrow
portion of the inlet member 272 and released from the column 270
through the narrow portion of the outlet member 274. A
chromatography or separation media is axially bound between the
upper and lower porous plates 284, 286. The upper and lower porous
plates 284, 286 are held firmly in place, for example, by crimping
the outer and inner layers 276, 278 of the column 270 into a
grooved region 288 of either plate.
[0089] Referring again to FIG. 14C, an outlet member 263 is shown.
The outlet member 263 depicted in FIG. 14C is integral to the lower
porous plate 260', that is, together they form a single unit, as
contrasted to the outlet member 274 and lower porous plate 286
shown in FIG. 15. The outlet member 263 can be lined with a
chemically inert material. The inlet member 272 shown in FIG. 15
can similarly be configured such that the inlet member 272 and
upper porous plate 284 are an integral unit.
[0090] A number of other embodiments are also possible. For
example, a composite column can include an upper porous plate in
slidable contact with an inner layer of the column, and
sufficiently spaced from an inlet end of the column to define a
module receiving region for receiving a sample module, and a lower
porous plate abutting an outlet tube, the lower porous plate held
firmly in place by crimping an outer layer of the column into a
grooved region of the plate. Alternatively, the upper porous plate
can be held firmly in place by crimping the outer layer of the
column into a grooved region of the upper plate, rather than being
slidable.
[0091] Referring to FIGS. 14B and 14D, the upper and lower porous
plates 256, 260 can be spaced from the ends of the column 250 to
provide inlet and outlet regions. For example, in FIG. 14B, the
upper porous plate 256 is spaced below the inlet end 258 to define
a module receiving region 266, and the lower porous plate 260' is
substantially flush with the outlet end of the column. As shown in
FIG. 14D, in another embodiment the lower porous plate 260'" may be
spaced above the outlet end to form an outlet region. In other
embodiments the upper and lower porous plates may be spaced at
different distances from their respective ends of the column. For
example, an inlet region defined by the positioning of the upper
porous plate may be substantially longer than an outlet region
defined by the positioning of the lower porous plate. In another
embodiment, both the upper and lower porous plates can be
substantially flush with their respective ends of the column.
[0092] A composite column including two or more layers can be
manufactured by any convenient process. For example, a co-extrusion
process or a co-molding process, where the two or more layers are
formed together.
[0093] Alternatively, a first layer can be formed, for example by
extrusion or molding, and a second layer added to the exterior
surface or interior surface of the first layer by any convenient
means, including coating, vacuum forming and thermal bonding. This
process can be repeated to add any number of additional composite
layers.
[0094] Another alternative method of manufacture includes
independently forming a first and second layer, for example by
extrusion or molding, and affixing the first and second layer to
one another using an adhesive intermediate layer. For example, an
adhesive layer can be applied to the exterior surface of a first
layer. A second layer can then be positioned about the exterior
surface of the first layer, and held in place by the adhesive
intermediate layer.
[0095] In yet another method of manufacture, a first layer can be
formed, for example by extrusion or molding, and then encapsulated
by a material forming the second layer, such that the innermost
layer and outermost layer are formed from the second material, and
a middle or intermediate layer is formed from a first material. For
example, the first layer may be formed from a rigid material such
as polyethylene, which is then encapsulated by a second material,
such as TEFLON. The resulting column has an innermost layer of
TEFLON, a middle layer of polyethylene and an outermost layer of
TEFLON. This mode of manufacture can be used to manufacture any of
the embodiments discussed above, in which case the layer referred
to above as the `outer layer`, would in fact form an intermediate
layer, as the outermost layer would be formed from the
encapsulation material, also forming the innermost layer.
[0096] The outer layer can be formed from a deformable material
and/or a rigid material. For example, the outer layer can be formed
from polypropylene, polyethylene, stainless steel, aluminum,
anodized aluminum, acetal, polycarbonate or glass. The inner layer
can be formed from a chemically inert material. For example, the
inner layer can be formed from a fluoropolymer, such as TEFLON,
TEFZEL, EFEP or PTFE. The inner layer can be a lining, sleeve, or
cladding. The inner layer may be impregnated in the outer layer or
may be formed by, coating, co-extrusion, anodizing, or bonding.
Inner layers of TEFLON or like materials may be formed by TEFLON
hardcoating or a similar technique. Forming an inner layer of
TEFLON on an aluminum outer layer or intermediate layer surface
through TEFLON hardcoating is an exemplary technique. The inner
layer can also be formed from a deformable material and/or a rigid
material. In one embodiment, the outer layer can be formed from
polypropylene and the inner layer formed from TEFLON.
[0097] The composite column designs described herein may be used in
any desired chromatography device or method, including all of the
chromatography devices and methods described herein and all of the
devices and methods described in U.S. patent application Ser. No.
08/968,287 filed Nov. 12, 1997 (now U.S. Pat. No. 6,086,766), U.S.
patent application Ser. No. 09/137,019 filed Aug. 20, 1998 (now
U.S. Pat. No. 6,132,605), U.S. patent application Ser. No.
09/137,278 filed Aug. 20, 1998 (now U.S. Pat. No. 6,139,733), U.S.
patent application Ser. No. 09/548,214 filed Apr. 12, 2000 (now
U.S. Pat. No. 6,221,252), U.S. patent application Ser. No.
09/548,261 filed Apr. 12, 2000 (now U.S. Pat. No. 6,294,087), and
pending U.S. patent application Ser. No. 09/687,801, filed Oct. 13,
2000. All of these applications and patents are incorporated herein
by reference.
[0098] In one embodiment, a composite chromatography column as
described above can be used in a liquid chromatography apparatus as
follows. Referring to FIGS. 16-18, there is shown a sealing
apparatus employing sealing head 300, which includes first head
piece 304, having body 306 with longitudinal axis 308. First head
piece 304 has outwardly-extending shoulder 310, first compression
face 312 that is located on shoulder 310, and contact face 314.
Part of contact face 314 has a slightly conical shape or other
concavity (exaggerated in FIGS. 17 and 18). First head piece 304
defines flow path 316 along axis 308. Second head piece 318, which
includes second compression face 320 and a compression force
receiving member extending thereabove, is sized to slidably receive
body 306 of first head piece 304. Elastomeric sealing member 322 is
at least partially situated between first compression face 312 and
second compression face 320.
[0099] Sealing head 300 and its components are sized to fit
slidably into composite column 324, having chamfered edges 326, and
chromatography media 328 bounded axially by porous plates 330 which
form a rigid stop within the column. The composite column 324 is
formed from an outer layer 332 and an inner layer 334. Materials
for the outer and inner layers 332, 334 are selected as described
above. Alternatively, the composite column 324 can include one or
more intermediate layers between the outer layer 332 and inner
layer 334.
[0100] The connection of the apparatus is shown in FIGS. 16 and 18.
As shown in FIG. 16, first head piece 304, elastomeric sealing
member 322, and second head piece 318 are oriented so that they may
slide into composite column 324. As shown in FIG. 18, after first
head piece 304, elastomeric sealing member 322, and second head
piece 318 are situated within composite column 324, and contact
face 314 is stopped at porous plate 330, additional downward force
on second head piece 318 causes first head piece 304 and second
head piece 318 to be moved toward each other, thus axially
compressing elastomeric sealing member 322 between first
compression face 312 and second compression face 320. The axial
compression of elastomeric sealing member 322 causes it to expand
laterally and press against composite column 324, thus forming a
seal.
[0101] As shown in FIG. 18, insertion of sealing head 300 can
create a close connection between contact face 314 and porous plate
330. Compressing elastomeric sealing member 322 between first
compression face 312 and second compression face 320, by pressing
second head piece 318 against elastomeric sealing member 322, which
in turn presses first head piece 304 against porous plate 330, can
maintain a close connection between contact face 314 and porous
plate 330 while forming a seal between sealing head 300 and
composite column 324.
[0102] In one combination, sealing head 300 is used to seal
composite column 324 having flexible walls. In other combinations,
sealing head 300 is part of a containment structure assembly for
receiving composite column 324. The containment structure assembly
may be pressurizable, such as a pressure vessel assembly that
receives composite column 324, compresses the flexible walls of
composite column 324, and provides uniform packing for
chromatography media 328 therein. A containment structure of this
type is discussed in U.S. Pat. No. 4,250,035 to McDonald, et al.,
which is incorporated herein by reference. Another type of
pressurizable containment structure is discussed in U.S. Pat. No.
5,601,708 to Leavesley, which is also incorporated herein by
reference. In other combinations, sealing head 300 is used to seal
composite column 324 having rigid walls.
[0103] The radial displacement of the outer surface of elastomeric
sealing member 322 accommodates a range of inner diameters of
composite column 324, permitting effective seals while relaxing
tolerances for the inner diameter of composite column 324 to
.+-.0.005".
[0104] Referring to FIGS. 19A-19C, there is shown an alternate
embodiment of a sealing apparatus employing sealing head 410, which
includes first head piece 412, second head piece 424, intermediate
head piece 428, and first and second annular elastomeric sealing
members 434, 436.
[0105] First head piece 412 has body 414 with longitudinal axis
416. First head piece 412 has outwardly extending shoulder 418, and
contact face 420. Part of contact face 420 has a slightly conical
shape or other concavity. First head piece 412 defines flow path
422 along axis 416.
[0106] Body 414 of first head piece 412 fits slidably through
second head piece 424, intermediate head piece 428, and through
first and second elastomeric sealing members 434, 436.
[0107] First elastomeric sealing member 434 is adjacent to both
shoulder 418 and intermediate head piece 428. Second elastomeric
sealing member 436 is adjacent to both intermediate head piece 428
and second head piece 424.
[0108] Sealing head 410 and its components are sized to fit
slidably into composite column 438, having an outer layer 446 and
an inner layer 448 having chamfered edges 440. The composite column
438 can optionally include one or more intermediate layers, as
described above. Material can be selected for the outer layer 446,
inner layer 448 and optional intermediate layers as described
above. Composite column 438 is filled with chromatography media bed
442, which is bounded axially by porous plates 444, 445.
[0109] The connection of the apparatus is shown in FIGS. 19B and
19C. As shown in FIG. 19B, first head piece 412, second head piece
424, intermediate head piece 428, and elastomeric sealing members
434, 436 are oriented so that they may slide into composite column
438. As shown in FIG. 19C, after sealing head 410 is situated
within composite column 438, first head piece 412 and second head
piece 424 are moved relative to each other. This relative movement
axially compresses first elastomeric sealing member 434 between
shoulder 418 and intermediate head piece 428 and also compresses
second elastomeric sealing member 436 between intermediate head
piece 428 and second head piece 424. The axial compression of
elastomeric sealing members 434, 436 causes them to expand
laterally and press against the interior surface of composite
column 438, thus forming seals.
[0110] As shown in FIG. 19C, insertion of sealing head 410 can
create a close connection between contact face 420 and porous plate
444. Compressing elastomeric sealing members 434, 436, by pressing
second head piece 424 against second elastomeric sealing member
436, which in turn presses second elastomeric sealing member 436
against intermediate head piece 428, intermediate head piece 428
against first elastomeric sealing member 434, first elastomeric
sealing member against shoulder 418, and contact face 420 against
porous plate 444, can maintain a close connection between contact
face 420 and porous plate 444 while forming a seal between sealing
head 410 and composite column 438.
[0111] Referring to FIG. 20, there is shown chromatography system
510 which includes a source of solvent 512, pump 514, sample module
550, liquid chromatography composite column 538, and sample
collection vessel 520. The composite column 538 is formed from two
or more layers, as described above. In this system, the sample to
be analyzed is preabsorbed onto media in sample module 550 prior to
pumping solvent into module 550 and into composite column 538 to
perform the separation procedure.
[0112] Referring to FIG. 21, it is seen that sample module 550
includes tube 552, porous plates 556, 557 (made of inert plastic
porous frits), and chromatography media 554 (only partially shown
in the figures) between porous plates 556, 557.
[0113] As appears from FIG. 24, sample module 550 is designed to
fit within composite column 638 at the entrance thereof and to be
sealably connected to the sealing head. The tube 552 is designed to
fit within composite column 638 with minimal space between the two;
in particular, there is 0.000" to 0.010" of radial clearance. The
tube 552 can be a composite tube formed from two or more layers. An
innermost layer can be formed from a chemically inert material, as
described above in reference to embodiments of composite columns. A
second layer, which can be the outermost layer or an intermediate
layer, can be formed from a rigid and deformable material, also as
described above in reference to composite columns.
[0114] Sample module 550 can be filled with media that is the same
as or is different from the media of composite column 638. The
sample is dissolved in the required solvent and added to the top of
sample module 550, where it is drawn into the media by capillary
action. This dissolution solvent is then removed by drying or
evaporation. Sample module 550 may also be placed in a vacuum
chamber to enhance the drying or evaporation. Heat may also be
applied.
[0115] After sample module 550 has dried, it can be placed directly
inside composite column 638 so that the lower porous plate 657 is
an in intimate contact with the surface of the separation media or
with a porous plate within the composite column on top of the
separation media.
[0116] Alternatively, sample module 550 can be placed in a remote
tube connected by a solvent line. Alternatively, the sample can be
dissolved in a separation solvent (or a weaker solvent), and added
to sample module 550 by any of the techniques described above. The
wet module can then be loaded into the column or into a remote
tube.
[0117] Examples of the types of complex samples where this
technique has particularly advantageous use include synthetic
organic reaction mixtures and natural product extracts, (e.g., from
fermentation broths or plants). These samples often need to be
dissolved in a solvent not compatible with the optimized separation
solvent. Solvents are organized according to their "solvent
strength," where hexanes have a value close to zero, and methanol
has a value of 0.95. Optimized separation eluents often have a
lower solvent strength; e.g., hexane:ethylacetate 1:1 has a solvent
strength of 0.295. If the sample needs to be dissolved in a strong
solvent such as methanol, there will be a solvent strength
difference of 0.655 seen initially after loading the sample onto
the column, and this will impair the separation of the sample. If
the sample dissolved in methanol is instead preadsorbed to the
media in the sample module and dried, the sample will not face this
impairment during separation.
[0118] Referring to FIGS. 22 and 23, sample modules 550 can be
supplied in racks 532, and a whole rack of sample modules 550 can
be efficiently prepared at one time rather than one at a time.
[0119] FIG. 24A shows the placement of a module 550 in a composite
column 638 and the sealing of the module 550 and composite column
638 to a sealing head used to deliver solvent. Sealing head 610 has
first head piece 612, second head piece 624, intermediate head
piece 628, and first and second annular elastomeric sealing members
634, 636.
[0120] First head piece 612 has body 614 with longitudinal axis
616. First head piece 612 has outwardly extending shoulder 618, and
contact face 620. Part of contact face 620 has a slightly conical
shape or other concavity. First head piece 612 defines flow path
622 along axis 616.
[0121] Body 614 of first head piece 612 fits slidably through
central openings in second head piece 624, intermediate head piece
628, and first and second elastomeric sealing members 634, 636.
[0122] Second head piece 624 has outwardly extending compression
force receiving member 646. Intermediate head piece 628 has narrow
portion 648 distal from second head piece 624.
[0123] First elastomeric sealing member 634 is adjacent to both
shoulder 618 and narrow portion 648 of intermediate head piece 628.
Second elastomeric sealing member 636 is adjacent to both
intermediate head piece 628 and second head piece 624.
[0124] Sample module 550 has tube 552 that contains second
chromatography media bed 554 bounded axially by second porous
plates 556, 557. The outer diameter of tube 552 is sized so that
sample module 550 fits into composite column 638. The inner
diameter of tube 552 is sized so that it may slidably receive
shoulder 618, first elastomeric sealing member 634, and narrow
portion 648 of intermediate head piece 628.
[0125] Intermediate head piece 628, second elastomeric sealing
member 636, and second head piece 624 are sized to fit slidably
into composite column 638, having chamfered edges 640, filled with
first chromatography media bed 642, which is bounded axially by
first porous plates 644.
[0126] Referring to FIG. 24B seals are formed with the apparatus by
inserting sample module 550 into composite column 638 so that
second porous plate 557 abuts first porous plate 644. Sealing head
610 is then inserted into composite column 638 and composite tube
552 of sample module 550, so that shoulder 618, first elastomeric
sealing member 634, and narrow portion 648 are within tube 552, and
contact face 620 abuts second porous plate 556. Sealing head 610
extends far enough into composite column 638 so that second
elastomeric sealing member 636 opposes the inner surface of
composite column 638.
[0127] Downward compressive force applied to outwardly extending
compression force receiving member 646 causes second head piece 624
to slide relative to first head piece 612 and transmits compressive
force to second elastomeric sealing member 636, intermediate head
piece 628, first elastomeric sealing member 634, shoulder 618,
second porous plate 556, first media bed 554, second porous plate
557, first porous plate 644, and first media bed 642. The
compressive force causes first and second elastomeric sealing
members 634, 636 to expand radially so that first elastomeric
sealing member 634 forms a seal with tube 552 and second
elastomeric sealing member 636 forms a seal with composite column
638.
[0128] The seals are released by applying an upward force to second
head piece 624, thereby reducing the compressive force on the
components of sealing head 610 and reducing the radial expansion of
elastomeric sealing members 634, 636.
[0129] Composite column 638 is formed from an outer layer 660 and
an inner layer 662. Preferably, the outer layer 660 is made of
high-density polyethylene and the inner layer 662 is a chemically
inert material, such as a fluoropolymer, for example PTFE, EFEP or
materials sold under the trade names TEFLON and TEFZEL.
Alternatively, the outer layer 660 can be made of polypropylene,
stainless steel, aluminum, anodized aluminum, acetal,
polycarbonate, glass or any other suitable material. The tube 552
is made of high-density polyethylene, but may be constructed of
other materials, including glass or stainless steel. As discussed
above, the tube 552 can be a composite tube formed of two or more
layers, including an innermost layer formed from a chemically inert
material, such as a fluoropolymer, for example, PTFE, EFEP, TEFLON
and TEFZEL, and a second layer made of a rigid, deformable
material, such as a high-density polyethylene, polypropylene,
stainless steel, aluminum, anodized aluminum, acetal,
polycarbonate, glass or the like. Preferably, elastomeric sealing
member 522 is made of a fluorocarbon polymer, such as that sold
under the trade name CHEMRAZ.
[0130] Composite chromatography columns and composite sample
modules, like those described above, that employ an inner layer
with a relatively low coefficient of friction (such as TEFLON) has
the further advantage of enhancing the capacity of porous members
to slide relative to the inner layer, thereby improving the axial
compression of the media when such porous members are pressed
against the media, for example, during the operation of sealing
heads that press against the porous members.
[0131] The invention has been described in terms of particular
embodiments. All of the columns discussed above can use the
composite structure described herein. The composite columns may
have 2, 3, 4, 5, 6 or any number of layers. Other embodiments are
within the scope of the following claims.
* * * * *