GB2110951A - Improvements in chromatography - Google Patents

Improvements in chromatography Download PDF

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Publication number
GB2110951A
GB2110951A GB08223535A GB8223535A GB2110951A GB 2110951 A GB2110951 A GB 2110951A GB 08223535 A GB08223535 A GB 08223535A GB 8223535 A GB8223535 A GB 8223535A GB 2110951 A GB2110951 A GB 2110951A
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United Kingdom
Prior art keywords
cartridge
cap
packing material
retention
radially
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
GB08223535A
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GB2110951B (en
Inventor
Carl Watson Rausch
Yury Tuvin
Uwe Dieter Neue
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Waters Associates Inc
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Waters Associates Inc
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Filing date
Publication date
Priority claimed from US06/001,540 external-priority patent/US4228007A/en
Application filed by Waters Associates Inc filed Critical Waters Associates Inc
Publication of GB2110951A publication Critical patent/GB2110951A/en
Application granted granted Critical
Publication of GB2110951B publication Critical patent/GB2110951B/en
Expired legal-status Critical Current

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6091Cartridges
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D15/00Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08Selective adsorption, e.g. chromatography
    • B01D15/10Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/12Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
    • B01D15/125Pre-filtration
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D15/00Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08Selective adsorption, e.g. chromatography
    • B01D15/10Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/20Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
    • B01D15/206Packing or coating
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D15/00Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08Selective adsorption, e.g. chromatography
    • B01D15/10Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/22Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/50Conditioning of the sorbent material or stationary liquid
    • G01N30/52Physical parameters
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6047Construction of the column with supporting means; Holders
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/50Conditioning of the sorbent material or stationary liquid
    • G01N30/52Physical parameters
    • G01N2030/522Physical parameters pressure
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6004Construction of the column end pieces
    • G01N30/6017Fluid distributors

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

A chromatography cartridge (20) stabilized by radial compression is disclosed with integral distributors each composed of two abutting thin plates (126, 128), one with generally radial slits (202) and the other with radially-displaced apertures (206). Also disclosed are a replaceable filter cap (130) which fits in the cartridge inlet and has screen (132) and a holder for radially compressing the cartridge with pressure sequentially generated by pistons and applied across a flexible sleeve which in use surrounds cartridge (20). Retaining member (118) has ring (124) which snap-fits into groove (121) so that screen (120) holds plates (126, 128), and the silica packing of the column in place. If screen (132) becomes blocked, inlet fitting (240) and filter cap (130) are removable so that the cap (130) can be replaced without dislodging the column packing, or the retaining members. <IMAGE>

Description

SPECIFICATION Improvements in chromatography In chromatography, a test fluid in which a chemical sample containing numerous substances is dissolved is passed through a column of packing material contained in a tube. Because different substances in the sample have different affinities for the packing material, the time at which each substance emerges from the column will vary. The presence of a substance in the output fluid is generally detected by measuring changes in the physico-chemical properties of the fluid. A plot of these properties versus time will exhibit response peaks corresponding to each of the substances.
To improve resolution between response peaks, it is desirable to provide uniform flow paths for the test liquid through the column. Irregular-sized voids between particles in the packing material allow portions of the test liquid to advance ahead of others, thereby defeating the separation performed by the column and leading to an overlapping of the responses, so that resolution between response peaks is lost Irregular-sized voids can occur within the packing and also at the interface between the packing and the tube wall.
The co-pending U.S. Patent application of McDonald et al., S.N. 848, 752, filed November 4, 1977 (a continuation of S.N. 638,301,filed December 8, 1975), entitled "'Radial Compression of Packed Beds", discloses eliminating irregular voids by radially compressing the packing material. Further, it discloses that voids between the packing material andthetubewall can be eliminated by deforming a plastic wall against the packing. The application discloses a variety of methods and apparatus for achieving radial compression and wall deformation.
These include initial radial compression at the time of filling and further compression during use; using a plastic cartridge preexpanded with gas internally while filling and then compressed with gas externally during use; using a steel cartridge pre-expended by heating and pressurized slurry filling to provide permanent radial compression on contraction; using external compression pressures of between 10 and 1000 psi (0.7 and 70 kg 10m2); and using cartridges with walls between 1 and 100 mils (.6025 and .25 cm) thick.
Another cause of degraded peak resolution is poor radial distribution of incoming and outgoing fluid.
With cartridges that have substantial transverse dimensions relative to the size ofthe particles of the packing material (although the transverse dimension is generally much less than the longitudinal dimension), it is necessary to create a radially uniform flow profile through the cartridge. Simply allowing the fluid to enter and leavethrough small openings along the longitudinal axis causes overlapping of response peaks because fluid traveling along the longer radially outward paths takes a longer time to traverse the column that fluid travelling along the centerline.
There are commercially-avialable cartridges which provide radial distribution. A preparative chromatography cartridge (30 cm x 5 cm) sold by Water Associates, Inc., uses a flat transverse plate with radially spaced holes; the holes communicate with a funnel chamber which moves the fluid between inlet and outlet conduits and the hole locations. A cartridge sold by Unimetrics Corporation under the Knauer trademark employs a thin plate inside the cartridge with radially-extending slits grouped in patterns of three so as to have the appearance of a bird foot print. Fluid moves radially in the slits while also flowing longitudinally through an abutting filter screen and then through a succession of fiber glass filters before reaching the packing material. In practice, mixing occurs in the series of filters, and peak resolution is thus degraded.
While both these cartridges distribute the fluid radially, neither they nor any others known have adequately eliminated another source of mixing, namely, regions of excessive volume within the distributor or the filter assembly. This excessive volume causes what is known as outer column peak spreading in which backmixing of separated substances occurs outside the column, resulting in poor resolution of response peaks.
A further source of degraded resolution is clogging of the filters provided at the inlet of the cartridges to retain the packing material. They can become clogged with foreign particles suspended on the test fluid. The above-mentioned Knauer cartridges can have its filter replaced but to do so requires removal of the cartridge retaining cap.
In its various aspects, the invention features: a chromatography cartridge having an integral distributorwith radial transfer means (e.g., a thin plate with generally radially-extending slits) and a thin plate with radially-displaced apertures that communicate betwen the radial transfer means and the packing material, the plate apertures and the radial transfer means having a negligible volume in comparison to the cartridge (e.g., less than 0.1 %); a replaceable filter cap placed in the inlet retention cap upstream of the retention screen, the filter assembly having a negligible volume in comparison to the cartridge; a plastic cartridge with snap-fit retention caps; a flow distributor with individual radially-extending passages for moving fluid radially and separate means for moving the fluid axially between ends of the radial passages and the packing material the distributor having a negligible volume in comparison to the cartridge; providing permanent radial compression of the packing material in a plastic carridge by using pressurized slurry filling to expand the plastic wall and then allowing the wall to contract; radially compressing a plastic cartridge by surrounding it with a pressure-transmitting flexible sleeve and putting pressure on the sleeve; performing liquid chormatography while radially compressing the packing material with greater than 1500 psi (105 kg/cm2) preferably between 2000-6000 psi) This print takes account of replacement documents later filed to enable the application to comply with the formal requirements of the Patents Rules 1978 or 1982.
(140-420 kg/cm2) externally applied pressure; using pistons of different cross sectional areas to put radially-inward pressure on a cartridge, the area being chosen so that operating force to successively actuate them be about the same; ejecting a cartridge from a cartridge holder by moving a pinion and through it a rack and pins to push on one end of the cartridge.
The invention provides a simple, rugged, relatively inexpensive, and improved chromatography cartridge. Permanent radial compression is provided by the plastic wall and pressurized slurry packing. The inner surface of the plastic wall conforms to the shape of individual particles. The cartridge is resistant to shock loads (mechanical, thermal, or chemical) which would destroy the packing in ordinary columns. The replaceable filter can be removed without removing the retention cap that retains the packing material and thereby disturbing the packing structure. The cartridge can be sealed in a simple manner to inlet and outlet end fittings by radial pressure on its ends. The distributor provides uni form radial distribution without also providing excessive mixing volume at the distributor.The integral plate distributor in the cartridge achieves distribution in minimum space and at low cost. Packing materials having a greater range of particle size distribution can be used with the same chromatographic efficiency.
The radial compression mechanism used in the cartridge holder is also simplified and improved. The greater external pressures (above 1500 psi) provided for radial compression improve uniformity in void size and thus improve resolution. The pressure transmitting flexible sleeve allows application of external pressure without contact between the working liquid and the cartridge. Pressure for radial compression can be applied manually by the piston arrangement, and the ejection mechanism makes for easy removal of the cartridge, all of which simplifies operation.
We turn now to description of the structure, manufacture, and operation of preferred embodiments of the invention, after first briefly describing the drawings.
Fig. 1 is a perspective view of the cartridge holder.
Fig. 2 is a cross-sectional view at 2-2 of Fig. 1, showing the cartridge holder unpressurized and outboard portions of the pressurizing arms broken away.
Fig. 3 is a cross-sectional view at 3-3 of Fig. 1, showing the chromatography cartridge within the holder and illustrating operation of the ejection mechanism.
Fig. 4 is a cross-sectional view at 4-4 of Fig. 2, showing a cross section of the cartridge and ilfusfrali ing operation of one pressurizing arm.
Fig. 5 is an enlarged longitudinal cross-sectional view at 5-5 of Fig. 1, showing the chromatography cartridge within the holder.
Fig. 6 is a longitudinal cross-sectional view of a #r5e#.red embodiment of the chromatograhy col YlfT;# ;9 ^ is a perspective view of the distributor hezv - p-- ,er r ed embodiment, with flow grooves shown enlarged.
Fig. 8 is an exploded perspective view of another preferred cartridge embodiment, showing an integ ral distributor in the column and the silica packing removed.
Referring to Fig. there is shown chromatography cartridge holder 10 with replaceable chromatography cartridge 20 removed. Sample liquid enters through inlet tube 12 (9 mil l.D.) (.0228 cm) and exits through outlet tube 14 (9 mil l.D.) (.0228 cm). Holder 1Q consists of base 16 in which pistons for pressurization are contained and cartridge chamber 18 in which replaceable cartridge 20 is radially compressed. Packing material 21 (spherical silica; 5-15 micron) is contained with cartridge 20.
Three pressurization arms 22,24, 26 are pivotally supported on shaft 28 which extends through coaxial holes 30 in arm supports 32 of base 16 (Fig. 2).
Nylon bushings and washers and steel spring washers (not shown) provide friction for arms 22,24, 26 on shaft 28. Each arm has camming surface 34 at its base (Fig. 4). The camming surfaces act against steel rollers 36 supported by shafts 37 on internal hard-coated aluminium guides 38. The guides ride within bushings 3q (oil impregnated bronze) held in bores of base 16 by retaining rings (not shown).
Guides 38 act against pistons 40,42,44 which slide within bores 46,48,50 of bronze cylinders 52,54,56.
O-rings 58 seal between the pistons and bores.
C-rings 59 seal between the cylinders and base 16.
Cylinders 52,54,56 seat against shoulders 60. Piston 40 has a 3/4 inch (1.9 cm) working diameter; piston 42 a 3/8 inch (0.95) diameter; piston 44 a 3/16 inch (0.475 cm) diameter. Flow restriction valves 62, 64 are supported between cylinders 54,56 downstream of pistons 42,44. Each valve includes a moveable member 68, a small diameter flow passage 70 in moveable member 68, a gasket 72 for sealing between cylinders 54,56 and member 68, and a spring 74 compressed between a shoulder 75 of base 16 and member 68. Piston 40 and cylinder 52 do not have a flowrestriction valve downstream. Return springs 76,78,80 between each piston and cylinder are preloaded to return the pistons to their starting positions.
Branch conduits connect the outlets of each piston and cylinder to central conduit 82. Adjustment plug 84 on one end of conduit 82 has an externally accessible slot 86 which is rotated to adjust the internal volume of the device. Cap 88 seals the opposite end of conduit 82. Vertical conduit 90 connects base 16to cartridge chamber 18 (Fig.3).
Pressure gauge 91 communicated with conduit 82.
Referring to Figs. 3 and 4, vertical conduit 92 in chamber 18 is a continuation of conduit 90. O-ring 94 seals the conduits at the interface between base 16 and chamber 18. Four cap screws 93 (Fig. 2) fasten chamber Q8to base 16. Chamber 18 consists principally of essurizsng cylinder 96, end caps 98, 100, and a cartridge election mechanism. Conduit 92 comrn###nicateswith pressurizing bore 102 in cylinder 96 Flexible sleeve 104 (Vitron rubber) is mounted within bore 102. Lips 106,108 of sleeve 104 fit into annular grooves 110, 112 at axial ends of cylinder 96.
End caps 98, 100 are secured to cylinder 96 by capscrews (not shown). No seals other than rubbery sleeve 104 are required for sealing between the end caps and the cylinder.
Supported within flexible sleeve 104 is replaceable chromatography cartridge 20, shown removed from the holder in Figs. 1 and 6. The cartridge consists of a high density polyethylene cylinder 116 (0.525 inch (1.25 cm) outside diameter and 0.100 inch (.025 cm) thick walls) and retention caps 118 with integral filter screens 120 (2 micron apertures). Caps 118 are retained in cartridge 114 by cooperation between annular grooves 121 in narrow-wall end portions 122 and annular protrusions 124 in the caps. Replaceable filter cap 130 with integral second filter screen (2 micron apertures) 132 is inserted inside the input retention cap.
Cartridge 20 fits closely within flexible sleeve 104, (Fig. 3 and 5) and abuts output fitting 134 at one axial end, and input fitting 136 at the other end. Fittings 134, 136 have male portions 138, 140 which fit tightly within the mating female portions of retention cap 118 on one end and filter cap 130 on the other end.
Inlet and outlet tubes 12, 14 are received within fittings 134, 136. The tubes communicate at their ends with distributor heads 142 (shown enlarged in Fig. 7) which radially transfer fluid from the tube to radially spaced locations in the cartridge at the input end and vice versa at the output. Referring to Fig. 7, radially direct grooves 144 (twelve shown, but eight preferred) move the fluid radially, chamber 146 in cooperation with the internal shoulders of fittings 134,136 moves the fluid circumferentially, and twenty4our axial grooves 148 move the fluid axially.
The ends of groove 148 communicate with filter screens in cartridge 114. Grooves 144, 148 are about 3 mils (.0075 cm) wide, and distributor heads 142 are 0.20 inches (0.5 cm) in diameter. Outlet fitting 134 has four holes 150 for receiving ejection pins 152 and is retained by end cap 98. Inlet fitting 136 slips through hole 151 in end cap 100 and is retained by removable cap 154, which threads onto external threads of end cap 100.
The ejection mechanism includes ejection handle 156, pinion gears 158, 160 fastened to each side of the handle, racks 162,164 sliding within bores 166, 168 in cylinder 96 and through holes in end cap 98 and secured to bracket 174 by nuts 176, and ejection pins 152 secured in bracket 1u4. Pinions 158, 160 and handle 156 rotate on shaft 178 which is supported in holes 179 in cylinder 96. Vertical members 184,186 integral with cylinder 96 cover pinions 158, 160.
Plastic cover 188 is mounted over the exposed portions of racks 162,164.
Referring to Fig. 8, there is shown another preferred embodiment of the invention. In place of distributor heads 142, flow distribution plates 126, 12i are inserted at each end of cartridge 20 between retention caps 118 and shoulders 119. Radial distribution plates 128 abut filter screens 120 and have curved slits 202 radially extending from central hole 204.
Plates 126 contact packing 21 and have three arcuate slits 206 positioned at the same radial location (0.20 inch (0.5 cm) diameter) as grooves 148 in distributor heads 142. Tubes 12, 14 extend flush with inward face 242 of male portion 240 of inlet fitting 236 so as to communicate through the thin filter screens with central hole 204 in plate 128. The outlet fitting (not shown) similarly has outlet tube 14 brought flush with its inward face.
Cartridge holder 10 is built following conventional manfacturing methods.
Cartridge 20 is filled with silica packing material 21 by passing through it a slurry of silica suspended in a pressurized low-viscosity liquid (e.g., Freon or methanol). One retention cap 118 and distributor plates 126, 128 are installed during filling and they trap silica while allowing the liquid to pass. After the cartridge is full, pressure from the liquid is removed, and wall 116, which was expanded during pressurized filling, contracts to permanently compress the silica. Excess silica at the inlet is then removed, and the second retention cap 118, distributor plates 126, 128, and filter cap x30 are installed.
To operate the chromatography cartridge holder, replaceable cartridge 20 is inserted within rubbery sleeve 104 by unscrewing removable cap 154, inserting male portion 140 of inletfitting 136 within the well formed by filter cap 130, and pushing the cartridge into sleeve 104 using fitting 136 as a handle. Cap 154 is then screwed onto end cap 100 to complete the insertion.
Pressure is applied around the sleeve 104 to radially compress cartridge 114 by sequential operation of presurizing arms 22,24,26; arm 22 raises the pressure to about 600 psi, 4.2 kg/cm2, arm 24 to about 1600 psi, kg/cm2, and arm 26 to about 2200 psi, .154kg/cm2. Cam surfaces 34 have straight portions 220 which retain each arm in the pressurizing position. Rotation of each handle between the positions illustrated in Fig. 4 cause cam surfaces 34 to push against rollers 36 and thereby move guides 38 inward against one of pistons 40,42,44. The areas of pistons 40,42,44 are selected to equally divide operating forces between the three handles.
Operation of arm 22 and associated piston 40 displaces the greatest volume of glycerin. This initial large displacement moves sleeve 104 tightly against cartridge 114, and begins compression of the silica within the column. Operation of handles 26,28 continue compression of the silica. Pistons 42,44 are progressively smaller owing to the nonlinear (approximately exponential) compression characteristics of the silica and surrounding polyethylene wall 116 and rubbery sleeve 104.
During pressurization, flow restriction valves 62, 64 at the outlet of pistons 42,44 provide no substantial flow restriction. Increasing pressure moves moveable member 68 away from body 66, compressing spring 74 and opening a wide flow passage between member 68 and body 66, past gasket 72.
Glycerin is sealed within chamber 18 by cooperation between lips 106,108 on rubbery sleeve 104 and annular grooves 110,112 in cylinder 96. Pressurization of the glycerin forces lips 106, 108 tightly against the radially outermost walls of grooves 110, 112, preventing the glycerin from flowing between the walls and the lips. Sleeve 104 also provides radially compressive forces on end portions 722 of cartridge 114 to seal the cartridge to inlet and outlet fittings 140, 138. The radially inward forces squeeze end portions 122, retention caps 118, and filter cap 130 against each other and against male portions 138, 140 of fittings 134, thereby sealing all possible outward fluid paths from tubes 12, 14 and the interior of cartridge 114.
When arm 26 has been moved into its pressurizing position, cartridge 20 is fully radially compressed and chromatography can begin. Test liquid is pumped under pressure into cartridge 20 through inlet tube 12, and emerges through outlet tube 14, which is connected to a detector (not shown) to measure solute concentrations.
If sufficient foreign particles enter through inlet tube 12 to clog filter screen 132 of filter cap 130 the cartridge may be removed, and the filter cap cleaned or replaced.
To remove cartridge 20, arms 22,24,26 are moved to their open position (shown in Fig. 1) in the reverse sequence used for pressurization - arm 26 first and arm 22 last. Flow restriction valves 62,64 slow travel of pistons 42,44 to prevent operator injury. Moveable members 68 press against gaskets 72, and fluid returns through small-diameter flow passages 70.
When arm 22 is released, spring 78 moves piston 40 back beyond the zero-pressure position, thereby creating a below atmospheric pressure at pressurizing bore 102 to pull sleeve 104 away from cartridge 20.
After pressure is removed, cartridge 20 is ejected by unscrewing cap 154 and rotating ejection handle 156 to the position shown in phantom in Figure 3.
This rotates pinions 158, 160, and through them moves racks 162, 164 and ejection pins 152. The pins, which extend through holes 150 in outlet fitting 134, press against the outlet end of cartridge 20, and move it axially to the location shown in phantom.
From this half withdrawn position, the cartridge is removed manually.
To minmize upstream-downstream concentration mixing in the cartridge and accompanying peak spreading in the output, test fluid entering through inlet tube 12 and exiting through outlet tube 14 is broken into a plurality of separate radially displaced streams by distributor heads 142 (Figs. 5 and 7). The separate streams enter and leave the cartridge through axial grooves 148 in distributor heads 142.
The internal volume of the distributor is less than about 3 to 5 microliters, and the fluid paths are short, thereby minimizing upstream-downstream mixing in the distributor. The 0.20 inch (0.5 cm) diameter of heads 142 positions axial grooves 148 at a radial location which divides the cartridge cross section into an inner circle and an outer ring, each with approximately the same area. By so distributing the fluid, each successive volume segment of incoming fluid in inlet tube 12 is spread uniformly across the cross section of cartridge 114, is moved through the cartridge all at substantially one axial location, and is removed from the cartridge by being transferred to substantially one axial location in outlet tube 14.
Without proper distribution of the incoming and outgoing flow, a given axial volume segment of incoming fluid would, due to initial outward radial spreading upon entry into the cartridge, move through the cartridge at axial locations that differ radially in a curved profile, with radially outward portions trailing portions moving through the center.
When such a curved profile is removed from a cartridge, upstream-downstream mixing and accompanying peak spreading necessarily results.
In the other preferred embodiment shown in Fig.
8, the radial flow passages are defined by slits 202 and the abutting surfaces of plate 126 and filter screen 120. Face 242 of distributor presses tightly againstfilterscreen 120,132to keep fluid within slits 202. Arcuate slits 206 axially transfer the radially displaced fluid to the packing material.
To avoid additional upstream-downstream concentration mixing in fittings 134, 136, and the other fluid connections to the cartridge, flow volume within the fittings and connections is minimized. In both distributor embodiments (Figs. 7 and 8), fluid travelling in tubes 12, 14 is divided abruptly into a plurality of small flow channels which are then routed to the desired radial locations. Further, filter screens 120, 132 are made of thin stainless stell mesh to minimize their volume. In distributor head 142 (Fig. 7), the small flow channels are defined by the individual radial grooves 144, chamber 146, and individual axial grooves 148. In the other preferred cartridge embodiment (Fig. 8), the flow channels are defined by the radial slits and arcuate slits.The high radial compression pressures tend to make the interior surface of polyethylene wall 116 of cartridge 20 conform to the shape of the silica particles, thus eliminating wall channeling wherein voids at the wall allow unevenly fast advance of the test liquid there. Experiments have observed that after compression impressions are left by the silica particles on the interior surface of wall 116.
The 0.100 inch (0.25 cm) thickness of wall 116 provides sufficient handling rigidity outside of holder 10 while also providing sufficient expansion during pressurized fill to give small but permanent radial compression to the silica.
Other embodiments of the invention will occur to those skilled in the art. For example,the cartridge wall thickness can be varied between about 0.005 and 0.250 inches (.00125 and 0.6 cm); and the number of radially directed grooves in distributor heads 142 could be fewer or greater than eight.
Further, there are many variations possible on the arrangement of plates 126,128 in Fig. 8. For example, the radial flow distribution function of radially split plate 128 could be performed, without the plate, byfilterscreen 120 or screen 132. Fluid would move radially within the filter mesh. Or the radial distribution could be achieved by moving plate 126 adjacent to face 242 and providing a small volume gap between face 242 and plate 126. In any of these variations it is, however, necessary to keep the flow volume inside the distributor small compared to the cartridge volume.
A most-preferred production model of the cartridge holder includes several small variations from the holder described above and shown in Figures 1 through 5. Cylinder 96 and base 16 are made from a single casting, eliminating the need for fasteners 92 and seal 94. Gauge 91 is moved to the face of base 16 on which plug 88 is located. Pinion covers 184 are rectangular rather than trapezoidal.
In a most preferred cartridge embodiment, the location of plates 126,128 is shifted from that shown in Fig. 8 to a location between the filter screens and face 242.

Claims (10)

CLAIMS 1. A cartridge for chromatography, said cartridge containing chromatographic packing material and comprising: a tubular body, said body having a flexible plastic wall capable of being radially expanded when subjected to the internal pressures arising during slurry packing of said packing material and of being radially compressed when subjected to external compression pressures during use, integral plastic end portions each having a cylindrical recess open at the end of the cartridge and an annular groove around the interior cylindrical surface of said recess, and retention caps secured in said end portions, each said cap comprising a tubular member, an annular ridge on said member adapted to be received by said annular groove in each said end portion, and a thin transversely oriented filter screen secured to said member, whereby said packing material is contained within said cartridge and is permanently radially compressed by said plastic wall after slurry packing pressure is removed, whereby said filter screens axially retain said packing material inside said cartridge, whereby said retention caps can be snapped into place in said end portions of said cartridge by applying axial force to said caps sufficient to snap said ridge into said groove, and whereby said cartridge may be sealed to inlet and outlet tubes carrying fluid chromatography samples by applying radial compression to said integral end portions, thereby squeezing said end portions and retention caps inward against a male fitting which may be inserted in said retention caps. 2. The cartridge of claim 1 further comprising a removeable filter cap, said filter cap including a tubular member having a cylindrical exterior surface dimensioned to fit tightly within the interior cylindrical surface of said tubular member of one said retention cap and a thin transversely oriented filter screen secured to one end of said tubular member, whereby said filter cap can be inserted in one said retention cap with its filter screen abutting said filter screen of said retention cap, whereby said filter cap can be removed and replaced when the pores of its filter screen have become clogged with particles, and whereby radial compression of a said end portion of said cartridge against a male fitting which carries the inlet tube and which may be inserted inside said filter cap will seal all the cylindrical interfaces between the fitting, filter cap, retention cap, and end portion, thereby providing a fluid-tight seal between the inlet tube and the cartridge. 3. A cartridge for chromatography, said cartridge containing chromatographic packing material and comprising: a tubular body, said body having a flexible plastic cylindrical wall capable of being radially compressed inward during use, retention caps at either end of said tubular body for axially retaining said packing material, said caps including a filter screen in contact with said packing material, and a removable filter cap, said filter cap including a tubular member having an exterior surface dimensioned to fit tightly within the interior cylindrical surface of said retention caps and a thin transversely oriented filter screen secured to one end of said tubular member, whereby said filter cap can be inserted in one said retention cap with its filter screen abutting said filter screen of said retention cap and whereby said filter cap can be removed and replaced when the pores of its filter screen have become clogged with particles, without having to remove said retention cap and thereby expose said packing material. 4. The cartridge of claim 2 wherein said exterior surface of said filter cap and said interior surface of said retention cap are cylindrical. 5. A cartridge for chromatography, said cartridge containing chromatographic packing material and comprising: a tubular body, said body having a flexible plastic cylindrical wall capable of being radially compressed inward during use; retention caps at either end of said tubular body for axially retaining said packing material; and inlet and outlet distributors for radially displacing entering and exiting chromatographicfluid, each said distribution including a radial distribution plate oriented transversely and positioned between said packing material and the inlet and outlet of said cartridge, said plate having a central hole and generally radially extending slits, and an axial distribution plate oriented transversely and on the packing material side of said means to move fluid radially, said plate having apertures located at radially spaced location to communicate with means to move fluid radially, whereby chromatographic fluid entering and exiting said cartridge travels axially through the apertures in said axial distribution plate and travels radially through said slits in said radial distribution plate, whereby the internal volume of said distributors is minimized so as to reduce upstream-downstream mixing of said chromatographic fluid and whereby the regions of fluid entry and exit from said packing material are restricted to radially-displaced locations. 6. A method of manufacturing a cartridge containing chromatographic packing material, compris ing the steps of: filling the plastic cartridge with packing material suspended in a pressurized liquid to form a slurry, whereby the pressurized liquid tends to expand the wall of said cartridge and removing the pressurized liquid, whereby the wall of said cartridge contracts and places the packing material under permanent radial compression. 7. A cartridge for chromatography substantially as hereinbefore described with reference to any one of the figures of the accompanying drawings. New claims or amendments to claims filed on 18/1/83. Superseded claims 1-7. New or amended claims 1 to 10.
1. A chromatography cartridge comprising a tubular body, having a flexible wall of plastics material capable of being radially compressed inward during use and containing packing material for liquid chromatography, a retention cap at each end of the body, each retention cap axially retaining the packing material and having a filter screen, and a radial flow distributor adjacent to one of the retention caps which operates to distribute liquid entering the tubular body radially across the packing material.
2. A chromatography cartridge as claimed in claim 1, the tubular body of which was radially expanded in manufacture by the pressure arising during slurry packing of the packing material into the body.
3. A chromatography cartridge as claimed in claim 1 or claim 2, wherein the radial flow distributor comprises integral end portions attached to the tubular body, each end portion having an open cylindrical recess and an annular groove around the interior surface of the recess, and wherein each retention cap comprises a tubular member having an annular ridge adapted to be received by one of said annular grooves and a thin transversely oriented filter screen secured to this tubular member.
4. A chromatography cartridge as clamed in claim 1 or claim 2, which includes a filter cap insertable in one of the retention caps, said filter cap comprising a tubular member having a cylindrical exterior surface which fits tightly within said retention cap and a thin transversely oriented filter screen secured to one end of said tubular member.
5. Achromatography cartridge as claimed in claim 4, wherein the filter cap can be removed and replaced when the pores of the filter screen become clogged.
6. A chromatography cartridge as claimed in claim 4, wherein the exterior surface of the filter cap and the interior of the retention cap are cylindrical.
7. A chromatography cartridge as claimed in claim 1, or claim 2, wherein the radial floe distributor includes a radial distribution plate oriented transversely with respect to the tubular body, said plate having a central hole and generally radially extending slits.
8. A chromatography cartridge as claimed in claim 1 or claim 2, wherein the radial flow distributor is an axial distribution plate oriented transversely with respect to the tubular body, said plate having apertures located at radially spaced locations.
9. A chromatography cartridge as claimed in claim 3, wherein the retention caps can be snapped into place in said integral end portions by applying axial force to the caps sufficient to snap the ridges into the annular grooves.
10. A chromatography cartridge as claimed in claim 1, substantially as hereinbefore described with reference to any one of the Figures of the accompanying drawings.
GB08223535A 1979-01-08 1979-12-28 Improvements in chromatography Expired GB2110951B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US06/001,540 US4228007A (en) 1979-01-08 1979-01-08 Chromatographic cartridge and holder
GB7944432A GB2038659B (en) 1979-01-08 1979-12-28 Chromatographic cartridge and holder

Publications (2)

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GB2110951A true GB2110951A (en) 1983-06-29
GB2110951B GB2110951B (en) 1983-11-16

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310867A2 (en) * 1987-10-05 1989-04-12 Shimadzu Techno-Research Inc. Chromatographic column
EP0377202A2 (en) * 1989-01-04 1990-07-11 CARLO ERBA STRUMENTAZIONE S.p.A. Method and mixing device for small volumes
FR2654835A1 (en) * 1989-11-23 1991-05-24 Rhone Poulenc Rech Chromatography microcolumns
GB2325868A (en) * 1997-06-06 1998-12-09 Amersham Pharm Biotech Ab Liner for the end plate of a chromatographic column
WO2011112144A1 (en) * 2010-03-12 2011-09-15 Ge Healthcare Bio-Sciences Ab Chromatography column assembly comprising a fixture for a plastic mesh

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310867A2 (en) * 1987-10-05 1989-04-12 Shimadzu Techno-Research Inc. Chromatographic column
EP0310867A3 (en) * 1987-10-05 1991-07-31 Shimadzu Techno-Research Inc. Chromatographic column
EP0377202A2 (en) * 1989-01-04 1990-07-11 CARLO ERBA STRUMENTAZIONE S.p.A. Method and mixing device for small volumes
EP0377202A3 (en) * 1989-01-04 1991-10-09 CARLO ERBA STRUMENTAZIONE S.p.A. Method and mixing device for small volumes
FR2654835A1 (en) * 1989-11-23 1991-05-24 Rhone Poulenc Rech Chromatography microcolumns
GB2325868A (en) * 1997-06-06 1998-12-09 Amersham Pharm Biotech Ab Liner for the end plate of a chromatographic column
US6224760B1 (en) 1997-06-06 2001-05-01 John Davies Chromatography column end arrangements
WO2011112144A1 (en) * 2010-03-12 2011-09-15 Ge Healthcare Bio-Sciences Ab Chromatography column assembly comprising a fixture for a plastic mesh
CN102782490A (en) * 2010-03-12 2012-11-14 通用电气健康护理生物科学股份公司 Chromatography column assembly comprising a fixture for a plastic mesh
US8562827B2 (en) 2010-03-12 2013-10-22 Ge Healthcare Bio-Sciences Ab Chromatography column assembly comprising a fixture for a plastic mesh
CN102782490B (en) * 2010-03-12 2015-03-25 通用电气健康护理生物科学股份公司 Chromatography column assembly comprising a fixture for a plastic mesh

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