Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
  • B01D15/08—Selective adsorption, e.g. chromatography
  • B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
  • B01D15/20—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
  • B01D15/206—Packing or coating
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
  • B01D15/08—Selective adsorption, e.g. chromatography
  • B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
  • B01D15/22—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/50—Conditioning of the sorbent material or stationary liquid
  • G01N30/56—Packing methods or coating methods
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/60—Construction of the column
  • G01N30/6052—Construction of the column body
  • G01N30/6082—Construction of the column body transparent to radiation
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/50—Conditioning of the sorbent material or stationary liquid
  • G01N30/56—Packing methods or coating methods
  • G01N2030/562—Packing methods or coating methods packing
  • G01N2030/565—Packing methods or coating methods packing slurry packing
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/60—Construction of the column
  • G01N30/6004—Construction of the column end pieces
  • G01N30/6021—Adjustable pistons
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T137/00—Fluid handling
  • Y10T137/0318—Processes

Definitions

• This invention resides in the field of preparative chromatography columns.
• Preparative chromatography is a separation technique used to extract individual chemical species from mixtures of species for purposes of obtaining the individual species in sufficient quantity and purity to be used for therapeutic or other procedures. Preparative chromatography thus differs from analytical chromatography whose purpose is simply to determine the presence or concentration of particular components in the mixture or to determine the composition of the entire mixture. Preparative chromatography is used, for example, for purifying monoclonal antibodies and other proteins, as well as for purifying vaccines and any variety of peptides.
• Preparative chromatography is commonly performed by passing the source mixture through a packed column that will bind the species of interest, then eluting the bound species column with an elution buffer once all of the other components in the source mixture have passed through the column or have been washed out of the column with a wash buffer.
• the binding of the species of interest is achieved by any of a variety of interactions between the mobile phase (which includes the source mixture) and the stationary phase (the column packing). Examples of these interactions are ion-exchange chromatography, affinity chromatography, and liquid-liquid or partition chromatography.
• Flow through a preparative chromatography column is generally in the axial direction, and the axial length of the column must be limited in order to avoid an excessive pressure drop through the column, since high pressure drops require a high mobile phase pump pressure, high power to drive the pump, or both.
• the typical preparative column thus has a diameter of at least several centimeters, and in some cases, a meter or more. Columns of large diameter present certain challenges, however, one of which is the difficulty in distributing the flow effectively across the width of the column.
• a uniform flow distribution is needed for good separation and resolving power and for maximal use of the column packing, and the larger the diameter the more difficult these are to achieve.
• Flow distributors are typically used at both ends of the column to address this problem.
• Another challenge which arises particularly in columns that are arranged vertically with downward flow, is the difficulty of packing the column in a manner that produces a uniform packing density in the column.
• a poorly packed bed will contain void spaces that cause flow channeling which can likewise reduce the contact between the mobile and stationary phases and thereby reduce the resolving power. Void spaces can be eliminated by applying pressure to the packing, and a sliding piston, also referred to as an "adaptor,” which also contains flow distribution channels, is commonly used for this purpose.
• a piston applying high pressure to the packing can lead to fracture or pulverization of portions of the packing material, particularly if the material is incompressible or fragile.
• the lowering of the adaptor must therefore be closely controlled to avoid such damage.
• the total amount of resin in the column, and hence the resin height, prior to compression must be known.
• the present invention resides in a preparative chromatography column whose wall includes a strip of transparent material that functions as a sight glass through which the height, the density, or both, of the column packing can be monitored as the column is being loaded with the packing material.
• the transparent strip can also allow the position of the adaptor to be monitored as the adaptor is being lowered onto the packing. While the major portion of the column wall is typically constructed of steel or other opaque material, the monitoring strip is transparent to allow monitoring to be performed through the column wall from the exterior of the column.
• FIG. l is a perspective view of a preparative chromatography column in accordance with the present invention.
• FIG. 2 is a cross section of the preparative chromatography column of FIG,. 1
• the strip of column wall occupied by the transparent material will at least have a component that is parallel to the longitudinal axis of the column.
• the strip can thus itself be parallel to the axis or it can be a spiral or otherwise angled with a tangential component and an axial component.
• a strip that is itself parallel to the column axis is preferred.
• the length of the strip in the axial direction can be equal to or less than the length of the column, provided that it has an axial length and position that brackets the range of bed heights that may be used in the column and that allows observation or detection of the adaptor position as it the adaptor approaches the bed.
• any transparent material that is rigid, that can withstand the column pressure, and that is inert to all liquids and other materials that will occupy the column, including biological fluids, wash buffers, and elution buffers, can be used for the monitoring strip.
• Preferred transparent materials are those that are also resistant to etching and other surface degradations that might reduce visibility.
• suitable materials are transparent polymers such as acrylic, polycarbonate, a styrenic polymer, a polyester, or a polyimide.
• Further examples are glass such as borosilicate glass, soda lime glass, lead glass, fused quartz, diamond, or sapphire.
• the strip can be plain or can have markings to indicate the height of the visualized packing or of the adaptor above the column floor.
• the transparent strip is preferably mounted in the column wall in such a manner that the strip is sealed along its edges to prevent leakage around the strip of any fluids from the column interior.
• the strip is also preferably shaped and mounted in such a manner that the inner surface of the strip does not interfere with, or otherwise influence, either the distribution of packing material in the column or the flow of liquid through the column.
• the column itself is a cylinder, which term is used herein according to its dictionary definition to mean the surface created by a straight line moving parallel to a fixed straight line and intersecting a fixed planar closed curve.
• a right circular cylinder is one in which the closed curve is a circle and the fixed straight line is the axis of the circle or any line that is perpendicular to the plane of the circle.
• the inward-facing surface of the strip is preferably of a concave curvature to match that of the inner wall surface of the column.
• Securement of the strip to the remainder of the column wall can be achieved by conventional means, although a preferred means is by providing the strip with a cross section in the form of a truncated wedge so that pressure from the column interior will force the edges of the strip against the contacting edges of the adjacent column wall to enhance the seal. Gasket materials can also be placed between the contacting edges to further enforce the seal. To compensate for any lessening of the column's structural integrity due to the inclusion of the transparent strip, a reinforcing flange or band can be placed around the outer surface of the column wall.
• Monitoring of the column packing through the strip of transparent material can be performed by instrumentation, including machine detection, automated illumination and the detection of reflected or non-absorbed light, or by visual observation. Monitoring by visual observation is preferred.
• FIG. 1 is a perspective view of the column 11, showing that the column is a right circular cylinder with a cylinder axis 12.
• the direction of flow of the source mixture, wash buffer(s), and elution buffer through the column is indicated by the arrow 13 which is parallel to the column axis 12.
• the column packing is placed in the column from above through the upper end of the column, and the height of the packing in the column interior is indicated by the dashed line 14.
• the adaptor 15 is also indicated by dashed lines.
• the column wall 16 is stainless steel except for the glass (or other transparent material) strip 17, and both the packed bed and the adaptor are visible through the transparent strip.
• FIG. 2 is a cross section of the column wall taken at mid height.
• the stainless steel portion 16 forms almost the entire circumference of the column wall, and the glass strip 17 occupies the remainder of the circumference.
• the longitudinal edges of the glass strip are not parallel but instead are angled to form a wedge, as are the edges of the adjacent steel, so that an internal column pressure that is higher than the external pressure will press the glass strip against the steel without danger that the strip will be forced out of the wall.
• the glass strip can be wrapped with a flat gasket material, or, as shown in the example shown in the Figure, strips 20, 21 of gasket material can be placed between the glass and the stainless steel, to further enforce the seal.
• the column wall can contain two or more transparent strips positioned at different locations around the column circumference. Other examples will be readily apparent.

Landscapes

• 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)

Priority Applications (3)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Citations (5)

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• 2010
  • 2010-06-10 US US12/797,986 patent/US20110139689A1/en not_active Abandoned
  • 2010-06-29 WO PCT/US2010/040450 patent/WO2011002796A1/en not_active Ceased
  • 2010-06-29 EP EP10794653.5A patent/EP2448646A4/en not_active Withdrawn
  • 2010-06-29 JP JP2012517866A patent/JP2012532317A/ja not_active Ceased
  • 2010-06-29 CA CA 2766093 patent/CA2766093C/en not_active Expired - Fee Related

Patent Citations (5)

Non-Patent Citations (1)

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