Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/30—Processes for preparing, regenerating, or reactivating
  • B01J20/305—Addition of material, later completely removed, e.g. as result of heat treatment, leaching or washing, e.g. for forming pores
  • B01J20/3064—Addition of pore forming agents, e.g. pore inducing or porogenic agents
• • 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
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/0006—Controlling or regulating processes
  • B01J19/0013—Controlling the temperature of the process
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/18—Stationary reactors having moving elements inside
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
  • B01J20/282—Porous sorbents
  • B01J20/283—Porous sorbents based on silica
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
  • B01J20/282—Porous sorbents
  • B01J20/285—Porous sorbents based on polymers
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
  • B01J8/0005—Catalytic processes under superatmospheric pressure
• • 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
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00049—Controlling or regulating processes
  • B01J2219/00162—Controlling or regulating processes controlling the pressure
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2220/00—Aspects relating to sorbent materials
  • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
  • B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2220/00—Aspects relating to sorbent materials
  • B01J2220/80—Aspects related to sorbents specially adapted for preparative, analytical or investigative chromatography
  • B01J2220/82—Shaped bodies, e.g. monoliths, plugs, tubes, continuous beds
• • 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
  • G01N30/52—Physical parameters
  • G01N2030/522—Physical parameters pressure
• • 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
  • G01N30/52—Physical parameters
  • G01N2030/524—Physical parameters structural properties
  • G01N2030/528—Monolithic sorbent material
• • 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
  • G01N2030/567—Packing methods or coating methods coating

Definitions

• This invention relates to separation systems and their components and
• Monolithic macroporous materials such as for example organic
• components for separation systems such as chromatographic or
• One class of such materials is formed as a monolithic
• macroporous polymer plug or solid support produced by polymerizing one or
• cross-linking agents as cross-linking agents, catalysts and small soluble polymers which can be
• the plug may be modified after being formed to add functional
• the plug or solid support is normally contained in a housing such as for
• the polymerization mixture may be added to the
• Zone spreading from mass transfer can be minimized by using non-
• macroporous polymeric monolithic plugs or solid supports use plugs or solid
• zone spreading by capturing sample and retaining it for a time. This may be
• the layers of porous sheets are held in a support
• resulting material is a macroporous membrane including pores from micropores
• This porous material has several disadvantages, such as for example:
• covering pore in this specification means pores that contribute to zone
• U.S. Patents 5,334,310; 5,453,185 and 5,728,457 each disclose a method of making macroporous poly(glycidyl methacrylate-co-ethylene glycol
• plugs formed according to these patents have a pore size distribution that is
• the macroporous polymers consist of interconnected aggregates
• molds such as for example molds having a diameter of more than 15 mm and
• the reversed phase media has very
• polymeric materials including permeable polymer support using irradiation
• permeable monolithic medium with covalently bonded particles having a controlled minute throughly convoluted surface configuration but with few or no
• UV or visible radiation e.g. UV-visible light
• polymerization mixture is polymerized in place with a porogen or solvent, to form
• openings means pores or channels or other openings that play a role in
• Pores generally
• Separation factors includes those factors that effect retention and
• openings such as channels or the like but not containing pores as defined
• shrinkage during polymerization is
• Shrinkage results in enlarged voids on the polymer surface and may result in
• the voids are mostly located in between the column
• the voids are
• AIBN which is a common initiator for the polymerization.
• the compensation for shrinkage is accomplished
• shrinkage is prevented by holding the column from
• shrinking or for avoiding shrinking are also used as described in greater detail below. It is believed that the externally applied pressure overcomes uneven
• hydrophillic solutions such as for example in the aqueous mobile
• the pressure applied during polymerization is selected in accordance with
• separation-effective opening size is controlled by selecting the
• some plugs tends to expand when exposed to
• separation-effective openings may shrink when polymerized others may not,
• non-fluidic pressure such as with a piston
• a polymerization mixture is applied to a column in the
• pressure is applied to the polymerization solution.
• pressure is applied to the polymerization solution.
• the pressure is maintained at a level above atmospheric pressure to prevent
• polymerization may be non-reactive or may be treated to increase adhesion to
• the polymerization mixture in some embodiments includes: (1) selected
• porogen The porogen, initiator, functional group to be added, additives,
• reaction conditions and the monomer and/or polymer are selected for a
• a chromatographic column in accordance with this invention preferably
• This plug serves as a support for a sample in chromatographic
• the permeable monolithic polymeric plug has smooth walls with no
• polymeric means monolithic polymeric permeable material having separation-
• One embodiment of column is made using a temperature controlled reaction chamber adapted to contain a polymerization mixture during
• the pressure is applied by a movable member having a smooth
• phase media include polystyrenes, polymethacrylates and their combinations.
• oligonucleotides and synthetic homopolymers In one embodiment a reversed
• phase media is based on poly(styrene-co-divinylbenzene).
• a reversed phase media is based on poly(stearyl)
• ethylene glycol dimethacrylate and monomers including styrene (ST) or
• MA methacrylates
• crosslinkers are greater than 40 percent by weight
• the ratio of divinylbenzene and styrene is a value of divinylbenzene
• the column may also be in the range of ratios
• the content of DVB in total monomers is preferably
• the content of DVB is 80%
• the plug may also include methacrylates with hydrophobic
• Ion exchange plugs are formed principally of methacrylate polymers.
• weak anion exchange plug is principally formed of polymers of glycidyl
• GMA methacrylate
• EDMA ethylene glycol dimethacrylate
• anion exchanger plug is principally polymers of glycidyl methacrylate, 2-
• the polymerization mixture may also include 1 , 4-butanediol,
• a weak cation exchanger plug is formed principally of
• strong cation exchanger plug is formed principally of glycidyl methacrylate, 2-
• This controlled modification may also improve the
• the modification conditions are:
• the polymer plugs may be formed in a column of any size or shape
• the components may
• a plurality of columns is connected in parallel in a
• chromatographic system that includes a pumping system, solvent system and
• the columns are permeable polymeric columns with high
• reaction is controlled by independent means
• electromagnetic radiation such as for example UV-vis, X-
• heat may be added from a heat source or removed by
• cooling means in contact with a significantly large portion of coolant of the
• variable intensity or variable wavelength X-rays may be used to control the polymerization rates of the
• the initiator is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
• the radiation may be used to control the
• the radiation sensitizers such as x-ray scintillators
• the wavelength of the luminescence should be any wavelength of the luminescence.
• a lower energy x-ray is used to initiate the polymerizations
• temperature and temperature gradient may be prevented with choice of a
• This stabilizing additive should have properties such that
• the reaction can proceed freely up to rate at which the desired polymer is
• DSTDP Disterylhiodipropionate
• the large diameter column is prepared by
• a polar solvent such as an aqueous solvent
• the characteristics can be altered in some columns by applying pressure. It is
• monolithic solid support of this invention has several advantages, such as for
• FIG. 1 is a schematic diagram of one embodiment of a process for
• FIG.2 is an assembly of a fixture for applying pressure to a glass column
• FIG. 3 is an assembly of another fixture for applying pressure to a stainless steel column during polymerization
• FIG. 4 is an assembly of still another fixture for applying pressure to a
• FIG. 5 is a Scanning Electron Microscopy (SEM) picture of the strong
• FIG.6 is a chromatogram showing peaks from a protein sample with a
• FIG. 7 is a photograph showing three columns with the one on the left
• FIG. 8 is a block diagram of a chromatographic system with an array of
• Fig. 9 is a chromatogram showing the chromatography separation
• FIG. 10 is a top view of a UV or visible light polymerization apparatus for
• FIG. 11 is a sectional side elevational view of the apparatus of FIG. 10.
• FIG. 12 is a schematic elevational view of an x-ray polymerization
• FIG. 13 is a top view of a portion of the apparatus of FIG. 12;
• FIG. 14 is an elevational sectional view of a portion of the apparatus of
• FIG. 12 taken through lines 14-14;
• FIG. 15 is an elevational sectional view taken through lines 15-15 of
• a polymerizable mixture is placed in a container with a porogen
• a separation system such as for example a chromatographic column.
• the polymerization is done in a container in which the plug is
• the mixture is polymerized while
• the compensation is accomplished by applying pressure during polymerization to at least maintain the integrity ofthe
• the polymers, monomers, initiators and mixtures thereof may provide poor reproducibility.
• the polymers, monomers, initiators and mixtures may provide poor reproducibility.
• pressure is
• polymerization may be non-reactive or may be treated to increase adhesion.
• the polymerization mixture includes at least one
• the polymerization mixture includes,
• urea formaldehyde or silica to form urea formaldehyde or silica plugs.
• a chromatographic column formed by these processes includes a
• opening size is controlled by the amount and type of porogen in the
• the pressures may be selected in a range of slightly above
• the permeable monolithic polymeric plug has smooth walls and substantially
• the plugs may have surface functional groups.
• hydrophobic surface groups such as phenolic groups may be
• surface groups may be added to increase capacity in reverse phase plugs.
• micropores or channeling openings in the walls over is formed principally of
• a weak ion exchange permeable monolithic polymeric plug is
• styrene Preferably the ratio of divinylbenzene and styrene is approximately in
• the column may also be in the ratio of divinylbenzene to styrene in a range
• DVB is also preferred.
• FIG. 1 there is shown a block diagram of one embodiment 10 of a
• step 16 of preparing the column for chromatographic run and the step 18 of
• polymerizing a mixture includes a monomer and or polymer capable of
• step 14 includes the substeps 20 of reacting the polymerization
• the inhomogeneous distribution ofthe empty space may be
• This process may also affect the separation-effective opening
• the washing step 22 is a conventional step intended to remove
• porogens and unreacted monomers or other ingredients that may be used for
• This step may be followed by reacting in a manner to add functional groups such as the
• the washing step causes swelling of the plug
• shrinkage may cause channeling
• pressure is applied to the swollen plug in one embodiment to prevent
• FIG. 2 there is shown a block diagram of a polymerizing apparatus
• the mechanism 25 is a piston with a smooth surface to
• the compression piston 27 moves inwardly into the
• the porogen can be removed by a solvent
• controlled environment 29 which is the preferred embodiment is a water bath
• the materials for this device can be any conventional materials know
• FIG. 3 there is shown a sectional view of one embodiment of the
• compression piston 112 and o-ring 110 form a tight seal inside the confinement
• the pressure cap 80 contains a fluid inlet port 33 fitted to the barrel
• the transfer mechanism 25 is then positioned as shown, creating a volume in
• a containment cap 604 is
• an alternate sealing arrangement such as an o-
• ring could as easily be used to provide either a face seal or a radial seal.
• fluid inlet 33 is connected to a controlled pressure source, such as a
• controllable fluid pump or regulated bottle of compressed gas
• the apparatus 28 is placed in a temperature-controlled
• Fluid pressure is then applied through the fluid inlet port 33, which
• This rod 106 communicates the force to the compression piston
• the retaining collar 104 contacts the shoulder 608 in
• the polymer apparatus 28 is separated from the column 1022 as an
• Chromatographic fittings are then installed on both ends.
• FIG. 4 there is shown a sectional view of another embodiment of
• apparatus 28 having a glass column casing 922, a piston head assembly 401 ,
• means of providing compression including, but not limited to springs, weights,
• the piston head assembly 401 comprises a piston 76, an o-ring 38 and
• plunger assembly 30 is pushed fully into the displacement chamber 60.
• the column 922 is filled with the reactant, and the containment plug 923 is
• containment plug 923 and the column 922 alternate methods; including, but
• a fluid pressure source is then applied through the fluid inlet port 33.
• This annular shoulder 42 also limits the distance that the piston can
• Chromatographic fittings are then installed on both ends.
• the surface of the resultant monolithic polymeric material will not be smooth or even, and may be more porous than the body of the monolithic polymeric
• FIG. 5 there is shown a Scanning Electron Microscopy (SEM) picture of a
• FIG. 6 there is shown a chromatogram having peaks from a protein
• FIG. 7 there is shown three plugs with the one on the left made with pressure during polymerization and the two on the right polymerized without
• FIG. 7 illustrates the discontinuities formed on the surface of
• FIG. 8 there is shown a block diagram of a preparatory liquid
• chromatographic system 101 having a pumping system 121 , a column and
• the column and detector array 141 includes a plurality of columns
• plugs are size-compensated
• the pumping system 121 supplies solvent to the column and
• pump array 135 supplies solvent to the column and detector array 141 from
• the controller 119 receives signals from detectors in the column
• collector system 117 accordingly in a manner known in the art.
• fraction collector system is the FOXY7 200 fraction collector available from Isco, Inc., 4700 Superior Street, Lincoln, NE 68504.
• the pumping system 121 To supply solvent to the pump array 135, the pumping system 121
• the controller 119 also controls the valves in the pump array
• the collector system 117 includes a fraction
• collector 141 to collect solute, a manifold 143 and a waste depository 145 to
• One or more fraction collectors are used to handle waste from the manifold 143.
• a manifold may be used to combine solute from more than one column and deposit them together in a single
• each column may deposit solute in its own receptacle or some of
• the columns each may deposit solute in its own corresponding receptacle and
• one embodiment of polymerization equipment includes a
• polymerization mixture comprises a monomer , polymer and a porogen.
• the polymerization mixture comprises includes a cross-linking reagent and a cross-linking monomer.
• the polymerization takes place in a closed container to avoid loss of
• the plug may have a tendency to swell during washing or during a
• a sample is located in juxtaposition with the plug and
• the components of the sample are separated one from the other as they are
• a plurality of samples are separated
• the plug is a permeable monolithic polymeric plug in the casing walls.
• the plug is a
• the permeable monolithic polymeric plug has smooth walls
• the plug is formed of vinyl polymers but may be
• The formed of others such as urea formaldehyde or silica.
• The may include surface
• channeling openings is formed principally of methacrylate polymer.
• his permeable monolithic polymeric plug is principally formed

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• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Physics & Mathematics (AREA)
• Thermal Sciences (AREA)
• Biochemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Treatment Of Liquids With Adsorbents In General (AREA)
• Polymerisation Methods In General (AREA)
• Processes Of Treating Macromolecular Substances (AREA)

Priority Applications (2)

Applications Claiming Priority (4)

Publications (1)

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Family Applications (1)

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Cited By (6)

Families Citing this family (73)

Citations (2)

Family Cites Families (114)

• 2002
  • 2002-06-26 US US10/180,350 patent/US6749749B2/en not_active Expired - Lifetime
• 2003
  • 2003-06-25 US US10/607,080 patent/US7074331B2/en not_active Expired - Lifetime
  • 2003-06-26 JP JP2004518030A patent/JP4721702B2/ja not_active Expired - Lifetime
  • 2003-06-26 EP EP03742297A patent/EP1515784A4/en not_active Withdrawn
  • 2003-06-26 EP EP13171755.5A patent/EP2664366A3/en not_active Withdrawn
  • 2003-06-26 WO PCT/US2003/020415 patent/WO2004002603A1/en not_active Ceased
• 2006
  • 2006-01-19 US US11/337,071 patent/US7922908B2/en not_active Expired - Lifetime
• 2007
  • 2007-10-31 US US11/932,526 patent/US8795529B2/en active Active
  • 2007-10-31 US US11/932,343 patent/US7922909B2/en not_active Expired - Lifetime

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