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
  • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
  • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
  • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
  • B01J20/3285—Coating or impregnation layers comprising different type of functional groups or interactions, e.g. different ligands in various parts of the sorbent, mixed mode, dual zone, bimodal, multimodal, ionic or hydrophobic, cationic or anionic, hydrophilic or hydrophobic
• • 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
  • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to 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
  • 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
  • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
  • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
  • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
  • B01J20/3244—Non-macromolecular compounds
• • 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
  • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
  • B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
  • B01D15/361—Ion-exchange
  • B01D15/364—Amphoteric or zwitterionic ion-exchanger

Definitions

• US 6,426,315 (Bergstr ⁇ m et al.) suggests to replace such a series of steps by using a multifunctional porous separation matrix, i.e. to present the different kind of matrices on a single separa- tion matrix. More specifically, US 6,426,315 relates to a process for preparing such multifunctional porous separation matrices by introducing different functionalities in different layers of the matrix.
• the ionisable functionality is partially electrostatically charged at the pH of adsorption of the target compound to the resin, and is either further charged or of oppo- site charge at the pH of deso ⁇ tion of the compound from the resin.
• the ionisable functionalities are selected from a specified group of possible functionalities.
• the ionisable functional group is derived from either 2-mercapto-l- methylimidazole or (-)phenylpropanolamine and coupled to a density of at least 150 ⁇ mol per millilitre of resin.
• Such a high ligand density is stated to provide a sufficient hydrophobicity to adsorb target compounds without the need of adding excessive amounts of salt to the liquid.
• US 5,945,520 discloses multifunctional ligands evenly coupled to a resin, which consequently can be described as a homogenous separation matrix.
• US 5,977,345 relates to an inside-out spatial installation method for a bifunc- tional reagent that crosslinks a polymer matrix. More specifically, this reference relates to an activated matrix, which can accommodate and optimize the spatial installation of affinity ligands while preventing the immobilization of excess ligand in the outer strata of the hydrogel bead.
• One aspect of the present invention is to provide a separation matrix, wherein the mass transport properties during adso ⁇ tion and/or deso ⁇ tion have been improved. This can be achieved by a separation matrix as described in claim 1.
• Figure 1 is a comparative ligand distribution plot of a prior art separation matrix with an even distribution of ligands.
• the porous parti- cle is an essentially spherical bead.
• the supports used in the present invention may be made of an inorganic material, such as glass or silica, or an organic material, such as one or more organic polymers. In an advantageous embodiment, the support is made from natural or synthetic polymers.
• the deactivated groups on the surface of the support cannot react with the second reagent, and no functional groups with be coupled at these sites.
• the deactivated groups are non-reactive in respect of the second reagent that comprises functionalities.
• the first reagent may also be denoted a "deactivating agent".
• the diffusion is controlled to gradually decrease towards the centre, and hence there will be an increasing capability to couple functional groups and provide ligands towards the further in you get. Since the number of available groups have been controlled by the deactivation step, in the second step, the amount of reagent is not cru- cial and there will be no need to control diffusion in the second step.
• said at least two different functionalities are present on different ligand kinds, and a separate chemical gradient is provided for each such ligand kind within the support.
• a separate chemical gradient is provided for each such ligand kind within the support.
• Such different gradients may be as discussed above in the context of the first aspect of the invention.
• two chemical gradients are provided in the support, one of which is a ligand density gradient. The effects and advantages of such gradients and combinations of gradients will be discussed in more detail below in the context of the process of liquid chromatography.
• Figure 7E shows two gradients of opposite direction within the support
• Figure 7F shows two gradients of the same direction but of different inclination within the support
• Figure 7G illustrates two gradients, one is in the centre of the particle and one surrounding the centre, similar to Figure 7C
• Figure 7H shows a support, wherein one ligand or functionality describes a planar curve and the other is a gradient similar to the one described in Figure 7B.
• a support having the kind of gradients shown in Figure 7H can e.g. be obtained by starting from a support material which has already been functionalised with ligand to a constant substitution degree and subsequently applying the method according to the invention to provide a gradient.
• Example 3 Positive gradient provided in toluene/water system (U1282081A
• a separation matrix comprising a density gradient of carboxymethyl (CM) cation-exchange ligands was prepared as follows.
• the gel was washed with 3x 30 ml of distilled water and transferred to a reaction vial containing a solution of 3-mercaptopropionic acid (1.5 ml) in water (5 ml) that had been adjusted to pH 12.5 by addition of a 50% aq. solution of NaOH. The reaction was left 16 hours under stirring at 50°C. After filtration of the reaction mixture, the gel was washed with 3x 30 ml of distilled water. Titration was used to confirm the average substitution degree, while the presence of ligand gradients is confirmed as below.
• Nd3+ versus lateral position.
• the intensity is high at the outer parts of a bead but gradually decreases when going into the middle of the bead, and finally levels off and/or becomes to low to be measured. In this case (and further on), measurements were done only about one radius of the beads.

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• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Solid-Sorbent Or Filter-Aiding Compositions (AREA)
• Treatment Of Liquids With Adsorbents In General (AREA)

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Citations (4)

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• 2003
  • 2003-10-31 SE SE0302911A patent/SE0302911D0/xx unknown
• 2004
  • 2004-11-01 WO PCT/SE2004/001583 patent/WO2005042131A1/en not_active Ceased
  • 2004-11-01 US US10/575,945 patent/US20070125711A1/en not_active Abandoned
  • 2004-11-01 JP JP2006537940A patent/JP2007510153A/ja active Pending
  • 2004-11-01 EP EP04800246A patent/EP1677887A1/en not_active Withdrawn
• 2010
  • 2010-01-25 US US12/692,671 patent/US8070958B2/en not_active Expired - Fee Related
• 2011
  • 2011-10-05 JP JP2011220566A patent/JP2012037530A/ja not_active Ceased

Patent Citations (4)

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