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Functionalized support material and methods of making and using functionalized support material

a functionalized support material and functional technology, applied in the field of functionalized support materials, can solve the problems of high mw biomolecules not being able to reach the media surface in time, slow and limited diffusion of high mw biomolecules, and high cost of chemistry both raw materials (monomer, ce salt) and processes,

Pending Publication Date: 2022-09-22
WR GRACE & CO CONN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is directed to cost-effective media suitable for use as cation and anionic exchange chromatographic materials. The invention provides functionalized support material and chromatographic materials that can be used in high-performance liquid chromatography (HPLC) and fast protein liquid chromatography (FPLC) columns. The functionalized support material is made by polymerizing monomers onto an intermediate product that has thiol groups thereon, using a reaction mixture that does not require an organic solvent. The resulting material has polymer chains that have positive and negative charges, as well as ionizable functional groups that can form a positive or negative charge via dissociation or association of an atom. The functionalized support material can also be made by reacting the support material with a second reactant, such as a divalent sulfur bond or a divalent oxygen bond. The invention also provides methods for making the functionalized support material and chromatographic materials. The technical effects of the invention include improved performance and reduced cost of chromatographic materials.

Problems solved by technology

In separation processes, such as protein purification, given the extremely high molecular weight (MW) and the slow moving of biomolecules, diffusion of the high MW biomolecules to the media surface is very slow and limited.
This chemistry is very costly in terms of both raw materials (monomer, Ce salt) and processes (e.g., process control, waste generation during cleanup and disposal, etc.).
However, such technologies are of high cost, and have not been realized commercially in large scale production.

Method used

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  • Functionalized support material and methods of making and using functionalized support material
  • Functionalized support material and methods of making and using functionalized support material

Examples

Experimental program
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examples

[0105]The following examples described processes for modifying the surfaces of media, including silica and polymeric resins, using the thiol oxidation polymerization chemistry of the present invention. It should be noted that although silica and poly(methylmethacrylate) particles are used in the following examples, other types of particles (or other support materials as discussed above) and particle surfaces (or other support material surfaces) could be modified using similar process.

[0106]One example below relates to porous inorganic media, a silica based ion exchange material, formed via a process consisting of two main steps: (1) bonding of silica surface with thiol group containing methoxysilane to form an initially bonded intermediate; and (2) free radical polymerization of ionic monomer(s), through the introduction of oxidizing agents such as sodium bromate, in the presence of the initially-bonded silica intermediate to generate surface radicals. The surface radicals initiated...

examples 1-5

[0118]As shown in FIG. 2, two different routes were utilized to introduce polymer chains containing anionic sulfonic acid groups onto the surface of silica particles. The first route involved initial bonding of thiol groups by reacting (3-mercaptopropyl)trimethoxysilane (thiol silane), followed by polymerization. The second route involved two surface modifying silanes: (i) thiol silane and (ii) 2-[methoxy(polyethyleneoxy)propyl]-trimethoxysilane (PEG silane) available from Gelest, Inc.

[0119]The main benefit for the second route, as described in the examples, was that the initially bonded silica was more hydrophilic and could be washed with water, while for the first one, some organic solvent, such as methanol or acetone, was used for clean-up and removal of unreacted / unattached silane reagents.

Initial Bonding, Route 1

[0120]100 grams of silica was rolled and mixed with 5 grams of (3-mercaptopropyl) trimethoxysilane in a 2 L round bottom flask on a rotavap (i.e., a rotary evaporator) ...

example 6

[0125]The following example utilized a reaction scheme as shown in FIG. 3. 25 grams of initially bonded silica having a 1000 Å median pore size, and a 75 μm average particle size was made as discussed above, but only thiol silane was used in the initial bonding step. (Elemental analysis of the bonded material showed that C=0.95%, S=0.53%.) The intermediate product (i.e., silica particles with thiol groups thereon) was mixed with 35 grams of (3-acrylamidopropyl)-trimethylammonum chloride (75% aqueous solution, available from TCI America), 2.31 grams of diallyldimethylammonium chloride (65% solution, available from Aldrich), and 200 ml of DI water in a 500 ml three necked round bottom flask using a setup as described in Examples 1-5.

[0126]After removing air from the system with nitrogen bubbling for 20 minutes, 1.0 grams of potassium bromate was added. The mixture was stirred and gradually heated to 65° C. and reacted at 65° C. for 2 hours. After the reaction, the mixture was cooled t...

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Abstract

Methods of making functionalized support material am disclosed. Functionalized support material suitable for use in chromatography columns or cartridges, such as in a high pressure liquid chromatography (HPLC) column or a fast protein liquid chromatography (FPLC) column, is also disclosed. Chromatography columns or cartridges containing the functionalized support material, and methods of using functionalized support material, such as a media (e.g., chromatographic material) in a chromatography column or cartridge, are also disclosed.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to functionalized support material suitable for use in chromatography columns or cartridges. The present invention further relates to chromatography columns or cartridges containing the functionalized support material, methods of making functionalized support material, and methods of using functionalized support material, for example, as separation media in a chromatography column or cartridge.BACKGROUND OF THE INVENTION[0002]Cation and anionic exchange chromatographic materials are known. Cation exchange chromatographic materials typically contain media having surface attached anionic groups such as sulfonic acid groups (e.g., S strong cation exchanger) and / or carboxylic acid groups (e.g., CM weak cation exchanger). Anion exchange chromatographic materials typically contain media having surface attached cationic groups such as quaternary ammonium (e.g., Q strong anion exchanger) and / or diethylaminoethyl (e.g., DEAE...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): B01J20/32B01J39/26B01J41/20B01J20/289B01J41/05B01J39/17B01J39/05B01D15/36C07K1/18
CPCB01J20/3272B01J39/26B01J41/20B01J20/3204B01J20/3219B01J20/289B01J41/05B01J39/17B01J39/05B01D15/362B01D15/363C07K1/18
Inventor GU, FENG
Owner WR GRACE & CO CONN
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