specific types
Typical carrier materials include polysaccharides, polypeptides and silica (Hou, US 4,639,513).
Carbonaceous materials
Modified carbonaceous materials: Kyrildis (US2002/0056686) teaches that carbonaceous materials such as carbon black, graphite and activated carbon, represent an important class of adsorbents that are used in many field such as purification and waste treatment but have not been used as a standard stationary phase in certain separation systems because carbon is a strong on-specific adsorbent despite carbon’s advantages over commercially available adsorbents (no corrosion problems, stable at a wide pH range unlike silica particles which are stable only in the pH range of 1-8, or are there any swelling problems with carbon products, which are stable in all organic solvents, unlike polysaccharide and/or polymer based chromatographic particles. Kyrildis teaches a chromatography column containing a stationary pahse that is at least a carbonaceous materials having attached at least one organic group such that the carbonaceous material having at least one organic group is capable of adsorbing at least one chemical species present in a mixture. For example, when cationic exchange processes are needed, a sulfonic acid, for instance, can be attached on the carbonaceous material and when anionic exchanges are needed, a quternary amine can be attached onto the carbonaceous material. A preferred process for attaching an organic group to the carbonaceous materials involves the reaction of at least one diazonium salt with a carbonaceous material in the absence of an externally applied current sufficint to reduce the diazonium salt.
Polyscharides:
The term “polysaccharide” includes compounds made up of many hundreds or even thousands monosaccharide units per molecule held together by glycoside linkages. Their MW are normally higher than about 5k and up into the millions of daltons. They are normally naturally occurring polymers such as starch, glycogen, cellulose, gum arabic, agar and chitin. (Hou, US 4,639,513).
Agarose is a typical polysaccharides, but cellulose has a robuster hydrogen bonding netword and is thus advantageous for providng a higher flow rate (US 13/201,647). Cellulose particles can be crosslinked as by adding a crosslinking agent such as epichlorohydrin (US 13/201,647).
Cellulose: Cellulose is a preferred polysaccharide for use as a substrate of an ion exchange matrix. Cellulose is a naturally occuring polysaccharide consisting of (1-4) linked glucose units. Sources include wood, pup, cotton, hemp, ramie or regennerated forms such as raon. Packing materials using polysaccharides have high alkali resistance Hou (US 4,639,513).
Ookuma (US5,196,527) discloses ion exchange fine cellulose particles which can be used as an affinity carrier.
Umeda (US2014/0128253) discloses a porous cellulose gel containing crosslinked cellulose particles having a particle diameter of from 1-2,000 um, a swelling degree of from 5-20 mL/g. A method producing the gel by adding to a suspension liquid of cellulose particles a crosslinking agent in an amount of from 4-12 times the amount of the cellulose monomer in terms of moles and an alkali in an amount of from 0.1 to 1.5 times the amount of the corsslinking agent in terms of moles is also disclosed.
Polypeptides
Polypeptides include compounds made up of many (tens, hundreds or even thousands) of amino acids linked through amide linkages (CONH) with elimination of water. The sequence of amino acids in the chain is of critical importance in the biological functioning of the polypetide and the chains may be relatively straight or coid or helical. In the case of certain types of polypeptides, such as keratins, they are cross linked by disulphide bonds of cysteine. Proteins which are also polypeptides and can be coiled and folded into very complex special patterns can be roughly classified into two groups on the basis of the extent of their coiling and folding. Those arranged as long linear molecules are called “fibrous proteins” and are relatively insoluble in water. Fibrous proteins include collage (the principal fibrous protein of skin, tendons, ligaments, cartilage, bone the cornea of the eye, etc), mysoin (one of the chief proteins in muscle), keratin (the major protein in hair) and fibrin (a protein iportant in blood clotting). Fibrous polypeptide are preferred polypeptides for carrier supports with keratin one of the most preferred. Of the keratinous polypeptides, animal fiber such as wool is preferred (Hou, US 4,639,513).
Synthetic polymers:
Polyacrylamide (Bio-Gel P)
Polystyrene:
In the case of polystyrene, a 3 D network is formed first and the functional groups are then introduced into benzene rings through chlormethylation.y
The most typical ion-exchange resins are based on cross-linked polystyrene The required active groups can be introduced after polymerization or substituted monomers can be used. For example, the cross linking is often acheived by adding 0.5-25% of divinylbenzene to sytrene at the polymerization process. Non-cross linked polymers are used only rarely because they are less stable. Cross linking decreases ion exchange capacity of the resin and prolongs the time needed to accomplish the ion exhcange processes. Particle size also influences the resin parameters; smaller particles have larger outer surface, but cause larger head loss in the column processes. Bill (US Patent Applicaiton No: 14/365,449, published as 10/364268).
–Microreticular forms of polystyrene (Styragel)
Poly(vinyl acetate) (Merck-l-Gel OR)
Poly(2-hydroxy ethylmethacrylate) (Spheron)
Polyacryloylmorpholine (Enzacryl)
Silica: See outline
Composite Resins
Polysacharides + other materials:
–-Agarose-Dextran:
The surface of core particles made of agarose has been modified using dextran (US 13/201,647). An commercial example is “SP Sepahrose SL™” from GE Healthcare Sciences.
Dextran-agarose composites are popular because of the widespread acceptance of agarose as a support for biochromatography. These materials are obtained by surface grafting dextran polymers into a macroporous, crosslinked agarose structure, which is then funcitonalized by introducing charged ligands.
Stone (J. Chromatography A, 1146 (2007) 202-215) compared the properties of agarose and dextran-grafted agarose cation exchangers with respect to protein adsorption equilibrium and rates and found that in spite of the reduction pore accessiblity, protein uptake rates were grealy increased with the dextrane grafted sulfopropyl matrices compared to the SP matrixes.
–Cellulose-Dextran: Matsumoto (US 13/201,647) discloses introduction of a cation exchange group such as a sulfone group into a base gel, which is made by adding a predetermined amount of polysaccharides having a limiting viscosity to porous cellulose particles (the free hydroxyl groups of the cellulose particles can be crosslinked with an agent such as epichlorohydrin). Examples of polysaccharides include agarose, dextran, pullulan and starch. According to the procedure, crosslkinked cellulose particles are reacted with epichlorohydrin to introduce an epoxy group, and then reacted with dextran sulfate having a predetermined limiting viscosity thereby adding dextran to the crosslinked cellulose particles. The amount of the polysaccharides to be added to the porous cellulose particles is represented by a change amount of the dry weight per unit volume before and after addition of the polysaccharides. According to the invention, the drug weight per unit volume of the porous cellulose gel is preferably 1.06-1.40 times the drug weight per unti volume of the porous cellulose particles.
–Pullulan–methacrylate: A strong cation exchange materix was obtained by introducing a ligand into a gel in which pullulan was immobilized to porous methacrylate particles through 2-bromoethanesulfone (US 13/201,647).
–Polysaccharide + synthetic polymer: (WO/1084/003053) discloses a modified polysaccharide material which coprises a 1. polysaccharide such as cellulose covalently bonded to 2. a synthetic polymer made from a polymericable compound which has a chemical group capable of being covalently coupled to said polysaccharide and a chemical group capable of transformation to an ionizable chemical group.
Polyacrylamide within porous silica:
DEAE-dextrane-methacrylate:
Polystyrne-silica-Dextran: It is known that adsorption performance for proteins is improved by using an ion exchagne adsorbent made of dextran derived hydrogel in which an ion exchange group is added to core particles made of polystyrene-silica (Journal of Chromatography A, 679 (1994) 11-22).
–Polystyrne-slica-hydrogel: In the so called HyperD particles, the gel is surrounded by polystyrene-silica composite material giving it the necessary physical hardness for use in HPLC. The soft hydrogel can possess chemical functions or ligands for protein separations. (Harvath, J. Chromatogr. A 679 (1994) 11-22).
–Polysacharide and synthetic polymer: (WO/1984/003053) discloses an orgnaic synethic polymer which carries chemical groups which are capable of coupling to polysaccharide and also which contains chemical groups which can proviede ion exchange capacity.
Polyethylemimine: It is known that adsorption characteristics for proteins are improved by using a chromatography packing material made by adding polyethyleniine to methacrylate polymer particles (US 13/201,647).
–Silica – polyethyleneimine (PEI): Chromatography media material, particularly anion exchangers containing primary and secondary amine functionality, have been prepared by coating the internal surface of porous silica materials with polyethyleneimine (PEI) followed by imobilization through crosslinking (Alpert, J. Chromatogr. 185, 275-392 (1979). Deorkar (US20080203029) discloses polymerica media preaapred using polymeric partciles derivatized (not cross-linked) with polyetheyleneimine.
High Density/Capacity/large scale:
Improvements in the structure of chromatography resin supports have made large scale chromatography a practical alternative to more conventional purificaiton methods. Rigid resins allow alrge volumes to be processed rapidly, and high ligand density gives the increased capacity necessary for large volumen processing (US 2011/0213126).