Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Cellular products or processes of preparing a cellular...
Reexamination Certificate
2001-03-05
2003-05-27
Foelak, Morton (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Cellular products or processes of preparing a cellular...
C521S030000, C521S031000, C521S146000, C521S149000, C521S150000, C525S332100, C525S332200, C525S370000, C525S371000, C526S336000
Reexamination Certificate
active
06569911
ABSTRACT:
TECHNICAL FIELD
The invention relates to the manufacture of media that can be used as support in various adsorption processes in order to enrich substances from various liquids, in cell culture, in synthesis taking place on supports and in other fields related to these fields.
The term media refers to the matrix plus the pore volume.
The stationary phase in liquid chromatography is composed of a matrix and is mostly in the form of porous or nonporous particles packed to a bed or in the form of a porous monolith. The matrix should be rigid enough to allow high flow rates without being compressed or broken, for instance when performing separations in columns packed with particles of small diameters. The matrix should also be chemically and physically inert and withstand extreme pH conditions.
In reversed phase chromatography (RPC), particularly for peptide and protein separation, silica gels have for a long time been the preferred stationary phase. These matrices are rigid enough to withstand high flow rates. However, silica gels are not stable above pH 8.0. During recent years there has been a growing interest in synthetic polymeric materials for use in reversed phase high performance liquid chromatography (HPLC), in particular resins based on polymerisation of mono-, di- etc vinyl compounds with particular emphasis of poly vinyl hydrocarbons such as copolymers between styrene and divinylbenzene). These media are often stable with eluents having pH within the range 1-14 and often give excellent separations. The amount of swelling may differ widely depending on fraction of cross-linker to monomer and the liquid they are contacted with. They normally comprise some free unreacted residual vinyl groups (again depending on fraction of cross-linker to monomer) and are not compressed by the pressures normally applied in HPLC.
Polymerisation of vinyl compounds in order to accomplish cross-linked polymerisates/copolymerisates may take place stepwise with a first step resulting in linear non-cross-linked polymers and then in a second step at an increased temperature cross-linking takes place (curing). Often nothing is removed or added between these two steps meaning that for instance significant amounts of initiators and monomers or oligomers with unreacted vinyl groups from the first step remains and are used in the second step. The polymerisate from the first step is characterised by being soft and possible to shape by heating. The second step is often called curing and thus results in a cross-linked copolymerisate. The concept of curing is often utilised in polymerisations, see for instance U.S. Pat. No. 4,977,222; EP 286071 (step e); WPI accession number JP 81-82583D (=JP 56122814) and WPI accession number 81-75832D (DD149672).
WPI accession number 91-257239 (=JP 03168204) describes a cross-linked product from which porogens, monomers, initiators etc are removed in a heating step.
Technical Problem With Prior Art Matrices Based on Polymerised Vinyl Compounds
The rigidity of the media is a key issue regarding its ability to withstand high pressures during packing of columns and separations. The packing of media in the form of particles are performed by injecting a suspension of the material into the column with a pressure of several hundred bar. During high performance liquid chromatography (HPLC) the pressure drop over the column can be as high as 200-400 bar.
In order to fulfil these needs a highly cross linked matrix is required. Further, the percentage of polymer matrix in the particle must not be too low. Unfortunately the higher percentage matrix in the media the more the media will swell in an organic solvent.
The ability of media based on vinyl compounds to swell in the presence of organic solvents is one of their major disadvantages when used as the stationary phase in applications requiring flow through the stationary phase, such as in chromatography utilising increased pressure. This becomes particularly troublesome in processes requiring changes in solvents, for instance when solvent gradients are used, such as in reversed phase chromatography (RPC).
OBJECTIVES OF THE INVENTION
A first objective is to provide methods for producing media that are improved concerning the above-mentioned drawbacks.
A second objective is to provide media in which these drawbacks have been reduced.
THE INVENTION
We have now discovered a method for reducing the swelling of vinyl based media without having to change the media composition. Accordingly, one aspect of the invention is a method of manufacturing a media for use as support in the technical field of the invention, preferably in processes requiring contact with organic solvents and optionally with application of liquid pressure. The starting media is a cross linked polymerisate of vinyl compounds, preferably a copolymerisate between a monovinyl compound and a compound exhibiting two or more, preferably two vinyl groups, so that the copolymerisate (media) will exhibit residual vinyl groups. This means that the copolymerisate used in the inventive process is ready-made in the sense that essentially all residual monomers and/or initiators remaining after polymerisation and/or porogens, if present during polymerisation, should have been removed. The characterising feature of the method is that the media (support) is subjected to a heating step, which preferably is carried out at reduced access of oxygen.
The temperature during the heating step should be such that the swellability is decreased. The actual temperature may vary depending on polymer and heating time. A prolonged heating can, for instance, compensate for a lower temperature. It is important not to heat to the extent that a decomposition starts that is harmful to the desired properties of the media. The heating temperature and time thus shall be such that carbonisation does not take place. Normally the temperature is below 500° C. and above 75° C. A representative interval is 120-350° C. with preference in many cases for the interval 180-300° C. These rules particularly apply for matrices based on unsaturated hydrocarbons (vinyl hydrocarbons), such as styrene divinyl benzene.
Reduced access of oxygen means that the heating step may be run under reduced atmospheric pressure or under an inert gas, for instance argon or nitrogen. The main point is that the oxygen pressure is reduced relative to partial oxygen pressure in air at atmospheric pressure. By this term is also contemplated that the matrix is protected from contact with the atmosphere due to being surrounded by a liquid, for instance a hydrocarbon liquid. Particles may for instance be suspended and a monolithic matrix soaked in an inert liquid, such as a hydrocarbon liquid. Often it is advantageous to combine an inert liquid with the application of an inert atmosphere above the liquid, for instance argon or nitrogen.
It has been found that the above-mentioned conditions for the heat treatment may result in matrices exhibiting a reduced back pressure in a packed bed.
It has also been found that it is difficult to prevent oxidation during the heat treatment and that formed oxidised groups have a negative impact on the performance if the media is used in chromatography. It has therefore been found beneficial to post-treat the matrices under conditions providing reduction of oxidised groups formed during the heat treatment. Illustrative reductive agents are for instance those that reduce carbonyl groups, such as in aldehydes and ketones, to alcohol groups or to hydrocarbons. Specifically can be mentioned sodium boro hydride and lithium aluminium hydride. Similar conditions as used elsewhere apply to the respective reductive agent.
The vinyl compound is a compound that exhibits a polymerizable carbon-carbon double bond, such as in vinyl hydrocarbons (vinyl aryls and alkenes), vinyl ethers, acrylates and methacrylates, acrylamides and methacrylamides etc. The term vinyl compound encompasses mono-, di-, tri- etc vinyl compounds. A specifically preferred group of vinyl compounds is the vinyl hydrocarbons, in particula
Arntsen Torunn
Fonnum Geir
Hagen Steinar
Karlson Jan Roger
Amersham Biosciences AB
Foelak Morton
Ronning, Jr. Royal N.
Ryan Stephen G.
LandOfFree
Manufacturing method and article produced by the method does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Manufacturing method and article produced by the method, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Manufacturing method and article produced by the method will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3085608