Method for producing microporous elements, the microporous...

Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample

Reexamination Certificate

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C422S105000, C422S283000, C264S239000, C264S257000

Reexamination Certificate

active

06451260

ABSTRACT:

The present invention relates to novel methods for producing microporous elements and microporous elements obtainable by such methods. The present invention also provides microporous elements comprising solid microparticles, which preferably modify the adsorptive properties of the microporous element. Described are also microporous elements which are linked to a support and/or a retainer as well as methods for their production. The present invention also relates to filter elements comprising the above-described microporous elements. Furthermore, the present invention relates to kits, diagnostic and pharmaceutical compositions comprising the aforementioned microporous or filter elements. Furthermore, the present invention relates to the use of the aforementioned microporous and filter elements in microfiltration, chromatography, adsorption/immobilization of organic and inorganic compounds as well as for the preparation and/or detection of such compounds.
There is an increasing demand in the area of analytical chemistry for devices capable of handling moderate to small sample volumes, in a manner which is rapid, gives high recovery and minimizes any possibility of sample contamination. Among other desired attributes are low cost, ease of manufacture and suitability for application with conventional equipment. Previous devices for micro filtration etc. involve the use of preformed filter material. Synthetic polymers such as nylon, methacrylate or semisynthetic polymers such as nitro cellulose, or cellulose acetate have been used over decades. Mostly the filter material is a nonwoven material which is formed from a web of synthetic or natural fibers. The fibers may or may not be bonded together by a binder. In general, discs are cut from the nonwoven material and positioned within a sample tube or the like. Problems in connection with this previous approach include an insufficient contact of the pre-cut filter disc to the wall of the filter tube leaving small gaps and thereby allowing the applied liquid sample to escape. In this context, the filter disc may be attached to the filter tube by an adhesive; additionally or alternatively, the filter disc may be welded into the filter tube by locally applying heat or by ultrasonic treatment. If the filter disc is attached to the filter tube by an adhesive, the adhesive may influence the filter properties of the material in an uncontrollable manner. The same holds true when the filter disc is welded into the filter tube by locally applying heat or by ultrasonic treatment. The problems discussed above are enhanced when the overall size of the filter element is reduced. It has therefore hitherto not been technically feasible to produce satisfactory filter elements with apertures of a diameter as low as several micrometer. When using an adsorptive filter containing granular adsorptive microparticles, the problem of dislocation might occur during processing of a liquid and also during transportation. Therefore, the microparticles are held for example in between two confining porous elements, such as frits, nets, annular or grooved retainers at both porous sides of the filter element. Even when embedded between fibers of teflon or glass, an upper porous retainer as well as a lower supporting frit, net or grooved element might be necessary.
Thus, the technical problem underlying the present invention is to provide a cost-effective method for producing a microporous element, which can be applied for most versions of analytical or micro preparative liquid chromatography such as ion exchange chromatography, reverse phase chromatography, hydrophobic interaction chromatography, adsorption chromatography at silica gels, affinity chromatography, immuno chromatography, for binding studies, the isolation of multi component binding complexes, for the screening of samples or for preventing the dislocation of microparticles, improved or simplified by applying selected suitable techniques, avoiding unspecific loss of biopolymers like peptides, proteins, nucleic acids, oligonucleotides, polysaccharides or derivatives thereof by presenting biocompatible surfaces, and saving cost by using expensive microparticle material in very small amounts. In addition transfer of separated substances from the filter to blotting membranes shall be rendered possible without having problems with dead volumes. The solution to the technical problem is achieved by providing the embodiments characterized in the claims.
Accordingly, the present invention relates to a method for producing a microporous element, comprising the steps of
a) applying a substance; and
b) causing solidification in spongy form of at least part of the substance.
In context with the present invention, the term “solidification in spongy form” means that the product contains void spaces.
In a preferred embodiment the method of the present invention the substance is present in a liquid phase. Said liquid phase may be preferably a solution or suspension of a polymer in a solvent and the solidification in spongy form is preferably caused by the action of a non-solvent for the polymer.
For a purpose of the present invention, the term “polymer” means natural or artificial substances made up of large molecules which are themselves made from combinations of small simple molecules which are identical or not, i.e. homo- and co-polymers. Polymers according to the present invention include also resins.
In a preferred embodiment the polymer is selected from the group consisting of polyvinyl esters, partially deacylated polyvinyl esters, cellulose derivatives, polyamides, polystyrene, poly(methyl methacrylate) and mixtures thereof. Preferably, said polymer comprises both hydrophilic and hydrophobic segments within its molecules.
In a particularly preferred embodiment the method of the present invention, the polymer is selected from the group consisting of poly(vinyl alcohol-co-ethylene), poly(vinyl alcohol-co-vinylacetate), ethylene acrylic acid copolymer, ethylene acrylic ester copolymer, ethylene acrylamide copolymer, acrylic acid vinylacetate copolymer, acrylamide vinylacetate copolymer, copolymer of acrylic acid ethylene diamine monoamide with vinylacetate, poly(vinyl alcoholco-styrene), poly(styrene-co-maleic acid) and glycerol ester derivatives thereof, acrylamide acrylic ester copolymer, and mixtures thereof.
In another preferred embodiment the method of the present invention the solvent is selected from the group consisting of dimethyl sulfoxide, dimethylformamide, dimethylacetamide, formamide, formic acid, acetic acid, 2,2,2-trichloro ethanol, toluene, tetrahydrofuran and mixtures thereof.
In a further preferred embodiment the solvent is comprised of at least two volatile non-solvents. Preferably, said solvent is removable at ambient temperatures or vacuum.
In a further preferred embodiment of the method of the present invention the solidification is achieved by evaporating the solvent and/or non-solvent. Preferably, the nonsolvent is selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, ammonia, ethylacetate, acetone, ethylene diamine, and mixtures thereof.
In another embodiment of the method according to the present invention the liquid phase is a hydrocolloid.
In a preferred embodiment the hydrocolloid is selected from the group consisting of low melting agarose, starch, polyvinyl alcohol, and mixtures thereof.
In a further preferred embodiment the layer of hydrocolloid solution is subjected to crosslinking by sodium tetraborate.
In another preferred embodiment the solidified hydrocolloid is desiccated and/or crosslinked.
In another embodiment of the method according to the present invention the liquid phase is a solution or suspension of one or more monomer(s) and the solidification is caused by polymerizing said monomer.
In a preferred embodiment the monomer(s) is (are) present in a solvent. Preferably, the monomer(s) comprise(s) one or more crosslinking monomers.
In a particularly preferred embodiment said monomers comprise a diamine and a diepoxide.
In a further preferred embo

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