Ge Healthcare Bio-sciences Ab

Gyros Patent Ab

Gyros Ab

Ge Healthcare Bioprocess R&d Ab

Anders Larsson

Nils Norrman

Andreas Axen

Helene Derand

Anders Hagvall

Per X Andersson

Ronnie Palmgren

Henrik Ihre

Hans Berg

Gunnar Glad

Philippe Busson

Dag Lindstrom

Ulrika Meyer

Eva Holmgren

David Buckley

Nicolas Thevenin

James Van Alstine

Mats Carlsson

Johan William Ohman

Ingemar Jonsson

Tobias Söderman

Andreas Axén

Maria Brännholm

Dag Lindström

Klas Allmer

Kajsa Stridsberg Fridén

Eva Von Heijne

Ralf Göran Andersson

Asa Rudstedt

Anette Ocklind

Sofia Söderberg

Maria Holm

The invention relates to a process for making porous cross-linked charged cellulosic polymeric membranes capable of binding to a target molecule. The invention provides methods for separating target molecules from other components in a solution comprising use of membranes obtainable by the process of the invention. The method has particular utility in separating proteins and nucleic acids from cell lysates and cultures.

Cross-linked cellulose membranes

The present invention relates to a method of manufacturing a chromatography matrix comprising providing a polysaccharide carrier comprising available hydroxyl groups; and reacting said hydroxyl groups with vinyl sulphonate to provide a sulphonate-functionalized (S-functionalized) cation exchanger. The hydroxyl groups of the carrier may be hydroxyls of the agarose polymer; or alternatively they may be provided on extenders such as polyhydroxyfunctional polymers. In one embodiment, the carrier is made of agarose with improved flow pressure properties.

Manufacture of chromatography matrices

The present invention relates to a method and a device for small scale reactions, such as sample preparation of a desired substance in a sample. In the method using the device samples mixed with functionalized magnetic particles are magnetically transferred between different working stations on the device. The method uses a hydrophobic surface, such as a Petri dish, provided with hydrophilic spots of, for example, agarose beads located on said hydrophobic surface and provided with buffers, reactants or ligands.

Method and device for small scale reactions

A microfluidic device adapted such that the flow of fluids within the device is controlled by different surfaces of the device having different surface characteristics. Preferably the device comprises a substrate not formed from a hydrated oxide material.

Microfluidic device

The present invention relates to separation of biomolecules. More closely, the invention relates to a method for production of a separation medium comprising hybrid particles of inorganic and organic material as well as the hybrid particles produced by this method. Finally, the invention relates to use of the hybrid particles for separation of biomolecules, preferably phosphoproteins. The method comprises the following steps: addition of inorganic metal oxide particles to an organic solution to form a mixture; and emulsification of the mixture to form porous hybrid particles, wherein the density of the porous hybrid particles is between 1.0 and 1.5 g/ml, and wherein the inorganic particles have a shape and size that maximizes their active surface area enabling the inorganic particles to interact with biomolecules.

Separation media for biomolecules comprising porous hybrid particles containing inorganic metal oxide nanoparticles

The invention relates to a process for making porous cross-linked cellulose membranes and processes for coupling a chromatography ligand to cross-linked cellulose membranes. The invention provides methods for separating a first component from a second component in a solution based upon a difference in the size of the first and second components, and methods for separating target molecules from other components in a solution comprising use of membranes obtainable by the process of the invention. The method has particular utility in separating proteins from cell lysates and cultures.

Process for cross-linking cellulose ester membranes

The present invention relates to a method of preparing an insoluble separation matrix, which method comprises salt-treatment of a polysaccharide gel followed by cross-linking of the polysaccharide polymers. In one embodiment, the method comprises providing an aqueous solution of a gelatable native polysaccharide; lowering the temperature of the polysaccharide solution to a value below its gelling point; salt-treatment by adding at least one salt to the resulting polysaccharide; and cross-linking the salt-treated polysaccharide. The polysaccharide may be prepared e.g. into particles, membranes or monoliths.

Method of preparing a separation matrix

A microfluidic device comprising a set of one or more, preferably more than 5, covered microchannel structures manufactured in the surface of a planar substrate. The device is characterized in that a part surface of at least one of the microchannel structures has a coat exposing a non-ionic hydrophilic polymer. The non-ionic hydrophilic polymer is preferably attached covalently directly to the part surface or to a polymer skeleton that is attached to the surface.

Microfluidic surfaces

The present invention relates to method of manufacturing a sulphonate-functionalized (S-functionalized) cation exchanger, which method comprises reacting olefinic groups with bisulphite in the presence of at least one amine oxide, such as N-methyl morpholine oxide (NMO). The olefinic groups of the carrier may be allyl groups; which may be provided on extenders such as polyhydroxyfunctional polymers. In one embodiment, the carrier is made of agarose with improved flow pressure properties.

Manufacture of a chromatography matrix

A method for covering a set of open microchannel structures which are fabricated on a planar surface made of plastics and which comprise two or more part areas that have different surface characteristics. The method comprises the steps of: a) providing the surface comprising the set of microchannel structures; b) providing a lid-forming sheet having on one side an even layer of a thermoglue; c) applying the side of the sheet having the thermoglue against the surface carrying the microchannel structure; d) heating the assembly created in step (c) to selectively liquefy the hot-melt adhesive while at the same time pressing the sheet material and the planar surface of the substrate together; e) permitting the resulting laminate-covered microchannel structure to cool. An assembly comprising (a) a planar substrate, the surface of which has a set of one or more open microchannel structures each of which comprises part areas representing different functionalities, and (b) a lid-forming material covering said set of microchannel structures and having one or more openings going from a microchannel structure to ambient atmosphere. The assembly is characterized in that the joint between said surface and said sheet material is a thermoglue that possibly has been cured.

Method for covering a microfluidic assembly

The present invention is a surface-modified base matrix comprised of a porous polymeric base matrix onto which branched hydrophilic polyhydroxy-functional polymers have been covalently attached, wherein the polyhydroxy-functional polymers are hyperbranched polymers presenting a degree of branching (DB) of at least about 0.2 and each polymer is tethered to the base matrix at two or more points. The present matrix can for example be a cross-linked carbohydrate material, such as agarose, and the hyperbranched hydrophilic polymer can e.g. be a copolymer of epichiorohydrin and a sugar. The invention also relates to a method of surface-modification of a porous base matrix by activating functional hydroxy groups thereon and contacting the activated matrix with a hydrophilic hyperbranched hydroxy-functional polymer.

Surface-modified base matrices

The present invention relates to a method of preparing a porous cross-linked polysaccharide chromatography matrix, which comprises to provide an aqueous solution of a gellable polysaccharide, wherein part of the hydroxyl groups are substituted with groups which are not susceptible to nucleophilic attack; to provide essentially spherical droplets of the substituted polysaccharide solution; to form a gel of the substituted polysaccharide solution; and to cross-link the gel by adding a cross-linking agent. The invention also encompasses a chromatography column packed with a matrix so produced as well as use thereof in e.g. protein purification.

Method of preparing a chromatography matrix

The present invention is a process of manufacture of one or more polysaccharide beads, comprising generating an aerosol of an aqueous polysaccharide solution, cooling the droplets of said aerosol in air to initiate gelling thereof and collecting droplets as gelled beads in a liquid or on a surface, characterised by adding a hydrophilic vapour pressure-lowering agent to said polysaccharide solution.

Manufacture of polysaccharide beads

The present invention relates to a method of producing one or more macroporous cross-linked polymer particles, which comprises polymerization and cross-linking of divinyl ether monomers in an inert solvent, in which method the polymerization is free radical initiated. The invention also relates to particles so produced, which are useful as separation medium e.g. in RPC or, after suitable derivatization, in other chromatographic methods.

Method of producing macroporous cross-linked polymer particles

The invention relates to a method of controlling flow of liquids in a micro channel structure. It comprises providing in said micro channel structure plugs () of polymer material in said structure, said polymer material in a first state blocking said channel from liquid flow, and in a second state providing a free path-way () for liquid flow. Energy is selectively applied so as to cause said polymer to enter a desired one of said first or second states. It also relates to a micro channel valve system, comprising a plurality of such plugs (). Additionally it comprises a chemical reactor, comprising a plurality of micro chambers interconnected by micro channels, having a valve system according to the invention.

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Uppsala, Sweden

Anders Larsson