Abstract: The present invention relates to certain new methods to select epitopes for antibodies. The present invention also provides a method of generating an antibody (e.g. a functional antibody) to a protein, said method comprising (i) identifying an antigenic epitope in said protein by exposing the protein to limited or restricted proteolysis by contacting the protein with at least one protease to form at least one digested, deconstructed or truncated version of the protein and at least one surface-exposed peptide that is cleaved off from the protein by the action of said protease and generating an antigenic epitope based on said surface-exposed peptide; and (ii) raising an antibody against the antigenic epitope. The present invention also provides antigenic epitopes and antibodies against such epitopes.

Abstract: One embodiment of the invention provides a system adapted and configured to generate a localized flow circulation zone. The system includes: a free-standing microfluidic pipette comprising three or more channels with exits separated from each other by an outer surface of the pipette; and a controller programmed to control fluid flows through each of the three or more channels to generate a localized recirculating fluid flow path outside the pipette. Liquid leaving the microfluidic pipette through at least one outlet channel exit is withdrawn through at least two inlet channel exits.

Abstract: Aspects of the present invention provide a freestanding microfluidic pipette with integrated wells for solution storage. Further aspects of the invention provide a holding interface to provide connectivity with external control components. One aspect of the invention provides a system for applying a microfluidic device in microscopy. The system includes: a microfluidic device having an elongated shape and defining one or more wells for solution storage and processing; and an interface adapted and configured to hold the microfluidic device in a freestanding manner and facilitate simultaneous connection of the one or more wells with a flow controller. Another aspect of the invention provides a method for utilizing a microfluidic device. The method includes: providing a device as described herein; positioning the device adjacent to a microscope; and actuating the interface to operate the microfluidic device.

Abstract: The present invention relates to a pharmaceutical combination comprising a CDK inhibitor and at least one antioxidant enzyme inhibitor for use in the treatment of cancer. The present invention also relates to a method for the treatment of cancer comprising administering to a subject in need thereof, a therapeutically effective amount of a CDK inhibitor and a therapeutically effective amount of at least one antioxidant enzyme inhibitor. The pharmaceutical combination of the present invention exhibits synergistic effect when used in the treatment of cancer.

Abstract: One embodiment of the invention provides a system adapted and configured to generate a localized flow circulation zone. The system includes: a free-standing microfluidic pipette comprising three or more channels with exits separated from each other by an outer surface of the pipette; and a controller programmed to control fluid flows through each of the three or more channels to generate a localized recirculating fluid flow path outside the pipette. Liquid leaving the microfluidic pipette through at least one outlet channel exit is withdrawn through at least two inlet channel exits.

Abstract: The present invention features a freestanding microfluidic pipette with both solution exchange capability and fluid re-circulation, enabling highly localized and contamination- free fluid delivery within a confined volume in the vicinity of the pipette exit. Preferably, the device features direct positioning, so the pipette can be directed at a point or object of interest, such as a biological or artificial cell, a defined surface area or a sensor element within an open volume, using micro- or nanopositioning techniques. One aspect of the invention provides a free-standing pipette. The free-standing pipette includes a microfluidic device comprising one or more channels with exits leading into an open-volume and a positioning device programmed to hold the microfluidic device at an angle from a horizontal axis.

Abstract: Aspects of the present invention provide a freestanding microfluidic pipette with integrated wells for solution storage. Further aspects of the invention provide a holding interface to provide connectivity with external control components. One aspect of the invention provides a system for applying a microfluidic device in microscopy. The system includes: a microfluidic device having an elongated shape and defining one or more wells for solution storage and processing; and an interface adapted and configured to hold the microfluidic device in a freestanding manner and facilitate simultaneous connection of the one or more wells with a flow controller. Another aspect of the invention provides a method for utilizing a microfluidic device. The method includes: providing a device as described herein; positioning the device adjacent to a microscope; and actuating the interface to operate the microfluidic device.

Abstract: Disclosed is a method for selective electrofusion of at least two fusion partners having cell-like membranes and cellular or subcellular dimensions, comprising the following steps: A) the fusion partners are brought into contact with each other and B) an electrical field of a strength sufficient to obtain fusion and highly focused on the fusion partners is applied. The fusion partners are independently selected from the group consisting of a single cell, a liposome, a proteoliposome, a synthetic vesicle, an egg cell, an enucleated egg cell, a sperm cell at any development stage and a plant protoplast.

Abstract: Disclosed is a method for selective electrofusion of at least two fusion partners having cell-like membranes and cellular or subcellular dimensions, comprising the following steps: A) the fusion partners are brought into contact with each other and B) an electrical field of a strength sufficient to obtain fusion and highly focused on the fusion partners is applied. The fusion partners are independently selected from the group consisting of a single cell, a liposome, a proteoliposome, a synthetic vesicle, an egg cell, an enucleated egg cell, a sperm cell at any development stage and a plant protoplast.

Abstract: The present invention features a freestanding microfluidic pipette with both solution exchange capability and fluid re-circulation, enabling highly localized and contamination- free fluid delivery within a confined volume in the vicinity of the pipette exit. Preferably, the device features direct positioning, so the pipette can be directed at a point or object of interest, such as a biological or artificial cell, a defined surface area or a sensor element within an open volume, using micro- or nanopositioning techniques. One aspect of the invention provides a free-standing pipette. The free-standing pipette includes a microfluidic device comprising one or more channels with exits leading into an open-volume and a positioning device programmed to hold the microfluidic device at an angle from a horizontal axis.

Abstract: Disclosed is a method for parallel delivery of agents to and/or into a cell structure, wherein at least two electrolyte-filled tubes are provided together with a counter electrode, the tubes being connected to a voltage or current generator, said agents being introduced into the electrolyte solution contained in the tubes, which are placed close to the cell structure, whereupon the agents are transported through the tubes to said cell structure and into the said structure through pores which have been formed by application of an electric field focused on the cell structure, resulting in electroporation of the cell structure. Also different applications of the method is disclosed, e.g. use of the method in order to transfer cell-impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure.

Abstract: Disclosed is a method for sequential delivery of agents to and/or into a cell structure, wherein an electrolyte-filled tube is provided together with a counter electrode, said tube is connected to a voltage or current generator, at least two agents are introduced in a discrete mode into the electrolyte solution contained in the tube, which is placed close to the cell structure, one agent at the time being transported through the tube to and/or into said cell structure in which a pore has been formed by application of an electric field focused on the cell structure, resulting in electroporation of the cell structure. Also different applications of the method is disclosed, e.g. us of the method in order to transfer cell-impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure.

Abstract: The present invention relates to methods of measuring electrical properties of a cell using electrode devices comprising tapered nanotips having submicrometer dimensions (“nanoelectrodes”) for insertion into a cell. The devices are used to measure electrical properties of the cell and, optionally, may be used to electroporate, the cell or subcellular structures within the cell. The invention also provides arrays of electrode devices having nanotips for simultaneously or sequentially measuring the electrical properties of cells (e.g., such as surface immobilized cells). The electrodes can be used to measure properties of ion channels and in HTS assays to identify drugs which affect the properties of ion channels. The invention additionally provides microfluidic systems adapted for use with the electrode devices having nanotips. In combination with the electrodes, the microfluidic systems provide cell-based biosensors for monitoring cellular responses to conditions, such as exposure to candidate drugs.

Abstract: The invention provides microfluidic systems for altering the solution environment around a nanoscopic or microscopic object, such as a sensor, and methods for using the same. The invention also provides a system and methods for modulating, controlling, preparing, and studying receptors.

Abstract: The instant invention provides plasma membrane vesicles, methods of making the same, and method of using the plasma membrane vesicles.

Abstract: Disclosed herein is a device comprising at least one supporting solid surface comprising at least one membraneophilic region; a covering layer that is at least partially immobilized to the membraneophilic region, said covering layer consisting of (i) a surfactant membrane, (ii) a lipid mimicking polymer, (iii) a surfactant or emulsion system or (iv) a liquid crystal; and a substance included in or bound to, connected to or associated with the covering layer. Also disclosed are methods wherein the device is used and use of the device.

Abstract: Disclosed is a method for sequential delivery of agents to and/or into a cell structure, wherein an electrolyte-filled tube is provided together with a counter electrode, said tube is connected to a voltage or current generator, at least two agents are introduced in a discrete mode into the electrolyte solution contained in the tube, which is placed close to the cell structure, one agent at the time being transported through the tube to and/or into said cell structure in which a pore has been formed by application of an electric field focused on the cell structure, resulting in electroporation of the cell structure. Also different applications of the method is disclosed, e.g. us of the method in order to transfer cell-impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure.

Abstract: The invention provides microfluidic systems for altering the solution environment around a nanoscopic or microscopic object, such as a sensor, and methods for using the same. The invention can be applied in any sensor technology in which the sensing element needs to be exposed rapidly, sequentially, and controllably, to a large number of different solution environments whose characteristics may be known or unknown.

Abstract: Disclosed herein are methods and devices for the formation of a monolayers comprising, for example, one or several phospholipids or cholesterol-conjugated nucleic acids. The monolayers are on or associated, for example, with a surface comprising a hydrophobic material.

Abstract: The invention provides microfluidic systems for altering the solution environment around a nanoscopic or microscopic object, such as a sensor, and methods for using the same. The invention can be applied in any sensor technology in which the sensing element needs to be exposed rapidly, sequentially, and controllably, to a large number of different solution environments whose characteristics may be known or unknown.