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: The invention provides a system, system components, and a method for rapidly obtaining and stably maintaining a cell in optimal contact with the cell-contacting surface of a sensor in a cell-based biosensor. In one aspect, the system maximizes the seal between a whole cell and the cell-contact surface of a patch clamp micropipette, maximizing the efficiency of a whole cell patch clamp recording.

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 invention provides hollow-tip-electrodes for spatially localized delivery of substances to one or more biological targets present in a population comprising target and non-target molecules, macromolecules, and/or cells. The invention also provides electrode plates for receiving one or more of such tips, tip-electrode plates comprising electrode plates comprising one or more electrode tips, and systems comprising tip-electrodes and containers for containing one or more biological targets, e.g., such as molecules, macromolecules, and/or cells. The invention further provides methods for using such systems and components thereof. In one preferred aspect, the systems are used for spatially confined electroporation of cells and cell structures. The invention facilitates high throughput screening of agents (e.g., such as drugs) that act on intracellular targets.

Abstract: Disclosed is a method for penetration of lipid bilayer membranes in order to insert at the tip of a hollow needle-shaped object, such as a micropipet-, into a container formed of a lipid bilayer membrane, wherein said container is placed between said needle-shaped object, with the tip of said needle-shaped object placed in contact with said conainer in such a way that it applies a mechanical force to the lipid membrane of said container, thus mechanically straining it, and a second electrode, whereupon a transient electric pulse of 1-to-103 V/cm is applied between the electrodes, resulting in a focused electrical field over said container C which induces a dielectric breakdown of the lipid bilayer causing the needle-shaped object to penetrate the container. Disclosed is also an electroinjection method based on the above method, wherein substances are introduced through the needle-shaped object and into the container after penetration of the needle-shaped object.

Abstract: The invention provides a system, system components, and a method for rapidly obtaining and stably maintaining a cell in optimal contact with the cell-contacting surface of a sensor in a cell-based biosensor. In one aspect, the system maximizes the seal between a whole cell and the cell-contact surface of a patch clamp micropipette, maximizing the efficiency of a whole cell patch clamp recording.

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 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: The invention relates to a method for permeabilization of a cell structure consisting of a single cell, an intracellular structure or an organelle comprising the following steps: (a) microelectrodes, preferably two carbon fiber electrodes or hollow fiber electrodes, are provided, (b) the microelectrodes are connected to a power supply, (c) the electrodes, individually controlled by high-graduation micromanipulators, are placed close to the cell structure at an appropriate inter-electrode distance, and (d) a highly focused electric field of a strength sufficient to obtain electroporation is applied between the electrodes. The method may be used in order to transfer cell impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure, in biosensors, in the treatment of tumours and neurodegenerative diseases and in the study of biophysical processes.

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: An apparatus and method are disclosed for electromanipulation of at least one cell or cell-like structure having cell-like membranes, the method comprising the steps: (a) at least one cell or cell-like structure is transported from one or more sample containers located on a chip through microchannel(s) located on said chip into a chamber located on said chip, wherein said chamber contains electrode(s) connected to a voltage generator, wherein said microchannel provides a fluid contact between the sample containers, (b) said cell or cell-like structure(s) is placed close to said at least one electrode, and (c) an electrical field is applied and focused on said cell or cell-like structure(s), said electrical field being of a strength sufficient to obtain pore-formation or fusion of said at least one cell or cell-like structure with another cell or cell-like structure(s) present in said chamber.

Abstract: The invention provides hollow-tip-electrodes for spatially localized delivery of substances to one or more biological targets present in a population comprising target and non-target molecules, macromolecules, and/or cells. The invention also provides electrode plates for receiving one or more of such tips, tip-electrode plates comprising electrode plates comprising one or more electrode tips, and systems comprising tip-electrodes and containers for containing one or more biological targets, e.g., such as molecules, macromolecules, and/or cells. The invention further provides methods for using such systems and components thereof. In one preferred aspect, the systems are used for spatially confined electroporation of cells and cell structures. The invention facilitates high throughput screening of agents (e.g., such as drugs) that act on intracellular targets.

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.

Abstract: The invention provides integrated systems comprising macroscale devices interfaced with microscale devices and methods for making these systems.

Abstract: The invention provides a system, system components, and a method for rapidly obtaining and stably maintaining a cell in optimal contact with the cell-contacting surface of a sensor in a cell-based biosensor. In one aspect, the system maximizes the seal between a whole cell and the cell-contact surface of a patch clamp micropipette, maximizing the efficiency of a whole cell patch clamp recording.

Abstract: Disclosed is a method for the production of a microscopic network of containers and nanotubes, constituted of surfactant membranes, said method comprising partitioning of one mother container into two daughter containers in communication with each other through a nanotube, followed by partitioning of one or both of the resulting daughter containers resulting in new daughter containers, wherein the partitioning of daughter containers is repeated until a desired number of containers is obtained. Also disclosed are microscopic networks of containers and nanotubes obtainable by the above mentioned method, and microscopic networks of at least two containers constituted of surfactant membranes and at least one nanotube constituted of surfactant membranes, said nanotube forming communication between said containers.

Abstract: Disclosed is a method for penetration of lipid bilayer membranes in order to insert at the tip of a hollow needle-shaped object, such as a micropipet-, into a container formed of a lipid bilayer membrane, wherein said container is placed between said needle-shaped object, with the tip of said needle-shaped object placed in contact with said conainer in such a way that it applies a mechanical force to the lipid membrane of said container, thus mechanically straining it, and a second electrode, whereupon a transient electric pulse of 1-to-103 V/cm is applied between the electrodes, resulting in a focused electrical field over said container C which induces a dielectric breakdown of the lipid bilayer causing the needle-shaped object to penetrate the container. Disclosed is also an electroinjection method based on the above method, wherein substances are introduced through the needle-shaped object and into the container after penetration of the needle-shaped object.

Abstract: The invention relates to a method for permeabilisation of a cell structure consisting of a single cell, an intracellular structure or an organelle comprising the following steps: (a) microelectrodes, preferably two carbon fibre electrodes or hollow fibre electrodes, are provided, (b) the microelectrodes are connected to a power supply, (c) the electrodes, individually controlled by high-graduation micromanipulators, are placed close to the cell structure at an appropriate inter-electrode distance, and (d) a highly focused electric field of a strength sufficient to obtain electroporation is applied between the electrodes. The method may be used in order to transfer cell impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure, in biosensors, in the treatment of tumours and neurodegenerative diseases and in the study of biophysical processes.

Abstract: Disclosed is a method for electromanipulation of at least one cell or cell-like structure having cell-like membranes, comprising the following consecutive steps: (a) at least one cell or cell-like structure is transported from one or more sample containers located on a chip through at least one microchannel located on said chip into a chamber located on said chip, wherein said chamber contains at least one electrode connected to a voltage generator, and wherein said microchannel provides a fluid contact between the sample containers, (b) either said at least one cell or cell-like structure is placed or aligned close to said at least one electrode, or said at least one electrode is placed or aligned close to said at least one cell or cell-like structure in said chamber, and (c) an electrical field is applied and focused on said at least one cell or cell-like structures, said electrical field being of a strength sufficient to obtain pore-formation in said at least one cell or cell-like structure or sufficient t