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 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: The present invention relates to a method for detection of receptor antagonists comprising the following steps: (I) a sample containing the receptor antagonist is fractionated by use of a liquid-based separation means, preferably capillary electrophoresis, (II) a fraction containing the receptor antagonist or modulator is fed directly to a biosensor (9) which is activated by an appropriate receptor agonist and, as a result of this activation, is generating a measurable response, said agonist being fed to the biosensor through the liquid-based separation means together with the antagonist or modulator, said activation of the biosensor (9) being pulsed by delivery of the receptor agonist to the biosensor for short period of times, said periods being separated by other periods when no agonist is delivered to the biosensor, and (III) the change of the response resulting from deactivation of the receptor agonist-activated biosensor by the receptor antagonist or modulator is measured, preferably by means of a patch

Abstract: The invention provides a method for detection of receptor- or ion channel-modulators (e.g., antagonists, blockers, etc.). The method comprises fractionating a sample by using a liquid-based separation means (e.g., such as a capillary electrophoresis device), and feeding the fractions containing the modulators directly to a biosensor. The biosensor is activatable by a receptor agonist and produces a measurable response as a result of this activation. Preferably, the agonist is fed to the biosensor through the liquid-based separation means, together with fractions containing the modulators (e.g., antagonists or blockers). The presence of a modulator is detected by monitoring a change in the response of the biosensor, e.g., by measuring changes in electrical properties of the biosensor (such as through patch clamp analysis).

Abstract: Method and apparatus for high-sensitivity fluorescence detection wherein (I) a sample comprising fluorescent molecules is made to flow through a channel structure (1) including a constricted region (2) with a dimension corresponding to the size of a tightly focused laser spot and with extremely thin, transparent walls; (II) a laser beam (3) is focused inside the constricted (2) and thus exciting molecules passing through the constricted region (2); and (III) the fluorescence emitted due to excitation is detected. This enables direct determination of the concentration of a sample without use of internal or external standards. A method for the production of a flow cell for use in the method or apparatus, wherein a part of a channel structure (1) is heated until its melting point is reached, followed by pulling of the structure to lengthen the melted region and make it thinner until it has a dimension corresponding to the size of a tightly focused laser spot at the diffraction limit.

Abstract: Method and apparatus for high-sensitivity fluorescence detection wherein (I) a sample comprising fluorescent molecules is made to flow through a channel structure (1) comprising a constricted region (2) with a dimension corresponding to the size of a tightly focused laser spot and with extremely thin, transparent walls, (II) a laser beam (3) is focused inside the constricted (2) and thus exciting molecules passing through the constricted region (2), and (III) the fluorescence emitted due to excitation is detected. This enables direct determination of the concentration of a sample without use of internal or external standards. A method for the production of a flow cell for use in said method or apparatus, wherein a part of a channel structure (1) is heated until its melting point is reached, followed by pulling of the structure to lengthen the melted region and make it thinner until it has a dimension corresponding to the size of a tightly focused laser spot at the diffraction limit.