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 computer program products for coordinating the movement of cells and other components in a microfluidic substrate with data acquisition. The microfluidic workstation may be used to examine the physiological responses of ion channels, receptors, neurons, and other cells to fluidic streams. The system may also be useful for screening compound libraries to search for novel classes of compounds, screening members of a given class of compounds for effects on specific ion channel proteins and receptors, and to rapidly determine dose-response curves in cell-based assays.

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

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 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) 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.