Abstract: The cell-delivery unit of a high-throughput electrophysiological testing system is implemented as a reusable movable unit suitable for repetitive delivery of cells to a disposable, multi-aperture patch-clamp tray. An electric field emanating from the patch aperture is used to align the dispenser with the aperture. A set of electrodes in the nozzle of the dispenser is used to detect the electric field and effect the alignment. According to another aspect of the invention, dielectrophoretic fields produced by sets of electrodes in the nozzle form a retaining cage that is used first to suspend a test cell directly above the patch aperture and then to urge the cell toward it. A movable cell sorter may also be coupled to the cell-delivery unit.

Abstract: A polymeric material such as PDMS is molded into an electrode structure containing a micron-size aperture for receiving and forming a giga-ohm seal with a biological membrane. One end of a tube is filled with uncured polymeric material and pressed against a support surface to prevent drainage. A conventional micropipette having a size suitable for sliding through the tube is introduced, tip first, into the tube and is allowed to fall through the polymeric material and rest against the support surface. The assembly is heated to cure the polymer and the micropipette is removed from the tube, thereby leaving a polymeric plug at the end of the tube with an aperture suitable in shape and size for patch-clamp giga-ohm seal electrode applications. A multi-well tray with a polymeric electrode plug in each well is constructed using the same approach.

Abstract: A fluorescent optical imaging system (10) produces two separate spots (S1 and S2) on a sample (12) by a pair of excitation laser beams (B1 and B2) that are generated by first and second lasers (L1 and L2). Excitation laser beams (B1 and B2) pass at slightly different angles, first through an aperture (15) of a 45° fold mirror (13), and then through an objective element (14). As a result, emission light beams (16, 18) are generated from each illuminated spot (S1 and S2) and are reflected and redirected by mirror (13) through a secondary lens (19) before reaching one of two detectors (PMT 1 and PMT 2). Emission beam (16) reflects off a second 45° mirror (22) prior to reaching detector (PMT 1), while emission beam (18) travels directly to (PMT 2). If desired, optical separation elements (24), such as dichroic filters, prisms, or gratings, can be positioned in front of each detector (PMT 1 and PMT 2).

Abstract: An optical mount, including a first plate, a second plate, an adjustment screw, and a locking screw. The second plate may include an adjustment bore having an adjustment bore thread and a slit separating a second plate flange from a second plate body and extends into the adjustment bore. The adjustment screw may engage the first plate for adjusting relative position of the first plate in relation to second plate. The locking screw may engage the second plate flange and the second plate body to press at least a portion of the adjustment bore thread into the adjustment screw thread for securing the adjustment screw. An attachment bore may be included for receiving an attachment. A method for using the optical mount is also disclosed.

Abstract: A perfusion-chamber structure includes a chamber plate with an extracellular compartment, a partition plate with an electrode aperture, and a foundation plate with an intracellular compartment. A gap between the chamber plate and the partition plate produces a channel for applying suction that draws extracellular solution from the extracellular compartment and facilitates the movement and positioning of a test cell over the electrode aperture. The positioning procedure for the test cell is accompanied by a slight positive pressure applied to the intracellular solution in the intracellular compartment of the perfusion chamber to cause upward fluid flow through the electrode aperture. When the cell is positioned over the electrode aperture, the positive pressure on the intracellular fluid is reversed to suction and the cell is seated thereby to form the seal.

Abstract: An optical mount, including a first plate, a second plate, an adjustment screw, and a locking screw. The second plate may include an adjustment bore having an adjustment bore thread and a list separating a second plate flange from a second plate body and extends into the adjustment bore. The adjustment screw may engage the first plate for adjusting relative position of the first plate in relation to second plate. The locking screw may engage the second pate flange and the second plate body to press at least a portion of the adjustment bore thread into the adjustment screw thread for securing the adjustment screw. An attachment bore may be included for receiving an attachment. A method for using the optical mount is also disclosed.

Abstract: A fluorescent optical imaging system (10) produces two separate spots (S1 and S2) on a sample (12) by a pair of excitation laser beams (B1 and B2) that are generated by first and second lasers (L1 and L2). Excitation laser beams (B1 and B2) pass at slightly different angles, first through an aperture (15) of a 45° fold mirror (13), and then through an objective element (14). As a result, emission light beams (16, 18) are generated from each illuminated spot (S1 and S2) and are reflected and redirected by mirror (13) through a secondary lens (19) before reaching one of two detectors (PMT 1 and PMT 2). Emission beam (16) reflects off a second 45° mirror (22) prior to reaching detector (PMT 1), while emission beam (18) travels directly to (PMT 2). If desired, optical separation elements (24), such as dichroic filters, prisms, or gratings, can be positioned in front of each detector (PMT 1 and PMT 2).

Abstract: An optical pathway selector is provided having a first direction selector, a second direction selector, and an actuator. The first direction selector is comprised of a substantially planar member having alternating reflecting and transparent portions. The first direction selector is disposed for rotation on an axle with the substantially planar member positioned askew to a first optical axis. The second direction selector has a configuration similar to that of the first direction selector and is disposed along the axle substantially parallel to the first direction selector. Additional direction selectors can be employed in a similar manner. A motor is connected to the axle for rotating the direction selectors. Alternatively, a motor moves the direction selector along a linear pathway in and out of the pathway of different light beams. The optical pathway selector is used to reflect a beam of light from the first optical axis to alternative optical axes or vice-versa.

Abstract: A fluorescent optical imaging system (10) produces two separate spots (S1 and S2) on a sample (12) by a pair of excitation laser beams (B1 and B2) that are generated by first and second lasers (L1 and L2). Excitation laser beams (B1 and B2) pass at slightly different angles, first through an aperture (15) of a 45° fold mirror (13), and then through an objective element (14). As a result, emission light beams (16, 18) are generated from each illuminated spot (S1 and S2) and are reflected and redirected by mirror (13) through a secondary lens (19) before reaching one of two detectors (PMT 1 and PMT 2). Emission beam (16) reflects off a second 45° mirror (22) prior to reaching detector (PMT 1), while emission beam (18) travels directly to (PMT 2). If desired, optical separation elements (24), such as dichroic filters, prisms, or gratings, can be positioned in front of each detector (PMT 1 and PMT 2).

Abstract: A scanning microscope. An objective lens receives light emitted from a sample in object space and propagates it to image space thereof. A collection lens receives light from the objective lens and propagates it to a focal point in image space of the collection lens. A motor has an axis of rotation that is offset from and extends in substantially the same direction as the optical axis. The motor rotates the objective lens about the axis of rotation to scan across a sample in object space of said objective lens. The sample is mounted on a stage. After each rotation of the objective lens, the stage is advanced in a radial direction with respect to the axis of rotation so that each subsequent scan covers a new part of the sample. For fluorescence microscopy, a laser light source is provided. A wavelength-selective beamsplitter directs the laser light toward the objective lens, while allowing fluorescence or reflected light emitted from the sample to pass through to the collection lens.

Abstract: A perfusion chamber includes a porous oocyte support structure. A continuously sloped top surface and a receiving well in the support structure entrap the underside of the oocyte, thereby localizing the cell in a predetermined fixed position within the reach of dedicated voltage-clamp microelectrodes. A test solution is delivered continuously at the top of the chamber, above the oocyte, and withdrawn from the bottom of the chamber, below the oocyte. The porosity of the support material enables the continuous perfusion of test solution around the membrane of the oocyte, including its bottom portion that is held firmly in contact with the holding well. The geometry of the holding well is selected such as to ensure the automatic and precise placement of the oocyte by gravity and to optimize the pressure distribution over its membrane, thereby minimizing the probability of rupture or other damage to the cell.

Abstract: An automated mechanism for guiding a microelectrode toward an oocyte placed in a perfusion chamber consists of a movable guide tube holding the electrode and a fixed guide collar in fixed relation to the target oocyte. Because the guide tube and guide collar are independently mounted, the alignment of the tip of the microelectrode is effected by its placement within the precisely aligned guide collar, irrespective of any fine misalignment of the guide tube. Accordingly, a change of microelectrode in the guide tube does not affect its final alignment toward the oocyte so long as the calibration of the guide collar is not disturbed, thereby providing a mechanism for maintaining the alignment of different microelectrodes successively mounted in the system without requiring recalibration.

Abstract: A device and a method are provided for holding a stereotactic probe in position after the probe has been precisely positioned by stereotactic procedures, such as brain surgery. The device, a stereotactic probe holder, is adjustable, as it is capable of being positioned to contact and grip a probe at a position between a stereotactic frame and a patient's head, and is suitable for holding the probe in a desired location. Methods of using the stereotactic probe holder are also provided. The invention is useful in maintaining the proper positioning of probes, such as deep brain stimulators, electrodes, cryoprobes, cannulae, and the like, after the initial placement of the probes during stereotactic surgery.

Abstract: A wavelength-selective mirror selector. A substantially planar wavelength-selective selective mirror holder is disposed askew to a common optical pathway. The holder has a plurality of mirrors mounted thereon and an axle attached normal thereto for rotating the holder so as to place a selected one of the mirrors in the common optical pathway. A motor is connected to the axle for rotating the mirror holder, either selectively or continuously. When a selected mirror is placed in the common optical pathway, the pathway is split so that an excitation light beam of one wavelength traveling along a source optical pathway from a light source is reflected by the mirror along the common optical pathway toward a sample, while light of a different wavelength propagating back along the common optical pathway passes through the mirror to travel along a detector optical pathway to a detector.

Abstract: The present invention discloses a package for electronic components which reduces the unwanted electronic noise generated by the package and which can be fabricated by conventional manufacturing techniques. Accordingly, a lid for a package housing is fabricated from beryllium oxide and contains a small hole. During assembly, a wire attached to one of the electronic components is inserted through the hole of this lid, and the lid is attached by conventional methods. Finally, the wire protruding through the hole is soldered to the lid, which completes the sealing of the housing and which provides for a hermetic environment for the enclosed electronic components.