Axon Instruments, Inc.

Applied Biosystems, LLC

Life Technologies Corporation

Alexander A Dromaretsky

Yuri Vladimirovich Osipchuk

Mark F Oldham

Charles Stuart Vann

Joy Roy

Dennis Lehto

Ian A Harding

Yuh-Min Chiang

Nigel P Beard

Umberto Ulmanella

David M Liu

Joon Mo Yang

Sergey V Ermakov

Maryam Shariati

John R Van Camp

Min Yue

Yuriy Roll

Branko Bem

Thomas C Au

Alan S Finkel

Alexei Savtchenko

John Van Camp

Systems and methods for multiple analyte detection include a system for distribution of a biological sample that includes a substrate, wherein the substrate includes a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber. The system may further include a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate and a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber. The substrate can be constructed of detection-compatible and assay-compatible materials.

Systems and methods for multiple analyte detection

A device for amplifying a nucleic acid sample may include a sample holder configured to receive a nucleic acid sample, a heating system configured to raise the temperature of the sample, a cooling system configured to lower the temperature of the sample, and a controller configured to operably control the heating system and the cooling system to cycle the device through a desired time-temperature profile. The cooling system may include at least one heat pipe and a heat sink and the at least one heat pipe may include a first portion disposed proximate to the sample holder and a second portion disposed proximate to the heat sink.

Cooling in a thermal cycler using heat pipes

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.

Detachable cell-delivery system for patch-clamp unit

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.

Polymeric electrode for electrophysiological testing

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. A retroreflector may be utilized in conjunction with the optical pathway selector to eliminate error due to non-planar surfaces or motion. The optical pathway selector may be used in epifluorescence imaging systems.

Optical pathway selector

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. A photo detector is placed at the image space focal point of the collection lens so as to convert the intensity of the light emitted from the sample at the focal point of the objective lens in object space to an electrical signal. To achieve high resolution, a light-path-altering optical element is inserted between the light source and the objective lens so as to translate the light centered on the axis of rotation to light centered on the optical axis of the objective lens, thereby filling the entrance pupil of the objective lens.

Scanning microscope

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.

Wavelength-selective mirror selector

Growing community of inventors

Irvine, CA, United States of America

Alexander A Dromaretsky