Bio-rad Laboratories, Inc.

Siemens Healthcare Diagnostics Gmbh

Paul J Patt

Daniel Y Chu

Xin Heng

Jeffry M Ceremony

Kun Guo

Amir Sadri

Roger C Tong

Evan Thrush

Nenad M Kircanski

Ariel Notcovich

Eli Hefner

Steven Swihart

Tal Rosenzweig

Trey Marlowe

Tom McCollum

John J Barich

Cliff Baldwin

Frank Shen

David Neaz

Don Flory

Mike Griffin

Ryan Short

Deepak K Doshi

Rhoel Rumbaoa

Dennis W Loring

Joel Talacki

Renee Lemaire-Adkins

Robert Archer

German Arciniegas

Mohiudeen Azhar

Frank Hsiung

Roy Barr

Daniel Chu

Nenad Kircanski

Ragavendar Madrassethuraman

Karan Mohan

Amir M Sadri

Tom Mccollum

Robert M Archer

Jeffry Mark Ceremony

Dennis Wayne Loring

Deepak Kumar Doshi

David John Guckenberger Jr

Garret Bautista

An optical discrimination apparatus adapted for use in PCR testing and the like. The apparatus includes a multi-color light emitter to emit excitation light, a sample holder configured to hold dye-marked nucleic acid fragments in a PCR solution at a position configured to receive the excitation light along a first direction, light emission collection optics configured to collect scattered excitation light and light emission (fluorescent emission) from the sample holder along a second direction that is approximately orthogonal to the first direction, a spectrally-dispersive element configured to spectrally disperse scattered light and emission light, and a spectral detector configured to receive the separated emission light and excitation light on different photosites of the spectral detector. Systems and methods are provided, as are other aspects.

Optical discrimination apparatus and methods adapted to monitor reactions

Analyte arrays such as solutes in a slab-shaped gel following electrophoresis, and particularly arrays that are in excess of 3 cm square and up to 25 cm square and higher, are imaged at distances of 5 cm or less by either forming sub-images of the entire array and stitching together the sub-images by computer-based stitching technology, or by using an array of thin-film photoresponsive elements that is coextensive with the analyte array to form a single image of the array.

Image capture for large analyte arrays

A method is provided for transporting a plurality of cells through a flow chamber, wherein the cells are initially immobilized on an internal surface of the flow chamber. The method comprises: selectively releasing the cells from the internal surface of the flow chamber; and flowing liquid through the flow chamber such that the released cells travel with the liquid, thereby transporting the cells through the flow chamber. Cells can be immobilized on or selectively released from the internal surface by applying or removing a trapping potential. The trapping potential can arise from an electric field gradient or an optical field gradient. Alternatively, cells can be selectively released from the surface using photocatalysis. Selective release allows cells to be individually observed or analyzed downstream, and can be based on a signal detected from one or more cells immobilized on the surface.

Optofluidic sorter

Systems, including apparatus and methods, for the microfluidic manipulation, dispensing, and/or sorting of particles, such as cells and/or beads.

On-demand particle dispensing system

Biological cells in a liquid suspension are counted in an automated cell counter that focuses an image of the suspension on a digital imaging sensor that contains at least 4,000,000 pixels each having an area of 2&#xd7;2 &#x3bc;m or less and that images a field of view of at least 3 mm. The sensor enables the counter to compress the optical components into an optical path of less than 20 cm in height when arranged vertically with no changes in direction of the optical path as a whole, and the entire instrument has a footprint of less than 300 cm. Activation of the light source, automated focusing of the sensor image, and digital cell counting are all initiated by the simple insertion of the sample holder into the instrument. The suspension is placed in a sample chamber in the form of a slide that is shaped to ensure proper orientation of the slide in the cell counter.

Compact automated cell counter

Particles are dispensed under controlled conditions to achieve an accurate number of particles by passing a suspension of the particles through a particle detecting device, obtaining a cumulative particle count, comparing the cumulative particle count with a target value, and shutting off the suspension flow once the particle count reaches the target value, all performed by automated means.

Particle dispensing apparatus and method

Rapid and uniform temperature changes in the wells of a microplate or any thin-walled plate that contains an array of reaction wells or sample receptacles are achieved by the use of heating and cooling elements with a vapor chamber interposed between such elements and the microplate. The upper surface of the vapor chamber and the underside of the sample plate in certain embodiments are complementary in shape, i.e., they have identical but oppositely directed contours in the areas around each of the sample receptacles, to provide continuous surface contact along the surface of each receptacle. In other embodiments, an intermediary plate is placed between the vapor chamber and the well plate, with the top surface of the intermediary plate being complementary in shape to the underside of the well plate.

Thermal cycler with vapor chamber for rapid temperature changes

Adherent cells bearing characteristics that are detectable only in the adherent state can be sorted on the basis of these characteristics independently of their adherent state, by applying a transformable label to the entire population of cells, both those bearing the characteristics of interest and those not, in their adherent state and identifying the locations of the cells of interest on the adherent surface. The cells of interest, or all cells other than those of interest, are then selectively treated to transform the labels and achieve differentiation between the cells of interest and the remaining cells. All cells are then released from the adherent state and sorted in the same manner as non-adherent cells but on the basis of whether the labels are transformed or not transformed.

Sorting of adherent cells by selective transformation of labels

A system for performing high-speed, high-resolution imaging cytometry includes a scanning region that is illuminated by light including at least first and second wavelength bands. The system also includes a cell transport mechanism that transports a cell through the scanning region such that the cell is illuminated. The system further includes a set of at least one linear light sensor, and an optical system that selectively directs light emitted from the cell to two portions of the linear light sensor set such that emitted light in a third wavelength band is primarily directed to a first portion of the linear light sensor set, and emitted light in a fourth wavelength band is primarily directed to a second portion of the linear light sensor set. The system repeatedly takes readings of light falling on the linear light sensor set while the cell is transported through the scanning region.

Serial-line-scan-encoded multi-color fluorescence microscopy and imaging flow cytometry

A flow cytometry system includes a flow element through which a cell is transported in a flowing fluid. The flow element includes a bore bounded by a wall. A light source is configured to illuminate the cell. An optical system receives light emanating from the cell and directs at least some of the received light to a light sensor. The optical system includes a numerical-aperture-increasing lens at a wall of the flow element. At least some of the received light passes through the numerical-aperture-increasing lens. The flow cytometry system may also include a beam splitter that directs two wavelength bands of the emanating light such that light in two wavelength band preferentially reach different sensing locations via different paths. The system may also include an optical element placed in one of the paths, shifting a focal location of the affected path to compensate for chromatic aberration of the numerical-aperture-increasing lens.

Cytometry system with solid numerical-aperture-increasing lens

A thermal cycling instrument for PCR and other reactions performed on multiple samples with temperature changes between sequential stages in the reaction procedure is supplied with a thermal block to provide rapid changes and close control over the temperature in each sample vessel and a pressure plate incorporated into a motorized lid that detects anomalies in the reaction vessels or in their positioning over the thermal block, and automatically adjusts the plate position to achieve an even force distribution over the sample vessels.

Thermal cycler with self-adjusting lid

Systems and methods for performing cytometry using a linear light sensor. An illumination field, a line scanned by the linear light sensor, or both are swept across a cell to be imaged. Relative motion between the cell and the swept illumination may be created using a movable optical component or components, by adhering cells to a plate and transporting the plate or by other techniques.

Line scan cytometry systems and methods

A system for performing high-speed, high-resolution imaging cytometry utilizes a line-scan sensor. A cell to be characterized is transported past a scan region. An optical system focuses an image of a portion of the scan region onto at least one linear light sensor, and repeated readings of light falling on the sensor are taken while a cell is transported though the scan region. The system may image cells directly, or may excite fluorescence in the cells and image the resulting light emitted from the cell by fluorescence. The system may provide a narrow band of illumination at the scan region. The system may include various filters and imaging optics that enable simultaneous multicolor fluorescence imaging cytometry. Multiple linear sensors may be provided, and images gathered by the individual sensors may be combined to construct an image having improved signal-to-noise characteristics.

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Danville, CA, United States of America

Paul J Patt