Becton Dickinson and Company Limited

Other

The General Hospital Corporation

Robert A Hoffman

Joseph T Trotter

Ming Yan

Alan M Stall

Bertram G Pinsky

Hans-Joachim Gross

Joseph R Lakowicz

Conor L Evans

Eric S Chase

Daniel Cramer

Pierre Bierre

Klaus W Berndt

William J Treytl

Dan E Thiel

Kenneth Earl Murchison

Andrew D Blidy

Leo J Hoffman, Jr

Anne Louise Jackson

Thomas Frey

Pierce Owen Norton

W Peter Hansen

Petra B Krauledat

Daniel W Cramer

Conor L Evan

A method for detecting a target cell surface molecule and classifying cell types in a fluid sample. The method involves the addition of a reagent to the fluid sample. The reagent includes nanoparticles with optical plasmonic resonances, and at least one fluorescent probe. The nanoparticles are a bio-optical probe for the target cell surface molecule. Each fluorescent probe targets a cell classification marker. The method further involves the acquisition of an image using dark field microscopy and fluorescence microscopy to detect and quantify the presence or absence of any cells in the fluid sample having the target cell surface molecule or having the cell classification marker.

Plasmonic nanoparticle immunoassay method

The present invention reagents and methods for setting up an instruments having a multiplicity of detector channels for analyzing a multiplicity of fluorescent dyes. The present invention is particularly applicable in the field of flow cytometry.

Instrument setup system for a fluorescence analyzer

A trail marking system having a plurality of trail markers, a remote control handset for selectively activating the trail markers, and a setting tool for setting and removing the trail markers. To use the trail marking system, a hunter attaches a trail marker into a tree using the setting tool. The trail markers contain externally perceivable indicators that can be selectively turned on an off. When the indicators in the trail markers are off, the trail markers are inconspicuous. However, when the indicators are activated, they are highly visible. The trail markers are selectively turned on an off using the remote control handset. As such, a hunter can selectively turn on and off the trail markers as he/she walks along the trail.

Remotely activated trail marker system and its method of use

An apparatus and method for examining particles in a flow stream of a flow cytometer, employing incoherent light sources, such as light emitting diodes (LEDs), and detectors. The light emitting diodes operate as the excitation light sources and emit light toward said flow stream, and the detectors detect light, in particular, fluorescent light, emanating from the particles in response to the excitation light striking the particles. A controller controls each of the light emitting diodes to emit their excitation light for a predetermined period during which the excitation light radiates onto particles of interest. The controller evaluates the detected light to ascertain characteristics of the particles, such as particle size, density and granularity. The apparatus and method can further employ one or more coherent and homogenous light emitting devices, such as a laser, as an additional excitation light source. The detectors can detect the LED-excited fluorescence or the laser-excited fluorescence from the particles, and the controller can evaluate both types of detected light to ascertain characteristics of the particles. Furthermore, the controller can control the LEDs to operate in a pulsed manner, which can be synchronized with the detection of the laser-excited fluorescence or light scatter. In addition, a substantially opaque panel having one or more slits can be positioned at the image plane upon which an image of the flow stream is projected, so that the slits will allow only a portion of the image to pass to the detector associated with the panel.

Apparatus and method employing incoherent light emitting semiconductor devices as particle detection light sources in a flow cytometer

This invention presents improved methodology for identification of nucleated cells in flow cytometric analysis when immunofluorescent dyes are also used. Briefly, in the method nucleic acids are stained with a fluorescent dye which can then be used to identify the nucleated cells by measurement of fluorescence on a flow cytometer. The improvement presented by this invention is the use of a saturating (or near saturating) amount of a nucleic acid dye, or mixture of dyes, which gives low fluorescence at excitation conditions, so as not to greatly interfere with the signals of the immunofluorescent dyes.

Use of dimly fluorescing nucleic acid dyes in the identification of nucleated cells

A multi-laser flow-cytometry system provides for inter-location emissions crosstalk cancellation, through either pulse subtraction or gating, to avoid false triggering based on shadow (pre- and post-) pulses that occur when red-excited red emissions are detected by a photodetector arranged to detect blue-excited red emissions. This overcomes a problem of undercounting of counting beads that led to misdeterminations of cell counts when blue-excited red fluorescence detections were used as a trigger. The approach also provides for more accurate quantitative data regarding fluorochrome emissions amplitudes.

Multi-illumination-source flow particle analyzer with inter-location

A method of flow cytometric analysis of leukocyte subpopulations using a fluorescence trigger and gating on light scatter vs. fluorescence. The methods are useful where light scatter parameters are unsatisfactory for identification of leukocyte subpopulations, for example when analyzing lysed blood samples without removal of lysing reagent or unbound label prior to analysis.

Method for preparation and analysis of leukocytes in whole blood

A fluorescence particle analyzer includes a flow tube through which particles marked with different fluorochromes pass from a first location to a second location. Emissions from the first and second locations are respectively imaged at respective first and second filter elements so that emissions that reach a photodetector from said first location are primarily filtered by the first filter element, while emission that reach the same photodetector from the second location are primarily filtered by the second filter element. The first filter element is selected to preferentially transmit emissions from a first fluorochrome at the expense of emissions from a second fluorochrome, while the second filter element is selected to preferentially transmit emissions from the second fluorochrome at the expense of emissions from the first fluorochrome. The first location is illuminated by a laser that preferentially excites the first fluorochrome at the expense of the second fluorochrome, while the second location is illuminated by a laser that preferentially excites the second fluorochrome at the expense of the first fluorochrome. The photodetector output includes a first pulse that corresponds predominately to the quantity of the first fluorochrome in the particle; subsequently, a second pulse appears corresponding predominantly to the quantity of the second fluorochrome in the particle. The use of the two filters minimizes cross talk between the fluorochrome emissions in the photodetector output pulses.

Particle analyzer with spatially split wavelength filter

Method and apparatus for performing phase fluorescence lifetime

A flow cytometer measures phase fluorescence lifetimes by the phase shift of a reference signal and an emission from a particle or cell in a flow chamber. An acoustic optic modulator modulates laser light with a sinusoidal wave of a predetermined frequency to excite particles or cells. Detectors respond to emissions of individual particles or cells in the form of an output signal pulse at the predetermined frequency. The output signal pulse is divided into equal pulses with each at the modulation frequency, the same amplitude and fidelity and amplitude. One part of the divided pulse is stripped of its envelope to pass the width thereof and out of band components are rejected. A variable amplifier passes a portion of the pulse above a present level. A delay line sets a central part of the signal at a predetermined point in time. A circuit limits the attenuated one part. A double balance mixer multiplies and the relates the limited signal with a reference signal to determine the phase shift. A method measures phase fluorescence lifetimes of cells or particles with fluorescent markers by passing individual cells or particles in a flow stream of a flow chamber in a flow cytometer.

Apparatus and method for phase resolved fluorescence lifetimes of

A method for cleaning cellular contamination in a flow cytometer comprising the sequential use of a strong oxidizing solution, particle-free neutral pH fluid and a weak acid.

Cleaning cycle for flow cytometers

A method and apparatus for cleaning cellular contamination in flow cytometer comprising the sequential use of a strong oxidizing solution, particle-free neutral pH fluid and a weak acid.

Growing community of inventors

Livermore, CA, United States of America

Robert A Hoffman