Other

Coulter Electronics, Inc.

Coulter International Corp.

Robert Cary Leif

Lidia M Vallarino

Carlos M Rodriguez

Stephen L Ledis

James L Wyatt

Robert Stewart Frank

Sean Yang

Weiyan Gong

Robert I Feinberg

Disclosed is a spectrofluorimetrically detectable luminescent composition consisting essentially of at least one energy transfer acceptor lanthanide(III) complex having an emission spectrum maximum in the range from 300 to 2000 nanometers and a luminescence-enhancing amount of at least one energy transfer donor selected from the group consisting of a fluorophore, a lumiphore, an organic compound, a salt of an organic ion, a metal ion, a metal ion complex, or a combination thereof. Such energy transfer donor enhances the luminescence of at least one energy transfer acceptor lanthanide(III) complex, with the conditions that the emission spectrum of any energy transfer donor differs from that of its energy transfer acceptor lanthanide(III) complex; and such energy transfer donor can be dissolved to form a unitary solution in a solvent having an evaporation rate at least as great as that of water.

Reagent system and method for modifying the luminescence of lanthanide(III) macrocyclic complexes

An apparatus and method for the automated preparation of treated monolayers of sample material, comprising: a centrifuge having a rotor () carrying removable chamber blocks (); sample and reagent dispensers () and control systems (). First, centrifugal force sediments sample material discretely to form a monolayer onto a receiving surface member () on one of the chamber blocks (), while the same centrifugal force opens a valve () in the chamber block () to drain sample material. Then, centrifugal force delivers sequentially into discrete chamber blocks () discrete treating agents, during which time the sampler material monolayer is held in place on the receiving surface member () by centrifugal force. Then, each chamber block () is drained centrifugally through its already opened valve (). Each treated sampler material is confined to an individual chamber block (). Batch and random access delivery of treating agents can be employed. Each chamber block () includes separate inlets for the sample and treating agents.

Centrifugal cytology system, chamber block and method for the preparation of treated monolayers of sample material

A tagged water-soluble polymer linked to a solid support is provided and includes a solid support optionally including a spacer sequence including one or more spacer monomer units attached to the solid support; and a water-soluble polymer covalently linked to the solid support or to the spacer sequence, the water-soluble polymer including a first cleavage segment including at least one monomer unit including a selectively cleavable link to the solid support or to the spacer sequence, where cleavage of the selectively cleavable link separates the water-soluble polymer from the solid support, a second segment including at least one monomer unit selected from a monomer unit linked to a reactive functionality able to be covalently coupled to a tag or linked to a tag, a third segment including one or more monomer units linked to a reactive functionality that can form a covalent bond with an analyte-binding species or an analyte, and optionally one or more spacer monomer units provided adjacent to any segment and/or between any two segments and/or within any one or more of the second segment and the third segment.

Conjugated polymer tag complexes

Disclosed are a spectrofluorimetrically detectable luminescent composition and processes for enhancing the luminescence of one or more lanthanide-containing macrocycles. The luminescent composition comprises a micelle-producing amount of at least one surfactant, at least one energy transfer acceptor lanthanide element macrocycle compound having an emission spectrum peak in the range from 500 to 950 nanometers, and a luminescence-enhancing amount of at least one energy transfer donor compound of yttrium or a 3-valent lanthanide element having atomic number 59-71, provided that the lanthanide element of said macrocycle compound and the lanthanide element of said energy transfer donor compound are not identical. The addition of gadolinium(III) in the presence of other solutes to both the prototype and the di-functionalized europium, samarium, and terbium macrocyclic complexes, which were taught in our U.S. Pat. Nos. 5,373,093 and 5,696,240, enhances their luminescence. Similar enhancements of luminescence also results for the mono-functionalized europium, samarium, and terbium macrocyclic complexes, which were taught in our U.S. Pat. No. 5,696,240. The enhanced luminescence afforded by the composition enables the detection and/or quantitation of many analytes in low concentrations without the use of expensive, complicated time-gated detection systems.

Reagent system and method for increasing the luminescence of lanthanide(III) macrocyclic complexes

Disclosed are a spectrofluorimetrically detectable luminescent composition and processes for enhancing the luminescence of one or more lanthanide-containing macrocycles. The luminescent composition comprises a micelle-producing amount of at least one surfactant, at least one energy transfer acceptor lanthanide element macrocycle compound having an emission spectrum peak in the range from 500 to 950 nanometers, and a luminescence-enhancing amount of at least one energy transfer donor compound of yttrium or a 3-valent lanthanide element having atomic number 59-71, provided that the lanthanide element of said macrocycle compound and the lanthanide element of said energy transfer donor compound are not identical. The addition of gadolinium(III) in the presence of other solutes to both the prototype and the difunctionalized europium, samarium, and terbium macrocyclic complexes, which were taught in our U.S. Pat. Nos. 5,373,093 and 5,696,240, enhances their luminescence. Similar enhancements of luminescence also results for the mono-functionalized europium, samarium, and terbium macrocyclic complexes, which were taught in our U.S. Pat. No. 5,696,240. The enhanced luminescence afforded by the composition enables the detection and/or quantitation of many analytes in low concentrations without the use of expensive, complicated time-gated detection systems.

The present invention provides an apparatus and method to determine individual red blood cell shape within a flow cytometric aperture. Cell shape is determined by measuring the asymmetry of a light scatter pattern produced by laser illumination of the cell within the aperture by light scatter detectors which collect light from specific angular regions of light scatter, and analyzing the asymmetry of the light scatter patters to determine the individual red blood cell shape. Embodiments of the invention further provide for the determination of red blood cell shape by measuring the asymmetry of a light scatter pattern and measuring electrical resistance of the red blood cell.

Apparatus and method for determination of individual red blood cell shape

Symmetrically di-functionalized water soluble macrocyclic complexes of lanthanide, actinide and yttrium ions were obtained by metal templated, Schiff-base, cyclic condensation of: (1) a functionalized 1,2-diaminoethane and a dicarbonyl compound selected from the group consisting of 2,6-dicarbonylpyridine, 2,6-diformylpyridine, 2,5-dicarbonylfuran, 2,5-diformylfuran, 2,5-dicarbonyl-thiophene and 2,5-diformylthiophene; or (2) 1,2-diaminoethane and a ring-substituted heterocyclic dicarbonyl compound selected from a group consisting of substituted 2,6-dicarbonylpyridine, substituted 2,6-diformylpyridine, substituted 2,5-dicarbonylfuran, substituted 2,5-diformylfuran; substituted 2,5-dicarbonyl thiophene, and substituted 2,5-diformylthiophene. Asymmetrically functionalized water soluble macrocyclic complexes of the lanthanide, actinide and yttrium ions were obtained by metal templated, Schiff-base, cyclic condensation of appropriately substituted diamine and dicarbonyl precursors, with such precursors contributing two heteroaromatic moieties (pyridine, furan, thiophene, or a combination thereof) to the resulting macrocyclic structure. The coordination complexes thus formed are kinetically stable in dilute aqueous solution. They are further reacted, or coupled, through a substituent on the 1,2-diaminoethane or on the pyridine, furan, or thiophene moieties, to one of the following: proteinaceous materials, polysaccharides, polynucleotides, other biologically compatible macromolecules or bridging molecules which, can be further reacted or coupled to the above mentioned substrates. These macrocyclic complexes are suitable in the preparation of reporter molecules and for magnetic resonance, radiation imaging and radiation therapy.

Macrocyclic complexes of yttrium, the lanthanides and the actinides

Functionalized water soluble macrocyclic complexes of lanthanide, actinide and yttrium ions were obtained by metal templated, Schiff-base, cyclic condensation of: (1) a functionalized 1,2-diaminoethane and a dicarbonyl compound selected from the group consisting of 2,6-dicarbonylpyridine, 2,6-diformylpyridine, 2,5-dicarbonylfuran, 2,5-diformylfuran, 2,5-dicarbonylthiophene and 2,5-diformylthiophene; or (2) 1,2-diaminoethane and a ring-substituted heterocyclic dicarbonyl compound selected from a group consisting of substituted 2,6-dicarbonylpyridine, substituted 2,6-diformylpyridine, substituted 2,5-dicarbonylfuran, substituted 2,5-diformylfuran; substituted 2,5-dicarbonyl thiophene, and substituted 2,5-diformylthiophene. Coordination complexes thus formed are kinetically stable in dilute aqueous solution. They are further reacted, or coupled, through a substituent on the 1,2-diaminoethane or on the pyridine, furan, or thiophene moieties, to one of the following: proteinaceous materials, polysaccharides, other biologically compatible macromolecules or bridging molecules which, can be further reacted or coupled to the above mentioned substrates. These macrocyclic complexes are suitable in the preparation of reporter molecules and for magnetic resonance, radiation imaging and radiation therapy.

Specified classes and subclasses of leukocyte blood cells are identified by immunohematology procedures, based on utilization of antigenic determinants on the cell surface, their reactivity with antibodies which fluoresce under known circumstances, and identified by utilization of principles of flow cytometry or morphology. This invention particularly concerns improvements in the lysing and fixing method used prior to detection and identifying of the cells. In this method, a whole blood sample first is incubated with a reagent including antibodies to the cell subclass to be identified, the antibodies having directly or indirectly made fluorescently responsive to a particular light (e.g. argon ion laser). The red blood cells then are lysed with a reagent containing saponin. Next follows a leukocyte fixing treatment, preferably using a cross-linking dialdehyde composition, such as glyoxal or glutaraldehyde. Details are given as to time, temperature, concentration, and the use of additives and stains, as well as the use of particular monoclonal antibodies in the preferred procedure.

Reagent system and method for identification, enumeration and

Disclosed is an optical flow system wherein individual particles, which are sequentially suspended in a fluid flow, are irradiated at a detection zone with an excitation source to generate radiation signals, which in turn are dispersed by a concave reflection grating for subsequent detection and measurement. The radiation signals which are not dispersed from the grating but are reflected from the grating, are further reflected by a conjugate mirror to form a projected image of the detection zone suitable for viewing with a screen or eyepiece.

Monitoring of a detection zone utilizing zero order radiation from a

Disclosed is an electro-optical transducer for simultaneously making optical measurements and electrical volume measurements on particles suspended in a flow stream passing through an orifice positioned inside an optically clear spherical element.

Orifice inside optical element

An improved particle sensing transducer apparatus and method for studying the physical properties of particles suspended in an electrolyte solution. The transducer apparatus includes a first chamber, at least a portion of which contains a quantity of the electrolyte solution with a first electrode disposed therein. A second chamber is provided, at least a portion of which contains a quantity of the electrolyte solution with a second electrode disposed therein. The transducer further includes an orifice for establishing a constricted electrical path by providing a passageway for a sample flow of electrolyte solution containing the particles between the two chambers. The improvement comprises a fluid retarding, ion conducting material, such as a gel, frit or membrane, interposed between the sample flow and at least one of the electrodes so as to pass an ionic current while retarding the electrolyte flow from the electrode.

Use of fluid retarding ion conducting material

Disclosed is a centrifugal cytology swinging bucket for providing multiple dispersions of fixed cells or other particles onto a microscope slide or similar substrate, the bucket comprising a slide holder for receiving a slide and a transparent sample block having a sample chamber with drill holes for fluid communication between fixative cups, such fixative cups having porous frits therein. The bucket further comprises a pair of holddowns each having an eccentric cam and a lever protruding therefrom.

Growing community of inventors

San Diego, CA, United States of America

Robert Cary Leif