Abstract: 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.

Abstract: 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.

Abstract: A method of using elongate multicellular organisms in conjunction with a specialized flow cytometer for drug discovery and compound screening. A stable, optically detectable linear marker pattern on each organism is used to construct a longitudinal map of each organism as it passes through the analysis region of the flow cytometer. This pattern is used to limit complex data analysis to particular regions of each organism thereby simplifying and speeding analysis. The longitudinal marker pattern can be used to alter signal detection modes at known regions of the organism to enhance sensitivity and overall detection effectiveness. A repeating pattern can also be used to add a synchronous element to data analysis. The marker patterns are established using known methods of molecular biology to express various indicator molecules. Inherent features of the organism can be rendered detectable to serve as marker patterns.

Abstract: The present invention is a flow cytometry-based hematology system useful in the analysis of biological samples, particularly whole blood or blood-derived samples. The system is capable of determining at least a complete blood count (CBC), a five-part white blood cell differential, and a reticulocyte count from a whole blood sample. The system preferably uses a laser diode that emits a thin beam to illuminate cells in a flow cell and a lensless optical detection system to measure one or more of axial light loss, low-angle forward scattered light, high-angle forward scattered light, right angle scattered light, and time-of-flight measurements produced by the cells. The lensless optical detection system contains no optical components, other than photoreactive elements, and does not include any moving parts. Finally, the system uses a unique system of consumable reagent tubes that act as reaction chambers, mixing chambers, and waste chambers for the blood sample analyses.

Abstract: This invention relates to the field of biological assays where cells can be classified and enumerated using flow cytometry optical instrumentation. The invention combines information from multi-angle, light scatter from the cell itself and multi-angle light scatter from small, optically resonant particles that are selectively bound to surface molecules on the cell to carry out classification and enumeration. This light scatter method enables an instrumentation system that is simple to use, inexpensive to build, and mechanically robust; making it suitable for use in remote clinical environments.

Abstract: The present invention is a flow cytometry-based hematology system useful in the analysis of biological samples, particularly whole blood or blood-derived samples. The system is capable of determining at least a complete blood count (CBC), a five-part white blood cell differential, and a reticulocyte count from a whole blood sample. The system preferably uses a laser diode that emits a thin beam to illuminate cells in a flow cell and a lensless optical detection system to measure one or more of axial light loss, low-angle forward scattered light, high-angle forward scattered light, right angle scattered light, and time-of-flight measurements produced by the cells. The lensless optical detection system contains no optical components, other than photoreactive elements, and does not include any moving parts. Finally, the system uses a unique system of consumable reagent tubes that act as reaction chambers, mixing chambers, and waste chambers for the blood sample analyses.

Abstract: An instrument for analyzing and dispensing objects larger than about 70 &mgr;m in diameter is based on a flow cytometer with a novel fluidic switch arrangement for diverting a portion of a sample stream in response to detector signals in a flow cell. The instrument is particularly adapted for dispensing multicellular test organisms like nematodes or large microspheres for use in screening large libraries of potential pharmaceutical agents. Hydrodynamic focussing is used to center and align the objects in the flow cell. The objects pass through a sensing zone where optical or other characteristics of the objects are detected. The detector signals are processed and used to operate a fluidic switch that is located downstream from the sensing zone. The fluid stream containing the detected objects emerges from the flow cell into air where a fluid stream controlled by the fluidic switch diverts portions of the stream containing no sample objects or sample objects not meeting predetermined characteristics.

Abstract: The high numerical aperture flow cytometer of the present invention includes a flow cell and a laser input. The laser input emits a beam of light that is oriented substantially orthogonally to the flow of blood cells through the flow cell such that laser light impinges upon the blood cells as they pass through the flow cell. A portion of the beam from the laser input that impinges upon the blood cells in the flow cell is scattered at a substantially right angle to the beam of laser input (“right angle scatter”). A second portion of the beam from the laser input that impinges upon the cells in the flow cell is scattered at a much lower angle than 90°.

Abstract: A method of using elongate multicellular organisms in conjunction with a specialized flow cytometer for drug discovery and compound screening. A stable, optically detectable linear marker pattern on each organism is used to construct a longitudinal map of each organism as it passes through the analysis region of the flow cytometer. This pattern is used to limit complex data analysis to particular regions of each organism thereby simplifying and speeding analysis. The longitudinal marker pattern can be used to alter signal detection modes at known regions of the organism to enhance sensitivity and overall detection effectiveness. A repeating pattern can also be used to add a synchronous element to data analysis. The marker patterns are established using known methods of molecular biology to express various indicator molecules. Inherent features of the organism can be rendered detectable to serve as marker patterns.

Abstract: The present invention is a flow cytometry-based hematology system useful in the analysis of biological samples, particularly whole blood or blood-derived samples. The system is capable of determining at least a complete blood count (CBC), a five-part white blood cell differential, and a reticulocyte count from a whole blood sample. The system preferably uses a laser diode that emits a thin beam to illuminate cells in a flow cell and a lensless optical detection system to measure one or more of axial light loss, low-angle forward scattered light, high-angle forward scattered light, right angle scattered light, and time-of-flight measurements produced by the cells. The lensless optical detection system contains no optical components, other than photoreactive elements, and does not include any moving parts. Finally, the system uses a unique system of consumable reagent tubes that act as reaction chambers, mixing chambers, and waste chambers for the blood sample analyses.

Abstract: A device and a method enable the rapid, quantitative evaluation of a large collection of ligands for binding affinity with a certain immobilized receptor, the improvements being that binding pan be detected without the need for a label and that binding is carried out in solution phase at a high rate. The instrument has at least two embodiments, one is based on a sensitive absorption photometer and the other on a sensitive light scatter photometer operating at a specific resonance wavelength, &lgr;R, of small, metallic, colloidal particles. The resonance is present in small particles having a complex refractive index with real part n(&lgr;) approaching 0 and imaginary part k(&lgr;) approaching {square root}2 simultaneously at a specific wavelength &lgr;R. The particles are substantially spherical and substantially smaller than &lgr;R. The receptor is immobilized on a suspension of such particles and ligand binding is detected by a change in optical absorption or light scatter at the resonance wavelength.

Abstract: A method of using elongate multicellular organisms in conjunction with a specialized flow cytometer for drug discovery and compound screening. A stable, optically detectable linear marker pattern on each organism is used to construct a longitudinal map of each organism as it passes through the analysis region of the flow cytometer. This pattern is used to limit complex data analysis to particular regions of each organism thereby simplifying and speeding analysis. The longitudinal marker pattern can be used to alter signal detection modes at known regions of the organism to enhance sensitivity and overall detection effectiveness. A repeating pattern can also be used to add a synchronous element to data analysis. The marker patterns are established using known methods of molecular biology to express various indicator molecules. Inherent features of the organism can be rendered detectable to serve as marker patterns.

Abstract: The high numerical aperture flow cytometer of the present invention includes a flow cell and a laser input. The laser input emits a beam of light that is oriented substantially orthogonally to the flow of blood cells through the flow cell such that laser light impinges upon the blood cells as they pass through the flow cell. A portion of the beam from the laser input that impinges upon the blood cells in the flow cell is scattered at a substantially right angle to the beam of laser input (“right angle scatter”). A second portion of the beam from the laser input that impinges upon the cells in the flow cell is scattered at a much lower angle than 90°.

Abstract: A device and a method enable the rapid, quantitative evaluation of a large collection of ligands for binding affinity with a certain immobilized receptor, the improvements being that binding pan be detected without the need for a label and that binding is carried out in solution phase at a high rate. The instrument has at least two embodiments, one is based on a sensitive absorption photometer and the other on a sensitive light scatter photometer operating at a specific resonance wavelength, &lgr;R, of small, metallic, colloidal particles. The resonance is present in small particles having a complex refractive index with real part n(&lgr;) approaching 0 and imaginary part k(&lgr;) approaching 2 simultaneously at a specific wavelength &lgr;R. The particles are substantially spherical and substantially smaller than &lgr;R. The receptor is immobilized on a suspension of such particles and ligand binding is detected by a change in optical absorption or light scatter at the resonance wavelength.

Abstract: An instrument for analyzing and dispensing objects larger than about 70 &mgr;m in diameter is based on a flow cytometer with a novel fluidic switch arrangement for diverting a portion of a sample stream in response to detector signals in a flow cell. The instrument is particularly adapted for dispensing multicellular test organisms like nematodes or large microspheres for use in screening large libraries of potential pharmaceutical agents. Hydrodynamic focussing is used to center and align the objects in the flow cell. The objects pass through a sensing zone where optical or other characteristics of the objects are detected. The detector signals are processed and used to operate a fluidic switch that is located downstream from the sensing zone. The fluid stream containing the detected objects emerges from the flow cell into air where a fluid stream controlled by the fluidic switch diverts portions of the stream containing no sample objects or sample objects not meeting predetermined characteristics.

Abstract: An instrument for analyzing and dispensing objects larger than about 70 &mgr;m in diameter is based on a flow cytometer with a novel fluidic switch arrangement for diverting a portion of a sample stream in response to detector signals in a flow cell. The instrument is particularly adapted for dispensing multicellular test organisms like nematodes or large microspheres for use in screening large libraries of potential pharmaceutical agents. Hydrodynamic focussing is used to center and align the objects in the flow cell. The objects pass through a sensing zone where optical or other characteristics of the objects are detected. The detector signals are processed and used to operate a fluidic switch that is located downstream from the sensing zone. The fluid stream containing the detected objects emerges from the flow cell into air where a fluid stream controlled by the fluidic switch diverts portions of the stream containing no sample objects or sample objects not meeting predetermined characteristics.

Abstract: An improved instrument that consists of an optical analyzer and a fluid switch using light scatter and fluorescence means to optically identify and activate fluidic sorting of multicellular organisms from live populations of organisms such as various life cycle stages of Caenorhabditis elegans, the larval stages of Drosophila melanogaster, and the embryonic stages of Danio rero. In the case where fluorescence from these organisms is very weak, comparatively high levels of electronic noise accompany the electronic signals that are generated by the fluorescence detector and its associated circuitry. Because these weak signals cannot be used to mark the presence of an organism, another, less noisy, signal must be used to gate fluorescence detection. A gate derived from the low-noise light scatter signal from the organism collected over an acceptance angle of at least 20 degrees. Such a light scatter signal unambiguously gates even weak fluorescence signals.

Abstract: The high numerical aperture flow cytometer of the present invention includes a flow cell and a laser input. The laser input emits a beam of light that is oriented substantially orthoganilly to the flow of blood cells through the flow cell such that laser light impinges upon the blood cells as they pass through the flow cell. A portion of the beam from the laser input that impinges upon the blood cells in the flow cell is scattered at a substantially right angle to the beam of laser input (“right angle scatter”). A second portion of the beam from the laser input that impinges upon the cells in the flow cell is scattered at a much lower angle than 90°. This scatter is termed “low angle forward scatter light” and has an angle of from about 2° to about 5° from the orientation of the original beam from laser input. A right angle scatter light detector is oriented to receive the previously mentioned right angle scatter light.

Abstract: Disclosed are an optical flow particle apparatus and method for conducting a particle light scatter-based immunoassay for simultaneously measuring the presence or amount of one or more analytes in a fluid sample, which involves the steps of:

Abstract: Disclosed are an optical flow particle apparatus and method for conducting a particle light scatter-based immunoassay for simultaneously measuring the presence or amount of one or more analytes in a fluid sample which involves the use of a reagent set for each analyte including first binding molecule-coated monodisperse microspheres and second binding molecule-coated colloidal particles in which at least one of the first or second binding molecules specifically binds a respective one of the analytes. In the case where more than one analytes are detected, each monodisperse microperse microsphere of a particular reagent set has a light scatter signal resolvable from that of microspheres of any other reagent set. Changes determined in the distributions of the measured light scatter signals for individual microspheres of each of the particular reagent sets are indicative of the presence or amount of the respective analyte(s) in the sample.