Iris International, Inc.

Bayer Corporation

Technicon Instruments Corporation

Siemens Medical Solutions Diagnostics

Gregory A Farrell

Bart Jan Wanders

Thomas H Adams

Warren Groner

Xiaodong Zhao

Brett LeBeau Jordan

Bruce E Behringer

James A Mawhirt

John F Cremins

Jack Cremins

Carol Quon

Edward Adam Epstein

Abraham Gordon

Kent M Negersmith

Joseph Carlucci

Kevin J Hanmann

Peter Schmitz

Joseph Raneri

John W Nelson

Particles such as blood cells can be categorized and counted by a digital image processor. A digital microscope camera can be directed into a flowcell defining a symmetrically narrowing flowpath in which the sample stream flows in a ribbon flattened by flow and viscosity parameters between layers of sheath fluid. A contrast pattern for autofocusing is provided on the flowcell, for example at an edge of a rear illumination opening. The image processor assesses focus accuracy from pixel data contrast. A positioning motor moves the microscope and/or flowcell along the optical axis for autofocusing on the contrast pattern target. The processor then displaces microscope and flowcell by a known distance between the contrast pattern and the sample stream, thus focusing on the sample stream. Blood cell images are collected from that position until autofocus is reinitiated, periodically, by input signal, or when detecting temperature changes or focus inaccuracy in the image data.

Autofocus systems and methods for particle analysis in blood samples

Aspects and embodiments of the instant disclosure provide a particle and/or intracellular organelle alignment agent for a particle analyzer used to analyze particles contained in a sample. An exemplary particle and/or intracellular organelle alignment agent includes an aqueous solution, a viscosity modifier, and/or a buffer.

Sheath fluid systems and methods for particle analysis in blood samples

The present disclosure relates to apparatus, systems, compositions, and methods for analyzing a sample containing particles. In some aspects the system comprises an analyzer which may be a visual analyzer. In one aspect, this disclosure relates to a particle imaging system comprising a flowcell through which a sample containing particles is caused to flow, and a high optical resolution imaging device which captures images for image analysis of samples. Other compositions, methods and features of this disclosure are disclosed herein.

Flowcell systems and methods for particle analysis in blood samples

Aspects and embodiments of the instant disclosure provide a particle and/or intracellular organelle alignment agent for a particle analyzer used to analyze particles contained in a sample. An exemplary particle and/or intracellular organelle alignment agent includes an aqueous solution, a viscosity modifier, and/or a buffer. Embodiments also encompass systems, compositions, and methods for analyzing a sample containing particles. Parrticles such as blood cells can be categorized and counted by a digital image processor. A digital microscope camera can be directed, for example using certain focusing techniques, into a flowcell defining a symmetrically narrowing flowpath in which the sample stream flows in a ribbon flattened by flow and viscosity parameters between layers of sheath fluid. Blood cell images can be collected and analyzed using dynamic range extension processes and systems.

Hematology systems and methods

Aspects and embodiments of the instant disclosure provide a particle and/or intracellular organelle alignment agent for a particle analyzer used to analyze particles contained in a sample. An exemplary particle and/or intracellular organelle alignment agent includes an aqueous solution, a viscosity modifier, and/or a buffer. Embodiments also encompass systems, compositions, and methods for analyzing a sample containing particles. Particles such as blood cells can be categorized and counted by a digital image processor. A digital microscope camera can be directed, for example using certain focusing techniques, into a flowcell defining a symmetrically narrowing flowpath in which the sample stream flows in a ribbon flattened by flow and viscosity parameters between layers of sheath fluid. Blood cell images can be collected and analyzed using dynamic range extension processes and systems.

A variable rate particle counter for adjusting the volumetric delivery rate of fluid to a flow cell based upon an initial particle count rate in order to effectively 'tune' the final dilution of sample sheath flow to the particle concentration of the sample. A sheath fluid syringe pump and a test sample syringe pump are driven by motors which are adjusted by a data analyzer. The data analyzer compares a particle count rate measured by a detection assembly to a predetermined reference value and determines if the count rate is too high or to low. Accordingly, one of several pump profiles is initiated to adjust the flow rate of the sheath fluid or test sample or both. Advantageously, the low cell count precision is improved and the upper limit cell count is expanded.

Variable rate particle counter and method of use

A reagent pump assembly for metering precise volumes of fluids, such as reagent, for an analytical instrument, such as a clinical hematology or flow cytometer instrument. The assembly includes a multilayer block having a plurality of diaphragm pumps interposed between two of the layers, controlled by application of one of vacuum or pressure, in sequence, to fill the reservoirs and expel the contents of the pump. One-way check valves are used to control the fluid flow from the reservoirs of fluids to the fluid outlet ports. The fluid outlet ports may be directly coupled to fluid inlet ports of a compatible unified flow circuit, which contains reaction chambers and a plurality of sample aliquots. Thus, the reagent pump assembly can be used to combine and mix a sample aliquots with a precise amount of reagent in a reaction chamber, preparatory for analyzing the reaction mixture.

Reagent pump assembly

A unified fluid cell circuit assembly for an analytical instrument, such as a clinical hematology, immunoassy or chemistry or a flow cytometry instrument. The assembly includes a unified fluid circuit, a shear valve, a fluid pump assembly, and a plurality of solenoid valves. The unified fluid circuit is made of a plurality of acrylic plates which have formed in the various plate surfaces chamber cavities, pneumatic, hydraulic and vent line, and valve cavities. The plates, when secured together, form a plurality of reaction chambers, a plurality of control valves and various lines as a network for controlling the flow and mixing of aliquots of a sample and fluids (rinse, reagents, etc.) to perform the reactions for analyzing the sample. The fluid pump assembly is connected to the unified flow circuit and has a plurality of diaphragm pumps which pump precise volumes of fluids. The solenoid valves provide the pressure and vacuum to operate the pumps and to provide a sample into the shear valve to form sample aliquots, and to mix the various aliquots with the reagents and diluents to form the reaction mixtures.

Unified fluid circuit assembly for a clinical hematology instrument

A method and apparatus for selecting a subset of a predetermined number of test sample aliquots to mix with respective reagents using a shear valve having a maximum predetermined number of aliquot loops in an analytical instrument, including without limitation a clinical hematology or a flow cytometer instrument. Each aliquot loop can be filled with a test sample aliquot. Selected ones of the aliquot loops can be filled with a rinse solution and, using bypass passages and valves, closed off from the rinse source and a vacuum source used to empty the rinse from the non-closed off aliquot loops. The vacuum source also is used to fill the non-closed off aliquot loops with the sample to be aliquotted, so that the closed off aliquot loop remains filled with rinse. The shear valve can then be shifted to a second position, where the reagents for the non-closed off aliquot loops are pumped through those aliquot loops to mix the selected sample aliquot loops with their respective reagents. Preferably, the reagent for the closed-off aliquot loop is not pumped and thereby conserved. The selective shear valve is usable in an analytical instrument, such as a clinical hematology instrument where it is possible to select from a standard panel of tests a particular one test or a particular combination of tests to perform. It is particularly useful when it is frequently desirable to perform only some of the full panel of tests, e.g., three or four of five standard blood chemistry tests, rather than always performing the full panel of tests.

Apparatus and methods for selecting a variable number of test sample

A valve comprises a first rigid layer having a substantially planar first surface, a second rigid layer having a substantially planar second surface facing the first surface and a substantially planar third surface opposite the second surface and a flexible layer positioned between the first and second surfaces. A valve chamber is demarcated by a concave surface in the substantially planar first surface and one surface of the flexible layer and at least one first fluid passageway in the first rigid layer opens into the valve chamber at the concave surface to alternatively apply a vacuum and pressure thereto. A fluid chamber is demarcated by another surface of the flexible layer and a concave-convex surface in the substantially planar second surface which comprises an inner circular convex portion and a concentric annular outer concave portion. At least two second fluid passageways in the second rigid layer open into the valve chamber at the convex surface. When a vacuum is applied to the valve chamber, the flexible layer flexes to space the other surface of the flexible layer apart from the concave-convex surface to permit communication between the at least two second fluid passageways and when a pressure is applied to the valve chamber, the flexible layer flexes to dispose the other surface of the flexible layer on the concave-convex surface to prevent communication between the at least two second fluid passageways.

Growing community of inventors

Ridgewood, NJ, United States of America

Gregory A Farrell