Hematology systems and methods
Inventors
Wanders, Bart J. • Farrell, Gregory A. • Adams, Thomas H. • Groner, Warren • Zhao, Xiaodong • Jordan, Brett • Cremins, Jack • Quon, Carol
Assignees
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Publication Number
US-10060846-B2
Publication Date
2018-08-28
Expiration Date
Abstract
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.
Core Innovation
The invention provides a method for imaging particles in a blood fluid sample using a particle analysis system configured for combined viscosity and geometric hydrofocusing. A sheath fluid having a viscosity different from the viscosity of the blood fluid sample is injected along a flowpath of a flowcell, and the blood fluid sample is injected from a sample fluid injection tube into the flowing sheath fluid so that the sample fluid stream decreases in thickness toward an image capture site.
The flowpath includes a decrease in flowpath size defined by a proximal flowpath transition zone portion having a proximal thickness and a distal flowpath transition zone portion having a distal thickness less than the proximal thickness. The viscosity difference between the sheath and blood fluid samples, in combination with the decrease in flowpath size and the flow rate of the sample, is effective to deliver cells from the injection tube to the image capture site in a nonzero transit time that is four seconds or less.
The description further emphasizes particle and intracellular organelle alignment liquid and a particle and intracellular organelle alignment liquid, with a "Wright-like" particle contrast agent for staining. It also describes image-based particle, nuclear, and granular morphological information, including nucleated red blood cells, for automated differential workflows, and improved morphology and distinguishability for automated WBC differentials.
Claims Coverage
The provided independent claim content centers on combined viscosity and geometric hydrofocusing in a narrowing flowcell, with three inventive features tied to sheath/blood viscosity difference, proximal and distal flowpath transition zones, and a nonzero transit time deliverability condition of four seconds or less.
Combined viscosity and geometric hydrofocusing in a flowcell
Imaging particles in a blood fluid sample using a particle analysis system configured for combined viscosity and geometric hydrofocusing by injecting a sheath fluid along a flowpath of a flowcell and injecting the blood fluid sample from a sample fluid injection tube into the flowing sheath fluid.
Proximal and distal flowpath transition zones defining thickness reduction
Defining a decrease in flowpath size by a proximal flowpath transition zone portion having a proximal thickness and a distal flowpath transition zone portion having a distal thickness less than the proximal thickness, so that the sample fluid stream decreases in thickness toward an image capture site.
Nonzero transit time deliverability condition (four seconds or less)
Using a sheath fluid having a viscosity different from the viscosity of the blood fluid sample, where the viscosity difference, together with the decrease in flowpath size and the flow rate of the sample, is effective to deliver cells from the sample fluid injection tube to the image capture site in a nonzero transit time that is four seconds or less.
The claim coverage is directed to co-flow of differently viscous sheath and blood fluids through a flowcell with narrowing transition zones that compress the sample stream thickness, while meeting a nonzero transit time deliverability condition of four seconds or less before imaging at the image capture site.
Stated Advantages
Delivers cells to the image capture site in a nonzero transit time that is four seconds or less.
Enables in-focus imaging using particle and intracellular organelle alignment liquid without lysing or shredding cells.
Improves morphology and distinguishability of cellular components for automated WBC differentials while reducing manual review.
Documented Applications
Imaging particles in a blood fluid sample using a particle analysis system with a flowcell and image capture site.
Automated differential workflows using image-based blood cell categorization including particle, nuclear, and granular morphological information, including nucleated red blood cells.
Differential counting and image analysis for blood-cell populations, including white blood cells and alignment of intracellular organelles.
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