Sheath fluid systems and methods for particle analysis in blood samples
Inventors
Farrell, Gregory A. • Wanders, Bart J. • Adams, Thomas H. • Groner, Warren • Zhao, Xiaodong
Assignees
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Publication Number
US-9470618-B2
Publication Date
2016-10-18
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.
Core Innovation
The invention relates to imaging a plurality of particles in a blood fluid sample by using a particle analysis system configured for combined viscosity and geometric hydrofocusing. A sheath fluid flows along a flowpath of a flowcell, where the sheath fluid viscosity differs from the sample fluid viscosity by a viscosity difference in a predetermined viscosity difference range, and the blood fluid sample is injected into the flowing sheath fluid so that a sample fluid stream is enveloped by the sheath fluid.
As the sample fluid stream and the sheath fluid flow through a reduction in flowpath size toward an imaging site, a viscosity hydrofocusing effect is induced by an interaction between the sheath fluid and the sample fluid stream associated with the viscosity difference. In combination, a geometric hydrofocusing effect is induced by an interaction between the sheath fluid and the sample fluid stream associated with the reduction in flowpath size, and this combined hydrofocusing is effective to provide a target imaging state in at least some of the plurality of particles at the imaging site.
The system further includes a viscosity agent in the sheath fluid that retains viability of cells in the sample fluid stream while the cells leave the sample fluid stream and extend into the flowing sheath fluid, leaving structure and content of the cells intact. The method images the plurality of particles at the imaging site, and the target imaging state is defined, in some embodiments, in terms of target particle orientation relative to a focal plane of an imaging device used to acquire images.
Claims Coverage
The independent claims are directed to two main inventive features: a method for imaging particles in a blood fluid sample using combined viscosity and geometric hydrofocusing with a viscosity agent that retains viability, and a corresponding imaging system with the same functional elements. The coverage centers on an interaction-based combined hydrofocusing approach, a flowpath size reduction toward an imaging site, a viscosity difference in a predetermined range, a viscosity agent preserving intact cell structure/content, and imaging at the imaging site.
Combined viscosity and geometric hydrofocusing with viscosity difference
Flowing a sheath fluid along a flowpath of a flowcell, the sheath fluid having a sheath fluid viscosity that differs from the sample fluid viscosity by a viscosity difference in a predetermined viscosity difference range; injecting the blood fluid sample into the flowing sheath fluid within the flowcell so as to provide a sample fluid stream enveloped by the sheath fluid; and flowing the sample fluid stream and the sheath fluid through a reduction in flowpath size toward an imaging site such that viscosity hydrofocusing, in combination with geometric hydrofocusing, provides a target imaging state in at least some of the plurality of particles at the imaging site.
Viscosity agent retaining viability while preserving cell structure and content
Providing a target imaging state while a viscosity agent in the sheath fluid retains viability of cells in the sample fluid stream, leaving structure and content of the cells intact when the cells extend from the sample fluid stream into the flowing sheath fluid.
Imaging plurality of particles at the imaging site
Imaging the plurality of particles at the imaging site.
System components implementing combined viscosity and geometric hydrofocusing
A flowcell having a flowpath and a sample fluid injection tube, the flowpath having a reduction in flowpath size; a sheath fluid input in fluid communication with the flowpath of the flowcell so as to transmit a flow of the sheath fluid along the flowpath of the flowcell; a blood fluid sample input in fluid communication with the injection tube of the flowcell so as to inject a flow of the blood fluid sample into the flowing sheath fluid within the flowcell; and an imaging device that images the plurality of particles at the imaging site.
Target imaging state defined by particle orientation relative to focal plane
A target imaging state in which the target imaging state is defined by the orientation of one or more target particles in the flow relative to the focal plane of an imaging device used to acquire images.
Orientation alignment requirement for non-spherical particles
A set of non-spherical particles that are aligned at least 90% within 20 degrees of a plane substantially parallel to the sample’s flow direction at the imaging site.
Across the independent claims, the invention is covered by a combined viscosity and geometric hydrofocusing framework using a predetermined viscosity difference and a reduction in flowpath size toward an imaging site, while a viscosity agent retains viability and preserves cell structure/content as cells extend into the sheath flow. Imaging is performed at the imaging site, and the target imaging state can be defined by particle orientation relative to the imaging device focal plane, including an alignment requirement for non-spherical particles.
Stated Advantages
Retains viability of cells while leaving structure and content of the cells intact when the cells extend from the sample fluid stream into the flowing sheath fluid.
Provides a target imaging state in at least some of the plurality of particles at the imaging site.
Documented Applications
Imaging a plurality of particles in a blood fluid sample for particle analysis using a particle analysis system and an imaging device at an imaging site.
Differential counting and morphological abnormality detection for white blood cell differentials, including neutrophils/lymphocytes/monocytes/eosinophils/basophils, and platelet analysis.
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