Flowcell systems and methods for particle analysis in blood samples
Inventors
Wanders, Bart J. • Adams, Thomas H. • Farrell, Gregory A. • Groner, Warren • Zhao, Xiaodong
Assignees
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Publication Number
US-10345217-B2
Publication Date
2019-07-09
Expiration Date
Abstract
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.
Core Innovation
The described invention provides a method for imaging particles included within a body fluid sample using a particle analysis system configured for combined viscosity and geometric hydrofocusing. A sheath fluid is injected along a flowpath of a flowcell, where the sheath fluid has a viscosity different from the viscosity of the body fluid sample, and the body fluid sample is injected from a sample fluid injection tube into the flowing sheath fluid to provide a sample fluid stream.
The flowcell flowpath is configured with a decrease in flowpath size such that the thickness of the sample fluid stream decreases from an initial thickness to a second thickness adjacent an image capture site. The decrease in flowpath size is defined by a proximal flowpath portion having a proximal thickness and a distal flowpath portion having a distal thickness less than the proximal thickness, with the downstream end of the sample fluid injection tube positioned distal to the proximal flowpath portion.
To improve imaging quality, the method limits cell imaging orientation misalignment in the body fluid sample to less than about 20% using symmetry in the decrease in flowpath size. The body fluid sample is defined to include serum, bone marrow aspirate, lavage fluid, effusions, exudates, cerebrospinal fluid, pleural fluid, peritoneal fluid, amniotic fluid, saliva, a seminal fluid, tears, sweat, milk, a cell suspension produced from a biopsy sample or a fecal sample, or a cell culture sample.
Claims Coverage
The provided claim content centers on imaging particles by injecting a viscosity-different sheath fluid and thinning a sample stream along a flowcell to an image capture site via a geometrically decreasing flowpath, while limiting cell imaging orientation misalignment to less than about 20% using symmetry. Dependent claim refinements further constrain stream thickness and thinning ratios, specify sheath-to-sample flow-rate ratio, define viable-cell transit timing to four seconds or less, and require imaging with a high optical resolution imaging device having optical resolution of 1 μm or lower.
Combined viscosity and geometric hydrofocusing imaging system method
A method for imaging particles using a particle analysis system configured for combined viscosity and geometric hydrofocusing, the particles included within a body fluid sample, the method comprising injecting a sheath fluid along a flowpath of a flowcell, the sheath fluid having a viscosity different from the viscosity of the body fluid sample.
Sample stream thinning using decrease in flowpath size
Injecting the body fluid sample from a sample fluid injection tube at a flow rate into the flowing sheath fluid within the flowcell so as to provide a sample fluid stream having a first thickness adjacent the injection tube, the flowpath of the flowcell having a decrease in flowpath size such that thickness of the sample fluid stream decreases from an initial thickness to a second thickness adjacent an image capture site.
Orientation misalignment limited by symmetry in flowpath decrease
Limiting cell imaging orientation misalignment in the body fluid sample to less than about 20% using symmetry in the decrease in flowpath size.
Proximal and distal flowpath thickness definition with injection-tube positioning
The decrease in flowpath size is defined by a proximal flowpath portion having a proximal thickness and a distal flowpath portion having a distal thickness less than the proximal thickness, and a downstream end of the sample fluid injection tube is positioned distal to the proximal flowpath portion.
Body fluid sample types for particle imaging
The body fluid sample comprises serum, bone marrow aspirate, lavage fluid, effusions, exudates, cerebrospinal fluid, pleural fluid, peritoneal fluid, amniotic fluid, saliva, a seminal fluid, tears, sweat, milk, a cell suspension produced from a biopsy sample or a fecal sample, or a cell culture sample.
The claim coverage is focused on combined viscosity and geometric hydrofocusing, sample stream thinning through a decreasing flowpath, and limitation of cell imaging orientation misalignment to less than about 20% using symmetry, with additional dependent claim constraints on thickness, flow-rate ratio, viable-cell transit timing, and imaging resolution.
Stated Advantages
Higher-quality imaging by improving cell imaging orientation alignment to less than about 20% misalignment.
Documented Applications
No documented applications found
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