Dynamic range extension systems and methods for particle analysis in blood samples
Inventors
Adams, Thomas H. • Wanders, Bart J. • Roche, John • Kasdan, Harvey L.
Assignees
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Publication Number
US-11946848-B2
Publication Date
2024-04-02
Expiration Date
Abstract
For analyzing a sample containing particles of at least two categories, such as a sample containing blood cells, a particle counter subject to a detection limit is coupled with an analyzer capable of discerning particle number ratios, such as a visual analyzer, and a processor. A first category of particles can be present beyond detection range limits while a second category of particles is present within respective detection range limits. The concentration of the second category of particles is determined by the particle counter. A ratio of counts of the first category to the second category is determined on the analyzer. The concentration of particles in the first category is calculated on the processor based on the ratio and the count or concentration of particles in the second category.
Core Innovation
The disclosed invention addresses measuring a cell count of a first cell type in a blood fluid sample that includes a second cell type. A method is provided in which a first volume of the sample is flowed through a hematology cell counter to determine a population of the second cell type. Images are then acquired of a first number of the first cell type and a second number of the second cell type within an imaging region of a flowcell, using an image capture device.
The invention calculates the cell count of the first cell type using the first number, the second number, and the population of the second cell type. The first cell type is different than the second cell type, enabling the analysis to rely on both counter-derived information for the second cell type population and image-based counts for the first and second cell types. A processor performs the calculation based on these inputs.
The disclosure also addresses dynamic/detection range extension and correction of misclassification when multiple particle species share a channel due to overlapping size and/or morphology. The disclosed approach uses ratio estimation based on image-derived counts/proportions together with a second-category population determined by the hematology cell counter, including examples of extending WBC upper detection limits and PLT lower detection limits.
Claims Coverage
Two independent claims are present (a method claim and a system claim). Both claims implement a multi-instrument approach that combines a hematology cell counter population for a second cell type with imaging-derived first and second numbers, and then uses those values to calculate a first cell type count.
Combining hematology cell counter population with image-derived first and second numbers
Flow a first volume of the sample through a hematology cell counter to determine a population of the second cell type; inject a second volume of the sample into a sheath fluid flowing within a flowcell, and acquire images of a first number of the first cell type and a second number of the second cell type; and use the first number, the second number, and the population of the second cell type to calculate a cell count of the first cell type, wherein the first cell type is different than the second cell type.
System architecture for counter-and-imaging based cell count calculation
Provide a system comprising a hematology cell counter, a flowcell configured to facilitate flow of a sample stream, an imaging apparatus configured to acquire images at an imaging region of the flowcell for a first number of the first cell type and a second number of the second cell type, and a processor coupled to the hematology cell counter and the imaging apparatus; use a tangible non-transitory computer readable medium storing a computer application that causes the processor to use the first number, the second number, and the population of the second cell type to calculate a cell count of the first cell type, wherein the first cell type is different than the second cell type.
Flow and sheath fluid flowcell imaging to acquire both cell types
Inject a second volume of the sample into a sheath fluid flowing within a flowcell, and use an image capture device to acquire images of a first number of the first cell type and a second number of the second cell type.
Processor calculation based on imaging counts and counter-derived population
Use the first number, the second number, and the population of the second cell type to calculate a cell count of the first cell type.
The independent claims define a method and a corresponding system that pair a hematology cell counter population for the second cell type with flowcell image capture of first and second numbers. Both claims require that the first and second cell types are different and that the first cell type count is computed using both image-derived numbers and the counter-determined second-cell-type population.
Stated Advantages
Processor-based calculation can be more accurate than determining the population of the first cell type by flowing the sample through a hematology cell counter.
Documented Applications
Measuring cell counts of different blood cell types in a blood fluid sample, including extending WBC upper detection limits and PLT lower detection limits.
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