Stable reference materials for automated hematology testing platforms
Inventors
Ebrahim, Alireza • Barry, James • DEVORE, KARL
Assignees
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Publication Number
US-12638462-B2
Publication Date
2026-05-26
Expiration Date
Abstract
This invention describes a method for preparation of stable hematology reference materials by producing synthetic hydrogel blood cell surrogates, which mimic human blood components in size, morphology, performance and functionality when analyzed using an automated hematology analyzer employing multiple detection technologies. Different hydrogel particles can be combined and mixed to prepare multi-parameter and multi-level hematology reference materials, which could be used for calibration, linearity verification, proficiency evaluation, and routine performance monitoring of modern automated hematology analyzers. These hydrogel particles can also be combined with processed and stabilized human blood components to prepare the reference materials of this invention.
Core Innovation
The invention relates to stable hematology reference materials (HRMs) comprising a suspension fluid and multiple fixed cellular components corresponding to different blood cell types. The HRM includes an RBC component comprising human erythrocytes fixed with a crosslinking agent, a platelet component comprising goat erythrocytes fixed with a crosslinking agent, a reticulocyte component comprising fixed human erythrocytes encapsulated with RNA, and a lymphocyte component comprising chicken erythrocytes fixed with a crosslinking agent.
The HRM also comprises monocyte, basophil, neutrophil, eosinophil, immature reticulocyte, immature granulocyte, and immature thrombocyte components, each made from fixed erythrocytes from specified non-human species with a crosslinking agent, with the reticulocyte and immature reticulocyte components additionally encapsulating fixed human erythrocytes with RNA. A nucleated red blood cell component comprises chicken erythrocytes fixed with a crosslinking agent, and each component exhibits a forward scatter profile or a side scatter profile at least 95% similar to its corresponding component in a human blood sample.
In additional embodiments, the HRM further includes hydrogel particles that are substantially similar to human red blood cells, human platelets, human reticulocytes, human lymphocytes, human monocytes, human basophils, human neutrophils, human eosinophils, immature human reticulocytes, immature human granulocytes, immature human thrombocytes, and nucleated human red blood cells, while the corresponding cellular components remain fixed with a crosslinking agent and the reticulocyte and immature reticulocyte components include RNA encapsulation. The suspension fluid is an isotonic neutral pH suspension fluid, and the document discusses tuning optical and light-scatter characteristics, including FSC/SSC and optional fluorescence/marker properties, to match target human cell types.
Claims Coverage
The independent claims are clm-00001 and clm-00018. Across these independent claims, the inventive coverage focuses on a multi-component HRM comprising fixed cell components and a suspension fluid, and a required minimum similarity of each component’s forward or side scatter profile to corresponding human blood cell components at least 95%.
Scatter-profile-matched multi-component fixed-cell HRM
A hematology reference material (HRM) comprising a suspension fluid and multiple fixed cellular components including an RBC component of human erythrocytes fixed with a crosslinking agent; a platelet component of goat erythrocytes fixed with a crosslinking agent; a reticulocyte component of fixed human erythrocytes encapsulated with RNA; and lymphocyte, monocyte, basophil, neutrophil, eosinophil, immature reticulocyte, immature granulocyte, immature thrombocyte, and nucleated red blood cell components of fixed erythrocytes from specified species, wherein each of said components exhibits a forward scatter profile or a side scatter profile that is at least 95% similar to its corresponding component in a human blood sample.
Scatter-profile-matched fixed-cell HRM with hydrogel-particle cell analogs
A hematology reference material (HRM) comprising a suspension fluid and multiple components where each blood-cell-type component comprises fixed erythrocytes with a crosslinking agent and RNA encapsulation for reticulocytes and immature reticulocytes, together with hydrogel particles substantially similar to the corresponding human blood cell type, wherein each of said components exhibits a forward scatter profile or a side scatter profile that is at least 95% similar to its corresponding component in a human blood sample.
Both independent claims define scatter-profile-matched HRMs made from multiple fixed cell components suspended in a fluid, with a required at-least-95% similarity of forward or side scatter profiles to corresponding human blood components. The second independent claim adds hydrogel particles substantially similar to human blood cell types alongside the fixed cellular components.
Stated Advantages
Provides stable hematology reference materials.
Enables calibration and monitoring on automated hematology analyzers via substantially similar optical and light-scatter characteristics to corresponding human blood components.
Supports blood-variable reference range use and, in embodiments, blood-typing control using hydrogel-presented blood group antigens.
Documented Applications
Calibration and linearity, proficiency, and routine monitoring on automated hematology analyzers using the HRM with matched scatter and optical properties.
Use as prophetic blood-typing control HRMs using hydrogel-presented blood group antigens (A, B with RhD or without).
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