Methods and systems for the detection and removal of pathogens from blood
Inventors
VAN BRUGGEN, Robin • Visser, Astrid Elisabeth
Assignees
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Publication Number
US-10994068-B2
Publication Date
2021-05-04
Expiration Date
Abstract
The invention relates to methods and systems for removal of pathogens from blood or blood products. The invention further relates to methods and systems for treatment and diagnosis of infection in the blood and/or sepsis in a patient in need thereof.
Core Innovation
The disclosed invention relates to removing and detecting pathogens in blood or a blood product comprising red blood cells by exploiting immune adherence clearance mediated by complement receptor 1 (CR1, CD35). The blood or blood product is separated into an RBC-rich component that is substantially free of white blood cells and platelets, and a second component that is substantially free of RBCs. Pathogens are bound to RBCs as opsonized or immune complexes, and RBC adhesion molecules become activated and are expressed on RBCs.
A first component comprising RBCs that have bound the pathogen is contacted with a leukocyte reduction filter or with a support selected from filters, microfibers, microparticles, beads, microspheres, arrays, glass slides, and microscope slides. The support comprises a non-specific RBC adhesion molecule binder that is polymer or a mixture of two or more polymers. The binder binds to adhesion molecules that become activated and are expressed on RBCs, thereby substantially depleting the first component of RBCs that have bound the pathogen.
The invention further provides system embodiments in which the separated and depleted components can be optionally combined and, in a patient context, returned to the patient. It also includes detection workflows based on capturing pathogen-bound RBCs on binder supports followed by pathogen detection, including cytometry and microscopy, and optional pathogen identification using PCR and MALDI-TOF MS.
Claims Coverage
The provided independent claims cover three main inventive method scopes: blood-product or blood methods with separation plus binder-supported depleting of pathogen-bound RBCs, a patient method that withdraws blood and returns the depleted components, and a blood-product method that contacts a substantially WBC/platelet-free RBC product with a non-specific RBC adhesion molecule binder implemented as a leukocyte reduction filter or polymer(s). Across the independent claims, the key inventive elements include RBC/WBC/platelet component separation and the use of a non-specific RBC adhesion molecule binder to substantially deplete RBCs that have bound a pathogen.
RBC/WBC/platelet component separation with pathogen-bound RBC targeting
A method for the removal of a pathogen selected from the group consisting of a bacterium, a virus, and a fungus from blood or a blood product comprising red blood cells, comprising separating said blood or blood product into at least two components, a first component comprising red blood cells (RBCs) and substantially free of white blood cells (WBCs) and platelets, and a second component comprising WBCs and platelets and substantially free of RBCs.
Non-specific RBC adhesion molecule binder on a leukocyte reduction filter or support
A method wherein contacting said first component with a leukocyte reduction filter or with a support selected from the group consisting of a filter, microfibers, microparticles, beads, microspheres, an array, glass slides and microscope slides, said support comprising a non-specific RBC adhesion molecule binder to substantially deplete the first component of RBCs that have bound the pathogen, wherein said non-specific RBC adhesion molecule binder is a polymer or a mixture of two or more polymers that binds to adhesion molecules that become activated and are expressed on RBCs.
Optionally combining depleted RBC component with WBC/platelet component
Optionally combining said first component that is substantially depleted of RBCs that have bound the pathogen and said second component.
Withdrawing blood from a patient and returning depleted components
A method for the removal of a pathogen selected from the group consisting of a bacterium, a virus and a fungus from blood of a patient in need thereof comprising withdrawing the blood from said patient; separating said blood into at least two blood components; contacting said first component with leukocyte reduction filter or with a support comprising a non-specific RBC adhesion molecule binder to substantially deplete the first component of RBCs that have bound the pathogen; optionally combining said first component that is substantially depleted of RBCs that have bound the pathogen and said second component; and returning said first component that is substantially depleted of RBCs that have bound the pathogen and said second component to said patient.
Continuous withdrawing and continuous return for patient treatment
A method wherein blood is continuously withdrawn from a patient and the first and second components are continuously returned to the patient.
Contacting a substantially WBC/platelet-free RBC blood product with binder
A method for the removal of a pathogen selected from the group consisting of a bacterium, a virus, and a fungus from a blood product comprising red blood cells, wherein the blood product is substantially free of white blood cells and platelets, comprising contacting said blood product with a non-specific RBC adhesion molecule binder, wherein said non-specific RBC adhesion molecule binder comprises a leukocyte reduction filter or a polymer or a mixture of two or more polymers that binds to adhesion molecules that become activated and are expressed on RBCs.
Binder as leukocyte reduction filter and/or polymer-coated presentation
A method further including coating a polymer or a mixture of two or more polymers on beads.
Across the independent claims, the coverage centers on removing bacterium, virus, or fungus pathogens from RBC-containing blood or blood products by separating RBCs from WBCs and platelets and contacting the RBC component with a non-specific RBC adhesion molecule binder. The binder is implemented using a leukocyte reduction filter or polymer that binds to adhesion molecules activated and expressed on RBCs to substantially deplete RBCs that have bound the pathogen, with patient-scoped embodiments including withdrawal and return of the depleted components.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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