Processing blood

Abstract

Methods ( 300 ), devices, and systems of processing blood are described. The method ( 300 ) comprises the steps of: obtaining ( 312 ) blood from a patient coupled to a single blood processing device to form a closed loop between the patient and the blood processing device; collecting ( 314 ) bulk mononuclear blood cells from the blood by leukapheresis implemented using the blood processing device in the closed loop; and enriching ( 316 ) concurrently target cells separated from non-target cells in the bulk mononuclear blood cells using the blood processing device in the closed loop.

1 . An apparatus for processing blood, said apparatus comprising:
 an inlet interface for coupling with a patient to receive blood directly from the circulation of said patient;   a leukapheresis module coupled to said inlet interface for collecting bulk mononuclear blood cells from said received blood;   an enrichment module coupled to said leukapheresis module for enriching concurrently target cells separated from non-target cells in said bulk mononuclear blood cells;   a target-cell modification module adapted to provide modification selected from the group consisting of cytotoxic T lymphocyte (CTL) activation; T regulatory cell (Treq) activation and genetically modified blood cells protected from human immunodeficiency virus (HIV) coupled to at least one of said leukapheresis module and said enrichment module, said modification module modifying said enriched target cells;   an outlet interface coupled to at least one of said leukapheresis module and said enrichment module for coupling with said patient to return enriched target cells to the circulation of said patient, said apparatus and said patient forming a closed loop when coupled together; and   a controller for automated control of operation of said inlet and outlet interfaces, said leukapheresis module, and said enrichment module.   
     
     
         2 . The apparatus as claimed in  claim 1 , wherein said controller comprises:
 a memory for storing data and instructions for automated control of operation of said inlet and outlet interfaces, said leukapheresis module, and said enrichment module; and   a processor coupled to said memory capable of accessing said data and said instructions, said processor adapted to perform said instructions for automated control of operation of said inlet and outlet interfaces, said leukapheresis module, and said enrichment module.   
     
     
         3 . (canceled) 
     
     
         4 . The apparatus as claimed in  claim 1 , further comprising means for returning said modified target-cells to said patient. 
     
     
         5 . The apparatus as claimed in  claim 1 , further comprising a non-target-cell modification module coupled to at least one of said leukapheresis module and said enrichment module, said non-target-cell modification module modifying non-target cells. 
     
     
         6 . The apparatus as claimed in  claim 5 , further comprising means for returning said modified non-target-cells to said patient. 
     
     
         7 . The apparatus as claimed in  claim 1 , further comprising at least one pump for circulating at least a portion of said blood within said apparatus. 
     
     
         8 . The apparatus as claimed in  claim 7 , further comprising a pump and at least one valve coupled to said inlet interface for providing said blood to said leukapheresis module and another pump and at least one valve coupled to said outlet interface for returning blood from said apparatus. 
     
     
         9 . The apparatus as claimed in  claim 1 , wherein said leukapheresis module comprises a centrifuge bowl that uses differential centrifugation to collect said mononuclear blood cells. 
     
     
         10 . The apparatus as claimed in  claim 9 , wherein said differential centrifugation is conducted by a continuous flow system. 
     
     
         11 . A method of processing blood, said method comprising the steps of:
 obtaining blood from a patient coupled to a single blood processing device to form a closed loop between said patient and said blood processing device;   collecting bulk mononuclear blood cells from said blood by leukapheresis implemented using said blood processing device in said closed loop;   enriching concurrently target cells separated from non-target cells in said bulk mononuclear blood cells using said blood processing device in said closed loop and;   modifying said enriched target cells, wherein said modification is selected from the group consisting of cytotoxic T lymphocyte (CTL) activation; T regulatory cell (Treq) activation and genetically modified blood cells protected from human immunodeficiency virus (HIV) in said closed loop.   
     
     
         12 . The method as claimed in  claim 11 , further comprising the step of discarding said non-target cells. 
     
     
         13 . The method as claimed in  claim 11 , further comprising maintaining continuous connection of said patient in said closed loop during processing of said target cells. 
     
     
         14 . The method as claimed in  claim 11 , further comprising the step of disconnecting said patient from said closed loop for a time interval during processing of said target cells. 
     
     
         15 . The method as claimed in  claim 11 , further comprising the step of concurrently monitoring said collecting and enriching steps. 
     
     
         16 . The method as claimed in  claim 11 , wherein said collecting and enriching steps are performed in different sections of said blood processing device. 
     
     
         17 . The method as claimed in  claim 11 , wherein said collecting step comprises using differential centrifugation to collect said mononuclear blood cells and said enriching step comprises using ligand capture to enrich said target cells. 
     
     
         18 . The method as claimed in  claim 17 , wherein said differential centrifugation is conducted by a continuous flow system. 
     
     
         19 . The method as claimed in  claim 17 , wherein said ligand is an antibody specific for a cell surface ligand. 
     
     
         20 . The method as claimed in  claim 19 , wherein the cell surface ligand is selected from the group consisting of epithelial cell adhesion molecules (EpCAM), selectins, adhesion molecule receptors, homing receptors, cytokine receptors, chemokine receptors, and enzymes. 
     
     
         21 . The method as claimed in  claim 19 , wherein the cell surface ligand is a cluster designation (CD) antigen. 
     
     
         22 . The method as claimed in  claim 21 , wherein the CD antigen is selected from the group consisting of CD1a, CD4, CD8, CD14, CD25, CD34, CD133, and CD143. 
     
     
         23 . The method as claimed in  claim 11 , wherein said target cells are selected from the group consisting of B cells, T cells, dendritic cells, monocytes, neutrophils, natural killer (NK) cells, T regulatory cells, T-helper cells, cytotoxic T lymphocytes (CTLs), hematopoietic stem cells (HSCs), hematopoietic progenitor cells, endothelial cells, epithelial cells, mesenchymal cells, lymphocytes, lymphokine-activated killer cells (LAKs), and tumor infiltrating lymphocytes (TILs). 
     
     
         24 . The method as claimed in  claim 23 , wherein said hematopoietic progenitor cells and said hematopoietic stem cells are enriched. 
     
     
         25 . The method as claimed in  claim 24 , wherein said hematopoietic stem cells and said hematopoietic progenitor cells are positive for at least one of CD34, CD133, and CD143. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . The method as claimed in  claim 11 , wherein said target cells are selected from the group consisting of malignant cells from blood, malignant cells from tissue, virally infected cells, bacterially infected cells, at least one virus, at least one bacterium, a parasite, fetal cells, and pathogenic effector cells. 
     
     
         33 . The method as claimed in  claim 11 , further comprising the step of returning non-target cells to the patient connected or disconnected in said closed loop. 
     
     
         34 . The method as claimed in  claim 11 , further comprising the step of modifying non-target cells and returning said non-target cells to the patient connected or disconnected in said closed loop. 
     
     
         35 . The method as claimed in  claim 11 , wherein target cell enrichment is effected by at least one of magnetics, fluorescent-activated cell sorting, microfluidics, solid support, acoustics, bioluminescence, antibody tagging, and enzyme substrate. 
     
     
         36 . The method as claimed in  claim 35 , wherein said particle is selected from the group consisting of a magnetic particle and a density modified particle. 
     
     
         37 . A system for processing blood, said system comprising:
 means for obtaining blood from a patient; and   a single blood processing device coupled to said obtaining means and said patient to form a closed loop between said patient and said blood processing device, said blood processing device comprising:
 means for collecting bulk mononuclear blood cells from said blood by leukapheresis implemented using said blood processing device in said closed loop; 
 means for enriching concurrently target cells separated from nontarget cells in said bulk mononuclear blood cells using said blood processing device in said closed loop; and 
 means for modifying target cells adapted to provide modification selected from the group consisting of cytotoxic T lymphocyte (CTL) activation; T regulatory cell (Treq) activation and genetically modified blood cells protected from human immunodeficiency virus (HIV) in said closed loop. 
   
     
     
         38 . The system as claimed in  claim 37 , further comprising means for discarding said non-target cells. 
     
     
         39 . The system as claimed in  claim 37 , further comprising means for concurrently monitoring the collecting and enriching of said collecting and enriching means, respectively. 
     
     
         40 . The system as claimed in  claim 37  wherein said collecting means uses differential centrifugation to collect said mononuclear blood cells and said enriching means uses ligand capture to enrich said target cells. 
     
     
         41 . The system as claimed in  claim 40  wherein said ligand is an antibody specific for a cell surface ligand.