Method and device for cell modification

Abstract

The invention relates to a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g. Furthermore, the invention relates to a method for modifying cells comprising the steps—introducing cells in a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber wherein and comprising at least one input/output port, —immobilizing the cells on the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g—maintaining the rotation of the rotation of the centrifugation chamber until the cells are modified.

1 . A cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g and wherein the cell modifying surfaces are selected from the group of cell modifying surfaces that are functionalized and those that can be functionalized for cell modification. 
     
     
         2 . A cell modification device according to  claim 1 , wherein the cell modifying surface is functionalized with at least one substance wherein the substance is selected from the group of substances that enhance proliferation of cells, that induce genetic modification and that induce cellular modification of cells. 
     
     
         3 . A cell modification device according to  claim 1 , wherein the cell modifying surface is functionalized with particles being functionalized with at least one substance selected from substances that enhance proliferation of cells, induce genetic modification, and induce cellular modification of cells. 
     
     
         4 . A cell modification device according to  claim 2 , wherein the substance enhancing proliferation of cells is selected from the group consisting of collagen types (I to VIII), fibronectin, gelatin, laminin, elastin, hyaluronic acid, keratan sulfate, chondroitin sulfate, heparin sulfate proteoglycans, poly-d-lysine, avidin, streptavidin, biotin, antibodies, antibodies against biotin or protein tags, protein tags like IIsopeptag, BCCP, Myc-tag, Calmodulin-tag, FLAG-tag, HA-tag, His-tag, Maltose binding protein-tag, Nus-tag, Glutathione-S-transferase-tag, Green fluorescent protein-tag, Thioredoxin-tag, S-tag, Softag 1, Softag 3, Strep-tag, SBP-tag, Ty tag, certia, poly lactate, polyvinyl alcohols, polysaccharides and dextran. 
     
     
         5 . A cell modification device according to  claim 2 , wherein the substance inducing cellular modification of cells is selected from the group consisting of agonistic or antagonistic antibodies, cytokines, growth factors, (de-)activating ligands, pharmacologically active substances, mitogens, DNA or RNA-modifying substances. 
     
     
         6 . A cell modification device according to  claim 2 , wherein the substance inducing genetic modification of cells is selected from the group consisting of a virus, viral particle, adenovirus, retrovirus, lentivirus, RNA, DNA, non-coding small or large RNAs (i.e. siRNA, miRNA, shRNA), DNA, mRNA- or shRNA-expression plasmids, DNA, protein, ligand, receptor, cytokine, stimulating or deactivating antibody, pharmacological agent, feeder cells. 
     
     
         7 . A cell modification device according to  claim 1 , wherein the cell modifying surface is located on the inner surface of the centrifugation chamber, a spiral-shaped element or on at least one cylindrical element. 
     
     
         8 . A cell modification device according to  claim 1 , characterized in that the centrifugation chamber comprises at least two cell modifying surfaces which are functionalized with the same or different at least one substance enhancing proliferation of cells, and/or inducing genetic modification and/or inducing cellular modification of cells. 
     
     
         9 . A method for modifying cells comprising the steps
 introducing cells in a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber wherein and comprising at least one input/output port,   immobilizing the cells on the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g   maintaining the rotation of the rotation of the centrifugation chamber until the cells are modified.   
     
     
         10 . A method according to  claim 9  wherein the cells are modified by bringing into contact with at least one cell modifying surface functionalized with at least one substance enhancing proliferation of cells, and/or inducing genetic modification and/or inducing cellular modification of cells. 
     
     
         11 . A method according to  claim 9  wherein the cells are modified by bringing into contact with at least one cell modifying surface functionalized with particles being functionalized with at least one substance enhancing proliferation of cells, and/or inducing genetic modification and/or inducing cellular modification of cells. 
     
     
         12 . A method according to  claim 9  wherein the cells are modified by immobilizing cells on at least one cell modifying surface and bringing into contact with particles being functionalized with at least one substance enhancing proliferation of cells, and/or inducing genetic modification and/or inducing cellular modification of cells. 
     
     
         13 . A method according to  claim 9  wherein the cells are subjected to at least two different gravitational forces. 
     
     
         14 . A cell composition modified by a method according to  claim 1 . 
     
     
         15 . A cell composition of  claim 14 , wherein the cell composition has at least two layers, the layers comprising modified cells of different cell types or cells of a different phenotype. 
     
     
         16 . A system for cell modification, comprising:
 a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber and at least one input/output port   a device to rotate the centrifugation chamber so as to apply a centrifugal force to cells.