Continuous flow chamber device for separation, concentration, and/or purification of cells

Abstract

The present invention relates to methods and apparatuses for cell separation. In particular, the invention relates to separation of a particular cell type from a mixture of different cell types based on the differential rolling property of the particular cell type on a substrate coated with molecules that exhibits adhesive property with the particular cell type. This technology is adaptable for use in implantable shunts and devices for cell trafficking or tumor neutralization.

1 . A method for separating, concentrating, and/or purifying a particular cell type from a mixture of cells comprising the steps of 
 providing a flow surface containing an adhesive molecule that selectively binds with the particular cell type; and    flowing the mixture of cells on the flow surface.    
   
   
       2 . The method of  claim 1 , wherein the particular type of cell is selected from the group consisting of CD34+ cell and hematopoietic stem and precursor cell (HSPC).  
   
   
       3 . The method of  claim 1 , wherein the substance is selected from the group consisting of NPPB, P-selectin, L-selectin, E-selectin, antibody specific against the particular cell type, cadherins, integrins, mucin-like family, immunoglobin superfamily and fragments thereof.  
   
   
       4 . The method of  claim 1 , wherein the flow surface is part of a separation chamber.  
   
   
       5 . The method of  claim 1 , wherein the flow surface is part of a microcapillary network.  
   
   
       6 . The method of  claim 1 , wherein the wall shear stress is about 1-10 dyn/cm 2 .  
   
   
       7 . The method of  claim 1 , wherein the particular cell type has a rolling speed less than half the rolling speed of the other cells in the mixture of cells.  
   
   
       8 . An implantable shunt for directing stem cell trafficking comprising a flow chamber, wherein a wall of the chamber contains an adhesive molecule that selectively binds with the stem cell.  
   
   
       9 . The implantable shunt of  claim 8 , wherein the stem cell is CD34+ hematopoetic stem cell.  
   
   
       10 . The implantable shunt of  claim 8 , wherein the molecule is selected from the group consisting of NPPB, P-selectin, L-selectin, E-selectin, antibody specific against the particular cell type, cadherins, integrins, mucin-like family, immunoglobin superfamily and fragments thereof.  
   
   
       11 . An implantable device for neutralizing tumor cells comprising a flow chamber, wherein a wall of the chamber contains an adhesive molecule that selectively binds with the tumor cells and a molecule that neutralizes the cancer cells.  
   
   
       12 . The implantable device of  claim 11 , wherein the adhesive molecule is selectin.  
   
   
       13 . The implantable device of  claim 11 , wherein the molecule that neutralizes the cancer cells is selected from the group consisting of TRAIL, Fas ligand, and chemotherapeutic drug.  
   
   
       14 . The implantable device of  claim 11 , wherein the molecule that neutralizes the cancer cells induces apoptosis in the tumor cells.  
   
   
       15 . A method for neutralizing tumor cells comprising the steps of 
 providing a flow surface containing an adhesive molecule that selectively binds with the tumor cells and a molecule that neutralizes the cancer cells; and    flowing the tumor cells on the flow surface.    
   
   
       16 . The method of  claim 15 , wherein the adhesive molecule is selected from the group consisting of NPPB, P-selectin, L-selectin, E-selectin, antibody specific against the particular cell type, cadherins, integrins, mucin-like family, immunoglobin superfamily and fragments thereof.  
   
   
       17 . The method of  claim 15 , wherein the molecule that neutralizes the cancer cells is selected from the group consisting of TRAIL, Fas ligand, and chemotherapeutic drug.  
   
   
       18 . The method of  claim 15 , wherein the molecule that neutralizes the cancer cells induces apoptosis in the tumor cells.  
   
   
       19 . The method of  claim 15 , wherein the flow surface is part of a separation chamber.  
   
   
       20 . The method of  claim 15 , wherein the flow surface is implanted in the circulatory system of a patient.