Cell patterning technique

Abstract

The present invention provides a masking system for selectively applying cells to predetermined regions of a surface. A mask is positioned adjacent to a surface to cover some portions of the surface while allowing other portions of the surface to remain uncovered. Cells then are applied to uncovered portions of the surface and the mask removed. Alternatively, a cell-adhesion promoter is applied to uncovered portions of the surface, and then cells are applied to the surface before or after removal of the mask from the surface. The masking system can be pre-coated, at least on those surfaces which will come into contact with cells, with a cell-adhesion inhibitor to resist absorption of cells and thereby avoid cell damage when the mask is removed (if cells are deposited prior to removal of the mask). A polymeric elastomeric mask that comes into cohesive-conformal contact with a surface to be patterned can be used.

1 . A method for patterning cells, comprising: 
 shielding a first portion of a surface of an article with a masking system comprising a cohesive mask in conformal contact with the surface of the article;    applying an agent through a channel within the masking system to a second portion of the surface of the article while preventing application of the agent to the first portion of the surface of the article; and    applying cells onto the agent.    
     
     
         2 . The method of  claim 1 , wherein the masking system comprises a flexible mask including a first surface and an opposing second surface, and the channel is one of a plurality of channels passing through the mask and connecting the first surface with the second surface.  
     
     
         3 . The method of  claim 2 , further comprising removing the masking system from the surface of the article.  
     
     
         4 . The method of  claim 1 , wherein the agent is a cell-adhesion promoter.  
     
     
         5 . The method of  claim 2 , further comprising removing the masking system from the surface of the article prior to the step of applying cells onto the agent.  
     
     
         6 . The method of  claim 5 , wherein the agent is a first agent and the method further comprises adding a second agent to the first portion of the surface.  
     
     
         7 . The method of  claim 6 , wherein the first agent is a cell-adhesion promoter.  
     
     
         8 . The method of  claim 7 , wherein the first agent is a protein.  
     
     
         9 . The method of  claim 8 , wherein the protein is fibronectin.  
     
     
         10 . The method of  claim 6 , wherein the second agent is a cell-adhesion inhibitor.  
     
     
         11 . The method of  claim 1 , wherein the first portion of the surface of the article is contiguous with the second portion.  
     
     
         12 . The method of  claim 2 , wherein the agent is a first agent and the method comprises pre-coating at least a portion of the masking system with a second agent prior to the shielding step.  
     
     
         13 . The method of  claim 12 , wherein the pre-coating step comprises: 
 contacting the first surface of the masking system with a substrate; and    coating the second agent onto the second surface and the plurality of channels of the masking system, wherein the first surface of the masking system is free of the second agent.    
     
     
         14 . The method of  claim 13 , wherein the shielding step comprises: 
 removing the masking system from the substrate; and    bringing the first surface of the masking system into conformal contact with the first portion of the surface of the article.    
     
     
         15 . The method of  claim 14 , wherein the first agent is a cell-adhesion promoter.  
     
     
         16 . The method of  claim 15 , wherein the second agent is a cell-adhesion inhibitor.  
     
     
         17 . The method of  claim 16 , further comprising removing the masking system from the surface of the article prior to applying the cells onto the first agent.  
     
     
         18 . The method of  claim 16 , further comprising removing the masking system from the surface of the article.  
     
     
         19 . The method of  claim 18 , further comprising adding a third agent to the first portion of the surface of the article.  
     
     
         20 . The method of  claim 19 , further comprising allowing the cells applied to the first agent to spread onto the third agent.  
     
     
         21 . The method of  claim 19 , wherein the first agent is a first cell-adhesion promoter and the third agent is a second cell-adhesion promoter.  
     
     
         22 . The method of  claim 21 , further comprising adding cells of a second type to the third agent.  
     
     
         23 . The method of  claim 1 , wherein the channel has a dimension for controlling the growth of a single cell.  
     
     
         24 - 34 . (canceled)  
     
     
         35 . A method for patterning cells, comprising: 
 providing an article having a first pattern of cells of a first type; and    applying an agent to a portion of the surface of the article, the portion being contiguous with the first pattern.    
     
     
         36 . The method of  claim 35 , wherein the agent is a cell-adhesion inhibitor for cells of the first type  
     
     
         37 . The method of  claim 35 , wherein the agent is a cell-adhesion promoter for cells of a second type.  
     
     
         38 . The method of  claim 37 , further comprising applying the cells of the second type onto the agent.  
     
     
         39 . The method of  claim 35 , wherein the providing step further comprises: 
 bringing a masking system in conformal contact with the portion of the surface of the article; and    applying a cell-adhesion promoter through a channel within the masking system.    
     
     
         40 . The method of  claim 39 , wherein the providing step further comprises pre-coating the masking system with a cell-adhesion inhibitor prior to the step of bringing the masking system in conformal contact with the surface of the article.  
     
     
         41 . An article comprising: 
 a first pattern of cells of a first type contiguous with a second pattern of cells of a second type.    
     
     
         42 - 47 . (canceled)