Guided deposition in spatial arrays

Abstract

An apparatus and method is provided for preparing and using a very large and diverse array of compounds on a substrate having rapidly accessible locations. The substrate contains cells in which the compounds of the array are located. Surrounding the cells is a non-wetable surface that prevents the solution in one cell from moving to adjacent cells. The compounds are delivered to the individual cells of the array by a micropipette attached to an X-Y translation stage.

What is claimed is:  
     
         1 . A method for conducting a plurality of reactions on a substrate, said substrate having a plurality of cells at predefined locations thereon, the location of each cell being encoded by information readable with electrical, magnetic or electromagnetic sensing means, said method comprising the following steps: 
 (a) selecting a first set of cells;    (b) decoding the locations of said first set of cells by said sensing means and delivering a first reactant to each of said first set cells;    (c) selecting a second set of cells;    (d) decoding the locations of said second set of cells by said sensing means and delivering a second reactant to each of said second set of cells; and    (e) simultaneously reacting said first reactant in each of said first set of cells and said second reactant in each of said second set of cells, wherein the first reactant is prevented from contacting the second set of cells and the second reactant is prevented from contacting the first set of cells.    
     
     
         2 . The method of  claim 1  where said step of delivering the first reactant to the first set of cells includes the following steps: 
 (a) identifying a reference mark on the substrate;  
 (b) moving a dispenser of said reactants a fixed distance and direction from said reference point such that the dispenser is positioned approximately above a first cell of the first set of cells;  
 (c) delivering the first reactant to the first cell; and  
 (d) repeating steps b and c for each remaining cell of the first set of cells.  
 
     
     
         3 . The method of  claim 1  wherein the first and second reactants are monomers.  
     
     
         4 . The method of  claim 3  wherein the monomers are selected from the group consisting of amino acids, nucleotides and saccharides.  
     
     
         5 . The method of  claim 1  wherein the first and second reactants are receptors.  
     
     
         6 . The method of  claim 1  wherein said substrate is a rotatable disk, and said steps of delivering reactants each includes the following steps: 
 (a) moving a dispenser of said reactants to the radial position of a first cell from said selected set of cells;  
 (b) rotating of said substrate with respect to the dispenser such tha the dispenser is positioned approximately above said first cell;  
 (c) delivering said reactant to said first cell;  
 (d) repeating steps a-c for each remaining cell of said selected set of cells.  
 
     
     
         7 . The method of  claim 1  wherein the first and second reactants are delivered to the cells from a micropipette.  
     
     
         8 . The method of  claim 1  wherein the first and second reactants are delivered in charged droplets from capillaries having electrodes attached thereto.  
     
     
         9 . The method of  claim 1  wherein the substrate has surface regions surrounding the plurality of cells, the surface regions having a hydrophobic surface.  
     
     
         10 . A method for conducting a plurality of reactions on a substrate, said substrate having a plurality of cells at predefined locations thereon, the method comprising the following steps: 
 (a) selecting a first set of cells and a second set of cells;    (b) delivering a solution of a first reactant to the first set of cells and a second reactant to the second set of cells;    (c) simultaneously conducting reactions of the first reactant in the first set of cells and of the second reactant in the second set of cells;    wherein regions of the substrate surrounding the first set of cells are covered with a layer of protecting groups that are non-wetting with respect to the solutions of the first and second reactants.    
     
     
         11 . The method of  claim 10  where said steps of delivering reactants each includes the following steps: 
 (a) identifying a reference mark on the substrate;  
 (b) moving a dispenser of said reactants a fixed distance and direction from said reference point such that the dispenser is positioned approximately above said first cell;  
 (c) delivering said reactant to said first cells; and  
 (d) repeating steps b and c for each remaining cell of the selected set of cells.  
 
     
     
         12 . The method of  claim 10  wherein the protecting groups are selected from the group consisting of alkyl silanes.  
     
     
         13 . An array of compounds on a substrate, said array comprising: 
 (a) a plurality of cells on which the individual compounds of the array are located;    (b) a layer of non-wetting protecting groups surrounding said cells.    
     
     
         14 . The array of  claim 13  wherein the protecting groups are selected from the group consisting of alkyl silanes.  
     
     
         15 . The array of  claim 13  wherein the compounds are polymers.  
     
     
         16 . The array of  claim 13  wherein the protecting groups are photolabile.  
     
     
         17 . A system for conducting reactions on selected cells, said system comprising the following elements: 
 (a) substrate on which a plurality of cells are disposed, the substrate having non-wetting protecting groups on regions surrounding the cells;    (b) one or more reservoirs for storing one or more reactants;    (c) means for dispensing the one or more reactants on selected cells of said substrate, said means for dispensing being mounted on an arm movable with respect to the substrate;    (d) an actuator for controlling the radial position of said arm with respect to said substrate; and    (e) processing means controlling the actuator such. that said reactants are delivered to predetermined cells in a predetermined sequence through said means for dispensing.    
     
     
         18 . The system of  claim 17  wherein the reactants are selected from the group consisting of receptors, amino acids, nucleotides, and saccharides.  
     
     
         19 . The system of  claim 17  wherein the protecting groups are photocleavably attached to the substrate.  
     
     
         20 . The system of  claim 17  wherein the protecting groups are selected from the group consisting of alkyl silanes.