Array of micromolded structures for sorting adherent cells

Abstract

An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

That which is claimed is: 
     
         1 . An apparatus for collecting or culturing cells or cell colonies, the apparatus comprising:
 a) a common substrate,
 the common substrate having a first surface and an opposed second surface, 
 the common substrate having a plurality of wells formed in the first surface in the form of an array, the wells in the common substrate defined by side walls, 
 wherein the common substrate is configured to allow cell growth on the first surface, and 
   b) a shared media reservoir, wherein the shared media reservoir extends across the plurality of wells formed in the first surface of the common substrate in the form of an array,   wherein the apparatus is configured to allow the retrieval of single cells or cell colonies individually segregated in the wells of the common substrate.   
     
     
         2 . The apparatus of  claim 1 , wherein the common substrate defines the shared media reservoir. 
     
     
         3 . The apparatus of  claim 1 , wherein the common substrate is formed from a flexible or elastomeric material. 
     
     
         4 . The apparatus of  claim 1 , further comprising a housing for supporting the common substrate. 
     
     
         5 . The apparatus of  claim 1 , wherein the shared media reservoir is configured to receive and/or contain a liquid media, wherein the liquid media comprises one or more cells to be cultured, wherein application of the liquid media containing the one or more cells to the shared media reservoir causes the one or more cells to be cultured to come into contact with the common substrate. 
     
     
         6 . The apparatus of  claim 1 , wherein common substrate comprises a cell growth supporting surface or a cell-growth compatible layer. 
     
     
         7 . The apparatus of  claim 1 , wherein the common substrate is coated with a biologically active molecule on at least the first surface thereof. 
     
     
         8 . The apparatus of  claim 1 , wherein the biologically active material is selected from the group consisting of a peptide, a protein, a carbohydrate, a nucleic acid, a lipid, a polysaccharide, a hormone, an extracellular matrix molecule, a cell adhesion molecule, a natural polymer, an enzyme, an antibody, an antigen, a polynucleotide, a growth factor, a synthetic polymer, polylysine, a drug, and any combination thereof 
     
     
         9 . The apparatus of  claim 1 , wherein the common substrate comprises one or more cell carriers, wherein the cell carriers are transparent or semitransparent. 
     
     
         10 . The apparatus of  claim 9 , wherein each of the one or more cell carriers is disposed in one of the wells such that each cell carrier engages the side walls of the well and is resiliently held in the one of the wells, the carriers configured to release from the substrate upon mechanical distortion of the common substrate. 
     
     
         11 . The apparatus of  claim 1  wherein:
 the wells in the common substrate are separated by walls, the walls have an average width of at least 2 micrometers, up to 1000 micrometers; 
 and the walls have an average height of at least 2 micrometers, up to 1000 micrometers; 
 the wells in the common substrate have floors, and the floors have an average thickness of from 2 to 500 micrometers. 
 
     
     
         12 . The apparatus of  claim 1  wherein:
 the wells in the common substrate are separated by walls, the walls have an average width of at least 2 micrometers, up to 1000 micrometers; 
 and the walls have an average height of at least 2 micrometers, up to 1000 micrometers; 
 the wells forming a cavity in the common substrate with a continuous opening from first surface of the substrate to the second opposed surface of the substrate. 
 
     
     
         13 . The apparatus of  claim 12 , wherein the wells forming a cavity with a continuous opening are substantially devoid of a floor. 
     
     
         14 . The apparatus of  claim 12 , wherein the shared media reservoir extends below the opposed second surface of the common substrate. 
     
     
         15 . The apparatus of  claim 1 , wherein the common substrate is formed from a flexible resilient polymeric material. 
     
     
         16 . The apparatus of  claim 15 , wherein the resilient polymeric material is selected from the group consisting of silicones, polyurethane, styrene-butadiene copolymer, polyolefin and polydiene elastomers, thermoplastic elastomers or combinations thereof 
     
     
         17 . The apparatus of  claim 1 , wherein the array is uniform or non-uniform. 
     
     
         18 . The apparatus of  claim 1 , wherein the array is arranged in an interdigitated pattern. 
     
     
         19 . The apparatus of  claim 1 , wherein the housing comprises a cassette formed from poly carbonate or glass. 
     
     
         20 . The apparatus of  claim 19 , wherein the cassette includes a scaffold.