Single cell capture with capture chips

Abstract

The present invention provides methods, systems, assemblies, and articles for capturing single cells with a capture chip. In certain embodiments, the capture chip comprises a substrate comprising a plurality of cell-sized dimples or wells that each allow a single cell to be captured from a cell suspension. In some embodiments, the dimples or wells of the capture chip align with the holes or wells of a multi-well through-hole chip, and/or a multi-well chip, such that the cell, or the contents of the single cell, may be transferred to a corresponding well of the multi-well chip. In particular embodiments, the bottom of each dimple or well of the capture chip has a positive electrical charge sufficient to attract cells from a cell suspension flowing over the dimples or wells.

We claim: 
     
         1 . A system comprising:
 a) a capture chip comprising a substrate comprising a plurality of cell-sized dimples or wells that each allow a single cell to be captured from a cell mixture; and   b) a multi-well through-hole chip, wherein said multi-well through-hole chip comprises a plurality of holes, and when combined with a backing or said capture chip, forms a multi-well chip which comprises a plurality of wells; and   wherein said plurality of cell-sized dimples or wells matches one-for-one, and aligns with, said plurality of holes in said multi-well through-hole chip.   
     
     
         2 . The system of  claim 1 , wherein some or all of said cell-sized dimples or wells each contain a single cell, and/or wherein said plurality of wells in said multi-well chip: i) have a volume of 50 and 5000 nl, and/or ii) comprise at least 300 wells. 
     
     
         3 . The system of  claim 1 , wherein said capture chip and said multi-well through-hole chip are attached to each other thereby forming said multi-well chip, and wherein some or all of said plurality of wells in said multi-well chip contain reagents that detach and/or lyse cells. 
     
     
         4 . The system of  claim 3 , wherein some or all of said cell-sized dimples or wells each contain a single cell. 
     
     
         5 . The system of  claim 1 , wherein said substrate comprises photoresist. 
     
     
         6 . The system of  claim 1 , wherein said substrate comprises an electrically conductive material. 
     
     
         7 . The system of  claim 6 , wherein said electrically conductive material is optically transparent. 
     
     
         8 . The system of  claim 6 , wherein said electrically conductive material comprises indium titanium oxide. 
     
     
         9 . The system of  claim 1 , wherein said substrate comprises a non-conductive material and an electrically conductive material. 
     
     
         10 . The system of  claim 1 , wherein each of said dimples or wells of said capture chip has a bottom and at least one side wall. 
     
     
         11 . The system of  claim 10 , wherein said bottom is composed of a material comprising an electrically conductive material, and said at least one side wall is composed of a non-conductive material. 
     
     
         12 . The system of  claim 11 , wherein said electrically conductive material is optically transparent, and wherein said capture chip comprises at least 50 dimples or wells. 
     
     
         13 . The system of  claim 11 , wherein said electrically conductive material comprises indium titanium oxide. 
     
     
         14 . The system of  claim 11 , wherein said at least one side wall is composed of a material comprising photoresist. 
     
     
         15 . The system of  claim 6 , further comprising: c) an electrical field generator configured to be electrically linked to said electrically conductive material. 
     
     
         16 . A method of loading a capture-chip with cells comprising:
 a) flowing a cell suspension over a capture-chip, wherein said capture-chip comprises a substrate with a plurality of cell-sized dimples or wells formed therein, and wherein said flowing causes a single cell to be captured in each of said plurality of cell-sized dimples or wells; and   b) washing said capture-chip such that excess cells from said cell suspension not captured in said plurality of dimples or wells are removed.   
     
     
         17 . The method of  claim 16 , wherein said substrate comprises non-conductive material and a first electrically conductive material. 
     
     
         18 . The method of  claim 17 , wherein each of said plurality of cell-sized dimples or wells comprises a bottom and at least one side. 
     
     
         19 . The method of  claim 18 , wherein said bottom comprises said first electrically conductive material, and said at least one side comprises said non-conductive material. 
     
     
         20 . The method of  claim 19 , wherein said first electrically conductive material is electrically linked to an electrical field generator, and wherein said electrical field generator imparts a positive charge to each of said dimple bottoms sufficient to attract cells from said cell suspension. 
     
     
         21 . The method of  claim 20 , wherein said substrate further comprises a second electrically conductive material, wherein said second electrically conductive material has zero or negative voltage with respect to said first electrically conductive material. 
     
     
         22 . The method of  claim 17 , wherein said electrically conductive material is optically transparent. 
     
     
         23 . The method of  claim 17 , wherein said electrically conductive material comprises indium titanium oxide. 
     
     
         24 . The method of  claim 19 , wherein said non-conductive material comprises photoresist, and wherein said capture-chip comprises at least 50 of said dimples.