Photothermal substrates for selective transfection of cells

Abstract

This invention provides novel tools for surgery on single cells and substrates/devices for delivery of reagents to selected cells. In certain embodiments the substrates comprise a surface comprising one or more orifices, where nanoparticles and/or a thin film is deposited on a surface of said orifice or near said orifice, where the nanoparticles and/or a thin film are formed of materials that heat up when contacted with electromagnetic radiation. In certain embodiments the pores are in fluid communication with microchannels containing one or more reagents to be delivered into the cells.

1 . A device for delivering an agent into a cell, said device comprising:
 a surface bearing nanoparticles and/or a thin film of a material that heats up when contacted with electromagnetic radiation.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . The device of  claim 1 , wherein said surface comprises a wall and/or floor of a well in a microtiter plate, a silicon or glass wafer, a microscope slide, a cell culture vessel, or a chamber or channel in a microfluidic device. 
     
     
         6 . The device of  claim 1 , wherein said surface comprises a surface of a chamber configured to contain cells and disposed for viewing with a microscope. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . The device according to  claim 1 , wherein said surface comprises one or more orifices, where said nanoparticles and/or thin film is deposited on a surface of said at least one of said orifices and/or near at one of said orifices. 
     
     
         11 . (canceled) 
     
     
         12 . The device of  claim 10 , wherein said surface comprises at least 5, at least 10, at least 15, at least 20, at least 25, at least 50, at least 100, at least 200, or at least 500 orifices each comprising a surface bearing nanoparticles and/or a thin film, and/or having said nanoparticle and/or thin film disposed near to said orifice(s). 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The device according to  claim 10 , wherein:
 said nanoparticles and/or a thin film are deposited on a wall and/or all around the lip of the orifice(s); and/or   said nanoparticles and/or a thin film are preferentially on one region of a wall or lip of the orifice(s); and/or   said nanoparticles and/or a thin film are deposited on the face of the surface and/or on the lip of an orifice on the same side on which cells are disposed; and/or   said nanoparticles and/or a thin film are deposited on the face of the surface and/or on the lip of an orifice opposite the side on which cells are disposed.   
     
     
         16 - 18 . (canceled) 
     
     
         19 . The device according to  claim 1 , wherein said nanoparticles and/or thin film comprise a thin film. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The device according to  claim 1 , wherein said nanoparticles and/or thin film comprise a material selected from the group consisting of a semiconductor, a metal, a metal alloy, a metal nitride, and a metal oxide, a transition metal, a transition metal alloy, a transition metal nitride, and a transition metal oxide. 
     
     
         23 . (canceled) 
     
     
         24 . The device of  claim 22 , wherein the nanoparticle and/or thin film comprise a material selected from the group consisting of gold, titanium (Ti), TiN, TiCn, and TiAlN. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The device of  claim 10 , wherein one or more of said orifices are in fluid communication with a chamber or a microchannel containing a reagent to be delivered into a cell. 
     
     
         28 - 29 . (canceled) 
     
     
         30 . The device of  claim 27 , wherein said device comprises a plurality of microchannels and different microchannels are in fluid communication with different orifices. 
     
     
         31 - 33 . (canceled) 
     
     
         34 . The device of  claim 27 , wherein said microchannel(s) are pressurized, under control of a pump, or fed by a gravity feed. 
     
     
         35 . The device of  claim 27 , wherein said device further comprises a controller that monitors and/or controls flow in said microchannel and controls timing and, optionally, location of the illumination of said surface. 
     
     
         36 . The device of  claim 1 , wherein said device is configured to replace the stage on an inverted microscope. 
     
     
         37 . The device of  claim 1 , wherein a cell is disposed on said surface. 
     
     
         38 - 39 . (canceled) 
     
     
         40 . A system for selectively opening delivering an agent into a cell, said system comprising:
 a device according to  claim 1 ; and   a source of electromagnetic energy capable of heating said nanoparticles or thin film.   
     
     
         41 - 44 . (canceled) 
     
     
         45 . A method of delivering a reagent into a cell, said method comprising:
 providing cells on a device according to  claim 1 , wherein said cells are disposed on said surface;   contacting said cells with said reagent; and   exposing a region of said surface to electromagnetic radiation thereby inducing heating of said thin film and/or particles where said heating forms bubbles that introduce openings in the membrane of cells in or near the heated region resulting in the delivery of said reagent into those cells.   
     
     
         46 - 51 . (canceled) 
     
     
         52 . A method of performing micromanipulations on a cell, said method comprising:
 contacting said cell with a microsurgery tool, said tool comprising a microcapillary having at and/or near the tip a film (coating) or nanoparticles that can be heated by application of electromagnetic energy;   applying electromagnetic energy to said tool whereby the temperature of said metal film or metal nanoparticles is increased resulting in the formation of an opening in the membrane of said cell, wherein the contact angle of said microsurgery tool with the cell and/or the polarization of the electromagnetic energy is varied to alter the size and/or shape of the opening introduced into said cell.   
     
     
         53 - 65 . (canceled)