Microfluidic laser-activated intracellular delivery systems and methods

Abstract

An intracellular delivery system and method are provided. The intracellular delivery system comprises a laser-activated surface and cells positioned at a distance from the laser-activated surface. A laser provided a laser pulse that is used to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells. The method of intracellular delivery comprises positioning a laser-activated surface at a distance from cells and applying a laser pulse from the laser to the surface to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells.

What is claimed is: 
     
         1 . A system, comprising:
 a container comprising an interior substrate coated with a film and a plurality of cells stationary on the film; and   a light source exterior to the container, the light source configured to direct laser pulses toward the film, wherein:
 the laser pulses selectively target the film to selectively disrupt specific cells in the plurality of cells, wherein the specific cells are selected based at least in part in images of the specific cells; and 
 the film is configured to convert optical energy from the laser pulses into mechanical energy to selectively disrupt the specific cells. 
   
     
     
         2 . The system of  claim 1 , wherein selectively disrupting the specific cells further comprises porating membranes of the specific cells. 
     
     
         3 . The system of  claim 2 , wherein cargo is delivered into the specific cells while the membranes of the specific cells are porated. 
     
     
         4 . The system of  claim 1 , wherein the film is further configured to convert the optical energy from the laser pulses into the mechanical energy through formation and contraction of microbubbles configured to generate a pressure wave that disrupts the specific cells. 
     
     
         5 . The system of  claim 1 , wherein the container further contains a fluid medium inside the container. 
     
     
         6 . The system of  claim 5 , wherein the fluid medium further comprises contrast-agent microbubbles. 
     
     
         7 . The system of  claim 5 , wherein a wavelength of the laser pulses is highly absorbed by the fluid medium. 
     
     
         8 . The system of  claim 5 , wherein the container comprises a fluid channel configured to provide at least one of stopped flow or turbulent flow of the fluid medium. 
     
     
         9 . The system of  claim 1 , wherein the film comprises at least one of a metallic film, a polymer film, an oxide film, a nitride film, and a semiconductor film. 
     
     
         10 . The system of  claim 1 , wherein the film is a continuous flat layer. 
     
     
         11 . A method of selectively disrupting specific cells, comprising:
 performing cell culture of a plurality of cells inside a container comprising an interior substrate coated with a film, wherein the plurality of cells is stationary on the film;   selecting specific cells in the plurality of cells to selectively disrupt, based at least in part on images of the specific cells; and   directing laser pulses toward the film, wherein the laser pulses selectively target the film to selectively disrupt the specific cells,   wherein selectively disrupting the specific cells comprises converting, by the film, optical energy from the laser pulses into mechanical energy.   
     
     
         12 . The method of  claim 11 , wherein selectively disrupting the specific cells further comprises porating membranes of the specific cells. 
     
     
         13 . The method of  claim 12 , further comprising delivering cargo into the specific cells while the membranes of the specific cells are porated. 
     
     
         14 . The method of  claim 11 , wherein converting the optical energy from the laser pulses into the mechanical energy comprises formation and contraction of microbubbles, using the microbubbles to generate a pressure wave, and disrupting the specific cells by the pressure wave. 
     
     
         15 . The method of  claim 11 , wherein the container further contains a fluid medium inside the container. 
     
     
         16 . The method of  claim 15 , wherein the fluid medium further comprises contrast-agent microbubbles. 
     
     
         17 . The method of  claim 15 , wherein a wavelength of the laser pulses is highly absorbed by the fluid medium. 
     
     
         18 . The system of  claim 15 , wherein the container provides a fluid channel configured to provide at least one of stopped flow or turbulent flow of the fluid medium. 
     
     
         19 . The method of  claim 11 , wherein the film comprises at least one of a metallic film, a polymer film, an oxide film, a nitride film, and a semiconductor film. 
     
     
         20 . The method of  claim 11 , wherein the film is a continuous flat layer.