Intracellular delivery

Abstract

A microfluidic system for causing perturbations in a cell membrane, the system including a microfluidic channel defining a lumen and being configured such that a cell suspended in a buffer can pass therethrough, wherein the microfluidic channel includes a cell-deforming constriction, wherein a diameter of the constriction is a function of the diameter of the cell.

What is claimed is: 
     
         1 . A microfluidic system for causing perturbations in a cell membrane, the system comprising:
 a microfluidic channel defining a lumen and being configured such that a cell suspended in a buffer can pass therethrough, wherein the microfluidic channel includes a cell-deforming constriction, wherein a diameter of the constriction is a function of the diameter of the cell.   
     
     
         2 . The microfluidic system of  claim 1  wherein the diameter of the constriction is substantially 20-99% of the diameter of the cell passing therethrough. 
     
     
         3 . The microfluidic system of  claim 2 , wherein a diameter of the constriction is substantially 60% of the diameter of the cell. 
     
     
         4 . The microfluidic system of  claim 1 , wherein the diameter of the constriction is selected to induce temporary perturbations of the cell wall large enough for a payload to pass through. 
     
     
         5 . The microfluidic system of  claim 4 , wherein the diameter of the constriction is also selected to reduce a likelihood that the cell will die as a result of the deformation. 
     
     
         6 . The microfluidic system of  claim 1  wherein a cross-section of the channel is selected from the group consisting of circular, elliptical, an elongated slit, square, hexagonal, and triangular. 
     
     
         7 . The microfluidic system of  claim 1  wherein the constriction includes an entrance portion, a centerpoint, and an exit portion. 
     
     
         8 . The microfluidic system of  claim 7  wherein the entrance portion defines a constriction angle, wherein the constriction angle is optimized to reduce clogging of the channel. 
     
     
         9 . The microfluidic system of  claim 7  wherein the entrance portion defines a constriction angle, wherein the constriction angle is optimized to improve delivery and cell viability. 
     
     
         10 . The microfluidic system of  claim 7  wherein the entrance portion defines a 90 degree constriction angle. 
     
     
         11 . The microfluidic system of  claim 1  further comprising a plurality of the microfluidic channels arranged in one of series and parallel. 
     
     
         12 . The microfluidic system of  claim 1 , further comprising a cell driver. 
     
     
         13 . The microfluidic system of  claim 12 , wherein the cell driver is selected from a group consisting of: a pressure pump, a gas cylinder, a compressor, a vacuum pump, a syringe, a syringe pump, a peristaltic pump, a manual syringe, a pipette, a piston, a capillary actor, a human heart, human muscle, and gravity. 
     
     
         14 . The microfluidic system of  claim 1 , wherein a fluid flow of the cell suspended in the buffer is channeled into the constriction, the diameter of the constriction being greater than the diameter of the cell passing therethrough, such that the cell is primarily compressed by the fluid flow. 
     
     
         15 - 59 . (canceled)