Systems for intracellular delivery of molecules from a cell medium into cells

Abstract

Embodiments of the present disclosure can include a method for convective intracellular delivery including providing cells and molecules to a microchannel having compressive surfaces, wherein the compressive surfaces define compression gaps having a height of from 20 and 80% of the average cell diameter, and a plurality of relaxation spaces disposed between the compressive surfaces, flowing the cell medium through the microchannel, wherein as the cell medium flows through the microchannel, the plurality of cells undergo a convective intracellular delivery process comprising: compressing the plurality of cells, wherein the compressing causes the plurality of cells to undergo a loss in intracellular volume Vloss, and passing the plurality of cells to a first relaxation space, wherein the plurality of cells undergo a gain in volume Vgain and absorb a portion of the plurality of molecules.

What is claimed is: 
     
         1 . A microchannel configured for a system for intracellular delivery of molecules from a cell medium into cells, the microchannel comprising:
 a first wall;   a second wall;   ridges protruding outwardly from the first wall and defining compression gaps between the ridges and the second wall; and   relaxation spaces disposed between the ridges;   wherein the ridges are arranged in a chevron pattern oriented with respect to a central flow axis of the microchannel;   wherein the first wall and the second wall are substantially planar to each other; and   wherein the compression gaps have a height, measured perpendicular to the second wall, of from 20 to 80% of an average cell diameter of the cells.   
     
     
         2 . The microchannel of  claim 1 , wherein a ridge angle formed by at least one ridge of the ridges is from 20 degrees to 90 degrees with respect to the central flow axis of the microchannel. 
     
     
         3 . The microchannel of  claim 2 , wherein the ridge angle is different for different ones of the ridges along the central flow axis of the microchannel. 
     
     
         4 . The microchannel of  claim 2 , wherein:
 the ridge angle is configured to facilitate movement of dead or damaged cells to a side wall of the microchannel thereby preventing clogging of the microchannel; and   the side wall extends between the first wall and the second wall.   
     
     
         5 . The microchannel of  claim 4  further comprising:
 a first outlet; and 
 a second outlet; 
 wherein the first outlet is positioned along the side wall and is configured to receive the dead or damaged cells; and 
 wherein the second outlet is positioned away from the side wall. 
 
     
     
         6 . A system for intracellular delivery of a plurality of molecules from a cell medium into a plurality of cells, the system comprising:
 a microchannel comprising:
 a first wall, a second wall, and a plurality of ridges that are arranged in a chevron pattern oriented with respect to a central flow axis of the microchannel, the first wall and the second wall being substantially planar to each other;
 wherein the plurality of ridges protrude outwardly from the first wall and define a plurality of compression gaps between the plurality of ridges and the second wall; and 
 wherein the plurality of compression gaps have a height, measured perpendicular to the second wall, of from 20 to 80% of an average cell diameter of the plurality of cells; and 
 
 a plurality of relaxation spaces disposed between the plurality of ridges. 
   
     
     
         6 . The system of  claim 6 , wherein one or both:
 a ridge angle formed by at least one ridge of the plurality of ridges is 30 degrees or 45 degrees with respect to the central flow axis of the microchannel; and   a width of at least one of the plurality of relaxation spaces is from 100 micrometers to 300 micrometers between two adjacent ones of the plurality of ridges.   
     
     
         8 . The system of  claim 6 , wherein the plurality of ridges comprise 1 ridge to 21 ridges, each ridge defining a separate one of the plurality of compression gaps. 
     
     
         9 . The system of  claim 6 , wherein the plurality of compression gaps are configured to allow simultaneous passing of multiple cells of the plurality of cells through each of the plurality of compression gaps. 
     
     
         10 . The system of  claim 6 , wherein:
 the plurality of compression gaps are configured to compress the plurality of cells as the plurality of cells passes through each of the compression gaps causing the plurality of cells to undergo a loss in intracellular volume (V loss ); and   the plurality of relaxation spaces are configured to allow the plurality of cells to undergo a gain in volume (V gain  ) and absorb a portion of the plurality of molecules from the cell medium.   
     
     
         11 . The system of  claim 6  further comprising one or more additional microchannels, sharing a common inlet with the microchannel and providing additional flow paths to the plurality of cells through the system, wherein:
 each of the one or more additional microchannels comprises an additional first wall, an additional second wall, and an additional plurality of ridges that are arranged in the chevron pattern oriented with respect to the central flow axis of the microchannel; 
 the additional plurality of ridges protrude outwardly from the additional first wall and define an additional plurality of compression gaps between the additional plurality of ridges and the additional second wall; and 
 the additional plurality of compression gaps have an additional height, measured perpendicular to the additional second wall, of from 20 to 80% of the average cell diameter of the plurality of cells. 
 
     
     
         12 . The system of  claim 6 , wherein each of the plurality of ridges has a rectangular shape, a cylindrical shape, a trapezoidal shape, or a triangular shape. 
     
     
         13 . The system of  claim 6 , wherein each of the plurality of ridges has a trapezoidal shape. 
     
     
         14 . The system of  claim 6 , wherein each of the plurality of ridges has a thickness from about 7 to about 30 microns. 
     
     
         15 . The system of  claim 6 , wherein the microchannel further comprises a second plurality of ridges protrude outwardly from the second wall toward the first wall. 
     
     
         16 . The system of  claim 6  further comprising one or more sheath flow inlets for hydrodynamic focusing of the cell medium within the microchannel. 
     
     
         17 . The system of  claim 16  further comprising a cell inlet for delivering the cell medium into the microchannel;
 wherein the cell inlet is positioned between two of the one or more sheath flow inlets. 
 
     
     
         18 . The system of  claim 16  further comprising a cell inlet for delivering the cell medium into the microchannel;
 wherein the cell inlet is surrounded by at least one of the one or more sheath flow inlets. 
 
     
     
         19 . The system of  claim 16  further comprising a cell inlet for delivering the cell medium into the microchannel;
 wherein the cell inlet is positioned downstream relative to at least one of the one or more sheath flow inlets. 
 
     
     
         20 . The system of  claim 6 , wherein at least one of the plurality of ridges comprises a cell adhesion entity or a passivation layer.