Microfluidic cellular membrane modification

Abstract

The present disclosure is drawn to microfluidic cellular membrane modification. In one example, a method of modifying cells can include pumping a fluid comprising cells in a forward direction through a microfluidic channel, applying an electric field within the microfluidic channel as cells flow in the forward direction through the electric field and beyond within the microfluidic channel, and pumping the fluid in a backward direction through the microfluidic channel, wherein cells flow in the backward direction returning through the electric field.

What is claimed is: 
     
         1 . A method of modifying cells, comprising:
 pumping a fluid comprising cells in a forward direction through a microfluidic channel;   applying an electric field within the microfluidic channel as cells flow in the forward direction through the electric field and beyond within the microfluidic channel; and   pumping the fluid in a backward direction through the microfluidic channel, wherein cells flow in the backward direction returning through the electric field.   
     
     
         2 . The method of  claim 1 , further comprising repeating pumping the fluid in the forward direction and the backward direction multiple times, wherein a portion of the cells flows through the electric field in both the forward and backward direction multiple times. 
     
     
         3 . The method of  claim 1 , wherein the electric field temporarily enlarges cell membrane pores, and wherein the method further comprises introducing a molecule into the cell through the cell membrane pores. 
     
     
         4 . The method of  claim 1 , wherein the electric field is a non-pulsating electric field having a magnitude of 0.01 V/μm to 10 V/μm. 
     
     
         5 . The method of  claim 1 , wherein the cells have a residence time during a single pass through the electric field of 0.01 ms to 10 s. 
     
     
         6 . The method of  claim 1 , wherein pumping the fluid in the forward direction and pumping the fluid in the backward direction is carried out using a bidirectional pump in fluid communication with the microfluidic channel. 
     
     
         7 . The method of  claim 6 , wherein the bidirectional pump is integrated within the microfluidic channel. 
     
     
         8 . The method of  claim 6 , wherein the bidirectional pump comprises a thermal resistor to move fluid via thermally-generated bubbles. 
     
     
         9 . The method of  claim 8 , further comprising ejecting a portion of the fluid displaced by the thermally-generated bubbles. 
     
     
         10 . The method of  claim 6 , wherein the microfluidic channel comprises a loop, wherein the bidirectional pump induces a net flow of fluid around the loop. 
     
     
         11 . The method of  claim 1 , wherein the microfluidic channel includes a constriction at a location where the electric field is applied, wherein the constriction is defined by a constricted cross-sectional area relative to a cross-sectional area compared to a region where the pumping occurs. 
     
     
         12 . The method of  claim 11 , wherein the fluid includes cells and wherein the constriction area is large enough to accommodate a single cell carried by the fluid. 
     
     
         13 . The method of  claim 1 , wherein the microfluidic channel has a serpentine shape crossing an electrode pair providing multiple electric fields along the microfluidic channel. 
     
     
         14 . A microfluidic system, comprising:
 a microfluidic device, comprising:
 a microfluidic channel having a pumping portion and an electric field portion, 
 an electrode pair positioned about the microfluidic channel to generate an electric field within the electric field portion and not within the pumping portion, and 
 a bidirectional pump in fluid communication with the microfluidic channel to pump fluid from the pumping portion alternately backward and forward multiple times through the electric field portion while the electric field is present; and 
   a controller, comprising a processor electrically coupled to the bidirectional pump and the electrode pair to control operation of the microfluidic device.   
     
     
         15 . The microfluidic system of  claim 14 , wherein the bidirectional pump comprises a thermal resistor to move fluid via thermally-generated bubbles, and the microfluidic device further includes an ejection nozzle in fluid communication with the bidirectional pump to eject a portion of the fluid displaced by the thermally-generated bubbles. 
     
     
         16 . The microfluidic system of  claim 14 , wherein the microfluidic channel is positioned over the electrode pair and the microfluidic channel has a serpentine shape crossing the electrode pair multiple times to provide multiple electric field portions. 
     
     
         17 . The microfluidic system of  claim 16 , wherein the bidirectional pump comprises a thermal resistor to move fluid via thermally-generated bubbles. 
     
     
         18 . The microfluidic system of  claim 14 , wherein the electric field portions include a constriction having a constricted cross-sectional area relative to a cross-sectional area of the pumping portion, wherein the cross-sectional areas are taken perpendicular to a direction of fluid flow through the microfluidic channel. 
     
     
         19 . The microfluidic system of  claim 18 , wherein the microfluidic device includes the fluid loaded within the microfluidic channel, wherein the fluid includes cells, and wherein the constricted cross-sectional area is large enough to accommodate a single cell carried by the fluid. 
     
     
         20 . The microfluidic system of  claim 14 , wherein the microfluidic channel comprises a loop wherein the bidirectional pump induces a net flow of fluid around the loop.