Microfluidic Vortex-Assisted Electroporation System and Method

Abstract

A system and method include delivering cells of interest to multiple traps via a channel connecting the traps, maintaining a vortex flow in the traps to trap the cells of interest in the traps, providing first molecules of interest to the traps, and providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps.

1 - 20 . (canceled) 
     
     
         21 . A method comprising:
 delivering particles of interest to multiple traps via fluid flowing along an axis through a channel connecting the traps;   maintaining a vortex flow in the traps to trap the particles of interest in the traps, wherein the vortex comprises a rotational flow around an axis perpendicular to the axis of flow through the channel; and   performing electroporation on the particles of interest while they are trapped in the traps.   
     
     
         22 . The method of  claim 21  wherein delivering the particles of interest is performed by transporting a first fluid solution containing the particles of interest via the channel at a speed such that the fluid has a Reynolds number of greater than 100 to create the vortex flow in the traps. 
     
     
         23 . The method of  claim 22  and further comprising providing first molecules of interest to the traps comprises using a second fluid solution containing the first molecules of interest while maintaining the vortex flow in the traps and removing the first solution. 
     
     
         24 . The method of  claim 23  wherein performing electroporation on the particles of interest comprises performing electroporation of the first molecules of interest into the particles of interest in the traps. 
     
     
         25 . The method of  claim 24  wherein electroporation is performed by providing an electric field in the traps suitable for electroporation of the first molecules of interest into the particles of interest. 
     
     
         26 . The method of  claim 25  wherein the electric field is provided by applying a voltage across the traps with a magnitude sufficient to cause an electric field strength across the traps of between 0.1 to 2 kV/cm. 
     
     
         27 . The method of  claim 24  wherein the first molecules of interest are selected from the group consisting of dyes, proteins, plasmids, DNA fragments, RNA fragments, and drugs. 
     
     
         28 . The method of  claim 24  wherein the first fluid solution comprises a body fluid and the particles comprise cancer cells. 
     
     
         29 . The method of  claim 24  and further comprising using a third fluid solution containing further molecules of interest while maintaining the vortex flow in the traps, the further molecules of interest being provided following electroporation of the first molecules of interest. 
     
     
         30 . The method of  claim 29  and further comprising performing electroporation of the second molecules of interest into the particles of interest in the traps. 
     
     
         31 . The method of  claim 30  and further comprising replacing the second fluid with additional fluids containing additional molecules of interest while maintaining the vortex flow in the traps. 
     
     
         32 . The method of  claim 30  wherein the vortex flow is maintained during the entire method. 
     
     
         33 . The method of  claim 22  wherein delivering particles of interest in solution to multiple traps via the channel connecting the traps includes providing the first solution to the channel via an inertial focusing region to cause the particles of interest to move close to the sides of the channel via fluidic forces. 
     
     
         34 . The method of  claim 33  wherein the channel breaks into multiple channels, each having opposing pairs of traps disposed along a length of the channels. 
     
     
         35 . A system comprising:
 a first channel having an inlet to receive a solution containing particles of interest;   a plurality of traps disposed along a length of the first channel downstream of the inlet, the size of each trap adapted to promote vortex flow within the traps while the solution is flowing through the first channel to trap the cells in the traps;   an outlet of the first channel disposed downstream from the plurality of traps; and   electrodes coupled to provide an electric field across the traps.   
     
     
         36 . The system of  claim 35  wherein the channel has a width such that the particles of interest traveling through the channel are approximately 30 percent or greater than the width of the channel. 
     
     
         37 . The system of  claim 35  wherein a second channel configured the same as the first channel is in parallel with the first channel. 
     
     
         38 . The system of  claim 37  and further comprising multiple inlets to the first and second channel inertial focusing regions, the inlets adapted to receive solutions from multiple sources including a cell solution and a molecule solution. 
     
     
         39 . The system of  claim 38  wherein the inlets are adapted to receive further solutions for incubation and flushing. 
     
     
         40 . The system of  claim 39  wherein the first and second channels each include five opposing pairs of traps serially disposed downstream from the inertial focusing region of each channel. 
     
     
         41 . The system of  claim 37  wherein each trap is approximately rectangular in shape. 
     
     
         42 . The system of  claim 41  wherein the traps have sides of between approximately 1 mm to 500 μm. 
     
     
         43 . The system of  claim 35  wherein the electrodes are positioned to electrically couple to fluid in a respective trap, each electrode comprising:
 a plurality of electrically conductive projections formed in an array to contact fluid in the trap without adversely affecting the vortex flow within the trap; and 
 a conductor coupled to the plurality of electrically conductive projections to provide electrical energy to the conductive projections. 
 
     
     
         44 . The system of  claim 35  wherein the system comprises multiple additional channels configured the same as the first channel. 
     
     
         45 . The system of  claim 35  wherein the first channel comprises more than five traps. 
     
     
         46 . A system comprising:
 a first channel having an inertial focusing region to move cells in a solution travelling through the first channel towards sides of the channel;   a plurality of traps disposed along a length of the first channel downstream of the inertial focusing region, the size of each trap adapted to promote vortex flow within the traps while the solution is flowing through the first channel to trap the cells in the traps;   an outlet of the channel disposed downstream from the plurality of traps; and electrodes coupled to provide an electric field across the traps.