Enhanced cell/bead encapsulation methods and apparatuses

Abstract

A microfluidic droplet system that employs flow-focusing methods to generate droplets of desired sizes for encapsulating particles, cells or beads. The microfluidic droplet system can comprise an air cavity that can be vibrated to reduce trapping of cells or beads in flow-focusing regions of the microfluidic droplet systems thereby increasing the encapsulation efficiency of the cells/beads.

What is claimed is: 
     
         1 . A microfluidic device, comprising:
 a first fluid channel configured to transport a first fluid;   a second fluid channel configured to transport a second fluid;   an output fluid channel disposed downstream from the first and the second fluid channels; and   a flow-focusing region, the first and the second fluid channels terminating in the flow-focusing region, the flow-focusing region comprising:
 an orifice disposed to output the first and the second fluids transported through the first and the second fluid channels into the output fluid channel; and 
 an air cavity placed upstream from the orifice. 
   
     
     
         2 . The microfluidic device, further comprising a piezo-electric transducer configured to vibrate the air cavity. 
     
     
         3 . A method of encapsulating a solid sample in a droplet, the method comprising:
 flowing a first fluid through a first fluid channel, the first fluid including the cell/bead;   flowing a second fluid through a second fluid channel;   forcing the first and the second fluids through an orifice into an output fluid channel; and   modulating a fluid flow parameter in a zone disposed upstream from the orifice,   wherein a flow rate of the second fluid is configured to generate droplets of the first fluid of a desired size, and   wherein the fluid flow parameter is configured to achieve a desired encapsulation efficiency.   
     
     
         4 . The method of  claim 3 , wherein a piezo-electric transducer is configured to vibrate the air cavity. 
     
     
         5 . The method of  claim 3 , wherein the solid sample comprises a cell. 
     
     
         6 . The method of  claim 3 , wherein the solid sample comprises a bead including an organic material. 
     
     
         7 . The method of  claim 3 , wherein the parameter is a frequency of vibration. 
     
     
         8 . The method of  claim 3 , wherein the parameter is an amplitude of vibration. 
     
     
         9 . The method of  claim 3 , wherein modulating the fluid flow parameter includes vibrating an air cavity disposed upstream from the orifice, wherein a vibration parameter of the air cavity is configured to achieve a desired encapsulation efficiency. 
     
     
         10 . The method of  claim 3 , wherein modulating the fluid flow parameter includes altering the fluid flow rate upstream from the orifice. 
     
     
         11 . The method of  claim 3 , wherein modulating the fluid flow parameter includes applying a standing wave to the first fluid channel and/or to the second fluid channel, the standing wave having a wavelength a multiple of (e.g., two, four, six, or more times) a width of the first fluid channel and/or to the second fluid channel. 
     
     
         12 . A microfluidic device, comprising:
 a first fluid channel configured to transport a continuous phase;   a second fluid channel configured to transport a dispersed phase, the dispersed phase comprising a solid sample having a plurality of particles;   a droplet generation region comprising:
 a mixing region configured to receive the continuous phase and the dispersed phase; and 
 an output fluid channel connected to the mixing region through an orifice; and 
   a fluid controller configured to:
 adjust at least one flow parameter of the continuous phase or the dispersed phase to trap the plurality of particles of the dispersed phase in the mixing region in a first mode such that the plurality of particles of the dispersed phase are prevented from flowing through the orifice; and 
 adjust at least one flow parameter of the continuous phase or the dispersed phase to allow the plurality of particles to flow through the orifice such that the plurality of particles are encapsulated in droplets of dispersed phase in a second mode. 
   
     
     
         13 . The microfluidic device of  claim 12 , wherein the at least one flow parameter includes a flow velocity. 
     
     
         14 . The microfluidic device of  claim 12 , wherein the at least one flow parameter includes a fluid pressure. 
     
     
         15 . The microfluidic device of  claim 12 , wherein in the first mode, the fluid controller is configured to adjust at least one flow parameter of the continuous phase or the dispersed phase to generate a vortex in a flow field of the dispersed phase in the mixing region. 
     
     
         16 . The microfluidic device of  claim 15 , wherein in the first mode, the fluid controller is configured to adjust at least one flow parameter of the continuous phase or the dispersed phase such that a distance (d gap ) between an outermost streamline of the vortex generated in flow field of the dispersed phase and an interface between the dispersed phase and the continuous phase is greater than or equal to a size of the plurality of particles. 
     
     
         17 . The microfluidic device of  claim 12 , wherein in the second mode, the fluid controller is configured to adjust at least one flow parameter of the continuous phase or the dispersed phase to dissipate vortices in a flow field of the dispersed phase in the mixing region. 
     
     
         18 . The microfluidic device of  claim 12 , wherein the continuous phase comprises a lipid. 
     
     
         19 . The microfluidic device of  claim 12 , wherein the dispersed phase comprises an aqueous material. 
     
     
         20 . The microfluidic device of  claim 12 , wherein the size of the plurality of particles is about 2.5 μm. 
     
     
         21 . The microfluidic device of  claim 12 , further comprising a third fluid channel configured to allow the flow of a buffer solution through the mixing region, a parameter of the flow of the buffer solution being configured to untrap particles having a size smaller than a desired size from the plurality of particles. 
     
     
         22 . A method of encapsulating a solid sample in a droplet, the method comprising:
 flowing a continuous phase through a first fluid channel at a first flow rate;   flowing a dispersed phase through a second fluid channel at a second flow rate, the dispersed phase comprising particles or cells;   trapping the particles or cells in a mixing region that receives the dispersed phase and the continuous phase; and   reducing the first flow rate to encapsulate the trapped particles or cells in droplets of the dispersed phase generated when the dispersed phase and the continuous phase exit the mixing region through an orifice.   
     
     
         23 . The method of  claim 22 , wherein a size of the particles or cells is less than or equal to a distance (d gap ) between an outermost streamline of a vortex formed in flow field of the dispersed phase and an interface between the dispersed phase and the continuous phase.