Integrated droplet-digital microfluidic system for on-demand droplet creation, mixing, incubation, and sorting of droplets in a cell trapping array

Abstract

Microfluidic devices, systems and methods are described herein. The devices, systems and methods provide for trapping particles, including cells. Methods of generating a droplet in a microfluidic device and collecting droplets from microfluidic devices are also disclosed herein.

1 . A microfluidic device comprising:
 a first layer including a plurality of co-planar electrodes;   a second layer disposed on top of the first layer, the second layer including a dielectric material patterned over the electrodes; and   a third layer disposed on top of the second layer, the third layer including microfluidic channels including:
 a trapping array including:
 a channel fluidly coupled to a first inlet and a second inlet for carrying a first fluid from the first inlet and/or a second fluid from the second inlet toward an outlet of the trapping array, the first fluid comprising one or more particles in solution; and 
 
   
       one or more traps extending away from the channel, each trap configured to receive and retain a trapped element from the channel;
 wherein each of the one or more traps include:
 a first end fluidly coupled to the channel to receive the trapped element from the channel; and 
 a second end fluidly coupled to the channel downstream from the first end, the second end being configured to retain the trapped element from the channel. 
 
 
     
     
         2 - 12 . (canceled) 
     
     
         13 . The microfluidic device of  claim 1 , wherein the trapped element is at least one particle. 
     
     
         14 . The microfluidic device of  claim 1 , wherein the trapped element is biological material, the biological material including one or more bacterial cells, human cells, mammalian cells, yeast cells, algae cells, plant cells, insect cells or fungal cells. 
     
     
         15 . The microfluidic device of  claim 1 , wherein the trapped element is a droplet. 
     
     
         16 . The microfluidic device of  claim 15 , wherein the droplet includes a particle content. 
     
     
         17 . The microfluidic device of any one of  claim 1 , wherein the first end of the trap has a width greater than a diameter of the trapped element and the second end of the trap has a width about equal to the diameter of the trapped element. 
     
     
         18 . The microfluidic device of  claim 17 , wherein the width of the first end of the trap is about 50 μm to receive the trapped element from the channel. 
     
     
         19 . The microfluidic device of  claim 1 , wherein the width of the second end of the trap is about 8 μm to retain the trapped element in the trap. 
     
     
         20 . The microfluidic device of  claim 1 , wherein a resistance in the channel downstream of the first end of the trap is greater than or equal to a resistance through the trap, such that when the trapped element is in the trap, the resistance in the channel downstream of the first end of the trap is less than the resistance through the trap. 
     
     
         21 - 31 . (canceled) 
     
     
         32 . A method of merging two or more droplets within a microfluidic device, the method comprising;
 trapping a first droplet in a trap of the microfluidic device by directing the first droplet towards the trap;   directing a second droplet towards the trap; and   as the second drop reaches the trap, actuating one or more electrodes positioned underneath the trap;   
       wherein each of the first droplet and the second droplet contain a single particle. 
     
     
         33 . (canceled) 
     
     
         34 . A method collecting a droplet from the microfluidic device of  claim 1 , the method comprising:
 directing the droplet towards the outlet of the microfluidic device; and   absorbing the droplet into a capillary-like structure;   
       wherein, once absorbed, the droplet can be transferred into a secondary recipient such as a second microfluidic device, a well-plate, a petri dish, a microscope slide, a microscope chamber, a culturing dish or other observational or growth chamber; 
       further comprising absorbing an oil phase of a fluid from the microfluidic device using an oleophilic hydrophobic material. 
     
     
         35 - 42 . (canceled) 
     
     
         43 . A microfluidic device comprising:
 an electrode layer including a plurality of electrodes;   a dielectric layer disposed on top of the electrode layer, the dielectric layer including a dielectric patterned over the plurality of electrodes; and   a channel layer disposed on top of the dielectric layer, the channel layer including:
 a droplet generator for generating droplets of fluid; and 
 a single cell droplet array including:
 a first inlet for receiving the droplets of fluid from the droplet generator; 
 a second inlet for receiving cells in solution; 
 a serpentine channel for carrying the droplets of fluid and/or the cells in solution from the first inlet and the second inlet, respectively, towards an outlet; and 
 
   
       one or more traps extending away from the channel, each trap configured to receive and retain cells in solution and droplets of fluid from the channel;
 wherein each of the one or more traps include: 
 a first end fluidly coupled to the serpentine channel to receive cells in solution and droplets of fluid from the serpentine channel; and 
 a second end fluidly coupled to the serpentine channel at a position downstream from the first end, the second end being configured to retain cells in solution and droplets of fluid from the channel; 
 and wherein, for each trap, the serpentine channel upstream of the first end of the trap is configured to provide for a volumetric flow rate through the trap that is higher than a volumetric flow rate downstream of the first end of the trap and upstream of the second end of the trap when there is no cell in the trap. 
 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The microfluidic device of  claim 43 , wherein the first end of the trap has a width of about 50 μm. 
     
     
         47 . The microfluidic device of  claim 43 , wherein the sepertine channel has a width of about 50 μm immediately after the first end of the trap. 
     
     
         48 . The microfluidic device of  claim 43 , wherein the serpentine channel downstream of the first end of the trap and upstream of the second end of the trap includes a curved portion that provides for a 180 degree turn for the fluid in the serpentine channel. 
     
     
         49 - 50 .(canceled) 
     
     
         51 . The microfluidic device of  claim 43 , wherein the first end has a first width greater than a diameter of the cell and the second end has a second width about equal to the diameter of the cells. 
     
     
         52 . The microfluidic device  claim 43 , wherein the second end of the trap has a width of about 8 μm to retain cells in solution in the trap. 
     
     
         53 - 57 . (canceled)