Vacuum-Loaded, Droplet-Generating Microfluidic Chips and Related Methods

Abstract

A microfluidic chip that can have a body defining a microfluidic network including a test volume, one or more ports, and one or more channels in fluid communication between the port(s) and the test volume. Gas can be removed from the test volume before a sample liquid is introduced therein by reducing pressure at a first one of the port(s), optionally while the liquid is disposed in the port. Liquid in the first port can be introduced into the test volume by increasing pressure at the first port. The microfluidic network can define one or more droplet-generating regions in which at least one of the channel(s) defines a constriction and/or two or more of the channels connect at a junction. Liquid flowing from the first port can pass through at least one of the droplet-generating region(s) and to the test volume.

1 . A microfluidic chip comprising:
 a body; and   a plurality of microfluidic networks defined by the body, each of the networks including:
 one or more ports; 
 a test volume that is in fluid communication with each of the port(s); 
 one or more channels, each in fluid communication between at least one of the port(s) and the test volume; and 
 one or more droplet-generating regions, each in fluid communication between at least one of the port(s) and the test volume and configured to produce droplets; 
 wherein:
 the one or more ports consist of a single port; or 
 the one or more ports comprise two or more ports and the network is configured such that, for each of the ports, fluid is permitted to flow from the port to each other of the ports without flowing through the test volume. 
 
   
     
     
         2 . (canceled) 
     
     
         3 . The chip of  claim 1 , wherein, for each of the port(s):
 the port has a minimum cross-sectional area, taken perpendicularly to the centerline of the port; and   for each of the channel(s) connected to the port, the portion of the channel that connects to the port has a minimum cross-sectional area, taken perpendicularly to the centerline of the portion of the channel, that is less than or equal to 90% of the minimum cross-sectional area of the port.   
     
     
         4 . The chip of  claim 1 , wherein each of the channel(s) has a maximum transverse dimension, taken perpendicularly to the centerline of the channel, that is less than 2 millimeters (mm). 
     
     
         5 . The chip of  claim 1 , wherein the body comprises:
 a planar portion having top and bottom faces connected by an edge, the planar portion defining the test volume and the channel(s) of each of the microfluidic networks; and   for each of the microfluidic networks, one or more protrusions extending from the top face, each of the protrusion(s) defining at least a portion of at least one of the port(s) of one of the microfluidic networks.   
     
     
         6 . The chip of  claim 1 , wherein for each of the networks, at least one of the droplet-generating region(s) includes an expansion region. 
     
     
         7 . The chip of  claim 6 , wherein the expansion region has:
 a minimum height that is greater than or equal to 150% of a maximum height of a portion of the network that exits into the expansion region in a direction toward the test volume; and   a constant portion and an expanding portion such that liquid is permitted to exit the portion of the network into the constant portion and flow to the expanding portion, wherein:
 the constant portion has a height that is substantially the same between the portion of the network and the expanding portion and is substantially equal to the minimum height of the expansion region; and 
 the expanding portion has a height that increases moving away from the constant portion. 
   
     
     
         8 . A method of loading a microfluidic chip, the method comprising for each of a plurality of microfluidic networks of the microfluidic chip:
 disposing a liquid within a first one of one or more ports of the microfluidic network, the network including:
 a test volume that is in fluid communication with each of the port(s); 
 one or more channels, each in fluid communication between at least one of the port(s) and the test volume; and 
 one or more droplet-generating regions, each in fluid communication between at least one of the port(s) and the test volume and configured to produce droplets; and 
   introducing at least a portion of the liquid into the test volume at least by:
 (1) reducing pressure at the first port such that gas flows from the test volume, through at least one of the channel(s), and out of the first port; and 
 (2) increasing pressure at the first port such that the portion of the liquid flows from the first port, through at least one of the droplet-generating region(s), and into the test volume. 
   
     
     
         9 . The method of  claim 8 , wherein the port(s) consist of the first port. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 8 , wherein:
 the first port has a minimum cross-sectional area, taken perpendicularly to the centerline of the first port; and   for each of the channel(s) connected to the first port, the portion of the channel that connects to the first port has a minimum cross-sectional area, taken perpendicularly to the centerline of the portion of the channel, that is less than or equal to 90% of the minimum cross-sectional area of the first port.   
     
     
         12 . The method of  claim 8 , wherein each of the channel(s) has a maximum transverse dimension, taken perpendicularly to the centerline of the channel, that is less than 2 mm. 
     
     
         13 . The method of  claim 8 , wherein at least one of the droplet-generating region(s) includes an expansion region. 
     
     
         14 . The method of  claim 13 , wherein the expansion region has:
 a minimum height that is greater than or equal to 150% of a maximum height of a portion of the network that exits into the expansion region in a direction toward the test volume; and   a constant portion and an expanding portion such that when the portion of the liquid exits the portion of the network, the portion of the liquid enters into the constant portion and flows to the expanding portion, wherein:
 the constant portion has a height that is substantially the same between the portion of the network and the expanding portion and is substantially equal to the minimum height of the expansion region; and 
 the expanding portion has a height that increases moving away from the constant portion. 
   
     
     
         15 . The method of  claim 8 , wherein reducing pressure at the first port is performed at least by reducing pressure within a vacuum chamber within which the chip is disposed. 
     
     
         16 . The method of  claim 15 , wherein increasing pressure at the first port is performed at least by venting the vacuum chamber. 
     
     
         17 . The method of  claim 8 , wherein, during reducing pressure at the first port, gas that flows out of the first port passes through the liquid. 
     
     
         18 . The method of  claim 8 , wherein:
 prior to reducing pressure at the first port, pressure at the first port is substantially ambient pressure; and   after increasing pressure at the first port, pressure at the first port is substantially ambient pressure.   
     
     
         19 . The method of  claim 18 , wherein, after introducing at least a portion of the liquid into the test volume, pressure within the test volume is substantially ambient pressure. 
     
     
         20 . The method of  claim 8 , wherein the liquid comprises an aqueous liquid and a non-aqueous liquid. 
     
     
         21 . The chip of  claim 6 , wherein:
 a minimum height of the expansion region is greater than or equal to 150% of a maximum height of a portion of the network that exits into the expansion region in a direction toward the test volume; and   a maximum height of the expansion region and a maximum height of the test volume are each between 15 and 120 μm.   
     
     
         22 . The method of  claim 13 , wherein:
 a minimum height of the expansion region is greater than or equal to 150% of a maximum height of a portion of the network that exits into the expansion region in a direction toward the test volume; and   a maximum height of the expansion region and a maximum height of the test volume are each between 15 and 120 μm.