Apparatus for mass producing a monodisperse microbubble agent

Abstract

An apparatus for mass producing monodisperse microbubbles includes a microfluidic flow focusing device, which includes a dispersed phase fluid supply channel having an outlet that discharges into a flow focusing junction, a continuous phase fluid supply channel having an outlet that discharges into the flow focusing junction, and a bubble formation channel having an inlet disposed at the flow focusing junction. The configuration of the flow focusing junction is such that, in operation, a flow of dispersed phase fluid discharging from the outlet of the dispersed phase fluid supply channel is engageable in co-flow by a focusing flow of continuous phase fluid discharging from the outlet of the at least one continuous phase fluid supply channel under formation of a gradually thinning jet of dispersed phase fluid that extends into the inlet of the bubble formation channel.

What is claimed is: 
     
         1 . An apparatus for mass producing monodisperse microbubbles, comprising:
 at least one microfluidic flow focusing device including:
 a dispersed phase fluid supply channel having an outlet that discharges into a flow focusing junction; 
 at least one continuous phase fluid supply channel having an outlet that discharges into the flow focusing junction; and 
 a bubble formation channel having an inlet disposed at the flow focusing junction, 
   the configuration of the flow focusing junction being such that, in operation, a flow of dispersed phase fluid discharging from the outlet of the dispersed phase fluid supply channel is engageable in co-flow by a focusing flow of continuous phase fluid discharging from the outlet of the at least one continuous phase fluid supply channel under formation of a gradually thinning jet of dispersed phase fluid that extends into the inlet of the bubble formation channel,
 wherein said bubble formation channel has a length that is much greater than its hydraulic diameter by a factor of at least ten. 
   
     
     
         2 . The apparatus according to  claim 1 , further comprising:
 a source of dispersed phase fluid, operably connected to an inlet of the dispersed phase fluid supply channel; and   a source of continuous phase fluid, operably connected to an inlet of the at least one continuous phase fluid supply channel.   
     
     
         3 . The apparatus according to  claim 2 , wherein the dispersed phase fluid is a gas, and the continuous phase fluid is a liquid 
     
     
         4 . The apparatus according to  claim 2 , wherein the dispersed phase fluid is a liquid, and the continuous phase fluid is a gas. 
     
     
         5 . The apparatus according to  claim 2 , wherein at least one of the dispersed phase fluid and the continuous phase fluid contains a surfactant suitable to populate a fluid interface between the dispersed phase fluid and the continuous phase fluid, and to thus stabilize bubbles of dispersed phase fluid within the continuous phase fluid. 
     
     
         6 . The apparatus according to  claim 2 , wherein the bubble formation channel is bounded by a wall having a portion of inner wall surface that extends substantially from the inlet of the bubble formation channel and in a longitudinal direction thereof, and that has a low wettability with respect to the continuous phase fluid. 
     
     
         7 . The apparatus according to  claim 6 , wherein the bubble formation channel is bounded by a wall having a portion of inner wall surface that extends substantially from the inlet of the bubble formation channel and in a longitudinal direction thereof, and that defines an inner wall surface enlarging provision. 
     
     
         8 . The apparatus according to  claim 7 , wherein the inner wall surface enlarging provision includes at least one of a longitudinally extending ridge, a longitudinally extending slot, and a roughened inner wall surface area. 
     
     
         9 . The apparatus according to  claim 7 , wherein said portion of inner wall surface with low wettability defines said inner wall surface enlarging provision. 
     
     
         10 . The apparatus according to  claim 1 , wherein bubble formation channel is substantially straight and substantially uniform in cross-section over its length. 
     
     
         11 . The apparatus according to  claim 1 , wherein the length of the bubble formation channel is greater than 1 mm. 
     
     
         12 . The apparatus according to  claim 1 , wherein the hydraulic diameter of the bubble formation channel is between 10 μm and 100 μm. 
     
     
         13 . The apparatus according to  claim 1 , further comprising:
 a bubble harvesting reservoir;   a transition channel, wherein said transition channel fluidly connects an outlet of the bubble formation channel to the bubble harvesting reservoir, and wherein said transition channel has a gradually increasing hydraulic diameter.   
     
     
         14 . The apparatus according to  claim 1 , wherein the at least one microfluidic flow focusing device has a substantially planar flow focusing geometry, such that the respective channels at least partially extend in a same plane. 
     
     
         15 . The apparatus according to  claim 1 , wherein the at least one microfluidic flow focusing device includes two continuous phase fluid supply channels,
 wherein the outlet of the dispersed phase fluid supply channel, the outlets of the two continuous phase fluid supply channels, and the inlet of the bubble formation channel define the flow focusing junction,   wherein the dispersed phase fluid supply channel is substantially aligned with the bubble formation channel, such that the inlet of the bubble formation channel is disposed opposite the outlet of the dispersed phase fluid supply channel, and   wherein the outlets of the two continuous phase fluid channels join the flow focusing junction from substantially opposite sides.   
     
     
         16 . The apparatus according to  claim 1 , wherein the continuous phase fluid supply channels include a tapering portion just upstream of their respective outlets.