Droplet sorting based on ionization mass spectrometry

Abstract

A method for aligning sequences of droplets in streams of an emulsion comprising target droplets and tag droplets, a tag droplet comprising first and second tags. A target droplet is split into first and second target droplets and a tag droplet is split into first and second tag droplets. Each of the first and second tag droplets comprise the first and second tags. The first target droplet and first tag droplet are in a first stream of droplets, and the second target droplet and second tag droplet are in a second stream of droplets. The method detects the first tag droplets and first target droplets in the first stream and the second tag droplets and second target droplets in the second stream, determines a first sequence of droplets in the first stream and a second sequence of droplets in the second stream, and compares these to align the sequences.

1 .- 40 . (canceled) 
     
     
         41 . A droplet splitting module for splitting a droplet into a first droplet and a second droplet, the droplet splitting module comprising:
 an inlet channel; and   a plurality of outlet channels;   wherein a first said outlet channel has a first channel width variation in a downstream direction of said first outlet channel configured to generate a first back-pressure in said first outlet channel; and   wherein a second said outlet channel has a second channel width variation in a downstream direction of said second outlet channel configured to generate a second back-pressure in said second outlet channel; and   wherein a ratio between a volume of said first droplet and a volume of said second droplet is controllable by controlling a ratio between said first back-pressure and said second back-pressure.   
     
     
         42 .- 54 . (canceled) 
     
     
         55 . A droplet splitting module according to  claim 41 , wherein the first outlet channel widens at a first region of the first outlet channel, and wherein the second outlet channel widens at a first region of the second outlet channel, and wherein the first region of the second outlet channel is closer to the inlet channel than the first region of the first outlet channel. 
     
     
         56 . A droplet splitting module according to  claim 41 , wherein a width of the second outlet channel is larger than a width of the first outlet channel. 
     
     
         57 . A droplet splitting module according to  claim 41 , the module further comprising:
 a first spacing fluid to separate a said droplet from a neighbouring said droplet,   a second spacing fluid to separate a said first droplet from a neighbouring said first droplet, and   a third spacing fluid to separate a said second droplet from a neighbouring said second droplet.   
     
     
         58 . A system comprising:
 a droplet splitting module according to  claim 41 , wherein said droplet comprises a plurality of constituents, and wherein said first droplet comprises a first fraction of said plurality of constituents and said second droplet comprises a second fraction of said plurality of constituents,   an analyser for analysing said constituents of said first fraction of said plurality of constituents in said first droplet,   a droplet sorting module for sorting said second droplet, and   a feedback system in communication with said analyser and said droplet sorting module, wherein said feedback system is configured to control said sorting of said second droplet in said droplet sorting module dependent on an outcome of said analysis of said constituents of said first fraction of said plurality of constituents in said first droplet in said analyser.   
     
     
         59 . A system according to  claim 58 , wherein said feedback system is further configured to initiate said sorting of said second droplet in said droplet sorting module in tandem with said analysis of said constituents of said first fraction of said plurality of constituents in said first droplet in said analyser. 
     
     
         60 . A system according to  claim 58 , wherein the system further comprises a delay line such that said second droplet is sorted in said droplet sorting module in tandem with said analysis of said constituents of said first fraction of said plurality of constituents in said first droplet. 
     
     
         61 . A microfluidic chip comprising:
 the droplet splitting module according to  claim 41 ;   a droplet sorting module for sorting said second droplet;   a first channel connecting said droplet splitting module and an analyser, the first channel configured to guide a said first droplet from said droplet splitting module to said analyser,   a second channel connecting said droplet splitting module and said droplet sorting module, the second channel configured to guide a said second droplet from said droplet splitting module to said droplet sorting module, and   a connector for connecting said droplet sorting module and a feedback system.   
     
     
         62 . A microfluidic chip according to  claim 61 , wherein the first channel comprises a fitting for a mass spectrometer emitter. 
     
     
         63 . A microfluidic chip according to  claim 61 , wherein the second channel comprises a delay line configured such that said second droplet is sorted in said droplet sorting module in tandem with an analysis of said constituents of said first fraction of said plurality of constituents in said first droplet by the analyser. 
     
     
         64 . A method of forming a pair of droplets, the method comprising:
 providing a droplet;
 splitting said droplet into a first droplet and a second droplet; 
   directing the first droplet to a first outlet channel, wherein the first said outlet channel has a first channel width variation in a downstream direction of said first outlet channel configured to generate a first back-pressure in said first outlet channel; and   directing the second droplet to a second outlet channel, wherein the second said outlet channel has a second channel width variation in a downstream direction of said second outlet channel configured to generate a second back-pressure in said second outlet channel, and
 wherein a ratio between a volume of said first droplet and a volume of said second droplet is controllable by controlling a ratio between said first back-pressure and said second back-pressure. 
   
     
     
         65 . A method according to  claim 64 , wherein said first droplet comprises a first fraction of said plurality of constituents and said second droplet comprises a second fraction of said plurality of constituents, and wherein the method further comprises:
 analysing said constituents of said first fraction of said plurality of constituents in said first droplet, and   sorting said second droplet dependent on an outcome of said analysis.