External control of reactions in microdroplets

Scale reduction of chemical reactions enables novel screening and synthesis approaches that facilitate a highly parallelized and combinatorial exploration of chemical space. Droplet-based microfluidics have evolved as a powerful platform to allow many chemical reactions within small volumes that each can be controlled and manipulated. A significant technical challenge is the ability to change the concentration of reactants inside a droplet. Here we describe a strategy that relies on the use of reactants that are soluble in both oil and water and allow a passive, diffusive exchange of reactants between the oil and aqueous phases to externally control composition of the droplets. We demonstrate the applicability of our approach by externally changing the pH inside microdroplets without the need for physical manipulation or droplet merging.

[1]  S. Radford,et al.  pH as a trigger of peptide beta-sheet self-assembly and reversible switching between nematic and isotropic phases. , 2003, Journal of the American Chemical Society.

[2]  F. Mugele,et al.  Droplets Formation and Merging in Two-Phase Flow Microfluidics , 2011, International journal of molecular sciences.

[3]  S. Boxer,et al.  Early steps of supported bilayer formation probed by single vesicle fluorescence assays. , 2002, Biophysical journal.

[4]  J. S. Johnson,et al.  Biocompatible surfactants for water-in-fluorocarbon emulsions. , 2008, Lab on a chip.

[5]  J. Sears,et al.  Partition coefficients for acetic, propionic, and butyric acids in a crude oil/water system , 1994 .

[6]  Jeong-Woo Choi,et al.  Electrochemical cell lysis device for DNA extraction. , 2010, Lab on a chip.

[7]  Antoine M. van Oijen,et al.  Single-particle kinetics of influenza virus membrane fusion , 2008, Proceedings of the National Academy of Sciences.

[8]  L. Mazutis,et al.  Dynamics of molecular transport by surfactants in emulsions , 2012 .

[9]  John A Rogers,et al.  High-resolution electrohydrodynamic jet printing. , 2007, Nature materials.

[10]  M. T. Gokmen,et al.  Porous Polymer Particles - A Comprehensive Guide to Synthesis, Characterization, Functionalization and Applications , 2012 .

[11]  P. Nollert,et al.  Lipid vesicle adsorption versus formation of planar bilayers on solid surfaces. , 1995, Biophysical journal.

[12]  J. Sangster Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry , 1997 .

[13]  Sang‐Hyun Oh,et al.  High-density arrays of submicron spherical supported lipid bilayers. , 2012, Analytical chemistry.

[14]  D. Weitz,et al.  Geometrically mediated breakup of drops in microfluidic devices. , 2003, Physical review letters.

[15]  Hsueh-Chia Chang,et al.  Microscale pH regulation by splitting water. , 2011, Biomicrofluidics.

[16]  P Yager,et al.  Formation of natural pH gradients in a microfluidic device under flow conditions: model and experimental validation. , 2001, Analytical chemistry.

[17]  M. Kubista,et al.  Absorption and fluorescence properties of fluorescein , 1995 .

[18]  Jong Wook Hong,et al.  Integrated nanoliter systems , 2003, Nature Biotechnology.

[19]  R. Rhinehart Model and Experimental Validation , 2016 .

[20]  M. Dixon The effect of pH on the affinities of enzymes for substrates and inhibitors. , 1953, The Biochemical journal.

[21]  D. Weitz,et al.  Droplet microfluidics for high-throughput biological assays. , 2012, Lab on a chip.

[22]  Hiroaki Suzuki,et al.  Electrochemical techniques for microfluidic applications , 2008, Electrophoresis.

[23]  Jay D Keasling,et al.  Microbioreactor arrays with parametric control for high-throughput experimentation. , 2004, Biotechnology and bioengineering.

[24]  P. Rohr,et al.  Continuous Micro Liquid‐Liquid Extraction , 2013 .

[25]  H. Imaishi,et al.  Microarrays of phospholipid bilayers generated by inkjet printing. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[26]  M. Textor,et al.  Supported lipid bilayer microarrays created by non-contact printing. , 2011, Lab on a chip.

[27]  A. Griffiths,et al.  High-resolution dose–response screening using droplet-based microfluidics , 2011, Proceedings of the National Academy of Sciences of the United States of America.