Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing.

Fluorescence-activated droplet sorting (FADS) has become a widely used technique for high-throughput screening applications. However, existing methods are very sensitive to fluctuating flow rates at the sorting junction, which can be caused by the pulsing effects of mechanical pumps, droplet aggregates or the accumulation of precipitates during lengthy biological screening applications. Furthermore, existing sorting devices allow only 2-way sorting. We present here a dielectrophoretic sorting system in which the droplets are sorted along multiple electrode pairs that run parallel to the channels. This enables highly reliable sorting (no errors were detected for more than 2000 sorting events) even when inverting the relative flow rates at a 2-way sorting junction from 80 : 20 to 20 : 80. Furthermore, our toolbox is scalable: we demonstrate on the example of a triple-colour sorting experiment with a total of four decoupled electrodes that multi-way sorting is feasible.

[1]  J. Ottino.  The Kinematics of Mixing: Stretching, Chaos, and Transport , 1989 .

[2]  S. Neidle.  Oxford handbook of nucleic acid structure , 1998 .

[3]  W. Deen.  Analysis Of Transport Phenomena , 1998 .

[4]  D. Goodin.  The cambridge dictionary of statistics , 1999 .

[5]  J. Stoker,et al.  The Department of Health and Human Services. , 1999, Home healthcare nurse.

[6]  Clayton M. Christensen,et al.  The Innovator's Prescription: A Disruptive Solution for Health Care , 2008 .

[7]  D. Weitz,et al.  Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. , 2009, Lab on a chip.

[8]  Caglar Elbuken,et al.  Detection of microdroplet size and speed using capacitive sensors , 2011 .

[9]  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.

[10]  Christoph A. Merten,et al.  Functional single-cell hybridoma screening using droplet-based microfluidics , 2012, Proceedings of the National Academy of Sciences.

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

[12]  Fabienne Courtois,et al.  Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution. , 2012, Chemistry & biology.

[13]  A. van den Berg,et al.  Label-free, high-throughput, electrical detection of cells in droplets. , 2012, The Analyst.

[14]  J. Köhler,et al.  Investigation of mixture toxicity of widely used drugs caffeine and ampicillin in the presence of an ACE inhibitor on bacterial growth using droplet-based microfluidic technique , 2015 .

[15]  G. Stephanopoulos,et al.  Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption , 2014, Nature Biotechnology.

[16]  A. Armston.  The immunoassay handbook , 2014, Annals of clinical biochemistry.

[17]  A. Cowled,et al.  NATIONAL ADVISORY COMMITTEE FOR AERONAUTICS , 2000 .

[18]  A. Abate,et al.  Identification and genetic analysis of cancer cells with PCR-activated cell sorting , 2014, Nucleic acids research.

[19]  D. Weitz,et al.  Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter. , 2014, Lab on a chip.

[20]  Adam Sciambi,et al.  Accurate microfluidic sorting of droplets at 30 kHz. , 2015, Lab on a chip.

[21]  R. Leblanc,et al.  Recent Progress in Colloid and Surface Chemistry with Biological Applications , 2015 .

[22]  F. Hollfelder,et al.  Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics , 2015, Nature Communications.

[23]  Christoph A. Merten,et al.  Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. , 2016, Lab on a chip.