Semi-automated on-demand control of individual droplets with a sample application to a drug screening assay.

Automated control of individual droplets in microfluidic channels offers tremendous potential for applications requiring high accuracy and minimal user involvement. The feasibility of active droplet control has been previously demonstrated with pressure-driven flow control and visual feedback, but the manual operation required to perform droplet manipulations limited the accuracy, repeatability, and throughput. The present study improves upon the aforementioned challenges with a higher-level algorithm capturing the dynamics of droplet motion for a semi-automated control system. With a simple T junction geometry, droplets can now be automatically and precisely controlled on-demand. Specifically, there is ±10% accuracy for droplet generation, ±1.3% monodispersity for 500 μm long droplets and ±4% accuracy for splitting ratios. On-demand merging, mixing, and sorting are also demonstrated as well as the application of a drug screening assay related to neurodegenerative disorders. Overall, this system serves as a foundation for a fully automated system that does not require valves, embedded electrodes, or complex multi-layer fabrication.

[1]  Robert Langer,et al.  Microfluidic platform for controlled synthesis of polymeric nanoparticles. , 2008, Nano letters.

[2]  D. Weibel,et al.  Bacterial growth and adaptation in microdroplet chemostats. , 2013, Angewandte Chemie.

[3]  Xiaoming Chen,et al.  Droplet Microfluidic System with On-Demand Trapping and Releasing of Droplet for Drug Screening Applications. , 2017, Analytical chemistry.

[4]  Jianhong Xu,et al.  Preparation of highly monodisperse droplet in a T‐junction microfluidic device , 2006 .

[5]  Antonio Ramos,et al.  Breakup length of AC electrified jets in a microfluidic flow-focusing junction , 2015, Microfluidics and Nanofluidics.

[6]  Piotr Garstecki,et al.  High-throughput automated droplet microfluidic system for screening of reaction conditions. , 2010, Lab on a chip.

[7]  R. Seemann,et al.  Flow field induced particle accumulation inside droplets in rectangular channels. , 2015, Lab on a chip.

[8]  Abraham P Lee,et al.  Passive droplet sorting using viscoelastic flow focusing. , 2013, Lab on a chip.

[9]  Rustem F Ismagilov,et al.  Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system. , 2004, Lab on a chip.

[10]  Dino Di Carlo,et al.  Drop formation using ferrofluids driven magnetically in a step emulsification device. , 2016, Lab on a chip.

[11]  T. Mohamed,et al.  Tau-derived-hexapeptide 306VQIVYK311 aggregation inhibitors: nitrocatechol moiety as a pharmacophore in drug design. , 2013, ACS chemical neuroscience.

[12]  Rustem F Ismagilov,et al.  Using nanoliter plugs in microfluidics to facilitate and understand protein crystallization. , 2005, Current opinion in structural biology.

[13]  A. Lee,et al.  Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis. , 2006, Lab on a chip.

[14]  R. Oleschuk,et al.  Magnetically manipulated droplet splitting on a 3D-printed device to carry out a complexometric assay. , 2017, Lab on a chip.

[15]  M. Tanyeri,et al.  Characterizing the performance of the hydrodynamic trap using a control-based approach , 2015 .

[16]  M.D. Armani,et al.  Using feedback control of microflows to independently steer multiple particles , 2006, Journal of Microelectromechanical Systems.

[17]  David A. Weitz,et al.  Controlled production of emulsion drops using an electric field in a flow-focusing microfluidic device , 2007 .

[18]  P. Dittrich,et al.  Recent Advances in the Analysis of Single Cells. , 2017, Analytical chemistry.

[19]  Carolyn L. Ren,et al.  A microfluidic chip integrated with droplet generation, pairing, trapping, merging, mixing and releasing , 2017 .

[20]  P. V. Danckwerts The Definition and Measurement of Some Characteristics of Mixtures , 1952 .

[21]  Ting-Hsiang Wu,et al.  High-speed droplet generation on demand driven by pulse laser-induced cavitation. , 2011, Lab on a chip.

[22]  Raghunathan Rengaswamy,et al.  Design of a model‐based feedback controller for active sorting and synchronization of droplets in a microfluidic loop , 2012 .

[23]  A. deMello,et al.  Pillar-induced droplet merging in microfluidic circuits. , 2008, Lab on a chip.

[24]  Liguo Chen,et al.  Electrowetting on dielectric device with crescent electrodes for reliable and low-voltage droplet manipulation. , 2014, Biomicrofluidics.

[25]  Mario Rotea,et al.  Microfluidic device incorporating closed loop feedback control for uniform and tunable production of micro-droplets. , 2010, Lab on a chip.

[26]  David Wong,et al.  Microfluidic droplet trapping, splitting and merging with feedback controls and state space modelling. , 2016, Lab on a chip.

[27]  Jason T. Stevens,et al.  Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation , 2011, Nature.

[28]  G. Whitesides,et al.  Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. , 2006, Lab on a chip.

[29]  G. Whitesides,et al.  Soft lithography for micro- and nanoscale patterning , 2010, Nature Protocols.

[30]  Ximin He,et al.  A double droplet trap system for studying mass transport across a droplet-droplet interface. , 2010, Lab on a chip.

[31]  V. Chodavarapu,et al.  Algal fluorescence sensor integrated into a microfluidic chip for water pollutant detection. , 2012, Lab on a chip.

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

[33]  Shih-Kang Fan,et al.  Manipulation of multiple droplets on N/spl times/M grid by cross-reference EWOD driving scheme and pressure-contact packaging , 2003, The Sixteenth Annual International Conference on Micro Electro Mechanical Systems, 2003. MEMS-03 Kyoto. IEEE.

[34]  Zuwen Wang,et al.  Closed-loop feedback control of droplet formation in a T-junction microdroplet generator , 2015 .

[35]  Hansen Bow,et al.  Microfluidics for cell separation , 2010, Medical & Biological Engineering & Computing.

[36]  D. Weibel,et al.  Rapid screening of antibiotic toxicity in an automated microdroplet system. , 2012, Lab on a chip.

[37]  Chun-Xia Zhao,et al.  Two-phase microfluidic flows , 2011 .

[38]  P. Garstecki,et al.  A precise and accurate microfluidic droplet dilutor. , 2017, The Analyst.

[39]  Hyung Jin Sung,et al.  On-demand acoustic droplet splitting and steering in a disposable microfluidic chip. , 2018, Lab on a chip.