Abstract
Digital microfluidics (DMF) is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DMF, discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by applying electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields (e.g., chemistry, biology, medicine, and environment). This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.
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Terry S C, Jerman J H, Angell J B. A gas chromatographic air analyzer fabricated on a silicon wafer. IEEE Transactions on Electron Devices, 1979, 26(12): 1880–1886
Reyes D R, Iossifidis D, Auroux P A, et al. Micro total analysis system. 1. Introduction, theory, and technology. Analitical Chemistry, 2002, 74(12): 2623–2636
Mugele F, Baret J C. Electrowetting: From basics to applications. Journal of Physics Condensed Matter, 2005, 17(28): R705–R774
Pollack M G, Shenderov A D, Fair R B. Electrowetting-based actuation of droplets for integrated microfluidics. Lab on a Chip, 2002, 2(2): 96–101
Washizu M. Electrostatic actuation of liquid droplets for microreactor applications. IEEE Transactions on Industry Applications, 1998, 34(4): 732–737
Cho S K, Fan S K, Moon H, et al. Towards digital microfluidic circuits: Creating, transporting, cutting and merging liquid droplets by electrowetting-based actuation. In: Proceedings of the Fifteenth IEEE International Conference on Micro Electro Mechanical Systems. Las Vegas: IEEE, 2002, 32–35
Cho S K, Moon H, Kim C J. Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. Journal of Microelectromechanical Systems, 2003, 12(1): 70–80
Berthier J. Microdrops and Digital Microfluidics. Norwich: William Andrew Inc., 2008
Wang W, Jones T B. Moving droplets between closed and open microfluidic systems. Lab on a Chip, 2015, 15(10): 2201–2212
Wheeler A R. Putting electrowetting to work. Science, 2008, 322 (5901): 539–540
Hsieh T H, Fan S K. Dielectric droplet manipulations by electropolarization forces. In: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems. Piskataway: IEEE, 2008, 641–644
Jones T B, Wang K L, Yao D J. Frequency-dependent electromechanics of aqueous liquids: Electrowetting and dielectrophoresis. Langmuir, 2004, 20(7): 2813–2818
Mugele F, Baret J C. Electrowetting: From basics to applications. Journal of Physics Condensed Matter, 2005, 17(28): R705–R774
Gupta R, Sheth D M, Boone T K, et al. Impact of pinning of the triple contact line on electrowetting performance. Langmuir, 2011, 27(24): 14923–14929
Chen L Q, Bonaccurso E. Electrowetting—From statics to dynamics. Advances in Colloid and Interface Science, 2014, 210: 2–12
Kang K H. How electrostatic fields change contact angle in electrowetting. Langmuir, 2002, 18(26): 10318–10322
Peykov V, Quinn A, Ralston J. Electrowetting: A model for contactangle saturation. Colloid & Polymer Science, 2000, 278(8): 789–793
Darhuber A A, Chen J Z, Davis J M, et al. A study of mixing in thermocapillary flows on micropatterned surfaces. Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences, 2004, 362(1818): 1037–1058
Darhuber A A, Valentino J P, Troian S M. Planar digital nanoliter dispensing system based on thermocapillary actuation. Lab on a Chip, 2010, 10(8): 1061–1071
Heron S R, Wilson R, Shaffer S A, et al. Surface acoustic wave nebulization of peptides as a microfluidic interface for mass spectrometry. Analytical Chemistry, 2010, 82(10): 3985–3989
Jin H, Zhou J, He X, et al. Flexible surface acoustic wave resonators built on disposable plastic film for electronics and lab-on-a-chip applications. Scientific Reports, 2013, 3: 2140
Pang H, Fu Y, Garcia-Gancedo L, et al. Enhancement of microfluidic efficiency with nanocrystalline diamond interlayer in the ZnO-based surface acoustic wave device. Microfluidics and Nanofluidics, 2013, 15(3): 377–386
Shilton R J, Mattoli V, Travagliati M, et al. Rapid and controllable digital microfluidic heating by surface acoustic waves. Advanced Functional Materials, 2015, 25(37): 5895–5901
Seemann R, Brinkmann M, Pfohl T, et al. Droplet based microfluidics. Reports on Progress in Physics, 2012, 75(1): 016601
Gu H, Duits M H G, Mugele F. Droplets formation and merging in two-phase flow microfluidics. International Journal of Molecular Sciences, 2011, 12(12): 2572–2597
Renaudot R, Agache V, Daunay B, et al. Optimization of liquid dielectrophoresis (LDEP) digital microfluidic transduction for biomedical applications. Micromachines, 2011, 2(4): 258–273
Renaudot R, Daunay B, Kumemura M, et al. Optimized micro devices for liquid-dielectrophoresis (LDEP) actuation of conductive solutions. Sensors and Actuators B: Chemical, 2013, 177: 620–626
Timonen J V I, Latikka M, Leibler L, et al. Switchable static and dynamic self-assembly of magnetic droplets on superhydrophobic surfaces. Science, 2013, 341(6143): 253–257
Ng A H C, Choi K, Luoma R P, et al. Digital microfluidic magnetic separation for particle-based immunoassays. Analytical Chemistry, 2012, 84(20): 8805–8812
Witters D, Knez K, Ceyssens F, et al. Digital microfluidics-enabled single-molecule detection by printing and sealing single magnetic beads in femtoliter droplets. Lab on a Chip, 2013, 13(11): 2047–2054
Shi D, Bi Q, He Y, et al. Experimental investigation on falling ferrofluid droplets in vertical magnetic fields. Experimental Thermal and Fluid Science, 2014, 54: 313–320
Choi K, Ng A H C, Fobel R, et al. Digital microfluidics. Annual Review of Analytical Chemistry, 2012, 5(1): 413–440
Kumar A, Williams S J, Chuang H S, et al. Hybrid opto-electric manipulation in microfluidics—Opportunities and challenges. Lab on a Chip, 2011, 11(13): 2135–2148
Takinoue M, Takeuchi S. Droplet microfluidics for the study of artificial cells. Analytical and Bioanalytical Chemistry, 2011, 400 (6): 1705–1716
Vergauwe N, Witters D, Atalay Y T, et al. Controlling droplet size variability of a digital lab-on-a-chip for improved bio-assay performance. Microfluidics and Nanofluidics, 2011, 11(1): 25–34
Yaddessalage J B. Study of the capabilities of electrowetting on dielectric digital microfluidics (EWOD DMF) towards the high efficient thin-film evaporative cooling platform. Dissertation for the Doctoral Degree. Arlington: The University of Texas at Arlington, 2013
Elvira K S, Leatherbarrow R, Edel J, et al. Droplet dispensing in digital microfluidic devices: Assessment of long-term reproducibility. Biomicrofluidics, 2012, 6(2): 022003
Yafia M, Najjaran H. High precision control of gap height for enhancing principal digital microfluidics operations. Sensors and Actuators B: Chemical, 2013, 186: 343–352
Chang J H, Pak J J. Twin-plate electrowetting for efficient digital microfluidics. Sensors and Actuators B: Chemical, 2011, 160(1): 1581–1585
Cui W, Zhang M, Zhang D, et al. Island-ground single-plate electrowetting on dielectric device for digital microfluidic systems. Applied Physics Letters, 2014, 105(1): 013509
Ko H, Lee J, Kim Y, et al. Active digital microfluidic paper chips with inkjet-printed patterned electrodes. Advanced Materials, 2014, 26(15): 2335–2340
Fobel R, Kirby A E, Ng A H C, et al. Paper microfluidics goes digital. Advanced Materials, 2014, 26(18): 2838–2843
Fobel R, Kirby A E, Wheeler A R. Paper microfluidics goes digital. In: Proceedings of 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS. Freiburg: Chemical and Biological Microsystems Society, 2013, 708–710
Dixon C, Kirby A E, Fobel R, et al. Paper digital microfluidics and paper spray ionization mass spectrometry. In: Proceedings of 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS. San Antonio: Chemical and Biological Microsystems Society, 2014, 2196–2198
Dixon C, Ng A H C, Fobel R, et al. An inkjet printed, roll-coated digital microfluidic device for inexpensive, miniaturized diagnostic assays. Lab on a Chip, 2016, 16(23): 4560–4568
Yafia M, Shukla S, Najjaran H. Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing. Journal of Micromechanics and Microengineering, 2015, 25(5): 057001
Taniguchi T, Torii T, Higuchi T. Chemical reactions in microdroplets by electrostatic manipulation of droplets in liquid media. Lab on a Chip, 2002, 2(1): 19–23
Ito T, Torii T, Higuchi T. Electrostatic micromanipulation of bubbles for microreactor applications. In: Proceedings of IEEE the Sixteenth Annual International Conference on Micro Electro Mechanical System. Kyoto: IEEE, 2003, 335–338
Sista R S, Eckhardt A E,Wang T, et al. Digital microfluidic platform for multiplexing enzyme assays: Implications for lysosomal storage disease screening in newborns. Clinical Chemistry, 2011, 57(10): 1444–1451
Boles D J, Benton J L, Siew G J, et al. Droplet-based pyrosequencing using digital microfluidics. Analytical Chemistry, 2011, 83(22): 8439–8447
Choi K, Boyaci E, Kim J, et al. A digital microfluidic interface between solid-phase microextraction and liquid chromatography— Mass spectrometry. Journal of Chromatography A, 2016, 1444: 1–7
Keng P Y, Chen S, Ding H J, et al. Micro-chemical synthesis of molecular probes on an electronic microfluidic device. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(3): 690–695
Dooraghi A A, Keng P Y, Chen S, et al. Optimization of microfluidic PET tracer synthesis with Cerenkov imaging. Analyst (London), 2013, 138(19): 5654–5664
Witters D, Vergauwe N, Ameloot R, et al. Digital microfluidic highthroughput printing of single metal-organic framework crystals. Advanced Materials, 2012, 24(10): 1316–1320
Shamsi M H, Choi K, Ng A H C, et al. A digital microfluidic electrochemical immunoassay. Lab on a Chip, 2014, 14(3): 547–554
Ng A H C, Lee M, Choi K, et al. Digital microfluidic platform for the detection of rubella infection and immunity: A proof of concept. Clinical Chemistry, 2015, 61(2): 420–429
Miller EM, Ng A H C, Uddayasankar U, et al. A digital microfluidic approach to heterogeneous immunoassays. Analytical and Bioanalytical Chemistry, 2011, 399(1): 337–345
Sista R S, Eckhardt A E, Srinivasan V, et al. Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. Lab on a Chip, 2008, 8(12): 2188–2196
Fair R B. Digital microfluidics: Is a true lab-on-a-chip possible? Microfluidics and Nanofluidics, 2007, 3(3): 245–281
Yoon J Y, Garrell R L. Preventing biomolecular adsorption in electrowetting-based biofluidic chips. Analytical Chemistry, 2003, 75(19): 5097–5102
Shah G J, Kim C J. Meniscus-assisted high-efficiency magnetic collection and separation for EWOD droplet microfluidics. Journal of Microelectromechanical Systems, 2009, 18(2): 363–375
Barbulovic-Nad I, Au S H, Wheeler A R. A microfluidic platform for complete mammalian cell culture. Lab on a Chip, 2010, 10(12): 1536–1542
Choi K, Ng A H C, Fobel R, et al. Automated digital microfluidic platform for magnetic-particle-based immunoassays with optimization by design of experiments. Analytical Chemistry, 2013, 85(20): 9638–9646
Huang C Y, Tsai P Y, Lee I C, et al. A highly efficient bead extraction technique with low bead number for digital microfluidic immunoassay. Biomicrofluidics, 2016, 10(1): 011901
Au S H, Shih S C C, Wheeler A R. Integrated microbioreactor for culture and analysis of bacteria, algae and yeast. Biomedical Microdevices, 2011, 13(1): 41–50
Shih S C C, Gach P C, Sustarich J, et al. A droplet-to-digital (D2D) microfluidic device for single cell assays. Lab on a Chip, 2015, 15 (1): 225–236
Eydelnant I A, Uddayasankar U, Li B, et al. Virtual microwells for digital microfluidic reagent dispensing and cell culture. Lab on a Chip, 2012, 12(4): 750–757
Bogojevic D, Chamberlain M D, Barbulovic-Nad I, et al. A digital microfluidic method for multiplexed cell-based apoptosis assays. Lab on a Chip, 2012, 12(3): 627–634
Fiddes L K, Luk V N, Au S H, et al. Hydrogel discs for digital microfluidics. Biomicrofluidics, 2012, 6(1): 014112
George S M, Moon H. Digital microfluidic three-dimensional cell culture and chemical screening platform using alginate hydrogels. Biomicrofluidics, 2015, 9(2): 024116
Au S H, Chamberlain M D, Mahesh S, et al. Hepatic organoids for microfluidic drug screening. Lab on a Chip, 2014, 14(17): 3290–3299
Nejad H R, Chowdhury O Z, BuatMD, et al. Characterization of the geometry of negative dielectrophoresis traps for particle immobilization in digital microfluidic platforms. Lab on a Chip, 2013, 13 (9): 1823–1830
Valley J K, Ningpei S, Jamshidi A, et al. A unified platform for optoelectrowetting and optoelectronic tweezers. Lab on a Chip, 2011, 11(7): 1292–1297
Kumar P T, Toffalini F, Witters D, et al. Digital microfluidic chip technology for water permeability measurements on single isolated plant protoplasts. Sensors and Actuators B: Chemical, 2014, 199: 479–487
Schell W A, Benton J L, Smith P B, et al. Evaluation of a digital microfluidic real-time PCR platform to detect DNA of Candida albicans in blood. European Journal of Clinical Microbiology & Infectious Diseases, 2012, 31(9): 2237–2245
Hung P Y, Jiang P S, Lee E F, et al. Genomic DNA extraction from whole blood using a digital microfluidic (DMF) platform with magnetic beads. Microsystem Technologies, 2015, 21: 1–8
Yehezkel T B, Rival A, Raz O, et al. Synthesis and cell-free cloning of DNA libraries using programmable microfluidics. Nucleic Acids Research, 2015, 44: 1–12
Welch E R F, Lin Y Y, Madison A, et al. Picoliter DNA sequencing chemistry on an electrowetting-based digital microfluidic platform. Biotechnology Journal, 2011, 6(2): 165–176
Kim H, Bartsch M S, Renzi R F, et al. Automated digital microfluidic sample preparation for next-generation DNA sequencing. Journal of Laboratory Automation, 2011, 16(6): 405–414
Kim H, Jebrail M J, Sinha A, et al. A microfluidic DNA library preparation platform for next-generation sequencing. PLoS One, 2013, 8(7): e68988
Wheeler A R, Moon H, Bird C A, et al. Digital microfluidics with inline sample purification for proteomics analyses with MALDI-MS. Analytical Chemistry, 2005, 77(2): 534–540
Wheeler A R, Moon H, Kim C J, et al. Electrowetting-based microfluidics for analysis of peptides and proteins by matrixassisted laser desorption/ionization mass spectrometry. Analytical Chemistry, 2004, 76(16): 4833–4838
Luk V N, Fiddes L K, Luk V M, et al. Digital microfluidic hydrogel microreactors for proteomics. Proteomics, 2012, 12(9): 1310–1318
Aijian A P, Chatterjee D, Garrell R L. Fluorinated liquid-enabled protein handling and surfactant-aided crystallization for fully in situ digital microfluidic MALDI-MS analysis. Lab on a Chip, 2012, 12 (14): 2552–2559
Acknowledgements
This work was supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20133201110009).
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Wang, H., Chen, L. & Sun, L. Digital microfluidics: A promising technique for biochemical applications. Front. Mech. Eng. 12, 510–525 (2017). https://doi.org/10.1007/s11465-017-0460-z
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DOI: https://doi.org/10.1007/s11465-017-0460-z