Skip to main content
Log in

Digital microfluidics: A promising technique for biochemical applications

  • Review Article
  • Published:
Frontiers of Mechanical Engineering Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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

    Article  Google Scholar 

  2. 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

    Article  Google Scholar 

  3. Mugele F, Baret J C. Electrowetting: From basics to applications. Journal of Physics Condensed Matter, 2005, 17(28): R705–R774

    Article  Google Scholar 

  4. 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

    Article  Google Scholar 

  5. Washizu M. Electrostatic actuation of liquid droplets for microreactor applications. IEEE Transactions on Industry Applications, 1998, 34(4): 732–737

    Article  Google Scholar 

  6. 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

    Google Scholar 

  7. 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

    Article  Google Scholar 

  8. Berthier J. Microdrops and Digital Microfluidics. Norwich: William Andrew Inc., 2008

    Google Scholar 

  9. Wang W, Jones T B. Moving droplets between closed and open microfluidic systems. Lab on a Chip, 2015, 15(10): 2201–2212

    Article  Google Scholar 

  10. Wheeler A R. Putting electrowetting to work. Science, 2008, 322 (5901): 539–540

    Article  Google Scholar 

  11. 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

    Google Scholar 

  12. Jones T B, Wang K L, Yao D J. Frequency-dependent electromechanics of aqueous liquids: Electrowetting and dielectrophoresis. Langmuir, 2004, 20(7): 2813–2818

    Article  Google Scholar 

  13. Mugele F, Baret J C. Electrowetting: From basics to applications. Journal of Physics Condensed Matter, 2005, 17(28): R705–R774

    Article  Google Scholar 

  14. 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

    Article  Google Scholar 

  15. Chen L Q, Bonaccurso E. Electrowetting—From statics to dynamics. Advances in Colloid and Interface Science, 2014, 210: 2–12

    Article  Google Scholar 

  16. Kang K H. How electrostatic fields change contact angle in electrowetting. Langmuir, 2002, 18(26): 10318–10322

    Article  Google Scholar 

  17. Peykov V, Quinn A, Ralston J. Electrowetting: A model for contactangle saturation. Colloid & Polymer Science, 2000, 278(8): 789–793

    Article  Google Scholar 

  18. 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

    Article  Google Scholar 

  19. 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

    Article  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  Google Scholar 

  22. 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

    Article  Google Scholar 

  23. 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

    Article  Google Scholar 

  24. Seemann R, Brinkmann M, Pfohl T, et al. Droplet based microfluidics. Reports on Progress in Physics, 2012, 75(1): 016601

    Article  Google Scholar 

  25. 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

    Article  Google Scholar 

  26. 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

    Article  Google Scholar 

  27. 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

    Article  Google Scholar 

  28. 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

    Article  Google Scholar 

  29. 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

    Article  Google Scholar 

  30. 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

    Article  Google Scholar 

  31. 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

    Article  Google Scholar 

  32. Choi K, Ng A H C, Fobel R, et al. Digital microfluidics. Annual Review of Analytical Chemistry, 2012, 5(1): 413–440

    Article  Google Scholar 

  33. 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

    Article  Google Scholar 

  34. Takinoue M, Takeuchi S. Droplet microfluidics for the study of artificial cells. Analytical and Bioanalytical Chemistry, 2011, 400 (6): 1705–1716

    Article  Google Scholar 

  35. 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

    Article  Google Scholar 

  36. 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

    Google Scholar 

  37. 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

    Article  Google Scholar 

  38. 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

    Article  Google Scholar 

  39. Chang J H, Pak J J. Twin-plate electrowetting for efficient digital microfluidics. Sensors and Actuators B: Chemical, 2011, 160(1): 1581–1585

    Article  Google Scholar 

  40. 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

    Article  MathSciNet  Google Scholar 

  41. 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

    Article  Google Scholar 

  42. Fobel R, Kirby A E, Ng A H C, et al. Paper microfluidics goes digital. Advanced Materials, 2014, 26(18): 2838–2843

    Article  Google Scholar 

  43. 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

    Google Scholar 

  44. 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

    Google Scholar 

  45. 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

    Article  Google Scholar 

  46. 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

    Article  Google Scholar 

  47. 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

    Article  Google Scholar 

  48. 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

    Google Scholar 

  49. 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

    Article  Google Scholar 

  50. Boles D J, Benton J L, Siew G J, et al. Droplet-based pyrosequencing using digital microfluidics. Analytical Chemistry, 2011, 83(22): 8439–8447

    Article  Google Scholar 

  51. 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

    Article  Google Scholar 

  52. 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

    Article  Google Scholar 

  53. 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

    Article  Google Scholar 

  54. 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

    Article  Google Scholar 

  55. 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

    Article  Google Scholar 

  56. 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

    Article  Google Scholar 

  57. 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

    Article  Google Scholar 

  58. 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

    Article  Google Scholar 

  59. Fair R B. Digital microfluidics: Is a true lab-on-a-chip possible? Microfluidics and Nanofluidics, 2007, 3(3): 245–281

    Article  Google Scholar 

  60. Yoon J Y, Garrell R L. Preventing biomolecular adsorption in electrowetting-based biofluidic chips. Analytical Chemistry, 2003, 75(19): 5097–5102

    Article  Google Scholar 

  61. 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

    Article  Google Scholar 

  62. 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

    Article  Google Scholar 

  63. 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

    Article  Google Scholar 

  64. 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

    Article  Google Scholar 

  65. 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

    Article  Google Scholar 

  66. 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

    Article  Google Scholar 

  67. 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

    Article  Google Scholar 

  68. 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

    Article  Google Scholar 

  69. Fiddes L K, Luk V N, Au S H, et al. Hydrogel discs for digital microfluidics. Biomicrofluidics, 2012, 6(1): 014112

    Article  Google Scholar 

  70. George S M, Moon H. Digital microfluidic three-dimensional cell culture and chemical screening platform using alginate hydrogels. Biomicrofluidics, 2015, 9(2): 024116

    Article  Google Scholar 

  71. 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

    Article  Google Scholar 

  72. 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

    Article  Google Scholar 

  73. 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

    Article  Google Scholar 

  74. 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

    Article  Google Scholar 

  75. 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

    Article  Google Scholar 

  76. 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

    Article  Google Scholar 

  77. 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

    Google Scholar 

  78. 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

    Article  Google Scholar 

  79. 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

    Article  Google Scholar 

  80. 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

    Article  Google Scholar 

  81. 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

    Article  Google Scholar 

  82. 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

    Article  Google Scholar 

  83. Luk V N, Fiddes L K, Luk V M, et al. Digital microfluidic hydrogel microreactors for proteomics. Proteomics, 2012, 12(9): 1310–1318

    Article  Google Scholar 

  84. 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

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20133201110009).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Liguo Chen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11465-017-0460-z

Keywords

Navigation