Abstract
Rapid and reliable micromixing requires continuous improvement to renovate more powerful microfluidics chip for chemosynthesis, biological assay, and drug purification. In this work, we realized rapid in-situ mixing in droplets on a closed electro-microfluidic chip. Electrowetting and 2.5 GHz acoustic wave streaming were coupled into a monolithic chip for the manipulation and active mixing of microdroplets, respectively. Finite-element analysis simulation provided three-dimensional illustrations of turbulent flow pattern, fluid velocity, and vortices core locations. We carried out mixing experiments on different scales from nanoscale molecules to microscale particles, accelerating mixing efficiency by more than 50 times compared with pure diffusion. In the enzyme catalytic reaction experiment for biological assay demonstration, mixing efficiency of biological samples improves by about one order of magnitude compared with conventional 96-well-plate assay. Limited temperature rising of mixing in microdroplets validates biological safety, which guarantees potentials of the chip in various biochemical analyses and medical applications.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ballard M, Owen D, Mills ZG et al (2016) Orbiting magnetic microbeads enable rapid microfluidic mixing. Microfluid Nanofluid 20:1–13. https://doi.org/10.1007/s10404-016-1750-1
Beebe DJ, Mensing GA, Walker GM (2002) Physics and Applications of microfluidics in biology. Annu Rev Biomed Eng 4:261–286. https://doi.org/10.1146/annurev.bioeng.4.112601.125916
Chang CC, Yang RJ (2007) Electrokinetic mixing in microfluidic systems. Microfluid Nanofluid 3:501–525. https://doi.org/10.1007/s10404-007-0178-z
Chen D, Xu Y, Wang J et al (2010) The AlN based solidly mounted resonators consisted of the all-metal conductive acoustic Bragg reflectors. VAC 85:302–306. https://doi.org/10.1016/j.vacuum.2010.07.001
Chen C-Y, Chen C-Y, Lin C-Y, Hu Y-T (2013) Magnetically actuated artificial cilia for optimum mixing performance in microfluidics. Lab Chip 13:2834. https://doi.org/10.1039/c3lc50407g
Cho SK, Moon H, Chang-Jin Kim (2003) Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. J Microelectromech Syst 12:70–80. https://doi.org/10.1109/JMEMS.2002.807467
Chun H, Kim HC, Chung TD (2008) Ultrafast active mixer using polyelectrolytic ion extractor. Lab Chip 8:764. https://doi.org/10.1039/b715229a
Cui W, Zhang H, Zhang H et al (2016) Localized ultrahigh frequency acoustic fields induced micro-vortices for submilliseconds microfluidic mixing. Appl Phys Lett. https://doi.org/10.1063/1.4972484
Darwin R, Reyes D, Iossifidis, Pierre-Alain Auroux † and, Manz* A (2002) Micro total analysis systems. 1. Introduction, theory, and technology. https://doi.org/10.1021/AC0202435
Ding X, Li P, Lin S-CS et al (2013) Surface acoustic wave microfluidics. Lab Chip 13:3626. https://doi.org/10.1039/c3lc50361e
El Moctar AO, Aubry N, Batton J (2003) Electro-hydrodynamic micro-fluidic mixer electronic supplementary information (ESI) available: video of effect of electric field on channel flow mixing. See http://www.rsc.org/suppdata/lc/b3/b306868b/. Lab Chip 3:273. https://doi.org/10.1039/b306868b
Enlund J, Martin D, Yantchev V, Katardjiev I (2008) Solidly mounted thin film electro-acoustic resonator utilizing a conductive Bragg reflector. Sens Actuators A 141:598–602. https://doi.org/10.1016/j.sna.2007.09.002
Friend J, Yeo LY (2011) Microscale acoustofluidics: Microfluidics driven via acoustics and ultrasonics. Rev Mod Phys 83:647–704. https://doi.org/10.1103/RevModPhys.83.647
Frommelt T, Kostur M, Wenzel-Schäfer M et al (2008) Microfluidic mixing via acoustically driven chaotic advection. Phys Rev Lett 100:1–4. https://doi.org/10.1103/PhysRevLett.100.034502
Fu YQ, Luo JK, Nguyen NT et al (2017) Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications. Prog Mater Sci 89:31–91. https://doi.org/10.1016/j.pmatsci.2017.04.006
Glasgow I, Aubry N (2003) Enhancement of microfluidic mixing using time pulsing. Lab Chip 3:114–120. https://doi.org/10.1039/B302569A
Hessel V, Löwe H, Schönfeld F (2005) Micromixers—a review on passive and active mixing principles. Chem Eng Sci 60:2479–2501. https://doi.org/10.1016/j.ces.2004.11.033
Hiromitsu S, Jin K, Emiko S et al (2015) Novel method for immunofluorescence staining of mammalian eggs using non-contact alternating-current electric-field mixing of microdroplets. Sci Rep 5:1–10. https://doi.org/10.1038/srep15371
Hong SO, Cooper-White JJ, Kim JM (2016) Inertio-elastic mixing in a straight microchannel with side wells. Appl Phys Lett. https://doi.org/10.1063/1.4939552
Jebrail MJ, Bartsch MS, Patel KD (2012) Digital microfluidics: a versatile tool for applications in chemistry, biology and medicine. Lab Chip 12:2452. https://doi.org/10.1039/c2lc40318h
Kim H, Min K-I, Inoue K et al (2016) Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing. Science 352:691–694. https://doi.org/10.1126/science.aaf1389
Le The H, Le Thanh H, Dong T et al (2015) An effective passive micromixer with shifted trapezoidal blades using wide Reynolds number range. Chem Eng Res Des 93:1–11. https://doi.org/10.1016/J.CHERD.2014.12.003
Lee MG, Choi S, Park JK (2009) Rapid laminating mixer using a contraction–expansion array microchannel. Appl Phys Lett 95:1–4. https://doi.org/10.1063/1.3194137
Lee CY, Wang WT, Liu CC, Fu LM (2016) Passive mixers in microfluidic systems: a review. Chem Eng J 288:146–160. https://doi.org/10.1016/j.cej.2015.10.122
Li Y, Liu C, Feng X et al (2014) Ultrafast microfluidic mixer for tracking the early folding kinetics of human telomere G-quadruplex. Anal Chem 86:4333–4339. https://doi.org/10.1021/ac500112d
Lim TW, Son Y, Jeong YJ et al (2011) Three-dimensionally crossing manifold micro-mixer for fast mixing in a short channel length. Lab Chip 11:100–103. https://doi.org/10.1039/C005325M
Liu C, Hu G, Jiang X, Sun J (2015) Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers. Lab Chip 15:1168–1177. https://doi.org/10.1039/C4LC01216J
Lynn NS, Martínez-López JI, Bocková M et al (2014) Biosensing enhancement using passive mixing structures for microarray-based sensors. Biosens Bioelectron 54:506–514. https://doi.org/10.1016/j.bios.2013.11.027
Madison AC, Royal MW, Fair RB et al (2017) Piezo-driven acoustic streaming in an electrowetting-on-dielectric digital microfluidics device. Microfluid Nanofluid 21:1–9. https://doi.org/10.1007/s10404-017-2012-6
Mugele F, Staicu A, Bakker R, van den Ende D (2011) Capillary Stokes drift: a new driving mechanism for mixing in AC-electrowetting. Lab Chip. https://doi.org/10.1039/c0lc00702a
Neild A, Ng TW, Sheard GJ et al (2010) Swirl mixing at microfluidic junctions due to low frequency side channel fluidic perturbations. Sens Actuators B 150:811–818. https://doi.org/10.1016/J.SNB.2010.08.027
Oberti S, Neild A, Wah Ng T (2009) Microfluidic mixing under low frequency vibration. Lab Chip 9:1435. https://doi.org/10.1039/b819739c
Pang W, Zhao H, Kim ES et al (2012) Piezoelectric microelectromechanical resonant sensors for chemical and biological detection. Lab Chip 12:29–44. https://doi.org/10.1039/C1LC20492K
Qu H, Yang Y, Chang Y et al (2017) On-chip integrated multiple microelectromechanical resonators to enable the local heating, mixing and viscosity sensing for chemical reactions in a droplet. Sens Actuators B Chem 248:280–287. https://doi.org/10.1016/j.snb.2017.03.173
Samiei E, Tabrizian M, Hoorfar M (2016) A review of digital microfluidics as portable platforms for lab-on a-chip applications. Lab Chip 16:2376–2396. https://doi.org/10.1039/C6LC00387G
Stokes GG (1845) On the theories of the internal friction of fluids in motion, and of the equilibrium and motion of elastic solids. Math Phys Pap 18:75–129. https://doi.org/10.1017/CBO9780511702242.005
Suh YK, Kang S (2010) A review on mixing in microfluidics. Micromachines 1:82–111. https://doi.org/10.3390/mi1030082
Tsai JH, Lin L (2002) Active microfluidic mixer and gas bubble filter driven by thermal bubble micropump. Sens Actuators A 97–98:665–671. https://doi.org/10.1016/S0924-4247(02)00031-6
Valencia PM, Basto PA, Zhang L et al (2018) Single-step assembly of homogenous lipid polymeric and lipid quantum dot nanoparticles enabled by microfluidic rapid mixing. https://doi.org/10.1021/nn901433u
Viefhues M, Eichhorn R, Fredrich E et al (2012) Continuous and reversible mixing or demixing of nanoparticles by dielectrophoresis. Lab Chip 12:485–494. https://doi.org/10.1039/C1LC20610A
Wang J, Chen W, Sun J et al (2014) A microfluidic tubing method and its application for controlled synthesis of polymeric nanoparticles. Lab Chip 14:1673–1677. https://doi.org/10.1039/C4LC00080C
Wang Z, Zhang H, Yang Y et al (2017) Wireless controlled local heating and mixing multiple droplets using micro-fabricated resonator array for micro-reactor applications. IEEE Access 5:25987–25992. https://doi.org/10.1109/ACCESS.2017.2766270
Whitesides GM (2011) What comes next? Lab Chip 11:191–193. https://doi.org/10.1039/C0LC90101F
Wiklund M (2012) Acoustofluidics 12: biocompatibility and cell viability in microfluidic acoustic resonators. Lab Chip 12:2018. https://doi.org/10.1039/c2lc40201g
Xie Y, Ahmed D, Lapsley MI et al (2012) Single-shot characterization of enzymatic reaction constants K m and k cat by an acoustic-driven, bubble-based fast micromixer. Anal Chem 84:7495–7501. https://doi.org/10.1021/ac301590y
Yang Z, Matsumoto S, Goto H et al (2001) Ultrasonic micromixer for microfluidic systems. Sens Actuators A 93:266–272. https://doi.org/10.1016/S0924-4247(01)00654-9
Yeo LY, Friend JR (2014) Surface acoustic wave microfluidics. Annu Rev Fluid Mech 46:379–406. https://doi.org/10.1146/annurev-fluid-010313-141418
Zhang Z, Wang Y, Zhang H et al (2017) Hypersonic poration: a new versatile cell poration method to enhance cellular uptake using a piezoelectric nano-electromechanical device. Small 13:1–10. https://doi.org/10.1002/smll.201602962
Acknowledgements
The authors acknowledge financial support from the Natural Science Foundation of China (NSFC no. 51375341), the 111 Project (B07014), Nanchang Institute for Microtechnology of Tianjin University, and the National High Technology Research and Development Program of China (863 Program no. 2015AA042603).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
None.
Informed consent
Yes.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary material 1 (AVI 7377 KB)
Rights and permissions
About this article
Cite this article
Lu, Y., Zhang, M., Zhang, H. et al. On-chip acoustic mixer integration of electro-microfluidics towards in-situ and efficient mixing in droplets. Microfluid Nanofluid 22, 146 (2018). https://doi.org/10.1007/s10404-018-2169-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10404-018-2169-7