In-plane microvortices micromixer-based AC electrothermal for testing drug induced death of tumor cells.

Herein, we first describe a perfusion chip integrated with an AC electrothermal (ACET) micromixer to supply a uniform drug concentration to tumor cells. The in-plane fluid microvortices for mixing were generated by six pairs of reconstructed novel ACET asymmetric electrodes. To enhance the mixing efficiency, the novel ACET electrodes with rotating angles of 0°, 30°, and 60° were investigated. The asymmetric electrodes with a rotating angle of 60° exhibited the highest mixing efficiency by both simulated and experimental results. The length of the mixing area is 7 mm, and the mixing efficiency is 89.12% (approximate complete mixing) at a voltage of 3 V and a frequency of 500 kHz. The applicability of our micromixer with electrodes rotating at 60° was demonstrated by the drug (tamoxifen) test of human breast cancer cells (MCF-7) for five days, which implies that our ACET in-plane microvortices micromixer has great potential for the application of drug induced rapid death of tumor cells and mixing of biomaterials in organs-on-a-chip systems.

[1]  Hongyuan Jiang,et al.  Continuous dielectrophoretic particle separation using a microfluidic device with 3D electrodes and vaulted obstacles , 2015, Electrophoresis.

[2]  Rangan Banerjee,et al.  Smart material platforms for miniaturized devices: implications in disease models and diagnostics. , 2016, Lab on a chip.

[3]  Nupura S. Bhise,et al.  A liver-on-a-chip platform with bioprinted hepatic spheroids , 2016, Biofabrication.

[4]  Dongqing Li,et al.  Electroosmotic flow with Joule heating effects. , 2004, Lab on a chip.

[5]  Chun Yang,et al.  DC-biased AC-electroosmotic and AC-electrothermal flow mixing in microchannels. , 2009, Lab on a chip.

[6]  Takehiko Kitamori,et al.  AC electroosmotic micromixer for chemical processing in a microchannel. , 2006, Lab on a chip.

[7]  Grissel Trujillo-de Santiago,et al.  Titles of chemical papers in British and foreign journals , 1850 .

[8]  H. Du,et al.  Simulation studies on electrothermal fluid flow induced in a dielectrophoretic microelectrode system , 2006 .

[9]  P. S. Gupta,et al.  Heat and mass transfer on a stretching sheet with suction or blowing , 1977 .

[10]  V. Hessel,et al.  Micromixers—a review on passive and active mixing principles , 2005 .

[11]  Liang Li,et al.  An active microfluidic mixer utilizing a hybrid gradient magnetic field , 2015 .

[12]  P. Georges,et al.  Molecular Dynamics of Biological Probes by Fluorescence Correlation Microscopy with Two-Photon Excitation , 2000, Journal of Fluorescence.

[13]  Hongyuan Jiang,et al.  An effective splitting-and-recombination micromixer with self-rotated contact surface for wide Reynolds number range applications. , 2013, Biomicrofluidics.

[14]  Fan-Gang Tseng,et al.  AC electroosmotic generated in-plane microvortices for stationary or continuous fluid mixing , 2007 .

[15]  D. Ingber,et al.  From 3D cell culture to organs-on-chips. , 2011, Trends in cell biology.

[16]  Castellanos,et al.  Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. I. Experimental measurements , 2000, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[17]  Lucas H. Hofmeister,et al.  Scaling and systems biology for integrating multiple organs-on-a-chip. , 2013, Lab on a chip.

[18]  Jiehong Wu,et al.  Micropumping of biofluids by alternating current electrothermal effects , 2007 .

[19]  John P. Wikswo,et al.  Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems , 2013, IEEE Transactions on Biomedical Engineering.

[20]  Phil Paik,et al.  Rapid droplet mixers for digital microfluidic systems. , 2003, Lab on a chip.

[21]  Christopher Moraes,et al.  On being the right size: scaling effects in designing a human-on-a-chip. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[22]  Yucheng Ding,et al.  A theoretical and numerical investigation of travelling wave induction microfluidic pumping in a temperature gradient , 2014 .

[23]  H. Morgan,et al.  Electrothermally induced fluid flow on microelectrodes , 2001 .

[24]  Oliver Geschke,et al.  A novel passive micromixer: lamination in a planar channel system , 2010 .

[25]  Takehiko Kitamori,et al.  Fluid mixing using AC electrothermal flow on meandering electrodes in a microchannel , 2012, Electrophoresis.

[26]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[27]  Hongyuan Jiang,et al.  A multifunctional resealable perfusion chip for cell culture and tissue engineering , 2016 .

[28]  Lung-Ming Fu,et al.  Passive mixers in microfluidic systems: A review , 2016 .

[29]  Hongyuan Jiang,et al.  AC Electrothermal Circulatory Pumping Chip for Cell Culture. , 2015, ACS applied materials & interfaces.

[30]  L. Fu,et al.  Microfluidic Mixing: A Review , 2011, International journal of molecular sciences.

[31]  A. Manz,et al.  Revisiting lab-on-a-chip technology for drug discovery , 2012, Nature Reviews Drug Discovery.

[32]  Wei Zhang,et al.  Gold nanoparticle ensembles as heaters and actuators: melting and collective plasmon resonances , 2006, Nanoscale Research Letters.

[33]  Hongyuan Jiang,et al.  Effect of the crossing-structure sequence on mixing performance within three-dimensional micromixers. , 2014, Biomicrofluidics.

[34]  C. Dalton,et al.  A novel alternating current multiple array electrothermal micropump for lab-on-a-chip applications. , 2015, Biomicrofluidics.

[35]  Mario Moisés Alvarez,et al.  Continuous flow micro-bioreactors for the production of biopharmaceuticals: the effect of geometry, surface texture, and flow rate. , 2014, Lab on a chip.

[36]  T. Mukherjee,et al.  A model for laminar diffusion-based complex electrokinetic passive micromixers. , 2005, Lab on a chip.

[37]  Sangmo Kang,et al.  A Review on Mixing in Microfluidics , 2010, Micromachines.

[38]  Ali Khademhosseini,et al.  Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering , 2016, Advanced healthcare materials.

[39]  L. Onsager.  Electric Moments of Molecules in Liquids , 1936 .

[40]  J. Cole.  On a quasi-linear parabolic equation occurring in aerodynamics , 1951 .

[41]  Michael J. Vellekoop,et al.  A highly uniform lamination micromixer with wedge shaped inlet channels for time resolved infrared spectroscopy , 2011 .

[42]  Hongyuan Jiang,et al.  A dual-core double emulsion platform for osmolarity-controlled microreactor triggered by coalescence of encapsulated droplets. , 2016, Biomicrofluidics.

[43]  Shen Liu,et al.  Injectable Stem Cell‐Laden Photocrosslinkable Microspheres Fabricated Using Microfluidics for Rapid Generation of Osteogenic Tissue Constructs , 2016 .

[44]  Xiangchun Xuan,et al.  Joule heating in electrokinetic flow , 2008, Electrophoresis.

[45]  Rasim Guldiken,et al.  Dual surface acoustic wave-based active mixing in a microfluidic channel , 2013 .

[46]  Hongyuan Jiang,et al.  Scaled particle focusing in a microfluidic device with asymmetric electrodes utilizing induced-charge electroosmosis. , 2016, Lab on a chip.

[47]  Yupan Wu,et al.  Enhanced model‐based design of a high‐throughput three dimensional micromixer driven by alternating‐current electrothermal flow , 2017, Electrophoresis.

[48]  H. Morgan,et al.  Ac electrokinetics: a review of forces in microelectrode structures , 1998 .