Tunable, pulsatile chemical gradient generation via acoustically driven oscillating bubbles.

We present a novel concept of generating both static and pulsatile chemical gradients using acoustically activated bubbles designed in a ladder-like arrangement. Furthermore, by regulating the amplitude of the bubble oscillation, we demonstrate that the chemical gradient profiles can be effectively tuned.

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

[2]  Won Gu Lee,et al.  Generating nonlinear concentration gradients in microfluidic devices for cell studies. , 2011, Analytical chemistry.

[3]  Tony Jun Huang,et al.  Milliseconds microfluidic chaotic bubble mixer , 2009 .

[4]  D. Irimia Microfluidic technologies for temporal perturbations of chemotaxis. , 2010, Annual review of biomedical engineering.

[5]  Alar Ainla,et al.  A microfluidic pipette for single-cell pharmacology. , 2010, Analytical chemistry.

[6]  Armando R Tovar,et al.  Lateral cavity acoustic transducer. , 2009, Lab on a chip.

[7]  Donald Wlodkowic,et al.  Dynamic analysis of apoptosis using cyanine SYTO probes: from classical to microfluidic cytometry. , 2009, Experimental cell research.

[8]  Tony Jun Huang,et al.  Surface acoustic wave (SAW) acoustophoresis: now and beyond. , 2012, Lab on a chip.

[9]  Richard Manasseh,et al.  Cavitation microstreaming patterns in single and multiple bubble systems , 2007, Journal of Fluid Mechanics.

[10]  Helen Song,et al.  Millisecond kinetics on a microfluidic chip using nanoliters of reagents. , 2003, Journal of the American Chemical Society.

[11]  Mehmet Toner,et al.  Microfluidic system for measuring neutrophil migratory responses to fast switches of chemical gradients. , 2006, Lab on a chip.

[12]  A. Folch,et al.  Biomolecular gradients in cell culture systems. , 2008, Lab on a chip.

[13]  G. Whitesides,et al.  Generation of Solution and Surface Gradients Using Microfluidic Systems , 2000 .

[14]  Daniel Ahmed,et al.  A millisecond micromixer via single-bubble-based acoustic streaming. , 2009, Lab on a chip.

[15]  Daniel M. Frances,et al.  Effect of oscillating fluid flow stimulation on osteocyte mRNA expression. , 2012, Journal of biomechanics.

[16]  A. Manz,et al.  Lab-on-a-chip: microfluidics in drug discovery , 2006, Nature Reviews Drug Discovery.

[17]  S. Ostrovidov,et al.  A microfluidic-based neurotoxin concentration gradient for the generation of an in vitro model of Parkinson's disease. , 2011, Biomicrofluidics.

[18]  A. Folch,et al.  A microfluidic platform for generation of sharp gradients in open-access culture. , 2010, Biomicrofluidics.

[19]  I-Kao Chiang,et al.  On-chip manipulation of single microparticles, cells, and organisms using surface acoustic waves , 2012, Proceedings of the National Academy of Sciences.

[20]  Kam W Leong,et al.  Microfluidic synthesis of multifunctional Janus particles for biomedical applications. , 2012, Lab on a chip.

[21]  Bingyun Sun,et al.  Synthesis, loading, and application of individual nanocapsules for probing single-cell signaling. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[22]  T. Leighton The Acoustic Bubble , 1994 .

[23]  M. Toner,et al.  Universal microfluidic gradient generator. , 2006, Analytical chemistry.

[24]  Chun Yang,et al.  Mixing enhancement for high viscous fluids in a microfluidic chamber. , 2011, Lab on a chip.

[25]  S. Boyden THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES , 1962, The Journal of experimental medicine.

[26]  G. Whitesides,et al.  Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device , 2002, Nature Biotechnology.

[27]  Martin Wiklund,et al.  Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices. , 2012, Lab on a chip.

[28]  Ovidiu Lipan,et al.  The use of oscillatory signals in the study of genetic networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Daniel Ahmed,et al.  A fast microfluidic mixer based on acoustically driven sidewall-trapped microbubbles , 2009 .

[30]  Boris N. Kholodenko,et al.  Signalling ballet in space and time , 2010, Nature Reviews Molecular Cell Biology.

[31]  Yu Sun,et al.  Microfluidic approaches for gene delivery and gene therapy. , 2011, Lab on a chip.

[32]  F. Djouad,et al.  Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs , 2009, Acta Pharmacologica Sinica.

[33]  Abraham P. Lee,et al.  Lateral air cavities for microfluidic pumping with the use of acoustic energy , 2011 .

[34]  J. Rädler,et al.  Chemotactic cell trapping in controlled alternating gradient fields , 2011, Proceedings of the National Academy of Sciences.

[35]  Albert Folch,et al.  Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. , 2005, Lab on a chip.

[36]  Cecile O. Mejean,et al.  Cell stimulation with optically manipulated microsources , 2009, Nature Methods.

[37]  William C. Messner,et al.  Probing Cellular Dynamics with a Chemical Signal Generator , 2009, PloS one.

[38]  Zigmond Sh Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. , 1977 .

[39]  Jie Xu,et al.  Oscillating bubbles: a versatile tool for lab on a chip applications. , 2012, Lab on a chip.

[40]  A. Regev,et al.  Impulse Control: Temporal Dynamics in Gene Transcription , 2011, Cell.

[41]  I-Kao Chiang,et al.  Three-dimensional continuous particle focusing in a microfluidic channel via standing surface acoustic waves (SSAW). , 2011, Lab on a chip.

[42]  S. Sadhal,et al.  Acoustofluidics 16: acoustics streaming near liquid-gas interfaces: drops and bubbles. , 2012, Lab on a chip.

[43]  H. Berg,et al.  A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli , 2010, Molecular systems biology.

[44]  M. Longuet-Higgins,et al.  Viscous streaming from an oscillating spherical bubble , 1998, Proceedings of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[45]  Eberhard Bodenschatz,et al.  Flow photolysis for spatiotemporal stimulation of single cells. , 2007, Analytical chemistry.

[46]  Nam-Trung Nguyen,et al.  Acoustically induced bubbles in a microfluidic channel for mixing enhancement , 2009 .

[47]  Tony Jun Huang,et al.  Microfluidic diagnostics for the developing world. , 2012, Lab on a chip.