Production of monodispersed micron-sized bubbles at high rates in a microfluidic device

A polydimethylsiloxane microchip consisting of a T-junction microchannel network and a thin glass capillary has been developed for the generation of microbubbles. The glass capillary is used to produce an ultrathin gas jet and to controllably block the straight liquid channel, thereby increasing the local liquid velocity near the intersection. Liquid flow rate, liquid viscosity, gas pressure, and inner diameter of the gas jet are varied to investigate the effect on bubble generation. Bubbles with a diameter down to 4.5 μm can be produced at a high rate of 7.5 kHz using a capillary with an inner diameter of 2 μm.

[1]  E. Stride,et al.  Novel methods for preparing phospholipid coated microbubbles , 2008, European Biophysics Journal.

[2]  Jyeshtharaj B. Joshi,et al.  Bubble Formation and Bubble Rise Velocity in Gas−Liquid Systems: A Review , 2005 .

[3]  A. Gañán-Calvo,et al.  Perfectly monodisperse microbubbling by capillary flow focusing. , 2001, Physical review letters.

[4]  S A Small,et al.  Spatio-temporal analysis of molecular delivery through the blood–brain barrier using focused ultrasound , 2007, Physics in medicine and biology.

[5]  Yonggang Zhu,et al.  Lab-on-a-chip in vitro compartmentalization technologies for protein studies. , 2008, Advances in biochemical engineering/biotechnology.

[6]  C. Ohl,et al.  Detachment and sonoporation of adherent HeLa-cells by shock wave-induced cavitation. , 2003, Biochimica et biophysica acta.

[7]  George M. Whitesides,et al.  Formation of monodisperse bubbles in a microfluidic flow-focusing device , 2004 .

[8]  Reginald B. H. Tan,et al.  A model for bubble formation and weeping at a submerged orifice with liquid cross-flow , 2003 .

[9]  Reginald B. H. Tan,et al.  A model for bubble formation and weeping at a submerged orifice , 2000 .

[10]  A. Klibanov,et al.  Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. , 2005, Bioconjugate chemistry.

[11]  Geoffrey Ingram Taylor,et al.  The formation of emulsions in definable fields of flow , 1934 .

[12]  W. Krause.  Contrast Agents II , 2002 .

[13]  W. McDicken,et al.  The acoustic response from individual attached and unattached rigid shelled microbubbles , 2008 .

[14]  Mark Borden,et al.  Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. , 2007, Annual review of biomedical engineering.

[15]  Philippe Marmottant,et al.  Role of the channel geometry on the bubble pinch-off in flow-focusing devices. , 2007, Physical review letters.

[16]  Paul A Dayton,et al.  On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging. , 2007, Lab on a chip.

[17]  P. Buttner,et al.  Eating Disorder Behaviors Are Increasing: Findings from Two Sequential Community Surveys in South Australia , 2008, PloS one.

[18]  Robin Shandas,et al.  Computational fluid dynamics analysis of microbubble formation in microfluidic flow-focusing devices , 2007 .

[19]  G. Luo,et al.  Shear force induced monodisperse droplet formation in a microfluidic device by controlling wetting properties. , 2006, Lab on a chip.

[20]  Hirokazu Miyoshi,et al.  Encapsulated ultrasound microbubbles: therapeutic application in drug/gene delivery. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[21]  Eleanor Stride,et al.  Novel microbubble preparation technologies , 2008 .

[22]  Reginald B. H. Tan,et al.  An improved model for bubble formation using the boundary-integral method , 2005 .

[23]  G. Whitesides,et al.  Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. , 2006, Lab on a chip.

[24]  Alexander L. Klibanov,et al.  Ultrasound Contrast Agents: Development of the Field and Current Status , 2002 .

[25]  Satoyuki Kawano,et al.  Microbubble formations in MEMS-fabricated rectangular channels: A high-speed observation , 2008 .

[26]  Shangfu Li,et al.  Controllable gas-liquid phase flow patterns and monodisperse microbubbles in a microfluidic T-junction device , 2006 .

[27]  Richard Manasseh,et al.  Frequencies of acoustically interacting bubbles , 2009 .

[28]  J. Hahn,et al.  Dual-channel method for interference-free in-channel amperometric detection in microchip capillary electrophoresis. , 2007, Analytical chemistry.

[29]  Paul A Dayton,et al.  Long-term stability by lipid coating monodisperse microbubbles formed by a flow-focusing device. , 2006, Langmuir : the ACS journal of surfaces and colloids.