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Multiple-channel emulsion chips utilizing pneumatic choppers for biotechnology applications

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Abstract

The formation of micro-scale monodispersed emulsions is crucial for a variety of applications such as cosmetics, food industry and biotechnology. In this study, a new microfluidic chip with a multiple-channel layout for high-throughput emulsions is reported. This chip generated fine-tuned and uniform microdroplets in liquids with a higher throughput for emulsification applications. It employed a combination of multiple hydrodynamic flow focusing and liquid-cutting devices called “active pneumatic choppers.” Experimental data indicated that oil-in-water microdroplets with diameters ranging from 6 to 120 μm can be successfully generated with a coefficient of variation less than 3.75%. The size of the droplets can be actively fine-tuned by using two approaches by adjusting relative sheath/sample flow velocity ratios and chopping frequency. Finally, two commonly used biocompatible materials, including collagen and calcium-alginate (Ca-alginate), were used to form microspheres by utilizing the liquid-cutting technique. The developed microfluidic chip is promising in various applications including biotechnology, nano-medicine and cosmetics.

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Abbreviations

Ca:

calcium

CCD:

charge-coupled device

DI water:

deionized water

DNA:

deoxyribonucleic acid

EMV:

electromagnetic valve

f EMV :

operating frequency of EMV

HLB:

hydrophilic lipophilic balance

MEMS:

micro-electro-mechanical-systems

Na:

sodium

PDMS:

polydimethylsiloxane

PCR:

polymerase chain reaction

SEM:

scanning electron microscope

V 1 :

sample flow velocity

V 2 :

sheath flow velocity

o/w:

oil-in-water

w/o:

water-in-oil

References

  • S.L. Anna, N. Bontoux, H.A. Stone, Formation of dispersions using ‘flow-focusing’ in microchannels. Appl. Phys. Lett. 82, 364–366 (2003)

    Article  Google Scholar 

  • R. Arshady, Microspheres and microcapsules: A survey of manufacturing techniques. Part II: Coacervation. Polym. Eng. Sci. 30, 905–914 (1990)

    Article  Google Scholar 

  • A. Berthold, K. Cremer, J. Kreuter, Collagen microparticles: Carriers for glucocorticosteroids. Eur. J. Pharm. Biopharm. 45, 23–29 (1998)

    Article  Google Scholar 

  • D.T. Birnbaum, L. Brannon-Peppas, Microparticle Drug Delivery Systems, in Drug Delivery Systems in Cancer Therapy (Humana, Totowa, NJ, 2003), pp 117–135

  • L.W. Chan, H.Y. Lee, P.W. Heng, Production of alginate micro-spheres by internal gelation using an emulsification method. Int. J. Pharm. 242, 259–262 (2002)

    Article  Google Scholar 

  • C.T. Chen, G.B. Lee, Formation of microdroplets in liquids utilizing active pneumatic choppers on a microfluidic chip. Journal of Microelectromechanical Systems 15, 1492–1498 (2006)

    Article  MathSciNet  Google Scholar 

  • S.C. Chen, Y.C. Wu, F.L. Mi, Y.H. Lin, L.C. Yu, H.W. Sung, A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross- linked by genipin for protein drug delivery. J. Control. Release 96, 285–300 (2004)

    Article  Google Scholar 

  • G. Coppi, V. Iannuccelli, M.T. Bernabei, R. Cameroni, Int. J. Pharm. 242, 263–266 (2002)

    Article  Google Scholar 

  • C. Dong, J.A. Rogers, Acacia-gelatin microencapsulated liposomes: Preparation, stability, and release of acetylsalicylic acid. Pharm. Res. 10, 141–146 (1993)

    Article  Google Scholar 

  • S. El-Mahdy, E.S. Ibrahim, S. Safwat, A. El-Sayed, H. Ohshima, K. Makino, N. Muramatsu, T. Kondo, Effects of preparation conditions on the monodispersity of albumin microspheres. J. Microencapsul. 15, 661–673 (1998)

    Google Scholar 

  • S.E. Friberg, K. Larsson, Food emulsions. (Marcel Dekker, USA, 1997), pp. 189–233

    Google Scholar 

  • G. Fundueanu, E. Esposito, D. Mihai, A. Carpov, J. Desbrieres, M. Rinaudo, C. Nastruzzi, Preparation and characterization of Ca-alginate microspheres by a new emulsification method. Int. J. Pharm. 170, 11–21 (1998)

    Article  Google Scholar 

  • P. Garstecki, I. Gitlin, W. DiLuzio, G.M. Whitesides, Formation of monodisperse bubbles in a microfluidic flow-focusing device. Appl. Phys. Lett 85, 2649–2651 (2004)

    Article  Google Scholar 

  • T. Hamouda, M.M. Hayes, Z. Cao, R. Tonda, K. Johnson, D.C. Wright, J. Brisker, J.R. Baker, A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species. J. Infect. Dis. 180, 1939–1949 (1999)

    Article  Google Scholar 

  • B. Han, L.L.H. Huang, D.T. Cheung, M.E. Nimni, Collagen derived matrices and related polypeptide growth factors: their potential for tissue repair and organ regeneration, in Tissue Engineering of Prosthetic Vascular Grafts, ed. by P. Zilla (Landes, 1999)

  • S.K. Hsiung, C.T. Chen, G.B. Lee, Micro-droplet formation utilizing microfluidic flow focusing and controllable moving-wall chopping techniques. J. Micromechanics Microengineering 16, 2403–2410 (2006)

    Article  Google Scholar 

  • F.Y. Hsu, S.C. Chueh, Y.J. Wang, Microspheres of hydroxyapatite/reconstituted collagen as supports for osteoblast cell growth. Biomaterials 20, 1931–1936 (1999)

    Article  Google Scholar 

  • L.L.H. Huang, M.E. Nimni, Preparation of type I collagen fibrillar matrices and the effects of collagen concentration on fibroblast contraction. Journal of Biomedical Engineering, Application, Basis, and Communications 5, 664–675 (1993)

    Google Scholar 

  • L.L.H. Huang, K.H. Chen, C.C. Huang, The development and prospects of tissue engineering. Formosan Journal of Medicine 5, 646–653 (2001)

    Google Scholar 

  • K.S. Huang, T.H. Lai, Y.C. Lin, Manipulating the generation of Ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles. Lab Chip 6, 954–957 (2006)

    Article  Google Scholar 

  • R. Katoh, Y. Asano, A. Furuya, K. Sotoyama, M. Tomota, Preparation of food emulsions using a membrane emulsification system. J. Membr. Sci. 113, 131–135 (1996)

    Article  Google Scholar 

  • T. Kawakatsu, Y. Kikuchi, M. Nakajima, Regular-sized cell creation in microchannel emulsification by visual microprocessing method. J. Am. Oil Chem. Soc. 74, 317–321 (1997)

    Article  Google Scholar 

  • T. Kawakatsu, C. Trägårdh, M. Nakajima, N. Oda, T. Yonemoto, The effect of the hydrophobicity of microchannels and components in water-and-oil emulsification. Colloids Surf., A Physicochem. Eng. Asp. 179, 29–37 (2001)

    Article  Google Scholar 

  • K.H. Kim, S. Gohtani, Y. Yamano, Effect of oil droplets on brittleness of o/w emulsion gel. J. Dispers. Sci. Technol. 18, 199–210 (1996)

    Article  Google Scholar 

  • T. Kojima, Y. Takei, M. Ohtsuka, Y. Kawarasaki, T. Yamane, H. Nakano, PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets. Nucleic Acids Res. 33, e150 (2005)

    Article  Google Scholar 

  • A.V. Korobko, W. Jesse, J.R.C. van der Maarel, Encapsulation of DNA by cationic diblock copolymer vesicles. Langmuir 21, 34–42 (2005)

    Article  Google Scholar 

  • G.B. Lee, B.H. Hwei, G.R. Huang, Micromachined pre-focused MxN f low switches for continuous sample injection. J. Micromechanics Microengineering 11, 654–661 (2001)

    Article  Google Scholar 

  • M. Leonarda, M.R.D. Boisseson, P. Huberta, F. Dalenconb, E. Dellacheriea, Hydrophobically modified alginate hydrogels as protein carriers with specific controlled release properties. J. Control. Release 98, 395–405 (2004)

    Article  Google Scholar 

  • S.M. Moghimi, A.C. Hunter, J.C. Murray, Nanomedicine: Current status and future prospects. FASEB J. 19, 311–330 (2005)

    Article  Google Scholar 

  • Y. Murata, K. Kofuji, S. Kawashima, Preparation of floating alginate gel beads for drug delivery to the gastric mucosa. J. Biomater. Sci., Polymer Ed. 14(6), 581–588 (2003)

    Article  Google Scholar 

  • K. Nakagawa, S. Iwamoto, M. Nakajima, A. Shono, K. Satoh, Microchannel emulsification using gelatin and surfactant-free coacervate microencapsulation. J. Colloid Interface Sci. 278, 198–205 (2004)

    Article  Google Scholar 

  • S. Okushima, T. Nisisako, T. Torii, T. Higuchi, Controlled production of monodisperse double emulsions by two-step droplet breakup in microfluidic devices. Langmuir 20, 9905–9908 (2004)

    Article  Google Scholar 

  • S. Omi, K. Katami, K. Taguchi, M. Iso, Synthesis of uniform PMMA microspheres employing modified SPG emulsification technique. J. Appl. Polym. Sci. 57, 1013–1024 (1995)

    Article  Google Scholar 

  • H.Y. Park, I.H. Song, J.H. Kim, W.S. Kim, Preparation of thermally denatured albumin gel and its pH-sensitive swelling. Int. J. Pharm. 175, 231–236 (1998a)

    Article  Google Scholar 

  • H.Y. Park, C.R. Choi, J.H. Kim, W.S. Kim, Effect of pH on drug delivery from polysaccharide tablets. Drug Deliv. 5, 13–18 (1998b)

    Article  Google Scholar 

  • Qurrat-ul-Ain, S. Sharma, G.K. Khuller, S.K. Garg, Alginate-based oral drug delivery system for tuberculosis: Pharmacokinetics and therapeutic effects. J. Antimicrob. Chemother. 51, 931–938 (2003)

    Article  Google Scholar 

  • F. Shahidi, X. Han, Encapsulation of food ingredients. Crit. Rev. Food Sci. Nutr. 33, 501–547 (1993)

    Article  Google Scholar 

  • S. Sugiura, M. Nakajima, S. Iwamoto, M. Seki, Interfacial tension driven monodispersed droplet formation from microfabricated channel array. Langmuir 17, 5562–5566 (2001a)

    Article  Google Scholar 

  • S. Sugiura, M. Nakajima, H. Ushijima, K. Yamamoto, M. Seki, J. Chem. Eng. Jpn. 34, 757–765 (2001b)

    Article  Google Scholar 

  • S. Sugiura, M. Nakajima, N. Kumazawa, S. Iwamoto, M. Seki, Characterization of spontaneous transformation-based droplet formation during microchannel emulsification. J. Phys. Chem., B 106 9405–9409 (2002)

    Article  Google Scholar 

  • S. Sugiura, T. Oda, Y. Izumida, Y. Aoyagi, M. Satake, A. Ochiai, N. Ohkohchi, M. Nakajima, Size control of calcium alginate beads containing living cells using micro-nozzle array. Biomaterials 26, 3327–3331 (2005)

    Article  Google Scholar 

  • Y.C. Tan, V. Cristini, A.P. Lee, Monodispersed microfluidic droplet generation by shear focusing microfluidic device. Sens. Actuators, B, Chem. 114, 350–356 (2005)

    Article  Google Scholar 

  • M.A. Unger, H.P. Chou, T. Thorsen, A. Scherer, S.R. Quake, Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288, 113–116 (2000)

    Article  Google Scholar 

  • A.L. Weiner, S.S. Carpenter-Green, E.C. Soehngen, R.P. Lenk, M.C. Popescu, Liposome–collagen gel matrix: A novel sustained drug delivery system. J. Pharm. Sci. 74(9), 922–925 (1985)

    Article  Google Scholar 

  • C. Wibowo, K.M. Ng, Product-oriented process synthesis and development: creams and pastes. AIChE J. 47, 2746–2767 (2001)

    Article  Google Scholar 

  • J.O. You, S.B. Park, H.Y. Park, S. Haam, C.H. Chung, W.S. Kim, Preparation of regular sized Ca-alginate microspheres using membrane emulsification method. J. Microencapsul. 18(4), 521–532 (2001)

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank partial financial support from the National Science Council in Taiwan. Access to major fabrication equipment at the Center for Micro/Nano Technology Research, National Cheng Kung University is also greatly appreciated.

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Authors and Affiliations

  1. Department of Engineering Science, National Cheng Kung University, Tainan, Taiwan, Republic of China

    Yen-Heng Lin, Cheng-Tso Chen & Gwo-Bin Lee

  2. Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China

    Lynn L. H. Huang

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  1. Yen-Heng Lin
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  2. Cheng-Tso Chen
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  4. Gwo-Bin Lee
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Correspondence to Gwo-Bin Lee.

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Lin, YH., Chen, CT., Huang, L.L.H. et al. Multiple-channel emulsion chips utilizing pneumatic choppers for biotechnology applications. Biomed Microdevices 9, 833–843 (2007). https://doi.org/10.1007/s10544-007-9096-9

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