Nebulizers of drug delivery are used in the medicine therapy for asthmatic patients in recent years. Although using liquid nebulization mechanism is able to transform the type of medicine becoming liquid to gaseous droplet, it is hard to control the size of gaseous droplet. In general, the size of medicine droplet must be smaller than 5 μm, and can be efficiently absorbed by alveoli of patients. Filtration by a nebulizer nozzle plate, the medicine droplet will be controlled smaller than 5 μm and can be efficiently absorbed by alveoli through inhalation and reach to the purpose of rapid drug-feeding.
For portable use, patients desire nebulizers, which have smaller size and lighter weight for easy carrying as well as longer battery working time for long-term use. Because micro-DMFCs have higher energy density than lithium-ion batteries and can directly use methanol fuels to generate electricity for long-term use, they could be used in portable nebulizers. However, external methanol-water mixing tanks and conduits that used for water management of DMFCs are difficult to be miniaturized and integrated into micro-DMFCs.
First study theme of this thesis focused on developing a novel fabrication process to fabricate the nebulizer nozzle plate of nebulizer drug-feeding systems by the laser ablation process and electroforming process. Moreover, this study developed different types of electro-deposited alloys for the electroforming of nebulizer nozzle plates. Further, this study developed a piezoelectric actuating system as a nebulizer to generate gaseous droplets, which were filtrated by the nebulizer nozzle plates. This study used a particle size counter to measure sizes of the gaseous droplets, and it verified the performance of the developed nebulizer nozzle plate.
Second study theme of this thesis focused on developing a micro direct methanol fuel cell (micro-DMFC), which was composed of an in-fuel cell microfluidic micromixer and DMFC components, for nebulizer use. This study demonstrated the micro-DMFC, with an internal mixing function, which was able to mix methanol fuel and water by the self-vortical micromixer inside itself. Design and testing results of the self-vortical micromixer integrated with the micro-DMFC showed the self-vortical micromixer was able to be operated in the micro-DMFC system.

[1] Frederic F Little and Martin Joyce-Brady, Trends in Nebulizer Therapy, Business Briefing: US Respiratory Care 2006, pp. 98-100.
[2] J.P. Mitchell and M.W. Nagel, “Particle Size Analysis of Aerosols from Medicinal Inhalers”, Powder Science and Technology in Japan, 2004, No. 22, pp. 32-65.
[3] L Olseni, J Palmer and P Wollmer, Quantitative evaluation of aerosol deposition pattern in the lung in patients with chronic bronchitis, Physiol, Meas. 1994, 15, pp. 41-48.
[4] M C Carrozza, A Menciassi, G Tiezzi and P Dario, The Development of a LIGA-microfabricated gripper for micromanipulation tasks, J. Micromech. Microeng. 1998, Vol.8, pp.141-143.
[5] S C Tzeng and W P Ma, Study of flow and heat transfer characteristics and LIGA fabrication of microspinnerets, J. Micromech. Microeng., 2003, vol.13, pp.670-679.
[6] Marc Madou, Fundamentals of Microfabrication, 2nd ed., CRC Press, 2002.
[7] E. W. Becker, W. Ehrfeld, P. Hagmann, A. Maner and D. Münchmeyer, Fabrication of microstructures with high aspect ratios and great structural heights by synchrotron radiation lithography, galvanoforming, and plastic moulding (LIGA process), Microelectronic Engineering, 1986, Vol.4, pp.35-56.
[8] C H Cheng, S C Chen and Z S Chen, Multilevel electroforming for the components of a microdroplet ejector by UV LIGA technology, J. Micromech. Microeng. 2005, Vol. 15, pp. 843-848.
[9] http://ec.europa.eu/environment/waste/weee_index.htm
[10] De Benedittis, A.; Di Cristoforo, A.; Majni, G.; Mengucci, P.; Watts, B.E.; Leccabue, F.; Vasco, E., Lead zirconate titanate deposited on RuO2 by pulsed laser ablation, Applied Surface Science, Vol. 109-110, 1997, pp. 299- 304.
[11] Kántor, Z.; Fogarassy, E.; Grob, A.; Grob, J.J.; Muller, D.; Prévot, B.; Stuck, R., Evolution of implanted carbon in silicon upon pulsed excimer laser annealing: epitaxial Si1−yCy alloy formation and SiC precipitation, Applied Surface Science, Vol. 109-110, 1997, pp. 305- 311
[12] Stietz, F.; Stuke, M.; Viereck, J.; Wenzel, T.; Träger, F., Fundamental reactions in laser ablation of metals: defect-initiated bond breaking, Applied Surface Science, Vol. 127-129, 1998, pp. 64-70
[13] Pfleging, W.; Vörckel, A.; Duddek, H.; Wesner, D.A.; Kreutz, E.W., Excimer-laser patterning of copper in LDE (laser dry etching), Applied Surface Science, Vol. 109-110, 1997, pp. 194- 200.
[14] Dyer, P.E.; Karnakis, D.M.; Key, P.H.; Sands, D., Fast photography of UV laser ablated metal films, Applied Surface Science, Vol. 109-110, 1997, pp. 168- 173.
[15] V. Oliveira, O. Conde, R. Vilar, UV Laser Micromachining of Ceramic Materials: Formation of Columnar Topographies, Advanced Engineering Materials, 2001, Vol. 3, pp. 75-81
[16] Nicolas, G.; Autric, M.; Marine, W.; Shafeev, G.A., Laser induced surface modifications on ZrO2 ceramics, Applied Surface Science, Vol. 109-110, 1997, pp. 289- 292.
[17] Bityurin, N.; Muraviov, S.; Alexandrov, A.; Malyshev, A., UV laser modifications and etching of polymer films (PMMA) below the ablation threshold, Applied Surface Science, Vol. 109-110, 1997, pp. 270- 274
[18] Lippert, Thomas; Dickinson, J.T.; Langford, S.C.; Furutani, H.; Fukumura, H.; Masuhara, H.; Kunz, T., Photopolymers designed for laser ablation – photochemical ablation mechanism, Applied Surface Science, Vol. 127-129, 1998, pp. 117-121
[19] Suzuki, Kenkichi; Matsuda, Masaaki; Hayashi, Nobuaki, Polymer resist materials for excimer ablation lithography, Applied Surface Science, Vol. 127-129, 1998, pp. 905-910
[20] D.B. Wolfe, J.B. Ashcom, J.C. Hwang, C.B. Schaffer, E. Mazur, G.M. Whitesides, Customization of Poly(dimethylsiloxane) Stamps by Micromachining Using a Femtosecond-Pulsed Laser, Advanced Materials, Vol. 15, 2003, pp. 62-65.
[21] Allard, M.; Boughaba, S.; Meunier, M., Laser micromachining of free-standing structures in SiO2-covered silicon, Applied Surface Science, Vol. 109-110, 1997, pp. 189- 193
[22] Weihua Wang; Leith, S.D.; Schwartz, D.T., Convective-diffusive mass transfer inside complex micro-molds during electrodeposition, J. Microelectromech. Syst., 2002, Vol. 11, pp. 118-124.
[23] Leith, S.D.; Schwartz, D.T., High-rate through-mold electrodeposition of thick (>200 μm) NiFe MEMS components with uniform composition, J. Microelectromech. Syst., 1999, Vol. 8, pp.384-392.
[24] S Ballandras, W Daniau, S Basrour, L Robert, M Rouillay, P Blind, P Bernede, D Robert, S Rocher, D Hauden, S Megtert, A Labeque, L Zewen, H Dexpert, R Comes, F Rousseaux, M F Ravert and H Launois, Deep etch x-ray lithography using silicon-gold masks fabricated by deep etch UV lithography and electroforming, J. Micromech. Microeng., 1995, Vol.5, pp.203-208.
[25] W Daniau, S Ballandras, L Kubat, J Hardin, G Martin and S Basrour, Fabrication of an electrostatic wobble micromotor using deep-etch UV lithography, nickel electroforming and a titanium sacrificial layer, J. Micromech. Microeng. 1995, Vol.5, pp.270-275.
[26] Nosang V. Myung, D.-Y. Park, B.-Y. Yoo, Paulo T.A. Sumodjo, Development of electroplated magnetic materials for MEMS, Journal of Magnetism and Magnetic Materials, 2003, Vol. 265, pp. 189-198.
[27] Yunn-Shiuan Liao and Ying-Tung Chen, Precision fabrication of an arrayed micro metal probe by the laser-LIGA process., J. Micromech. Microeng., 2005, vol.15, pp.2433-2440.
[28] Richard Holliday and Paul Goodman, Going for gold, Gold’s Growing Importance for the modern electronics industry, IEE Review, Vol.48, Issue 3, 2002, pp.15 – 19.
[29] Takehiko Sato, Yuji Matsui, Masanori Okada, Kyohei Murakawa, and Zenzo Henmi, Palladium with a Thin Gold Layer as a Sliding Contact Material, IEEE Transactions on Components, Hybrids, and Manufacturing Technology, Vol.4, Issue 1, 1981, pp.10-14.
[30] Ikuhiro Andoh, Hiromichi Koyama, Shigeo Shioiri, and Michiko Endo, Characteristic of Palladium Gold Sliding Contact for Connectors, IEEE Transactions on Components, Hybrids, and Manufacturing Technology, Vol.5, Issue 4, 1982, pp.502-507.
[31] Simeon J. Krumbein and Morton Antler, Corrosion Inhibition and Wear Protection of Gold Plated Connector Contacts, IEEE Transactions of Parts, Materials and Packaging, Vol.4, No.1, pp.3-11, 1968.
[32] Olof A. Svedung, Lars-Gunnar Johansson, and Nils-Gosta Vannerberg, Corrosion of Gold-Coated Contact Materials Exposed to Humid Atmospheres Containing Low Concentrations of SO2 and NO2, IEEE Transactions on Components, Hybrids, and Manufacturing Technology, 1983, Vol.6, No.3, pp.349-355.
[33] Olof A. Svedung, Lars-Gunnar Johansson, and Nils-Gosta Vannerberg, The Influence of NO2 and Cl2 at Low Concentrations in Humid Atmospheres on the Corrosion of Gold-Coated Contact Material, IEEE Transactions on Components, Hybrids, and Manufacturing Technology, 1986, Vol.9, No.3, pp.286-292.
[34] Kei-ichi Yasuda, Shigeru Umemura, and Takeshi Aoki, Degradation Mechanisms in Tin- and Gold-Plated Connector Contacts, IEEE Transactions on Components, Hybrids, and Manufacturing Technology, 1987, Vol.10, No.3, pp.456-462.
[35] Rod Martens and Michael G. Pecht, An investigation of the electrical contact resistance of corroded pore sites on gold plated surfaces, IEEE Transactions on Advanced Packaging, 2000, Vol.23, Issue 3, pp.561-567.
[36] R. Freudenberger, J. Ganz, F. Kaspar, E. Marka, R. Michal, Contact and connection properties of autocatalytically increased gold-deposits, Electrical Contacts, 1996, Proceedings of the Forty-Second IEEE Holm Conference Joint with the 18th International Conference on Electrical Contacts, 1996, pp.461-466.
[37] Chen, Nelson, New demand and challenges for gold-bump technology, Solid State Technology, 2005, Vol.48, pp.71-72.
[38] C. A. Morse, N. R. Aukland and H. C. Hardee 1995 A statistical comparison of gold and palladium-nickel plating systems for various fretting parameters Proceedings of the Forty-First IEEE Holm Conference (Electrical Contacts) pp. 33-51
[39] F. H. Reid 1984 Palladium-nickel as a gold substitute: an evaluation for electronic connectors Platinum Metals Review 28, 54-55.
[40] Kenneth Hickey, Michelle Gerrity, Karen Nolan and Stafford Johnson European Patent: Orifice plate coated with palladium-nickel alloy European patent number: 1943101.
[41] Edward J. Martens, III United States Patent: Method and apparatus for dispensing liquids in aerosolized from with minimum spillage US patent number: 6386462.
[42] H.F. Morris, M. Manz, W. Stoffer and D. Weir 1992 Casting alloys: the materials and "the clinical effects" Advances in Dental Research 6, 28-31.
[43] N J Grimaudo 2001 Biocompatibility of nickel and cobalt dental alloys General Dentistry 49, 498-503.
[44] J. Muris and A. J. Feilzer 2006 Micro analysis of metals in dental restorations as part of a diagnostic approach in metal allergies Neuro Endocrinol Lett. 27, 49-52.
[45] Dagmar Ditrichova, Simona Kapralova, Martin Tichy, Vlastislava Ticha, Jitka Dobesova, Eva Justova, Miroslav Eber and Petr Pirek 2007 Oral lichenoid lesions and allergy to dental materials Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 151, 333-339.
[46] Scott Borland and Gary Baker United States Patent: Method for the construction of an aperture plate for dispensing liquid droplets US patent number: 6235177.
[47] W. Sharpe, D. Lavan, R. Edwards, Mechanical properties of LIGA-deposited nickel for MEMS, Proc. of Transducers 1997 International Conference on Solid State Sensors and Actuators, Chicago, IL, June 16-19, 1997.
[48] T. Christenson, T. Buchheit, D. Schmale, R. Bourcier, Mechanical and metallographic characterization of LIGA fabricated nickel and 80% Ni-20% Fe permalloy, Proc. of MRS Symposium 518 (1998) 185-190.
[49] T. Buchheit, T. Christenson, D. Schmale, D. Lavan, Understanding and tailoring the mechanical properties of LIGA fabricated materials, Proc. of MRS Symposium 546 (1998) 121-126.
[50] Yunn-Shiuan Liao and Ying-Tung Chen, Precision fabrication of an arrayed micro metal probe by the laser-LIGA process., J. Micromech. Microeng., 2005, Vol.15, pp.2433-2440.
[51] http://www.specialtytest.com/
[52] http://www.industrialinstruments.com/
[53] Stoney G G, 1909, The tension of thin metallic film deposited by electrolysis, Proc. R. Soc. A, 82, 172-175.
[54] V.N. Inkin, A.Y. Kolpakov, S.I. Oukhanov, V.I. Barbakov, M.E. Galkina, I.U. Goncharov, Change of internal stress of carbon superhard condensates at a process of annealing, Diamond and Related Materials, Vol.13, 2004, pp.1474-1479.
[55] Shusen Huang and Xin Zhang, Extension of the Stoney formula for film-substrate systems with gradient stress for MEMS applications, J. Micromech. Microeng. Vol.16, 2006, pp.382-389.
[56] E. Mazza, S. Abel, and J. Dual, Experimental determination of mechanical properties of Ni and Ni-Fe microbars, Microsyst. Technolo., Vol. 2, 1996, p197-202.
[57] W. Sharpe, D. Lavan, and R. Edwards, Mechanical properties of LIGA-deposited nickel for MEMS, in Transducers 1997 International Conference on Solid State Sensors and Actuators, Chicago, IL, June 16-19, 1997.
[58] T. Christenson, T. Buchheit, D. Schmale, and R. Bourcier, Mechanical and metallographic characterization of LIGA fabricated nickel and 80% Ni-20% Fe permalloy, in Proc. MRS Symposium, Vol.518, 1998, pp.185-190.
[59] T. Buchheit, T. Christenson, D. Schmale, and D. Lavan, Understanding and tailoring the mechanical properties of LIGA fabricated materials, in MRS Symposium Proceedings, Vol.546, 1998, pp.121-126.
[60] Basrour S, Robert L, Ballandras S and Hauden D, Mechanical characterization of microgrippers realized by LIGA technique transducers, in Transducers 1997 International Conference on Solid State Sensors and Actuators, Chicago, IL, June 16-19, 1997, pp.599-602.
[61] Sotirova-Chakarova G S and Armyanov S A, The internal stress in Ni, NiFe, CoFe and CoNi layers measured by bent strip method, J. Electrochem. Soc., Vol.137, 1990, pp.3551-3558.
[62] Manceau J F, Robert L, Bastien F O, Oytana C and Biwersi S, Measurement of residual stresses in a plate using a vibrational technique application to electrolytic nickel coatings, J. Microelectromech. Syst., 1996, Vol.5, pp.243-249.
[63] N.T. Nguyen, and Z. Wu, “Micromixers-a review”, J. Micromech. Microeng., 2005, Vol. 15, pp. R1-R16.
[64] L.C. Waters, S.C. Jacobson, N. Kroutchinina, J. Khandurina, R.S. Foote, and J.M. Ramsey, “Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing”, Anal. Chem., 1998, Vol. 70, pp. 158-162.
[65] M. Volpert, C.D. Meinhart, I. Mezic, and M. Dahelh, “An actively controlled micromixer”, Proceedings of MEMS ASME IMECE, pp. 483-487, 1999.
[66] Y.K. Lee, J. Deval, P. Tabeling, and C.M. Ho, “Chaotic mixing in electrokinetically and pressure driven micro flow”, Proceedings of the IEEE MEMS, pp. 483-486, 2001.
[67] X. Niu, and Y.K. Lee, “Efficient spatial-temporal chaotic mixing in microchannels”, J. Micromech. Microeng., 2003, Vol. 13, pp. 454-462.
[68] M.H. Oddy, J.G. Santiago, and J.C. Mikkelsen, “Electrokinetic instability micromixing”, Anal. Chem., 2001, Vol. 73, pp. 5822-5832.
[69] L.H. Lu, K.S. Ryu, and C. Liu, “A magnetic microstirrer and array for microfluidic mixing”, J. Microelectromech. Syst., Vol. 11, pp. 462-469, 2002.
[70] Z. Yang, H. Goto, M. Matsumoto, and R. Maeda, “Active micromixer for microfluidic systems using lead-zirconate-titanate (PZT)-generated ultrasonic vibration”, Electrophoresis, 2000, Vol. 21, pp. 116-119.
[71] R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref, and D.J. Beebe, “Passive mixing in a three-dimensional serpentine microchannel”, J. Microelectromech. Syst., 2000, Vol. 9, pp. 190-197.
[72] A.D. Stroock, S.K.W. Dertinger, A. Ajdari, I. Mezic, H.A. Stone, and G.M. Whitesides, “Chaotic mixer for microchannels”, Science, 2002, Vol. 295, pp. 647-651.
[73] C.P. Jen, C.Y. Wu, Y.C. Lin, and C.Y. Wu, “Design and simulation of the micromixer with chaotic advection in twisted microchannels”, Lab on a Chip, 2003, Vol. 3, pp. 77-81.
[74] Lu, G. Q.; Wang, C. Y. Development of micro direct methanol fuel cells for high power applications. Journal of Power Sources, 2005, 144, 141-145.
[75] Koripella, C. R.; Ooms, W. J.; Wilcox, D. L.; Bostaph, J. W. Direct Methanol Fuel Cell System and Method of Fabrication. U. S. Patent 6,387,559, 2000.
[76] Bostaph, J. W.; Koripella, C. R.; Fisher, A. M. Direct Methanol Fuel Cell System Including an Integrated Methanol Sensor and Method of Fabrication. U. S. Patent 6,696,189, 2000.
[77] Neutzler, J.; Bostaph, J. W.; Fisher, A. M. Direct Methanol Fuel Cell Including a Water Management System and Method of Fabrication. U. S. Patent 6,660,423, 2000.
[78] Gottesfeld, S. Methods and Apparatuses for a Pressure Driven Fuel Cell System. U. S. Patent 6,686,081, 2001.
[79] Bostaph, J. W.; Marshall, D. S. Direct Methanol Fuel Cell Including a Water Recovery and Recirculation System and Method of Fabrication. U. S. Patent 6,727,016, 2001.
[80] Tajima, N.; Sakaue, E.; Matsuoka, K. Fuel Cell. U. S. Patent 7,318,969, 2008.
[81] Volpert, M.; Meinhart, C. D.; Mezic, I.; Dahelh, M. An actively controlled micromixer, Proceedings of MEMS ASME IMECE, 1999; pp. 483-487.
[82] Lee, Y. K.; Deval, J.; Tabeling, P.; Ho, C. M. Chaotic mixing in electrokinetically and pressure driven micro flow, Proceedings of the IEEE MEMS, 2001; pp. 483-486.
[83] Niu, X.; Lee, Y. K. Efficient spatial-temporal chaotic mixing in microchannels. J. Micromech. Microeng., 2003, 13, 454-462.
[84] Oddy, M. H.; Santiago, J. G.; Mikkelsen, J. C. Electrokinetic Instability Micromixing. Anal. Chem., 2001, 73, 5822-5832.
[85] Lu, L.–H.; Ryu, K. S.; Liu, C. A magnetic microstirrer and array for microfluidic mixing. J. Microelectromech. Syst., 2002, 11, 462-469.
[86] Yang, Z.; Goto, H.; Matsumoto, M.; Maeda, R. Active micromixer for microfluidic systems using lead-zirconate-titanate (PZT)-generated ultrasonic vibration. Electrophoresis, 2000, 21, 116-119.
[87] Liu, R. H.; Stremler, M. A.; Sharp, K. V.; Olsen, M. G.; Santiago, J. G.; Adrian, R. J.; Aref, H.; Beebe, D. J. Passive mixing in a three-dimensional serpentine microchannel. J. Microelectromech. Syst., 2000, 9, 190-197.
[88] Stroock, A. D.; Dertinger, S. K. W.; Ajdari, A.; Mezic, I.; Stone, H. A.; Whitesides, G. M. Chaotic mixer for microchannels. Science, 2002, 295, 647-651.
[89] Bertsch, A.; Heimgartner, S.; Cousseau, P.; Renaud, P. 3D micromixers-downscaling large scale industrial static mixers, Proceedings of the IEEE MEMS, 2001; pp. 507-510.
[90] Bertsch, A.; Heimgartner, S.; Cousseau, P.; Renaud, P. Static micromixers based on large-scale industrial mixer geometry. Lab on a Chip, 2001, 1, 56-60.
[91] Kim, D. S.; Lee, I. H.; Kwon, T. H.; Cho, D.-W. A barrier embedded Kenics micromixer. J. Micromech. Microeng., 2004, 14, 1294-1301.
[92] Kim, D. S; Lee, S. W.; Kwon, T. H.; Lee, S. S. A barrier embedded chaotic micromixer. J. Micromech. Microeng., 2004, 14, 798-805.
[93] A. Bertsch, S. Heimgartner, P. Cousseau, and P. Renaud, “3D micromixers-downscaling large scale industrial static mixers”, Proceedings of the IEEE MEMS, pp 507-510, 2001.
[94] A. Bertsch, S. Heimgartner, P. Cousseau, and P. Renaud, “Static micromixers based on large-scale industrial mixer geometry”, Lab on a Chip, Vol. 1, pp. 56-60, 2001.
[95] D.S. Kim, I.H. Lee, T.H. Kwon, and D.W. Cho, “A barrier embedded Kenics micromixer”, J. Micromech. Microeng., 2004, Vol. 14, pp. 1294-1301.
[96] Part, S.-J.; Kim, J. K.; Park, J.; Chung, S.; Chung, C.; Chang, J. K. Rapid three-dimensional passive rotation micromixer using the breakup process. J. Micromech. Microeng., 2004, 14, 6-14.
[97] T.J. Johnson, D. Ross, and L.E. Locascio, “Rapid microfluidic mixing”, Anal. Chem., 2002, Vol. 74, pp. 45-51.
[98] B. He, B.J. Burke, X. Zhang, R. Zhang, F.E. Regnier, “A picoliter-volume mixer for microfluidic analytical systems”, Anal. Chem., 2001, Vol. 73, pp. 1942-1947.
[99] L.H. Lu, K.S. Ryu, and C. Liu, “A magnetic microstirrer and array for microfluidic mixing”, J. Microelectromech. Syst., 2002, Vol. 11, pp. 462-469.
[100] R.U. Seidel, D.Y. Si, W. Menz, and M. Esashi, “Capillary force mixing device as sampling module for chemical analysis”, Proceedings of the Transducers, pp 438-441, 1999.
[101] D. Bokenkamp, A. Desai, X. Yang, Y.C. Tai, Marzluff EM, Mayo SL, “Microfabricated silicon mixers for submillisecond quench-flow analysis”, Anal. Chem., 1998, Vol. 70, pp. 232-236.
[102] H.Y. Wu, C.H. Liu, “A novel electrokinetic micromixer”, Sensors and Actuators A, 2005, Vol. 118, pp. 107-115.
[103] M. Jain, K. Nandakumar, “Novel index for micromixing characterization and comparative analysis”, Biomicrofluidics, September, 4(3): 031101, 2010 [Online].