本論文以實驗方式探討高黏度複合材料造粒應用於肝癌栓塞微球，研究工作主要分為三個部分：第一部分探討雙流體霧化器，液體主要成分為褐藻膠與氣體為空氣，探討研究內容包含液體質量流率、氣體質量流率和氣/液質量流率等參數對霧化錐角、霧化粒徑、霧化粒徑分布等噴霧品質影響，第二部分探討微球形貌類型並定義球形量與拖尾量。第三部分液態氮為收集液體，利用冷凍收集法產出微球並控制形貌。
第一部份實驗結果提供雙流體霧化器操作參數，結果亦顯示操作條件設定為液體質量流率 0.067 g/s，氣體質量流率 0.086 g/s，氣液質量比 1.28，粒徑主要分布在88.5~248.9 μm，此時霧化角度 20~28 度及微球形貌類型包括球型和球型拖尾，結果亦顯示隨氣體質量流率遞增、球形拖尾現象遞減，當氣體質量流率到達某一定值，微球可達無拖尾，但會產生空心包覆狀態，並且進一步結果顯示顆粒大小與速度影響氯化鈣產生凝膠化的反應時間影響球形量與拖尾量；綜合結果可知調整氣液質量流率參數將微球球形量提高至 0.95、拖尾量低於 0.2，以提供肝癌栓塞微球生產製程所需。第二部分實驗結果顯示，微球生產形貌會受到液滴尺度、飛行速度、停留在收集液表面的時間、收集液表面張力頸縮現象及氯化鈣凝膠化反應速率影響而產生微球形貌包括球型、球型拖尾、扇形拖尾、橢圓及不規則形狀，而本研究為生產真圓微球，利用球形量及拖尾量定義微球變形程度及拖尾長度，最後研究顯示綜合最佳參數收集液表面張力 74 dyn/cm、收集距離 31 cm 和收集液濃度 1.1 %，可產出粒徑尺度 75~250 µm 微球球形量皆高於 0.95、拖尾量皆低於 0.09 高真圓度肝癌栓塞微球。由於第二部分結果顯示實驗操作因素影響參數包括顆粒尺寸、速度、收集液表面張力、濃度和收集距離等，為解決液面頸縮所造成的影響，進一步開發液態氮冷凍收集技術，故第三部分實驗利用液態氮沸點-195.79°C 使液滴在沒入之前已受蒸發的氮氣冷卻，在液態氮液面上方就先在表面結成一層薄冰，取代液態顆粒掉入液態，解決液滴形貌在收集液面上所受的諸多限制，並產出微球粒徑範圍 36.1~211.5 μm。

This research aims at the production of microspheres to meet the requirements for the clinical trials. The droplet formation of high viscosity fluid which containing many spcies of the pharmaceutical excipients and medicines is rather difficult to produce by tradition processes. Hence flow focusing techniques with liquid and gas was developed to produce microspheres for medical applications. The goal of research is to produce the microsphere with diameters ranging from 100 μm to 300 μm to meet the required specifications of the medical applications. Result show that the particle size and spray angle can be controlled by liquid mass flow rate, air mass flow rate and air/liquid mass flow ratio. This research also controlled the morphology of microspheres including spherical, spherical with tail and hollow wrap ball. It is concluded that our microspheres satisfy the requirements of microspheres in medical applications and solved the problem that microsphere producing tailing. The results show that spherical morphology microspheres on the operating conditions are set to 0.067 g/s of liquid mass flow rate, 0.086 g/s of gas mass flow rate and 1.28 of mass ratio of gas and liquid. The atomization angle is from 20 to 28 degrees with diameters ranging from 88.5 μm to 248.9 μm to meet the required specifications of the medical applications. And the result show that the best parameters to produce hepatoma embolization microspheres on spherical amount with 0.95 and amount of tail with 0.09 are on the collection of liquid surface tension on 74 dyn/cm, collection distance on 31 cm and collection concentration on 1.1 %. The results show that the experimental factors include particle size, velocity, surface tension, concentration and collection distance of the collected liquid. In order to solve the problem of liquid necking, this research also development of frozen collection technology to produce high spherical amount microspheres.

[1] Aligner, M. and Witting, S.(1980), ” Swirl and Counterswirl Efferts in Prefilming Airblast Atomization”, Trans. ASME, J. Eng. Power, vol. 102, pp.706-710
[2] Ashgriz, N.(2011), “Handbook of atomization and sprays: Capillary Instability of Free Liquid Jets,” p. 8-14.
[3] Beck, J., Lefebvre, A.H. and Koblish, T. (1989), “Air Blast Ayomization at conditions of Low Air Velocity,” Paper No, AIAA, 89-0217.
[4] Beck, J., Lefebvre, A.H. and Koblish, T.R., “Liquid Sheet Distintegration by Impinging Air Streams,” Atomization and Sprays, Vol.1, No. 2, pp.155-170, 1991
[5] Beck, J., Lefebvre, A.H. (1991), ” Airblast Atomization at Conditions of Low Air Velocity,” J. Propulsion, vol. 7, No.2
[6] Chan, E.S.(2009), “Prediction models for shape and size of ca-alginate macrobeads produced through extrusion–dripping method,” Journal of Colloid and Interface Science, Vol.338, pp.63-72.
[7] Chen, S. Kevin and Lefebvre, Arthur H. (1994), ”Spray Cone Angle of Effervescent Atomizers, “ Atomization and Sprays, Vol.4, pp.291-301.
[8] Dang, T.D., Joo, S.W. (2013), “Preparation of tadpole-shaped calcium alginate microparticles with sphericity control,” Colloids and Surfaces B: Biointerfaces, Vol.102, pp.766-771.
[9] Davarci, F. (2017), “The influence of solution viscosities and surface tension on calcium-alginate microbead formation using dripping technique,” Food Hydrocolloids, Vol.62, pp.119-127.
[10] Dorman, R. G. (1952), “The Atomization of Liquid in a Flat Spray,” British J. Applphys., Vol. 3, pp.189-192.
[11] Fraser, R. P., Eisenklam, P., Dombrowski, N. and Hasson, D. (1962), “Drop Formation from Rapidly Moving Sheets,” A. I. Ch. E .J., Vol. 8, No. 5, pp.672-680.
[12] Haenlein, A., “Disintegration of a Liquid Jet,” NACA-TM-659, 1932.
[13] Heinzen, C., Berger, A. and Marison, L. (2002), “Use of vibration technology for jet break-up for encapsulation of cells and liquids in monodisperse microcapsules,” Journal of Colloid and Interface Science, Vol. 417, pp. 121-130.
[14] Lefebvre, A. H. (1989), “Atomization and Sprays,” Hemisphere Pulishing Corporation, New York, pp.1-11.
[15] McCuan, J. (1997), “Retardation of Plateau-Rayleigh instability: a distinguishing characteristic among perfectly wetting fluids,” arXiv preprint math/9701214.
[16] Muller, T.(2016), “Simulation of the primary breakup of a high-viscosity liquid jet by a coaxial annular gas flow,“ Journal of Multiphase Flow, Vol.87, pp.212-228.
[17] Ohnesorge, W. (1936), “Formation of Drop by Nozzles and the Breakup of Liquid Jet,” Z. Angew.Math. Mech., Vol. 16, pp. 355-358.
[18] Press, C., Gupta, A. K. and Semerjian, H.G., “Aerodynamic Effects on Fuel Spray Characteristics: Air-assisr Atomizer,“ HTD-Vol.104, pp.111-119, 1988
[19] Qian, L.(2016), “Numerical Models for Viscoelastic Liquid Atomization Spray,” Energies, Vol.9, No. 12, pp.1079.
[20] Rayleigh, L. (1878), “On the instability of jets,” Proceedings of the London mathematical society, vol.10, 1.1:4-13.
[21] Rayleigh, L. (1879), “On the capillary phenomena of jets, “Proc. R. Soc. London. p. 71-97.
[22] Rizkalla, A. A. and Lefebvre, A.H. (1975),”Influence of Liquid Properties on Airblast Atomizer Spray Characteristics, J.Eng.Power, pp. 173-179.
[23] Rizkalla, A. A. and Lefebvre, A.H. (1975),”Influence of Air and Liquid properties on Airblast Atomization,” J.Fluids.,vol. 97, pp.316-320.
[24] Rizk, N.K. and Lefebvre, A.H. (1983), “Influence of Atomizer Design Feature on Mean Drop Size,” AIAA Journal, Vol.21, No. 8, pp. 1139-1142.
[25] Rizk, N. K. and Lefebvre, A.H. (1984), “Spray Characteristics of Plain-ject Airblast Atomizer,“ Transtion of The Asme, Vol.106.
[26] Sattelmayer, T. and Witting, S. (1986), “Intermal Flow Effects in Prefilming Airblast Atomizers Mechanisms of Atomization and Droplet Spectra,” ASME Journal of Engineering for Gas Turbine and Power, Vol.108, pp.465-472.
[27] Weber, C. (1931), “Zum zerfall eines flüssigkeitsstrahles,” ZAMM‐Journal of Applied Mathematics and Mechanics/Zeitschrift für Angewandte Mathematik und Mechanik, 11.2: 136-154.
[28]許耀仁(1993)，「氣衝式平面噴嘴液模霧化特性之研究」， 國立成功大學碩士論文。
[29]楊國明(2006)，「藥物釋放之親疏水性乙基纖維素/羥丙基纖維素摻合微粒的製備與其藥物釋放之研究」，國立成功大學博士論文。