微流體裝置應用於生物醫學領域，經常被使用在分離細胞或蛋白質。在製作微流體裝置時，高分子(如聚甲基丙烯酸甲酯，PMMA)是被看好的製作材料，因為價廉且易加工的特性。但高分子表面的濕潤性質侷限應用的範圍，因此會使用表面處理的技術，來改變高分子表面的濕潤性質，擴大應用的範圍。因此在為流裝體裝置中，改良微流道表面濕潤性以突破侷限，是一個重要的議題。

根據先前的研究，金屬玻璃鍍層具有抗菌、抗血小板與癌細胞沾黏等良好的生物相容性質，本研究使用磁控濺鍍方式將數種金屬玻璃鍍覆於微流道表面上進行測試，而微流道由PMMA加工後製成。測試過程首先將不同濃度的蛋白質溶液注入微流道，之後在溶液出口處收集溶液進行BCA (bicinchoninic acid)濃度分析，可得知蛋白質溶液的損失量。

在不同蛋白質濃度的研究中使用的對照組為未鍍膜之微流道和有電漿蝕刻但未鍍膜微流道。實驗結果證明，具金屬玻璃鍍層之微流道透過離子轟擊改質表面性質，使得蛋白質吸附量高於未鍍膜之微流道。而具金屬玻璃鍍層之微流道與有電漿蝕刻之未鍍膜微流道相比，具鍍覆鋯基(ZrCuAlNi)及鈀基(PdCuSi)金屬玻璃鍍層之微流道因有良好之疏水性質，皆表現出減少蛋白質吸附的特性，另一方面鍍覆具有良好之親水性質的鎢基(WNiB)金屬玻璃鍍層之微流道，則表現出增加蛋白質吸附的特性。

最後，在螢光染色實驗中，利用螢光染劑將蛋白質染色、分析其吸附面積，此分析結果與BCA之分析結果相符。

整體而言，鋯基及鈀基金屬玻璃鍍層之微流道能有效減少蛋白質吸附，鎢基金屬玻璃鍍層之微流道能有效增加蛋白質吸附。

Microfluidic devices have been widely applied for biological analyses, such as separation of cells or proteins. In general, polymer materials have been used for microfluidic device fabrication, for their low cost and ease of production. However, biological molecular adsorption is a major problem in polymer microchannels, which depends on their surface properties. Improving polymer microchannel surface properties to reduce molecular adsorption is therefore an important issue.

A previous work demonstrated that Thin File Metallic Glass (TFMG) has good biocompatibility, less adhesion to platelet and cancer cells and antibacterial properties. In this study, Poly(methyl methacrylate) (PMMA) material was used to fabricate microchannel. Many types of TFMG were deposited on a microchannel surface via a magnetron sputtering system. The microchannels were tested using a protein solution, which was prepared using a Bovine Serum Albumin (BSA) protein in a Phosphate buffered saline (PBS) solution. Analysis was performed using the bicinchoninic acid (BCA) method, and comparison was made of bare, etched-bare, and TFMG-coated microchannel samples.

The adsorption by the TFMG sample was found to be higher than the bare sample because the surface properties of TFMG was modified due to plasma treatment in deposition processes. Comparison of the etched-bare (plasma treatment) and TFMG samples adsorption show that ZrCuAlNi (Z-TFMG) and PdCuSi (P-TFMG) have lower adsorption than that of the etched-bare sample because TFMGs are more hydrophobic. On the other hand, WNiB (W-TFMG), chosen for its hydrophilic property, showed more adsorption result. Results obtained using fluorescent microscope analysis, which dyes protein in order to calculate protein adsorption areas, were consistent with that obtained with the BCA method.

[1] D.J. Harrison, K. Fluri, K. Seiler, Z. Fan, C.S. Effenhauser, A.J.S. Manz, Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip, 261(5123) (1993) 895-897.
[2] D.J. Harrison, A. Manz, Z. Fan, H. Luedi, H.M.J.A.c. Widmer, Capillary electrophoresis and sample injection systems integrated on a planar glass chip, 64(17) (1992) 1926-1932.
[3] V. Faustino, S.O. Catarino, R. Lima, G. Minas, Biomedical microfluidic devices by using low-cost fabrication techniques: A review, Journal of biomechanics 49(11) (2016) 2280-2292.
[4] I. Ahmed, H.M. Iqbal, Z.J.A.J.f.S. Akram, Engineering, Microfluidics engineering: Recent trends, valorization, and applications, 43(1) (2018) 23-32.
[5] M. Toner, G. Truskey, R. Kapur, Microfluidic Device For Cell Separation And Uses Thereof, Google Patents, 2019.
[6] V. Dolník, S. Liu, S. Jovanovich, Capillary electrophoresis on microchip, ELECTROPHORESIS: An International Journal 21(1) (2000) 41-54.
[7] L. Mou, X. Jiang, Materials for microfluidic immunoassays: a review, Advanced healthcare materials 6(15) (2017) 1601403.
[8] C.-W. Tsao, Polymer microfluidics: Simple, low-cost fabrication process bridging academic lab research to commercialized production, Micromachines 7(12) (2016) 225.
[9] K. Ren, J. Zhou, H. Wu, Materials for microfluidic chip fabrication, Accounts of chemical research 46(11) (2013) 2396-2406.
[10] C. Pipatpanukul, R. Amarit, A. Somboonkaew, B. Sutapun, A. Vongsakulyanon, P. Kitpoka, T. Srikhirin, M. Kunakorn, Microfluidic PMMA‐based microarray sensor chip with imaging analysis for ABO and RhD blood group typing, Vox sanguinis 110(1) (2016) 60-69.
[11] J. Liu, T. Pan, A.T. Woolley, M.L. Lee, Surface-modified poly (methyl methacrylate) capillary electrophoresis microchips for protein and peptide analysis, Analytical chemistry 76(23) (2004) 6948-6955.
[12] A. Tserepi, E. Gogolides, A. Bourkoula, A. Kanioura, G. Kokkoris, P.S. Petrou, S.E. Kakabakos, Plasma Nanotextured Polymeric Surfaces for Controlling Cell Attachment and Proliferation: A Short Review, Plasma Chemistry and Plasma Processing 36(1) (2016) 107-120.
[13] H. Bi, S. Meng, Y. Li, K. Guo, Y. Chen, J. Kong, P. Yang, W. Zhong, B. Liu, Deposition of PEG onto PMMA microchannel surface to minimize nonspecific adsorption, Lab on a Chip 6(6) (2006) 769-775.
[14] K. Tsougeni, P.S. Petrou, D.P. Papageorgiou, S.E. Kakabakos, A. Tserepi, E. Gogolides, Controlled protein adsorption on microfluidic channels with engineered roughness and wettability, Sensors and Actuators B: Chemical 161(1) (2012) 216-222.
[15] A. Loureiro, A.S. Abreu, M.P. Sárria, M.C. Figueiredo, L.M. Saraiva, G.J. Bernardes, A.C. Gomes, A. Cavaco-Paulo, Functionalized protein nanoemulsions by incorporation of chemically modified BSA, RSC Advances 5(7) (2015) 4976-4983.
[16] W. Norde, Adsorption of proteins from solution at the solid-liquid interface, Advances in colloid and interface science 25 (1986) 267-340.
[17] J.D. Andrade, Protein adsorption, Plenum Press1985.
[18] C.A. Haynes, W. Norde, Globular proteins at solid/liquid interfaces, Colloids and surfaces B: Biointerfaces 2(6) (1994) 517-566.
[19] M. Zhu, P. Fuks, G. Carta, Protein adsorption in anion exchange resins – effects of polymer grafting, support structure porosity, and protein size, Journal of Chemical Technology & Biotechnology 93(7) (2018) 1948-1958.
[20] D. Jiang, Z. Liu, X. He, J. Han, X. Wu, Polyacrylamide strengthened mixed-charge hydrogels and their applications in resistance to protein adsorption and algae attachment, RSC Advances 6(53) (2016) 47349-47356.
[21] T. Khampieng, V. Yamassatien, P. Ekabutr, P. Pavasant, P. Supaphol, Protein adsorption and cell behaviors on polycaprolactone film: The effect of surface topography, Advances in Polymer Technology 37(6) (2018) 2030-2042.
[22] S. Rege, R. Yang, J. Tóth, Adsorption: Theory, Modeling, and Analysis, Marcel Dekker New York, 2002.
[23] S. Kumar, R. Nussinov, Close‐range electrostatic interactions in proteins, ChemBioChem 3(7) (2002) 604-617.
[24] E. Gogolides, K. Ellinas, A. Tserepi, Hierarchical micro and nano structured, hydrophilic, superhydrophobic and superoleophobic surfaces incorporated in microfluidics, microarrays and lab on chip microsystems, Microelectronic Engineering 132 (2015) 135-155.
[25] K. Tsougeni, P.S. Petrou, A. Tserepi, S.E. Kakabakos, E. Gogolides, Nano-texturing of poly (methyl methacrylate) polymer using plasma processes and applications in wetting control and protein adsorption, Microelectronic Engineering 86(4-6) (2009) 1424-1427.
[26] J.J. Kruzic, Bulk metallic glasses as structural materials: a review, Advanced Engineering Materials 18(8) (2016) 1308-1331.
[27] S.J.M.G.A. Kavesh, Metals Park, Ohio. , 36-73, Principles of Fabrication(of Metallic Glasses), (1978).
[28] H.J.A.M. Chen, Thermodynamic considerations on the formation and stability of metallic glasses, 22(12) (1974) 1505-1511.
[29] W.L.J.M.b. Johnson, Bulk glass-forming metallic alloys: Science and technology, 24(10) (1999) 42-56.
[30] H.-W. Jeong, S. Hata, A. Shimokohbe, Micro-forming of thin film metallic glass by local laser heating, Technical Digest. MEMS 2002 IEEE International Conference. Fifteenth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No. 02CH37266), IEEE, 2002, pp. 372-375.
[31] A. Inoue, A.J.A.M. Takeuchi, Recent development and application products of bulk glassy alloys, 59(6) (2011) 2243-2267.
[32] H. Ida, M. Seiryu, N. Takeshita, M. Iwasaki, Y. Yokoyama, Y. Tsutsumi, E. Ikeda, S. Sasaki, S. Miyashita, S. Sasaki, Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application, Acta biomaterialia 74 (2018) 505-517.
[33] P.-S. Chen, H.-W. Chen, J.-G. Duh, J.-W. Lee, J.S.-C.J.S. Jang, C. Technology, Characterization of mechanical properties and adhesion of Ta–Zr–Cu–Al–Ag thin film metallic glasses, 231 (2013) 332-336.
[34] C.-Y. Chuang, J.-W. Lee, C.-L. Li, J.P.J.S. Chu, C. Technology, Mechanical properties study of a magnetron-sputtered Zr-based thin film metallic glass, 215 (2013) 312-321.
[35] H.-W. Jeong, S. Hata, A.J.J.o.m.s. Shimokohbe, Microforming of three-dimensional microstructures from thin-film metallic glass, 12(1) (2003) 42-52.
[36] M. Ashby, A.J.S.M. Greer, Metallic glasses as structural materials, 54(3) (2006) 321-326.
[37] A. Inoue, Stabilization of metallic supercooled liquid and bulk amorphous alloys, Acta materialia 48(1) (2000) 279-306.
[38] J.C. Wataha, C. Hanks, R.G. Craig, In vitro effect of metal ions on cellular metabolism and the correlation between these effects and the uptake of the ions, Journal of biomedical materials research 28(4) (1994) 427-433.
[39] L. Liu, C. Qiu, Q. Chen, S. Zhang, Corrosion behavior of Zr-based bulk metallic glasses in different artificial body fluids, Journal of alloys and compounds 425(1-2) (2006) 268-273.
[40] S. Hiromoto, A.-P. Tsai, M. Sumita, T. Hanawa, Effect of chloride ion on the anodic polarization behavior of the Zr65Al7. 5Ni10Cu17. 5 amorphous alloy in phosphate buffered solution, Corrosion Science 42(9) (2000) 1651-1660.
[41] F. Hadjoub, W. Metiri, A. Doghmane, Z. Hadjoub, Bulk metallic glass matrix composite for good biocompatibility, IOP Conference Series: Materials Science and Engineering, IOP Publishing, 2012, p. 012038.
[42] J.P. Chu, J. Jang, J. Huang, H. Chou, Y. Yang, J. Ye, Y.-C. Wang, J. Lee, F. Liu, P. Liaw, Thin film metallic glasses: Unique properties and potential applications, Thin Solid Films 520(16) (2012) 5097-5122.
[43] C.-L. Li, J.-C. Chang, B.-S. Lou, J.-W. Lee, J.P. Chu, Fabrication of W-Zr-Si thin film metallic glasses and the influence of post-annealing treatment, Journal of Non-Crystalline Solids 482 (2018) 170-176.
[44] J.P. Chu, C.-Y. Wang, L. Chen, Q. Chen, Annealing-induced amorphization in a sputtered glass-forming film: In-situ transmission electron microscopy observation, Surface and Coatings Technology 205(8-9) (2011) 2914-2918.
[45] F. Liu, F. Yang, Y. Gao, W. Jiang, Y. Guan, P. Rack, O. Sergic, P.K. Liaw, Micro-scratch study of a magnetron-sputtered Zr-based metallic-glass film, Surface and Coatings Technology 203(22) (2009) 3480-3484.
[46] J.P. Chu, C.-C. Yu, Y. Tanatsugu, M. Yasuzawa, Y.-L. Shen, Non-stick syringe needles: Beneficial effects of thin film metallic glass coating, Scientific reports 6 (2016) 31847.
[47] P.-T. Chiang, G.-J. Chen, S.-R. Jian, Y.-H. Shih, J.S.-C. Jang, C.-H. Lai, Surface antimicrobial effects of Zr61Al7. 5Ni10Cu17. 5Si4 thin film metallic glasses on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Candida albicans, Fooyin Journal of Health Sciences 2(1) (2010) 12-20.
[48] J.P. Chu, T.-Y. Liu, C.-L. Li, C.-H. Wang, J.S. Jang, M.-J. Chen, S.-H. Chang, W.-C. Huang, Fabrication and characterizations of thin film metallic glasses: Antibacterial property and durability study for medical application, Thin Solid Films 561 (2014) 102-107.
[49] C.-H. Chang, C.-L. Li, C.-C. Yu, Y.-L. Chen, S. Chyntara, J.P. Chu, M.-J. Chen, S.-H. Chang, Beneficial effects of thin film metallic glass coating in reducing adhesion of platelet and cancer cells: Clinical testing, Surface and Coatings Technology 344 (2018) 312-321.
[50] W. Diyatmika, C.-C. Yu, Y. Tanatsugu, M. Yasuzawa, J.P. Chu, Fibrinogen and albumin adsorption profiles on Ni-free Zr-based thin film metallic glass, Thin Solid Films (2019).
[51] I. Dion, X. Roques, H. Baquey, E. Baudet, B. Basse Cathalinat, N.J.B.-m.m. More, engineering, Hemocompatibility of diamond-like carbon coating, 3(1) (1993) 51-55.
[52] S.-L. Huang, M.-S. Chao, R.-C. Ruaan, J.-Y.J.E.P.J. Lai, Microphase separated structure and protein adsorption of polyurethanes with butadiene soft segment, 36(2) (2000) 285-294.
[53] Z. Li, C. Zhang, L. Liu, Wear behavior and corrosion properties of Fe-based thin film metallic glasses, Journal of Alloys and Compounds 650 (2015) 127-135.
[54] D. Mattox, Film Formation, Adhesion, Surface Preparation and Contamination Control, Handbook of physical vapor deposition (PVD) processing, Noyes publications, Westwood, New Jersey, USA, 1998.
[55] R.A. Surmenev, A review of plasma-assisted methods for calcium phosphate-based coatings fabrication, Surface and Coatings Technology 206(8-9) (2012) 2035-2056.
[56] P.J. Kelly, R.D. Arnell, Magnetron sputtering: a review of recent developments and applications, Vacuum 56(3) (2000) 159-172.
[57] H.H. Tran, W. Wu, N.Y. Lee, Ethanol and UV-assisted instantaneous bonding of PMMA assemblies and tuning in bonding reversibility, Sensors and Actuators B: Chemical 181 (2013) 955-962.
[58] F. Rupp, R.A. Gittens, L. Scheideler, A. Marmur, B.D. Boyan, Z. Schwartz, J.J.A.b. Geis-Gerstorfer, A review on the wettability of dental implant surfaces I: theoretical and experimental aspects, 10(7) (2014) 2894-2906.
[59] L.G. Halsey, D. Curran-Everett, S.L. Vowler, G.B. Drummond, The fickle P value generates irreproducible results, Nature methods 12(3) (2015) 179.
[60] Z. An, H. Jia, Y. Wu, P.D. Rack, A.D. Patchen, Y. Liu, Y. Ren, N. Li, P.K. Liaw, Solid-solution CrCoCuFeNi high-entropy alloy thin films synthesized by sputter deposition, Materials Research Letters 3(4) (2015) 203-209.
[61] D. Hetemi, J. Pinson, Surface functionalisation of polymers, Chemical Society Reviews 46(19) (2017) 5701-5713.
[62] Y. Jeyachandran, E. Mielczarski, B. Rai, J. Mielczarski, Quantitative and qualitative evaluation of adsorption/desorption of bovine serum albumin on hydrophilic and hydrophobic surfaces, Langmuir 25(19) (2009) 11614-11620.