現今紙基微流道分析裝置在快篩領域中迅速地發展，因為它具有低成本、方便與用完即丟等優點。然而，傳統紙基晶片的管道大多是單直通管道且無法控制選擇性薄膜在管道中的截面積。此外，應用於分析時需要有一定的樣品量。在此篇論文中，我們利用摺紙技術設計出微小化的立體管道並且將樣品儲液槽整合於裝置上，有助於降低電壓與減少樣品的使用量，故可提高整體濃縮效率，節省不必要的浪費。為了確認流體可以在立體管道中流動，我們利用電流監測法觀察電滲流 (EOF) 證明此裝置的可行性。在此裝置中我們只須20 μl，10-5 M的樣品量與30伏特的電壓，即可使濃縮倍率快速達到100倍。同時我們使用更稀薄的樣品濃度 (10-6 M) 來進行相同的實驗也成功地達到相同的倍率，此舉證明了我們的裝置可使濃縮效果更快更有效率。最後，為了證明此裝置的實用性，我們使用結合著螢光粒子的牛血清白蛋白 (FITC-BSA) 來進行實驗，其結果顯示蛋白質也能在此裝置中被預濃縮，其樣品濃度可提升至近100倍且僅需30 μl，10-6 M的樣品量與40伏的電壓。

Microfluidic paper-based analytical devices (µPADs) have been developed intensively for rapid screening because of their low cost, convenience and disposable nature. However, traditional devices are mostly a straight channel and we can not control the cross-sectional area of selective membrane in these devices. Besides, they required significant sample volumes when was used in analysis experiments. In this thesis, we utilized the origami technique to design a three-dimensional channel and embed the reservoir into the device. In this manner, the application voltage and sample volume are reduced; hence, the preconcentration effectiveness is enhanced while avoiding sample waste. We measured the EOF velocity by the current-monitoring method to verify the feasibility that fluid can flow in the three-dimensional channel. We required a sample of only 20 μl and applied 30 V, after which the concentration was quickly enhanced to 100-fold from the initial concentration of 10-5 M in this device. To further demonstrate the device feasibility, we diluted the sample concentration to 10-6 M and repeated the experiment. The results show that the concentration can be also increased 100-fold, thereby validating that the device can concentrate samples quickly and efficiently.
Finally, we used fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) as target molecules, the concentration of which was 10-6 M, and applied a voltage of 40 V in a concentration experiment to further verify the practical application. The results demonstrate that the concentration increased nearly 100-fold with only a 30 μl sample.

1. Chin, C.D., V. Linder, and S.K. Sia, Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip, 2007. 7(1): p. 41-57.
2. Yager, P., G.J. Domingo, and J. Gerdes, Point-of-care diagnostics for global health. Annu Rev Biomed Eng, 2008. 10: p. 107-44.
3. Yager, P., et al., Microfluidic diagnostic technologies for global public health. Nature, 2006. 442(7101): p. 412-8.
4. Haeberle, S. and R. Zengerle, Microfluidic platforms for lab-on-a-chip applications. Lab Chip, 2007. 7(9): p. 1094-110.
5. Gubala, V., et al., Point of care diagnostics: status and future. Anal Chem, 2012. 84(2): p. 487-515.
6. Mao, X. and T.J. Huang, Microfluidic diagnostics for the developing world. Lab Chip, 2012. 12(8): p. 1412-6.
7. Chin, C.D., V. Linder, and S.K. Sia, Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip, 2012. 12(12): p. 2118-34.
8. Martinez, A.W., et al., Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal Chem, 2010. 82(1): p. 3-10.
9. Martinez, A.W., et al., Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed Engl, 2007. 46(8): p. 1318-20.
10. Martinez, A.W., S.T. Phillips, and G.M. Whitesides, Three-dimensional microfluidic devices fabricated in layered paper and tape. Proc Natl Acad Sci U S A, 2008. 105(50): p. 19606-11.
11. Luo, L., X. Li, and R.M. Crooks, Low-voltage origami-paper-based electrophoretic device for rapid protein separation. Anal Chem, 2014. 86(24): p. 12390-7.
12. Song, Y., et al., Point-of-care technologies for molecular diagnostics using a drop of blood. Trends Biotechnol, 2014. 32(3): p. 132-9.
13. Ridker, P.M., Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention. Circulation, 2003. 107(3): p. 363-369.
14. Rosenfeld, T. and M. Bercovici, 1000-fold sample focusing on paper-based microfluidic devices. Lab Chip, 2014. 14(23): p. 4465-74.
15. Moghadam, B.Y., K.T. Connelly, and J.D. Posner, Isotachophoretic preconcenetration on paper-based microfluidic devices. Anal Chem, 2014. 86(12): p. 5829-37.
16. Sustarich, J.M., B.D. Storey, and S. Pennathur, Field-amplified sample stacking and focusing in nanofluidic channels. Physics of Fluids, 2010. 22(11): p. 112003.
17. Burgi, D.S. and R.L. Chien, Optimization in Sample Stacking for High-Performance Capillary Electrophoresis. Anal Chem, 1991. 63(18): p. 2042-2047.
18. Wang, Y.C., A.L. Stevens, and J. Han, Million-fold preconcentration of proteins and peptides by nanofluidic filter. Anal Chem, 2005. 77(14): p. 4293-9.
19. Ko, S.H., et al., Nanofluidic preconcentration device in a straight microchannel using ion concentration polarization. Lab Chip, 2012. 12(21): p. 4472-82.
20. Yang, R.J., H.H. Pu, and H.L. Wang, Ion concentration polarization on paper-based microfluidic devices and its application to preconcentrate dilute sample solutions. Biomicrofluidics, 2015. 9(1): p. 014122.
21. Hung, L.-H., H.-L. Wang, and R.-J. Yang, A portable sample concentrator on paper-based microfluidic devices. Microfluidics and Nanofluidics, 2016. 20(5).
22. Park, S., et al., Capillarity ion concentration polarization as spontaneous desalting mechanism. Nat Commun, 2016. 7: p. 11223.
23. Jeon, H., et al., Ion concentration polarization-based continuous separation device using electrical repulsion in the depletion region. Sci Rep, 2013. 3: p. 3483.
24. Gong, M.M., et al., Nanoporous membranes enable concentration and transport in fully wet paper-based assays. Anal Chem, 2014. 86(16): p. 8090-7.
25. Yeh, S.H., K.H. Chou, and R.J. Yang, Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices. Lab Chip, 2016. 16(5): p. 925-31.
26. Cate, D.M., et al., Recent developments in paper-based microfluidic devices. Anal Chem, 2015. 87(1): p. 19-41.
27. Carrilho, E., A.W. Martinez, and G.M. Whitesides, Understanding wax printing: a simple micropatterning process for paper-based microfluidics. Anal Chem, 2009. 81(16): p. 7091-5.
28. Hong, S., R. Kwak, and W. Kim, Paper-Based Flow Fractionation System Applicable to Preconcentration and Field-Flow Separation. Anal Chem, 2016. 88(3): p. 1682-7.
29. Gong, M.M., et al., Direct DNA Analysis with Paper-Based Ion Concentration Polarization. J. Am. Chem. Soc., 2015. 137(43): p. 13913-9.
30. Abelev, G.I. and E.R. Karamova, Performance of multistep immunochemical reactions by counterflow isotachophoresis on nitrocellulose membranes—I. Immunoblotting. 1988.
31. Wang, J., et al., Exceeding 20,000-fold concentration of protein by the on-line isotachophoresis concentration in poly(methyl methacrylate) microchip. Electrophoresis, 2009. 30(18): p. 3250-6.
32. Khandurina, J., et al., Microfabricated porous membrane structure for sample concentration and electrophoretic analysis. Anal Chem, 1999. 71(9): p. 1815-9.
33. Holtzel, A. and U. Tallarek, Ionic conductance of nanopores in microscale analysis systems: where microfluidics meets nanofluidics. J Sep Sci, 2007. 30(10): p. 1398-419.
34. Dydek, E.V. and M.Z. Bazant, Nonlinear dynamics of ion concentration polarization in porous media: The leaky membrane model. AIChE Journal, 2013. 59(9): p. 3539-3555.
35. Kim, D., et al., Non-equilibrium electrokinetic micro/nano fluidic mixer. Lab Chip, 2008. 8(4): p. 625-8.
36. Kim, S.J., et al., Concentration polarization and nonlinear electrokinetic flow near a nanofluidic channel. Phys Rev Lett, 2007. 99(4): p. 044501.
37. Choi, E., et al., Non-equilibrium electrokinetic micromixer with 3D nanochannel networks. Lab Chip, 2015. 15(8): p. 1794-8.
38. Kim, S.J., et al., Direct seawater desalination by ion concentration polarization. Nat Nanotechnol, 2010. 5(4): p. 297-301.
39. Mauritz, K.A. and R.B. Moore, State of understanding of nafion. Chem Rev, 2004. 104(10): p. 4535-85.
40. Kim, S.J., Y.A. Song, and J. Han, Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications. Chem Soc Rev, 2010. 39(3): p. 912-22.
41. Han, S.I., et al., Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization. Lab Chip, 2016.
42. Phan, D.-T., et al., Sample concentration in a microfluidic paper-based analytical device using ion concentration polarization. Sensors and Actuators B: Chemical, 2016. 222: p. 735-740.
43. Kim, S.J., L.D. Li, and J. Han, Amplified electrokinetic response by concentration polarization near nanofluidic channel. Langmuir, 2009. 25(13): p. 7759-65.
44. Leung, V., et al., Streaming potential sensing in paper-based microfluidic channels. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2010. 364(1-3): p. 16-18.
45. Chen, C.L. and R.J. Yang, Effects of microchannel geometry on preconcentration intensity in microfluidic chips with straight or convergent-divergent microchannels. Electrophoresis, 2012. 33(5): p. 751-7.
46. Ibanez, R., D.F. Stamatialis, and M. Wessling, Role of membrane surface in concentration polarization at cation exchange membranes. Journal of Membrane Science, 2004. 239(1): p. 119-128.
47. Krol, J., Concentration polarization with monopolar ion exchange membranes: current-voltage curves and water dissociation. Journal of Membrane Science, 1999. 162(1-2): p. 145-154.
48. Schoch, R.B., J. Han, and P. Renaud, Transport phenomena in nanofluidics. Reviews of Modern Physics, 2008. 80(3): p. 839-883.
49. Ng, J.M., et al., Components for integrated poly(dimethylsiloxane) microfluidic systems. Electrophoresis, 2002. 23(20): p. 3461-73.
50. McDonald, J.C., et al., Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis, 2000. 21(1): p. 27-40.
51. Rubinstein, I. and B. Zaltzman, Electro-osmotically induced convection at a permselective membrane. Physical Review E, 2000. 62(2): p. 2238-2251.
52. Huang, K.-D. and R.-J. Yang, Formation of ionic depletion/enrichment zones in a hybrid micro-/nano-channel. Microfluidics and Nanofluidics, 2008. 5(5): p. 631-638.
53. Mani, A., T.A. Zangle, and J.G. Santiago, On the propagation of concentration polarization from microchannel-nanochannel interfaces. Part I: Analytical model and characteristic analysis. Langmuir, 2009. 25(6): p. 3898-908.