當作一個陣列形式的金奈米粒子鍍膜聚雙甲基矽氧烷表面上之可切斷胜肽的固相合成已被證實。這裡我們以5個色胺酸當作例子、異相交鏈劑當作錨狀試劑、t-Boc保護基/三氟醋酸當作保護基和去保護基試劑以及還原劑來做為切斷胜肽。這個審慎地設計的方法，其內所使用之試劑和溶劑都可和聚雙甲基矽氧烷高分子基材相容；在所有合成步驟過程中的共價鍵生成也藉由衰減全反射傅立葉轉換紅外線光譜儀、原子力顯微鏡和螢光儀來鑑定。此外利用質譜儀來鑑定每一個步驟的產物而估計最後得到5個色胺酸的產率為接近43％。由於聚雙甲基矽氧烷可製備出有彈性的模子，所以這樣的胜肽合成可以在ELISA plate的96孔槽裡面或在已有圖案的聚雙甲基矽氧烷基材上當作一個工具，並藉由光或質譜來發展分析實驗。我們應用此方法在PDMS上合成出kemptide胜肽的微陣列並藉由偵測化學冷光的方式鑑定蛋白質激酶A可磷酸化於kemptide胜肽絲胺酸的側鏈上。

Solid state synthesis of cleavable peptides on the surface of gold nanoparticle-coated poly(dimethylsiloxane) (PDMS) substrate was demonstrated as an array format using a 5-mer molecule of poly-Trp5 as an example and heterobifunctional crosslinkers as the anchoring layer, t-Boc chemistry/ trifluoroacetic acid (TFA) for protection and de-protection, and reducing agents for peptide cleavage. The method was judiciously designed to use reagents and solvents that are compatible with the PDMS polymer substrate and the formation of the covalent binding during the synthesis steps were monitored by Infrared spectroscopy (IR), Atomic Force Microscopy (AFM) and Fluorescence spectroscopy. The products of each step were characterized by mass spectrometry and the final production yield of the 5-mers was estimated to be near 43%. Due to flexible molding techniques for PDMS fabrication, such peptide synthesis can be implemented inside a traditional 96-well ELISA plate or on a patterned PDMS substrate for assay developments using either the light or MS detection. We applied the method to fabricate kemptide peptide microarrays on PDMS and demonstrated that protein kinase A (PKA) could phosphorylate the serine residue by chemiluminescence detection.

1 Fodor, S. P. A. et al. Light-directed, spatially addressable parallel. Science, 251, 767-773 (1991).
2 McGall, G. et al. Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists. Proceedings of the National Academy of Sciences, 93, 13555-13560 (1996).
3 Singh-Gasson, S. et al. Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nature biotechnology, 17, 974-978 (1999).
4 Pellois, J. P. et al. Individually addressable parallel peptide synthesis on microchips. Nature biotechnology, 20, 922-926 (2002).
5 Frank, R. Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron, 48, 9217-9232 (1992).
6 Frank, R. The SPOT-synthesis technique: synthetic peptide arrays on membrane supports—principles and applications. Journal of immunological methods, 267, 13-26 (2002).
7 Xu, Q. & Lam, K. S. Protein and chemical microarrays—powerful tools for proteomics. BioMed Research International, 2003, 257-266 (2003).
8 Houseman, B. T., Gawalt, E. S. & Mrksich, M. Maleimide-functionalized self-assembled monolayers for the preparation of peptide and carbohydrate biochips. Langmuir, 19, 1522-1531 (2003).
9 Falsey, J. R., Renil, M., Park, S., Li, S. & Lam, K. S. Peptide and small molecule microarray for high throughput cell adhesion and functional assays. Bioconjugate chemistry, 12, 346-353 (2001).
10 Salisbury, C. M., Maly, D. J. & Ellman, J. A. Peptide microarrays for the determination of protease substrate specificity. Journal of the American Chemical Society, 124, 14868-14870 (2002).
11 Lesaicherre, M.-L., Uttamchandani, M., Chen, G. Y. & Yao, S. Q. Developing site-specific immobilization strategies of peptides in a microarray. Bioorganic & medicinal chemistry letters, 12, 2079-2083 (2002).
12 MacBeath, G. & Schreiber, S. L. Printing proteins as microarrays for high-throughput function determination. Science, 289, 1760-1763 (2000).
13 Su, J. & Mrksich, M. Using Mass Spectrometry to Characterize Self‐Assembled Monolayers Presenting Peptides, Proteins, and Carbohydrates. Angewandte Chemie International Edition, 41, 4715-4718 (2002).
14 Min, D.-H., Tang, W.-J. & Mrksich, M. Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor. Nature biotechnology, 22, 717-723 (2004).
15 Wegner, G. J., Lee, H. J. & Corn, R. M. Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging. Analytical Chemistry, 74, 5161-5168 (2002).
16 Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society, 85, 2149-2154 (1963).
17 Duffy, D. C., McDonald, J. C., Schueller, O. J. & Whitesides, G. M. Rapid prototyping of microfluidic systems in poly (dimethylsiloxane). Analytical chemistry, 70, 4974-4984 (1998).
18 Lee, J. N., Park, C. & Whitesides, G. M. Solvent compatibility of poly (dimethylsiloxane)-based microfluidic devices. Analytical chemistry, 75, 6544-6554 (2003).
19 Lahann, J. et al. Reactive polymer coatings: a first step toward surface engineering of microfluidic devices. Analytical chemistry, 75, 2117-2122 (2003).
20 Liu, Y., Fanguy, J. C., Bledsoe, J. M. & Henry, C. S. Dynamic coating using polyelectrolyte multilayers for chemical control of electroosmotic flow in capillary electrophoresis microchips. Analytical chemistry, 72, 5939-5944 (2000).
21 Yang, T., Jung, S.-y., Mao, H. & Cremer, P. S. Fabrication of phospholipid bilayer-coated microchannels for on-chip immunoassays. Analytical chemistry, 73, 165-169 (2001).
22 Makamba, H., Hsieh, Y.-Y., Sung, W.-C. & Chen, S.-H. Stable permanently hydrophilic protein-resistant thin-film coatings on poly (dimethylsiloxane) substrates by electrostatic self-assembly and chemical cross-linking. Analytical chemistry, 77, 3971-3978 (2005).
23 Sung, W.-C., Chang, C.-C., Makamba, H. & Chen, S.-H. Long-term affinity modification on poly (dimethylsiloxane) substrate and its application for ELISA analysis. Analytical chemistry, 80, 1529-1535 (2008).
24 Sung, W.-C., Chen, H.-H., Makamba, H. & Chen, S.-H. Functionalized 3D-hydrogel plugs covalently patterned inside hydrophilic poly (dimethylsiloxane) microchannels for flow-through immunoassays. Analytical chemistry, 81, 7967-7973 (2009).
25 Chen, H.-H., Sung, W.-C., Liang, S.-S. & Chen, S.-H. Functional Fluorinated Modifications on a Polyelectrolyte Coated Polydimethylsiloxane Substrate for Fabricating Antibody Microarrays. Analytical chemistry, 82, 7804-7813 (2010).
26 Wang, A.-J., Xu, J.-J., Zhang, Q. & Chen, H.-Y. The use of poly (dimethylsiloxane) surface modification with gold nanoparticles for the microchip electrophoresis. Talanta, 69, 210-215 (2006).
27 Luo, C. et al. PDMS microfludic device for optical detection of protein immunoassay using gold nanoparticles. Lab on a Chip, 5, 726-729 (2005).
28 Wang, B. et al. Chitosan-mediated synthesis of gold nanoparticles on patterned poly (dimethylsiloxane) surfaces. Biomacromolecules, 7, 1203-1209 (2006).
29 Zhang, Q., Xu, J.-J., Liu, Y. & Chen, H.-Y. In-situ synthesis of poly (dimethylsiloxane)–gold nanoparticles composite films and its application in microfluidic systems. Lab Chip, 8, 352-357 (2008).
30 Wu, W.-Y., Bian, Z.-P., Wang, W., Wang, W. & Zhu, J.-J. PDMS gold nanoparticle composite film-based silver enhanced colorimetric detection of cardiac troponin I. Sensors and Actuators B: Chemical, 147, 298-303 (2010).
31 Wang, W. et al. Aptamer-based PDMS–gold nanoparticle composite as a platform for visual detection of biomolecules with silver enhancement. Biosensors and Bioelectronics, 26, 3110-3114 (2011).
32 Min, D.-H. & Mrksich, M. Peptide arrays: towards routine implementation. Current opinion in chemical biology, 8, 554-558 (2004).
33 Panicker, R. C., Huang, X. & Yao, S. Q. Recent advances in peptide-based microarray technologies. Combinatorial chemistry & high throughput screening, 7, 547-556 (2004).
34 Fritz, J. L. & Owen, M. J. Hydrophobic recovery of plasma-treated polydimethylsiloxane. The Journal of Adhesion, 54, 33-45 (1995).
35 Efimenko, K., Wallace, W. E. & Genzer, J. Surface modification of Sylgard-184 poly (dimethyl siloxane) networks by ultraviolet and ultraviolet/ozone treatment. Journal of Colloid and Interface Science, 254, 306-315 (2002).
36 Hu, S. et al. Surface-directed, graft polymerization within microfluidic channels. Analytical chemistry, 76, 1865-1870 (2004).
37 Frey, B. L. & Corn, R. M. Covalent attachment and derivatization of poly (L-lysine) monolayers on gold surfaces as characterized by polarization-modulation FT-IR spectroscopy. Analytical Chemistry, 68, 3187-3193 (1996).