表面增強拉曼散射（Surface-enhanced Raman scattering, SERS）是一項具有卓越靈敏度和特異性的感測技術，適合應用於生物分子檢測。癌症診斷，這是早期檢測至關重要的領域，已經藉著SERS應用取得很大的進展。本研究旨在善用SERS的特性，檢測不同癌期的肺癌血漿樣本。我們以InGaN量子井（quantum wells, QWs）研製SERS基板，並優化鈦（Ti）附著層的厚度，希望能得到最強、最穩定的訊號。
我們發現，擁有Ti附著層的SERS基板與肺癌期別呈現較顯著的線性關係，特別是在波數1525 cm⁻¹處的峰值強度。這項研究對於癌症診斷具有重大意義，因為它不僅能區分不同癌期的訊號，還能在極短(30分鐘)的時間內完成。

Surface-enhanced Raman scattering (SERS) is a transformative technique known for its exceptional sensitivity and specificity in the domain of biomolecule detection and disease identification. Cancer diagnosis, a realm where early detection plays a pivotal role, has made much progress through SERS. This study embarks on the mission to harness the power of SERS, with a dual aim of detecting lung cancer and categorizing its various stages. The research incorporates Quantum Wells (QWs) into SERS substrates and hinges on optimizing the thickness of Titanium (Ti) adhesion layers. The synergy of these elements, QWs-SERS, emerges as a promising tool for diagnosing lung cancer.
The SERS substrate featuring Ti adhesion layers exhibits an improved linear relationship between peak intensity, notably at wavenumber 1525 cm⁻¹, and different stages of lung cancer. This study holds great significance for cancer diagnosis as it not only offers the ability to distinguish different cancerous states but also opens a path for rapid (< 30 min) cancer screening.

[1] Giovanna, M. S. C., Marcela, O. S., Rui, M. R., & Letícia, F.L. (2023). Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. International Journal of Molecular Sciences, 24(3), 2505. DOI: 10.3390/ijms24032505
[2] Bird, R. E., Wallace, T. W., & Yankaskas, B. C. (1992). Analysis of cancers missed at screening mammography. Radiology, 184(3), 613–617.
DOI: 10.1148/radiology.184.3.1509041
[3] Berrington de Gonzalez, A., Berg, C. D., Visvanathan, K., & Robson, M. (2009). Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. Journal of the National Cancer Institute, 101(3), 205–209. DOI: 10.1093/jnci/djn440
[4] Lei, J., Yang, D.F., Li, R., Dai, Z. X., Zhang, C. L., Yu, Z. W., Wu, S. F., Pang, L., Liang, S. S., & Zhang, Y. (2021). Label-free surface-enhanced Raman spectroscopy for diagnosis and analysis of serum samples with different types lung cancer. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 261, 1386-1425. DOI: 10.1016/j.saa.2021.120021
[5] Li, X. Z., Yang, T. Y., Li, C. S., Song, Y. T., Lou, H., Guan, D. G., & Jin, L. L. (2018). Surface Enhanced Raman Spectroscopy (SERS) for the Multiplex Detection of Braf, Kras, and Pik3ca Mutations in Plasma of Colorectal Cancer Patients. Theranostics, 8(6), 1678-1689. DOI: 10.7150/thno.22502
[6] Zhang, K., Liu, X. J., Man, B. Y., Yang, C., Zhang, C., Liu, M., Zhang, Y. H., Liu, L. S., & Chen, C. S. (2018). Label-free and stable serum analysis based on Ag-NPs/PSi surface-enhanced Raman scattering for noninvasive lung cancer detection. Biomedical Optics Express, 9(9), 4345-4358. DOI: 10.1364/BOE.9.004345
[7] Feng, J., Li, X., Cheng, H., Huang, W. Y., Kong, H. X., Li, Y. Q., & Li, L. J. (2019). A boronate-modified molecularly imprinted polymer labeled with a SERS-tag for use in an antibody-free immunoassay for the carcinoembryonic antigen. Microchimica Acta, 186, 774. DOI: 10.1007/s00604-019-3972-x
[8] Bao, X., Wang, S., Liu, X., & Li, G. (2023). Highly sensitive detection of CYFRA21-1 with a SERS sensing platform based on the MBs enrichment strategy and antibody-DNA-mediated CHA amplification. Frontiers in Bioengineering and Biotechnology, 11. DOI: 10.3389/fbioe.2023.1251595
[9] Katrin, K. (2007). Surface-enhanced Raman scattering. Physics Today, 60(11), 40–46. DOI: 10.1063/1.2812122
[10] Tania, D. (2022). Microplastic pollutant detection by Surface Enhanced Raman Spectroscopy (SERS): a mini-review. Nanotechnology for Environmental Engineering, 8, 41–48. DOI: 10.1007/s41204-022-00223-7
[11] Ding, S. Y., Yi, J., Li, J. F., Ren, B., Wu, D.Y., Panneerselvam, R., & Tian, Z. Q. (2016). Nanostructure-based plasmon-enhanced Raman spectroscopy for surface analysis of materials. Nature Reviews Materials, 1(6). DOI:10.1038/natrevmats.2016.21
[12] Cong, S., Liu, X. H., Jiang, Y. X., Zhang, W., & Zhao, Z. G. (2020). Surface Enhanced Raman Scattering Revealed by Interfacial Charge-Transfer Transitions. The Innovation, 1(3). DOI: 10.1016/j.xinn.2020.100051
[13] Álvarez-Puebla, R. A. (2012). Effects of the Excitation Wavelength on the SERS Spectrum. The Journal of Physical Chemistry Letters, 3(7), 857–866. DOI:10.1021/jz201625j
[14] Kneipp, K., Kneipp, H., Itzkan, I., Dasari, R. R., & Feld, M. S. (2002). Surface-enhanced Raman scattering and biophysics. Journal of Physics: Condensed Matter, 14(18), R597–R624. DOI:10.1088/0953-8984/14/18/202
[15] Li, P., Long, F., Chen, W., Chen, J., Chu, P. K., & Wang, H. (2019). Fundamentals and Applications of Surface-enhanced Raman Spectroscopy (SERS) Based Biosensors. Current Opinion in Biomedical Engineering, 13, 51-59. DOI: 10.1016/j.cobme.2019.08.008
[16] Kahraman, M., Mullen, E.R., Korkmaz, A., & Wachsmann-Hogiu, S. (2017). Fundamentals and applications of SERS-based bioanalytical sensing. Nanophotonics, 6(5), 831-852. DOI: 10.1515/nanoph-2016-0174
[17] Karadan, P., Aggarwal, S., Anappara, A. A., Narayana, C., & Barshilia, H. C. (2018). Tailored periodic Si nanopillar based architectures as highly sensitive universal SERS biosensing platform. Sensors and Actuators B: Chemical, 254, 264–271. DOI: 10.1016/j.snb.2017.07.088
[18] Li, X., Yang, T., Li, C. S., Wang, D., Song, Y., & Jin, L. (2017). Detection of EGFR mutation in plasma using multiplex allele-specific PCR (MAS-PCR) and surface enhanced Raman spectroscopy. Scientific Reports, 7(1). DOI: 10.1038/s41598-017-05050-4
[19] Garcia-Rico, E., Alvarez-Puebla, R. A., & Guerrini, L. (2018). Direct surface-enhanced Raman scattering (SERS) spectroscopy of nucleic acids: from fundamental studies to real-life applications. Chemical Society Reviews, 47(13), 4909–4923. DOI: 10.1039/c7cs00809k
[20] Tian, S., Neumann, O., McClain, M. J., Yang, X., Zhou, L., Zhang, C., Nordlander, P., & Halas, N. J. (2017). Aluminum Nanocrystals: A Sustainable Substrate for Quantitative SERS-Based DNA Detection. Nano Letters, 17(8), 5071–5077. DOI: 10.1021/acs.nanolett.7b02338
[21] Chien, F.C., Zhang, T. F., Chen, C., Nguyen, T. A. N., Wang, S.-Y., Lai, S. M., Lin, C. H., Huang, C. K., & Lai, K. Y. (2021). Nanostructured InGaN Quantum Wells as a Surface-Enhanced Raman Scattering Substrate with Expanded Hot Spots. ACS Applied Nano Materials, 4(3), 2614–2620. DOI:10.1021/acsanm.0c03265
[22] Knight, M. W., King, N. S., Liu, L., Everitt, H. O., Nordlander, P., & Halas, N. J. (2013). Aluminum for Plasmonics. ACS Nano, 8(1), 834–840. DOI: 10.1021/nn405495q
[23] Habibullah, G., Viktorova, J., & Ruml, T. (2021). Current Strategies for Noble Metal Nanoparticle Synthesis. Nanoscale Research Letters, 16(1). DOI: 10.1186/s11671-021-03480-8
[24] Hsin Feng, S., & Yang, S.-T. (2019). The new 8th TNM staging system of lung cancer and its potential imaging interpretation pitfalls and limitations with CT image demonstrations. Diagnostic and Interventional Radiology, 25(4), 270–279. DOI: 10.5152/dir.2019.18458
[25] Abnormal Raman Scattering by Plasma of Patients With Cancer. (1987). JNCI: Journal of the National Cancer Institute, 78(3), 587-589. DOI: 10.1093/jnci/78.3.587
[26] Rein, A. J., Saperstein, D. D., Pines, S. H., & Radlick, P. C. (1976). Blood plasma investigations by resonance raman spectroscopy: Detection of carotenoid pigments. Experientia, 32(10), 1352–1354. DOI: 10.1007/bf01953136
[27] Marshall, C. P., & Olcott Marshall, A. (2010). The potential of Raman spectroscopy for the analysis of diagenetically transformed carotenoids. Philosophical Transactions of the Royal Society A: Mathematical, 368(1922), 3137–3144.
DOI: 10.1098/rsta.2010.0016
[28] Zha, W. L., Cheng, Y., Yu, W., Zhang, X. B., Shen, A. G., & Hu, J. M. (2015). HPLC assisted Raman spectroscopic studies on bladder cancer. Laser Physics Letters, 12(4). DOI: 10.1088/1612-2011/12/4/045701
[29] Omenn, G. S., Goodman, G. E., Thornquist M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens Jr, F. L., Valanis, B., Williams Jr, J.H., Barnhart, S., Cherniack, M. G., Brodkin, C. A., Hammar, S. (1996). Risk Factors for Lung Cancer and for Intervention Effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. Journal of the National Cancer Institute, 88(21), 1550-1559.
DOI: 10.1093/jnci/88.21.1550.
[30] Middha, P., Weinstein, S. J., Männistö, S., Albanes, D., & Mondul, A. M. (2018). β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine. Nicotine & Tobacco Research, 21(8), 1045–1050. DOI: 10.1093/ntr/nty115
[31] Lahiri, B., Dylewicz, R., De La Rue, R. M., & Johnson, N. P. (2010). Impact of titanium adhesion layers on the response of arrays of metallic split-ring resonators (SRRs). Optics Express, 18(11). DOI: 10.1364/oe.18.011202
[32] Todeschini, M., Bastos da Silva Fanta, A., Jensen, F., Wagner, J. B., & Han, A. (2017). Influence of Ti and Cr Adhesion Layers on Ultrathin Au Films. ACS Applied Materials & Interfaces, 9(42), 37374–37385. DOI: 10.1021/acsami.7b10136