請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99811完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃念祖 | zh_TW |
| dc.contributor.advisor | Nien-Tsu Huang | en |
| dc.contributor.author | 劉軒瑜 | zh_TW |
| dc.contributor.author | Hsuan-Yu Liu | en |
| dc.date.accessioned | 2025-09-17T16:45:18Z | - |
| dc.date.available | 2025-09-18 | - |
| dc.date.copyright | 2025-09-17 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-07 | - |
| dc.identifier.citation | [1] W. H. Organization. "Ten threats to global health in 2019." https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 (accessed.
[2] J. M. A. Blair, M. A. Webber, A. J. Baylay, D. O. Ogbolu, and L. J. V. Piddock, "Molecular mechanisms of antibiotic resistance," Nature Reviews Microbiology, vol. 13, no. 1, pp. 42-51, 2015/01/01 2015, doi: 10.1038/nrmicro3380. [3] C. J. L. Murray et al., "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis," The Lancet, vol. 399, no. 10325, pp. 629-655, 2022/02/12/ 2022, doi: https://doi.org/10.1016/S0140-6736(21)02724-0. [4] T. Jesudason, "WHO publishes updated list of bacterial priority pathogens," The Lancet Microbe, vol. 5, no. 9, 2024, doi: 10.1016/j.lanmic.2024.07.003. [5] C. S. Ho et al., "Antimicrobial resistance: a concise update," The Lancet Microbe, vol. 6, no. 1, 2025, doi: 10.1016/j.lanmic.2024.07.010. [6] C. J. H. von Wintersdorff et al., "Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer," Frontiers in Microbiology, Review vol. Volume 7 - 2016, 2016. [Online]. Available: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00173. [7] J. A. Ayukekbong, M. Ntemgwa, and A. N. Atabe, "The threat of antimicrobial resistance in developing countries: causes and control strategies," Antimicrobial Resistance & Infection Control, vol. 6, no. 1, p. 47, 2017/05/15 2017, doi: 10.1186/s13756-017-0208-x. [8] D. A. Goldmann et al., "Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals: A Challenge to Hospital Leadership," JAMA, vol. 275, no. 3, pp. 234-240, 1996, doi: 10.1001/jama.1996.03530270074035. [9] C. A. Michael, D. Dominey-Howes, and M. Labbate, "The Antimicrobial Resistance Crisis: Causes, Consequences, and Management," Frontiers in Public Health, Review vol. Volume 2 - 2014, 2014. [Online]. Available: https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2014.00145. [10] S. Baker, N. Thomson, F.-X. Weill, and K. E. Holt, "Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens," Science, vol. 360, no. 6390, pp. 733-738, 2018/05/18 2018, doi: 10.1126/science.aar3777. [11] Y. Zhu, H. W. E., and Q. and Yang, "Clinical Perspective of Antimicrobial Resistance in Bacteria," Infection and Drug Resistance, vol. 15, no. null, pp. 735-746, 2022/01/01 2022, doi: 10.2147/IDR.S345574. [12] W. H. Organization, WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. 2024. [13] M. Naghavi et al., "Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050," The Lancet, vol. 404, no. 10459, pp. 1199-1226, 2024/09/28/ 2024, doi: https://doi.org/10.1016/S0140-6736(24)01867-1. [14] A. H. Holmes et al., "Understanding the mechanisms and drivers of antimicrobial resistance," The Lancet, vol. 387, no. 10014, pp. 176-187, 2016, doi: 10.1016/S0140-6736(15)00473-0. [15] A. R. M. Coates, H. Yanmin, H. James, and P. and Yeh, "Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction," Expert Review of Anti-infective Therapy, vol. 18, no. 1, pp. 5-15, 2020/01/02 2020, doi: 10.1080/14787210.2020.1705155. [16] G. Orhan, A. Bayram, Y. Zer, and I. Balci, "Synergy Tests by E Test and Checkerboard Methods of Antimicrobial Combinations against Brucella melitensis," Journal of Clinical Microbiology, vol. 43, no. 1, pp. 140-143, 2005, doi: 10.1128/jcm.43.1.140-143.2005. [17] J. Meletiadis, S. Pournaras, E. Roilides, and J. Walsh Thomas, "Defining Fractional Inhibitory Concentration Index Cutoffs for Additive Interactions Based on Self-Drug Additive Combinations, Monte Carlo Simulation Analysis, and In Vitro-In Vivo Correlation Data for Antifungal Drug Combinations against Aspergillus fumigatus," Antimicrobial Agents and Chemotherapy, vol. 54, no. 2, pp. 602-609, 2010, doi: 10.1128/aac.00999-09. [18] Y. Liu, Z. Tong, J. Shi, R. Li, M. Upton, and Z. Wang, "Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria," Theranostics, Review vol. 11, no. 10, pp. 4910-4928, 2021, doi: 10.7150/thno.56205. [19] D. Doern Christopher, "When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing," Journal of Clinical Microbiology, vol. 52, no. 12, pp. 4124-4128, 2014, doi: 10.1128/jcm.01121-14. [20] G. J. Sullivan, N. N. Delgado, R. Maharjan, and A. K. Cain, "How antibiotics work together: molecular mechanisms behind combination therapy," Current Opinion in Microbiology, vol. 57, pp. 31-40, 2020/10/01/ 2020, doi: https://doi.org/10.1016/j.mib.2020.05.012. [21] T. Bollenbach, "Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution," Current Opinion in Microbiology, vol. 27, pp. 1-9, 2015/10/01/ 2015, doi: https://doi.org/10.1016/j.mib.2015.05.008. [22] R. H. Clark, B. T. Bloom, A. R. Spitzer, and D. R. Gerstmann, "Empiric Use of Ampicillin and Cefotaxime, Compared With Ampicillin and Gentamicin, for Neonates at Risk for Sepsis Is Associated With an Increased Risk of Neonatal Death," Pediatrics, vol. 117, no. 1, pp. 67-74, 2006, doi: 10.1542/peds.2005-0179. [23] P. A. Masters, T. A. O'Bryan, J. Zurlo, D. Q. Miller, and N. Joshi, "Trimethoprim-Sulfamethoxazole Revisited," Archives of Internal Medicine, vol. 163, no. 4, pp. 402-410, 2003, doi: 10.1001/archinte.163.4.402. [24] D. Yahav, G. Giske Christian, A. Grāmatniece, H. Abodakpi, H. Tam Vincent, and L. Leibovici, "New β-Lactam–β-Lactamase Inhibitor Combinations," Clinical Microbiology Reviews, vol. 34, no. 1, pp. 10.1128/cmr.00115-20, 2020, doi: 10.1128/cmr.00115-20. [25] M. Shirley, "Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections," Drugs, vol. 78, no. 6, pp. 675-692, 2018/04/01 2018, doi: 10.1007/s40265-018-0902-x. [26] I. Gajic et al., "Antimicrobial Susceptibility Testing: A Comprehensive Review of Currently Used Methods," Antibiotics, vol. 11, no. 4, doi: 10.3390/antibiotics11040427. [27] M. Benkova, O. Soukup, and J. Marek, "Antimicrobial susceptibility testing: currently used methods and devices and the near future in clinical practice," Journal of Applied Microbiology, vol. 129, no. 4, pp. 806-822, 2020, doi: 10.1111/jam.14704. [28] L. B. Reller, M. Weinstein, J. H. Jorgensen, and M. J. Ferraro, "Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices," Clinical Infectious Diseases, vol. 49, no. 11, pp. 1749-1755, 2009, doi: 10.1086/647952. [29] A. Vasala, V. P. Hytönen, and O. H. Laitinen, "Modern Tools for Rapid Diagnostics of Antimicrobial Resistance," Frontiers in Cellular and Infection Microbiology, Review vol. Volume 10 - 2020, 2020. [Online]. Available: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00308. [30] G. Kahlmeter, G. Giske Christian, J. Kirn Thomas, and E. Sharp Susan, "Point-Counterpoint: Differences between the European Committee on Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute Recommendations for Reporting Antimicrobial Susceptibility Results," Journal of Clinical Microbiology, vol. 57, no. 9, pp. 10.1128/jcm.01129-19, 2019, doi: 10.1128/jcm.01129-19. [31] R. Soltani, H. Khalili, and F. Shafiee, "Double-disk synergy test for detection of synergistic effect between antibiotics against nosocomial strains of staphylococcus aureus," Journal of Research in Pharmacy Practice, vol. 1, no. 1, 2012. [Online]. Available: https://journals.lww.com/jrpp/fulltext/2012/01010/double_disk_synergy_test_for_detection_of.5.aspx. [32] R. L. White, D. S. Burgess, M. Manduru, and J. A. Bosso, "Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test," Antimicrobial Agents and Chemotherapy, vol. 40, no. 8, pp. 1914-1918, 1996, doi: 10.1128/aac.40.8.1914. [33] S. Laishram, A. K. Pragasam, Y. D. Bakthavatchalam, and B. Veeraraghavan, "An Update on Technical, Interpretative and Clinical Relevance of Antimicrobial Synergy Testing Methodologies," Indian Journal of Medical Microbiology, vol. 35, no. 4, pp. 445-468, 2017/10/01/ 2017, doi: https://doi.org/10.4103/ijmm.IJMM_17_189. [34] Y. G. Ju, H. J. Lee, H. S. Yim, M.-G. Lee, J. W. Sohn, and Y. K. Yoon, "In vitro synergistic antimicrobial activity of a combination of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam against carbapenem-resistant Acinetobacter baumannii," Scientific Reports, vol. 12, no. 1, p. 7541, 2022/05/09 2022, doi: 10.1038/s41598-022-11464-6. [35] P. J. Petersen, P. Labthavikul, C. H. Jones, and P. A. Bradford, "In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis," Journal of Antimicrobial Chemotherapy, vol. 57, no. 3, pp. 573-576, 2006, doi: 10.1093/jac/dki477. [36] A. Lekhan and J. Turner Raymond, "Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations," Microbiology Spectrum, vol. 12, no. 10, pp. e01047-24, 2024, doi: 10.1128/spectrum.01047-24. [37] A. V. Nguyen, M. Yaghoobi, M. Azizi, M. Davaritouchaee, K. W. Simpson, and A. Abbaspourrad, "Ladder-shaped microfluidic system for rapid antibiotic susceptibility testing," Communications Engineering, vol. 2, no. 1, p. 15, 2023/04/03 2023, doi: 10.1038/s44172-023-00064-5. [38] S. C. Kim, S. Cestellos-Blanco, K. Inoue, and R. N. Zare, "Miniaturized Antimicrobial Susceptibility Test by Combining Concentration Gradient Generation and Rapid Cell Culturing," Antibiotics, vol. 4, no. 4, pp. 455-466doi: 10.3390/antibiotics4040455. [39] C. Heuer, J.-A. Preuss, M. Buttkewitz, T. Scheper, E. Segal, and J. Bahnemann, "A 3D-printed microfluidic gradient generator with integrated photonic silicon sensors for rapid antimicrobial susceptibility testing," Lab on a Chip, 10.1039/D2LC00640E vol. 22, no. 24, pp. 4950-4961, 2022, doi: 10.1039/D2LC00640E. [40] M. Osaid et al., "A multiplexed nanoliter array-based microfluidic platform for quick, automatic antimicrobial susceptibility testing," Lab on a Chip, 10.1039/D1LC00216C vol. 21, no. 11, pp. 2223-2231, 2021, doi: 10.1039/D1LC00216C. [41] W. Zeng et al., "Hand-powered vacuum-driven microfluidic gradient generator for high-throughput antimicrobial susceptibility testing," Biosensors and Bioelectronics, vol. 205, p. 114100, 2022/06/01/ 2022, doi: https://doi.org/10.1016/j.bios.2022.114100. [42] J. Sun, Y. Ren, J. Ji, Y. Guo, and X. Sun, "A novel concentration gradient microfluidic chip for high-throughput antibiotic susceptibility testing of bacteria," Analytical and Bioanalytical Chemistry, vol. 413, no. 4, pp. 1127-1136, 2021/02/01 2021, doi: 10.1007/s00216-020-03076-8. [43] J. Bae, H. Jeon, and T. Kim, "Full-Combinatorial Concentration Gradient Array with 3D Micro/Nanofluidics for Antibiotic Susceptibility Testing," Analytical Chemistry, vol. 96, no. 14, pp. 5462-5470, 2024/04/09 2024, doi: 10.1021/acs.analchem.3c05501. [44] W.-B. Lee, C.-C. Chien, H.-L. You, F.-C. Kuo, M. S. Lee, and G.-B. Lee, "Rapid antimicrobial susceptibility tests on an integrated microfluidic device for precision medicine of antibiotics," Biosensors and Bioelectronics, vol. 176, p. 112890, 2021/03/15/ 2021, doi: https://doi.org/10.1016/j.bios.2020.112890. [45] E. Sweet et al., "3D microfluidic gradient generator for combination antimicrobial susceptibility testing," Microsystems & Nanoengineering, vol. 6, no. 1, p. 92, 2020/11/02 2020, doi: 10.1038/s41378-020-00200-7. [46] S. Kim, F. Masum, J.-K. Kim, H. J. Chung, and J. S. Jeon, "On-chip phenotypic investigation of combinatory antibiotic effects by generating orthogonal concentration gradients," Lab on a Chip, 10.1039/C8LC01406J vol. 19, no. 6, pp. 959-973, 2019, doi: 10.1039/C8LC01406J. [47] Z. Liu, H. Sun, and K. Ren, "A Multiplexed, Gradient-Based, Full-Hydrogel Microfluidic Platform for Rapid, High-Throughput Antimicrobial Susceptibility Testing," ChemPlusChem, vol. 82, no. 5, pp. 792-801, 2017/05/01 2017, doi: https://doi.org/10.1002/cplu.201600654. [48] X. Li et al., "Combinatorial screening SlipChip for rapid phenotypic antimicrobial susceptibility testing," Lab on a Chip, 10.1039/D2LC00661H vol. 22, no. 20, pp. 3952-3960, 2022, doi: 10.1039/D2LC00661H. [49] D. Yang et al., "Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system," Lab on a Chip, 10.1039/D3LC00647F vol. 23, no. 18, pp. 3961-3977, 2023, doi: 10.1039/D3LC00647F. [50] K. Churski et al., "Rapid screening of antibiotic toxicity in an automated microdroplet system," Lab on a Chip, 10.1039/C2LC21284F vol. 12, no. 9, pp. 1629-1637, 2012, doi: 10.1039/C2LC21284F. [51] W. R. Premasiri, J. C. Lee, A. Sauer-Budge, R. Théberge, C. E. Costello, and L. D. Ziegler, "The biochemical origins of the surface-enhanced Raman spectra of bacteria: a metabolomics profiling by SERS," Analytical and Bioanalytical Chemistry, vol. 408, no. 17, pp. 4631-4647, 2016/07/01 2016, doi: 10.1007/s00216-016-9540-x. [52] C.-Y. Liu et al., "Rapid bacterial antibiotic susceptibility test based on simple surface-enhanced Raman spectroscopic biomarkers," Scientific Reports, vol. 6, no. 1, p. 23375, 2016/03/21 2016, doi: 10.1038/srep23375. [53] D. A. Nazarovskaia et al., "Bimetallic AuAg-coated porous silicon nanowire platform for rapid SERS-based antibiotic susceptibility testing," Results in Surfaces and Interfaces, vol. 19, p. 100524, 2025/05/01/ 2025, doi: https://doi.org/10.1016/j.rsurfi.2025.100524. [54] C.-C. Liao et al., "A microfluidic microwell device operated by the automated microfluidic control system for surface-enhanced Raman scattering-based antimicrobial susceptibility testing," Biosensors and Bioelectronics, vol. 191, p. 113483, 2021/11/01/ 2021, doi: https://doi.org/10.1016/j.bios.2021.113483. [55] S.-J. Lin et al., "An antibiotic concentration gradient microfluidic device integrating surface-enhanced Raman spectroscopy for multiplex antimicrobial susceptibility testing," Lab on a Chip, 10.1039/D2LC00012A vol. 22, no. 9, pp. 1805-1814, 2022, doi: 10.1039/D2LC00012A. [56] C. V. Raman and K. S. Krishnan, "A New Type of Secondary Radiation," Nature, vol. 121, no. 3048, pp. 501-502, 1928/03/01 1928, doi: 10.1038/121501c0. [57] U. K. Sur, "Surface-enhanced Raman spectroscopy," Resonance, vol. 15, no. 2, pp. 154-164, 2010/02/01 2010, doi: 10.1007/s12045-010-0016-6. [58] H. J. Butler et al., "Using Raman spectroscopy to characterize biological materials," Nature Protocols, vol. 11, no. 4, pp. 664-687, 2016/04/01 2016, doi: 10.1038/nprot.2016.036. [59] S. Mosca, C. Conti, N. Stone, and P. Matousek, "Spatially offset Raman spectroscopy," Nature Reviews Methods Primers, vol. 1, no. 1, p. 21, 2021/03/11 2021, doi: 10.1038/s43586-021-00019-0. [60] M. Fleischmann, P. J. Hendra, and A. J. McQuillan, "Raman spectra of pyridine adsorbed at a silver electrode," Chemical Physics Letters, vol. 26, no. 2, pp. 163-166, 1974/05/15/ 1974, doi: https://doi.org/10.1016/0009-2614(74)85388-1. [61] D. L. Jeanmaire and R. P. Van Duyne, "Surface raman spectroelectrochemistry: Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode," Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, vol. 84, no. 1, pp. 1-20, 1977/11/10/ 1977, doi: https://doi.org/10.1016/S0022-0728(77)80224-6. [62] A. Campion, J. Ivanecky III, C. Child, and M. Foster, "On the mechanism of chemical enhancement in surface-enhanced Raman scattering," Journal of the American Chemical Society, vol. 117, no. 47, pp. 11807-11808, 1995. [63] S.-Y. Ding et al., "Nanostructure-based plasmon-enhanced Raman spectroscopy for surface analysis of materials," Nature Reviews Materials, vol. 1, no. 6, p. 16021, 2016/04/26 2016, doi: 10.1038/natrevmats.2016.21. [64] K. A. Willets and R. P. Van Duyne, "Localized Surface Plasmon Resonance Spectroscopy and Sensing," Annual Review of Physical Chemistry, vol. 58, no. Volume 58, 2007, pp. 267-297, 2007, doi: https://doi.org/10.1146/annurev.physchem.58.032806.104607. [65] J. Langer et al., "Present and Future of Surface-Enhanced Raman Scattering," ACS Nano, vol. 14, no. 1, pp. 28-117, 2020/01/28 2020, doi: 10.1021/acsnano.9b04224. [66] A. Balčytis et al., "From Fundamental toward Applied SERS: Shared Principles and Divergent Approaches," Advanced Optical Materials, vol. 6, no. 16, p. 1800292, 2018/08/01 2018, doi: https://doi.org/10.1002/adom.201800292. [67] F. Inscore, C. Shende, A. Sengupta, H. Huang, and S. Farquharson, "Detection of Drugs of Abuse in Saliva by Surface-Enhanced Raman Spectroscopy (SERS)," Applied Spectroscopy, vol. 65, no. 9, pp. 1004-1008, 2011/09/01 2011, doi: 10.1366/11-06310. [68] R. A. Halvorson and P. J. Vikesland, "Surface-Enhanced Raman Spectroscopy (SERS) for Environmental Analyses," Environmental Science & Technology, vol. 44, no. 20, pp. 7749-7755, 2010/10/15 2010, doi: 10.1021/es101228z. [69] A. Pallaoro, M. R. Hoonejani, G. B. Braun, C. D. Meinhart, and M. Moskovits, "Rapid Identification by Surface-Enhanced Raman Spectroscopy of Cancer Cells at Low Concentrations Flowing in a Microfluidic Channel," ACS Nano, vol. 9, no. 4, pp. 4328-4336, 2015/04/28 2015, doi: 10.1021/acsnano.5b00750. [70] 顧啟耀, "整合氣液微流道與表面增強拉曼光譜基板進行吸附性代謝物分離之細菌鑑別," 碩士, 生醫電子與資訊學研究所, 國立臺灣大學, 台北市, 2024. [Online]. Available: https://hdl.handle.net/11296/8jxfmp [71] K.-W. Chang, H.-W. Cheng, J. Shiue, J.-K. Wang, Y.-L. Wang, and N.-T. Huang, "Antibiotic Susceptibility Test with Surface-Enhanced Raman Scattering in a Microfluidic System," Analytical Chemistry, vol. 91, no. 17, pp. 10988-10995, 2019/09/03 2019, doi: 10.1021/acs.analchem.9b01027. [72] M. Morháč and V. Matoušek, "Peak Clipping Algorithms for Background Estimation in Spectroscopic Data," Applied Spectroscopy, vol. 62, no. 1, pp. 91-106, 2008/01/01 2008. [Online]. Available: https://opg.optica.org/as/abstract.cfm?URI=as-62-1-91. [73] S. Akbarzadeh, H. Khajesharifi, and M. Thompson, "Simultaneous Determination of Streptomycin and Oxytetracycline Using a Oracet-Blue/Silver-Nanoparticle/Graphene-Oxide/Modified Screen-Printed Electrode," Biosensors, vol. 10, no. 3, doi: 10.3390/bios10030023. [74] V. Doern Gary and M. Brecher Stephen, "The Clinical Predictive Value (or Lack Thereof) of the Results of In Vitro Antimicrobial Susceptibility Tests," Journal of Clinical Microbiology, vol. 49, no. 9_Supplement, pp. S11-S14, 2011/09/01 2011, doi: 10.1128/jcm.00580-11. [75] "Synergism Testing: Broth Microdilution Checkerboard and Broth Macrodilution Methods," in Clinical Microbiology Procedures Handbook, 2016, pp. 5.16.1-5.16.23. [76] A. Asif, H. Mohsin, R. Tanvir, and Y. Rehman, "Revisiting the Mechanisms Involved in Calcium Chloride Induced Bacterial Transformation," (in English), Frontiers in Microbiology, Opinion vol. Volume 8 - 2017, 2017-November-07 2017, doi: 10.3389/fmicb.2017.02169. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99811 | - |
| dc.description.abstract | 抗生素抗藥性已成為全球公共衛生的重大挑戰，造成許多細菌感染難以治療，且與高死亡率相關。為了提升治療效果並延緩抗藥性的發展，組合性抗生素治療被視為一項重要策略，尤其適用於多重耐藥性菌株的感染情形。然而目前進行細菌鑑定和抗生素敏感性試驗 (antimicrobial susceptibility testing, AST) 動用許多勞力、所花費的時間較長，而且也只能關注在單一種抗生素上。為了解決上述的問題，我們開發了一種整合微流道和表面增強拉曼散射 (surface-enhanced Raman scattering, SERS) 的系統，簡化傳統AST繁雜的流程並實現原位檢測。此外，微流道能夠產生兩倍的抗生素濃度梯度，並且能夠在微流井 (microwell) 裡混合兩種抗生素，得到36種不同的抗生素組合。此外微流井也可以捕捉細菌，與抗生素混合進行培養後，利用SERS進行量測，根據SERS的訊號便可測得微量抑制濃度指數 (fractional inhibitory concentration index, FICI)。為了驗證本研究的可行性，我們在此裝置上使用卡那黴素 (kanamycin) 非抗藥性和抗藥性的大腸桿菌 (Escherichia coli) 進行測試。整體而言，這個系統可以執行組合抗生素敏感性試驗，並具有操作簡單、樣本使用量少和分析時間更短的優勢。 | zh_TW |
| dc.description.abstract | Antimicrobial resistance poses a significant global public health challenge, making many bacterial infections difficult to treat and contributing to high mortality rates. Combinatory antimicrobial therapy has been recognized as a crucial strategy to enhance treatment efficacy and slow the development of resistance, particularly for infections caused by multidrug-resistant strains. However, current bacterial identification and antimicrobial susceptibility testing (AST) procedures are labor-intensive, time-consuming, and can only focus on single antibiotic treatment. To address the above issues, we report a system integrating microfluidics and surface-enhanced Raman scattering (SERS) to simplify the conventional AST workflow and perform in situ detection. Besides, the microfluidics can generate two-fold antibiotic concentration gradients and enable mixing two antibiotics within microwells, resulting in 36 individual antibiotic combinations. Additionally, the microwells can capture bacteria, which are incubated with antibiotics and analyzed using SERS. Fractional inhibitory concentration index (FICI) values can then be calculated based on SERS signals. To demonstrate the feasibility of this thesis, kanamycin-susceptible and -resistant Escherichia coli strains were tested on our device. This system can perform combinatory AST with a simple operation, fewer sample requirements, and shorter analysis time. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-17T16:45:18Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-17T16:45:18Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii ABSTRACT iv CONTENTS v LIST OF FIGURES vii LIST OF TABLES xiii Chapter 1 Introduction 1 1.1 Research Background 1 1.1.1 Antimicrobial Resistance (AMR) 1 1.1.2 Mechanisms of Antibiotic Interactions 3 1.1.3 Challenges in Combinatory Antimicrobial Susceptibility Testing (AST) 5 1.2 Literature Review 6 1.2.1 Conventional Methods for Combinatory AST 6 1.2.2 Microfluidics for AST 8 1.2.3 Surface-Enhanced Raman Scattering (SERS)-based AST 14 1.3 Research Motivation 17 Chapter 2 SERS Theory 19 2.1 Raman Scattering 19 2.2 Surface-Enhanced Raman Scattering (SERS) 20 Chapter 3 Materials and Methods 22 3.1 Design and Fabrication of the Microfluidic Device 22 3.1.1 Design of the Microfluidic Device 22 3.1.2 Fabrication Process of the Microfluidic Device 23 3.2 Bacterial Sample Preparation 24 3.3 Broth Microdilution and Checkerboard Assay 25 3.4 Bright-Field and Fluorescence Microscopy Setup and Image Analysis 26 3.5 SERS Setup and Measurement 26 3.5.1 Fabrication of the SERS Substrates 26 3.5.2 Optical Setup for SERS Measurement 27 3.5.3 SERS Measurements and Data Analysis 28 3.6 Preparation of Bacterial Supernatant for SERS Detection 29 3.7 Operational Procedures of the Device 29 Chapter 4 Results and Discussion 33 4.1 One-Dimensional Concentration Gradient Generation (1D CGG) 33 4.2 Two-Dimensional Concentration Gradient Generation (2D CGG) 35 4.3 Distribution of Microbeads in Microwells 37 4.4 Fluorescence-Based AST 39 4.4.1 Single-Antibiotic AST 39 4.4.2 Combinatory AST 43 4.5 SERS-AST 45 4.5.1 Single-Antibiotic AST 45 4.5.2 Combinatory AST 49 Chapter 5 Conclusion 51 Chapter 6 Future Work 54 REFERENCES 57 | - |
| dc.language.iso | en | - |
| dc.subject | 微流體技術 | zh_TW |
| dc.subject | 組合抗生素敏感性試驗 | zh_TW |
| dc.subject | 表面增強拉曼散射 | zh_TW |
| dc.subject | Surface-enhanced Raman scattering (SERS) | en |
| dc.subject | Combinatory antimicrobial susceptibility testing (cAST) | en |
| dc.subject | Microfluidics | en |
| dc.title | 使用濃度梯度產生器微流道晶片結合表面增強拉曼散射進行組合抗生素敏感性試驗 | zh_TW |
| dc.title | Developing a Concentration Gradient Generator Microfluidics Integrating Surface-Enhanced Raman Scattering for Combinatory Antimicrobial Susceptibility Testing | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 王玉麟;韓吟宜;林鼎晸 | zh_TW |
| dc.contributor.oralexamcommittee | Yuh-Lin Wang;Yin-Yi Han;Ding-Zheng Lin | en |
| dc.subject.keyword | 組合抗生素敏感性試驗,微流體技術,表面增強拉曼散射, | zh_TW |
| dc.subject.keyword | Combinatory antimicrobial susceptibility testing (cAST),Microfluidics,Surface-enhanced Raman scattering (SERS), | en |
| dc.relation.page | 62 | - |
| dc.identifier.doi | 10.6342/NTU202504146 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-08-13 | - |
| dc.contributor.author-college | 電機資訊學院 | - |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-113-2.pdf 未授權公開取用 | 9.85 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。