研究生: |
林泰濬 Lin, Tai-Chun |
---|---|
論文名稱: |
檢測腹膜透析液中血管內皮生長因子之快速微流體生物感測器 Rapid microfluidic biosensor for the detection of Vascular Endothelial Growth Factor in peritoneal dialysate |
指導教授: |
傅龍明
Fu, Lung-Ming |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 工程科學系 Department of Engineering Science |
論文出版年: | 2024 |
畢業學年度: | 112 |
語文別: | 英文 |
論文頁數: | 49 |
中文關鍵詞: | VEGF 、微流體晶片 、ELISA 、點照護 |
外文關鍵詞: | VEGF, Microfluidic chip, ELISA, Point of care |
相關次數: | 點閱:44 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
2021 年腎臟相關疾病為台灣十大死因中排名第九,如何預防甚至控制慢性腎臟病 (Chronic Kidney Disease, CKD) 病情成為國人重要課題。由於腎臟的損傷為不可逆,因此醫療上只能透過生活作息的控制避免病情惡化,若不幸惡化成末期腎臟病變 (End Stage Renal Disease, ESRD) 則只能透過透析治療或是器官移植維持人體運作。
透析治療分為血液透析與腹膜透析,血液透析可透過醫護人員操作並定期追蹤病情,相反的腹膜透析可不需醫護人員操作的優點,但同時缺乏有效且穩定的長期追蹤手段,若有不慎可能引發腹膜炎,甚者產生如腹膜纖維化等病變。
為了追蹤腹膜的狀態,學界發現生物標誌物,如癌症抗原 125 (Cancer Antigen 125, CA125)、血管內皮生長因子 (Vascular Endothelial Growth Factor, VEGF)、乙型轉化生長因子 (Transforming Growth Factor Beta, TGF-β1) 可做為臨床分析的標準。
本研究提出檢測 VEGF 之微流體系統,透過微流體晶片的特性有效降低樣品與試劑體積,結合檢測機台達成快速和易操作之特性,只需傳統ELISA一半的檢測時間,達到點照護 (Point of care, POC) 的特點。可行性分析透過腹膜透析液作為樣本,獲得平均91.16 %的回收率。
In 2021, kidney related disease ranked ninth among the top ten causes of death in Taiwan. How to prevent and control Chronic Kidney Disease (CKD) has become an important issue for the people. Since kidney damage is irreversible, medical intervention can only control the progression of the disease through lifestyle management to prevent deterioration. If, unfortunately, it progresses to End-Stage Renal Disease (ESRD), the only options for sustaining bodily functions are either through dialysis treatment or organ transplantation.
Dialysis treatment is divided into hemodialysis and peritoneal dialysis. Hemodialysis will be performed by medical personnel with regular monitoring of the patient's condition. On the contrary, peritoneal dialysis offers the advantage of not requiring direct involvement of medical personnel. However, it comes with the inherent risks associated with the absence of effective and stable long-term tracking methods. Unintentionally, neglecting to monitor the condition may lead to peritonitis, and in severe cases, complications such as peritoneal fibrosis may occur.
To monitor the condition of the peritoneum, the academic community has identified biomarkers such as Cancer Antigen 125 (CA125), Vascular Endothelial Growth Factor (VEGF), and Transforming Growth Factor beta 1 (TGF-β1) as standards for clinical analysis. This study proposes a microfluidic system for detecting VEGF. Utilizing the characteristics of microfluidic chips effectively reduces the sample and reagent volumes. By combining with a detection platform, it achieves the characteristics of rapid and easy operation, requiring only half the testing time compared to traditional ELISA, catering to the features of point of care. Feasibility analysis using peritoneal dialysis fluid as a sample yielded an average recovery rate of 91.16 %.
[1]Gubala, V., Harris, L. F., Ricco, A. J., Tan, M. X., & Williams, D. E. (2012). Point of care diagnostics: status and future. Analytical Chemistry, 84(2), 487-515.
[2]Tseng, C. C., Kung, C. T., Chen, R. F., Tsai, M. H., Chao, H. R., Wang, Y. N., & Fu, L. M. (2021). Recent advances in microfluidic paper-based assay devices for diagnosis of human diseases using saliva, tears and sweat samples. Sensors and Actuators B: Chemical, 342, 130078.
[3]Kalantar-Zadeh, K., Jafar, T. H., Nitsch, D., Neuen, B. L., & Perkovic, V. (2021). Chronic kidney disease. The Lancet, 398(10302), 786-802.
[4]Levey, A. S., & Coresh, J. (2012). Chronic kidney disease. The Lancet, 379(9811), 165-180.
[5]Webster, A. C., Nagler, E. V., Morton, R. L., & Masson, P. (2017). Chronic kidney disease. The Lancet, 389(10075), 1238-1252.
[6]Hamed, S. A. (2019). Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: presentations, causes, and treatment strategies. Expert Review of Clinical Pharmacology, 12(1), 61-90.
[7]Pastan, S., & Bailey, J. (1998). Dialysis therapy. New England Journal of Medicine, 338(20), 1428-1437.
[8]Sinnakirouchenan, R., & Holley, J. L. (2011). Peritoneal dialysis versus hemodialysis: risks, benefits, and access issues. Advances in Chronic Kidney Disease, 18(6), 428-432.
[9]Gokal, R., & Mallick, N. P. (1999). Peritoneal dialysis. The Lancet, 353(9155), 823-828.
[10]Terri, M., Trionfetti, F., Montaldo, C., Cordani, M., Tripodi, M., Lopez-Cabrera, M., & Strippoli, R. (2021). Mechanisms of peritoneal fibrosis: focus on immune cells–peritoneal stroma interactions. Frontiers in Immunology, 12, 607204.
[11]Zhou, Q., Bajo, M. A., Del Peso, G., Yu, X., & Selgas, R. (2016). Preventing peritoneal membrane fibrosis in peritoneal dialysis patients. Kidney International, 90(3), 515-524.
[12]Nielsen, J. B., Hanson, R. L., Almughamsi, H. M., Pang, C., Fish, T. R., & Woolley, A. T. (2019). Microfluidics: innovations in materials and their fabrication and functionalization. Analytical Chemistry, 92(1), 150-168.
[13]Battat, S., Weitz, D. A., & Whitesides, G. M. (2022). An outlook on microfluidics: the promise and the challenge. Lab on a Chip, 22(3), 530-536.
[14]Whitesides, G. M. (2006). The origins and the future of microfluidics. Nature, 442(7101), 368-373.
[15]Robinson, C. J., & Stringer, S. E. (2001). The splice variants of vascular endothelial growth factor (VEGF) and their receptors. Journal of Cell Science, 114(5), 853-865.
[16]Carmeliet, P. (2005). VEGF as a key mediator of angiogenesis in cancer. Oncology, 69(Suppl. 3), 4-10.
[17]Muller, Y. A., Li, B., Christinger, H. W., Wells, J. A., Cunningham, B. C., & De Vos, A. M. (1997). Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proceedings of the National Academy of Sciences, 94(14), 7192-7197.
[18]Takahashi, H., & Shibuya, M. (2005). The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clinical science, 109(3), 227-241.
[19]McMahon, G. (2000). VEGF receptor signaling in tumor angiogenesis. The Oncologist, 5(S1), 3-10.
[20]Campochiaro, P. A., & Akhlaq, A. (2021). Sustained suppression of VEGF for treatment of retinal/choroidal vascular diseases. Progress in Retinal and Eye Research, 83, 100921.
[21]Kariya, T., Nishimura, H., Mizuno, M., Suzuki, Y., Matsukawa, Y., Sakata, F., Maruyama, S., Takei, Y., & Ito, Y. (2018). TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis. American Journal of Physiology-Renal Physiology, 314(2), F167-F180.
[22]Bilican, I., & Guler, M. T. (2020). Assessment of PMMA and polystyrene based microfluidic chips fabricated using CO2 laser machining. Applied Surface Science, 534, 147642.
[23]Duffy, D. C., McDonald, J. C., Schueller, O. J., & Whitesides, G. M. (1998). Rapid prototyping of microfluidic systems in poly (dimethylsiloxane). Analytical Chemistry, 70(23), 4974-4984.
[24]Ko, C. H., Liu, C. C., Huang, K. H., & Fu, L. M. (2023). Finger pump microfluidic detection system for methylparaben detection in foods. Food Chemistry, 407, 135118.
[25]Bai, Y., Koh, C. G., Boreman, M., Juang, Y. J., Tang, I. C., Lee, L. J., & Yang, S. T. (2006). Surface modification for enhancing antibody binding on polymer-based microfluidic device for enzyme-linked immunosorbent assay. Langmuir, 22(22), 9458-9467.
[26]Silva-Neto, H. A., Arantes, I. V., Ferreira, A. L., do Nascimento, G. H., Meloni, G. N., de Araujo, W. R., Paixão, T. R., & Coltro, W. K. (2023). Recent advances on paper-based microfluidic devices for bioanalysis. TrAC Trends in Analytical Chemistry, 158, 116893.
[27]Hoshino, K., Huang, Y. Y., Lane, N., Huebschman, M., Uhr, J. W., Frenkel, E. P., & Zhang, X. (2011). Microchip-based immunomagnetic detection of circulating tumor cells. Lab on a Chip, 11(20), 3449-3457.
[28]Chen, C. A., Yuan, H., Chen, C. W., Chien, Y. S., Sheng, W. H., & Chen, C. F. (2021). An electricity-and instrument-free infectious disease sensor based on a 3D origami paper-based analytical device. Lab on a Chip, 21(10), 1908-1915.
[29]Chen, K. H., Liu, C. C., Lu, S. Y., Chen, S. J., Sheu, F., & Fu, L. M. (2022). Rapid microfluidic analysis detection system for sodium dehydroacetate in foods. Chemical Engineering Journal, 427, 131530.
[30]Pattanayak, P., Singh, S. K., Gulati, M., Vishwas, S., Kapoor, B., Chellappan, D. K., Anand, K., Gupta, G., Jha, P. K., Gupta, P. K., Prasher, P., Dua, K., Dureja, H., Kumar, D., & Kumar, V. (2021). Microfluidic chips: recent advances, critical strategies in design, applications and future perspectives. Microfluidics and Nanofluidics, 25, 1-28.
[31]Anagu, L. O., & Andoh, N. E. (2022). Vaccine development: from the laboratory to the field. In Vaccinology and Methods in Vaccine Research (pp. 95-131). Academic Press.
[32]Sakamoto, S., Putalun, W., Vimolmangkang, S., Phoolcharoen, W., Shoyama, Y., Tanaka, H., & Morimoto, S. (2018). Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites. Journal of Natural Medicines, 72, 32-42.
[33]Mayerhöfer, T. G., Pipa, A. V., & Popp, J. (2019). Beer's law‐why integrated absorbance depends linearly on concentration. ChemPhysChem, 20(21), 2748-2753.
[34]Oshina, I., & Spigulis, J. (2021). Beer–Lambert law for optical tissue diagnostics: current state of the art and the main limitations. Journal of Biomedical Optics, 26(10), 100901-100901.
[35]Hao, N., Chiou, T. T. Y., Wu, C. H., Lei, Y. Y., Liang, P. L., Chao, M. C., Yang, H., & Chen, J. B. (2019). Longitudinal changes of PAI-1, MMP-2, and VEGF in peritoneal effluents and their associations with peritoneal small-solute transfer rate in new peritoneal dialysis patients. BioMed Research International, 2019.
[36]Jovanović, N. Ž., Žunić, S. S., Trbojević-Stanković, J. B., Laušević, Ž. D., Nešić, D. M., & Stojimirović, B. B. (2019). The relationship between vascular endothelial growth factor (VEGF) in the serum and drained dialysate with the quality of peritoneal dialysis and peritoneal membrane transport rates. Archives of Biological Sciences, 71(1), 187-194.
[37]Li, X. R., Yang, S. K., Zeng, B. Y., Tian, J., Liu, W., & Liao, X. C. (2023). Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study. Nefrología (English Edition), 43(3), 335-343.