石墨烯場效應電晶體應用於DNA生醫感測晶片之元件整合和效能評估的研究

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：148

、訪客IP：3.15.218.254

姓名

蕭偉傑(Wei-Jie Xiao) 查詢紙本館藏

畢業系所

能源工程研究所

論文名稱

石墨烯場效應電晶體應用於DNA生醫感測晶片之元件整合和效能評估的研究
(The integration and performance study on DNA biosensor based on the graphene field effect transistor)

相關論文

★ 捲對捲乾轉印方法於製作高效能石墨烯透明導電膜之研究	★ 利用氟素高分子摻雜於提升石墨烯導電膜的效能與穩定性之研究
★ 以石墨烯混成陶瓷粉末於製作高導熱及高電阻之聚亞醯胺薄膜的研究	★ 以奈米銅催化輔助控制多孔石墨烯之孔隙結構及其於超級電容之研究
★ 研究超潔淨石墨烯之場效電晶體於提升基因感測器之效能	★ 利用氟化自組裝膜輔助轉印石墨烯薄膜及其於場效電晶體特性之研究
★ 多孔石墨烯邊界態之氮改質於超級電容的效能研究	★ 添加氟化石墨烯於奈米高分子複合材料以增強防腐性能
★ 石墨烯功能性改質於鋰離子電池負極材料之研究	★ 紫外光輻照於輔助轉印高品質石墨烯之研究
★ 氟化石墨烯複合結構於鋰離子電池的人工固態電解質界面膜之研究	★ 超高附著力之氟化石墨烯薄膜於固態磨潤之研究
★ 真空壓印於二維材料轉印製程之研究	★ 氟化石墨烯複合結構在鋰金屬電池中的雙功能陽極之機制探討
★ 氟化石墨烯複合材料塗層於多功能披覆之研究	★ 三維結構之微孔石墨烯於超級電容器之應用與研究

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 ( 永不開放)

摘要(中)

本研究主要利用化學氣相沉積(CVD)的石墨烯轉印至二氧化矽的基板並利用蒸鍍的方式製作電極，將石墨烯當作場效應電晶體(FET)的通道製成的生醫晶片平台，特色在於簡單的製作方法，並且以無標籤式且實時性的感測癌症EBV DNA的濃度，透過狄拉克點的電性訊號變化並轉換成濃度區間的趨勢線，感測當前EBV DNA的濃度，相較於醫學的量測法，例如:磁核共振、電腦斷層掃描或聚合酶連鎖反應，石墨烯場效應電晶體GFET的感測時間短且成本耗費低的優勢都比醫學的方法有潛力，但石墨烯感測器目前需要克服的問題，例如:轉印的殘留物或是感測時的專一性都還是研究中的挑戰。
實驗過程分成上閘極式石墨烯場效應電晶體(TG-GFET)和平面式石墨烯場效應電晶體(PG-GFET)，TG-GFET因為其結構簡單較早被提出討論，而PG-GFET則因為電晶體有較多漏電流的問題，後來解決後被廣泛使用。PG-GFET的閘極材料與通道的距離固定，穩定性較高，且根據文獻模擬的結果，電晶體的通道被平面閘極的電場所影響效果比上閘極的高，所以在實驗中，平面式閘極的靈敏度略高約0.1 V/nM。本實驗的感測器可以達到檢測極限(LoD)於1 pM的濃度，而檢測的線性範圍位於1 pM到10 nM ，其中線性回歸率R2=0.99，表示此感測器可以提供有效的平台用於感測癌症DNA。

摘要(英)

Biosensor research has been addressed as an interesting field recently. Within different kinds of developed biosensing technologies, field-effect transistor (FET) based biosensors stand out due to their attractive features, such as ultra-sensitivity detection, mass production capability, and low- cost manufacturing, have exhibited enhanced performance in the sensing of small biomolecules, heavy metals, pH, protein and DNA. In control experiments with mismatched DNA oligomers, the impact of the mismatch position, and the different number of mismatch oligomers on the DNA hybridization strength was confirmed. experimental results demonstrate that our G-FET high selectivity even in the serum environment.
We compare two different ways fabricated FET and tested, both top-gate FET and plane-gate FET can receive a promising result as DNA biosensor, and plane-gate have some attractive features, such as cost-effective fabrication procedure and easy integration into an IC-chip, beneficial for portable and IoT compatible, due to high field effect to graphene channel, plane-gate have higher sensitivity than top-gate. Our biosensor revealed high selectivity and limit of detection receive 1 pM, the detection linear range at 1 pM to 10 nM (R2=0.99) and sensitivity can reach 0.03 V/nM, shows high reliability and characteristic.

關鍵字(中)

★ 石墨烯
★ 電晶體
★ 生物感測器

關鍵字(英)

★ Graphene
★ FET
★ Biosensor

論文目次

目錄
摘要 i
Abstract ii
目錄 iv
圖目錄 vi
表目錄 viii
第一章、緒論 1
第二章、文獻回顧 2
2-1石墨烯簡介 2
2-2 去氧核醣核酸(DNA) 3
2-2-1 癌症 4
2-2-2 臨床評估DNA的方法 4
2-3石墨烯電化學感測器 5
2-4螢光式感測器 7
2-5石墨烯電晶體(Graphene Field Effect Transistor, GFET) 8
2-5-1背閘極電晶體(back-gated FET) 9
2-5-2離子感測式電晶體(ion-sensitive FET,ISFET) 10
2-6德拜長度(Debye screen) 13
2-7石墨烯電荷中性點(charge neutral point, CNP) 14
2-8功能化石墨烯表面 16
2-8-1 共價官能化表面 17
2-8-2 非共價官能化表面 19
2-9 實驗動機 21
第三章、實驗流程與分析方法 23
3-1 試片製作與元件製備 23
3-1-1 合成石墨烯 23
3-1-2 轉印石墨烯 24
3-1-3 元件電極製備 25
3-2 生醫晶片量測 26
3-3 實驗藥品材料介紹 26
3-4 實驗和分析儀器介紹 27
3-4-1常壓化學氣相沉積(atmospheric pressure chemical vapor deposition, AP-CVD) 27
3-4-2旋轉塗佈機(spin coater) 28
3-4-3原子力顯微鏡(atomic force microscope, AFM) 28
3-4-4拉曼光譜儀(raman spectroscopy, Raman) 29
3-4-5半導體直流電性量測系統(IV ststem) 30
第四章、結果與討論 30
4-1石墨烯的特性分析 30
4-2石墨烯電晶體特性 31
4-3功能化石墨烯表面分析 32
4-4利用螢光顯微鏡確認DNA於石墨烯上 33
4-5 Probe DNA固定化對石墨烯電晶體的影響 35
4-5-2上閘極與平面閘極的電晶體特性 35
4-6 Target DNA雜合對轉移特性曲線的影響 36
4-7 PBS濃度和FET結構對靈敏度的影響 38
4-8 感測之選擇性分析 39
4-9 生醫晶片在血清環境的選擇性 40
第五章、結論 42
第六章、未來工作 43
參考文獻 44

參考文獻

參考文獻
[1] Wang, Y., et al., Label-free electrochemical immunosensor based on flower-like Ag/MoS2/rGO nanocomposites for ultrasensitive detection of carcinoembryonic antigen. Sensors and Actuators B: Chemical, 2018. 255: p. 125-132.
[2] Ouyang, Q., et al., Two-Dimensional Transition Metal Dichalcogenide Enhanced Phase-Sensitive Plasmonic Biosensors: Theoretical Insight. The Journal of Physical Chemistry C, 2017. 121(11): p. 6282-6289.
[3] Zhang, Y., et al., Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS nano, 2010. 4(6): p. 3181-3186.
[4] Namdari, P., H. Daraee, and A. Eatemadi, Recent advances in silicon nanowire biosensors: synthesis methods, properties, and applications. Nanoscale research letters, 2016. 11(1): p. 406.
[5] Forsyth, R., A. Devadoss, and O.J. Guy, Graphene field effect transistors for biomedical applications: Current status and future prospects. Diagnostics, 2017. 7(3): p. 45.
[6] Syu, Y.-C., W.-E. Hsu, and C.-T. Lin, Field-effect transistor biosensing: Devices and clinical applications. ECS Journal of Solid State Science and Technology, 2018. 7(7): p. Q3196.
[7] Tang, X., et al., Chemically deposited palladium nanoparticles on graphene for hydrogen sensor applications. Scientific reports, 2019. 9(1): p. 1-11.
[8] Salvo, P., et al., Graphene-based devices for measuring pH. Sensors and Actuators B: Chemical, 2018. 256: p. 976-991.
[9] Andronescu, C. and W. Schuhmann, Graphene-based field effect transistors as biosensors. Current Opinion in Electrochemistry, 2017. 3(1): p. 11-17.
[10] Ping, J., et al., Scalable production of high-sensitivity, label-free DNA biosensors based on back-gated graphene field effect transistors. ACS nano, 2016. 10(9): p. 8700-8704.
[11] Staudenmaier, L., Verfahren zur Darstellung der Graphitsäure. Berichte der deutschen chemischen Gesellschaft, 1898. 31(2): p. 1481-1487.
[12] Berger, C., et al., Ultrathin epitaxial graphite: 2D electron gas properties and a route toward graphene-based nanoelectronics. The Journal of Physical Chemistry B, 2004. 108(52): p. 19912-19916.
[13] Munief, W.-M., et al., Reduced graphene oxide biosensor platform for the detection of NT-proBNP biomarker in its clinical range. Biosensors and Bioelectronics, 2019. 126: p. 136-142.
[14] Chen, X.D., et al., Fast Growth and Broad Applications of 25-Inch Uniform Graphene Glass. Adv Mater, 2017. 29(1).
[15] Arbach, H., et al., Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). J Virol, 2006. 80(2): p. 845-53.
[16] Chan, K.C.A., et al., Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med, 2017. 377(6): p. 513-522.
[17] Su, S., et al., Two-dimensional nanomaterials for biosensing applications. TrAC Trends in Analytical Chemistry, 2019. 119: p. 115610.
[18] Heyn, C., et al., In vivo MRI of cancer cell fate at the single‐cell level in a mouse model of breast cancer metastasis to the brain. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine, 2006. 56(5): p. 1001-1010.
[19] Kuehl, H., et al., Can PET/CT replace separate diagnostic CT for cancer imaging? Optimizing CT protocols for imaging cancers of the chest and abdomen. Journal of Nuclear Medicine, 2007. 48(1): p. 45S.
[20] Cui, F., Z. Zhou, and H.S. Zhou, Measurement and Analysis of Cancer Biomarkers Based on Electrochemical Biosensors. Journal of The Electrochemical Society, 2019. 167(3): p. 037525.
[21] Rahman, M., et al., A graphene oxide coated gold nanostar based sensing platform for ultrasensitive electrochemical detection of circulating tumor DNA. Analytical Methods, 2020. 12(4): p. 440-447.
[22] Zhang, H.-F., D.-P. Wu, and X.-J. Ning, Atomistic mechanism for graphene based gaseous sensor working. Applied Surface Science, 2019. 470: p. 448-453.
[23] Yoon, H.J., et al., Carbon dioxide gas sensor using a graphene sheet. Sensors and Actuators B: Chemical, 2011. 157(1): p. 310-313.
[24] Chen, X., et al., In situ growth of FeOOH nanoparticles on physically-exfoliated graphene nanosheets as high performance H2O2 electrochemical sensor. Sensors and Actuators B: Chemical, 2020. 313: p. 128038.
[25] Yagati, A.K., et al., Label-free and direct detection of C-reactive protein using reduced graphene oxide-nanoparticle hybrid impedimetric sensor. Bioelectrochemistry, 2016. 107: p. 37-44.
[26] Rakhi, R.B., et al., Novel amperometric glucose biosensor based on MXene nanocomposite. Sci Rep, 2016. 6: p. 36422.
[27] Singh, R., S. Hong, and J. Jang, Label-free Detection of Influenza Viruses using a Reduced Graphene Oxide-based Electrochemical Immunosensor Integrated with a Microfluidic Platform. Sci Rep, 2017. 7: p. 42771.
[28] Ping, J., et al., Simultaneous determination of ascorbic acid, dopamine and uric acid using high-performance screen-printed graphene electrode. Biosens Bioelectron, 2012. 34(1): p. 70-6.
[29] Ibau, C., et al., Gold interdigitated triple-microelectrodes for label-free prognosticative aptasensing of prostate cancer biomarker in serum. Biosens Bioelectron, 2019. 136: p. 118-127.
[30] Canbaz, M.C., C.S. Simsek, and M.K. Sezginturk, Electrochemical biosensor based on self-assembled monolayers modified with gold nanoparticles for detection of HER-3. Anal Chim Acta, 2014. 814: p. 31-8.
[31] Hashkavayi, A.B., et al., Ultrasensitive electrochemical aptasensor based on sandwich architecture for selective label-free detection of colorectal cancer (CT26) cells. Biosens Bioelectron, 2017. 92: p. 630-637.
[32] Mandal, T.K., Y.R. Lee, and N. Parvin, Red phosphorus decorated graphene oxide nanosheets: label-free DNA detection. Biomater Sci, 2019. 8(1): p. 125-131.
[33] Hu, Y., et al., Photoelectrochemical sensing for hydroquinone based on porphyrin-functionalized Au nanoparticles on graphene. Biosens Bioelectron, 2013. 47: p. 45-9.
[34] Goldsmith, B., et al., Temperature dependence of the noise amplitude in graphene and graphene oxide. physica status solidi (RRL)–Rapid Research Letters, 2009. 3(6): p. 178-180.
[35] Pud, S., et al., Liquid and back gate coupling effect: toward biosensing with lowest detection limit. Nano Lett, 2014. 14(2): p. 578-84.
[36] Sonmez, B.G., O. Ertop, and S. Mutlu, Modelling and Realization of a Water-Gated Field Effect Transistor (WG-FET) Using 16-nm-Thick Mono-Si Film. Sci Rep, 2017. 7(1): p. 12190.
[37] Wang, C., et al., A label-free and portable graphene FET aptasensor for children blood lead detection. Sci Rep, 2016. 6: p. 21711.
[38] Tu, J., et al., Graphene FET Array Biosensor Based on ssDNA Aptamer for Ultrasensitive Hg(2+) Detection in Environmental Pollutants. Front Chem, 2018. 6: p. 333.
[39] Gurney, R.W., Theory of Electrical Double Layers in Adsorbed Films. Physical Review, 1935. 47(6): p. 479-482.
[40] Piccinini, E., et al., Pushing the Boundaries of Interfacial Sensitivity in Graphene FET Sensors: Polyelectrolyte Multilayers Strongly Increase the Debye Screening Length. The Journal of Physical Chemistry C, 2018. 122(18): p. 10181-10188.
[41] Chen, T.Y., et al., Label-free detection of DNA hybridization using transistors based on CVD grown graphene. Biosens Bioelectron, 2013. 41: p. 103-9.
[42] Wu, S., et al., Vapor–solid growth of high optical quality MoS2 monolayers with near-unity valley polarization. ACS nano, 2013. 7(3): p. 2768-2772.
[43] Chen, S., et al., Donor effect dominated molybdenum disulfide/graphene nanostructure-based field-effect transistor for ultrasensitive DNA detection. Biosens Bioelectron, 2020. 156: p. 112128.
[44] Xu, S., et al., Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor. Nat Commun, 2017. 8: p. 14902.
[45] Chen, K.-I., B.-R. Li, and Y.-T. Chen, Silicon nanowire field-effect transistor-based biosensors for biomedical diagnosis and cellular recording investigation. Nano Today, 2011. 6(2): p. 131-154.
[46] Zhu, J., et al., Graphene-Based FET Detector forE. coliK12 Real-Time Monitoring and Its Theoretical Analysis. Journal of Sensors, 2016. 2016: p. 1-9.
[47] Lin, C.-T., et al., Label-Free Electrical Detection of DNA Hybridization on Graphene using Hall Effect Measurements: Revisiting the Sensing Mechanism. Advanced Functional Materials, 2013. 23(18): p. 2301-2307.
[48] Georgakilas, V., et al., Functionalization of graphene: covalent and non-covalent approaches, derivatives and applications. Chem Rev, 2012. 112(11): p. 6156-214.
[49] Zhang, X., et al., Ultrasensitive Field-Effect Biosensors Enabled by the Unique Electronic Properties of Graphene. Small, 2019: p. e1902820.
[50] Dikin, D.A., et al., Preparation and characterization of graphene oxide paper. Nature, 2007. 448(7152): p. 457-60.
[51] Tahara, K., et al., Effect of radical fluorination on mono- and bi-layer graphene in Ar/F2 plasma. Applied Physics Letters, 2012. 101(16): p. 163105.
[52] Rahsepar, M., F. Foroughi, and H. Kim, A new enzyme-free biosensor based on nitrogen-doped graphene with high sensing performance for electrochemical detection of glucose at biological pH value. Sensors and Actuators B: Chemical, 2019. 282: p. 322-330.
[53] Chakarova-Kack, S.D., et al., Application of van der Waals density functional to an extended system: adsorption of benzene and naphthalene on graphite. Phys Rev Lett, 2006. 96(14): p. 146107.
[54] Cooper, M.A., Optical biosensors in drug discovery. Nat Rev Drug Discov, 2002. 1(7): p. 515-28.
[55] Zhou, L., et al., Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of Cancer Biomarkers. Nano-Micro Letters, 2019. 11(1).
[56] Fernandes, E., et al., Functionalization of single-layer graphene for immunoassays. Applied Surface Science, 2019. 480: p. 709-716.
[57] Guo, S.R., et al., Label free DNA detection using large area graphene based field effect transistor biosensors. J Nanosci Nanotechnol, 2011. 11(6): p. 5258-63.
[58] Kim, D.H., et al., Detection of Alpha-Fetoprotein in Hepatocellular Carcinoma Patient Plasma with Graphene Field-Effect Transistor. Sensors (Basel), 2018. 18(11).
[59] Wu, G., M. Meyyappan, and K.W.C. Lai. Graphene field-effect transistors-based biosensors for Escherichia coli detection. in 2016 IEEE 16th International Conference on Nanotechnology (IEEE-NANO). 2016. IEEE.
[60] Yue, W., et al., An electricity-fluorescence double-checking biosensor based on graphene for detection of binding kinetics of DNA hybridization. RSC Advances, 2017. 7(70): p. 44559-44567.
[61] Liu, Y., et al., Giant enhancement in vertical conductivity of stacked CVD graphene sheets by self-assembled molecular layers. Nat Commun, 2014. 5: p. 5461.
[62] Maidin, N.N.M., et al., Interaction of graphene electrolyte gate field-effect transistor for detection of cortisol biomarker. 2018. 2045: p. 020022.
[63] Nekrasov, N., et al., Graphene-Based Sensing Platform for On-Chip Ochratoxin A Detection. Toxins (Basel), 2019. 11(10).
[64] Ping, J., et al., Scalable Production of High-Sensitivity, Label-Free DNA Biosensors Based on Back-Gated Graphene Field Effect Transistors. ACS Nano, 2016. 10(9): p. 8700-4.
[65] Minot, E.D., et al., Carbon nanotube biosensors: The critical role of the reference electrode. Applied Physics Letters, 2007. 91(9): p. 093507.
[66] Miskovic, Z.L. and N. Upadhyaya, Modeling Electrolytically Top-Gated Graphene. Nanoscale Res Lett, 2010. 5(3): p. 505-511.
[67] Fu, W., et al., Biosensing near the neutrality point of graphene. Science Advances, 2017. 3(10): p. e1701247.
[68] Letowski, J., R. Brousseau, and L. Masson, Designing better probes: effect of probe size, mismatch position and number on hybridization in DNA oligonucleotide microarrays. J Microbiol Methods, 2004. 57(2): p. 269-78.
[69] Peterson, A.W., L.K. Wolf, and R.M. Georgiadis, Hybridization of mismatched or partially matched DNA at surfaces. Journal of the American Chemical Society, 2002. 124(49): p. 14601-14607.
[70] Zhang, L., M.F. Miles, and K.D. Aldape, A model of molecular interactions on short oligonucleotide microarrays. Nature biotechnology, 2003. 21(7): p. 818-821.

指導教授

蘇清源(Ching-Yuan Su)

審核日期

2020-7-30

推文