應用表面電漿感測器於生物分子作用之動力學研究和構形分析

在表面電漿共振感測器之感測表面上，進行適當的處理程序以固定生物分子，可擴展此量測技術於生醫之應用範圍。

β型類澱粉胜肽的聚集、C反應蛋白的免疫偵測和多點DNA晶片 ... 資料載入處理中... 跳到主要內容 臺灣博碩士論文加值系統 ::: 網站導覽| 首頁| 關於本站| 聯絡我們| 國圖首頁| 常見問題| 操作說明 English |FB專頁 |Mobile 免費會員 登入| 註冊 功能切換導覽列 (165.22.59.181)您好！臺灣時間：2021/11/2523:44 字體大小：       ::: 詳目顯示 recordfocus 第1筆/ 共1筆  /1頁 論文基本資料 摘要 外文摘要 目次 參考文獻 電子全文 紙本論文 論文連結 QRCode 本論文永久網址: 複製永久網址Twitter研究生:胡文品研究生(外文):Wen-PinHu論文名稱:應用表面電漿感測器於生物分子作用之動力學研究和構形分析論文名稱(外文):Kineticsstudyandconformationanalysisofbiomolecularinteractionsbyapplyingsurfaceplasmonicsensors指導教授:張冠諒指導教授(外文):Guan-LiangChang學位類別:博士校院名稱:國立成功大學系所名稱:醫學工程研究所碩博士班學門:工程學門學類:綜合工程學類論文種類:學術論文論文出版年:2006畢業學年度:95語文別:英文論文頁數:119中文關鍵詞:表面電漿共振影像系統量測、多點DNA晶片製作、β型類澱粉胜肽聚集、動力學分析、免疫檢測、C反應蛋白、表面電漿生醫感測器外文關鍵詞:SPRimaging、DNAchip、Immnuodetection、Kineticsanalysis、C-reactiveprotein、β-amyloidpeptide、Surfaceplasmonresonance相關次數: 被引用:2點閱:298評分:下載:62書目收藏:0 在表面電漿共振感測器之感測表面上，進行適當的處理程序以固定生物分子，可擴展此量測技術於生醫之應用範圍。

β型類澱粉胜肽的聚集、C反應蛋白的免疫偵測和多點DNA晶片，在搭配表面電漿共振生醫感測或影像系統的使用下進行評估與量測，是本論文主要研究的三種生醫感測應用。

第一個研究目的是觀測β型類澱粉胜肽的自我聚集，與在金屬離子誘導下的聚集反應。

C反應蛋白的免疫量測目的是設計表面電漿共振生醫感測器於五元體與單體C反應蛋白的辨識量測，以獲得更準確的量測結果。

最後一個研究目的是提出一種製作多點DNA晶片的實用方法，並將晶片用於表面電漿共振影像系統的量測中。

為了研究β型類澱粉胜肽(1-40)聚集，可溶性的類澱粉胜肽首先被固定在表面電漿共振感測片的表面上，在自然或在金屬離子的誘導下觀測聚集的反應。

動力學參數是使用一階動力學模型分析資料後取得。

金屬離子螯合劑EDTA也用在實驗量測中，以測試此螯合劑對金屬離子誘導生成之β型類澱粉胜肽聚集物的破壞效果。

結果顯示β型類澱粉胜肽的聚集在金屬離子的誘導下表現出多種不同的傾向。

二價銅離子可以誘導β型類澱粉胜肽產生最快速的初期聚集反應，但卻不能促進大型β型類澱粉胜肽聚集物的產生。

金屬離子螯合劑EDTA可破壞經金屬離子誘導生成的β型類澱粉胜肽聚集物。

在C反應蛋白的免疫偵測中，為了使固定在感測表面之抗體皆能排列整齊，三種單株抗體（C8,8D8,9C9）都透過蛋白G而被固定在感測表面上。

實驗量測結果顯示，表面電漿共振生醫感測器於辨識單體與五元體的C反應蛋白上，具有高準確度。

在多點DNA晶片的量測上，在晶片的製作過程中，直接使用以短序列的硫醇化單股DNA（1μM）和oligo(ethyleneglycol)(OEG)（50μM）硫醇混合在磷酸二氫鉀內的溶液。

商業化的軟體Oligo則應用於計算DNA二級結構形成的可能性。

DNA雜交實驗則在兩種不同溫度下進行，以了解溫度對雜交的影響。

依據在表面電漿共振影像系統進行的量測，結果證實此種多點DNA晶片製作方法的可行性。

DNA二級結構對於雜交的影響程度，則可由提升實驗溫度來減少。

表面電漿共振檢測技術之量測結果，容易受到感測表面的化學修飾或採取的生物分子固定方法的影響。

在此研究中所使用的幾項方法，成功地順利完成實驗的量測，也可應用於其他生物分子的量測中。

本論文中的表面電漿共振檢測技術應用成果，將可提供其他研究者在使用此技術進行生醫檢測時的參考。

Withthesuitableimmobilizationsofbiomoleculesonthesensingsurfaceofsurfaceplasmonresonance(SPR)sensors,theycanbeextendedasusefultoolsinthestudiesofbiomolecularinteractions.Inthisdissertation,thestudyofβ-amyloid(Aβ)peptideaggregation,theimmunodetectionofC-reactiveprotein(CRP),andthefabricationofamultispotDNAchipwereevaluatedbytheSPRsensingorimagingtechniqueswhichconstructedthethreespecificapplications.TheaimoffirstapplicationistoobservetheprocessofAβaggregationwithorwithouttheexistenceofmetalions.TheimmunodetectionofCRPistoemploySPRbiosensorinthemeasurementofpentamerandmodifiedCRPswithlessfalsesignals.Finally,apracticalmethodtofabricateamultispotDNAchipisproposedandevaluatedbyaSPRimager.SolubleAβ(1-40)peptideisimmobilizedonthesurfaceofSPRchipandtheaggregatingreactionoccursspontaneouslyorundertheinductionofmetalions.Afirst-orderkineticsmodelisappliedtoanalysisthedataforgettingthekineticparameters.Ametalchelator,EDTA,isusedintheexperimentsfortestingitseffectonthedisruptionofAβaggregatesinducedbymetalions.ResultsrevealedthemetalionspromotedAβaggregationwithvariouspropensities.Cu(II)couldinducearapidestinitialAβaggregation,butitdidnotpromotetheformationoflargeAβaggregates.TheAβaggregatesinducedbymetalionscouldbedisruptedbythechelator,EDTA.Forconstructingsurfacewithawell-orderimmobilizationofantibodies,thethreemonoclonalantibodies(Mabs),C8,8D8,and9C9areimmobilizedonaproteinGlayerintheimmunodetectionofCRP.InallexperimentsofdetectingCRP,nofalseresultswereobservedintherecognitionofmodifiedandpentamerCRPs.InordertoprepareamultispotDNAchip,thiolatedsingle-strandedDNAs(ssDNAs)(1μM)withshortsequencesandoligo(ethyleneglycol)(OEG)alkanethiol(50μM)mixedin1MKH2PO4isusedtospotontheSPRsensingchip.Thecommercialprogram,Oligo,isappliedtocalculateofpossibilityonformationofDNAsecondarystructure.TheexperimentsofDNAhybridizationareperformedattwodifferenttemperaturesforinterpretingtheeffectoftemperatureonDNAhybridization.AccordingtotheresultsfromtheDNAhybridizingexperimentsevaluatedontheSPRimagingsystem,thefabricationmethodformakingamultispotDNAchipwasproveditsfeasibility.TheeffectofDNAsecondarystructureonhybridizationwasverifiedthatcouldbeminimizedbyraisingexperimentaltemperature.TheexperimentalreslutsobtainedfromtheSPRtechniquesareeasilyaffectedbychemicalsurfacemodificationsandbiomolecularimmobilizationsonthesensingsurface.Theseveralmethodsusedinthisdissertationaresuccessfullyappliedintheexperiments,andtheyalsocanbeusedinotherbiomoleculardetections.TheexperimentalresultscanprovidetheusefulexamplesofapplyingSPRtechniquesinthebiomedicalexaminationstootherrelatedresearchers. Chapter1.Introduction11.1ModernBiosensors11.2SurfacePlasmonResonanceTechnique31.2.1TypicalSPRInstrument91.2.2SPRImagingSystem101.3MotivationsandObjectives111.4ResearchFrameworkoftheDissertation131.5Applications141.5.1β-amyloidPeptideAggregation141.5.2ImmunodetectionofC-reactiveProtein(CRP)161.5.3DNAarray191.6Organization22Chapter2.PrinciplesofSPRBiosensors242.1DispersionRelationofSurfacePlamons242.2SpatialExtensionoftheSPFieldsandPropagationoftheSPs282.3ExcitationofSurfacePlasmonsbyLight292.4ReflectivityofthePrismCoupling332.5SPsonaThinFilm362.6ImmobilizationStrategiesforBiomolecules392.6.1ProteinAdsorption392.6.2CovalentBinding402.6.2.1ImmobilizationviaBio-specificReaction422.6.2.2ImmobilizationviaDNAHybridization432.6.3Dextran43Chapter3.MaterialsandMethods453.1Investigationofβ-amyloidPeptideAggregation453.1.1ReagentsandAβSamplePreparation453.1.2ConditionsforExperiments463.1.3ImmobilizationofAβPeptide463.1.4KineticsModel483.2ImmunosensingPentamerandModifiedCRP483.2.1Materials483.2.2ConditionsfortheSPRMeasurement513.2.3TheImmobilizationsofProteinGandMabs513.2.4MeasurementsofpCRPandmCRP543.3MultispotDNAChipandtheDNAHybridization543.3.1Reagents543.3.2CalculationofDNASecondaryStructure553.3.3ArrayingApproachforMakingaMultispotDNAChip563.3.4TheProceduresofExperiments59Chapter4.ResultsandDiscussion604.1ObservationsofAβAggregations604.1.1ControlandAnti-AβAntibodyBindingAssays604.1.2AggregationofAβPeptidesunderthePresenceofMetalIons634.1.3KineticAnalysisofAβPeptideAggregation694.1.4EffectofEDTAonMetalIon-inducedAβAggregations704.1.5Discussion724.2TheSpecificRecognitionforSensingPentamerandModifiedCRP764.2.1ChemicalImmobilizationofMabC8forDetectingpCRP764.2.2ImmobilizationofProteinG784.2.3ImmobilizationofMabs794.2.4RecognitionofpCRPandmCRP804.2.5DetectionLimitationofSPRTechniqueforCRP844.2.6DiscussionofResultsfortheCRP854.3DNAExperimentsPerformedbyUsingtheMultispotDNAChip884.3.1FabricationofaMultispotDNAChip884.3.2ThePredictionofDNASecondaryStructure894.3.3ControlExperimentsatTwoTemperatures904.3.4HybridizationReactionsofTargetc-Bandc-CatTwoTemperatures944.3.5DiscussiononFabricationofDNASpotsonSPRChip98Chapter5.ConclusionandRecommendations1005.1Summary1005.2RecommendationsandPerspectives102References105 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