1273231 九、發明說明： 【發明所屬之技術領域】 本發明係有關於一種利用電光效應調變表面電漿共振 之檢測方法與檢測裝置，尤指藉外加電壓調變電光效應之 一種表面電漿共振之檢測方法與檢測裝置，係測量光強度 隨外加電壓之變化，以得知待測物中如生化物質之濃度， 在應用上可以進行以下檢測：藥物濃度檢測、藥物與血清 球蛋白之親和性檢測、化學物成分檢測、環境污染物檢測 等。 【先前技術】 物質中的自由電荷可受變動的電磁場驅動作反覆運動 ，其電荷密度隨時間或空間的反覆變化為一種電漿震盪 (plasma oscillation)的現象。在物質中傳播的電磁波遭遇介 電常數(dielectric constant)不同的物質之介面時，若電磁波 的電場極化方向與波長滿足適當的共振條件，該電磁波的 電磁場可與物質中的電漿震盪耦合，形成表面電漿共振 (surface plasma resonance)。上述共振條件為電磁波激發表 面電漿子（surface plasmon)時須符合的動量與能量守衡條 件，電磁波因激發表面電漿子將造成散逸能量損失，又表 面電漿子的特性係隨介面兩侧物質之介電常數變化，故可 藉電磁波能量損失隨電磁波波長的變化測量該介面兩側物 質之介電常數。具體而言，電磁波能量損失的極大值出現 在相當於表面電漿子能量的表面電漿共振波長處，此表面 1273231 電漿共振波長則決定於介面兩侧物質之介電常數。1273231 IX. Description of the invention: [Technical field to which the invention pertains] The present invention relates to a detection method and a detection device for modulating surface plasma resonance using an electro-optical effect, in particular to a surface plasma by means of an applied voltage modulation electro-optic effect The detection method and detection device of the resonance measure the change of the light intensity with the applied voltage to know the concentration of the biochemical substance in the test object, and the following detection can be performed in the application: the drug concentration detection, the affinity of the drug and the serum globulin Sex detection, chemical composition detection, environmental pollutant detection, etc. [Prior Art] The free charge in a substance can be driven by a variable electromagnetic field to repetitively move, and its charge density changes with time or space as a phenomenon of plasma oscillation. When an electromagnetic wave propagating in a substance encounters an interface of a substance having a different dielectric constant, if the direction and wavelength of the electric field of the electromagnetic wave satisfy an appropriate resonance condition, the electromagnetic field of the electromagnetic wave can be coupled with the plasma oscillation in the substance. Surface plasma resonance is formed. The above resonance condition is a momentum and energy balance condition that must be met when the electromagnetic wave excites the surface plasmon. The electromagnetic wave will cause the dissipation energy loss due to the excitation of the surface plasmon, and the surface plasmon characteristics are on both sides of the interface. The dielectric constant of the substance changes, so the dielectric constant of the material on both sides of the interface can be measured by the energy loss of the electromagnetic wave as the wavelength of the electromagnetic wave changes. Specifically, the maximum value of the electromagnetic wave energy loss occurs at the surface plasma resonance wavelength corresponding to the surface plasmon energy, and the surface 1273231 plasma resonance wavelength is determined by the dielectric constant of the substance on both sides of the interface.
積體光學表面電漿共振檢測裝置利用上述表面電裝共 振現象的檢測原理，常應用於生物和生化檢測系統，其具 有無須彳示S己、即時分析、具專一性、靈破度局、及可大旦 平行檢測等優點。應用此技術可即時動態分析待測物之變 化，故可應用在如化學氣體檢測、各類溶液檢測、污染監 控、生物晶片等領域。此外，應用積體光學技術所製作的 表面電漿共振檢測裝置，具有結構堅固、體積小、可攜性 佳、高靈敏度的優點，而且所製作之檢測裝置尚可與其他 積體光學兀件整合在單一晶片上，構成功能多樣化之光積 體電路，未來的發展深具應用之潛力。 貝 傳統的積體光學表面電漿共振檢測裝置使用頻譜儀， 以測量表面電漿共振波長隨檢測物特性之變化，故盆檢測 裝置的敏感度受限於頻譜儀的解析度。為了避免震動造成 頻譜儀的量測誤差，頻譜儀須玫置在避震台上，這不作使 使用的領域 增加’且由於體積龐大，只能架設在實驗 至 〃不利於戶外之實地量測，限制了檢測裝置 【發明内容】 針對上述傳統的積體来風主 陷，如敏感度受限於頻=1面㈣共振檢測裝置的缺 使用領域受限等問題’本發明要求造成的高，本與 電漿共振之檢測方法與檢^ :種電光效應調變表^ 、表置’係測量光強度隨外加電 1273231 壓之變化以進行檢測。該檢測方法包含以下步驟：（1)決定 一輸出光強度相對於該外加電壓變化之一電光調變關係； (2)根據該電光調變關係決定一回歸直線斜率；（3)根據該回 歸直線斜率決定材料特性與濃度。該檢測裝置係製於一基 板表面，且包含：一波導區，係設於該基板之一面，且具 有一感測波導區、一輸入端與一輸出端，該感測波導區上 覆蓋有一金屬層，以及一電極部，以於該感測區之兩側外 加一電壓。本發明利用電光效應調變表面電漿共振條件， 乃測量波導區的輸出端之電磁波強度’以得知該電磁波強 度隨感測波導區兩侧之外加電壓的變化，從而推知與感測 波導區接觸的待測物之介電常數，或如生化物質濃度等與 介電常數相關的特性。下文以應用於一積體光學表面電漿 共振檢測裝置之實施例為例，說明本發明之一種電光調變 表面電漿共振之檢測方法與檢測裝置，並以生化物質濃度 測量的例子說明其具體應用。 【實施方式】 第一圖係本發明之一種積體光學表面電漿共振檢測裝 置的示意圖，第二圖係本發明之一種積體光學表面電漿共 振檢測裝置中的感測波導區垂直於波導方向的截面示意圖 (朝負Y-方向觀之）。如第一與第二圖所示，本發明之一 種積體光學表面電漿共振檢測裝置包含：以具優良電光效 應特性之錕酸裡晶體材料為一基板1，其具法向量為銳酸 鋰晶體的X方向之一切面2 (X-cut surface);設於該基板1 1273231 之該切面2且具一感測波導區3與一參考波導區4之波導 區，係經鈦擴散將鈦離子局部攙入鈮酸鋰晶體之切面2形 成波導，以沿鈮酸鋰晶體γ方向（波導方向）傳播電磁波， 該感測波導區3與該參考波導區4之一端設有二者共有之 一輸入端5，以將波源產生的輸入電磁波導入該感測波導 區3與該芩考波導區4中，該感測波導區3與該參考波導 區4之另一端分別設有一感測輸出端6與一參考輸出端 7，以輸出感測輸出電磁波與參考輸出電磁波，且感測波 導區3與參考波導區4形成一 γ形分岔結構，其具夾半角 約0.5度之一分岔處8，更且感測波導區3上覆蓋有材料 為金之一金屬層9，其厚度為30nm，其内部自由電子與感 測波區3中傳播的電磁波搞合激發產生表面電漿子 (surface plasmon)，又更且該波導區上覆蓋有材料為二氧化 矽之一隔離層1 〇，其於感測波導區3具有一開口，此隔 離層1 0可避免在量測時參考波導區4受置於感測波導區 3上之待測物丄χ干擾；以及具兩電極端i 2、丄3與兩 電極輸入端1 4、1 5之電極部，以於感測波導區3之兩 侧產生可調變的外加電壓，且該兩電極端1 2、丄3上覆 蓋有材料為二氧化矽之一絕緣層丄6，其於感測波導區3 上有一部份開口，以避免有外加電壓時待測物丄丄中的液 體造成該兩電極端1 2、1 3間的短路。 利用上述本發明之一種積體光學表面電漿共振檢測裝 置，如第一與第二圖所示，將待測物丄丄置於感測波導區 3上，施一外加電壓於兩電極端1 4、1 5，此外加電壓 1273231 於基板1之切面2上之感測波導區3產生平行於Z-方向之 電場’此電場因電光效應使感測波導區3的介電常數產生 變化，故改變外加電壓可調變產生表面電漿子的共振條 件，亦即改變感測波導區3上的金屬層9因表面電漿共振 產生的電磁波吸收（表面電漿共振吸收）特性，同時改變感 測輸出端6的輸出電磁波強度，又此表面電漿共振吸收隨 外加電壓的變化率與待測物1 1之介電常數相關，故可測 量感測輸出端6的輸出電磁波強度隨外加電壓的變化，以 推知與待測物之介電常數相關之特性，如生化物質的濃度 等。請注意，本發明之一種積體光學表面電漿共振檢測裝 置中，對於基板、波導區與電極所使用的材料與其製作方 式，以及基板之切面和波導方向與晶體結構的關係並無特 別限定。 以下說明上述本發明之一種積體光學表面電漿共振檢 測裝置之具體應用。如第一與第二圖所示，將待測物11 置於感測波導區3上，以一波源產生輸入電磁波，並以如 光纖耦接之方式將輸入電磁波導入波導區的輸入端5，以 光功率計測量感測輸出端6與參考輸出端7之感測輸出電 磁波與參考輸出電磁波之功率，從而計算得到一電磁波相 對強度，係感測輸出電磁波的功率與參考輸出電磁波的功 率之比值，並改變外加電壓調變表面電漿共振條件，以測 量得到該電磁波相對強度與外加電壓之關係。使用白光作 為輸入電磁波之波源時，表面電漿共振吸收的特性曲線如 第三圖所示，係電磁波相對強度與電磁波波長的關係圖， 10 1273231 強_波的部分能量，故其相對 強度具有-極小值，係出現於相當於表 面電漿共振波長Up。、λρ+ 的表 ，感測 ===表*電漿共振條件亦隨之改變使上述 波=定3=。若以具賴大於表_共振 斤同長U°)的雷射作為輸人電磁波之波源，如 弟二圖所不’輪出端所測得之電磁波相對強 - 與Ϊ +)將隨外加電壓v a變化，日士 又 0 加電，的變化率係決定於待測物之 寺測物的介電常數決定於其所:生 度隨外加電壓V a的變化之回歸磁波相對強 ^ , n 、 潭之斜率的絕對值隨濃度變 直線之：：：濃度2>濃度1 ;如第五圖所示，係回歸 :=的絕對值與濃度間的關係圖，其中可 、=Γ對值與濃度間有明顯的正相關，據此，可藉 者，直，之斜率精確測量待測物中生化物質之濃度。再 確性右二大器之使用，將可進-步提昇檢測之精 學表面Ϊ: 雜訊之能力。故本發明之-種積體光 體積小二 =測裝置具有精確度高、雜鳴力強、 球蛋μΓ 統成本降低等優點。以人體的血清 蛋白為相物，本發日狀已柄” 1273231 先學表面電漿共振檢測裝置可用於檢測 治療心臟病的藥物）之濃度。 斷趴-種 之應調變表面電漿共振之檢測方法 度時，利制物之_特性與濃 州甩光效應以一外加雷懕哺絲主^ ㈣ce _咖職腦ce)之條件電聚共振 1::測:⑴量測輸出光強度隨外加 :=，該光強度可為如第四圖所示之電磁波相對： 又 的輪出光波長可依待測材料的種類來it摆# 光波長的不同，檢職置的敏感度會用” 擇具有最錄献的級絲 ^、選 到其相對應的回歸直線3度;外t電壓變化的關係，得 第五圖所示；(3)使用、::與浪度之關係如第四圖與 得到的回鋒直線斜率；了^或標準材料）進行檢測所 料，以内插的方式，計曾旦料特性）關係的校準資 應的濃度（或材料特性）i此、到的回歸直線斜率所對 性）。 ）猎此決定待測物的濃度（或材料特 總而言之’本發明完全符合 ，和產業上的利用性。以新嶺性和泰而言 _電光輕測量表面電漿共振效應，故可避免使用ς 局成本與限制使用領域的頻譜儀，同時突破限制傳統的二 測糸統之敏感度’更可藉由配合鎖相放大器之使用，進: 步提昇檢測之精確性、穩定度與濾'除雜訊之能力。就產業 1273231 上的利用性而言，利用本發明所衍生的產品，當可充分滿 足目前市場的需求。 本發明在上文中已以較佳實施例揭露，然熟習本項技 術者應理解的是，該實施例僅用於描繪本發明，而不應解 讀為限制本發明之範圍。應注意的是，舉凡與該實施例等 效之變化與置換，均應設為涵蓋於本發明之範疇内。因此 ，本發明之保護範圍當以下文之申請專利範圍所界定者為 準。 【圖式簡單說明】 第一圖係本發明之一種積體光學表面電漿共振檢測裝 ^ 置的示意圖。 ' 第二圖係本發明之一種積體光學表面電漿共振檢測裝 置中的感測波導區垂直於波導方向的截面不意圖（朝負γ_ 方向觀之）。 Φ 第三圖係電磁波相對強度與電磁波波長的關係示意圖 〇 第四圖係電磁波相對強度隨外加電壓的變化之回歸直 線不意圖。 第五圖係回歸直線之斜率的絕對值與濃度間的關係示 意圖。 【主要元件符號說明】 1基板The integrated optical surface plasma resonance detecting device utilizes the above-mentioned surface electrical electrification resonance phenomenon detection principle, and is often applied to biological and biochemical detection systems, which have no need to indicate self, immediate analysis, specificity, spiritual breakage, and It can be used for parallel detection of large Dan. This technology can be used to dynamically analyze changes in the analytes, so it can be applied in areas such as chemical gas detection, various types of solution detection, pollution monitoring, and biochips. In addition, the surface plasma resonance detecting device manufactured by the integrated optical technology has the advantages of strong structure, small volume, good portability, high sensitivity, and the detection device can be integrated with other integrated optical components. On a single wafer, a diversified optical complex circuit is formed, and the future development has great potential for application. The conventional integrated optical surface plasma resonance detection device uses a spectrometer to measure the surface plasma resonance wavelength as a function of the characteristics of the detector, so the sensitivity of the basin detection device is limited by the resolution of the spectrum analyzer. In order to avoid the measurement error of the spectrum analyzer caused by the vibration, the spectrum analyzer must be placed on the shock absorber, which does not increase the field of use. And because of its large size, it can only be set up in the field to measure the field. Limiting the detection device [Summary of the Invention] In view of the above-mentioned conventional integrated body, the wind is mainly trapped, such as the sensitivity is limited by the frequency = 1 surface (four) resonance detection device, the lack of use of the field, etc. The detection method and the detection of the resonance of the plasma are as follows: the electro-optical effect modulation table ^, the table-set is the measurement of the light intensity with the change of the applied voltage 1273231 for detection. The detecting method comprises the following steps: (1) determining an electro-optic modulation relationship of an output light intensity with respect to the applied voltage change; (2) determining a regression line slope according to the electro-optic modulation relationship; (3) according to the regression line The slope determines the material properties and concentration. The detecting device is mounted on a surface of a substrate, and comprises: a waveguide region disposed on one side of the substrate, and having a sensing waveguide region, an input end and an output end, the sensing waveguide region is covered with a metal a layer and an electrode portion for applying a voltage to both sides of the sensing region. The invention utilizes the electro-optical effect to modulate the surface plasma resonance condition, and measures the electromagnetic wave intensity at the output end of the waveguide region to know the change of the electromagnetic wave intensity with the applied voltage on both sides of the sensing waveguide region, thereby inducing contact with the sensing waveguide region. The dielectric constant of the analyte or the property related to the dielectric constant such as the concentration of the biochemical. Hereinafter, an embodiment of an electro-optical modulation surface plasma resonance detection method and a detection device according to an embodiment of an integrated optical surface plasma resonance detecting device will be described, and an example of biochemical substance concentration measurement is described. application. [Embodiment] The first figure is a schematic diagram of an integrated optical surface plasma resonance detecting device of the present invention, and the second drawing is a sensing waveguide region in the integrated optical surface plasma resonance detecting device of the present invention which is perpendicular to the waveguide. A schematic cross-section of the direction (viewed in the negative Y-direction). As shown in the first and second figures, an integrated optical surface plasma resonance detecting apparatus of the present invention comprises: a crystal material of tannic acid having excellent electrooptic effect characteristics as a substrate 1 having a normal vector of lithium lithate An X-cut surface of the crystal in the X direction; a waveguide region provided on the substrate 2 1273231 and having a sensing waveguide region 3 and a reference waveguide region 4, which is titanium nitride diffused by titanium The section 2 of the lithium niobate crystal is partially infiltrated to form a waveguide to propagate electromagnetic waves along the γ direction (waveguide direction) of the lithium niobate crystal, and the sensing waveguide region 3 and one end of the reference waveguide region 4 are provided with one input The terminal 5 is configured to introduce an input electromagnetic wave generated by the wave source into the sensing waveguide region 3 and the reference waveguide region 4. The sensing waveguide region 3 and the other end of the reference waveguide region 4 are respectively provided with a sensing output terminal 6 and a reference output terminal 7 for outputting the sensed output electromagnetic wave and the reference output electromagnetic wave, and the sensing waveguide region 3 and the reference waveguide region 4 form a gamma-shaped bifurcation structure having a half angle of about 0.5 degrees and a branching point 8 Further, the sensing waveguide region 3 is covered with a material of gold. A metal layer 9 having a thickness of 30 nm, the internal free electrons and the electromagnetic waves propagating in the sensing wave region 3 are combined to generate a surface plasmon, and the waveguide region is covered with a material for oxidation. An isolation layer 1 〇 having an opening in the sensing waveguide region 3, the isolation layer 10 avoiding interference of the object to be detected placed on the sensing waveguide region 3 by the reference waveguide region 4 during measurement And an electrode portion having two electrode terminals i 2, 丄 3 and two electrode input terminals 14 and 15 for generating an adjustable applied voltage on both sides of the sensing waveguide region 3, and the two electrode terminals 1 2 The crucible 3 is covered with an insulating layer 丄6, which is an insulating layer 二6, which has a portion of the opening in the sensing waveguide region 3 to prevent the liquid in the object to be tested from being applied to the two electrode terminals when an applied voltage is applied. 1 2, 1 3 short circuit. Using the above-described integrated optical surface plasma resonance detecting device of the present invention, as shown in the first and second figures, the object to be tested is placed on the sensing waveguide region 3, and an applied voltage is applied to the two electrode terminals. 4, 1 5, in addition, a voltage of 1273231 is applied to the sensing waveguide region 3 on the slice 2 of the substrate 1 to generate an electric field parallel to the Z-direction. This electric field changes the dielectric constant of the sensing waveguide region 3 due to the electro-optical effect. Changing the applied voltage can change the resonance condition of the surface plasmon, that is, changing the electromagnetic wave absorption (surface plasmon resonance absorption) characteristic of the metal layer 9 on the sensing waveguide region 3 due to the surface plasma resonance, and changing the sensing The output electromagnetic wave intensity of the output terminal 6 and the rate of change of the surface plasma resonance absorption with the applied voltage are related to the dielectric constant of the object to be tested 1 1 , so that the output electromagnetic wave intensity of the sensing output terminal 6 can be measured as a function of the applied voltage. To infer the characteristics related to the dielectric constant of the analyte, such as the concentration of biochemical substances. Note that in the integrated optical surface plasma resonance detecting apparatus of the present invention, the material used for the substrate, the waveguide region and the electrode, the manner in which the substrate is used, and the relationship between the cut surface of the substrate and the waveguide direction and the crystal structure are not particularly limited. The specific application of the above-described integrated optical surface plasma resonance detecting device of the present invention will be described below. As shown in the first and second figures, the object to be tested 11 is placed on the sensing waveguide region 3, an input electromagnetic wave is generated by a wave source, and the input electromagnetic wave is introduced into the input end 5 of the waveguide region in a manner such as fiber coupling. Measuring, by the optical power meter, the power of the sensing output electromagnetic wave and the reference output electromagnetic wave of the sensing output terminal 6 and the reference output terminal 7, thereby calculating a relative intensity of the electromagnetic wave, and sensing a ratio of the power of the output electromagnetic wave to the power of the reference output electromagnetic wave, And changing the applied voltage modulation surface plasma resonance condition to measure the relationship between the relative intensity of the electromagnetic wave and the applied voltage. When white light is used as the wave source of the input electromagnetic wave, the characteristic curve of the surface plasma resonance absorption is shown in the third figure, which is the relationship between the relative intensity of the electromagnetic wave and the wavelength of the electromagnetic wave, and the partial energy of the strong wave of 10 1273231, so the relative intensity has - The minimum value appears to correspond to the surface plasma resonance wavelength Up. Table of λρ+ , sensing === Table * The plasma resonance condition is also changed so that the above wave = 3 =. If the laser is larger than the table _ resonance jin and the length U ° as the wave source of the input electromagnetic wave, such as the second wave of the figure, the electromagnetic wave measured by the wheel is relatively strong - and Ϊ +) will be applied with the applied voltage The change of va, the change of the Japanese and the 0, the rate of change is determined by the dielectric constant of the test object of the object to be tested. The return magnetic wave is relatively strong with the change of the applied voltage V a ^ , n , The absolute value of the slope of the pool is linear with the concentration:::concentration 2>concentration 1; as shown in the fifth figure, the regression is: the relationship between the absolute value of the = and the concentration, where the value of There is a significant positive correlation between the two, according to which, the borrower, straight, the slope accurately measures the concentration of biochemical substances in the analyte. The use of the second right remedy will further improve the surface of the test: the ability of noise. Therefore, the volume of the light of the present invention is small. The measuring device has the advantages of high precision, strong noise, and reduced cost of the egg. Taking the serum protein of the human body as a phase, the hair of the hair has been stalked. 1273231 The surface plasma resonance detecting device can be used to detect the concentration of drugs for treating heart disease. The sputum-species should be modulated by surface plasma resonance. When detecting the method degree, the _ characteristics of the product and the twilight effect of the strong state are added to the condition of the Thunder feeding main ^ (4) ce _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Plus: =, the light intensity can be as shown in the fourth figure: The wavelength of the round light can be different depending on the type of material to be tested. The sensitivity of the inspection position will be selected. The most prevailing grade wire ^, selected to its corresponding regression line 3 degrees; the relationship between the external t voltage change, as shown in the fifth figure; (3) use, ::: and the relationship between the wave as the fourth figure The linear slope of the obtained return line; the ^ or standard material) is measured, and the concentration (or material property) of the calibration resource in the interpolated manner is calculated. Sexuality). Hunting determines the concentration of the analyte (or the material in general) 'The invention is fully compliant, and industrially useful. In the case of Xinling and Hetai _ electro-optic light measurement of surface plasma resonance effect, it can avoid the use of ς The cost of the bureau and the limited spectrum analyzer in the field of use, while breaking through the sensitivity of the traditional two-measure system, can be combined with the use of lock-in amplifiers, step-by-step detection accuracy, stability and filtering In terms of the utilization on the industry 1273231, the products derived from the present invention can fully satisfy the needs of the current market. The present invention has been disclosed in the preferred embodiments above, but is familiar to those skilled in the art. It is to be understood that the present invention is not intended to limit the scope of the present invention. It should be noted that variations and substitutions equivalent to the embodiment are intended to be Therefore, the scope of the present invention is defined by the scope of the following claims. [First Description of the Drawings] The first drawing is an integrated optical surface of the present invention. A schematic diagram of a slurry resonance detecting device. The second drawing is a cross-section of the sensing waveguide region perpendicular to the waveguide direction in an integrated optical surface plasma resonance detecting device of the present invention, which is not intended to be viewed in the negative γ_ direction. Φ The third figure is the relationship between the relative intensity of electromagnetic waves and the wavelength of electromagnetic waves. The fourth figure is the regression line of the relative intensity of electromagnetic waves with the applied voltage. The fifth figure is the relationship between the absolute value of the slope of the regression line and the concentration. [Main component symbol description] 1 substrate
c S 13 1273231 2基板的切面 3感測波導區 4参考波導區 5輸入端 6感測輸出端 7爹考輸出端 8波導區的分岔處 9金屬層 1 0隔離層 1 1待測物 1 2電極端 1 3電極端 1 4電極輸入端 1 5電極輸入端 1 6絕緣層c S 13 1273231 2 section of the substrate 3 sensing waveguide region 4 reference waveguide region 5 input terminal 6 sensing output terminal 7 reference output terminal 8 waveguide region of the junction 9 metal layer 10 isolation layer 1 1 object 1 2 electrode end 1 3 electrode end 1 4 electrode input end 1 5 electrode input end 1 6 insulation layer