1342389 玖、發明說明： 【發明所屬之技術領域】 本發明是有關於一種奈米技術，且特別是有關於一種使用奈米技術的 生物感測器。 【先前技術】 現有光纖及波導感知器的原理是雷射光在去彼覆材料光纖 或波導元件中，經由全反射在波導内傳播並在反射介面上產生瞬逝波 (evanacent wave，EW)。在垂直反射介面距離小於瞬逝波電場有效範圍内（約 為入射光波波長；〇,因折射率的變化(Δη)或厚度改變（Δ(1)造成反射光強 度的改變而有效即時的觀察及量測分子間交互作用，進而求得分子間動力 學參數(例如結合常數L及解離常數L等），它的優點是不需要經由沖洗手 續而此即時觀測在瞬逝波電場有效範圍内生物分子（包括蛋白質、dna或化 學分子等）的交互侧，如先將已知之蛋自質岐在波導表面並和相對應 之被測試蛋白f產生交互作用’並麵逝波有效距離細_存在瞬逝波 電场’而S1蛋白質分子交互剌產生的折射率變化及厚度變化㈣量測反 射光強度大小可即時量測蛋白質之間的動力學常數，現有_逝波感知器 (隱escent Wave sensor )中多以光纖或平面波導為元件偵測靈敏度相 對較低’無法直接朗在臨床診斷上，再加上瞬逝波電場的有效翻較長 (、勺500nm)如心即時價測少數生物分子並能有效隔離其他分子的干擾現 有的方糾無法達到。如結合表面電聚波⑶rface pi咖a spw) 杨料面上被激發可在距離金屬介面更㈣有效距離（約測⑽）内探測 刀子的乂互作用’而可即時量測其動力學參數。然而的產生亦是藉由 全反射產生瞬逝波再由瞬逝波激發spw因此卿發生的條件較瞬逝波^趨 厭格並在_較電較短的有效距_產生局部電場（1QCaUzed el=_gnetlc fleld)而能即時觀察少數分子的交互作用。然而卿感 知益、制折醉和厚度的變化其_綠度仍然無法達到臨床醫學的要 6 1342389 求本申请發明專利主要是在結合光纖或波導元件產生ew並在金屬（金、 銀）奈米粒子表面上產生卿，同時在金或銀奈米粒子表面吸附（label ing) 染料刀子(dye molecule)(包括螢光及拉曼(Raman)活性染料分子）可藉由 金屬奈米粒子表面上SPW激發染料分子而產生螢光或表面增強拉曼散射 (surface enhanced Raman scattering, SERS)光譜信號。同時因金屬奈 米粒子的存在造成瞬逝波電場在金屬奈米粒子附近更形成增強的局部電 %，而有效的增加產生螢光或SERS的信號的效率大幅提高偵測靈敏度並同 時保留即時量測分子間交互作用的能力，它可應用在臨床醫學上或其他更 低/辰度的生物分子、化學分子間交互作用的即時量測。除此之外本申請發 明專利方法及裝置亦有潛能進行單一分子（single m〇lecule)的交互作用即 時量測。如以光纖為例，瞬逝波在全反射的條件下可穿透反射介面的深度 dp可表示為： dp=--- ⑴ 2m2(nrd2 sin2 (9-1)-^ 其中’ λ為入射光波長，0為產生全反射的入射角度’ Πι、以分別為在 岔介質（核心光纖fiber core)和疏介質（反應介質reactive medium )的 折射係數’ nrel=Ill/n：；(如第一圖）。 本申请發明中’當所使用的波導為多模光纖mode optical fiber)它可擁有多個入射角(9之雷射光在光纖中傳播，當核心光纖表面附著 生物分子，例如抗體’然後再將已經附著螢光染料分子之抗原和待測之抗 原（target antigen) —併注入到反應腔中而在核心光纖表面形成競爭型 之複合試劑（competitive biological assay，CBA)，如第二圖（a)，利用 瞬逝波激發螢光抗原的機制’而有效的即時量測螢光信號變化，當待測的 抗原濃度愈高，則產生的螢光信號越弱，如第二圖（b) 螢光信號可由光纖的尾端亦可在光纖的雷射光輸入端量測螢光信號， 除此之外’生物分子間亦可在核心光纖表面形成三明治型複合試劑 7 1342389 (sandwitch biological assay, SBA)即〈抗體I待測之抗原I附著螢光分 子之抗體〉，經由瞬逝波激發螢光信號。它和競爭型不同，待測的抗原濃度 越高所產生的勞光信號越大，如第三圖。 為了量測生物分子之間的交互作用及其動力學參數(Ka、Kd)，反應式可 寫成： [A]+[B] t; [Α]·[Β] (2)1342389 发明, INSTRUCTION DESCRIPTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a nanotechnology, and more particularly to a biosensor using nanotechnology. [Prior Art] The principle of the existing optical fiber and waveguide perceptron is that the laser light propagates in the waveguide through total reflection in the optical fiber or waveguide element of the material to be coated and generates an evanacent wave (EW) on the reflection interface. In the effective range of the vertical reflection interface distance is less than the effective range of the evanescent wave electric field (about the wavelength of the incident light wave; 〇, due to the change of the refractive index (Δη) or the thickness change (Δ(1) causes the change of the reflected light intensity to be effective and immediate observation Measuring the interaction between molecules, and then obtaining the intermolecular kinetic parameters (such as the binding constant L and the dissociation constant L, etc.), it has the advantage that it is not necessary to observe the biomolecule in the effective range of the evanescent wave electric field through the flushing procedure. The interaction side of the protein (including protein, DNA or chemical molecule, etc.), such as the known egg self-massing on the surface of the waveguide and interacting with the corresponding protein f to be tested, and the effective distance of the surface wave is fine _ existence elapsed The refractive field change and thickness variation produced by the wave electric field' and the interaction of the S1 protein molecules (4) Measure the intensity of the reflected light to instantly measure the kinetic constant between proteins, which is currently used in the hidden light wave sensor. Most of the fiber-optic or planar waveguides have relatively low sensitivity for component detection, which cannot be directly diagnosed in clinical diagnosis, and the effective turn-over of the evanescent wave field is longer (the spoon is 500 nm). The heart immediately measures the number of biomolecules and can effectively isolate the interference of other molecules. Existing methods can not be achieved. For example, combined with surface electroconvergence (3) rface pi a spw), the surface of the yang is excited to be more effective distance (4) from the metal interface ( In the test (10)), the 乂 interaction of the knives is detected and the kinetic parameters can be measured immediately. However, the generation is also caused by the total reflection, and the evanescent wave is excited by the evanescent wave. Waves tend to be versatile and produce a local electric field (1QCaUzed el=_gnetlc fleld) at a shorter effective distance than _, and can instantly observe the interaction of a few molecules. However, the perception of benefit, the change of drunk and the thickness of _ The greenness still cannot reach the clinical medicine. 6 1342389 The invention patent of the present invention mainly produces ew in combination with optical fiber or waveguide elements and produces qing on the surface of metal (gold, silver) nanoparticles, while in gold or silver nanoparticles. Label ing dye molecules (including fluorescent and Raman reactive dye molecules) can generate fluorescence or a table by exciting the dye molecules on the surface of the metal nanoparticles. Enhanced surface-enhanced Raman scattering (SERS) spectral signals. At the same time, due to the presence of metal nanoparticles, the evanescent wave electric field forms an enhanced local electric % near the metal nanoparticles, and effectively increases the fluorescence or The efficiency of the SERS signal greatly increases the detection sensitivity while retaining the ability to measure intramolecular interactions in real time. It can be applied to clinical medicine or other lower/instantaneous real-time measurements of interactions between biomolecules and chemical molecules. In addition, the method and apparatus for inventing the patent of the present application also have the potential to perform single-molecular interaction (Single m〇lecule) interaction real-time measurement. For example, in the case of an optical fiber, the depth dp of the evanescent wave that can penetrate the reflective interface under total reflection can be expressed as: dp=--- (1) 2m2(nrd2 sin2 (9-1)-^ where λ is the incident light The wavelength, 0 is the incident angle of total reflection ' Π ι , to the refractive index of the 岔 medium (core fiber core) and the reductive medium (reactive medium) ' nrel = Ill / n:; (as shown in the first figure In the invention of the present application, 'when the waveguide used is a mode optical fiber, it can have multiple incident angles (9 laser light propagates in the optical fiber, and when the core fiber surface is attached with biomolecules, such as antibodies' then The antigen and the target antigen to which the fluorescent dye molecule has been attached are injected into the reaction chamber to form a competitive biological assay (CBA) on the surface of the core fiber, as shown in the second figure (a) ), using the mechanism of the evanescent wave to excite the fluorescent antigen, and effectively measuring the change of the fluorescent signal, when the concentration of the antigen to be tested is higher, the fluorescent signal generated is weaker, as shown in the second figure (b) The optical signal can be the tail of the fiber The fluorescent signal can also be measured at the laser light input end of the fiber. In addition, a biosynthesis can form a sandwich composite reagent 7 1342389 (sandwitch biological assay, SBA) on the surface of the core fiber. The antigen I attaches to the antibody of the fluorescent molecule>, and the fluorescent signal is excited by the evanescent wave. Unlike the competitive type, the higher the concentration of the antigen to be measured, the larger the light signal generated, as shown in the third figure. The interaction between molecules and their kinetic parameters (Ka, Kd), the reaction formula can be written as: [A]+[B] t; [Α]·[Β] (2)
其中 44 dt 為結合生物分子(biomolecules complex)的反應速率，c為 待測生物分子的濃度，Ka、Kd分別為結合常數和解離常數，第四圖為生物分 子IgG和anti-IgG間的交互作用，利用本方法及多模光纖(直徑為1〇〇〇/^ 在不同濃度下即時偵測的螢光反應和Ka、Kd動力學常數。 【發明内容】 為了更進一步提高偵測靈敏度同時仍然保有即時量測分子間交互作用 φ 及動力學常數的能力，本申請發明專利提出利用瞬逝波（EW)激發奈米金 屬（如金或銀）粒子表面並產生表面電漿波（spff)同時再由spw激發附著 在金屬奈米粒子表面之螢光染料分子產生螢光信號以增強螢光強度（如第 五圖）。由於金屬奈米粒子在瞬逝波有效範圍内並在金屬奈米粒子附近產生 瞬逝波電場的局部增強效果而增縣面電漿波的電場強度，進而大幅提高 藉由表面脑發螢光紐強度以達到提高制錄度的目的。以一個 15nm為直徑的金屬奈米粒子，它可附著⑽_2⑻個螢光染料分子並由多 換光纖所產生多個人射角可在反射介面上產生全反射，而滿足在金屬奈米 粒子表面產絲面錢波共振的條件，因此可在整個錢奈米粒子表面激 1342389 發SPW，由於SPW電場的有效距離約為2〇〇nm，較瞬逝波電場更為局部化 (localization) ’當螢光染料分子附著在金屬奈米粒子表面並且在奈米粒 子表面SPW的電場有效範圍内（2〇〇围），它可被SPW激發而產生螢光信號， 或稱之為表面電漿波偶合之激發螢光（surface piasma COUpied fluorescence，SPCF)。因SPCF具有特定的方向性，其傳播角度由SPCF的 頻率（temporal frequency)c〇f&金屬奈米粒子表面上SPW的波數(wave number)ks來決定《同時SPCF的螢光強度較傳統激發螢光強度高1〇倍以上， 再加上金屬奈米粒子可局部增強瞬逝波電場的特性，而大幅增強金屬奈米 粒子表面SPW電場強度而大幅提高SPCF的信號強度，除此之外更同時激發 金屬奈米粒子表面10()-20()螢光染料分子而制螢統號放大的效果。本 申清發明專繼合多模光纖、金屬奈米粒子不僅增強瞬逝波局部電場以及 金屬奈米粒子表面SPff電場強度，以及同時更可激發整個金屬奈米粒子表 面上的螢光騎分子可大幅增崎光產生效率以及魏錢強度達到大幅 提昇偵測靈敏度的目的。除此之外，因瞬如皮Ew和表面電衆波sptf電場的 局部性’本帽發蚊可即時量測生物分子間的交互侧，而無需如傳統 方法中例如酵素聯接免疫吸附分析法㈤SA)需要繁複的沖洗手續以排除 其它可能產生交互作用的生物分子的影響以達到即時量測的目的。 【實施方式】 第五圖是本申4發明專利高靈敏度分子交互個即時量測方法及裝置 中SPCF光纖感知器的示意圖，雷射光⑽）透觸微物鏡（ι〇)滿足光 纖數值孔徑㈤eri(：al Aperture，NA)偶合條件而有效將φ射光輸入到 除去披覆材料的多模光纖（2Q)中，雷射光在核心光纖表面產生全反射並 同時產生瞬逝波i纖表面上可事先附著抗體（3Q)，再和反應介質中待測 之h原（4G)和在金或銀奈綠子（5Q)表面上已附著螢光分子（7〇)之 抗體⑽）相結合，在域表面上，形成三〈抗體㈤丨抗原㈤丨 9 1342389 附著登光染料分子之抗體（60)之金奈米粒子⑽）〉（如第五圖），其中金 屬奈米粒子表面已事先完成崎螢光染料分子和抗體的手續，由入射雷射 光在核心光絲®產蝴較，再紐私光齡面上已形紅三明治複 合試劑（SBA)之金奈辣子的表面產生的表面電毅朗時激發螢光染料 分子而產生螢光信號SPCF。螢光信號可利用第五圖中透過光學濾光裝置 (90)和光碰裝置（1〇〇)在雷射光輸出端即時測量榮光信號而獲得抗原、 机體之間的交互作用和動力學參數(Ka、Kd)亦可在光纖側面（如第六圖）即 時里測螢光#號。本申請發明專利中所使用的螢光染料分子(例如FITC)如 改為拉曼活性（Raman active)染料分子（例如Cy3. 5等）可經由光散射 Chght scattering：)激發表面增強拉曼散射信號（SERS)信號，並透過分 光光譜儀可即時量測SERS光譜以達到同時定性和定量即時測量生物分子或 化學分子之間交互作用的目的。 螢光仏號亦可利用反射式凹面光柵(c〇ncave reflecti〇n gratjng)(如 第七圖）量取螢光信號或SERS信號，除此之外，本申請發明專利亦可發展 成為多通道之SPCF光纖感知裝置(如第八圖）。在第八圖中，不同多模核心 光纖（】】0)表面可附著不相同之三明治複合試劑之金屬奈米粒子（5〇)，在反 應腔内（140)使得SPCF螢光或SERS信號可藉由不同中心波長之光學濾光裝 • 置（90)配合二維光偵測裝置（130)例如CCD等在多通道光纖的尾端或在光 纖的側端即時偵測螢光信號以達到同時即時量測不同生物分子間交互作用 及其動力學參數的目的《它亦可利用反射式四面光柵或分光光譜儀進行 SERS信號光譜分析的即時量測以達到可鑑別生物分子的定量、定性分析和 分子間交互作用之動力學參數的即時測量。 同理本申請發明專利亦可將多模光纖以平面多模波導（21 〇)(planar wave guide)取代(如第九圖），平面多模波導表面經處理後吸附生物分子如 抗體、蛋白質等和在金屬奈米粒子表面已附著螢光染料分子或拉曼活性染 料分子之不同生物分子形成三明治型（22〇)、（230)或競爭型之生物複合 1342389 6式劑（assay)而將由平面多模波導（210)傳播之雷射光在反射介面產生全 反射並同時產生瞬逝波再經由瞬逝波電場的局部化特性和金奈米粒子可造 成瞬逝波的電場局部化和增強化的結果激發金奈米粒子表面上的表面電漿 波進而激發SPCF之螢光信號和sers信號並在平面多模波導側面利用光學 濾光裝置(90)和二維光偵檢裝置（130)即時偵測螢光或SERS信號建構成為 一維平面多模波導微陣列（m i cro_array )生物分子或化學分子交互作用和 動力學參數即時測量之裝置及量測方法。 【圖式簡單說明】 第一圖瞬逝波產生示意圖。 第二圖競爭型生物複合試劑及螢光偵測示意圖。 第三圖三明治型生物複合試劑及螢光偵測示意圖。 第四圖生物分子IgG-anti IgG利用多模光纖之螢光反應及動力學常 數實驗結果。 第五圖「SPCF光纖感知器光學架構」示意圖。 第六圖SPCF螢光信號偵測光學架構示意圖。 第七圖SPCF螢光信號和SERS信號偵測光學架構示意圖。 第八圖多通道多模光纖「SPCF光纖感知器光學架構」示音圖。 第九圖二維平面多模波導微陣列裝置示意圖。 【主要元件符號說明】 (10)顯微物鏡 (20)除去彼覆材料的多模光纖 (30)抗體 (40)待測試抗原 (42)非待測試抗原 (45)附著螢光分子之待測試抗原 (50)金奈米粒子 (60)附著螢光分子之抗體 1342389 (70)螢光染料分子 (80)附著螢光染料分子抗體之金奈米粒子 (90)光學濾光裝置 (100)光偵檢裝置 (110)多模核心光纖 (120)孔徑 (130)二維光偵儉裝置 (140)反應腔 (150)反射式凹面光柵 (200)激發雷射光源 # (210)平面多模波導 (220)抗體（一）和在金奈米粒子表面已附著螢光染料 分子（一）之抗體（一）和抗原（一）形成之三明治型複 合試劑 (230)抗體（二）和在金奈米粒子表面已附著螢光染料 分子（二）之抗體（二）和抗原（二）形成之三明治型複 合試劑Among them, 44 dt is the reaction rate of biomolecules complex, c is the concentration of biomolecules to be tested, Ka and Kd are binding constants and dissociation constants respectively, and the fourth figure is the interaction between biomolecule IgG and anti-IgG. Using this method and multimode fiber (diameter 1 〇〇〇 / ^ fluorescence reaction and Ka, Kd kinetic constant detected at different concentrations) [Invention content] In order to further improve the detection sensitivity while still retaining The ability to measure the intermolecular interaction φ and the kinetic constant in real time, the invention patent of the present application proposes to use an evanescent wave (EW) to excite the surface of a nano metal (such as gold or silver) particles and generate a surface plasma wave (spff) while The fluorescent dye molecules attached to the surface of the metal nanoparticles are excited by spw to generate a fluorescent signal to enhance the fluorescence intensity (as shown in the fifth figure). Since the metal nanoparticles are in the effective range of the evanescent wave and in the vicinity of the metal nanoparticles Producing a local enhancement effect of the evanescent wave electric field and increasing the electric field strength of the plasma wave of the county surface, thereby greatly increasing the intensity of the surface fluorescing light to achieve the purpose of improving the recording degree. A metal nanoparticle with a diameter of 15 nm, which can attach (10)_2(8) fluorescent dye molecules and generate multiple reflection angles from multiple optical fibers to produce total reflection on the reflective interface, and to satisfy the surface of the metal nanoparticle. The condition of the surface wave resonance, so that the surface of the entire Chennai particle can be excited by 1342389 SPW. Since the effective distance of the SPW electric field is about 2〇〇nm, it is more localized than the evanescent wave electric field. The dye molecules are attached to the surface of the metal nanoparticles and within the effective range of the electric field of the SPW surface of the nanoparticle (2〇〇), which can be excited by the SPW to generate a fluorescent signal, or an excitation of the surface plasma wave coupling. Surface piasma COUpied fluorescence (SPCF). Because SPCF has a specific directionality, its propagation angle is determined by the SPCF frequency (c temporal) c〇f & the wave number ks of the SPW on the surface of the metal nanoparticles. Decided that "the fluorescence intensity of SPCF is more than 1〇 higher than the traditional excitation fluorescence intensity, and the metal nanoparticle can locally enhance the characteristics of the evanescent wave electric field, and greatly enhance the metal naphthalene. The SPW electric field intensity on the surface of the particle greatly increases the signal intensity of the SPCF, and in addition, it simultaneously excites the surface of the metal nanoparticle by 10()-20() fluorescent dye molecules to produce a fluorescing effect. The multi-mode fiber and the metal nanoparticle not only enhance the local electric field of the evanescent wave and the SPff electric field intensity of the surface of the metal nanoparticle, but also stimulate the fluorescent rider on the surface of the entire metal nanoparticle to greatly increase the light generation. The efficiency and the strength of the Wei money have greatly improved the detection sensitivity. In addition, due to the locality of the skin Ew and the surface electric wave sptf electric field, the cap hair mosquito can instantly measure the interaction side between biomolecules. There is no need for traditional methods such as enzyme-linked immunosorbent assay (V) SA) to require complicated washing procedures to eliminate the effects of other biomolecules that may interact to achieve immediate measurement. [Embodiment] The fifth figure is a schematic diagram of the SPCF fiber optic sensor in the high-sensitivity molecular interaction real-time measurement method and device of the present invention. The laser light (10) is transparent to the optical objective lens (5) eri ( :al Aperture, NA) coupling condition to effectively input φ light into the multimode fiber (2Q) with the covering material removed, the laser light generates total reflection on the surface of the core fiber and simultaneously generates an evanescent wave. The antibody (3Q) is combined with the h-genogen (4G) to be tested in the reaction medium and the antibody (10) to which the fluorescent molecule (7〇) is attached on the surface of the gold or silver navel (5Q), on the surface of the domain. On the top, the formation of three <antibody (five) antimony antigen (5) 丨 9 1342389 attached to the dyeing agent molecule (60) of the gold nanoparticles (10))> (as shown in the fifth figure), wherein the surface of the metal nanoparticles has been completed in advance The procedures for dye molecules and antibodies are generated by the incident laser light at the core filament yarn, and the surface generated by the surface of the red-sandwich composite reagent (SBA) of Chennai Spicy. Fluorescent dye molecules Fluorescent signal SPCF. The fluorescence signal can be obtained by instantaneously measuring the glory signal at the laser light output through the optical filter device (90) and the light-collecting device (1〇〇) in the fifth figure to obtain the interaction between the antigen and the body and the kinetic parameters ( Ka, Kd) can also measure the fluorescent ## on the side of the fiber (as shown in the sixth figure). Fluorescent dye molecules (e.g., FITC) used in the invention of the present application, such as Raman active dye molecules (e.g., Cy3. 5, etc.), can excite surface-enhanced Raman scattering signals via light scattering: The (SERS) signal, and the SERS spectrum can be measured instantaneously by spectroscopic spectrometer to achieve simultaneous qualitative and quantitative measurement of the interaction between biomolecules or chemical molecules. The fluorescent nickname can also use a reflective concave grating (c〇ncave reflecti〇n gratjng) (as shown in the seventh figure) to measure the fluorescent signal or the SERS signal. In addition, the invention patent of the present application can also be developed into multiple channels. SPCF fiber sensing device (as shown in Figure 8). In the eighth figure, the different multimode core fibers (0) can be attached with different metal composite nanoparticles (5〇) of the sandwich composite reagent, and the SPCF fluorescence or SERS signal can be made in the reaction chamber (140). The optical filter device (90) with different center wavelengths is used to cooperate with a two-dimensional photodetecting device (130) such as a CCD to detect the fluorescent signal at the end of the multi-channel optical fiber or at the side end of the optical fiber. The purpose of measuring the interaction between different biomolecules and its kinetic parameters in real time. It can also perform real-time measurement of SERS signal spectral analysis by means of reflective four-sided grating or spectroscopic spectrometer to achieve quantitative, qualitative analysis and molecular identification of biomolecules. Instant measurement of the kinetic parameters of the interaction. Similarly, the invention patent of the present application can also replace the multimode optical fiber with a planar multimode waveguide (such as the ninth diagram), and the surface of the planar multimode waveguide is treated to adsorb biomolecules such as antibodies, proteins, etc. Forming a sandwich (22〇), (230) or competitive biocomposite 1342389 6 an agent with a different biomolecule to which a fluorescent dye molecule or a Raman-active dye molecule has been attached to the surface of the metal nanoparticle. The multi-mode waveguide (210) propagates laser light to generate total reflection at the reflective interface and simultaneously generates an evanescent wave and then localizes the electric field via the evanescent wave and the gold nanoparticle can cause localization and enhancement of the electric field of the evanescent wave. As a result, the surface plasma waves on the surface of the gold nanoparticles are excited to excite the SPCF fluorescence signal and the sers signal, and the optical filter device (90) and the two-dimensional optical detection device (130) are instantly detected on the side of the planar multimode waveguide. Fluorescence or SERS signals are constructed as a device and measurement method for real-time measurement of biomolecular or chemical molecular interactions and kinetic parameters of a one-dimensional planar multimode waveguide microarray (mi cro_array). [Simple description of the diagram] The first diagram shows the evanescent wave generation. The second figure is a competitive bioreagent and a schematic diagram of fluorescence detection. The third figure is a sandwich type bio-reagent and a schematic diagram of fluorescence detection. The fourth figure biomolecule IgG-anti IgG utilizes the fluorescence reaction of the multimode fiber and the results of the kinetic constant experiment. Figure 5 is a schematic diagram of the optical structure of the SPCF fiber optic sensor. Figure 6 is a schematic diagram of the SPCF fluorescent signal detection optical architecture. The seventh diagram shows the optical architecture of the SPCF fluorescent signal and the SERS signal detection. Figure 8 shows the multi-channel multimode fiber "SPCF fiber optic sensor optical architecture" sound map. Figure 9 is a schematic diagram of a two-dimensional planar multimode waveguide microarray device. [Explanation of main component symbols] (10) Microscope objective (20) Removal of multi-mode fiber (30) antibody of the material (40) Anti-test antigen (42) Non-test antigen (45) Attached to the fluorescent molecule to be tested Antigen (50) gold nanoparticles (60) antibody to fluorescent molecule 1342389 (70) fluorescent dye molecule (80) attached to fluorescent dye molecule antibody gold nanoparticle (90) optical filter device (100) light Detection device (110) multimode core fiber (120) aperture (130) two-dimensional optical detection device (140) reaction cavity (150) reflective concave grating (200) excitation laser source # (210) planar multimode waveguide (220) Antibody (I) and a sandwich-type complex reagent (230) antibody (II) formed by attaching a fluorescent dye molecule (I) to the surface of the gold nanoparticles (I) and the antigen (I) and in Chennai a sandwich-type composite reagent formed by attaching a fluorescent dye molecule (2) to an antibody (2) and an antigen (2) on the surface of the rice particle