200842357 九、發明說明： 【發明所屬之技術領域】 本發明係關於一種生醫感測器，詳言之，係關於一種應 用於免疫球蛋白E檢測之彎曲平板波生醫感測器；免疫球 蛋白E是過敏性疾病的主要判定標的，所以本發明係關於 一種過敏感測晶片之研發。 【先前技術】 因為人類對於健康問題的重視與需求日益增加所以導致 生物科技與生醫檢測產業的快速發展，其中又以可以結合 半導體1C產業科技的生物晶片（BioChips)或生醫微機電系 統（BioMEMS)最引人著目。人體的免疫系統具有保護身體 免於受病毒、細菌、癌細胞及微生物侵害的功能，但如果 免疫糸統過度反應’則會造成過敏症、休克，甚至致死。 其中日盈嚴重的過敏性疾病之檢測，主要判定標的是病患 血清中免疫球蛋白E(IgE)之濃度值。習知血液試藥檢驗法 用以檢驗血液中之免疫球蛋白E濃度，不但耗時而且費用 很高，而準確度卻只有60%〜70%左右而已，且檢測時間冗 長。而市場上雖已有一些高準確度及高靈敏度之過敏檢測 儀器（allergy test kits)，但其價格相當高、須耗費較多的 測試液且不易微小化，故需較高之製造成本。因此，有必 要提供一種創新且具進步性的免疫球蛋白E檢測技術與元 件，以解決上述問題。 η 聲波感測器非常適合應用於質量之感測，最早出現的產 品是剪應力振盪器（TSM Resonat〇r)與表面聲波感測器 120400.doc 200842357 (SAW sensor)，近十年來由於微機電系統（MEMS)技術之進 步’也帶動其他各種聲波感測器的發展（例如Fpw sensor)。到目前為止，有關聲波感測器最詳細深入的探 討’可參考Balllantine、White及Richard等人之著作與文 獻[參考先前技術列表編號1-5之文獻]，其中針對各種聲波 感測器的原理、構造以及應用有相當完整的介紹。 在液體特性的量測方面，尤其是黏滯性與質量密度，過 去的研究主要是利用剪力水平板波（Shear H〇riz()ntal_ Acoustic Plate Mode，SH-APM)、表面聲波與彎曲平板波這 二種感測器’其共同點都是應用交指式傳感器（IDT)，但 疋彼此間仍有很大的差異。剪力水平板波感測器是利用剪 力水平板波，其波動位移向量與板面平行與波傳方向垂 直，因此若有液體附於感測器表面（也就是波傳經過的區 域）’液體的黏滯性會對感測器表面產生剪應力，進而改 變剪力水平板波的波速與衰減，是一個很好的黏滯性感測 器[參考先前技術列表編號6-9之文獻];Martin等人[參考先 前技術列表編號10之文獻]則使用ST-CUT石英晶片，製作 出剪力水平板波感測器可以感測到流體的黏滯性與密度。 在表面聲波感測器方面，Nomura等人[參考先前技術列 表編號11-14之文獻]與Leidl等人[參考先前技術列表編號 15之文獻]以36〇XY-cut之LiNb03壓電晶體為底材，可以同 時產生SH-type之表面波（或稱為Love_Wave type表面波）與 Rayleigh-type之表面波，並以實驗與理論說明前者可量測 黏滞性而後者可量測密度，這主要是由KRayleigh_type之 120400.doc 200842357 表面波具有表面的位移向量的關係。 在彎曲平板波感測器方面，主要是由White等人[參考先 前技術列表編號16-22之文獻]於U.C.Berkeley發展而成， 並且將其應用於化學、生物、氣體、力量等的感測器，其 中，Martin與White等人[參考先前技術列表編號22之文獻] 更將彎曲平板波感測器應用於液體之黏滯性與密度的量 測，顯示待測液體的黏滯性與密度分別對應到彎曲平板波 的衰減與相位速度。 上述四種聲波感測器，以FPW元件具有最低的操作頻率 以及最高的質量靈敏度等優點。而傳統的彎曲平板波元件 缺少底電極[參考先前技術列表編號23-24之文獻]使其穩定 性與訊號比（S/N)較差，且選擇彎曲平板波元件之壓電材 料時，需注意該材料是否具有高機電耦合係數、與基板之 黏附性佳、低聲速（低操作頻率）、環境抵抗性強、製程容 易並且與積體電路製程相容等特性。此外，相關研究指出 胱胺酸-戊二酸（Cystamine-Glutaraldehyde)固定抗體，其具 有良好的吸附率且於再現性明顯比傳統的吸附方法為佳 [參考先前技術列表編號25之文獻]。 先前技術列表： 1. D. S. Ballantine et. al., Acoustic wave sensors · Theory, Design, and Physico-chemical Application，Academic Press，1997, New York. 2. Michael Thompson & David C. Stone, Surface-Launched Acoustic Wave Sensors, John Wiley & Sons. Inc. 1997, USA. 3. Μ· E. Motamedi and R.M. White，’’Acoustic sensor’’，in semiconductor 120400.doc 200842357 sensors，edited by S.M· Sze，John Wiely & Sons，Inc.，1994, New York. 4. R. M. Richard, "Acoustic sensors for physical, chemical and biochemical applications/11998 IEEE Internal Frequency Control Symposium, (1998) p.587-594. 5. M. J. Vellekoop, 11 Acoustic wave sensors and their technology^ 1997 Ultrasonics proceedings, (1997) p.7-14. 6. I. Esteban et. al.5 "Using a formal mathematics software for SH-APM sensor modeling，" Sensors and Actuators A，67,（1998) ρ·77-83·200842357 IX. Description of the invention: [Technical field of invention] The present invention relates to a biomedical sensor, in particular, to a curved flat wave biomedical sensor applied to immunoglobulin E detection; an immunoglobulin Protein E is the primary criterion for allergic diseases, so the present invention relates to the development of an oversensitive wafer. [Prior Art] Because of the increasing emphasis on human health and the increasing demand for biomedicine and biomedical testing, the biochips (BioChips) or biomedical MEMS (which can be combined with the technology of semiconductor 1C industry) BioMEMS) is the most eye-catching. The body's immune system protects the body from viruses, bacteria, cancer cells and microbes, but if the immune system overreacts, it can cause allergies, shock, and even death. Among them, the detection of allergic diseases with severe daily income is mainly determined by the concentration of immunoglobulin E (IgE) in the serum of the patient. The traditional blood test method is used to test the concentration of immunoglobulin E in blood, which is time-consuming and costly, but the accuracy is only about 60%~70%, and the detection time is long. Although there are some high-accuracy and high-sensitivity allergy test kits on the market, their prices are quite high, they require a lot of test liquid, and they are not easy to miniaturize, so higher manufacturing costs are required. Therefore, it is necessary to provide an innovative and progressive immunoglobulin E detection technology and components to solve the above problems. The η acoustic wave sensor is very suitable for mass sensing. The earliest products are the shear stress oscillator (TSM Resonat〇r) and the surface acoustic wave sensor 120400.doc 200842357 (SAW sensor). Advances in system (MEMS) technology have also led to the development of various other acoustic sensors (such as Fpw sensor). So far, the most detailed and in-depth discussion of sonic sensors can be found in the works and literature of Balllantine, White and Richard [refer to the literature of the prior art list number 1-5], which is the principle of various acoustic sensors. , construction and application have a fairly complete introduction. In the measurement of liquid properties, especially viscosity and mass density, the past research mainly used shear wave horizontal wave (Shear H〇riz () ntal_ Acoustic Plate Mode, SH-APM), surface acoustic wave and curved plate The two sensors of the wave's common point are the application of interdigital sensors (IDT), but there are still great differences between them. Shear horizontal plate wave sensor is a horizontal wave with shear force. The wave displacement vector is parallel to the plate surface and perpendicular to the wave direction. Therefore, if liquid is attached to the surface of the sensor (that is, the area through which the wave passes) The viscosity of the liquid will cause shear stress on the surface of the sensor, which will change the wave velocity and attenuation of the plate wave at the shear force level. It is a good viscous sensor [refer to the literature of the prior art list No. 6-9]; Martin et al. [refer to the literature of prior art list number 10] use ST-CUT quartz wafers to create a shear horizontal plate wave sensor that senses the viscosity and density of the fluid. In terms of surface acoustic wave sensors, Nomura et al. [refer to the literature of the prior art list number 11-14] and Leild et al. [refer to the literature of the prior art list number 15] based on a 36-inch XY-cut LiNb03 piezoelectric crystal. The material can simultaneously generate SH-type surface waves (or called Love_Wave type surface waves) and Rayleigh-type surface waves, and experimentally and theoretically demonstrate that the former can measure viscosity while the latter can measure density, which is mainly It is the relationship of the displacement vector of the surface wave by the KRayleigh_type 120400.doc 200842357 surface wave. In the case of curved flat wave sensors, it was developed mainly by UC Bererkeley by White et al. [refer to the literature of the prior art list No. 16-22] and applied to sensing of chemistry, biology, gas, force, etc. , in which Martin and White et al. [refer to the literature of the prior art list No. 22], the curved plate wave sensor is applied to the measurement of the viscosity and density of the liquid, showing the viscosity and density of the liquid to be tested. Corresponding to the attenuation and phase velocity of the curved plate wave, respectively. The above four acoustic sensors have the advantages of the lowest operating frequency and the highest quality sensitivity of the FPW components. However, the conventional curved plate wave element lacks the bottom electrode [refer to the literature of the prior art list No. 23-24], which makes the stability and the signal ratio (S/N) poor, and when selecting the piezoelectric material of the curved plate wave component, it is necessary to pay attention to Whether the material has high electromechanical coupling coefficient, good adhesion to the substrate, low sound speed (low operating frequency), strong environmental resistance, easy process and compatibility with the integrated circuit process. In addition, related studies indicate that Cystamine-Glutaraldehyde-immobilized antibodies have a good adsorption rate and are reproducible better than conventional adsorption methods [refer to the literature of Prior Art List No. 25]. List of prior art: 1. DS Ballantine et. al., Acoustic wave sensors · Theory, Design, and Physico-chemical Application, Academic Press, 1997, New York. 2. Michael Thompson & David C. Stone, Surface-Launched Acoustic Wave Sensors, John Wiley & Sons. Inc. 1997, USA. 3. Μ· E. Motamedi and RM White, ''Acoustic sensor'', in semiconductor 120400.doc 200842357 sensors,edited by SM· Sze,John Wiely & Sons, Inc., 1994, New York. 4. RM Richard, "Acoustic sensors for physical, chemical and biochemical applications/11998 IEEE Internal Frequency Control Symposium, (1998) p.587-594. 5. MJ Vellekoop, 11 Acoustic wave sensors and their technology^ 1997 Ultrasonics proceedings, (1997) p.7-14. 6. I. Esteban et. al.5 "Using a formal mathematics software for SH-APM sensor modeling," Sensors and Actuators A ,67,(1998) ρ·77-83·
7. M. G. Schweyer et. aL，”Acoustic plate mode sensor for aqueous mercury，’’ Sensor and Actuators B，35, (1996) p.170-175. 8. C. Dejous et. al. 5 ffShear horizontal acoustic plate mode(SH-APM) sensor for biological media，" Sensor and Actuators B，27, (1995) p452-456. 9. T. Sato et. al·，"Shear horizontal acoustic plate mode viscosity sensor，” Japan Journal of Applied physics 32 (5B), (1993) p.2392-2395. 10. S. J. Martine and A. J. Ricco, f,Sensing in liquids using acoustic plate mode devices/* MTech. Dig. Int. Electron. Dev. Meeting, (1987) p.290-293. 11. T. Nomura and T. Yasuda, "Measurement of acoustic properties of liquids using SH-type surface acoustic waves/* 1990 IEEE Ultrasonics symposium proceedings, (1990) ρ·307-310. 12. T. Nomura, M. Uchiyama，A. Saitoh, S. Furukawa，’’Measurement of acoustic properties of liquid using SH-and R-mode surface acoustic wave/1 1998 IEEE Internal Frequency Control Symposium, (1998) 120400.doc 200842357 p.645-651.13. S. Furukawa, K. Muzusaki, M. shintani，and T. Nomura， "Characteristics of leaky SAW propagating along liquid/LiNb03/sapphire structure and its application to liquid sensor,n 1997 IEEE Ultrasonics symposium proceedings, (1993) p.355-358. 14. S. Furukawa et. al.5 ,fCharacteristics of leaky surface acoustic wave propagation along liquid/layered-substrates and their application to liquid sensor ?ff 1993 IEEE Ultrasonics symposium proceedings, (1997) p.433-436.7. MG Schweyer et. aL, "Acoustic plate mode sensor for mixtures mercury,'' Sensor and Actuators B, 35, (1996) p. 170-175. 8. C. Dejous et. al. 5 ffShear horizontal acoustic plate mode (SH-APM) sensor for biological media," Sensor and Actuators B,27, (1995) p452-456. 9. T. Sato et. al·,"Shear horizontal acoustic plate mode viscosity sensor,” Japan Journal of Applied physics 32 (5B), (1993) p.2392-2395. 10. SJ Martine and AJ Ricco, f, Sensing in liquids using acoustic plate mode devices/* MTech. Dig. Int. Electron. Dev. Meeting, (1987 P.290-293. 11. T. Nomura and T. Yasuda, "Measurement of acoustic properties of liquids using SH-type surface acoustic waves/* 1990 IEEE Ultrasonics symposium proceedings, (1990) ρ·307-310. 12 T. Nomura, M. Uchiyama, A. Saitoh, S. Furukawa, ''Measurement of acoustic properties of liquid using SH-and R-mode surface acoustic wave/1 1998 IEEE Internal Frequency Control Symposium, (1998) 120400.doc 200842357 p.6 - ru ru ru 1993) p.355-358. 14. S. Furukawa et. al.5, fCharacteristics of leaky surface acoustic wave propagation along liquid/layered-substrates and their application to liquid sensor ?ff 1993 IEEE Ultrasonics symposium proceedings, (1997) p .433-436.
15. A. Leidl，I· Oberlack，U. Schaber，B. Mader, S. Drost，"surface acoustic wave device and applications in liquid sensing/* Smart Material and Structures 6(6)，（1997) p.680-388· 16. B. J. Costello, B. A. Martin, and R. M. White, "Ultrasonic plate waves for biochemical measurements,ff 1989 Ultrasonic symposium，（1989) p.977-981 · 17. S. W. Wenzel and R. M. White, MFlexural plate-wave gravimetric sensor，" sensor and Actuators A : Physical，22,（1990) ρ·700·703· 18. S. W. Wenzel and R. M. White, ftFlexural plate wave sensor: chemical vapor sensing and electrostrictive excitation，” 1989 Ultrasonic symposium, (1989) p.595-598. 19. S. W. Wenzel and R. M. White, "Analytic comparison of the sensitivities of bulk-wave，surface wave，and flexural plate-wave ultrasonic gravimetric sensors，" Appl. Phys. Lett· 54,（1988) ρ·1976-1978. 20. R. M. White et. al.? nplate-mode ultrasonic oscillator sensors/* IEEE Trans· Ultrasonic Ferroelec· Freq· contr·，34,（1987) ρ·162· 171. 120400.doc -9- 200842357 21. S. W. Wenzel and R. M White, ,fA multisensor employing an ultrasonic Lamb-wave oscillator，” IEEE Trans. Electron Device 35(6)，（1988) p.735-743. 22. B. A. Martin, S. W. Wenzel and R. M. White, ?fViscosity and density sensing with ultrasonic plate wave，’’ Sensors and Actuators A，22,（1990) p.704-708. 23. US 7,109,633 B2 Sep. 19, 2006 Marc S. Weinberg, Brian Cunningham et. al.15. A. Leidl, I. Oberlack, U. Schaber, B. Mader, S. Drost, "surface acoustic wave device and applications in liquid sensing/* Smart Material and Structures 6(6), (1997) p.680 -388· 16. BJ Costello, BA Martin, and RM White, "Ultrasonic plate waves for biochemical measurements, ff 1989 Ultrasonic symposium, (1989) p.977-981 · 17. SW Wenzel and RM White, MFlexural plate-wave Gravimetric sensor," sensor and Actuators A : Physical,22,(1990) ρ·700·703· 18. SW Wenzel and RM White, ftFlexural plate wave sensor: chemical vapor sensing and electrostrictive excitation,” 1989 Ultrasonic symposium, (1989 </ br> </ br> </ br> 1988) ρ·1976-1978. 20. RM White et. al.? nplate-mode ultrasonic oscillator sensors/* IEEE Trans· Ultrasonic Ferroelec· Fr Eq· contr·, 34, (1987) ρ·162· 171. 120400.doc -9- 200842357 21. SW Wenzel and R. M White, ,fA multisensor employing an ultrasonic Lamb-wave oscillator,” IEEE Trans. Electron Device 35(6), (1988) p.735-743. 22. BA Martin, SW Wenzel and RM White, ?fViscosity and density sensing with ultrasonic plate wave, '' Sensors and Actuators A, 22, (1990) p.704 -708. 23. US 7,109,633 B2 Sep. 19, 2006 Marc S. Weinberg, Brian Cunningham et. al.
24. Brian Cunningham，Marc Weinberg，Jane Pepper，Chris Clapp，Rob Bousquet，Brenda Hugh, Richard Kant, Chris Daly，Eric Hauser， "Design，fabrication and vapor characterization of a microfabricated flexural plate resonator sensor and application to integrated sensor arrays", Sensor abdActuator B, Vol. 73, 2001, pp. 112-123. 25. Shu-Fen Chou, Win-Lin Hsu, Jing-Min Hwang, Chien-Yuan Chen, ’’Development of an immunosensor for human ferritin, a nonspecific tumor marker，based on a quartz crystal microbalancef,5 Analytica ChimicaActa ? Vol. 453, 2002, pp.181-189. 【發明内容】 本發明之目的在於提供一種應用於免疫球蛋白E檢測之 彎曲平板波生醫感測器，其包括：一彎曲平板波元件及一 自我組裝單分子層結構。該彎曲平板波元件具有一矽基板 腔體。該自我組裝單分子層結構設置於該矽基板腔體之 中。該自我組裝單分子層結構包括：一基板、一自我組裝 單分子層及複數個免疫球蛋白E抗體。該基板具有一第一 120400.doc -10- 200842357 表面及一第二表面，該第二表面相對於該第一表面，該第 一表面設置於該腔體。該自我組裝單分子層具有複數個自 我、’且裝單刀子’ 4等自我組裝單分子間隔地沉積設置於該 基板之該第二表面。每一免疫球蛋白E抗體具有一頭端氨 基（amino)及一結合端，該頭端連接該自我組裝單分子乙醛 基（aldehyde)，該結合端用以與一免疫球蛋白E抗原作專一 性結合，*中，兩者之三度空間結構為彼此互補，具有相 當的親合力。24. Brian Cunningham, Marc Weinberg, Jane Pepper, Chris Clapp, Rob Bousquet, Brenda Hugh, Richard Kant, Chris Daly, Eric Hauser, "Design,fabrication and vapor characterization of a microfabricated flexural plate resonator sensor and application to integrated sensor arrays" ;, Sensor abdActuator B, Vol. 73, 2001, pp. 112-123. 25. Shu-Fen Chou, Win-Lin Hsu, Jing-Min Hwang, Chien-Yuan Chen, ''Development of an immunosensor for human ferritin, A nonspecific tumor marker, based on a quartz crystal microbalancef, 5 Analytica ChimicaActa ? Vol. 453, 2002, pp. 181-189. SUMMARY OF THE INVENTION It is an object of the present invention to provide a curved plate wave for immunoglobulin E detection. A biomedical sensor comprising: a curved plate wave element and a self-assembled monolayer structure. The curved plate wave element has a crucible substrate cavity. The self-assembled monolayer structure is disposed in the crucible substrate cavity. The self-assembled monolayer structure comprises: a substrate, a self-assembled monolayer, and a plurality of immunoglobulin E antibodies. The substrate has a first 120400.doc -10- 200842357 surface and a second surface opposite the first surface, the first surface being disposed in the cavity. The self-assembled monolayer has a plurality of self-assembled single molecules, such as a self-assembled single-plate 4, deposited on the second surface of the substrate at intervals. Each immunoglobulin E antibody has a head amino group and a binding end, and the head end is linked to the self-assembling monomolecular aldehyde group, and the binding end is used for specificity with an immunoglobulin E antigen. In combination, the three-dimensional structure of the two is complementary to each other and has considerable affinity.
本發明之該自我組裝單分子層可利用簡單之浸泡式沉積 薄膜技術製成，並且’該等自我_單分子自我組裝所形 成之結構具有最小熱動態、且可精確控制結構之長度、能 均勻的覆蓋基板、具有極高的生物相容性與在室溫下具有 較高之自我形成速率等特性。 _本發明之生醫感測ϋ之製作係結合奈米科技與微機電技 術故7L件具有較薄的厚度尺寸，所以其相速度會比大部 分的液體低（-般液體中聲波速度為9⑽〜· m/s)，造成 該生醫感測器在量測液體時因為傳遞波速較慢，所以不會 造成任何能量輻射到液體中。以，本發明之該生醫感測 益適合於量測液體，特別是生物感測及化學感測。 再者’因為該生醫感測器的厚度僅有幾個微米厚，且薄 :的質量密度非常低，故整個元件具有非常高的質量感測 靈敏度。因此，利用本發明之生醫感測器以檢驗血液中之 免疫球蛋白E濃度時，其具有高準確度、冑靈敏度、低操 作頻率、檢測時間短以及成本較低等優點。 120400.doc -11- 200842357 【實施方式】 參考圖1，其顯示本發明應用於免疫球蛋白E檢測之、彎曲 平板波（Flexural Plate Wave，FPW)生醫感測器。該生醫感 測器1包括一彎曲平板波元件10及一自我組裝單分子層結 構20 °該彎曲平板波元件1〇具有矽基板腔體11，該矽基板 腔體11具有一平面111。在本實施例中，該彎曲平板波元 件10係為一半導體元件，其元件佈局設計圖如1A(在此為 俯視圖）所示，該彎曲平板波元件丨〇主要的設計參數為交 指式傳感器（Interdigital transducer，IDT)電極間距、交指 式傳感器電極對數、交指式傳感器電極重疊長度與輸入/ 輸出埠（I/O)之延遲長度，並配合理論公式之推導而求出最 佳化彎曲平板波元件的中心頻率以及質量靈敏度等重要輸 出特性。 該彎曲平板波元件1 〇的製作流程如圖丨B至圖丨E所示。 參考圖1B，首先利用高溫爐管以1〇5(rc成長5〇〇〇 A厚的二 氧化矽（Si〇2)薄膜102於一基板101(在本實施例中為矽基 板）之二相對側面，且利用低壓化學氣體沉積系統（1胃 pressure chemical vapor deposition，LPCVD)沉積 1500A厚 的低應力氮化石夕（Si#4)薄膜i〇3於該二氧化石夕薄膜i〇2上， 再利用電子束蒸鍍機沉積系統（E_gUn evap〇rat〇r)沉積一層 鉻（C〇/金（Au)薄膜1〇4於一側面之該氮化矽薄膜1〇3上，其 中，該鉻（Cr)/金（Au)薄膜1〇4之該鉻之厚度為20〇a，而該 金之厚度為1500A。本發明kFPW元件之低應力氮化矽 (SisN4)薄膜1〇3上沉積鉻（Cr)/金（Au)底電極（即該鉻/金薄膜 120400.doc -12- 200842357 • 1G4)，以增加傳統彎曲平板波（FPW)元件的敎性與訊雜 . 比（S/N)。 多考Θ 1C接下來利用射頻濺鑛機（rf-sputter)沉積高 悛貝的氧化鋅（ZnO)壓電薄臈丨〇5，再將該氧化辞壓電薄膜 1〇5經微影及蝕程定義其_。該氧化鋅㈣薄㈣5 之材料具有高機電麵合係數 '與基板之黏附性佳、低聲速 (低操作頻率）、4境抵抗性強、製程容易並且與積體電路 1程相容等優點。配合參考請及圖1E，經旋塗與微影 一層光阻106 ’再利用電子束蒸鍍機沉積鉻/金之IDT電極 107，並以掀舉法（hft_off)定義該電極ι〇7，以形成一組輸 入父指式傳感器12及一組輸出交指式傳感器13。其中，該 輸入乂指式傳感器12係以逆壓電效應來將加入於盆上的電 訊號轉變成彈性波動來輸出，此一彈性波經過一段延遲時 間後，將接觸到該輸出交指式傳感器13，並以正壓電效應 來將所接收到的彈性波轉變成交流訊號來輸出，而輸出訊 • 號的振幅及相位取決於交指式傳感器的幾何形狀。 * ®2A至圖2D顯示為Fpw元件表面、剖面、懸浮薄膜及 薄膜沉積元件結構之電子掃晦顯微鏡（SEm)圖，由上述該 等圖中可明顯得知： Μ ⑷ZnO薄膜表面呈現極緻密的粒狀（平均直徑約⑽)且 分佈均勻； (b) ZnO薄膜其橫剖面則呈現很緊密的柱狀排列社構. 、⑷㈣元件的Zn0/Si3N4/ Si〇2/_浮薄板（°厚度約為 • 6μηι);及 120400.doc -13- 200842357 (d)FPw”_腔體結構’懸浮薄板與梦基板呈現約為 k 123度的夾角。 參考圖3,本發明所沉積之氧化鋅薄膜經伽分析，可 明顯看出其c軸選向的（002)繞射角度出現在2β=34 32，與 JCPDS資料表中顯示的34.42幾乎完全符合，而且其繞射強 度很高，半高寬值只有0.352，所以證明本發明所沉積的 ΖηΟ薄膜確實具有十分優良的壓電特性，這是製作㈣感 冑元件最關鍵的製程之-。另外，其繞射強度與半高寬值 (full-width at half-maximum，FWHM)會隨基板溫度上升而 增加。 名弓曲平板波兀件丨0係藉由微質量密度或黏滯係數的變 化而感測出相速度的改變，且該彎曲平板波元件10具有較 薄的厚度尺寸。因此，該彎曲平板波元件10適合於量測液 體特別疋生物感測及化學感測。在本實施例中，該彎曲 平板波元件10係使用一交指式傳感器（Interdigitai • 以抓8(111(^，IDT)及壓電耦合效應來產生並偵測波。要注意 的疋，該交指式傳感器可包括一輸入交指式傳感器12及一 輸出交指式傳感器13，其設置於該彎曲平板波元件1〇上， 且相對於該矽基板腔體11之該平面111。其中，該輸入交 指式傳感器12及該輸出交指式傳感器13係作為該彎曲平板 波元件10之輸入/輸出端子。另外，只要在該輸入交指式 傳感态12及該輸出交指式傳感器13之間設置一放大器（圖 未不出）即可組成一彎曲平板波延遲線震盪器。 輪入父4曰式傳感器用以將該彎曲平板波元件1 Q之電訊 120400.doc -14- 200842357 5虎轉換成一彈性波，該輸出交指式傳感器用以將該彈性波 轉變換一交流訊號並輸出。該放大器係用以放大該彈性 波。该彈性波衰減的改變係由於黏性的變化被該輸出交指 式傳感器反映在信號幅度之變化上。較佳地，該彎曲平板 波元件10之操作頻率在之間。 該自我組裝單分子層結構2〇設置於該矽基板腔體U之該 平面111 °遠自我組裝單分子層結構2〇包括：一基板2 i、 一自我組裝單分子層22及複數個免疫球蛋白e抗體23。其 中’該基板21具有一第一表面2U及一第二表面212，該第 一表面212相對於該第一表面211，該第一表面211設置於 該矽基板腔體11之該平面U1。在本實施例中，該基板21 係為一金屬基板。其中，該金屬基板係為金，或者，該金 屬基板可為鉻/金合金。較佳地，該第一表面2丨丨及該第二 表面212係為平坦之表面。 該自我組裝單分子層22具有複數個自我組裝單分子 221，該等自我組裝單分子221間隔地設置於該基板21之該 第二表面212。在本實施例中，該自我組裝單分子層22係 利用下列步驟：首先，將該基板21之該第二表面212滴入 稀釋的胱胺酸溶液浸置一小時，接著滴入稀釋的戊二醛溶 液浸置一小時，最後滴入稀釋的硼氫化鈉溶液三十分鐘， 每一步驟完成後皆以去離子水（DI_Water)清洗（在本實施例 中為二—人），之後乾燥即完成自我組裝單分子層22。該等 自我組裝單分子221係藉由各相鄰自我組裝單分子221間之 氫鍵、離子鍵或凡德瓦力，以硫分子與該第二表面212(在 120400.doc -15- 200842357 本實施例中為金平面）整齊地排列吸附。每一免疫球蛋白E 抗體23具有一頭端231及一結合端232，其中，每一免疫球 蛋白E抗體23大致呈一 γ字形。該頭端231連接該自我組裝 單分子221，該結合端232用以與一免疫球蛋白e抗原30結 合0 其中，在沉積該等免疫球蛋白E抗體23於該自我組裝單 分子層22之前，可先利用磷酸鹽緩衝液（ph〇sphate buffered saline，PBS)清洗該自我組裝單分子層22，再利用 稀釋之免疫球蛋白E抗體以37。(：浸置二小時並用清洗緩衝 液清洗該自我組裝單分子層22(在本實施例中為三次），之 後再利用牛血清蛋白（b〇vine serum aibumin，BSA)以37°C浸 置30分鐘，以增加該等免疫球蛋白e抗體23與免疫球蛋白e 抗原3〇之專一性結合度，以製作完成本發明之可吸附免疫 球蛋白E之自我組裝單分子層結構2〇(如圖4所示）。 參考圖5及圖6，其分別為本發明所沉積之胱胺酸_戊二 醛自我組裝單分子層之歐傑電子光譜儀（AES)元素分析結 果圖及傅立葉轉換紅外光譜儀（FTIR)鍵結分析結果圖，從 汶一圖中可證明與推論此自我組裝單分子層之元素組成、 化學鍵的形式皆符合預期。 圖7顯不本發明金表面之原子力顯微鏡（afm)微結構 圖。圖8顯示本發明胱胺酸_戊二醛自我組裝單分子層之原 子力顯微鏡（AFM)微結構圖。圖9顯示本發明IgE抗體吸附 於胱胺酸-戊二醛的原子力顯微鏡（AFM)微結構圖。圖1〇顯 不本發明IgE抗體與igE抗原結合後的原子力顯微鏡（AFM) 120400.doc 200842357 微結構圖。參考圖7至圖10，從該等圖中可以明顯看出胱 胺酸-戊二駿的細微分子結構呈均勻分佈以有效吸附免疫 球蛋白Ε抗體，進而成功進行免疫球蛋白ε抗原之專一結 合。 圖11Α及圖11Β分別為胱胺酸-戊二醛自我組裝單分子層 /IgE抗體與0.707 gg/mLIgE抗原層沉積前與沉積後之FPw 生醫微感測器頻譜響應圖。由圖丨丨A及圖11 b二圖顯示 出’ FPW元件在未吸附IgE抗原層前之中心頻率為 22·675ΜΗζ，而吸附igE抗原層後之中心頻率為 22·67125ΜΗζ，且質量感測度高達172〇〇 cm2/g。 本發明之生醫感測器1之製作係結合奈米科技與微機電 技術，故元件具有較薄的厚度尺寸，所以其相速度會比大 部分的液體低（一般液體中聲波速度為9〇〇〜15〇〇 m/s)，造 成該生醫感測器1在量測液體時因為傳遞波速較慢，所以 不會ie成任何月b里輕射到液體中。因此，本發明之該生醫 感測器1適合於量測液體，特別是生物感測及化學.感測。 再者，因為該生醫感測器！的厚度僅有幾個微米厚，且 薄板的質量岔度非常低，故整個元件具有非常高的質量感 測靈敏度。因此，利用本發明之生醫感測器丨以檢驗血液 中之免疫球蛋白E濃度時，其具有高準確度、高靈敏度、 低操作頻率、檢測時間短以及成本較低等優點。 本發明選擇具有高優值特性之氧化鋅（Zn〇)作為彎曲平 板波7L件之壓電層，並且本發明結合生物科技之胱胺酸_ 戊二醛自我組裝單分子層（SAMs)技術與微機電系統 120400.doc -17- 200842357 (MEMS)技術，提出一種創新的且具進步性（有底電極設計） 的彎曲平板波生醫感測器，以應用在日益嚴重的過敏j生疾 病之檢測，主要判定標的是病患血清中免疫球蛋白e之濃 度值。 惟上述實施例僅為說明本發明之原理及其功效，而非用 以限制本發明。因此，習於此技術之人士對上述實施例進 打修改及變化仍不脫本發明之精神。本發明之權利範圍應 如後述之申請專利範圍所列。 【圖式簡單說明】 圖1顯不本發明結合胱胺酸_戊二醛自我組裝單分子層/免 疫球蛋白E抗體與彎曲平板波元件以應用於免疫球蛋白£抗 原檢測之生醫感測器結構示意圖； 圖1A顯示本發明FPW元件的元件佈局設計圖； 圖1B至1E顯示本發明FPW元件之製作步驟示意圖； 圖2八顯示本發明211〇薄膜的表面8£]^圖，· 圖2B顯示本發明Zn0薄膜的剖面結構sem圖； 圖2C顯示本發明FPW元件的懸浮薄板§εμ圖； 圖2D顯示本發明FPW背部蝕刻後的結構sem圖； 圖3顯示本發明Zn〇薄膜的XRD分析結果圖，· 圖4顯示本發明之胱胺酸_戊二醛自我組裝單分子層/免疫 球蛋白E抗體結構與免疫球蛋白£抗原結合之示意圖； 圖5顯示本發明胱胺酸-戊二醛的自我組裝單分子層的 AES元素分析結果圖； 圖6顯示本發明胱胺酸-戊二醛的自我組裝單分子層的 120400.doc -18- 200842357 * FT-IR鍵結分析結果圖； * 圖7顯示本發明金表面之原子力顯微鏡（AFM)微結構 圖； 圖8顯示本發明胱胺酸-戊二醛自我組裝單分子層之原子 力顯微鏡（AFM)微結構圖； 圖9顯示本發明igE抗體吸附於胱胺酸-戊二醛的原子力 顯微鏡（AFM)微結構圖； 圖10顯示本發明IgE抗體與IgE抗原結合後的原子力顯微 ® 鏡（AFM)微結構圖； 圖ΠΑ顯示本發明胱胺酸-戊二醛SAM/；[gE抗體與0.707 pg/mLIgE抗原層沉積前之FPW生醫微感測器頻譜響應 圖；及 圖11B顯示本發明胱胺酸·戊二醛SAM/IgE抗體與〇·7〇7 pg/mLIgE抗原層沉積後之FPW生醫微感測器頻譜響應圖。 【主要元件符號說明】 本發明應用於免疫球蛋白E檢測之彎曲平板波生 醫感測器 10 11 12 13 20 21 22 彎曲平板波元件 矽基板腔體 輸入交指式傳感器 輸出交指式傳感器 自我組裝單分子層結構 基板 自我組裝單分子層 120400.doc -19- 200842357 23 免疫球蛋白E抗體 30 免疫球蛋白E抗原 101 基板 102 二氧化矽薄膜 103 氮化矽薄膜 104 鉻（Cr)/金（Au)薄膜 105 氧化鋅壓電薄膜 106 光阻 107 交指式傳感器（IDT)電極 111 平面 211 第一表面 212 第二表面 221 自我組裝單分子 231 頭端 232 結合端 120400.doc -20-The self-assembled monolayer of the present invention can be fabricated by a simple immersion deposition thin film technique, and the structure formed by the self-single molecule self-assembly has minimal thermal dynamics and can precisely control the length of the structure and can be uniform The cover substrate has the characteristics of high biocompatibility and high self-forming rate at room temperature. _ The production of the biomedical sensor 本 of the present invention combines nanotechnology and microelectromechanical technology, so that the 7L piece has a thin thickness dimension, so its phase velocity is lower than that of most liquids (the sound velocity in a liquid is 9 (10) ~· m/s), causing the biomedical sensor to measure the liquid because the transmission wave speed is slow, so no energy is radiated into the liquid. Thus, the biosensory benefit of the present invention is suitable for measuring liquids, particularly biosensing and chemical sensing. Furthermore, because the thickness of the biomedical sensor is only a few microns thick and thin: the mass density is very low, the entire component has a very high mass sensing sensitivity. Therefore, when the biomedical sensor of the present invention is used to examine the concentration of immunoglobulin E in blood, it has the advantages of high accuracy, sensitivity, low operating frequency, short detection time, and low cost. 120400.doc -11- 200842357 [Embodiment] Referring to Fig. 1, there is shown a flexural plate wave (FPW) biomedical sensor applied to immunoglobulin E detection according to the present invention. The biomedical sensor 1 includes a curved plate wave element 10 and a self-assembled monolayer structure 20. The curved plate wave element 1 has a 矽 substrate cavity 11, and the 矽 substrate cavity 11 has a flat surface 111. In the present embodiment, the curved flat wave component 10 is a semiconductor component, and its component layout design is as shown in FIG. 1A (herein, a top view). The main design parameter of the curved flat wave component is an interdigital sensor. (Interdigital transducer, IDT) electrode spacing, interdigitated sensor electrode pairs, interdigitated sensor electrode overlap length and input/output 埠 (I/O) delay length, and the theoretical formula is derived to find the optimal bending Important output characteristics such as center frequency and mass sensitivity of the plate wave element. The manufacturing flow of the curved flat wave wave element 1 丨 is as shown in FIG. Referring to FIG. 1B, first, a high-temperature furnace tube is used to grow a 5 〇〇〇A thick cerium oxide (Si〇2) film 102 on a substrate 101 (in this embodiment, a ruthenium substrate). Side, and using a low pressure chemical vapor deposition system (LPCVD) to deposit a 1500A thick low-stressed nitride (Si#4) film i〇3 on the dioxide film i〇2, and then Depositing a layer of chromium (C〇/gold (Au) film 1〇4 on one side of the tantalum nitride film 1〇3 by an electron beam evaporation machine deposition system (E_gUn evap〇rat〇r), wherein the chromium ( The thickness of the chromium of the Cr)/gold (Au) film 1〇4 is 20〇a, and the thickness of the gold is 1500A. The chromium of the low-stressed tantalum nitride (SisN4) film 1〇3 of the kFPW element of the present invention is deposited. Cr)/gold (Au) bottom electrode (ie, chrome/gold film 120400.doc -12- 200842357 • 1G4) to increase the flexibility and interference of conventional curved flat wave (FPW) components. (S/N) Multi-Test 1C Next, using a rf-sputter to deposit high-millimeter zinc oxide (ZnO) piezoelectric thin 臈丨〇 5, and then the oxidized piezoelectric film 1 〇 5 It is defined by lithography and etch. The zinc oxide (four) thin (four) 5 material has a high electromechanical surface-coupling coefficient, good adhesion to the substrate, low sound velocity (low operating frequency), strong resistance to 4 environments, and easy process. It is compatible with the integrated circuit 1 step. For reference, please refer to Figure 1E, spin-coating and lithography layer photoresist 106' to re-deposit the chrome/gold IDT electrode 107 by electron beam evaporation machine, and use the lifting method (hft_off) The electrode ι7 is defined to form a set of input father finger sensors 12 and a set of output interdigital sensors 13. The input finger sensors 12 are added to the basin by an inverse piezoelectric effect. The electrical signal is converted into an elastic wave to output. After a delay time, the elastic wave contacts the output interdigital sensor 13 and converts the received elastic wave into an alternating signal by a positive piezoelectric effect. The amplitude and phase of the output signal depend on the geometry of the interdigital sensor. * ® 2A to 2D show the electronic broom microscope (SEm) of the Fpw component surface, profile, suspended film, and thin film deposition component structure. By It can be clearly seen in the above figures: Μ (4) The surface of ZnO thin film is extremely dense granular (average diameter about (10)) and evenly distributed; (b) The cross section of ZnO thin film shows a very tight columnar structure. (4) (4) The Zn0/Si3N4/Si〇2/_ floating sheet of the component (° thickness is approximately 6 μηι); and 120400.doc -13- 200842357 (d) FPw"_cavity structure" suspended sheet and the dream substrate are approximately k 123 The angle of the degree. Referring to FIG. 3, the zinc oxide film deposited by the present invention has a gamma analysis, and it can be clearly seen that the (002) diffraction angle of the c-axis direction appears at 2β=34 32, which is almost completely consistent with the 34.42 shown in the JCPDS data sheet. Moreover, the diffraction intensity is very high, and the full width at half maximum is only 0.352, so that the ΖηΟ film deposited by the present invention proves to have very excellent piezoelectric characteristics, which is the most critical process for fabricating (four) sensing elements. In addition, the diffraction intensity and full-width at half-maximum (FWHM) increase as the substrate temperature rises. The curved plate wave element 丨 0 senses a change in phase velocity by a change in micromass density or viscous coefficient, and the curved plate wave element 10 has a thin thickness dimension. Therefore, the curved plate wave element 10 is suitable for measuring liquid, particularly biological sensing and chemical sensing. In the present embodiment, the curved plate wave element 10 uses an interdigital sensor (Interdigitai • to generate and detect waves by grabbing 8 (111 (^, IDT) and piezoelectric coupling effects. Note that this The interdigital sensor may include an input interdigital sensor 12 and an output interdigital sensor 13 disposed on the curved flat wave wave element 1 相对 and opposite to the plane 111 of the 矽 substrate cavity 11 . The input interdigital sensor 12 and the output interdigital sensor 13 are used as input/output terminals of the curved flat wave element 10. Further, as long as the input interdigital sensing state 12 and the output interdigital sensor 13 are An amplifier (not shown) can be arranged to form a curved flat wave delay line oscillator. The parent 4 inch sensor is used to tune the curved flat wave component 1 Q 120400.doc -14- 200842357 5 The tiger converts into an elastic wave, and the output interdigital sensor converts the elastic wave into an alternating current signal and outputs the same. The amplifier is used to amplify the elastic wave, and the change of the elastic wave attenuation is caused by a change in viscosity. Output The finger sensor is reflected in the variation of the signal amplitude. Preferably, the operating frequency of the curved plate wave element 10 is between. The self-assembled monolayer structure 2 is disposed on the plane of the 矽 substrate cavity U. The far self-assembling monolayer structure 2 includes: a substrate 2 i, a self-assembled monolayer 22, and a plurality of immunoglobulin e antibodies 23. wherein the substrate 21 has a first surface 2U and a second surface 212 The first surface 212 is disposed on the plane U1 of the 矽 substrate cavity 11 with respect to the first surface 211. In the embodiment, the substrate 21 is a metal substrate. The metal substrate is made of gold, or the metal substrate may be a chromium/gold alloy. Preferably, the first surface 2丨丨 and the second surface 212 are flat surfaces. The self-assembled monolayer 22 has a plurality of The self-assembled single molecules 221 are disposed at intervals on the second surface 212 of the substrate 21. In the present embodiment, the self-assembled monolayer 22 utilizes the following steps: First, the The first of the substrate 21 The surface 212 was dropped into the diluted cystine acid solution for one hour, then diluted into the diluted glutaraldehyde solution for one hour, and finally the diluted sodium borohydride solution was added dropwise for thirty minutes, and each step was completed. The ionized water (DI_Water) is cleaned (in this embodiment, the two-human), and then dried to complete the self-assembled monolayer 22. The self-assembled single molecule 221 is made up of hydrogen between each adjacent self-assembled single molecule 221 The bond, the ionic bond or the van der Waals force is aligned with the second surface 212 (the gold plane in this embodiment in 120400.doc -15-200842357). Each immunoglobulin E antibody 23 has a head end 231 and a binding end 232, wherein each immunoglobulin E antibody 23 has a substantially gamma shape. The head end 231 is coupled to the self-assembling single molecule 221 for binding to an immunoglobulin e antigen 30, wherein before depositing the immunoglobulin E antibody 23 in the self-assembling monolayer 22, The self-assembled monolayer 22 can be washed first with phosphate buffered saline (PBS) and then with the diluted immunoglobulin E antibody at 37. (: immersed for two hours and washed the self-assembled monolayer 22 (three times in this example) with a washing buffer, followed by immersion with bovine serum albumin (BSA) at 37 ° C. Minutes to increase the specificity of binding of the immunoglobulin e antibody 23 to the immunoglobulin e antigen 3〇 to prepare the self-assembled monolayer structure of the adsorbable immunoglobulin E of the present invention. 4)) Referring to FIG. 5 and FIG. 6, which are the results of the elemental analysis of the Auger electron spectrometer (AES) of the deposited cysteine-glutaraldehyde self-assembled monolayer, and the Fourier transform infrared spectrometer ( FTIR) bond analysis results, from the Wenyi diagram can prove and infer the elemental composition of the self-assembled monolayer, the form of chemical bonds are in line with expectations. Figure 7 shows the atomic force microscope (afm) microstructure of the gold surface of the present invention Figure 8 shows an atomic force microscope (AFM) microstructure of the cysteine-glutaraldehyde self-assembled monolayer of the present invention. Figure 9 shows an atomic force microscope (AFM) of the IgE antibody of the present invention adsorbed to cystine-glutaraldehyde. ) Figure 1. Figure 1 shows the atomic force microscope (AFM) after binding of the IgE antibody of the present invention to the igE antigen 120400.doc 200842357 Microstructure chart. Referring to Figures 7 to 10, it is apparent from these figures that cystine - The fine molecular structure of glutarylene is uniformly distributed to effectively adsorb immunoglobulin Ε antibody, and thus the specific binding of immunoglobulin ε antigen is successfully carried out. Figure 11Α and Figure 11 are cystine-glutaraldehyde self-assembled single molecules. The spectral response of the FPw biomedical microsensor before and after deposition of the layer/IgE antibody and the 0.707 gg/mLIgE antigen layer. Figure 丨丨A and Figure 11 b show that the FPW element is in the unadsorbed IgE antigen layer. The center frequency of the front is 22·675ΜΗζ, and the center frequency after adsorbing the igE antigen layer is 22.67125ΜΗζ, and the mass sensitivity is as high as 172〇〇cm2/g. The production of the biomedical sensor 1 of the present invention is combined with nanometer. Technology and MEMS technology, so the components have a thin thickness, so the phase velocity will be lower than most of the liquid (the sound velocity in the liquid is generally 9 〇〇 15 〇〇 m / s), resulting in the medical sense Detector 1 when measuring liquid Since the transmitted wave velocity is slow, it does not shine into the liquid in any month b. Therefore, the biomedical sensor 1 of the present invention is suitable for measuring liquids, particularly biosensing and chemical sensing. Moreover, since the thickness of the biomedical sensor! is only a few micrometers thick, and the quality of the thin plate is very low, the entire component has a very high mass sensing sensitivity. Therefore, the medical sense of the present invention is utilized. When the detector is used to test the concentration of immunoglobulin E in blood, it has the advantages of high accuracy, high sensitivity, low operating frequency, short detection time, and low cost. The present invention selects zinc oxide (Zn〇) having high-value characteristics as a piezoelectric layer of a curved flat wave 7L piece, and the present invention combines the biotechnology of cystine-glutaraldehyde self-assembled monolayer (SAMs) technology with MEMS 120400.doc -17- 200842357 (MEMS) technology, proposes an innovative and progressive (bottomed electrode design) curved flat wave biomedical sensor for use in increasingly serious allergies Detection, the main criterion is the concentration of immunoglobulin e in the patient's serum. However, the above-described embodiments are merely illustrative of the principles of the invention and its effects, and are not intended to limit the invention. Therefore, those skilled in the art can make modifications and changes to the above embodiments without departing from the spirit of the invention. The scope of the invention should be as set forth in the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the biosensor sensing of immunoglobulin £ antigen detection in combination with cystine-glutaraldehyde self-assembled monolayer/immunoglobulin E antibody and curved plate wave element. 1A is a schematic view showing the layout of the FPW device of the present invention; FIGS. 1B to 1E are views showing the steps of fabricating the FPW device of the present invention; and FIG. 2 is a view showing the surface of the 211-inch film of the present invention. 2B shows a cross-sectional structure sem diagram of the Zn0 film of the present invention; FIG. 2C shows a §εμ diagram of the suspended sheet of the FPW element of the present invention; FIG. 2D shows a sem diagram of the FPW back etched in the present invention; FIG. 3 shows an XRD of the Zn〇 film of the present invention. Figure 4 shows a schematic diagram of the binding of the cystine-_glutaraldehyde self-assembled monolayer/immunoglobulin E antibody structure of the present invention to the immunoglobulin £ antigen; Figure 5 shows the cystine-pentyl group of the present invention. Figure of AES elemental analysis of self-assembled monolayer of dialdehyde; Figure 6 shows the results of FT-IR bonding analysis of self-assembled monolayer of cystine-glutaraldehyde of the present invention 120400.doc -18- 200842357 ; * Figure 7 shows Atomic force microscopy (AFM) microstructure of the gold surface of the present invention; Figure 8 shows an atomic force microscope (AFM) microstructure of the cysteine-glutaraldehyde self-assembled monolayer of the present invention; Figure 9 shows the adsorption of the igE antibody of the present invention Atomic force microscopy (AFM) microstructure of cystine-glutaraldehyde; Figure 10 shows an atomic force microscopy (AFM) microstructure of the IgE antibody of the invention combined with IgE antigen; Figure ΠΑ shows cystine of the invention - glutaraldehyde SAM /; [gE antibody and 0.707 pg / mLIgE antigen layer before deposition FPW biomedical microsensor spectrum response map; and Figure 11B shows the present invention cystine acid · glutaraldehyde SAM / IgE antibody and 〇 · Spectrum response of FPW biomedical microsensor after deposition of 7〇7 pg/mLIgE antigen layer. [Main component symbol description] The present invention is applied to a curved flat wave biomedical sensor for immunoglobulin E detection. 10 11 12 13 20 21 22 Curved plate wave element 矽 substrate cavity input interdigital sensor output interdigital sensor self Assembly of monolayer structure substrate self-assembled monolayer 120400.doc -19- 200842357 23 Immunoglobulin E antibody 30 Immunoglobulin E antigen 101 Substrate 102 Ceria film 103 Tantalum nitride film 104 Chromium (Cr) / gold ( Au) film 105 zinc oxide piezoelectric film 106 photoresist 107 interdigitated sensor (IDT) electrode 111 plane 211 first surface 212 second surface 221 self-assembled single molecule 231 head end 232 bonding end 120400.doc -20-