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 免疫系統過度反應，則會造成過敏症、休克，甚至致死。 其中日益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-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 要提供一種創新且具進步性的免疫球蛋白:檢=術= 件’以解決上述問題。 聲波感測器非常適合應用於質量之感 σ曰& 4 /别最早出現的產 口口疋剪應力振盪器（TSM Resonat〇r)鱼志工级 ;兴表面聲波感測器 120400.doc 1333068 (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 Horizontal-Acoustic Plate Mode， SH-APM) 、 表面 聲波與 彎曲平 板波這 三種感測器，其共同點都是應用交指式傳感器（IDT)，但 是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）’液體的黏滞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滞性與密度。 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’這主要是由於Rayleigh type之 120400.doc 1333068 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 W @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 性與訊鱿比（S/N)較差，且選擇彎曲平板波元件之壓電材 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-戊二搭（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 1333068 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," 1998 IEEE Internal Frequency Control Symposium, (1998) p.587-594. 5. M. J. Vellekoop, "Acoustic wave sensors and their technology," 1997 Ultrasonics proceedings, (1997) p.7-14. 6. I. Esteban et. al., "Using a formal mathematics software for SH-APM sensor modeling," Sensors and Actuators A, 67,（1998) p.77-83·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; immunoglobulin E is the main 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 the more serious tests for allergic diseases, the main criterion is the concentration of immunoglobulin E (IgE) in the serum of patients. The conventional blood test method is used to test the concentration of immunoglobulin E in blood, which is not only time-consuming but also expensive. The accuracy is only about 60% to 70%, and the detection time is long. Although there are some high-accuracy and high-sensitivity allergy test kits on the market, but their prices are quite high, they require a lot of test liquid and are not easy to miniaturize, so higher manufacturing is required. Provide an innovative and progressive immunoglobulin: test = surgery = piece 'to solve the above problems. Acoustic sensor is very suitable for the sense of quality σ曰 & 4 / the earliest appearance of the mouth and mouth 疋 shear stress oscillator (TSM Resonat〇r) fish syllabus; Xing surface acoustic wave sensor 120400.doc 1333068 (SAW sensor), the advancement of microelectromechanical systems (MEMS) technology in the past decade has 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 studies mainly used Shear Horizontal-Acoustic Plate Mode (SH-APM), surface acoustic wave and curved flat wave. The commonality of the detectors is the application of interdigitated sensors (IDTs), but there are still large differences between them. The shear horizontal plate wave sensor uses the shear force horizontal plate wave 'its wave displacement vector is parallel to the plate surface and perpendicular to the wave direction'. Therefore, if liquid is attached to the sensor surface (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 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. This is mainly due to the Rayleigh type 120400.doc 1333068 surface wave with the surface displacement vector relationship. 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 viscosity and density of the liquid W @ shows 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], and the stability and the signal-to-noise ratio (S/N) are poor, and the piezoelectric material of the curved plate wave element is selected to be noted. 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 antibody has a good adsorption rate and is reproducible better than conventional adsorption methods [Refer to the literature of prior art list No. 25]» Previous Technology List: 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 1333068 sensors, edited by SM Sze, John Wiely & Sons, Inc., 1994, New York. 4. RM Richard, "Acoustic sensors for physical, chemical and biochemical applications," 1998 IEEE Internal Frequency Control Symposium, (1998) p.587-594. 5. MJ Vellekoop, " Acoustic wave sensors and their technology," 1997 Ultrasonics proceedings, (1997) p. 7-14. 6. I. Esteban et. al., "Using a formal Mathematics software for SH-APM sensor modeling," Sensors and Actuators A, 67, (1998) p.77-83·
7. M. G. Schweyer et. al.，"Acoustic plate mode sensor for aqueous mercuiy," Sensor and Actuators B, 35, (1996) p.170-175. 8. C. Dejous et. al. , "Shear 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.2392-2395.7. MG Schweyer et. al., "Acoustic plate mode sensor for aqueous mercuiy," Sensor and Actuators B, 35, (1996) p.170-175. 8. C. Dejous et. al. , "Shear 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, "Sensing in liquids using acoustic plate mode devices," "Tech. 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) p.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," 1998 IEEE Internal Frequency Control Symposium, (1998) 120400.doc 1333068 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," 1997 IEEE Ultrasonics symposium proceedings, (1993) p.355-358. 14. S. Furukawa et. al., "Characteristics of leaky surface acoustic wave propagation along liquid/layered-substrates and their application to liquid sensor 1993 IEEE Ultrasonics symposium proceedings, (1997) p.433-436.10. SJ Martine and AJ Ricco, "Sensing in liquids using acoustic plate mode devices,""Tech. 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) p.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," 1998 IEEE Internal Frequency Control Symposium, (1998) 120400.doc 1333068 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," 1997 IEEE Ultrasonics symposium proceedings, (1993) p.355-358 14. S. Furukawa et. al., "Characteristics of leaky surface acoustic wave propagation along liquid/layered-substrates and their application to liquid sensor 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," 1989 Ultrasonic symposium, (1989) p.977-981.15. 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," 1989 Ultrasonic symposium, (1989) p.977-981.
17. S. W. Wenzel and R. M. White, "Flexural plate-wave gravimetric sensor," sensor and Actuators A ： Physical, 22, (1990) p.700-703. 18. S. W. Wenzel and R. M. White, "Flexural 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) p.1976-1978. 20. R. M. White et. al., "plate-mode ultrasonic oscillator sensors," IEEE Trans. Ultrasonic Ferroelec. Freq. contr., 34, (1987) p.162-171. 120400.doc 1333068 21. S. W. Wenzel and R. M White, "A 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, "Viscosity 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 microbalance", Analytica ChimicaActa , Vol. 453, 2002, pp. 181-189. 【發明内容】17. SW Wenzel and RM White, "Flexural plate-wave gravimetric sensor," sensor and Actuators A : Physical, 22, (1990) p.700-703. 18. SW Wenzel and RM White, "Flexural plate wave Sensor: chemical vapor sensing and electrostrictive excitation, " 1989 Ultrasonic symposium, (1989) p.595-598. 19. SW Wenzel and RM White, "Analytic comparison of the sensitivities of bulk-wave, surface wave, and flexural plate -wave ultrasonic gravimetric sensors," Appl. Phys. Lett. 54, (1988) p.1976-1978. 20. RM White et. al., "plate-mode ultrasonic oscillator sensors," IEEE Trans. Ultrasonic Ferroelec Freq. contr., 34, (1987) p.162-171. 120400.doc 1333068 21. SW Wenzel and R. M White, "A 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, "Viscosity 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 microbalance", Analytica ChimicaActa , Vol 453, 2002, pp. 181-189. [Summary of the Invention]
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- 1333068 表面及一第二表面，該篦-主尤^ 第一表面相對於該第一表面，該第 一表面設置於該腔體。該自我组裝單分子層具有複數個自 我組裝單分子，該等自我組裝翠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-頭端氨 基（—°)及—結合端’朗端連接該自我組料分子乙酿 基（aldehyde)，該結合端用以與—免疫球蛋W抗原作專- 性結合，其中，兩者之三度空間結構為彼此互補，具有相 當的親合力。 /發明之該自我組裝單分子層可㈣簡單之浸泡式沉積 薄膜技術製成’並且’該等自我組裝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 均句的覆蓋基板、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。 本發明之生醫感測器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 該生醫感測器在量測液體時因為傳遞波速較慢，所以不會 ，成任何能量輕射到液體中。因此，本發明之該生醫感測 器適合於量測液體，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、高靈敏度、低操 作頻率、檢測時間短以及成本較低等優點。 120400.doc • η · 1333068 【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包括一靑曲平板波元件1 〇及一自我組裝單分子層結 構2〇。該彎曲平板波元件10具有矽基板腔體η，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1Α(在此為 俯視圖）所示’該彎曲平板波元件10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/ 輸出璋（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10的製作流程如圖1B至圖1E所示。 參考圖1B ’首先利用高溫爐管以1050〇c成長5〇〇〇 a厚的二 氧化矽（Si〇2)薄膜1〇2於一基板1〇丨（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（丨〇w pressure chemical vapor deposition，LPCVD)沉積 1500A厚 的低應力氮化矽（Si3N4)薄膜l〇3於該二氧化矽薄膜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 絡（Cr)/金（Au)薄膜104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200A，而該 金之厚度為1500A。本發明於FPW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· 1333068 104)，以增加傳統彎曲平板波（Fpw)元件的穩定性與訊雜 比（S/N) 〇 參考圖1C，接下來利用射頻減鑛機（RF_Sputter)沉積高 優質的氧化鋅（Zn〇)壓電薄膜105，再將該氧化辞壓電薄臈 1〇5經微影及蝕刻製程定義其圖形❶該氧化鋅壓電薄膜1〇5 之材料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 製程相容等優點。配合參考圖1D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（丨ift-〇ff)定義該電極1〇7，以形成一組輸 入交指式傳感器12及一組輸出交指式傳感器13。其中，該 輸入交指式傳感器12係以逆壓電效應來將加入於其上的電 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= 號的振幅及相位取決於交指式傳感器的幾何形狀。 圖2A至圖2D顯示為FPWiL件表面、剖面、懸浮薄膜及 薄膜 >儿積兀件結構之電子掃瞄顯微鏡（SEM)圖，由上述該 等圖中可明顯得知： ~ (a) ZnO薄膜表面呈現極緻密的粒狀（平均直徑約且 分佈均勻； (b) ΖηΟ薄膜其橫剖面則呈現很緊密的柱狀排列結構； ⑷㈣元件的Zn0/Si3N4/ Si(Vsi懸浮薄板（厚度約為 6μιη);及 120400.doc -13· 1333068 • ⑷FPW背部㈣腔體結構，懸浮薄板㈣基板呈現約為 - 123度的夾角。 參考圖3纟發明所沉積之氧化鋅薄膜經分析，可 明顯看出其c軸選向的(002)繞射角度出現在20=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Fpw感 # :則元件最關鍵的製程之一。另外’其繞射強度與半高寬值 (full-wldth at half-maximum’ FWHM)會隨基板溫度上升而 增加。 該考曲平板波元件1〇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，特別是生物感測及化學感測。在本實施例中，該彎曲 平板波元件1〇係使用一交指式傳感器（Interdighal φ tranSdUCer，IDT)及壓電耦合效應來產生並偵測波。要注意 的是，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10上， 且相對於該矽基板腔體丨丨之該平面lu。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 波兀件10之輸入/輸出端子。另外，只要在該輸入交指式 傳感器12及該輸出交指式傳感器13之間設置—放大器（圖 未不出）即可組成—彎曲平板波延遲線震盪器。 該輪入交指式傳感器用以將該彎曲平板波元件1〇之電訊 120400.docSUMMARY OF THE INVENTION It is an object of the present invention to provide a curved plate wave biomedical sensor for use in immunoglobulin E detection 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- 1333068 surface and a second surface, the first surface being opposite the first surface, the first surface being disposed in the cavity. The self-assembling monolayer has a plurality of self-assembled single molecules, and the self-assembled green molecules are deposited at intervals on the second surface of the substrate. Each immunoglobulin E antibody has a -terminal amino group (-°) and a binding end 'lang end is attached to the self-organizing molecule aldehyde, and the binding end is used for the immunoglobulin W antigen. - Sexual union, in which the three dimensional structures of the two are complementary to each other and have considerable affinity. /The invention of the self-assembled monolayer can be made of (4) simple immersion deposition film technology and the structure formed by the self-assembled single molecule self-assembly has minimal thermal dynamics and can accurately control the length and energy of the structure. The sentence covers the substrate, has a very high biocompatibility and has a high self-forming rate at room temperature. The production of the biomedical sensor of the present invention is combined with nanotechnology and microelectromechanical technology, so that the component has a thin thickness dimension, so its phase velocity is lower than that of most liquids (the sound velocity in a liquid is generally 9〇〇). ~15〇〇m/s), causing the biomedical sensor to measure the liquid because the transmission wave speed is slow, so it does not, any energy is lightly injected into the liquid. Thus, the biomedical sensor of the present invention is suitable for measuring liquids, particularly biosensing and chemical sensing. Furthermore, since the thickness of the biomedical sensor is only a few micrometers thick and the mass density of the thin plate 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, high sensitivity, low operating frequency, short detection time, and low cost. 120400.doc • η · 1333068 [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 torsion plate wave element 1 and a self-assembled monolayer structure 2〇. The curved plate wave element 10 has a meandering substrate cavity η having 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. 1 (herein, it is a top view). The main design parameter of the curved flat wave component 10 is an interdigital sensor ( Interdigital transducer, IDT) electrode spacing, interdigitated sensor electrode pairs, interdigitated sensor electrode overlap length and input/output 璋 (I/O) delay length, and the theoretical formula is derived to find the optimal curved plate Important output characteristics such as the center frequency of the wave element and mass sensitivity. The manufacturing flow of the curved flat wave element 10 is as shown in FIGS. 1B to 1E. Referring to FIG. 1B', a 5 〇〇〇a thick cerium oxide (Si 〇 2) film 1 〇 2 is grown on a substrate 1 〇丨 (in this embodiment, a ruthenium substrate) by using a high temperature furnace tube at 1050 〇c. On the opposite side, a 1500A thick low-stress tantalum nitride (Si3N4) film l〇3 is deposited on the yttrium oxide film i〇2 by a low pressure chemical vapor deposition (LPCVD) system. Depositing a layer of (Cr)/gold (Au) film 104 on one side of the tantalum nitride film 1〇3 by using an electron beam evaporation deposition system (E_gun evap〇rat〇r), where the chromium (Cr) The thickness of the chromium of the gold (Au) film 1〇4 is 200A, and the thickness of the gold is 1500A. The present invention deposits a chromium (Cr)/gold (Au) bottom electrode (ie, the chromium/gold film 120400.doc -12·1333068 104) on a low stress tantalum nitride (SisN4) film 1〇3 of a FPW element to increase Stability and signal-to-noise ratio (S/N) of conventional curved flat wave (Fpw) components 〇 Referring to FIG. 1C, a high-quality zinc oxide (Zn〇) piezoelectric film 105 is deposited by using a radio frequency reducer (RF_Sputter). The oxide thin film 臈1〇5 is further defined by a lithography and etching process. The material of the zinc oxide piezoelectric film 1〇5 has a high electromechanical coupling coefficient, good adhesion to a substrate, and low sound velocity ( Low operating frequency), strong environmental resistance, easy process and compatibility with integrated circuit process. Referring to FIG. 1D and FIG. 1E, the chrome/gold IDT electrode 107' is deposited by spin coating and lithography of a photoresist 106, and the electrode is defined by the lift method (丨ift-〇ff). 1〇7 to form a set of input interdigitated sensors 12 and a set of output interdigital sensors 13. Wherein, the input interdigital sensor 12 converts the electric signal added thereto into an elastic wave by an inverse piezoelectric effect to output 'this elastic wave will contact the output interdigital sensor after a delay time 13, and the positive piezoelectric effect is used to convert the received elastic wave into an alternating signal for output, and the amplitude and phase of the output = sign depends on the geometry of the interdigital sensor. 2A to 2D show an electron scanning microscope (SEM) image of the surface, cross section, suspended film, and film of the FPWiL member, which is apparent from the above figures: ~ (a) ZnO The surface of the film is extremely dense (average diameter and uniform distribution; (b) ΖηΟ film has a very close columnar structure in cross section; (4) (4) Zn0/Si3N4/Si (Vsi suspended sheet) 6μιη); and 120400.doc -13· 1333068 • (4) FPW back (four) cavity structure, suspended sheet (four) substrate exhibits an angle of about -123 degrees. Referring to Figure 3, the zinc oxide film deposited by the invention is analyzed, it is obvious The (002) diffraction angle of the c-axis selection appears at 20=34 32, which is almost completely consistent with the 34.42 shown in the JCPDS data sheet and its diffraction intensity is very high. The half-height value is only 0.352, so the invention is proved. The deposited ΖηΟ film does have very good piezoelectric properties, which is one of the most critical processes for fabricating Fpw Sense#: and its 'diffraction intensity and half-maximum' FWHM ) will rise with the substrate temperature The test plate wave element 1 is sensed by a change in the micromass density or the viscous coefficient, and the curved plate wave element 10 has a thinner thickness dimension. The curved plate wave element 10 is suitable for measuring liquid, in particular, biological sensing and chemical sensing. In the embodiment, the curved flat wave element 1 uses an interdigital sensor (Interdighal φ tranSdUCer, IDT) and The piezoelectric coupling effect is used to generate and detect the wave. It should be noted that the interdigital sensor may include an input interdigital sensor 12 and an output interdigital sensor 13 disposed on the curved flat wave component 10, And the plane lu relative to the 矽 substrate cavity 。, wherein the input interdigital sensor 12 and the output interdigital sensor 13 are used as input/output terminals of the curved slab wave member 10. In addition, as long as Between the input interdigital sensor 12 and the output interdigital sensor 13 - an amplifier (not shown) can be formed - a curved flat wave delay line oscillator. The wheel interdigitated sensor is used to Bending flat wave component 1 电 telecommunications 120400.doc