CMOS-MEMS懸臂樑感測平台於生化感測之應用與薄膜電晶體嵌入式換能性能之探討

懸臂樑的彎曲變形特性是許多傳統應力感測系統的核心元件。近年來逐漸帶起一股生物啟發之感測與致動技術的研究風潮。因此本研究利用生物分子專一性造成微懸臂樑的彎曲變形特性，以建構積體電路相容的微懸臂樑感測平台。同時，藉由嵌入式薄膜電晶體的製作，作為感測器訊號性能轉換機制之探討，達到降低製造的成本和提高元件感測可靠度的目的。在生物分子感測應用上，抗菌胜肽(Antimicrobial Peptide, AMP)為先天性免疫中的一員，具有不同的抗病原機制或免疫調節的能力。神經壞死病毒則造成全球海水養殖魚苗的高死亡率及重大損失。因此，針對魚類神經壞死病毒(nervous necrosis viruses, NNV)與兩種不同的抗菌胜肽，利用免標定 (label-free)的光學式微懸臂樑感測平台來定性定量彼此間對中和病毒的效力。而此中和病毒效力的強弱可由實驗上即時(real-time)的表面應力量測結果，利用吸附模型萃取出親和力以及吸附常數。結果顯示，抗菌胜肽TH1-5較cSALF ，在此兩參數的萃取上分別展現2.1倍與4.43倍的差異，代表TH1-5對於病毒有較強及較快的吸附效力。此結果提供了定量的證據來證實抗菌蛋白透過凝集病毒顆粒來阻擋NNV 吸附寄主細胞。此研究未來可應用在相關抗菌胜肽及其藥物或疾病的快篩。在傳感機制上，本研究首度提出低成本的薄膜電晶體式懸臂樑，將電晶體埋藏於懸臂樑高應力承受處作為訊號讀取轉化的依據。利用直流電性參數量測以及低頻雜訊量測(1/f)，分析元件在承受外加的壓縮應變與其局部區域上殘留應力的關係。外加的壓縮應變是用來模擬生物分子鍵結後所造成的元件微小電流改變；而薄膜沉積過程中局部所形成的本質應力，其在飽和電流的影響上則造成顯著的差異。實驗結果說明，這雙重藕合的外加與本質應力會造成生物分子辨識過程中的複雜性，使得量測結果缺少再現性。藉由飽和區汲極電流的變化作為懸臂樑彎曲量的感測指標，此元件最佳的零敏度為53 nA/μm。此外，應力的施加亦造成元件在遷移率及臨界電壓分別為-1.58 cm2/V-s and -75 mV的變化。此兩參數同步的減少，會因臨界電壓變化所導致的汲極電流增幅，反而補償了遷移率變化所導致的電流減少。低頻雜訊量測特性分析則顯示元件本質的雜訊為1.34 nA，低於文獻上所發表的單晶矽式的懸臂樑。然而，氧化層缺陷密度需在高應力的施加下，才會略為減少。此結果說明在目前量測元件性能的應力施加區間內，缺陷的效應對於整體電性應可忽略。最後，針對殘留應力所造成整片晶圓上不同元件間性能的變化作出探討，發現元件懸浮後，由於記憶的殘留應力差異，可使各別元件的汲極飽和電流造成顯著的差異。因此本研究藉由量測元件的起始汲極飽和電流以及適當選取汲極飽和電流對轉導的比值，可成功的建立感測元件壓應力與其性能間的關聯，此線性分散特性曲線(correlation coefficients R>0.978) 可作為後續性能校正之用，藉此消除元件間性能的差異，有利於未來多工陣列化大量資料分析的應用。

關鍵字

懸臂樑；生物感測器；抗菌胜肽神經壞死病毒；薄膜電晶體；殘留應力；低頻雜訊量測；元件性能差異；校正方法

並列摘要

The bendable microcantilever (MCL) which was the central element in many mechanical stress sensors have proven to be a valuable tool in the advancing fields of biologically inspired sensing or actuating system. This study focuses on the development of CMOS compatible microcantilever for novel biomolecular detection and the characterization of Thin-film Transistor (TFT)-embedded signal transduction. The evolution towards transistor- based readout technique can provide the growing need for a compact device with multiplexed sensing of multiple biomarkers in the future. In biomolecular application, this work reports the label-free binding kinetics of fish-infected grouper nervous necrosis virus (NNV) and selected antimicrobial peptides (AMP) by optical-readout-based microcantilever sensors. AMPs, the vital member in an innate immunity, can be promising candidates in the fight against pathogens or can exhibit other physiological functions by modulating immune response of infected cells. Grouper NNV which primarily cause mass mortality of many marine cultured fish species, and two selected AMPs in this study were found to inhibit viruses by agglutinating its virions to form aggregates. The binding affinity and kinetic rate constants of molecular recognition events calculated for NNV-AMP(TH1-5) compared to NNV-AMP(cSALF) were found to be 2.1-fold and 4.43-fold, respectively, indicating TH1-5 effectively bind with NNV more than cSALF. Therefore, the microcantilever biosensing technique provides a potential and useful screening of AMPs for affinity to NNVs. In the study of signal transduction technique, the low-cost poly-Si TFT-embedded MCL is firstly reported. The comprehensive electrical investigation of current-voltage characteristics, transfer and low-frequency noise (1/f) characteristics was performed to further characterize the signal transduction under in-situ residual stress and externally compression stress for monitoring deflection. Meanwhile, the residual stress that was induced by inherent thin-film process variation resulted in a wide range of initial saturation drain currents, and the external compression stress for simulation of biomolecular recognition-induced surface stress mainly exhibited a small change in saturation drain current. As a result, coupled effect of electrical responses was found to be complex for measurement of biomolecular recognition. The result of change in saturation drain current under external stresses showed the best sensitivity of 53 nA/μm. A comparable change of mobility and threshold voltage were also noticed about -1.58 cm2/V-s and -75 mV, respectively under the applied compressive bending of 50 μm. The decrease of both parameters indicates the resulting drain current change is the trade-off of mobility and threshold voltage. By 1/f noise analysis, the obtained current noise level of 1.34 nA is lower than the reported value for piezoresistive MOSFET noise. Also, interface trap generation tends to be reduced under highly compressive strain, while trap density change can be considered as negligibly small within the proper range of compressive loading. Moreover, MCL residual stresses that yield initial curvature may also induce an appreciable shift of initial saturation current due to the memorized strain effect. Therefore, this study demonstrated that the effect of varied residual stresses contributed to the sensor sensitivity can be successfully decoupled from that of external compression stresses by measuring the initial saturation current and maintaining the drain current-to-transconductance ratio. As a result of a linear correlation (correlation coefficients R>0.978) for sensor sensitivity with respect to the initial saturation current associated with the residual stress, this finding provides an approach for the TFT-embedded sensor calibration to suppress the device-to-device variation, enabling the potential of multiplexing array in the future.

並列關鍵字

Microcantilever ； Biosensor ； Antimicrobial peptide ； Nervous necrosis virus ； Thin film transistor ； Residual stress ； Low-frequency noise ； Performance discrepancy ； Calibration method

參考文獻

[1]R. R. Tummala, "Moore's law meets its match," IEEE Spectr. 43 (6), 44-49 (2006).

[2]J. R. Barnes, R. J. Stephenson, M. E. Welland et al., " Photothermal spectroscopy with femtojoule sensitivity using a micromechanical device," Nature 372 (6501), 79-81 (1994).

[3]W. P. King, T. W. Kenny, K. E. Goodson et al., "Design of atomic force microscope cantilevers for combined thermomechanical writing and thermal reading in array operation," J. Microelectromech. Syst. 11 (6), 765-774 (2002).

[4]R. Berger, E. Delamarche, H. P. Lang et al., "Surface stress in the self-assembly of alkanethiols on gold," Science 276 (5321), 2021-2024 (1997).

[5]J. Sambrook, D.W. Russell, "Molecular cloning: a laboratory manual," Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2001)

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CMOS-MEMS懸臂樑感測平台於生化感測之應用與薄膜電晶體嵌入式換能性能之探討

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