基于SPR和石墨烯FET的无标记亲和型生物医学传感器研究

发布时间：2018-06-29 00:56

本文选题：表面亲和型生物医学传感器 + 表面等离子体共振　；参考：《南开大学》2014年博士论文

【摘要】：随着生物医学领域的研究不断深入,用于生物医学检测以及生化分析的传感器技术被提出了越来越高的要求。为了从生物医学检测中获取更高质量的信息,应用先进传感技术和敏感材料的新型生物医学传感器技术已经成为近年来学术界的研究热点。近年来,新型生物医学传感器开始向自动化、微型化与集成化和在线连续监测等方向发展。在这种发展趋势下,一种基于生物分子间特异性结合的新型生物医学传感器——表面亲和型生物医学传感器得到了越来越多的关注。表面亲和型生物医学传感器不再使用传统的基于酶和各种标记手段,能够在微小尺度的集成传感器件上实现对目标生物分子的无标记、特异性定量检测。在本文中,我们对表面亲和型生物医学传感器领域中的两个热点研究方向,即表面等离子体共振(Surface plasmon resonance, SPR)生物医学传感器(第二到第四章)和石墨烯场效应管(Graphene field-effect transistor, GFET)生物医学传感器(第五到第八章)分别进行了研究。本文所述的研究中贯彻一种思路,即尽可能将传感器小型化和集成化,以期能用最少量的仪器设备、最低的功耗、最小的器件体积和最少的生物样品消耗完成对所需的生物信息高质量获取。SPR和GFET器件的设计、制作和应用都遵循这一思路。其中,SPR生物医学传感器是一种先进的光学传感技术,本文中涉及SPR部分的具体研究内容主要包括： 1.基于小型商用光谱仪设备,设计了一种光谱(波长)调制型SPR传感器。通过观测一定波段内复色光的衰减全反射(Attenuated total reflection, ATR)光强,检测在SPR敏感膜一侧发生的折射率变化和生物分子亲和引起的等效折射率变化。 2.根据透明液体对光束的折射作用,设计了一种实现多通道SPR扫描的检测机制。通过使用不同折射率的光学耦合液,将入射光束引导到不同的检测通道上,取代了传统多通道SPR传感系统使用的机械扫描机制,缩小了传感器的体积并简化了扫描操作。 3.通过对实验过程中发现的噪声信号的分析,设计了一种依靠多通道分时扫描提供实时更新的SPR光强参考基线的检测机制。实验证明,通过实时刷新参考基线,可以显著改善SPR检测的噪声水平。本文的另一部分研究工作中,基于石墨烯场效应管的生物医学传感器是一种使用近年来极为热门的石墨烯材料的电子学传感器。本文中对GFET器件的研究主要包括： 1.基于化学蒸镀沉积(Chemical vapor deposition, CVD)方法的石墨烯合成。通过总结CVD石墨烯的合成条件,摸索并总结出了一套快速、简捷且低成本制备适用于传感器制作的石墨烯材料的方法。 2.基于微机电系统(Micro-Electro-Mechanical System, MEMS)加工工艺的传感器件制造。MEMS工艺是一种基于IC设计技术总结的用于制作微米尺度器件的标准工艺。本文详细总结了基于MEMS工艺的石墨烯场效应管传感器件设计和制造流程。 3.石墨烯器件的电场效应和电子学特性研究。通过对石墨烯在受到带电微粒掺杂时的转移特性和噪声水平进行实验测量和理论分析,本文总结了石墨烯场效应管在用作传感器时的使用规范和优化准则。 4.通过对核酸分子间的互补配对杂交和生物分子特异性结合的动力学过程及其生物学机制进行了深入研究,并基于此对石墨烯进行生化修饰,实现了器件对小分子激素生物标志物脱氢表雄甾酮(Dehydroepiandrosterone,DHEA-S)的无标记、特异性定量检测。在验证器件可以用于生物医学传感器的同时,解决了现存的表面亲和型传感器检测小分子的难题。
[Abstract]:In recent years , a new biomedical sensor based on advanced sensing technology and sensitive material has become a hot spot in the academic community in recent years . In recent years , a new biomedical sensor with advanced sensing technology and sensitive material has become a hot spot in the academic community in recent years . In recent years , a novel biomedical sensor _ surface affinity type biomedical sensor based on the specific binding of biomolecules has been paid more and more attention .

In this paper , we study two hot topics in the field of surface affinity biomedical sensors , namely Surface plasmon resonance ( SPR ) biomedical sensors ( Chapters 2 to 4 ) and graphene field effect transistors ( GFET ) biomedical sensors ( Chapters V to VIII ) .

Among them , SPR biomedical sensor is an advanced optical sensing technology , in this paper , the specific research content of SPR section mainly includes :

1 . Based on the small commercial spectrometer equipment , a kind of spectral ( wavelength ) modulation SPR sensor is designed . By observing the attenuation total reflection ( ATR ) intensity of the complex light in a certain wavelength band , the refractive index change and the equivalent refractive index change caused by the biological molecules are detected on the side of the SPR sensitive film .

2 . According to the refraction effect of the transparent liquid on the light beam , a detection mechanism for realizing the multi - channel SPR scanning is designed . By using the optical coupling liquid with different refractive indexes , the incident light beam is guided to different detection channels , the mechanical scanning mechanism used by the conventional multi - channel SPR sensing system is replaced , the volume of the sensor is reduced and the scanning operation is simplified .

3 . Based on the analysis of the noise signal found during the experiment , a detection mechanism of SPR light intensity reference baseline based on multi - channel time - sharing scanning is designed . Experimental results show that the noise level of SPR detection can be significantly improved by refreshing the reference baseline in real time .

In another part of this paper , the biomedical sensor based on graphene field effect tube is an electronic sensor using graphene material which is very popular in recent years . The research of GFET device mainly includes :

1 . Synthesis of graphene based on chemical vapor deposition ( CVD ) method . By summarizing the synthesis conditions of CVD graphene , a rapid , simple and low - cost method for preparing graphene material suitable for sensor fabrication is also summarized .

2 . The fabrication of sensor parts based on Micro Electro - Mechanical System ( MEMS ) processing technology . MEMS technology is a standard process for manufacturing micron scale devices based on IC design technology . The design and manufacturing flow of graphene field effect tube sensor based on MEMS technology are summarized in detail .

3 . The electric field effect and the electronic properties of graphene devices are studied . Through the experimental measurement and theoretical analysis of the transfer characteristics and the noise level of the graphene in the doping process of charged particles , the usage specification and the optimization criterion of the graphene field effect tube as sensors are summarized in this paper .

4 . Through the research on the dynamic process and biological mechanism of complementary paired hybridization and biomolecule - specific binding between nucleic acid molecules , and based on the biochemical modification of the graphene , the label - free and specific quantitative detection of the dehydroepiandrosterone of the small molecule hormone biomarker is realized by the device , and the problem that the existing surface affinity type sensor detects small molecules is solved while the verification device can be used for biomedical sensors .
【学位授予单位】：南开大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318;TP212

【共引文献】