Development of Aptamer Functionalized ZnO Micro-ring resonators for BioSensing

用于生物传感的适体功能化氧化锌微环谐振器的开发

• 批准号: 2111221
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2111221
• 关键词: Development; Aptamer; Functionalized; ZnO; Micro

The aim of this PhD project is to develop a new biological sensing platform that will combine optical and electrical detection of a wide range of potential diseases, pathogens and toxins into a compact real time device capable of carrying out point of care diagnosis. A micro ring resonator (MRR) is a refractive index-based sensor. In a ring resonator light propagates in the form of circulating waveguide modes, which are a result of the total internal reflection of the light along the curved boundary of the ring between high and low refractive index materials. The light is coupled into the ring via an adjacent linear waveguide located within a few hundred nanometers. The circulating waves form a constructive interference pattern when the wavelength are divisors of the ring circumference. These are the so-called resonance frequencies of the ring resonator. These optical modes are sensitive to the evanescent field surrounding the waveguide, hence a bio-molecular binding event will cause a change in the resonance frequency. The change in the field is larger the closer the target protein is to the actual resonator. Recently short single stranded DNA strands, so called aptamers, have been drawing attention as the potential replacement of antibodies in sensor devices. The advantage of aptamers is that they are smaller than antibodies and hence bring the target proteins much closer to the sensing components, which results in a potential increase in the response. The potential for these systems is in the detection of proteins, both for infectious diseases and food toxins, with the possibility to achieve multi-channel sensors by utilizing arrays of MRRs. The project will also look to utilize aptamer functionalized ZnO to realize Field Effect Transistors (FETs) that can operate as electrical based bio sensor. The aptamer-FET based detector has a high sensitivity; a small perturbation in charge distribution near the channel will result in a marked change in the current, an order of magnitude difference is expected when directly comparing an aptamer FET with an antibody FET. In addition, the device can have high selectivity, enhanced by the use of multiple aptamer-FETs in an array, each probing for a different protein. As a result it will be possible to determine the protein fingerprint in any liquid sample. The detector can be operated at a low supply voltage of typically 3 V. This means that the translational potential of this work is most relevant to regions where laboratory infrastructure is scarce, technical ability is limited and time is short. This could mean UK primary care, where there is huge pressure for a quick diagnosis, improved accuracy of infection diagnosis and improved antibiotic stewardship, but also in a developing world setting. The final stage of the project will seek to combine these 2 sensors into one where ZnO is used as both the channel material in the aptamer-FET and the waveguide in the aptamer-MRR, allowing the combination of both the optical and electrical sensing device in a single sensor occupying the same space. The advantage of this is that the two techniques will provide a control of each other without the need of additional experiments or multiple sensors on one device. Although this approach will be applicable for a wide variety of proteins, the initial work will focus on one important example: aflatoxin B1. Aflatoxins are one of the most dangerous of the mycotoxins and they are the secondary metabolic products of the fungal genus Aspergillus. The most toxic compound is aflatoxin B1, which affects not only human, but also other primates, mammals, fish, birds and rodents. It mainly affects the liver function. In addition aflatoxin B1 is considered to be the most toxic natural hepatocarcinogen. As a result many countries have limits to the amount of aflatoxin that can be present in foodstuff, for example the European Union has set the limit at 2 ug kg-1 for aflatoxin B1.

该博士项目的目的是开发一种新的生物传感平台，该平台将联合收割机光学和电学检测广泛的潜在疾病，病原体和毒素结合到一个紧凑的真实的时间设备中，能够进行护理点诊断。微环谐振器（MRR）是一种基于折射率的传感器。在环形谐振器中，光以循环波导模式的形式传播，这是光沿着高折射率材料和低折射率材料之间的环的弯曲边界的全内反射的结果。光通过位于几百纳米内的相邻线性波导耦合到环中。当波长是环周长的约数时，循环波形成相长干涉图样。这些是所谓的环形谐振器的谐振频率。这些光学模式对波导周围的倏逝场敏感，因此生物分子结合事件将引起谐振频率的变化。目标蛋白质越接近实际谐振器，场的变化越大。最近，短的单链DNA链，所谓的适体，已经引起人们的注意，作为潜在的替代抗体的传感器设备。适体的优点是它们比抗体小，因此使靶蛋白更接近传感组件，这导致响应的潜在增加。这些系统的潜力在于检测蛋白质，包括传染病和食物毒素，并有可能通过利用MRR阵列实现多通道传感器。该项目还将利用适体功能化ZnO来实现场效应晶体管（FET），可以作为基于电的生物传感器。基于适体-FET的检测器具有高灵敏度;通道附近电荷分布的小扰动将导致电流的显著变化，当直接比较适体FET与抗体FET时，预计会有一个数量级的差异。此外，该装置可以具有高选择性，通过在阵列中使用多个适体FET来增强，每个适体FET探测不同的蛋白质。因此，将有可能确定任何液体样品中的蛋白质指纹。该检测器可以在通常为3 V的低电源电压下工作。这意味着这项工作的转化潜力与实验室基础设施稀缺、技术能力有限且时间短的地区最相关。这可能意味着英国的初级保健，在那里有巨大的压力，快速诊断，提高感染诊断的准确性和改善抗生素管理，但也在发展中国家的环境。该项目的最后阶段将寻求将这2个传感器联合收割机组合成一个传感器，其中ZnO用作适体-FET中的通道材料和适体-MRR中的波导，允许在占据相同空间的单个传感器中组合光学和电学传感装置。这样做的优点是，这两种技术将提供彼此的控制，而不需要额外的实验或在一个设备上的多个传感器。虽然这种方法将适用于各种蛋白质，但最初的工作将集中在一个重要的例子：黄曲霉毒素B1。黄曲霉毒素是曲霉属真菌的次级代谢产物，是最危险的真菌毒素之一。毒性最大的化合物是黄曲霉毒素B1，它不仅影响人类，而且影响其他灵长类动物、哺乳动物、鱼类、鸟类和啮齿动物。主要影响肝功能。此外，黄曲霉毒素B1被认为是毒性最大的天然肝癌原。因此，许多国家对食品中黄曲霉毒素的含量有限制，例如，欧洲联盟将黄曲霉毒素B1的限量定为2微克/千克。