Surface-Bound Electrochemical Glycation Sensors

表面结合电化学糖基化传感器

• 批准号: 1792318
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1792318
• 关键词: Surface; Bound; Electrochemical; Glycation; Sensors

This research project combines molecular receptors and materials based surface technology to develop sensors for the detection and quantification of disease specific markers at the chemistry and biology interface. The main target of this project is to develop diagnostic sensors. The objectives of this project include organic synthesis, materials chemistry, and nanotechnology. The project will result in a novel sensor system consisting of molecular based receptors suitable for the direct analysis and quantification of glycated proteins that have associated with diseases such as diabetes and Alzheimer's disease (AD). The project will also provide an excellent environment for the development of a PhD student. Since, the project will immerse the student in both synthetic chemistry and materials chemistry at the chemistry and biology interface as well providing training in analytical chemistry.Our aim is to develop effective sensors for determining the levels of protein glycation for diabetic patients, with the aim of quantifying particular diagnostic (glycation) biomarkers that are related to the progression of diseases, such as diabetes and AD. The successful realization of these challenges could lead to an overall improvement in the diagnosis, monitoring, and treatment of the increasingly wide range of disease states that are associated with uncontrolled levels of glucose in the bloodstream. Monitoring and Treatment is perhaps the most exciting aspect of the project since early stage diagnosis will allow early intervention/treatment and hence the possibility to cure a condition before the patient is even aware of symptoms. Obviously this aspect of the project will also allow for the evaluation of particular interventions/treatments and ultimately an improvement in the efficiency of a particular treatment strategy.Simple molecular receptors will be prepared to allow their attachment to both gold and hydrophilic indium tin oxide (ITO) coated glass surfaces. These receptors will then be used to prepare on-surface based sensors. We will use ferrocene as the electrochemical read-out unit for binding; given the system is modular this ferrocene unit can be replaced with different electrochemical units once the concept has been validated. In the first instance a monoboronic acid receptor will incorporated into the system. We have extensive experience in preparing multi receptor probes therefore the receptors will be improved by the addition of multiple boronic acids (or other receptor units) in order to enhance binding with specific glycated proteins.In order to examine the electrical conductivity behavior of the sensor, the boronic acid receptors will be attached to a gold surface. The sensor surfaces will be prepared using an alpha lipoic acid (ALA) appended boronic acids. The surface coverage of the receptors will be varied by adding simple alkyl thiols, thus diluting the concentration of active receptors on the surface. It is predicted that the binding of the boronic acids with glycated proteins will affect the electrochemical behavior of the ferrocene appended receptor. The gold surface will then report on the changes in electrochemistry of the ferrocene and changes in the electrochemical properties will be used to quantify binding of the sensor with a specific glycated proteins. Siloxane-based chemistry will also be used to develop sensors with hydrophilic surfaces. In particular redox-active monolayers covalently assembled on indium-tin-oxide (ITO)-coated glass will be prepared and evaluated. The ultimate aim of the project is to generate sensor materials capable of high-throughput detection and analysis.

该研究项目结合了分子受体和基于材料的表面技术，以开发用于在化学和生物学界面检测和定量疾病特异性标志物的传感器。本项目的主要目标是开发诊断传感器。该项目的目标包括有机合成，材料化学和纳米技术。该项目将产生一种新型传感器系统，该系统由分子受体组成，适用于直接分析和定量与糖尿病和阿尔茨海默病（AD）等疾病相关的糖化蛋白。该项目还将为博士生的发展提供良好的环境。由于，该项目将使学生沉浸在合成化学和材料化学的化学和生物学接口，以及提供分析化学的培训，我们的目标是开发有效的传感器，用于确定糖尿病患者的蛋白质糖化水平，目的是量化与疾病进展相关的特定诊断（糖化）生物标志物，如糖尿病和AD。这些挑战的成功实现可能会导致在诊断，监测和治疗与血液中葡萄糖水平不受控制相关的越来越广泛的疾病状态方面的全面改善。监测和治疗可能是该项目最令人兴奋的方面，因为早期诊断将允许早期干预/治疗，因此有可能在患者意识到症状之前治愈疾病。显然，该项目的这一方面也将允许对特定干预/治疗进行评估，并最终提高特定治疗策略的效率。将制备简单的分子受体，使其能够附着在金和亲水性氧化铟锡（ITO）涂层的玻璃表面。然后，这些受体将用于制备表面传感器。我们将使用二茂铁作为结合的电化学读出单元;考虑到系统是模块化的，一旦概念得到验证，该二茂铁单元可以用不同的电化学单元替换。在第一种情况下，将单硼酸受体掺入系统中。我们在制备多受体探针方面有着丰富的经验，因此我们将通过添加多个硼酸（或其他受体单元）来改善受体，以增强与特定糖基化蛋白的结合。为了检测传感器的导电行为，硼酸受体将附着在金表面。传感器表面将使用添加有硼酸的α-硫辛酸（ALA）制备。受体的表面覆盖度将通过添加简单的烷基硫醇来改变，从而稀释表面上活性受体的浓度。据预测，硼酸与糖基化蛋白质的结合将影响二茂铁附加受体的电化学行为。然后，金表面将报告二茂铁的电化学变化，电化学性质的变化将用于量化传感器与特定糖化蛋白质的结合。基于硅氧烷的化学也将用于开发具有亲水表面的传感器。特别是氧化铟锡氧化物（ITO）涂层玻璃上共价组装的氧化还原活性单层将被制备和评估。该项目的最终目标是生成能够进行高通量检测和分析的传感器材料。