Surface-Bound Electrochemical Glycation Sensors
Lead Research Organisation:
University of Bath
Department Name: Chemistry
Abstract
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.
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.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509589/1 | 01/10/2016 | 30/09/2021 | |||
| 1792318 | Studentship | EP/N509589/1 | 01/10/2016 | 31/12/2019 | Maria Odyniec |
| Description | This research has focused on the development of novel molecular diagnostics to be able to detect disease specific markers of 'non communicable diseases (NCDs)'. NCD's tend to be of long duration with physiological and genetic origins. Alzheimer's and cancer are two examples of such diseases, To develop a diagnostic, the differences between diseased and healthy states need to be identified. Often with NCD's there is a change in the chemical make up of a cell or cells. These small micro-environmental changes in cells or tissues including; increased levels of reactive oxygen species (ROS), changes in enzyme activity and differences in pH, can have destructive effects. There is a plethora of small molecule diagnostics which can detect these changes, however many lack selectivity. A significant problem with NCD's is that the cell often requires the marker it is over expressing, at lower concentration to function normally. Therefore, molecular sensors designed to detect a single disease marker in a complex system may yield false positive signals. In this research we have sought to develop dual-activated diagnostic systems which incorporate an 'AND' logic gate. This means that the sensor can only be activated in the presence of two activating analytes. In the presence of one analyte the sensor will not turn on. We have also sought to develop a theranostics; The combination of diagnostics and therapy. Theranostics is a novel concept which has gained traction in recent years. It is particularly useful in surgery, where a surgeon can inject a 'masked sensor' which activates in cancerous tissues. Once the sensor is activated it will also release a cytotoxic drug, causing any diseased tissue left behind to be treated. This is a type of targeted therapy. |
| Exploitation Route | The molecules that I am trying to design and synthesise in this project are put forward for in vivo and in vitro studies with collaborators. If those molecules are successful in these studies i.e. are able to enter cells they have potential for use in the healthcare and biotechnology sectors. These sensors can be modified to have more favourable wavelengths for imaging applications, or they can be incorporated into point of care devices. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |