Developing an On-Chip Reagentless Cancer screen

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

The development of portable diagnostics with low processing requirements has the potential to improve diagnostic testing in the wider community. Label-free biosensing methods based on electrochemical impedance and capacitance are proven to be highly sensitive, and with a focus on easy miniaturisation and quicker results, these devices are a practical improvement on the multi-step, labelled (sandwich) assays currently available. Additionally, the electrochemical nature of these techniques results in ready integration of methods into microelectronic and microfluidic cells, and an overall reduced complexity in the procedures required for conducting the eventual bioassay. Electrochemical impedance spectroscopy (EIS) in biosensing, as modelled on a Randles equivalent circuit, allows changes at an interface to be detected via variance in the charge transfer resistance (RCT) and capacitance (CDL) of the redox probe in solution. By modifying the interface across which these processes occur with specific receptors, impedance and capacitance may be measured as a function of target capture.3 To date, a range of bioreceptors have been immobilized onto interfaces, commonly utilising gold and carbon electrodes, with varying success. For example, Q. Xu et al. have previously created an impedimetric assay for alpha-synuclein associated with Parkinson's disease, with a clinically significant range and a sensitivity of 3.1 ng mL-1, however in many other projects fouling caused by the non-specific binding of species in biological fluids remains problematic. Currently there are relatively few cancer biomarkers in clinical use and a significant proportion of available assays are directed at treatment selection rather than diagnosis. This project will look to create a platform for the detection of auto-antibodies indicated in early-stage cancer by integrating antigen and antigen-mimic receptors into an electrode surface. Specifically there will be a focus on the use of non-fouling polymer films in the functionalisation of the electrode in order to result in a test with high specificity. Future work will then concentrate on the development of these electrodes into an electrochemical biosensor using impedance and capacitance spectroscopy, with levels of sensitivity suitable for clinical use. Novelty of the research methodology: the use of new peptide receptors to capture antibody epitopes; the design, generation and characterisation of new electrode confined polymer supports; the optimisation of analytical methodologies based on function analysis. This project falls within the EPSRC Physical sciences and Healthcare technologies themes, and specifically the optimising treatments research area. The project also relates directly to the EPSRC strategic themes of Manufacturing the Future (clinical technology, polymer developments, supramolecular chemistry), and Analytical Science. New, highly sensitive, analytical detection platforms are, additionally, of relevance to the Global Uncertainties theme.This project will be conducted in collaboration with Osler Diagnostics, Oxford, UK.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513295/1 01/10/2018 30/09/2023
2368355 Studentship EP/R513295/1 01/04/2019 30/09/2022 Tara Catherine Lurshay