Point-of-care, electronic detection of pathogenic bacteria using redox-active biomarkers

Overview

This project invested in developing new sophisticated, label-free electronic sensor arrays with the potential to accelerate biomarker discovery, facilitate early diagnosis, transfer clinical testing to point-of-care and provide the multiplexed, high-sensitivity diagnostics required for personalized and stratified medicine. In collaboration with colleagues at the University of Leeds, a novel, biocompatible self-assembled monolayer (SAM) has been produced that enables the integration of functional probe-molecules, such as antibodies, with underlying electronic circuitry. The project also evolved a new approach for monitoring molecular interactions electronically.

In detail

The aim of this project was to establish and evaluate a point-of-care diagnostic to provide rapid, sensitive and specific Neisseria meningitidis screening. This diagnostic tool would combine microelectronic devices fabricated using the same, low-cost technology developed in the semiconductor industry, with molecular probes targeting N. meningitidis specific markers allowing quantitative and rapid screening in a single, simple readout, portable device. The technology developed through this programme would be relevant to the detection of a wide range of pathogenic bacteria and the longer-term vision is to provide a versatile technology to enable rapid diagnosis of bacterial infection at point-of-care.

In collaboration with colleagues at the University of Leeds, a novel, biocompatible self-assembled monolayer (SAM) has been developed that enables the integration of functional probe-molecules, such as antibodies, with underlying electronic circuitry. The SAM consists of an alkane-component that ensures formation of a well-packed monolayer, a PEG-component that ensures functionality of the immobilized protein while minimizing non-specific protein adsorption and a functional amine group to permit chemo-selective protein immobilization. The project has developed a new approach for monitoring molecular interactions electronically. The strategy uses charge-sensitive redox labels incorporated into an immobilized protein layer. Formation of the protein-ligand complex modifies the electrostatic environment local to the redox label, resulting in a shift in the formal potential.

The next-generation of electronic biosensors will ideally require limits of detection down to just a few molecules in a finger-prick of blood. This will demand a step change in sensor technology, requiring high miniaturization and vastly increased sensitivity. Research is now being undertaken to investigate ultra-sensitive nanoelectronic sensors based on high-density arrays of single-electron transistors (SETs).
The project now includes the Department of Chemistry at the University and has led to collaborations with the University of Leeds and with the Hitachi Cambridge Laboratory.

Ouputs

Grants

• Thomas Krauss, BBSRC, Label-free, Real-time, Spatial-resolution (LRS) immunoassay: 2D mapping of extracellular signalling molecules, £181,954.14

Publications

• Catenazzi, M.C., Jones, H., Wallace, I., Clifton, J., Chong, J.P., Jackson, M.A., Macdonald, S., Edwards, J., Moir, J.W. (2014). A large genomic island allows Neisseria meningitidis to utilize propionic acid, with implications for colonisation of the human nasopharynx. Molecular Microbiology, doi: 10.1111/mmi.12664
• Murray, J., Nowak, D., Pukenas, L., Azhar, R., Guillorit, M., Wälti, C., Critchley, K., Johnson, S., & Bon, R.S. (2014). Solid phase synthesis of functionalised SAM-forming alkanethiol-oligoethyleneglycols. J. Mater. Chem. B DOI: 10.1039/C4TB00573B