Multimodal electrochemical and nanoplasmonic biosensors using ferrocene-crowned nanoparticles for kinase drug discovery applications

• Electrochemical impedance, open circuit potential and differential pulse volammetry are combined on a flow cell for parallel sensing of an array of electrodes.
• Gold nanoparticles and a thiolated ferrocenyl compound are used as reagents to provide extra sensing capabilities.
• Localised surface plasmon resonance is used to provide further signal validation.
• Protein phosphorylation driven by kinases is successfully detected with the multimodal sensors.

The use of on-chip multimodal sensing approaches is very promising towards integrated biosensing systems, which measure different parameters involved in biomolecular interactions and provide automated validation of true positives. In this report, we investigate a proof of concept that enables multiple detection technologies for screening inhibitors of kinase activity, which is a crucial process in drug discovery applications. We demonstrate the integration of electrochemical techniques on the same chip, namely, differential pulse voltammetry, impedance spectroscopy, and direct open circuit potential measurements. Gold nanoparticles that attach to the thio-phosphorylated proteins facilitate localised surface plasmon resonance detection. The addition of thiolated ferrocene, which attaches to the nanoparticles like a crown, enables sensitive electrochemical amperometric detection of kinase activity. This novel multimodal biosensor provides a more rigorous measurement of biomolecules, with wide significance in biomedical, environmental, and pharmaceutical applications.

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