NISED - A Nanoparticle Immunoassay based on Single-entity Electrochemical Detection

• Applicant: Professor Dr. Bernhard Wolfrum
• Subject Area: Microsystems
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446370753

The aim of this proposal is to investigate a new analytical technique for rapid and selective quantification of biomolecules using single-entity electrochemical detection on a chip. We will make use of thiol-linked silver nanoparticles with recognition molecules including antibodies and aptamers for specifically binding target molecules in solution. The sensor system will comprise an array of closely spaced and individually addressable electrodes for capturing and detecting nanoparticles. Some of the electrodes will be functionalized with recognition molecules via thiol-gold interactions to serve as capture probes for the target molecules during a preliminary incubation phase with the analyte. After incubation and exposure to functionalized nanoparticles, a reductive pulse will be applied to the capture electrodes to release bound nanoparticles by breaking the metal-sulfur bonds. The released particles will subsequently be detected at adjacent detection electrodes via impact electrochemistry. During this process, the silver nanoparticles will be oxidized generating short and defined current spikes. As the frequency of nanoparticle impacts depends on the mass transport of particles to the detection electrode, the rate of recorded current spikes will reflect the number of captured nanoparticles and the concentration of the target molecules in the analyte. A microfluidic confinement will ensure a detection efficiency of the nanoparticles close to 100%. Overall, the proposed concept will provide a highly sensitive immunoassay with electronic readout based on single-entity nanoparticle detection. As a proof of concept we will investigate the performance of this assay for the selective detection of insulin in serum as well as whole blood.

• DFG Programme: Research Grants