Immuno-biosensor for heart failure markers

Postdoc project Denis Dorokhin

The aim of this project is to investigate the sensitivity and selectivity of biosensor technology for the detection of biomarkers for chronic heart failure. The biomarker model system is N-terminal pro-Brain Natriuretic Peptide (NT-proBNP), a 76-amino-acid peptide secreted by ventricular and atrial myocytes in response to increased mechanical stress. Studies have shown NT-proBNP measurements to be useful in the diagnosis of heart failure and risk stratification of patients with different cardiac pathologies, e.g. patients with possible complications are characterised by significantly higher NT-proBNP levels. The concentration of NT-proBNP in blood plasma can increase from picograms/ml for healthy adults to several tens of nanograms/ml for patients with heart failure.

The research involves the study of association and dissociation processes in a magnetic-label biosensor system and methods to improve the biologically-specific binding processes. Superparamagnetic particles functionalised with antibodies specific to the biomarker are used in a sandwich immunoassay. The particles capture the biomarker molecules in the sample solution; applied magnetic fields allow for both the controlled transport of particles and biomarkers through the bulk sample to the sensor surface, as well as the actuation of particles at the sensor surface. An optical detection method is used: particles are detected in an evanescent optical field formed on the sensor surface (see Fig1).

In this PhD project we will investigate the kinetics and specificity of association and dissociation processes. The understanding of these processes is important for signal optimisation and background reduction respectively. Our investigations will involve measurements of the presence and concentration of particles at the sensor surface, their height above the surface, and their rotational properties. The dependence of association and dissociation on the molecular mobility of binding sites will be investigated by attaching tethers onto particles and surfaces.

This project is part of the TRIUMPH project of the Center for Translational Molecular Medicine (CTMM, see www.ctmm.nl).