Magnetic particle actuation for functional biosensors

PhD project Xander Janssen

Master students: Machteld Lamers, Ben de Clercq, Joost van Noorloos.

Molecular processes play a major role in the biology of the human body. As a consequence, molecular-level information can be very effectively used for medical diagnostics. Particles with nanometer to micrometer sizes are widely used as carriers and labels in bio-analytical assays. An important class of particles used in in-vitro diagnostics are so-called superparamagnetic particles, which consist of magnetic nanoparticles embedded inside a non-magnetic matrix. The absence of magnetic material in biological samples allows for a controlled application of magnetic fields. Superparamagnetic particles are therefore powerful because they can be easily manipulated and reliably detected inside complex biological fluids. These properties are exploited in magnetic-label biosensors, in which magnetic particles are used as labels to measure the concentration of target molecules in a biological sample.

In this project we have investigated the properties of superparamagnetic particles and developed new techniques for a novel generation of biosensors -- called multifunctional biosensors -- in which the concentration as well as a functional property of biological molecules can be determined (Janssen et al, Biosensors Bioelectronics, 2008 and 2009). This is done using controlled magnetic manipulation of the magnetic particles that are bound as a label to the molecules. The application of translational forces as well as rotational torque can reveal information about the properties of the biological molecules such as bond forces and torsional stiffness.

One highlight is that we have been able to measure the torsional stiffness of a protein complex using rotational excitation of the particles. As a model system we used protein G on the particles and IgG on a polystryrene surface. The protein G binds selectively to the crystallisable part of the IgG antibody. The angular orientation of the particles show an oscillating behavior upon applying a rotating magnetic field. The amplitude of the oscillation decreases with increasing antibody concentration, which we attribute to the formation of multiple bonds between the particle and the substrate. By evaluating the details of the oscillatory behavior, we found a lower limit of the torsional modulus of the IgG-protein G complex of 6×10-26 Nm2. The torsional modulus is two orders of magnitude larger than values for dsDNA found in literature. We attribute the  difference to the structural properties of the molecules: DNA is a long and flexible chain-like molecule, whereas the protein G and IgG molecules are globular due to molecular folding.