The demand for easy to use and cost effective medical technologies inspires scientists to develop innovative lab-on-chip technologies for point-of-care in vitro diagnostic testing. To fulfill medical needs, the tests should be rapid, sensitive, quantitative, and miniaturizable, and need to integrate all steps from sample-in to result-out. Here, we review the use of magnetic particles actuated by magnetic fields to perform the different process steps that are required for integrated lab-on-chip diagnostic assays. We discuss the use of magnetic particles to mix fluids, to capture specific analytes, to concentrate analytes, to transfer analytes from one solution to another, to label analytes, to perform stringency and washing steps, and to probe biophysical properties of the analytes, distinguishing methodologies with fluid flow and without fluid flow (stationary microfluidics). Our review focuses on efforts to combine and integrate different magnetically actuated assay steps, with the vision that it will become possible in the future to realize integrated lab-on-chip biosensing assays in which all assay process steps are controlled and optimized by magnetic forces.

Ensembles of magnetic particles are known to align and aggregate into multi-particle clusters in an applied magnetic field, and the physical laws governing these processes are well described in literature. However, it has been elusive how to achieve the opposite process, i.e. the disaggregation of particle clusters in a magnetic field. We report a novel method to disaggregate clusters of superparamagnetic microparticles using time-dependent magnetic fields. The disaggregating field is designed to generate repulsive dipole-dipole forces between the particles and to stabilize the disaggregated particles on a physical surface. We demonstrate the disaggregation of large clusters of several tens of particles, within about one minute, using fields generated by a multipole electromagnet. After the disaggregation process the particles are uniformly distributed over the surface and ready for further lab-on-chip processing. Our results represent a novel methodology to disaggregate magnetic particle clusters and thereby improve the effectiveness and reproducibility of biological assays based on magnetic microparticles.

The mechanical properties of the cell membrane and the subjacent actin cortex are determinants of a variety of processes in immunity and cell division. The lipid bilayer itself and its connection to the actin cortex are anisotropic. An accurate description of the mechanical structure of the cell membrane and the involved dynamics therefore necessitates a measurement technique that can capture the inherent anisotropy of the system. Here, we combine magnetic particle actuation with rotational and translational particle tracking to simultaneously measure the mechanical stiffness of monocytic cells in three rotational and two translational directions. When using particles that bind via integrins to the cell membrane and the subjacent cortex, we measured an isotropic stiffness and a characteristic power-law dependence of the shear modulus on the applied frequency. When using particles functionalized with immunoglobulin G, we measured an anisotropic stiffness with a 10-fold-reduced value in one dimension. We suggest that the observed reduced stiffness in the plane of the cell membrane is caused by a local detachment of the lipid bilayer from the subjacent cytoskeletal cortex. We expect that our technique will enable new insights into the mechanical properties of the cell membrane that will help us to better understand membrane processes such as phagocytosis and blebbing.

Magnetic microparticles, assembled into chains that are actuated with rotating magnetic fields, can be used as microstirrers to promote fluid transport and biochemical reactions in microfluidic systems. We show that, within a certain range of magnetic field rotation frequency, the microstirrers exhibit a coherent collective motion: the rotating magnetic particle chains move throughout the volume of a flat fluid cell and generate very strong (~1 mm s(-1)) and global (9 mm) vortical fluid flows, with many eddy-type substructures that fluctuate continuously in time, resembling turbulent flow. The collective motion makes the microstirrers not only defy gravity, but also move against magnetic field gradients. The induced fluid flow is directly related to the stirring rate and the amount of magnetic particle chains. The observed behavior is caused by the magnetic and hydrodynamic interactions between the magnetic microparticles and the fluid. We utilized the phenomenon of swarming particles to enhance biochemical assays with magnetic capture particles (4000 μL(-1)) and IgG targets (500 pM). When compared to a reference system of sedimented magnetic capture particles, magnetic actuation leads to both a ~9 times increase in the initial assay kinetics as well as a ~7 times increase of target capture signal after 30 minutes.

The application of magnetic particles in biomedical research and in-vitro diagnostics requires accurate characterization of their magnetic properties, with single-particle resolution and good statistics. Here, we report intra-pair magnetophoresis as a method to accurately quantify the field-dependent magnetic moments of magnetic particles and to rapidly generate histograms of the magnetic moments with good statistics. We demonstrate our method with particles of different sizes and from different sources, with a measurement precision of a few percent. We expect that intra-pair magnetophoresis will be a powerful tool for the characterization and improvement of particles for the upcoming field of particle-based nanobiotechnology.