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.

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.

The upcoming generations of high-sensitive and miniaturized biosensing systems need target capture methods that are as efficient and as rapid as possible, with targets ranging from molecules to cells. Capture of the targets can be achieved using particles coated with affinity molecules, but there are still fundamental questions as to the processes that limit the association rates. In this paper we quantify and compare the reaction rates of particle-based target capture with different types of actuation, namely (i) passive thermal transport, (ii) fluid agitation by vortex mixing, and (iii) actively rotating particles. In the experiments, we use fluorescent nanoparticles as targets which are biochemically captured by magnetic microparticles, and the capture efficiency is quantified using fluorescence microscopy with single target resolution. The data unravel the contributions of volume transport, near-surface alignment, and the chemical reaction to the overall rate constant of association. Vortex mixing versus passive transport gives an increase of the reaction rate constant by more than an order of magnitude, implying that the encounter frequency as well as the near-surface alignment probability are increased. The importance of near-surface alignment is underscored by the data of active particle rotation; the binding probability per encounter is 4-fold enhanced on rotating capture particles. We discuss the implications of our results for different biological systems and for the development of novel actuation methods in particle-based target capture.