Microfluidic mixing becomes a necessity when thorough sample homogenization is required in small volumes of fluid, such as in lab-on-a-chip devices. For example, efficient mixing is extraordinarily challenging in capillary-filling microfluidic devices and in microchambers with stagnant fluids. To address this issue, specifically designed geometrical features can enhance the effect of diffusion and provide efficient mixing by inducing chaotic fluid flow. This scheme is known as “passive” mixing. In addition, when rapid and global mixing is essential, “active” mixing can be applied by exploiting an external source. In particular, magnetic mixing (where a magnetic field acts to stimulate mixing) shows great potential for high mixing efficiency. This method generally involves magnetic beads and external (or integrated) magnets for the creation of chaotic motion in the device. However, there is still plenty of room for exploiting the potential of magnetic beads for mixing applications. Therefore, this review article focuses on the advantages of magnetic bead mixing along with recommendations on improving mixing in low Reynolds number flows (Re ≤ 1) and in stagnant fluids.

Recent global events have distinctly demonstrated the need for fast diagnostic analysis of targets in a liquid sample. However, microfluidic lab-on-a-chip devices for point-of-care diagnostics can suffer from slow analysis due to poor mixing. Here, we experimentally explore the mixing effect within a microfluidic chamber, as obtained from superparamagnetic beads exposed to an out-of-plane (vertical) rotating magnetic field. Various magnetic protocols are explored, and the level of sample homogeneity is measured by determining the mixing efficiency index. In particular, we introduce a method to induce effective mixing in a microfluidic chamber by the actuation of the same beads to perform global swarming behavior, a collective motion of a large number of individual entities often seen in nature. The microparticle swarming induces high fluid velocities in initially stagnant fluids, and it can be externally controlled. The method is pilot-tested using a point-of-care test featuring a bioluminescent assay for the detection of antibodies. The mixing by the magnetic beads leads to increased assay kinetics, which indeed reduces the time to sensor readout substantially. Magnetic microparticle swarming is expected to be beneficial for a wide variety of point-of-care devices, where fast homogeneity of reagents does play a role.

Magnetic microbeads have been widely used for the capturing of biomarkers, as well as for microfluidic mixing for point-of-care diagnostics. In magnetic micromixing, microbead motion is generated by external electromagnets, inducing fluid kinetics, and consequently mixing. Here, we utilize an in-plane rotating magnetic field to induce magnetic bead mixing in a circular microfluidic chamber that allows better access with (optical) readout than for existing micromixing approaches. We analyze the magnetic bead dynamics, the induced fluid profiles and we quantify the mixing performance of the system. The rotating field causes the combination of (1) a global rotating flow counter to the external field rotation induced by magnetic particles moving along the chamber side wall, with (2) local flow perturbations induced by rotating magnetic bead clusters in the central area of the chamber, rotating in the same direction as the external field. This combination leads to efficient mixing performance within 2 min of actuated magnetic field. We integrate magnetic mushroom-shaped features around the circumference of the chamber to generate significantly higher global fluid velocities compared with the no-mushroom configuration, but this results in less efficient mixing due to the absence of the central rotating bead clusters. To validate and understand the experimental results and to predict further enhancement of mixing, we carry out numerical simulations of induced fluid profiles and their corresponding mixing indices, and we explore the additional effect of integrating geometrical structures. The micromixing method we introduce here is particularly suitable for microfluidic devices in which the biochemical assay happens in a microfluidic chamber under no-flow conditions, i.e., with initially stagnant fluids, and for which the time-to-result is critical, such as in point-of-care diagnostics.