Dynamic magnetic particle actuation for integrated lab-on-chip biosensing

The demand for easy to use and cost effective medical technologies inspires scientists to develop innovative lab-on-chip technologies for in-vitro diagnostic testing. We study the use of magnetic particles actuated by magnetic fields to perform different microfluidic handling steps of an integrated biosensing assay.[1] We have developed numerical models to simulate the collective particle behavior[2] and the different binding processes involved in an assay[3]. The models are compared to experimental data and are used to develop novel magnetic actuation technologies. In this paper we will report results of two magnetically actuated processes (see Fig. 1): (1) capture of targets from a fluid and (2) manipulation of particle distributions near a physical boundary. We have investigated the affinity capture process of molecular targets by magnetic particles (see Fig. 2). We quantified association rate constants of the capture process for different types of magnetic particle actuation within a fluid, based on rotating chains of magnetic particles[4]. We found that without magnetic actuation, depletion zones in the target concentration form near the particles. Using magnetic field gradients and rotating fields to respectively move and rotate chains of particles within the fluid (Fig. 2a), particle-fluid interactions can be enhanced to effectively reduce the depletion zones (Figure 2b). Using numerical Brownian dynamics simulations of the capture process (Fig. 2c), we have confirmed these effects and computed similar rate constants (Fig. 2d). Lastly, we have characterized association rate constants for various types of actuation, for varying magnetic actuation parameters and as a function of the magnetic particle concentration. We find that capture rates can be increased by almost two orders of magnitude. In addition, we have developed a number of methods to manipulate particle distributions at a sensing surface (see Fig. 1b). To disaggregate particles, we applied alternating magnetic fields near a surface[5], exploiting repulsive magnetic dipole-dipole interactions between the particles. Even better redistribution of particles can be achieved by means of magnetic rotaphoresis, i.e. redistribution of particles by rotationally actuating them near a surface, which causes aggregates to translate along the surface while gradually breaking into smaller fragments (Fig. 3). In summary, we show that magnetic fields can be used to perform key process steps within a microfluidic assay, and we expect that the reported methods will be very useful in future lab-on-chip sensing applications based on magnetic particles. [1] A. van Reenen, A. M. de Jong, J. M. J. den Toonder, M. W. J. Prins, Lab Chip, 2014, DOI: 10.1039/c3lc51454d. [2] A. van Reenen, Y. Gao, M. A. Hulsen, A. M. de Jong, J. M. J. den Toonder, M. W. J. Prins, Phys Rev E Stat Nonlin Soft Matter Phys, 2014, 89, 042306. [3] A. van Reenen, A. M. de Jong, M. W. J. Prins, J. Phys. Chem. B 2013, 117, 1210–8. [4] Y. Gao, A. van Reenen, M. A. Hulsen, A. M. de Jong, M. W. J. Prins, J. M. J. den Toonder, Microfluid. Nanofluidics 2013, 14, 265–274. [5] Y. Gao, A. van Reenen, M. A. Hulsen, A. M. de Jong, M. W. J. Prins, J. M. J. den Toonder, Lab Chip 2013, 13, 1394–401