Enhanced Microfluidic Sample Homogeneity and Improved Antibody-Based Assay Kinetics Due to Magnetic Mixing

Abstract

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.

Transport and mixing by metachronal waves in nonreciprocal soft robotic pneumatic artificial cilia at low Reynolds numbers

“…68 A specific example is the need for mixing in confined micro-reaction chambers of point-of-care devices in order to enhance the speed and reproducibility of diagnostic testing; 69 artificial cilia can potentially provide this function since they operate at the right length scale and they offer a fully integrated solution. 70 However, fluid transport and mixing by cilia in confined spaces have not attracted much attention. Recently, we analyzed the fluid transport in a confined channel by pneumatic artificial cilia submerged in a viscous fluid and actuated by trapezoidal pressure waves using a combination of experiments and numerical simulations.…”

Magnetic bead mixing in a microfluidic chamber induced by an in-plane rotating magnetic field

“…(i) The basic modes of magnetic bead motion in the absence and presence of a magnetic field and magnetic gradients and the relevant forces. Image adapted from (Shanko et al 2021) (ii) Schematic of the working principle of mushrooms in a circular array around the chamber circumference of a microfluidic chip, and when applying an inplane counterclockwise rotating external magnetic field. Only half of the chamber is shown here (color figure online) disk like structures (Nagaoka et al 2005).…”

“…Recently, we have shown that applying an out-of-plane rotating magnetic field can induce global swarming of magnetic microbeads in a circular microfluidic chamber, leading to chaotic fluid flow and effective mixing (Shanko et al 2021).We found that under certain conditions, increased fluid kinetics due to the motion of the magnetic beads contribute to faster and more efficient immunoassay sensing. However, an out-of-plane configuration will hinder optical visualization.…”

Alternating Magnetic Field-Promoted Nanoparticle Mixing: The On-Chip Immunocapture of Serum Neuronal Exosomes for Parkinson’s Disease Diagnostics

“…40 Herein, we have sought to control the collective motion of magnetic immunoparticles through the use of alternating (AC) magnetic fields, generated by off-the-shelf electromagnets, spanning simple-printed microfluidic channels; we observe that this promotes capture efficiencies within a few tens of minutes, which are typically (otherwise) only achieved across many hours. 41 Magnetic field switching also promotes a controlled in situ exosome washing and lysing (Scheme 1A) prior to a dual marker α-syn and syntenin-1 (synt-1) electrochemical quantification at disposable 32-multielectrode arrays (Scheme 1B). The entire methodology was validated through the analysis of 72 patient samples, with a resolved strong statistical correlation between α-syn expression in neuronal (L1CAM+) exosome and PD status.…”