Multiphysics model for designing magnetic bead collection processes on centrifugal microfluidic platforms

Abstract

Immunoassays require high sensitivity and specificity for the detection of low-abundance analytes in complex matrices such as blood plasma. The use of functionalized magnetic beads can increase assay sensitivity by selectively binding and concentrating target analytes, facilitating their separation. However, magnetophoretic bead collection still represents a critical bottleneck. It must be performed repeatedly throughout sequential mixing, washing, and dilution steps, which is time-consuming and prone to cumulative bead loss, ultimately reducing assay performance. Here, we present a comprehensive framework for the design of magnetic bead collection systems integrated on a rotating microfluidic (lab-on-a-disc) platform. We establish a finite-element multiphysics model of bead collection that couples magnetophoretic forces, centrifugal effects, magnetophoresis-induced convection, and cooperative bead motion. The model is experimentally validated on a dedicated setup using Dynabeads M270. Increased bead collection speed is attributed to convection-enhanced transport and bead aggregation into chains. The model enables systematic investigation of geometric parameters, fluid viscosity, bead properties, and rotational protocols, as well as the efficiency of various permanent magnet configurations. We investigate magnet arrangements, vary the rotational speed between 300 and 800 rpm, and the magnet-fluid distance between 2 and 6 mm. Within this range, our results show, for any targeted collection fraction, a linear decrease in collection time with increasing magnet-fluid distance and an exponential reduction with decreasing rotational speed. Beyond performance gains, this predictive in silico framework reduces the reliance on costly trial-and-error optimization and can accelerate assay development.