Magnetic activated cell sorting (MACS) pipette tip for immunomagnetic bacteria separation

Abstract

Magnetic activated cell sorting is a well-established technology to sort target cells from heterogeneous cell populations based on their specific surface receptors. However, conventional bulk separators rely on irregular and dense ferromagnetic matrices that can cause variances in separation purity and recovery. Recent microfluidic separators typically use narrow and two-dimensional laminar flows that can lead to low separation throughput. Here, we present a magnetizable micropipette tip incorporating a ferromagnetic matrix of nickel meshes that have regular and rectangular micropores. The functional pipette tip can be transiently magnetized by permanent magnets, thereby enabling the efficient capture and release of target cells by simple pipetting. We performed parametric studies to investigate optimal separation protocols such as the number of mesh layers and pipetting repetitions. We then applied the functional pipette tip for separation of bacterial cells from whole blood, confirming that the separation quality is sufficient for downstream cell culture and analysis. The magnetizable pipette tip provides high-throughput separation, processing 1 mL of blood within 7 min, and high-recovery separation, recovering ≈90.5% of the bacterial cells spiked into blood.