Deformability-induced lift force in spiral microchannels for cell separation

Abstract

We introduce a novel combination of deformability-induced lift force (FD) and secondary Dean flow in spiral microchannel translated into a label-free purification approach applicable to mammalian cells, processing of millions of cells per min, up to high purities and recovery.

Purifying stem cell‐derived red blood cells: a high‐throughput label‐free downstream processing strategy based on microfluidic spiral inertial separation and membrane filtration

“…As shown in Figure 1c, smaller nuclei are positioned closer to the inner wall while larger cells are observed closer to the channel centreline. As we previously reported (Guzniczak et al, 2020), there is a distinct hydrodynamic behavior of cells of the same size but different deformability at sufficiently elevated flowrate. Stiff cells remain focused close to the inner wall, while their softer counterparts experience additional drag (as a consequence of the additional deformability‐induced lift force [F D ]; Hur, Henderson‐MacLennan, McCabe, & Di Carlo, 2011) and they travel across the channel to be equilibrated near the outer wall.…”

“…Enucleated and nucleated cells occupy the same section of the channel (enucleated: 100 ± 24 µm, 123 ± 22 µm, and 131 ± 23 µm; nucleated: 110 ± 20 µm, 125 ± 15 µm, and 134 ± 11 µm [mean ± SD ] at 0.2, 0.4, and 0.6 ml/min, respectively) with a substantial overlap in the lateral equilibrium position (AUC = 0.62, 0.51, and 0.52, for 0.2, 0.4, and 0.6 ml/min, respectively) closer to the channel centreline. Increasing the flow rate to 1 ml/min triggered the characteristic shift, recently reported and characterized in Guznizcak et al (2020) of more deformable enucleated cells toward the outer wall to the equilibrium lateral position at 36 ± 21 µm, while less deformable nucleated cells recapitulated the unfocused transition pattern (103 ± 32 µm) observed for enucleated cells at 0.8 ml/min (103 ± 33 µm). Except for the lowest applied flow rate, nuclei always remained focused along the inner wall in a tight stream (151 ± 23 µm at 0.4 ml/min, 156 ± 11 µm at 0.6 ml/min, 158 ± 11 µm at 0.8 ml/min, and 154 ± 18 µm at 1 ml/min).…”

“…DNA is known for being “sticky” molecule and causing fouling of surfaces (Timmins & Nielsen, 2011). Inertial focusing in spiral microchannels has been proposed as “membrane‐free” filtration, capable of continuous and high‐throughput separation based on size and deformability (Bhagat et al, 2008; Guzniczak et al, 2020). By processing the sample in spiral microchannel, a majority (>98%) of the nuclei are depleted, prolonging the life‐span of the filter membrane.…”

Changes of Inertial Focusing Position in a Triangular Channel Depending on Droplet Deformability and Size

“…Deformability is a useful cell biomarker that can be used for the separation of cell types or phenotypes. For example, cancer cells are generally more deformable than healthy cells [ 47 , 48 ], and the cell separation based on deformability has been demonstrated with an inertial microfluidic device with a rectangular cross-section channel [ 18 ] and spiral channel [ 39 ]. Hur at al.…”

“…However, if the viscosity decreases below 5 cSt, the focusing position moves back toward the channel wall again [ 18 , 38 ]. Microparticles or cells can be separated depending on the deformability using this difference in focusing position using a straight channel [ 18 ] and spiral channel [ 39 ].…”