Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels

Abstract

Viscoelasticity-induced particle migration has recently received increasing attention due to its ability to obtain high-quality focusing over a wide range of flow rates. However, its application is limited to low throughput regime since the particles can defocus as flow rate increases. Using an engineered carrier medium with constant and low viscosity and strong elasticity, the sample flow rates are improved to be one order of magnitude higher than those in existing studies. Utilizing differential focusing of particles of different sizes, here we present sheathless particle/cell separation in simple straight microchannels that possess excellent parallelizability for further throughput enhancement. The present method can be implemented over a wide range of particle/cell sizes and flow rates. We successfully separate small particles from larger particles, MCF-7 cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from RBCs in different straight microchannels. The proposed method could broaden the applications of viscoelastic microfluidic devices to particle/cell separation due to the enhanced sample throughput and simple channel design.Continuous manipulation and separation of particles and cells is important for a wide range of applications in biology, 1,2 medicine, 2,3 and industry. [4][5][6] Microfluidic systems have been proven to be promising tools for particle/cell manipulation with higher sensitivity and accuracy than their macroscale counterparts. The last decade has seen extensive development of microfluidic approaches for particle/cell manipulation that resort to immunocapture, 7 externally applied physical fields, [8][9][10][11][12][13][14][15][16][17][18] microfiltration, 19,20 gravitational sedimentation, 21 or deterministic lateral migration. 22,23 More recently, cross-streamline migration induced by the hydrodynamic effects of carrier media, such as inertia 24,25 and viscoelasticity, 26,27 has shown its promise for effective particle/cell manipulation without need of labeling and external force fields. Particles and cells can be separated based on the size-dependent nature of hydrodynamic forces. Briefly, the inertial lift scales as F a ∝ , where a is the particle diameter. There are several cell types of biological and clinical interest with separable size ranges: epithelial tumor cells (15-25 µm in diameter), blood cells (erythrocytes are 6-8 µm biconcave disks and peripheral blood lymphocytes are 7-10 µm in diameter), and bacteria (1-3 µm). Inertial migration in Newtonian fluids has been intensively studied and implemented in high-throughput label-free separation devices for cell separation. [28][29][30][31][32][33][34] Recently, particle migration induced by viscoelasticity has begun to attract increasing attention due to its simple focusing pattern and potential for achieving efficient focusing over a wide range of flow rates. 35,36 In a viscoelastic medium, elasticity coupled with non-negligible inertia will drive particles towards the channel centerline, whic...

Sheathless Focusing and Separation of Diverse Nanoparticles in Viscoelastic Solutions with Minimized Shear Thinning

“…The low focusing efficiencies of the origamis are due to their small dimensions and hollowness, which lead to reduced area of thrust surface and thus make their focusing more challenging. On the other hand, the successful focusing for very small κ is valid for a wide range of channel dimensions based on our previous 19 and present observations. We believe that the origamis can be better focused in the low-viscosity viscoelastic solutions by further reducing the channel dimensions.…”

“…The off-center focusing stems from the enhanced compressive normal stress at the near-center side of a large particle ( κ > 0.25-0.3). 19,25 We have previously reported this off-center focusing in microchannels with dimensions of ~10 µm. 19 The present finding shows that such focusing pattern still exists in a wide range of dimensions, making sheathless separation of nanoparticles from larger ones feasible.…”

Particle manipulations in non-Newtonian microfluidics: A review

“…6a) has been demonstrated to result in fluid and particle properties dependent equilibrium positions in straight rectangular microchannels. Liu et al [110] observed in a straight rectangular microchannel with AR ¼ 2 differential elasto-inertial focusing of 5 mm and 15 mm diameter particles in 2000 ppm PEO solution (Fig. 6b).…”

“…Sheath-free particle separation in viscoelastic fluid flows has also been implemented in single straight rectangular microchannels. Liu et al [110] utilized the differential elasto-inertial focusing to separate PS particles by size in 2000 ppm PEO solution flows through rectangular microchannels with a high AR. They further applied their technique to separate MCF-7 cancer cells from RBCs in a 100 mm wide/50 mm high microchannel (i.e., AR ¼ 2:0), and RBCs from Escherichia coli (E. coli) in a 40 mm wide/10 mm high microchannel (i.e., AR ¼ 4:0) (Fig.…”

“…(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) [110]. Later, Li et al [109] presented a systematic experimental study of multiple parametric effects on a binary separation of 5 mm and 10 mm diameter PS particles in viscoelastic fluid flows through straight rectangular microchannels.…”