High throughput viscoelastic particle focusing and separation in spiral microchannels

Abstract

Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15 µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15 µm particles at a sample flow rate of 1 mL/min—a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.

Rapid prototyping for high-pressure microfluidics

“…Based on the measurements of similar compounds by others, the fluid mechanical properties of the solution (1.5 MDa, 0.5 mg/ml hyaluronic acid in PBS) may be roughly estimated as a zero-shear viscosity of about 5 mPa s, and a relaxation time of about 10 ms. With a characteristic channel width of 100 µm, the highest tested flow rate of 2.4 ml/min would correspond to a Reynolds number of about 8 and to a Weissenberg number of about 40. The observed focusing characteristics are consistent with results by others investigating flows with a similar Elasticity Number, here El = Wi/Re = 4.8 12 , 13 .…”

Label-Free Isolation of Exosomes Using Microfluidic Technologies

“…To further improve size-selective separation of EV subpopulations, a viscoelastic technique was employed in combination with DNA mediation . Although this integrated method increased exosome isolation efficiency, it is not a label-free approach, as the addition of capture molecules like DNA aptamers can alter exosome properties, subsequently causing inaccurate characterization of the isolated exosomes and compromising their clinical application. − Very recently, Zhou et al . presented a viscoelastic focusing technique in a reverse wavy microchannel structure to separate exosomes from cell culture supernatant (Figure B).…”

“…To minimize the quantity of polymer added in such applications, efforts could be undertaken to control the intensity of the inertial or elastic force, which define lateral flow-induced migration of particles, by tuning the flow rate and the geometry of the microchannel. Although finding an optimal flow condition in such platforms is still challenging, microfluidic devices with complex geometries, including a series of microchannels with several curvatures (triangular, circular or semicircular cross sections), have shown some success in manipulating the flow profile for fine-tuning of particles trajectories. − …”

Biomedical Applications of Microfluidic Devices: A Review

“…Recently, inertial microfluidic platforms based on viscoelastic fluids have shown promising results in precisely focusing and manipulating particles [ 43 ]. Kumar et al [ 44 ] investigated particles focusing in spiral channels at higher flow rates compared to previously reported values using a non-Newtonian viscoelastic fluid. The utilization of viscoelastic fluids exerts a new elastic force on particles shifting the equilibrium position from the inner wall of the curved channel to the outer wall, which is helpful for cytometry applications ( Figure 3 ).…”

“… Inertial and secondary flow examples: ( a ) viscoelastic non-Newtonian spiral device, reprinted with permission from [ 44 ], Copyright 2021, Springer Nature; ( b ) serpentine device, reprinted with permission from [ 1 ], Copyright 2016, Springer Nature; ( c ) successive contraction and extraction channels, reprinted with permission from [ 38 ], Copyright 2013, Royal Society of Chemistry; ( d ) top surface slanted grooves configuration, reprinted with permission from [ 39 ], Copyright 2017, IEEE; and ( e ) Herringbone structure, reprinted with permission from [ 40 ], Copyright 2021, Wiley-VCH GmbH. …”