Modulation of aspect ratio for complete separation in an inertial microfluidic channel

Abstract

Inertial microfluidics has been attracting considerable interest in recent years due to immensely promising applications in cell separations and sorting. Despite the intense attention, the moderate efficiencies and low purity of the reported devices have hindered their widespread acceptance. In this work, we report on a simple inertial microfluidic system with high efficiency (>99%) and purity (>90%). Our system builds on the concept of two-stage inertial migration which permits precise prediction of particle or cell position within the microchannel. Our design manipulates the inertial equilibrium positions by modulating channel aspect ratio to achieve a complete separation. Here, we successfully demonstrate a complete separation of particles and isolation of rare cells in blood spiked with human prostate epithelial tumor (HPET) cells. Based on the planar structure, large separation spacing and predictable focusing, we envision promising applications and easy integration of our system with existing lab-on-a-chip systems for cell separations.

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

“…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, which is more desirable for focusing and further manipulation compared to the pure inertial focusing.…”

Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers

“…Inertial microfluidic devices can employ various channel structures for different functions. Straight channels with fine-tuned aspect ratios 14,22,28 or microstructures 15,18,29 are frequently used as particle focusers by reducing the focusing positions. Straight channels have the best parallelizability and the simplest design rules among all structure types.…”

Particle Focusing in Curved Microfluidic Channels

“…These forces allow for the precise alignment of particles in a flow at throughputs orders of magnitudes higher than in previous microfluidic technologies. The high throughput nature of inertial focusing has enabled a range of microfluidic technologies for biomedical applications from separation technologies [8][9][10][11][12] , to automated sample preparations 13,14 , to novel cell analysis techniques such as cell deformability cytometry 15 and the isolation of circulating tumor cells from blood 16,17 .…”

“…These forces allow for the precise alignment of particles in a flow at throughputs orders of magnitudes higher than in previous microfluidic technologies. The high throughput nature of inertial focusing has enabled a range of microfluidic technologies for biomedical applications from separation technologies [8][9][10][11][12] , to automated sample preparations 13,14 , to novel cell analysis techniques such as cell deformability cytometry 15 and the isolation of circulating tumor cells from blood 16,17 .It is generally accepted that inertial focusing in straight channels is dependent on two main parameters: Reynolds number, defined as Re C 5 rU Max D h /m, where r is the fluid density, m is the fluid viscosity, U Max > 3/2U Avg is the maximum velocity of the fluid and D h is the hydraulic diameter of the channel defined as D h 5 2hw/(h 1 w) where h and w are the height and width of the channel cross section respectively, and the particle confinement ratio, l 5 a/D h , where a, is the particle size. Prior research has determined a minimum threshold for inertial focusing to occur such that l .…”