Sorting of Particles Using Inertial Focusing and Laminar Vortex Technology: A Review

Abstract

The capability of isolating and sorting specific types of cells is crucial in life science, particularly for the early diagnosis of lethal diseases and monitoring of medical treatments. Among all the micro-fluidics techniques for cell sorting, inertial focusing combined with the laminar vortex technology is a powerful method to isolate cells from flowing samples in an efficient manner. This label-free method does not require any external force to be applied, and allows high throughput and continuous sample separation, thus offering a high filtration efficiency over a wide range of particle sizes. Although rather recent, this technology and its applications are rapidly growing, thanks to the development of new chip designs, the employment of new materials and microfabrication technologies. In this review, a comprehensive overview is provided on the most relevant works which employ inertial focusing and laminar vortex technology to sort particles. After briefly summarizing the other cells sorting techniques, highlighting their limitations, the physical mechanisms involved in particle trapping and sorting are described. Then, the materials and microfabrication methods used to implement this technology on miniaturized devices are illustrated. The most relevant evolution steps in the chips design are discussed, and their performances critically analyzed to suggest future developments of this technology.

Keywords: inertial focusing; inertial micro-fluidics; lab on a chip; micro-fluidics; vortex technology.

Figure 1

A schematic of inertial particle focusing in a (a) tubular, (b) square, and (c) rectangular channel.

Figure 2

(a) The particles randomly flowing in a straight channel undergo two opposite lift forces: The wall effect lift force F_LW and the shear-gradient lift force F_LS, resulting in lateral equilibrium positions depending on the channel section. (b) At the entrance of the reservoir, the particles experience F_LS, which increases with their size: The larger blue particles are pushed toward the vortex center and trapped, meanwhile the smaller red ones flow in the main stream. Adapted from [83].

Figure 3

Design of the micro-channels used by Park et al. [81]. (a) Straight square channel. For the experiments, the micro-channel length was varied between 0.5 and 3 mm. (b) Multi orifice channel. All the structures are 70 µm high (H). Adapted from [81].

Figure 4

Design and working principle of the device of Hur et al. [56]. The larger cells remain trapped in the lateral chamber, while the smaller ones flow within the main channel, due to the dependence of the lift force on the particles’ dimension. Wr₁ and Wr₂ indicate the chamber dimensions, and Wc is the chamber width. All of the structures are 70 µm high (H). The dashed paths indicate the fluid streamlines followed by the large (blue) and small (red) particles. Adapted from [62].

Figure 5

Vortex chip design of Sollier et al. [83]. The chip consists of eight channels (40 um wide, 80–85 um high) in parallel, with eight reservoirs (W_R = 480 um, L_R = 720 um) for each of them. The input channels of length L_C allow the focus of the randomly injected particles. Adapted from [85].

Figure 6

Schematic layout of the reservoir geometry tested by Paiè et al. [80]. Lateral channels of length L were added to the standard reservoirs [85] and joined together by a connection channel W wide. The dashed paths indicate the fluid streamlines followed by the big (blue) and small (red) particles. Adapted from [87].

Figure 7

Scheme of the size-selective separation in micro-chambers with three outlets proposed by Wang and Papautsky [88]. At the chamber entrance, the particles are arranged in a two-focus position near the channel walls. The large particles (blue) undergo a larger shear-gradient induced lift force, being pushed in the chamber and exiting through the two later outlets (LAT), while the smaller particles (red) remain in the main channel exiting through the main outlet (OUT). The dashed paths indicate the fluid streamlines followed by the big (blue) and small (red) particles. Adapted from [88].

Figure 8

Cross-sectional view of the boundary surface (white dashed line) at the entrance of the micro-chamber increasing the r/R ratio. The red area represents the main flow exiting through the main outlet, while the blue area indicates the flow exiting through the lateral outlets. Increasing the r/R ratio, the boundary shifts toward the channel walls, allowing the sorting of particles of different dimensions. Adapted from [89].

Figure 9

Inertial micro-fluidic multimodal separation designed by Wang et al. [81]. The micro-fluidic resistance network comprises two sorting chambers and three exits for particles, relying on their dimensions. Adapted from [88].

Figure 10

Schematic picture of two vortex sorting units integrated into a device for double sorting and purification. In the insets, a schematic detail of the device operation (I) at the second inlet stage IN2, and (II) in the second chamber. Adapted from [90].

Figure 11

3D sorting Lab on a Chip developed by Volpe et al. [75] on PMMA through fs-laser technology. The particles exiting through the lateral outlets (LAT) are collected in a multi-well plate, while the others flow through the main exit OUT. The ratio between the resistance of the LAT and the OUT is 20. The channels are 60 μm high and 50 μm wide. The chamber’s dimensions are 480 μm × 540 μm. Adapted from [83].