In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re ≪ 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon.

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Fundamentals and applications of inertial microfluidics: a review

Lattice Boltzmann methods for multiphase flow and phase-change heat transfer

Microfluidics has experienced massive growth in the past two decades, and especially with advances in rapid prototyping researchers have explored a multitude of channel structures, fluid and particle mixtures, and integration with electrical and optical systems towards solving problems in healthcare, biological and chemical analysis, materials synthesis, and other emerging areas that can benefit from the scale, automation, or the unique physics of these systems. Inertial microfluidics, which relies on the unconventional use of fluid inertia in microfluidic platforms, is one of the emerging fields that make use of unique physical phenomena that are accessible in microscale patterned channels. Channel shapes that focus, concentrate, order, separate, transfer, and mix particles and fluids have been demonstrated, however physical underpinnings guiding these channel designs have been limited and much of the development has been based on experimentally-derived intuition. Here we aim to provide a deeper understanding of mechanisms and underlying physics in these systems which can lead to more effective and reliable designs with less iteration. To place the inertial effects into context we also discuss related fluid-induced forces present in particulate flows including forces due to non-Newtonian fluids, particle asymmetry, and particle deformability. We then highlight the inverse situation and describe the effect of the suspended particles acting on the fluid in a channel flow. Finally, we discuss the importance of structured channels, i.e. channels with boundary conditions that vary in the streamwise direction, and their potential as a means to achieve unprecedented three-dimensional control over fluid and particles in microchannels. Ultimately, we hope that an improved fundamental and quantitative understanding of inertial fluid dynamic effects can lead to unprecedented capabilities to program fluid and particle flow towards automation of biomedicine, materials synthesis, and chemical process control.

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Inertial microfluidic physics

Bone marrow transplant.

When Segre and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future.

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Inertial Focusing in Microfluidics

Inertial microfluidics has gained significant attention since first being proposed in 2007 owing to the advantages of simplicity, high throughput, precise manipulation, and freedom from an external field. Superior performance in particle focusing, filtering, concentrating, and separating has been demonstrated. As a passive technology, inertial microfluidics technology relies on the unconventional use of fluid inertia in an intermediate Reynolds number range to induce inertial migration and secondary flow, which depend directly on the channel structure, leading to particle migration to the lateral equilibrium position or trapping in a specific cavity. With the advances in micromachining technology, many channel structures have been designed and fabricated in the past decade to explore the fundamentals and applications of inertial microfluidics. However, the channel innovations for inertial microfluidics have not been discussed comprehensively. In this review, the inertial particle manipulations and underlying physics in conventional channels, including straight, spiral, sinusoidal, and expansion-contraction channels, are briefly described. Then, recent innovations in channel structure for inertial microfluidics, especially channel pattern modification and unconventional cross-sectional shape, are reviewed. Finally, the prospects for future channel innovations in inertial microfluidic chips are also discussed. The purpose of this review is to provide guidance for the continued study of innovative channel designs to improve further the accuracy and throughput of inertial microfluidics.

Channel innovations for inertial microfluidics

Microfluidic technologies for isolating cells of interest from a heterogeneous sample have attracted great attentions, due to the advantages of less sample consumption, simple operating procedure, and high separation accuracy. According to the working principles, the microfluidic cell sorting techniques can be categorized into biochemical (labeled) and physical (label-free) methods. However, the inherent drawbacks of each type of method may somehow influence the popularization of these cell sorting techniques. Using the multiple complementary isolation principles is a promising strategy to overcome this problem, therefore there appears to be a continuing trend to integrate two or more sorting methods together. In this review, we focus on the recent advances in microfluidic cell sorting techniques relied on both physical and biochemical principles, with emphasis on the mechanisms of cell separation. The biochemical cell sorting techniques enhanced by physical principles and the physical cell sorting techniques enhanced by biochemical principles, are first introduced. Then, we highlight on-chip magnetic-activated cell sorting, on-chip fluorescence-activated cell sorting, multi-step cell sorting and multi-principle cell sorting techniques, which are based on both physical and biochemical separation mechanisms. Finally, the challenges and future perspectives of the integrated microfluidics for cell sorting are discussed.

Recent advances in microfluidic cell sorting techniques based on both physical and biochemical principles

In this work, we design and fabricate a miniaturized spiral-shaped microchannel device which can be used for high-throughput particle/cell ordering, enrichment, and purification. To probe into the flow rate regulation mechanism, an experimental investigation is carried out on the focusing behaviors of particles with significantly different sizes in this device. A complete picture of the focusing position shifting process is unfolded to clarify the confusing results obtained from flow regimes with different dominant forces in past research. Specifically, with the increase of the flow rate, particles are observed to first move towards the inner wall under the dominant inertial migration, then stabilize at a specific position and finally shift away from the inner wall due to the alternation of the dominant force. Novel phenomena of focusing instability, co-focusing, and focusing position interchange of differently sized particles are also observed and investigated. Based on the obtained experimental data, we develop and validate, for the first time, a five-stage model of the particle focusing process with increasing flow rate for interpreting particle behaviors in terms of the competition between inertial lift and Dean drag forces. These new experimental findings and the proposed process model provide an important supplement to the existing mechanism of inertial particle flow and enable more flexible and precise particle manipulation. Additionally, we examine the focusing behaviors of bioparticles with a polydisperse size distribution to validate the explored mechanisms and thus help realize efficient enrichment and purification of these particles.

High-throughput inertial particle focusing in a curved microchannel: Insights into the flow-rate regulation mechanism and process model

This paper elucidates the particle focusing mechanisms in a symmetrical serpentine microchannel. The particle trajectories and the fluid fields in serpentine microchannels are explored via the numerical simulation based on a lattice Boltzmann method (LBM)-immersed boundary method (IBM) model. Experiments are also performed to verify the obtained simulation results. The investigation results help us to clearly understand the important role of the Dean flow for particle focusing in symmetrical serpentine microchannels. The balance of the inertial lift force and the Dean flow drag force at lower flow intensities leads the particles to flow near the sidewalls. As the flow intensity becomes stronger, the alternation of the Dean flow direction has special hydrodynamic effects to focus or separate particles of different sizes. Because of the volume effects, large particles are more prone to rotate with the Dean vortex and can be separated from the small particles at specific flow intensities. We envision that the simulation results of the focusing behaviors of particles would be of great significance for efficiently designing and optimizing inertial microfluidics.

Numerical simulation of particle focusing in a symmetrical serpentine microchannel

This paper presents an improved understanding of the dynamic focusing process and lateral migration dynamics of microparticles throughout a classic spiral microchannel at finite Reynolds numbers A novel two-stage model is proposed to elucidate the particle focusing process along the channel Specifically, we find that particle migration undergoes a two-stage development comprising the formation of the particle array (stage I) and the shifting of the focusing position after particles are well focused (stage II) Variations in particle focusing ratio and lateral focusing position under different migration lengths and different driving flow rates are quantitatively investigated and analyzed Results show that the cross-sectional Dean flow affects the particle migration dynamics throughout the channel more significantly at large Reynolds numbers It is also found that an unstable focusing phenomenon occurs at the intermediate channel region in addition to at the outlets A state diagram is then generated to illustrate the occurrence and development of this interesting focusing instability along the channel In addition, the focusing performances of a mixture of different size particles are investigated to reveal the multi-particle separation process and mechanism The small particle is found to contribute more significantly to the variation in the relative positions of multi-particles These improved understandings of the particle focusing mechanisms provide insights into the device optimization and the operation protocol improvement

Di Jiang

Papers

Channel innovations for inertial microfluidics

Recent advances in microfluidic cell sorting techniques based on both physical and biochemical principles

High-throughput inertial particle focusing in a curved microchannel: Insights into the flow-rate regulation mechanism and process model

Numerical simulation of particle focusing in a symmetrical serpentine microchannel

Inertia-induced focusing dynamics of microparticles throughout a curved microfluidic channel