Bone marrow transplant.

Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.

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3D Printing of Inertial Microfluidic Devices.

Blood and blood products are critical components of health care. Blood components perform distinct functions in the human body and thus the ability to efficiently fractionate blood into its individual components (i.e., plasma and cellular components) is of utmost importance for therapeutic and diagnostic purposes. Although conventional approaches like centrifugation and membrane filtration for blood processing have been successful in generating relatively pure fractions, they are largely limited by factors such as the required blood sample volume, component purity, clogging, processing time and operation efficiency. In this work, we developed a high-throughput inertial microfluidic system for cell focusing and blood plasma separation from small to large volume blood samples (1–100 mL). Initially, polystyrene beads and blood cells were used to investigate the inertial focusing performance of a single slanted spiral microchannel as a function of particle size, flow rate, and blood cell concentration. Afterwards, blood plasma separation was conducted using an optimised spiral microchannel with relatively large dimensions. It was found that the reject ratio of the slanted spiral channel is close to 100% for blood samples with haematocrit (HCT) values of 0.5% and 1% under an optimal flow rate of 1.5 mL min−1. Finally, through a unique multiplexing approach, we built a high-throughput system consisting of 16 spiral channels connected together, which can process diluted samples with a total flow rate as high as 24 mL min−1. The proposed multiplexed system can surmount the shortcomings of previously reported microfluidic systems for plasma separation and cell sorting in terms of throughput, yield and operation efficiency.

Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation

Microfluidics is a growing field of study because these devices offer novel and versatile approaches for addressing a range of scientific problems. Microfluidics have been used in separations, cell analysis, and microreactors, to illustrate a few applications. Microfluidics have been defined in terms of microliter volumes or micrometer dimensions of channels. For this review, we utilize the latter definition, where microfluidic channels range from 1-1000 µm in width or height. Microfluidic devices are fabricated in a host of ways, with a large variety of materials. Indeed, device material can affect flow, absorptivity, biocompatibility, and function of microfluidic components.

Microfluidics: Innovations in Materials and Their Fabrication and Functionalization.

Muscle-Inspired MXene Conductive Hydrogels with Anisotropy and Low-Temperature Tolerance for Wearable Flexible Sensors and Arrays

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

A review of flexible force sensors for human health monitoring.

In this paper, we present a novel impedance microcytometer integrated with inertial focusing and liquid electrode techniques for high-throughput cell counting and discrimination. The inertial prefocusing unit orders cells into a determinate train to reduce the possibility of cell adhesions and ensure that only one cell passes through detection region at a time, which improves the accuracy of downstream detection. The liquid electrodes are constructed by inserting Ag/AgCl wires into the electrode chambers filled with flowing highly conductive electrolyte solutions, which have a high detection sensitivity while requiring a simple fabrication process. The effects of main sample flow rate, feed flow rate in electrode chambers, and feed solution type on measured impedance signals are experimentally explored. On the basis of the optimized system, we establish a linear relationship between the amplitude of impedance peaks and the volume of size-calibrated particles and achieve a high detection throughput of ∼500...

Microfluidic Impedance Cytometer with Inertial Focusing and Liquid Electrodes for High-Throughput Cell Counting and Discrimination.

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

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.

Wenlai Tang

Papers

Channel innovations for inertial microfluidics

A review of flexible force sensors for human health monitoring.

Microfluidic Impedance Cytometer with Inertial Focusing and Liquid Electrodes for High-Throughput Cell Counting and Discrimination.

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

Numerical simulation of particle focusing in a symmetrical serpentine microchannel