Fluid Manipulation Research Articles

Fully Automated Continuous Centrifugal Microfluidics Isolates Natural Killer Cells with High Performance and Minimal Stress.

Natural killer (NK) cells are a part of the innate immune system, providing the first line of defense against cancer cells and pathogens at an early stage. Hence, they are attracting attention as a valuable resource for allogeneic cell immunotherapy. However, NK cells exist with limited proportion in blood, and obtaining sufficient clinical-grade NK cells with highly viable and minimal stress is critical for successful immune cell therapy. Conventional purification methods via immunoaffinity or density gradient centrifugation had several limitations in yield, purity, and cellular stress, which might cause an increased risk for graft versus host disease and reduced efficacy due to NK cell malfunction, exhaustion, and apoptosis. Moreover, reducing the variations of isolation performance caused by the manual process is another unmet need for uniform quality of the living drug. Here, an automated system using an NK disc (NKD) based on continuous centrifugal microfluidics (CCM) technology was developed to isolate NK cells from whole blood with high yield, purity, reproducibility, and low stress. The CCM technology, which operates fluidic manipulation under disc rotation, enabled precise extraction of the ultra-thin target fluid layer generated by blood centrifugation. Compared to the conventional manual method, the CCM-NKD isolated NK cells with higher yield (recovery rate) and purity, while maintaining better reproducibility. Furthermore, since the CCM-NKD maintained substantially milder centrifugation conditions (120 ×g for 10 min) compared to the conventional approach (1200 ×g for 20 min), it showed reduced cellular stress and increased antioxidant capacity in the isolated NK cells. Based on the results, the CCM-NKD is expected to be a useful tool to provide highly intact and viable cell weapons for successful immune cell therapy.

Reversible bonding of microfluidics: Review and applications.

With the development of microfluidic technology, new materials and fabrication methods have been constantly invented in the field of microfluidics. Bonding is one of the key steps for the fabrication of enclosed-channel microfluidic chips, which have been extensively explored by researchers globally. The main purpose of bonding is to seal/enclose fabricated microchannels for subsequent fluid manipulations. Conventional bonding methods are usually irreversible, and the forced detachment of the substrate and cover plate may lead to structural damage to the chip. Some of the current microfluidic applications require reversible bonding to reuse the chip or retrieve the contents inside the chip. Therefore, it is essential to develop reversible bonding methods to meet the requirements of various applications. This review introduces the most recent developments in reversible bonding methods in microfluidics and their corresponding applications. Finally, the perspective and outlook of reversible bonding technology were discussed in this review.

Microfluidic Templated Stem Cell Spheroid Microneedles forDiabetic Wound Treatment.

Wound dressing patches based on stem cells have demonstrated promising potential in the treatment of diabetic wounds, while their capabilities in the maintenance of cell stemness, effective exchange of cellular substance, and precise targeting of the stem cells remain to be promoted. Here, a novel stem cell spheroid loaded microneedle (MN@SPs) patch is presented using microfluidic templating technology. By leveraging the precise fluid manipulation capabilities of the microfluidic template, stem cell spheroids (SPs) with uniform size can be generated in situ. The resulting SPs exhibit advanced viability and cell functions, as evidenced by the overexpressed genes related to extracellular matrix organization and angiogenesis. By loading these SPs into the microneedles (MNs), the platform enables the precise delivery and exchange of multiple active substances, which contribute to advanced neovascularization, collagen deposition, and tissue reconstruction of diabetic wounds. Overall, this microfluidic-engineered stem cell therapy platform demonstrates significant promise in promoting wound healing.

Minireview on Fluid Manipulation Techniques for the Synthesis and Energy Applications of Two-Dimensional MXenes: Advances, Challenges, and Perspectives

A new frontier in the design and applications of useful micro- and nanomaterials was unlocked by the combination of fluid mechanics with modern engineered technologies. Fluidic methods allow for the exact and active spatiotemporal manipulation of matter, which has enormous potential for the fabrication of advanced nanoplatforms with flexible material characteristics. Fluidic technologies bestow some advantages over conventional experimental methods, such as quick sample processing and precise fluid control during assays. When combined with different two-dimensional (2D) materials, these fluidic techniques opened up a new era in the area of material science and engineering. MXenes, the youngest family of layered 2D materials, have attracted great scientific attention as a result of their peculiar properties and are used for a multitude of applications. This review discusses the magnificent relationship between MXenes and fluid manipulation technique nanofluidics in the domain of energy research. This article proclaims a concise review of the synthesis, energy applications, challenges, and future outlook of MXenes in fluidic research. An emphasis is given to the applications of MXene-based fluidic techniques in the field of energy harvesting and storage. This analysis will provide anew insight into MXenes in the field of fluid manipulation techniques that followed custom approaches in the past and researchers to move toward a new direction in the future. This examinative article will fill a major gap in fluidic research in the world of materials. And to the best part of our perception, this is the first review that offers an overview of the combination of fluidics and MXenes for application, particularly in energy harvesting and storage devices.

Laser patterned nitrocellulose-based microfluidic devices: Applications in fluid manipulation and immunoassay

This work describes a new fabrication method to produce nitrocellulose-based microfluidic devices using CO2 laser ablation. This method requires only two simple steps: thermal bonding of a nitrocellulose membrane to a waxy film, and selective ablation of the membrane. The hollow microstructures created by selective ablation offer robust fluid barriers. With the optimized laser power and laser speed, two-dimensional fluid flow devices (2D) can be fabricated with fluid barrier width of 117 ± 11 µm and narrowest channel width of 81 ± 11 µm. This simple yet high resolution method can also be used for fabrication of a three-dimensional fluid flow device (3D) by simply bonding a stack of fabricated 2D devices. Fluidic delay and mixing tools in form of micropillar structures were created concurrently to device fabrication using the CO2 laser ablation. The phenomena of the fluidic delay and mixing were also evaluated by mathematical simulation which showed that micropillar structures not only delay the flow but also lead it into different directions and velocities causing passive fluidic mixing. A new nitrocellulose well plate fabricated using this method exhibited flexibility of device fabrication, superior sensitivity, less reagent consumption, and shorter analysis time than the conventional well plate.

CFD analysis on blood flow inside a symmetric stenosed artery: Physiology of a coronary artery disease.

This research article interprets the computational fluid dynamics analysis on blood flow inside a symmetric stenosed artery. The current problem models the blood flow inside the left coronary artery as having a symmetric stenosis in the central region. A comprehensive physiological examination of coronary artery disease is numerically evaluated by using the computational fluid dynamics toolbox Open-Field Operation And Manipulation. There are no assumptions of mild stenosis taken into account since the considered stenosis has an exactly measured length, height and position, etc. The blood flow problem is modeled for the non-Newtonian Casson fluid with unsteady, laminar, and incompressible flow assumptions. The underlying problem is solved numerically in its dimensional form. A thorough graphical analysis is provided on the blood flow simulations, pressure profile, velocity line graphs, pressure line graphs, and streamlines for the left coronary artery having a symmetric stenosis formation. The considered artery is divided into three sections, i.e. pre-stenosis, post-stenosis, and stenosis region, and the velocity and pressure line graphs are plotted for these considered regions. The graphical illustrations provide a detailed analysis of how the blood flow is affected inside the left coronary artery due to coronary artery disease. These pre- and post-stenosis velocity line graphs reveal two intriguing results: In the pre-stenosis zone, the velocity increases with increasing axial coordinate length, whereas in the post-stenosis region, the velocity decreases with rising axial coordinate length. It is evident that as the flow moves toward the stenosis region, the flow profile rises; yet, after passing through the stenosis zone, the flow profile begins to fall as the flow moves away from the stenosis region.

Pulsed laser micro drilling act on Perspex intended for microfluidic devices

An amorphous material with excellent shape memory effect (SME) like Perspex is a versatile material with broad applications in the bio-related field. Moreover, its extravagant properties like biological behavior, antimicrobial capacity, and porosity make it a choice for ophthalmologic devices, drug delivery, and microfluidic-based chromatography. However, its brittleness property and the formation of brittle-ductile transition make it a complex and delicate material for machining processes. A laser beam is an idiosyncratic tool used in engineering to biomedical fields. Compared to other lasers, the CO2 laser has a longer wavelength of 10.6 µm, which makes it the best choice for processing transparent material like Perspex. In this research CO2 laser micro-drilling (CLMD) act has been performed to design micro-holes on Perspex by tailoring the scan tracks of the laser. The movement of scanning tracks was controlled, and the beam functionalities' process windows were handled through adequate parametric settings like scan mode, machining speed, power, and pulsed frequency. The selection of optimal control factors is crucial for the adequate dimensional characteristics of holes, such as circularity and conicity. In continuation, multi-response optimization using RSM was employed to acquire the desired values of CLMD responses. Thus, the current CLMD approach may emanate its proprietary in fabricating micro-holes designed for a microfluidic device as an integrated inlet–outlet connector for fluidic manipulation. The findings of this research may be a worthy contribution to the biomedical field, as the designed holes by the current process on Perspex have not yet been addressed in any articles.

Low-cost fluorescence microscope with microfluidic device fabrication for optofluidic applications

Optofluidic devices have revolutionized the manipulation and transportation of fluid at smaller length scales ranging from micrometers to millimeters. We describe a dedicated optical setup for studying laser-induced cavitation inside a microchannel. In a typical experiment, we use a tightly focused laser beam to locally evaporate the solution laced with a dye resulting in the formation of a microbubble. The evolving bubble interface is tracked using high-speed microscopy and digital image analysis. Furthermore, we extend this system to analyze fluid flow through fluorescence-Particle Image Velocimetry (PIV) technique with minimal adaptations. In addition, we demonstrate the protocols for the in-house fabrication of a microchannel tailored to function as a sample holder in this optical setup. In essence, we present a complete guide for constructing a fluorescence microscope from scratch using standard optical components with flexibility in the design and at a lower cost compared to its commercial analogues.

Editorial for the Special Issue on Droplet-Based Microfluidics: Design, Fabrication, and Applications

Microfluidics is a rapidly growing field of research that involves the manipulation and analysis of fluids in small-scale channels, usually with dimensions ranging from sub-micrometer to sub-millimeter [...].

Improved Liquid Collection on a Dual-Asymmetric Superhydrophilic Origami.

Manipulating fluid with an open channel provides a promising strategy to simplify the current systems. Nevertheless, spontaneous on-surface fluid transport with large flux, high speed, and long distance remains challenging. Inspired by scallop shells, here a shell-like superhydrophilic origami (S-SLO) with multiple-paratactic and dual-asymmetric channels is presented to improve fluid collection. The origami channel can capture various types of liquids, including droplets, flow, and steam, and then transport collected liquid unidirectionally. The S-SLO with 2mm depth can reach maximum flux of 450mLh-1 , which is five times the capacity of a flat patterned surface with similar dimension. To diversify the function of such interface, the SLO is further integrated with a superhydrophobic zirconium carbide/silicone coating for enhanced condensation via the collaboration of directional fluid manipulation and a radiative cooling layer. Compared with the unmodified parallel origami, the shell-like origami with a radiative cooling layer shows a 56% improvement in condensate efficiency as well as the directional liquid drainage. This work demonstrates a more accessible design for the optimization of on-surface fluid control, and the improved performance of liquid transport should extend the applications of bioinspired fluid-manipulating interfaces.

Methodologies, technologies, and strategies for acoustic streaming-based acoustofluidics

Acoustofluidics offers contact-free manipulation of particles and fluids, enabling their uses in various life sciences, such as for biological and medical applications. Recently, there have been extensive studies on acoustic streaming-based acoustofluidics, which are formed inside a liquid agitated by leaky surface acoustic waves (SAWs) through applying radio frequency signals to interdigital transducers (IDTs) on a piezoelectric substrate. This paper aims to describe acoustic streaming-based acoustofluidics and provide readers with an unbiased perspective to determine which IDT structural designs and techniques are most suitable for their research. This review, first, qualitatively and quantitatively introduces underlying physics of acoustic streaming. Then, it comprehensively discusses the fundamental designs of IDT technology for generating various types of acoustic streaming phenomena. Acoustic streaming-related methodologies and the corresponding biomedical applications are highlighted and discussed, according to either standing surface acoustic waves or traveling surface acoustic waves generated, and also sessile droplets or continuous fluids used. Traveling SAW-based acoustofluidics generate various physical phenomena including mixing, concentration, rotation, pumping, jetting, nebulization/atomization, and droplet generation, as well as mixing and concentration of liquid in a channel/chamber. Standing SAWs induce streaming for digital and continuous acoustofluidics, which can be used for mixing, sorting, and trapping in a channel/chamber. Key challenges, future developments, and directions for acoustic streaming-based acoustofluidics are finally discussed.

Addressable microfluidics technology for non-sacrificial analysis of biomaterial implants in vivo.

Tissue regeneration-promoting and drug-eluting biomaterials are commonly implanted into animals as a part of late-stage testing before committing to human trials required by the government. Because the trials are very expensive (e.g., they can cost over a billion U.S. dollars), it is critical for companies to have the best possible characterization of the materials' safety and efficacy before it goes into a human. However, the conventional approaches to biomaterial evaluation necessitate sacrificial analysis (i.e., euthanizing a different animal for measuring each time point and retrieving the implant for histological analysis), due to the inability to monitor how the host tissues respond to the presence of the material in situ. This is expensive, inaccurate, discontinuous, and unethical. In contrast, our manuscript presents a novel microfluidic platform potentially capable of performing non-disruptive fluid manipulations within the spatial constraints of an 8 mm diameter critical calvarial defect-a "gold standard" model for testing engineered bone tissue scaffolds in living animals. In particular, here, addressable microfluidic plumbing is specifically adapted for the in vivo implantation into a simulated rat's skull, and is integrated with a combinatorial multiplexer for a better scaling of many time points and/or biological signal measurements. The collected samples (modeled as food dyes for proof of concept) are then transported, stored, and analyzed ex vivo, which adds previously-unavailable ease and flexibility. Furthermore, care is taken to maintain a fluid equilibrium in the simulated animal's head during the sampling to avoid damage to the host and to the implant. Ultimately, future implantation protocols and technology improvements are envisioned toward the end of the manuscript. Although the bone tissue engineering application was chosen as a proof of concept, with further work, the technology is potentially versatile enough for other in vivo sampling applications. Hence, the successful outcomes of its advancement should benefit companies developing, testing, and producing vaccines and drugs by accelerating the translation of advanced cell culturing tech to the clinical market. Moreover, the nondestructive monitoring of the in vivo environment can lower animal experiment costs and provide data-gathering continuity superior to the conventional destructive analysis. Lastly, the reduction of sacrifices stemming from the use of this technology would make future animal experiments more ethical.

Sharp-edge-based acoustofluidic chip capable of programmable pumping, mixing, cell focusing, and trapping

Precise manipulation of fluids and objects on the microscale is seldom a simple task, but, nevertheless, crucial for many applications in life sciences and chemical engineering. We present a microfluidic chip fabricated in silicon–glass, featuring one or several pairs of acoustically excited sharp edges at side channels that drive a pumping flow throughout the chip and produce a strong mixing flow in their vicinity. The chip is simultaneously capable of focusing cells and microparticles that are suspended in the flow. The multifunctional micropump provides a continuous flow across a wide range of excitation frequencies (80 kHz–2 MHz), with flow rates ranging from nl min−1 to μl min−1, depending on the excitation parameters. In the low-voltage regime, the flow rate depends quadratically on the voltage applied to the piezoelectric transducer, making the pump programmable. The behavior in the system is elucidated with finite element method simulations, which are in good agreement with experimentally observed behavior. The acoustic radiation force arising due to a fluidic channel resonance is responsible for the focusing of cells and microparticles, while the streaming produced by the pair of sharp edges generates the pumping and the mixing flow. If cell focusing is detrimental for a certain application, it can also be avoided by exciting the system away from the resonance frequency of the fluidic channel. The device, with its unique bundle of functionalities, displays great potential for various biochemical applications.

A facile microfluidic chip design for DNA detection using dengue serotypes as a proof-of-concept case study

Dengue fever is caused by any of the four serotypes of dengue viruses, DENV-1, DENV-2, DENV-3 and DENV-4 spread by mosquito bites and is important to distinguish between them due to lack of cross-protective neutralizing antibodies for each serotype. Secondary infections also put individuals at higher risk for severe dengue illness than those who have not been previously infected. Current preferred assays include reverse transcription-PCR (RT-PCR) and ELISA. To enable on-field diagnosis of dengue serotypes, the detection process would need to be simplified or at least semi-automated. A downstream detection module was conceptualized and fabricated to detect the amplified DNA from the provided PCR mix (product) of previously developed modular microfluidic chips involving sample loading, cell lysis, RNA extraction and RT-PCR. Further, to ensure accuracy, each serotype assay necessitates a positive control, negative control and test sample, which constitutes 3 separate channels for the diagnosis of just 1 serotype. In this study, a 6-channel bi-assay microfluidic chip was designed with pre-loaded diluent and cyanine dye, sample chamber for loading, sequential fluidic sample mixing, and integrated membranes for simultaneous (6-channel) fluidic manipulation from a single actuation source. Positive samples will turn the dye from blue to violet while the negative controls will remain blue. The integrated membranes provided color contrast and facilitated the manipulation of the samples to the same line of sight for simultaneous analysis, paving the way for automated color analysis via smartphone.

Fluid manipulation via multifunctional lubricant infused slippery surfaces: principle, design and applications.

Water-repellent interfaces with high performance have emerged as an indispensable platform for developing advanced materials and devices. Inspired by the pitcher plant, slippery liquid-infused porous surfaces (SLIPSs) with reliable hydrophobicity have proven to possess great potential for various applications in droplet and bubble manipulation, droplet energy harvesting, condensation, fog collection, anti-icing, and anti-biofouling due to their excellent properties such as persistent surface hydrophobicity, molecular smoothness, and fluidity. This review aims to introduce the development history of interaction between SLIPSs and fluids as well as the design principles, preparation methods, and various applications of some of the more typical SLIPSs. The fluid manipulation strategies of the slippery surfaces have been proposed including the wettability pattern, oriented micro-structure, and geometric gradient. At last, the application prospects of SLIPSs in various fields and the challenges in the design and fabrication of slippery surfaces are analyzed. We envision that this review can provide an overview of the fluid manipulating processes on slippery surfaces for researchers in both academic and industrial fields.

Implantable microfluidics: methods and applications.

Implantable microfluidics involves integrating microfluidic functionalities into implantable devices, such as medical implants or bioelectronic devices, revolutionizing healthcare by enabling personalized and precise diagnostics, targeted drug delivery, and regeneration of targeted tissues or organs. The impact of implantable microfluidics depends heavily on advancements in both methods and applications. Despite significant progress in the past two decades, continuous advancements are still required in fluidic control and manipulation, device miniaturization and integration, biosafety considerations, as well as the development of various application scenarios to address a wide range of healthcare issues. In this review, we discuss advancements in implantable microfluidics, focusing on methods and applications. Regarding methods, we discuss progress made in fluid manipulation, device fabrication, and biosafety considerations in implantable microfluidics. In terms of applications, we review advancements in using implantable microfluidics for drug delivery, diagnostics, tissue engineering, and energy harvesting. The purpose of this review is to expand research ideas for the development of novel implantable microfluidic devices for various healthcare applications.

Flow control in paper-based microfluidic channel by using hydrophobic tape barrier on the paper surface

Paper-based microfluidics offers a simple, cost-effective, and versatile platform for fluid manipulation and analysis. Despite significant advancements in paper fluidics, the flow control in paper channel remains a challenging task. In this regard, we have developed a flow delay channel in paper using rectangular tape patterns on the paper surface. We have investigated the effect of hydrophobic tape barriers with varying widths. The designing and cutting of the hydrophobic tape and paper channel was performed by CO2 laser machine using CorelDraw software. Once cut, the tape barriers were attached to the paper surface and then passed through the roller press machine for proper adhesion of tape pattern onto the paper’s surface. From experiments, we observed that by increasing the width of tape, the delay also increased. The hydrophobic tape on the paper surface caused resistance to the flowing fluid. Due to this surface resistance, flow velocity reduced, and the time delay increased. We believe that our novel approach will provide an alternative method of flow control for paper-based microfluidic devices and can be utilized in various food quality sensors and lateral flow devices.

Understanding electrohydrodynamic (EHD) performance of corona discharge via particle image velocimetry (PIV)

Electrohydrodynamic (EHD) pumping through corona discharge has found many interesting applications, as it does not require any mechanical moving parts. However, understanding the EHD performance of the corona discharge is crucial for a controllable manipulation of the fluids. This study investigates the pumping performance of an in-house built corona discharge setup for inducing circular motions in the fluids. Silicone oils of different kinematic viscosities are used as the EHD fluid. The EHD performance/fluid characteristics are studied experimentally using particle image velocimetry (PIV) under different DC corona voltages and their results are verified using the continuity equation. Additionally, an analytical model is derived using the Navier–Stokes equations. A clear scaling effect of the corona voltage is seen for the EHD fluid. The EHD fluid exhibits higher velocities at high corona voltages with low perturbation frequency (< 3 Hz) which is attributed to a sloshing motion in the fluid. This naturally occurring sloshing (out-of-plane) motion can be utilized when mixing is desired in the fluid. The results of this study can be used for contact-less and controllable manipulation of dielectric fluids (i.e., silicone oils) for potential applications in emulsion formation and separation.Graphical abstract

Engineered Switchable-Wettability Surfaces for Multi-Path Directional Transportation of Droplets and Subaqueous Bubbles.

Conventional engineered surfaces for fluid manipulation are hindered by the set wettability, and thus they can only achieve spontaneous transport of single-phase fluid, namely liquid or gas. Moreover, fluid transport systems that are robust to path defects have yet to be fully explored. Here, unprecedentedly, a universal wettability switching strategy is developed for achieving programmable directional transport of both droplets and subaqueous bubbles on a dumbbell-patterned functional surface (DPFS), featuring in strong robustness, high efficiency, and effective cost. By tuning the superwettability of DPFS through octadecyltrichlorosilane treatment and ultraviolet-C selective irradiation, the transport fluid can alternate between liquid and gas. The material's switchable superwettability regulates the fluid directed dynamics within the confined pattern, in which the sustaining fluid propelling relies on the surface energy difference between the starting and terminal sites. This enables the construction of multiple channels, which works synergistically with ultralow-volume-loss transport to impart the fluidic system with strong robustness against path defects. Underlying the completion of complex microfluidics tasks, spatially-selective cooling devices and subaqueous gas microreactors are successfully demonstrated. This energy-consumption-free fluid transport system opens a new avenue for on-chip programmable fluid manipulation, promoting innovative applications requiring rational control of two-phase fluid transport.

Dynamic morphological transformations in soft architected materials via buckling instability encoded heterogeneous magnetization

The geometric reconfigurations in three-dimensional morphable structures have a wide range of applications in flexible electronic devices and smart systems with unusual mechanical, acoustic, and thermal properties. However, achieving the highly controllable anisotropic transformation and dynamic regulation of architected materials crossing different scales remains challenging. Herein, we develop a magnetic regulation approach that provides an enabling technology to achieve the controllable transformation of morphable structures and unveil their dynamic modulation mechanism as well as potential applications. With buckling instability encoded heterogeneous magnetization profiles inside soft architected materials, spatially and temporally programmed magnetic inputs drive the formation of a variety of anisotropic morphological transformations and dynamic geometric reconfiguration. The introduction of magnetic stimulation could help to predetermine the buckling states of soft architected materials, and enable the formation of definite and controllable buckling states without prolonged magnetic stimulation input. The dynamic modulations can be exploited to build systems with switchable fluidic properties and are demonstrated to achieve capabilities of fluidic manipulation, selective particle trapping, sensitivity-enhanced biomedical analysis, and soft robotics. The work provides new insights to harness the programmable and dynamic morphological transformation of soft architected materials and promises benefits in microfluidics, programmable metamaterials, and biomedical applications.