Surface Cleaning of Oil Contaminants Using Bulk Nanobubbles.

The removal of oil from solid surfaces, such as textiles and plates, remains a challenge due to the strong binding affinity of the oil. Conventional methods for surface cleaning often require surfactants and mechanical abrasion to enhance the cleaning process. However, in excess, these can pose adverse effects on the environment and to the material. This study investigated how bulk nanobubble water can clean oil microdroplets deposited on surfaces like glass coverslips and dishes. Microscopy imaging and further image analysis clearly revealed that these microdroplets detached from both hydrophobic and hydrophilic surfaces when washed with bulk nanobubble water within a fluidic microchannel. Oil contaminant cleaning was also conducted in water as mobile phase to mimic the circumstances that occur in a dishwasher and washing machine. Cleaning on a larger scale also proved very successful in the removal of oil from a porcelain bowl. These results indicate that nanobubble water can easily remove oil contaminants from glass and porcelain surfaces without the assistance of surfactants. This is in stark contrast to negligible results obtained with a control solution without nanobubbles. This study indicates that nanobubble technology is an innovative, low-cost, eco-friendly approach for oil removal, demonstrating its potential for broad practical applications.

Protein array processing software for automated semiquantitative analysis of serum antibody repertoires.

Effective immunotherapies activate natural antitumor immune responses in patients undergoing treatment. The ability to monitor immune activation in response to immunotherapy is critical in measuring treatment efficacy over time and across patient cohorts. Protein arrays are systematically arranged, large collections of annotated proteins on planar surfaces, which can be used for the characterization of disease-specific and treatment-induced antibody repertoires in individuals undergoing immunotherapy. However, the absence of appropriate image analysis and data processing software presents a substantial hurdle, limiting the uptake of this approach in immunotherapy research. We developed a first, automated semiquantitative open-source software package for the analysis of widely used protein macroarrays. The software allows accurate single array and inter-array comparative studies through the tackling of intra-array inconsistencies arising from experimental disparities. The innovative and automated image analysis process includes adaptive positioning, background identification and subtraction, removal of null signals, robust statistical analysis, and protein pair validation. The normalized values allow a convenient semiquantitative data analysis of different samples or timepoints. Enabling accurate characterization of sample series to identify disease-specific immune profiles or their relative changes in response to treatment may serve as a diagnostic or predictive tool of disease.

Microfluidic encapsulation of DNAs in liquid beads for digital PCR application.

Droplet-based microfluidics and digital polymerase chain reaction (PCR) hold significant promise for accurately detecting and quantifying pathogens. However, existing droplet-based digital PCR (ddPCR) applications have been relying exclusively on single emulsion droplets. Single emulsion droplets may not be suitable for applications such as identifying the source and pathways of water contamination where the templates must be protected against harsh environmental conditions. In this study, we developed a core-shell particle to serve as a protective framework for DNAs, with potential applications in digital PCR. We employed a high-throughput and facile flow-focusing microfluidic device to generate liquid beads, core-shell particles with liquid cores, which provided precise control over process parameters and consequently particle characteristics. Notably, the interfacial interaction between the core and shell liquids could be adjusted without adding surfactants to either phase. As maintaining stability is essential for ensuring the accuracy of digital PCR (dPCR), we investigated parameters that affect the stability of core-shell droplets, including surfactants in the continuous phase and core density. As a proof of concept, we encapsulated a series of human faecal DNA samples in the core-shell droplets and the subsequent liquid beads. The core-shell particles ensure contamination-free encapsulation of DNA in the core. The volume of the core droplets containing the PCR mixture is only 0.12 nL. Our experimental results indicate that the liquid beads formulated using our technique can amplify the encapsulated DNA and be used for digital PCR without interfering with the fluorescence signal. We successfully demonstrated the ability to detect and quantify DNA under varying concentrations. These findings provide new insights and a step change in digital PCR that could benefit various applications, including the detection and tracking of environmental pollution.

Asymmetrical Obstacles Enable Unilateral Inertial Focusing and Separation in Sinusoidal Microchannel.

Inertial microfluidics uses the intrinsic fluid inertia in confined channels to manipulate the particles and cells in a simple, high-throughput, and precise manner. Inertial focusing in a straight channel results in several equilibrium positions within the cross sections. Introducing channel curvature and adjusting the cross-sectional aspect ratio and shape can modify inertial focusing positions and can reduce the number of equilibrium positions. In this work, we introduce an innovative way to adjust the inertial focusing and reduce equilibrium positions by embedding asymmetrical obstacle microstructures. We demonstrated that asymmetrical concave obstacles could break the symmetry of original inertial focusing positions, resulting in unilateral focusing. In addition, we characterized the influence of obstacle size and 3 asymmetrical obstacle patterns on unilateral inertial focusing. Finally, we applied differential unilateral focusing on the separation of 10- and 15-µm particles and isolation of brain cancer cells (U87MG) from white blood cells (WBCs), respectively. The results indicated an excellent cancer cell recovery of 96.4% and WBC rejection ratio of 98.81%. After single processing, the purity of the cancer cells was dramatically enhanced from 1.01% to 90.13%, with an 89.24-fold enrichment. We believe that embedding asymmetric concave micro-obstacles is a new strategy to achieve unilateral inertial focusing and separation in curved channels.

Body Forces Drive the Apparent Line Tension of Sessile Droplets.

The line tension of a three-phase contact line is implicated in a wide variety of interfacial phenomena, but there is ongoing controversy, with existing measurements spanning six orders of magnitude in both signs. Here, we show that computationally obtained magnitudes, sign changes, and nontrivial variations of apparent line tension can be faithfully reproduced in a parsimonious model that incorporates only liquid-substrate interactions. Our results suggest that the origin for the remarkable variation lies in the failure of a widely used estimation method to eliminate body forces, leading measured line tensions to behave like an extensive quantity.

Nanobubble technologies: Applications in therapy from molecular to cellular level.

Nanobubbles are gaseous entities suspended in bulk liquids that have widespread beneficial usage in many industries. Nanobubbles are already proving to be versatile in furthering the effectiveness of disease treatment on cellular and molecular levels. They are functionalized with biocompatible and stealth surfaces to aid in the delivery of drugs. At the same time, nanobubbles serve as imaging agents due to the echogenic properties of the gas core, which can also be utilized for controlled and targeted delivery. This review provides an overview of the biomedical applications of nanobubbles, covering their preparation and characterization methods, discussing where the research is currently focused, and how they will help shape the future of biomedicine.

Recent microfluidic advances in submicron to nanoparticle manipulation and separation.

Manipulation and separation of submicron and nanoparticles are indispensable in many chemical, biological, medical, and environmental applications. Conventional technologies such as ultracentrifugation, ultrafiltration, size exclusion chromatography, precipitation and immunoaffinity capture are limited by high cost, low resolution, low purity or the risk of damage to biological particles. Microfluidics can accurately control fluid flow in channels with dimensions of tens of micrometres. Rapid microfluidics advancement has enabled precise sorting and isolating of nanoparticles with better resolution and efficiency than conventional technologies. This paper comprehensively studies the latest progress in microfluidic technology for submicron and nanoparticle manipulation. We first summarise the principles of the traditional techniques for manipulating nanoparticles. Following the classification of microfluidic techniques as active, passive, and hybrid approaches, we elaborate on the physics, device design, working mechanism and applications of each technique. We also compare the merits and demerits of different microfluidic techniques and benchmark them with conventional technologies. Concurrently, we summarise seven standard post-separation detection techniques for nanoparticles. Finally, we discuss current challenges and future perspectives on microfluidic technology for nanoparticle manipulation and separation.

Fabrication and characterization of core-shell microparticles containing an aqueous core.

Core-shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core-shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core-shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core-shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.

Dynamic Behaviours of Monodisperse Double Emulsion Formation in a Tri-Axial Capillary Device.

We investigated experimentally, analytically, and numerically the formation process of double emulsion formations under a dripping regime in a tri-axial co-flow capillary device. The results show that mismatches of core and shell droplets under a given flow condition can be captured both experimentally and numerically. We propose a semi-analytical model using the match ratio between the pinch-off length of the shell droplet and the product of the core growth rate and its pinch-off time. The mismatch issue can be avoided if the match ratio is lower than unity. We considered a model with the wall effect to predict the size of the matched double emulsion. The model shows slight deviations with experimental data if the Reynolds number of the continuous phase is lower than 0.06 but asymptotically approaches good agreement if the Reynolds number increases from 0.06 to 0.14. The numerical simulation generally agrees with the experiments under various flow conditions.

Tuning particle inertial separation in sinusoidal channels by embedding periodic obstacle microstructures.

Inertial microfluidics functions solely based on the fluid dynamics at relatively high flow speed. Thus, channel geometry is the critical design parameter that contributes to the performance of the device. Four basic channel geometries (i.e., straight, expansion-contraction, spiral and serpentine) have been proposed and extensively studied. To further enhance the performance, innovative channel design through combining two or more geometries is promising. This work explores embedding periodic concave and convex obstacle microstructures in sinusoidal channels and investigates their influence on particle inertial focusing and separation. The concave obstacles could significantly enhance the Dean flow and tune the flow range for particle inertial focusing and separation. Based on this finding, we propose a cascaded device by connecting two sinusoidal channels consecutively for rare cell separation. The concave obstacles are embedded in the second channel to adapt its operational flow rates and enable the functional operation of both channels. Polystyrene beads and breast cancer cells (T47D) spiking in the blood were respectively processed by the proposed device. The results indicate an outstanding separation performance, with 3 to 4 orders of magnitude enhancement in purity for samples with a primary cancer cells ratio of 0.01% and 0.001%, respectively. Embedding microstructures as obstacles brings more flexibility to the design of inertial microfluidic devices, offering a feasible new way to combine two or more serial processing units for high-performance separation.

Enhanced Blood Plasma Extraction Utilising Viscoelastic Effects in a Serpentine Microchannel.

Plasma extraction from blood is essential for diagnosis of many diseases. The critical process of plasma extraction requires removal of blood cells from whole blood. Fluid viscoelasticity promotes cell migration towards the central axis of flow due to differences in normal stress and physical properties of cells. We investigated the effects of altering fluid viscoelasticity on blood plasma extraction in a serpentine microchannel. Poly (ethylene oxide) (PEO) was dissolved into blood to increase its viscoelasticity. The influences of PEO concentration, blood dilution, and flow rate on the performance of cell focusing were examined. We found that focusing performance can be significantly enhanced by adding PEO into blood. The optimal PEO concentration ranged from 100 to 200 ppm with respect to effective blood cell focusing. An optimal flow rate from 1 to 15 µL/min was determined, at least for our experimental setup. Given less than 1% haemolysis was detected at the outlets in all experimental combinations, the proposed microfluidic methodology appears suitable for applications sensitive to haemocompatibility.

Emerging technologies for PFOS/PFOA degradation and removal: A review.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are highly recalcitrant anthropogenic chemicals that are ubiquitously present in the environment and are harmful to humans. Typical water and wastewater treatment processes (coagulation, flocculation, sedimentation, and filtration) are proven to be largely ineffective, while adsorption with granular activated carbon (GAC) has been the chief option to capture them from aqueous sources followed by incineration. However, this process is time-consuming, and produces additional solid waste and air pollution. Treatment methods for PFOS and PFOA generally follow two routes: (1) removal from source and reduce the risk; (2) degradation. Emerging technologies focusing on degradation are critically reviewed in this contribution. Various processes such as bioremediation, electrocoagulation, foam fractionation, sonolysis, photocatalysis, mechanochemical, electrochemical degradation, beams of electron and plasma have been developed and studied in the past decade to address PFAS crisis. The underlying mechanisms of these PFAS degradation methods have been categorized. Two main challenges have been identified, namely complexity in large scale operation and the release of toxic byproducts. Based on the literature survey, we have provided a strength-weakness-opportunity-threat (SWOT) analysis and quantitative rating on their efficiency, environmental impact and technology readiness.

Multiphysics microfluidics for cell manipulation and separation: a review.

Multiphysics microfluidics, which combines multiple functional physical processes in a microfluidics platform, is an emerging research area that has attracted increasing interest for diverse biomedical applications. Multiphysics microfluidics is expected to overcome the limitations of individual physical phenomena through combining their advantages. Furthermore, multiphysics microfluidics is superior for cell manipulation due to its high precision, better sensitivity, real-time tunability, and multi-target sorting capabilities. These exciting features motivate us to review this state-of-the-art field and reassess the feasibility of coupling multiple physical processes. To confine the scope of this paper, we mainly focus on five common forces in microfluidics: inertial lift, elastic, dielectrophoresis (DEP), magnetophoresis (MP), and acoustic forces. This review first explains the working mechanisms of single physical phenomena. Next, we classify multiphysics techniques in terms of cascaded connections and physical coupling, and we elaborate on combinations of designs and working mechanisms in systems reported in the literature to date. Finally, we discuss the possibility of combining multiple physical processes and associated design schemes and propose several promising future directions.

Investigation of viscoelastic focusing of particles and cells in a zigzag microchannel.

Microfluidic particle focusing has been a vital prerequisite step in sample preparation for downstream particle separation, counting, detection, or analysis, and has attracted broad applications in biomedical and chemical areas. Besides all the active and passive focusing methods in Newtonian fluids, particle focusing in viscoelastic fluids has been attracting increasing interest because of its advantages induced by intrinsic fluid property. However, to achieve a well-defined focusing position, there is a need to extend channel lengths when focusing micrometer-sized or sub-microsized particles, which would result in the size increase of the microfluidic devices. This work investigated the sheathless viscoelastic focusing of particles and cells in a zigzag microfluidic channel. Benefit from the zigzag structure of the channel, the channel length and the footprint of the device can be reduced without sacrificing the focusing performance. In this work, the viscoelastic focusing, including the focusing of 10 µm polystyrene particles, 5 µm polystyrene particles, 5 µm magnetic particles, white blood cells (WBCs), red blood cells (RBCs), and cancer cells, were all demonstrated. Moreover, magnetophoretic separation of magnetic and nonmagnetic particles after viscoelastic pre-focusing was shown. This focusing technique has the potential to be used in a range of biomedical applications.

Transient Solubility Gradients Mediate Oversaturation during Solvent Exchange.

Solvent exchange facilitates high-density nucleation of sessile nanodroplets or nanobubbles by successively wetting a surface with two solvents of contrasting solubility with respect to a target species. Yet the key physical mechanisms underlying its efficacy have yet to be theoretically explained. We develop a minimal model for solvent exchange, for the prototypical example of water and ethanol as the solvents and nitrogen as the target species. Our calculations show that solvent exchange is mediated by transient solubility gradients that dominate over the intrinsic concentration gradient of nitrogen in the incipient moments after exchange. Solubility gradients advect nitrogen toward the substrate during ethanol-water exchange but away from it in water-ethanol exchange, consistent with the directionality observed in experiments.

Measuring the effective surface tension of a floating liquid marble using X-ray imaging.

A liquid marble (LM) is a droplet coated with microparticles that isolate the liquid interior from its surroundings, making it perfectly non-wetting. This attractive feature allows the LM to perform useful tasks such as coalescence, targeted delivery, and controlled release. The non-wetting characteristic also allows the LM to float on a carrier liquid. The growing number of applications in digital microfluidics requires further insights into the fundamental properties of a LM such as its effective surface tension. Although the coating provides the LM with various desirable characteristics, its random construction presents a major obstacle to accurate optical analysis. This paper presents a novel method to measure the effective surface tension of a floating LM using X-ray imaging and curve fitting procedures. X-ray imaging reveals the true LM liquid-air interface hidden by the coating particles. Analysis of this interface showed that the effective surface tension of a LM is not significantly different from that of its liquid content. This indicates that the particle coating might not have significantly altered the behaviour of the liquid interface. We also found that our method is sensitive enough to detect the variations across individual LMs.

Inertial Microfluidic Purification of Floating Cancer Cells for Drug Screening and Three-Dimensional Tumor Models.

Floating cancer cells can survive the programmed death anoikis process after detaching from the extracellular matrix for the anchorage-dependent cells. Purification of viable floating cancer cells is essential for many biomedical studies, such as drug screening and cancer model development. However, the floating cancer cells are mixed with dead cells and debris in the medium supernatant. In this paper, we developed an inertial microfluidic device with sinusoidal microchannels to continuously remove dead cells and debris from viable cells. First, we characterized the differential inertial focusing properties of polystyrene beads in the devices. Then, we investigated the effects of flow rate on inertial focusing of floating MDA-MB-231 cells. At an optimal flow condition, purification of viable cells was performed and the purity of live cells was increased significantly from 19.9% to 76.6%, with a recovery rate of 69.7%. After separation, we studied and compared the floating and adherent MDA-MB-231 cells in terms of cell proliferation, protrusive cellular structure, and the expression of cyclooxygenase (Cox-2) which is related to epithelial-mesenchymal transition (EMT) changes. Meanwhile, drug screening of both floating and adherent cancer cells was conducted using a chemotherapeutic drug, doxorubicin (Dox). The results revealed that the floating cancer cells possess 30-fold acquired chemoresistance as compared to the adherent cancer cells. Furthermore, a three-dimensional (3D) double-cellular coculture model of human mammary fibroblasts (HMF) spheroid and cancer cells using the floating liquid marble technique was developed.

How Bulk Nanobubbles Might Survive.

The existence of bulk nanobubbles has long been regarded with scepticism, due to the limitations of experimental techniques and the widespread assumption that spherical bubbles cannot achieve stable equilibrium. We develop a model for the stability of bulk nanobubbles based on the experimental observation that the zeta potential of spherical bubbles abruptly diverges from the planar value below 10 µm. Our calculations recover three persistently reported-but disputed-properties of bulk nanobubbles: that they stabilize at a typical radius of ∼100 nm, that this radius is bounded below 1 µm, and that it increases with ionic concentration.

Direct Measurement of the Contents, Thickness, and Internal Pressure of Molybdenum Disulfide Nanoblisters.

Nanoblisters have attracted attention due to their ability to controllably modulate the properties of two-dimensional materials. The accurate measurement or estimation of their properties is nontrivial and largely based on Hencky's theory. However, these estimates require a priori knowledge of material properties and propagate large errors. Here we show, through a systematic atomic force microscopy study, several strategies that lead to vastly enhanced characterization of nanoblisters. First, we find that nanoblisters may contain both liquid and gas, resolving an ongoing debate in the literature. Second, we demonstrate how to definitively determine the membrane thickness of a nanoblister and show that Hencky's theory can only reliably predict membrane thicknesses for small aspect ratios and small membrane thicknesses. Third, we develop a novel technique to measure the internal pressures of nanoblisters, which quantitatively agrees with Hencky's theory but carries a 1 order smaller propagated error.