Microfluidics and Nanofluidics最新文献

The migration and proliferation of cancer cells within the extracellular matrix play a critical role in cancer metastasis, enabling cancer cells to move between the blood and lymph vessels and surrounding tissues and form tumors. The heterogeneous oxygen conditions in the tumor microenvironment (TME) also affect cancer cell behaviors. However, the behaviors of cancer cells in the extremely low oxygen concentration gradients in the TME are poorly understood. The present study evaluated the behaviors of cultured cancer cells using microfluidic devices capable of precise oxygen concentration control. MDA-MB-231 cells mixed within a collagen gel were placed in the device and observed for 24 h under various oxygen concentration gradients with different oxygen levels and slopes. The cell distribution changed depending on the oxygen concentration gradient, with cell proliferation being the primary factor, with some contribution of aerotaxis. Aerotaxis directed the migration of MDA-MB-231 cells toward higher oxygen concentrations within the 2–6% O₂ range and lower oxygen concentrations within the 7–12% O₂ range. These results demonstrate the utility of microfluidic devices for analyzing cancer cell behaviors under oxygen concentration gradients at oxygen levels similar to those in the TME and show that cancer cells exhibit different aerotactic behaviors at specific oxygen concentrations.

Zoledronic acid (ZA), the third-generation nitrogen-containing bisphosphonate, is one of the most effective bisphosphonates and is used as a highly potent inhibitor of bone resorption with no adverse effects on bone mineralization. It is also used to treat multiple cancers, such as lung cancer, bone cancer, breast cancer, and prostate cancer. A microfluidic system can generate an adjustable flow rate and pressure inside multiple channels with the desired shape and dimensions, which are often fabricated from PDMS polymer. Among the advantages of these systems are precise control of environmental conditions, reduction of user intervention, and reduced time and reagent volumes. The microfluidic method, as a simple and cost-effective process with high capability, leads to particle size control, narrow size distribution, and the spherical shape of nanoparticles. With the rapid development of microfluidic technology, the preparation of particles with controlled size, morphology, and composition would be possible with this approach. In this study, to the best of our knowledge, the evaluation of the cytotoxic activity of microfluidic synthesized chitosan-zoledronic acid (CS-ZA) nanoparticles has been investigated for the first time in order to develop new cancer therapy strategies by using pharmaceutical nanotechnology. A microfluidic synthesis of nanoparticles with a narrow size distribution and uniform morphology through the ionic gelation of chitosan (CS) with ZA without a crosslinker was explained in detail in the previous article (Khayati et al., Int J Biol Macromol 234, 2023). This study aimed to evaluate the cytotoxic effect of the best microfluidic synthesized nanoparticles with ZA solution as core flow, CS as sheath flow, and flow ratios of ZA/CS = 0.5 (denoted by MFCSZA0.5) along with synthesized bulk nanoparticles (BCSZA) on the A549 lung cancer cell line through an MTT cell viability assay and a flow cytometric apoptosis assay. The results indicate that MFCSZA0.5 demonstrated significantly greater antitumor activity compared to BCSZA and free ZA. The in vitro drug release from MFCSZA0.5 microfluidic synthesized nanoparticles depicted a gradual, sustained release profile compared to BCSZA synthesized in bulk conditions. However, both of these nanoparticles exhibit promising carriers for intracellular delivery of ZA molecules, which ultimately affect cancer cell viability. The microfluidic method demonstrated a high drug entrapment efficiency compared to the bulk method, and it showed a more controlled in-vitro release of the drug. The synthesized nanoparticles in both microfluidic and bulk methods were found to have an anticancer effect comparable to the free ZA drug.

Graphical abstract

A microfluidic system for immunohistochemistry providing improved staining uniformity and more convenient operation is designed, prototyped, and tested. The chip is comprised of two parts: a plastic (polycarbonate PC) sliding cover that forms a chamber over a glass slide with a mounted sample tissue section. Staining reagents and labeled antibodies are successively pipetted into the chamber and flow over the tissue section by gravity. Staining uniformity is improved in channel design optimization. The plastic cover includes structural features to modify the flow field and reduce the mixing of successive loadings. Flow characteristics are optimized using finite element modeling. The approach shows substantially more uniform staining, as demonstrated quantitatively by image processing of stained samples.

Lab-on-a-disc (LoD) devices utilize centrifugal force to regulate fluid movement and are widely employed in biochemical applications. LoDs facilitate biochemical analysis by integrating different essential steps such as mixing samples and reagents, separating target components from the sample, and detecting analytes in a single platform. This integration on a single disc substrate enables the miniaturization and automation of various biochemical workflows. However, current LoD systems frequently rely on active valves, which increase complexity and limit versatility. To address these challenges, this study employed 3D printing technology to develop a 3D-structured tilt capillary valve acting as a passive control mechanism. Tilt capillary valves with inclination angles ranging from 50° to 80° were fabricated, and their burst rotational speeds and repeatability were compared with those of conventional capillary and slope valves. The tilt capillary valve demonstrated superior performance, achieving high-speed fluid control with relative standard deviations ranging from 1.5 to 2.1%. This improvement was attained by distributing the effects of centrifugal and gravitational forces along the inclined flow path. Additionally, the capillary structure stabilized the effects of surface tension, further enhancing reproducibility. These findings suggest that the developed tilt capillary valve enhances the LoD system performance, enabling more precise and rapid fluid control. The enhanced passive valve presented in this study can be implemented in advanced microfluidic device designs, presenting considerable potential for biochemical assays, point-of-care applications, environmental monitoring, and food safety testing.

Droplet microfluidics is a rapidly evolving area of research with significant implications in bioengineering, drug delivery, chemical synthesis, environmental monitoring, and micro-scale electronics manufacturing. Recent advancements in droplet generation methods, including the use of electric fields and acoustic waves, have been driven by related technological developments. These innovations have enabled the creation of droplets with a wide range of sizes, shapes, and compositions, opening new frontiers for droplet microfluidic applications. This study reviews recent advances in droplet formation within microfluidic channels, beginning with an overview of droplet microfluidics and followed by an analysis of the various techniques used for droplet formation. The paper examines the impact of channel geometry, fluid flow rates, and channel wall surface properties on droplet formation. Additionally, it discusses the control of microfluidic droplets and the diverse applications of droplet microfluidics. The study also analyzes the morphological changes of droplets in response to variations in different controlling factors and presents an overview of compound droplet microfluidics, highlighting its technological aspects and significance across various applications. The influential factors governing the dynamics of compound droplets and their respective effects are briefly reviewed throughout the study. In conclusion, the paper identifies the major challenges and opportunities associated with microfluidic droplet dynamics and outlines emerging areas based on this technology. Overall, it provides a comprehensive overview of recent developments in droplet formation within microfluidic channels.

To evaluate the potential use of phage-displayed recombinant antibody fragments as biorecognition elements on microfluidic paper-based devices (µPADs), phage-displayed VL and soluble VL antibody fragments were immobilized on the chitosan-modified surface of µPADs to detect glycine-extended gastrin 17 (G17-Gly) an integral peptide biomarker for colorectal cancer. Additionally, the phage shaft displaying the scFv antibody fragment, used as a detection probe, was conjugated with gold nanoparticles (GNPs) and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and UV–visible spectroscopy (UV–Vis). Following the microfluidic sandwich immunoassay, the mean intensity of the color spots was quantitatively analyzed using an image analysis program. Peptide calibration curves showed a linear relationship between the intensity of the color spot signal and the logarithm of the peptide concentration within the ranges of 10⁻⁶–5 × 10⁻¹ µM (R² = 0.98) for the phage-VL fragment and 10⁻⁴–1 µM (R² = 0.97) for the soluble VL fragment, with limits of detection (LOD) of 0.9 and 29 pM, respectively. The proposed µPAD-based immunoassay with the desirable LODs without further amplification provides a simple, versatile means for detecting biomarkers and pathogens of interest.

The freezing of droplets is a complex interdisciplinary research topic involving physics, chemistry, and computational science. This phenomenon has attracted considerable attention due to its significant applications in aerospace, meteorology, materials science, cryobiology, and pharmaceutical development. The development of microfluidic technology provides an ideal platform for microscopic physical research. In this study, we designed a spiral-shaped milli-reactor with a T-junction microchannel to generate digital droplets for studying and observing the digital freezing process of droplets. During the study of the recalescence and solidification processes of digital droplets dynamically moving in microchannels, we found that although the digital generation of droplets in our channel aligns well with the literature, achieving the digitalization of the droplet freezing process is very challenging. Even the initial phase of freezing (the recalescence process) exhibits significant randomness. A key feature of the randomness in the freezing process is the nucleation position of droplets within the channel, which significantly impacts the digital characteristics and hinders digital freezing. During the investigation of freezing randomness, we identified five distinct nucleation profiles, which largely determine the evolution of the freezing front and the duration of the recalescence phase. However, upon studying the motion velocity of the freezing front, we found that these velocities are temperature-dependent. This aligns with the results of our phase-field simulations and experimental findings, indicating that the release of latent heat during the recalescence process is stable. Additionally, the randomness in freezing may also stem from the deformation of droplets during the solidification process. In this study, we identified two distinct solidification modes during the freezing phase: one initiating from the droplet’s head or tail and the other starting from the middle, with the latter causing significant droplet deformation. Through statistical analysis, we further explored the influence of flow rate variation on the digital clustering of droplet freezing and discovered flow rate parameters that optimize freezing digitalization. For instance, when the oil phase flow rate is fixed, varying the water phase flow rate initially increases and then decreases the flatness factor, reaching a maximum at a water phase flow rate of (Q_w = 0.5 , text {mL/min}), indicating optimal clustering of droplets. The findings of this study provide new perspectives and approaches for controlling droplet freezing in microfluidic systems, while also offering significant insights into the unique behaviors and phenomena of nucleation and solidification processes at the microscale.

In this paper, we propose a unified framework to describe three key atomic-scale fluid properties-density, viscosity, and slip length-within nanoscale channels. These properties, which deviate significantly from bulk behavior, are expressed using simple power-law models as functions of the nanochannel height. The proposed framework accurately captures experimental and simulation data, providing a more flexible and interpretable alternative to existing complex or disparate models. The key advantage of our model lies in its mathematical properties. Continuity and a continuous derivative ensure seamless implementation into numerical simulations and theoretical predictions, leading to more understandable, stable, and accurate results. Additionally, the model adheres to physical principles, predicting convergence to bulk properties as channel size increases. Further, compared to existing exponential models, the unified power-law modeling approach offers several advantages. It provides flexibility by capturing nonlinear relationships and diverse data curvatures, interpretability through physically meaningful parameters, and adaptability for integration with other functions to model complex phenomena. Its simplicity facilitates easy parameter estimation, model interpretation, and computational efficiency. Moreover, its robustness makes it less sensitive to outliers and noise while maintaining fewer parameters that directly correspond to underlying physics and scaling laws. Hence, the proposed model’s simplicity, smoothness, physical validity, and generality establish it as a significant heuristic tool for the efficient design and optimization of nanoscale devices, utilizing theory and simulations across a wide range of applications.

The study presents a novel approach leveraging electroosmotic flow actuation within a charged obstruction-laden microchannel to improve mixing and transport. Through comprehensive numerical simulations that solve the coupled modified Poisson-Nernst-Planck and Navier–Stokes equations, and accounts for finite ion size and ionic cloud overflow across nano-conduits, we evaluate the mixing performance and flow throughput for various obstruction arrangements within a microchannel by quantifying outlet tracer distributions, scalar dissipation rate, finite-time Lyapunov exponent (FTLE) fields, and average outlet velocities. Our results reveal that charged obstructions outperform uncharged counterparts in mixing performance, while parallel obstruction arrangements yield higher velocities and better mixing as compared to alternate arrangements. Surface charge density at the surfaces plays a critical role, with both low and high values facilitate effective mixing, albeit higher surface charge densities promote increased flow rates. However, distinct mixing mechanisms are observed at the low and the high surface charge cases as revealed by FTLE analysis while moderate values of surface charge delineate poor mixing performance. Notably, subsequent obstructions with axially overlapped zones emerge as a critical design for efficient mixing, a configuration previously unexplored. Exploiting these findings, we propose a simplified channel design with fewer obstructions, achieving excellent mixing and higher throughput while ensuring fabrication simplicity. The flow characteristics qualitatively agree with previous experiments but uniquely explore the impact of axially overlapping subsequent obstructions on mixing. The present approach holds promise for the design of various porous microfluidic systems utilizing the existing fabrication technologies, with broad applicability in mechanotransduction and other biomedical devices.

This study numerically investigated the enhancement of micromixing efficiency through integrating surface acoustic waves (SAWs) and hyper-elastic channel walls, modeled using a power-law fluid representative of human blood flow. The governing equations are systematically divided into zeroth, first, and second orders based on perturbation theory. This facilitates the development of a fully coupled two-way fluid–structure interaction (FSI) framework implemented via the Arbitrary Lagrangian–Eulerian (ALE) method. The combination of SAWs and hyper-elastic materials demonstrated a marked improvement in mixing efficiency, increasing from 0 to 0.99, alongside a significant reduction in pressure drop within the microchannel. The interaction between SAWs and the deformable walls induces localized instabilities and shear stresses that effectively disrupt the laminar flow, promoting enhanced mixing. The study highlights the critical role of hyper-elastic walls in modulating normal forces on the fluid and reducing pressure drop, offering insights into the interaction between fluid viscosity, acoustic pressure fields, and flow dynamics. These findings provide a framework for designing micromixers with optimized efficiency and reduced channel length, offering practical advancements in microfluidic systems.