Search Results (106)

Enzyme immobilisation within Metal–organic Frameworks (MOFs) provides a promising strategy for improving enzyme dispersion and local environment control, although the resulting performance depends strongly on the host materials, enzyme type and immobilisation conditions. Conventional in situ biomimetic mineralisation typically produces enzyme–MOF composites (enzyme@MOFs) with irregular morphologies, broad particle size distributions and aggregation, which can compromise catalytic performance and reproducibility. This study presents a flow-based microfluidic biomimetic mineralisation strategy for preparing horseradish peroxidase-encapsulated ZnBDC-NH₂ MOF composites. A flow-focusing microfluidic chip containing multiple rectangular baffle structures was designed to enhance transverse mixing, extend the effective residence time, and mitigate clogging during particle formation. Under the selected conditions, homogeneous HRP@ZnBDC-NH₂ particles with an average hydrodynamic diameter of 868.5 nm and a polydispersity index of 0.266 were obtained. The homogeneous HRP@ZnBDC-NH₂ showed an encapsulation efficiency of 56.17% and a loading content of 1.49%. Michaelis–Menten analysis gave a Km value of 52.49 μM for HRP@ZnBDC-NH₂, suggesting improved apparent substrate affinity compared with the corresponding bulk-synthesised sample. The results support the use of baffle-structured microfluidics as a controllable platform for enzyme@MOF synthesis, while further studies on enzyme leaching, reusability, long-term stability and extended chip operation are required to evaluate its operational robustness. Full article

This study applies the Constructal Design method to the geometric optimization of a branched symmetric concentration divider for calibrating ultrasound devices used to monitor tumor response with dynamic contrast. Accurate calibration ensures image quality and diagnostic reliability. The geometry consists of a three-dimensional, tree-shaped flow network with two inlets and three outlets, where inlet 1 carries water containing contrast particles, while inlet 2 carries only water. Laminar flow simulations are performed using Computational Fluid Dynamics (CFD) with Ansys Fluent, assuming no-slip wall conditions and zero-pressure outlets. The analysis investigates the effects of the inlet velocity ratio, the diameter ratio, and the vertical positions of the central outlet and inlet tubes, while keeping the total volume and inlet diameter constant. Additionally, velocity, pressure, particle distributions, flow partition ratio, and hydraulic resistance are evaluated. Results show nearly linear concentration responses among the outlets (100%, 50%, and 0%) when the device approaches geometric symmetry with equal inlet velocities, demonstrating efficient control of flow splitting. Although the diameter ratio imposes a trade-off with hydraulic resistance, geometric symmetry combined with Constructal Design promotes improved flow uniformity and enhanced performance, with potential applications in microfluidic mixers that require precise intermediate concentrations. Full article

Post-processing remains a major bottleneck in the fabrication of microfluidic devices using Digital Light Processing Stereolithography (DLP-SLA) 3D printing, where unpolymerized resin trapped within internal structures must be removed without damaging delicate features such as thin membranes, valves, and pumps. Manual flushing is slow, inconsistent, and prone to structural failure, especially as device complexity and port counts increase. Here, we present the first fully automated flushing system for DLP-SLA microfluidic devices, enabled by a standardized chip-to-chip (C2C) interconnect architecture and an electronically controlled pneumatic routing platform. A reusable 32-port flushing interface chip provides alignment, sealing, and modular coupling to arbitrary device chips through integrated microgaskets, while a network of electronic pressure controllers, differential pressure sensors, and multi-port rotary valves enable precise, programmable application of pressure, vacuum, and solvent conditions. We introduce a fluidic-circuit model of the system that relates applied pressure to the pressure drop across device structures and experimentally validate this model using channels with varying fluidic resistances. Using this platform, we demonstrate robust flushing of both passive (straight and serpentine channels) and active (valves, pumps) microfluidic elements, as well as application-specific devices including mixers and concentration-gradient generators. Our system eliminates manual handling, improves valve membrane survival, and provides repeatable flushing across a broad range of device geometries. This work establishes a scalable foundation for automated post-processing in 3D-printed microfluidics and significantly advances the practicality of DLP-SLA fabrication for complex, multi-layered microfluidic devices. Full article

Today, microfluidics has become a revolutionary field of engineering due to its wide range of applications, including lab-on-a-chip devices, microscale biochemical reactors, drug delivery systems, and disease diagnostics. Efficient fluid mixing has been a significant challenge in these systems due to the dominance of laminar flow and low-Reynolds number conditions, where mixing relies primarily on slow molecular diffusion. It is very difficult to achieve rapid mixing and homogeneous mixing within a limited length. In this study, a bioinspired passive micromixer is developed based on the cristae architecture of mitochondria, which is known for maximizing surface area and transport efficiency in biological systems. The micromixer incorporates cristae-like microstructures within a straight microchannel to produce continuous flow deflection, stretching, and folding, thereby promoting chaotic advection without relying on external energy sources. It also includes mitochondrial granules, such as micropillars, within the channel to disrupt streamline flow. Thus, a numerical investigation was conducted to design four different micromixer geometries: conventional T-channel, and T-channels with a single, double and triple matrix of cristae. The analysis was performed in COMSOL Multiphysics, in which “Laminar flow” and “Transport of diluted species” physics were used, and a stationary study was executed. Simulations were conducted at different Reynolds numbers (Re = 0.1–100) to observe the feasibility of the proposed designs. For analysis, the mixing index and concentration profiles at the outlet and along the length were also examined. The results showed that the high cristae density channel performed well, achieving a mixing index of 95.85% at Re = 0.1 and 85.84% at Re = 100, proving that the proposed mitochondria-inspired cristae Mito-mixer delivers efficient mixing over a broad Reynolds-number range while maintaining a compact, length-efficient design. Full article

Lipid nanoparticles (LNPs) have emerged as a groundbreaking delivery platform, revolutionizing the development of nucleic acid-based medicines for gene delivery and gene therapy. This review provides an insightful industrial perspective on the production process of LNPs, focusing on cutting-edge manufacturing equipment, downstream processing and the crucial transition from laboratory to large scale. While LNP production in the discovery phase relies on a small scale (µL to mL) for screening various LNP formulation candidates, transferring to preclinical (up to hundreds of mL) and clinical/commercial scales (up to liters) requires a robust and reproducible manufacturing process. Thus, mixing technologies throughout these scales must be carefully selected and require precision, scalability and high reproducibility to meet the target quality of the LNP drug product. Key mixing technologies in mRNA-LNP production primarily include microfluidic systems and impinging jet mixers (IJMs). In this review, we discuss key critical process parameters (CPPs) in LNP preparation, including flow rate ratio (FRR) or total flow rate (TFR), in relation to associated critical quality attributes (CQAs) across multiple manufacturing scales. We further assess the impact of downstream processing, specifically tangential flow filtration (TFF), on the formulation’s CQAs. In particular, the review highlights the importance of maintaining CQAs along each step of the process and emphasizes the role of robust analytical methods in ensuring product quality and safety. Additionally, we touch on current challenges associated with these advanced delivery vehicles, such as their long-term stability, and introduce the readership to innovative stabilization strategies aimed to extent LNP shelf-life. Full article

Lipid-based delivery systems (LDS), including lipid nanoparticles (LNPs) and liposomes, have become indispensable tools in modern biomedicine owing to their biocompatibility, capacity to encapsulate diverse therapeutic agents, and potential for targeted delivery. Despite their clinical success, conventional batch-based manufacturing methods are hindered by variability, limited scalability, and complex processing steps, slowing their broader translation. Microfluidic technologies offer a transformative solution by enabling precise fluid handling, rapid mixing, and reproducible production of LDS with tunable physicochemical attributes such as particle size, lamellarity, and drug-loading efficiency. This review highlights advances in microfluidic design strategies, including hydrodynamic flow focusing, staggered herringbone mixers, and toroidal micromixers, and evaluates how critical parameters such as flow rate, solvent composition, and lipid concentration influence LDS performance. Furthermore, we discuss the application of microfluidics in drug delivery, nucleic acid therapeutics, and vaccine platforms, underscoring its role in improving scalability, quality control, and clinical translation. Finally, we examine current challenges, including throughput limitations and solvent handling, while outlining future directions for integrating emerging materials and additive manufacturing to optimize LDS fabrication. Collectively, microfluidic platforms provide a promising pathway for next-generation lipid nanomedicines with enhanced precision, reproducibility, and therapeutic efficacy. Full article

Acoustofluidics has emerged as a transformative technology for contact-free manipulation of microparticles and fluids in microscale systems. Although bulk acoustic waves (BAWs) are known to displace inhomogeneous fluids through acoustic radiation force acting at fluid interfaces, the capability of surface acoustic waves (SAWs) to produce analogous relocation phenomena remains largely unexplored. This study addresses a critical gap in acoustofluidic theory by presenting the first comprehensive finite element method investigation of SAW-driven motion of inhomogeneous fluid confined within microchannels of widths equal to one full or one-half SAW wavelength. Unlike BAW-based system that generate uniform pressure fields across channel heights, SAW devices exhibit inherently nonuniform vertical pressure distributions and intense near-boundary streaming—features that fundamentally alter fluid relocation dynamics. Our simulations demonstrate that despite high-frequency operation (6.65 MHz) and strong ARF, standing SAW fields fail to achieve stable fluid relocation in both initially stable and unstable configurations due to vertical pressure stratification and rapid floor-level streaming. Nevertheless, these same characteristics generate vigorous transverse folding flows that enable exceptionally rapid homogenization, offering a distinct acoustofluidic mechanism for on-chip mixing. These findings not only elucidate fundamental physical differences between BAW and SAW actuation in multiphase microfluidic systems but also establish design principles for SAW-induced microfluidic mixers. The results provide crucial theoretical guidance for device optimization where rapid homogenization is desired over stable stratification. Full article

3D printing offers great potential for rapid and cost-effective fabrication of microfluidic lab-on-a-chip systems. Through a comparative approach, we implemented staggered herringbone mixer (SHM), Tesla mixer, and split and recombine mixer (SAR), along with a basic unperturbed channel into one chip and performed comparative mixing efficiency experiments. We also introduced a phaseguide-based, T-shaped stop structure at the Y-shaped inlets for bubble-free and parallel filling. The structures were analyzed with two poorly mixable dye solutions at flow rates ranging from 1 µL/min to 200 µL/min. The mixing efficiency was evaluated using optical gray value analysis and compared against diffusion-based mixing. The fluid-aligning phaseguides in the 3D-printed system were shown to work. Among the three different mixing structures tested, SHM exhibited the best mixing efficiency at all tested flow rates. Uniformly designed SHM structures contain a region of poor mixing between the two zones of turbulence. In a non-uniform design, fluid breakers were placed between two SHM units to redirect poorly mixed fluids to the edges, resulting in 100% mixing efficiency across all measured flow rates. These results, especially SHM with fluid breakers, support the development of cost-effective injection-molded lab-on-a-chip systems with improved mixing functionalities at close range instead of simple long-length meandric systems. Full article

Micromixers are crucial for rapid and homogeneous mixing in lab-on-a-chip systems. This study presents a novel passive micromixer that synergistically combines a Zigzag channel with D-shaped obstacles to enhance mixing across a broad Reynolds number (Re) range of 0.1–50. The design leverages flow splitting, recombination, and the generation of localized high-velocity streams to effectively disrupt laminar flow. A comprehensive parametric study optimized key geometric parameters, including obstacle dimensions (b₂, a₂) and the number of mixing units (n). Results show that optimizing b₂ to 500 μm and increasing a₂ to 250 μm significantly enhances mixing efficiency. Mechanistic analysis reveals that centrifugal forces in the Zigzag channel work synergistically with obstacle-induced perturbations to stretch and fold the fluid interface, promoting transverse transport. The optimized mixer, fabricated and experimentally validated, achieves a high mixing index (>0.85) under all Re conditions. This work provides valuable design insights for developing efficient, compact micromixers for micro-total analysis systems. Full article

Microfluidics enables precise manipulation of scarce Traditional Chinese Medicine (TCM) samples while accelerating analysis and enhancing sensitivity. Device-level structures explain these gains: staggered herringbone and serpentine mixers overcome low-Reynolds-number constraints to shorten diffusion distances and reduce incubation time; flow-focusing or T-junction droplet generators create one-droplet–one-reaction compartments that suppress cross-talk and support high-throughput screening; “Christmas-tree” gradient generators deliver quantitative dosing landscapes for mechanism-aware assays; micropillar/weir arrays and nanostructured capture surfaces raise surface-to-volume ratios and probe density, improving capture efficiency and limits of detection; porous-membrane, perfused organ-on-a-chip architectures recreate apical–basolateral transport and physiological shear, enabling metabolism-aware pharmacology and predictive toxicology; wax-patterned paper microfluidics (µPADs) use capillary networks for instrument-free metering in field settings; and lab-on-a-disc radial channels/valves exploit centrifugal pumping for parallelised workflows. Framed by key performance indicators—sensitivity (LOD/LOQ), reliability/reproducibility, time-to-result, throughput, sample volume, and sustainability/cost—this review synthesises how such structures translate into value across TCM quality/safety control, toxicology, pharmacology, screening, and delivery. Emphasis on structure–function relationships clarifies where microfluidics most effectively closes gaps between chemical fingerprints and biological potency and indicates practical routes for standardisation and deployment. Full article

Polymeric nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) are widely used in drug delivery, yet scalable and reproducible production methods remain a major challenge. In this study, we combine experimental nanoprecipitation and computational fluid dynamics (CFD) modeling to optimize PLGA nanoparticle formulation using both traditional batch and microfluidic methods. While Design of Experiments (DoE) was used to optimize the batch process, microfluidic mixing was systematically explored by varying flow parameters such as the flow rate ratio (FRR) and total flow rate (TFR). We compared two microfluidic mixer designs with Y-junction and three-inlet junction geometries to evaluate their impact on the mixing efficiency and nanoparticle formation. Experimental results revealed that the three-inlet design produced smaller, more uniform nanoparticles with superior post-lyophilization stability. CFD simulations confirmed these findings by displaying velocity fields and PLGA concentration gradients, demonstrating significantly more homogeneous mixing and efficient interfacial contact in the three-inlet configuration. Furthermore, simulated outlet concentrations were used to predict the nanoparticle size via theoretical modeling, which closely agreed with the experimental data. This integrated approach highlights the importance of microfluidic geometry in controlling nanoparticle nucleation dynamics and provides a framework for rational design of scalable nanomedicine production systems. Full article

Rapid mixing is widely prevalent in the field of microfluidics, encompassing applications such as biomedical diagnostics, drug delivery, chemical synthesis, and enzyme reactions. Mixing efficiency profoundly impacts the overall performance of these devices. However, at the micro-scale, the flow typically presents as laminar flow due to low Reynolds numbers, rendering rapid mixing challenging. Leveraging the vortices within a droplet of the Taylor flow and inducing chaotic convection within the droplet through serpentine channels can significantly enhance mixing efficiency. Based on this premise, we have developed a droplet micromixer that integrates the T-shaped channels required for generating Taylor flow and the serpentine channels required for inducing chaotic convection within the droplet. We determined the range of inlet liquid flow rate and gas pressure required to generate Taylor flow and conducted experimental investigations to examine the influence of the inlet conditions on droplet length, total flow rate, and mixing efficiency. Under conditions where channel dimensions and liquid flow rates are identical, Taylor flow achieves a nine-fold improvement in mixing efficiency compared to single-phase flow. At low Reynolds number (0.57 ≤ Re ≤ 1.05), the chip can achieve a 95% mixing efficiency within a 2 cm distance in just 0.5–0.8 s. The mixer proposed in this study offers the advantages of simplicity in manufacturing and ease of integration. It can be readily integrated into Lab-on-a-Chip devices to perform critical functions, including microfluidic switches, formation of nanocomposites, synthesis of oxides and adducts, velocity measurement, and supercritical fluid fractionation. Full article

Background/Objectives: Microfluidic mixing has become the gold standard procedure for manufacturing nucleic acid lipid-based delivery systems, offering precise control over critical process parameters. The choice and design of microfluidic mixers are often seen as a key driving force affecting the critical quality attributes of the resulting lipid nanoparticles (LNPs). Methods: This study aimed to evaluate LNPs manufactured using two low-cost microfluidic mixers alongside manual mixing (pipette mixing (PM)), followed by characterization studies using orthogonal analytics as well as expression studies to establish whether low-cost microfluidic manufacturing methods are suitable for bench-scale and high-throughput research. Results: The results show that all manufacturing methods can produce LNPs with sizes ranging between 95 and 215 nm with high encapsulation (70–100%), and enhanced analytics showed variations between the LNPs produced using the different mixers. Despite these differences, pipette mixing production of LNPs demonstrated its application as a high-throughput screening tool for LNPs, effectively distinguishing between different formulations and predicting consistent expression patterns both in vitro and in vivo. Conclusions: Overall, these results validate the use of low-cost microfluidic mixers without compromising the efficiency and integrity of the resulting LNPs. This study supports the increased accessibility of small-scale LNP manufacturing and high-throughput screening. Full article

Proteins can act as suitable biomarkers for the prognosis and diagnosis of certain conditions and can help us gain an understanding of the fundamental processes that occur inside an organism. In this work, we present a fully automated machine learning-assisted label-free method for the electrical detection of proteins in an integrated microfluidic chip using multi-frequency impedance cytometry and off-the-shelf components for realizing an automated and programmable fluid control system. We verify the robustness of our mixing method on our custom microfluidic mixer composed of polydimethylsiloxane (PDMS) serpentine channels optically using a fluorescent sandwich immunoassay and comparing the results with a commercial benchtop mixer. Salivary IL-6 is a biomarker for oral squamous cell carcinoma (OSCC), and we have demonstrated that our system can be used for the detection of quantification of Interleukin-6 (IL-6) levels in a solution using the impedance response of beads conjugated with the protein of interest, which passes through the microfluidic chip with reasonable accuracy (96%). Although we have demonstrated the detection and quantification of IL-6, our system can be adapted to any protein of interest with slight modification in the reagents and bead-binding protocols. Full article

Background/Objectives: In the quest for sustainable and biocompatible materials, silk fibroin (SF), derived from natural silk, has emerged as a promising candidate for nanoparticle production. This study aimed to fabricate silk fibroin particles (SFPs) using a novel swirl mixer previously presented by our group, evaluating their characteristics and suitability for drug delivery applications, including magnetic nanoparticles and dual-drug encapsulation with curcumin (CUR) and 5-fluorouracil (5-FU). Methods: SFPs were fabricated via microfluidics-assisted desolvation using a swirl mixer, ensuring precise mixing kinetics. Comprehensive physicochemical characterisation, including size, polydispersity index (PDI), zeta potential, and secondary structure analysis, was conducted. Further, CUR/5-FU-loaded magnetic core SFPs were assessed for cytotoxicity in vitro using breast cancer cell lines and for biodistribution and targeting efficiency in a murine breast cancer model. Results: The swirl mixer produced SFPs with sizes below 200 nm and uniform distributions (PDI < 0.20) with size stability for up to 30 days. Encapsulation efficiencies were 37% for CUR and 82% for 5-FU, with sustained drug release profiles showing 50% of CUR and 70% of 5-FU released over 72 h. In vitro studies demonstrated sustained cytotoxic effects, and cell cycle arrest at the G2/M phase in breast cancer cell lines, with minimal toxicity in non-cancerous cells. Cellular uptake assays confirmed efficient drug delivery to the cytoplasm. In vivo biodistribution studies revealed increased tumour-specific drug accumulation with magnetic guidance. Haematoxylin & Eosin (H&E) staining indicated enhanced tumour necrosis in treated groups compared to controls. Conclusions: This study underscores the utility of the swirl mixer for efficient and scalable fabrication of bio-inspired SFPs, supporting their application in targeted cancer drug delivery. These findings align with and advance previous insights into the use of microfluidics and desolvation methods, paving the way for improved therapeutic strategies in breast cancer treatment. Full article