Search Results (455)

Blood is a widely used sample for diagnosing diseases such as malaria and diabetes. While diagnostic techniques have advanced, sample preparation remains labor-intensive, requiring steps like mixing and centrifugation. Microfluidic technologies have automated parts of this process, including cell lysis, yet challenges persist. Electrical lysis offers a chemical-free, continuous approach, but lysing small cells like red blood cells requires high electric fields, which can damage electrodes and cause system failures. Here, we present a microfluidic device utilizing ion concentration polarization (ICP) for rapid blood cell lysis at 75 V. Fluorescence imaging confirmed the formation of an ion depletion region near the Nafion^® nanochannel membrane, where the electric field was concentrated across the entire microchannel width. This phenomenon enabled the efficient trapping and lysis of blood cells under these conditions. Continuous blood injection achieved a lysis time of 0.3 s with an efficiency exceeding 99.4%. Moreover, lysed cell contents accumulated near the Nafion membrane, forming a concentrated lysate. This approach eliminates the need for high-voltage circuits or chemical reagents, offering a simple yet effective method for blood cell lysis. The proposed device is expected to advance lab-on-a-chip and point-of-care diagnostics by enabling rapid and continuous sample processing. Full article

Microfluidics is a powerful tool with extensive applications, including chemical synthesis and biological detection. However, the limited channel size and high viscosity of samples/reagents make it difficult to fully mix liquids and improve the reaction efficiency inside microfluidic chips. Active mixing by rotors has been proven to be an effective method to promote mixing efficiency via a magnetic field. Here, we numerically investigated the mixing performance of rotors with different shapes (bar-shaped, Y-shaped, and cross-shaped). We systematically studied the influence of the arrangement of multiple cross-rotors and the rotation rate on mixing performance. The results are promising for instructing the design and manipulation of rotors for in-channel mixing. Full article

Due to the need for reproducible, scalable, and environmentally friendly nanomaterial synthesis methods, an increasing amount of scientific interest revolves around microfluidic technologies. In this context, the present paper proposes a new three-dimensional (3D) spiral microfluidic platform designed and tested for the simultaneous synthesis and surface functionalization of magnetite (Fe₃O₄) nanoparticles with salicylic acid (SA). The microreactor was fabricated from overlaid polymethylmethacrylate (PMMA) sheets and assembled into a compact, reusable chip architecture, allowing continuous reagent mixing and enhanced hydrodynamic control. The performed physicochemical analyses confirmed that on-chip synthesized Fe₃O₄@SA NPs exhibit crystallinity, a uniform spherical morphology, a narrow size distribution, excellent colloidal stability, and successful surface functionalization. In vitro cytotoxicity assays using MRC-5 lung fibroblasts and HaCaT keratinocytes revealed a concentration-dependent response, identifying a safe dose range below 610 µg/mL. The integrated design, efficient synthesis, and favorable biocompatibility profile position this 3D microfluidic platform as a promising tool for scalable nanomaterial production in biomedical and environmental applications. Full article

The possibility of tightly controlling the cellular microenvironment within microfluidic devices represents an important step toward precision analysis of cellular phenotypes in vitro. Microfluidic platforms that allow both long-term mammalian cell culture and dynamic modulation of the culture environment can support quantitative studies of cells’ responses to drugs. Here, we report the design and testing of a novel microfluidic device of simple production (single Polydimethylsiloxane layer), which integrates a micromixer with vacuum-assisted cell loading for long-term mammalian cell culture and dynamic mixing of four different culture media. Finite element modeling was used to predict flow rates and device dimensions to achieve diffusion-based fluid mixing. The device showed efficient mixing and dynamic exchange of media in the cell-trapping chambers, and viability of mammalian cells cultured for long-term in the device. This work represents the first attempt to integrate single-layer microfluidic mixing devices with vacuum-assisted cell-loading systems for mammalian cell culture and dynamic stimulation. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. 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

Microfluidic modulation spectroscopy-infrared (MMS) offers a label-free, high-sensitivity approach for quantifying changes in protein secondary structures under native solution conditions. MMS subtracts the solvent backgrounds from sample signals by alternately flowing proteins and matched buffers through a microfluidic chamber, yielding clear amide I spectra from microliter volumes. In this study, we validated MMS on canonical globular proteins, bovine serum albumin, mCherry, and lysozyme, demonstrating accurate detection and resolution of α-helix, β-sheet, and mixed-fold structures. Applying MMS to the intrinsically disordered protein Tau, we detected environment-driven shifts in transient conformers: both the acidic (pH 2.5) and alkaline (pH 10) conditions increased the turn/unordered structures and decreased the α-helix content relative to the neutral pH, highlighting the charge-mediated destabilization of the labile motifs. Hyperphosphorylation of Tau yielded a modest decrease in the α-helical fraction and an increase in the turn/unordered structures. Comparison of monomeric and aggregated hyperphosphorylated Tau revealed a dramatic gain in β-sheet and a loss in turn/unordered structures upon amyloid fibril formation, confirming MMS’s ability to distinguish disordered monomers from amyloids. These findings establish MMS as a robust platform for detecting protein secondary structures and monitoring aggregation pathways in both folded and disordered systems. The sensitive detection of structural transitions offers opportunities for probing misfolding mechanisms and advancing our understanding of aggregation-related diseases. Full article

This study presents the synthesis of chitosan nanoparticles (CSNPs) using a microfluidic device. Microfluidic rapid mixing enables fast nucleation for small-sized nuclei, but a high PDI value like 0.956 shows uncontrollable growth of small nuclei, resulting in the formation of larger and more variable aggregates at room temperature. High temperatures play a key role in controlling the growth of CSNPs to enhance uniformity. Temperatures of 40 °C and 50 °C promote controlled interactions among small nuclei, while increasing the temperature to 80 °C further accelerated the curing process, suitable for synthesizing CSNPs with various sizes. At 80 °C, size regulation can be achieved by changing the TPP concentration, which controls surface curing and affects the size as well. These results emphasize the impact of elevated temperature and precise TPP concentration for product quality control and modulation in CSNPs’ synthesis. Full article

Concentration gradient generation plays a pivotal role in advancing applications across drug screening, chemical synthesis, and biomolecular studies, yet conventional methods remain constrained by labor-intensive workflows, limited throughput, and inflexible gradient control. This study presents a novel multilayer microfluidic chip leveraging shear flow-driven partitioning–recombination mechanisms to enable the flexible and high-throughput generation of concentration gradient droplets. The chip integrates interactive upper and lower polydimethylsiloxane (PDMS) layers, where sequential fluid distribution and recombination are achieved through circular and radial channels while shear forces from the oil phase induce droplet formation. Numerical simulations validated the dynamic pressure-driven concentration gradient formation, demonstrating linear gradient profiles across multiple outlets under varied flow conditions. The experimental results revealed that the shear flow mode significantly enhances mixing uniformity and droplet generation efficiency compared to continuous flow operations, attributed to intensified interfacial interactions within contraction–expansion serpentine channels. By modulating hydrodynamic parameters such as aqueous- and oil-phase flow rates, this system achieved tunable gradient slopes and droplet sizes, underscoring the intrinsic relationship between flow dynamics and gradient formation. The proposed device eliminates reliance on complex channel networks, offering a compact and scalable platform for parallelized gradient generation. This work provides a robust framework for optimizing microfluidic-based concentration gradient systems, with broad implications for high-throughput screening, combinatorial chemistry, and precision biomolecular assays. Full article

Microfluidics-based mixing methods have attracted increasing attention due to their great potential in bio-related and material science fields. The combination of acoustics and microfluidics, called acoustofluidics, has been shown to be a promising tool for precise manipulation of microfluids and micro-objects. In general, achieving robust mixing performance in an efficient and simple manner is crucial for microfluidics-based on-chip devices. When surface acoustic waves (SAWs) are introduced into microfluidic devices, the acoustic field can drive highly controllable acoustic streaming flows through acoustofluidic interactions with micro-solid structures, which have the advantages of label-free operation, flexible control, contactless force, fast-response kinetics, and good biocompatibility. Therefore, the design and application of various SAW micromixers have been demonstrated. Herein, we present a comprehensive overview of the latest research and development of SAW-based micromixers. Specifically, we discuss the design principles and underlying physics of SAW-based acoustic micromixing, summarize the distinct types of existing SAW micromixers, and highlight established applications of SAW micromixing technology in chemical synthesis, nanoparticle fabrication, cell culture, biochemical analysis, and cell lysis. Finally, we present current challenges and some perspectives to motivate further research in this area. The purpose of this work is to provide an in-depth understanding of SAW micromixers and inspire readers who are interested in making some innovations in this research field. Full article

The controllable transport of droplets on solid surfaces is crucial for many applications, from water harvesting to bio-analysis. Herein, we propose a novel droplet transport controlling method, reconfigurable orbital electrowetting (ROEW) on inclined slippery liquid-infused porous surfaces (SLIPS), which enables controllable transport and dynamic handling of droplets by non-contact reconfiguration of orbital electrodes. The flexible reconfigurability is attributed to the non-contact wettability modulation and reversibly deformable flexible electrodes. ROEW graphically customizes stable wettability pathways by real-time and non-contact printing of charge-orbit patterns on SLIPS to support the continuous transport of droplets. Benefiting from the fast erase-writability of charges and the movability of non-contact electrodes, ROEW enables reconfiguration of the wetting pathways by designing electrode shapes and dynamically switching electrode configurations, achieving controllable transport of various pathways and dynamic handling of droplet sorting and mixing. ROEW provides a new approach for reconfigurable, electrode-free arrays and reusable microfluidics. Full article

Micromixing is a crucial process in microfluidic systems. In biochemical and chemical analysis, the sample is usually tested with reagents. These solutions must be well mixed for the reaction to be possible, generally using micromixers manufactured with sophisticated and expensive technology. The present work shows the design and evaluation of micromixers fabricated with LTCC (low-temperature co-fired ceramics) and FDM (fused deposition modeling) technologies for the development of functional and complex geometries. Two-dimensional planar serpentine and 3D chaotic convection serpentine micromixers were manufactured and implemented in an automated microanalytical system using photometric methods. To evaluate the performance of the micromixers, flow, mixing and absorbance measurements were carried out. Green tape and PP materials were used and showed good resistance to the acidic chemical solutions. The devices presented achieved mixing times in seconds, a reduced dispersion due to their aspect ratio, high sensitivity, and precision in photometric measurement. The optical sensing cells stored sample volumes in a range of 10 to 600 µL, which allowed the reduction of reagent consumption and waste generation. These are ideal characteristics for in situ measurement, portable, and low-cost applications focused on green chemistry and biochemistry. Full article

The Polydimethylsiloxane (PDMS) SlipChip is a microfluidic platform enabling fluid manipulation without pumps or valves, simplifying operation and reducing reagent use. High-viscosity silicone oils (e.g., 5000–10,000 cSt) improve sealing but frequently block microfluidic channels, reducing usability. In contrast, low-viscosity oils (50–100 cSt) reduce blockages but may compromise sealing. This study addresses these challenges by optimizing the viscosity of silicone oil and the curing conditions of PDMS. Low-viscosity silicone oil (50 cSt) was identified as optimal, ensuring smooth slipping and reliable sealing without blockages. Curing conditions were also adjusted to balance adhesion and stiffness as follows: lower temperatures (50–60 °C) enhanced van der Waals adhesion, while higher temperatures (80 °C) increased stiffness. A mixed curing approach (80 °C for the top layer and 60 °C for the bottom layer) further improved performance. Biocompatibility testing using human osteosarcoma cells demonstrated minimal cytotoxicity with 50 cSt oil, supporting cell viability (95%) comparable to traditional multiwell plates. These findings provide practical guidelines for fabricating reliable and biocompatible SlipChips. Full article

A spiral microfluidic chip (SMC) and multi-spiral microfluidic chip (MSMC) for lipid nanoparticle (LNP) production were fabricated using a CO₂ laser engraving method, using perfluoropolyether (PFPE) and poly(ethylene glycol) diacrylate as photopolymerizable base materials. The SMC includes a spiral microchannel that enables rapid fluid mixing, thereby facilitating the production of small and uniform LNPs with a size of 72.82 ± 24.14 nm and a PDI of 0.111 ± 0.011. The MSMC integrates multiple parallel SMC structures, which enables high-throughput LNP production without compromising quality and achieves a maximum production capacity of 960 mL per hour. The LNP fabrication technology using SMC and MSMC has potential applications in the pharmaceutical field due to the ease of chip fabrication, the simplicity and cost-effectiveness of the process, and the ability to produce high-quality LNPs. 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