Search Results (466)

Microfluidic paper-based analytical devices (µPADs) are promising for point-of-care testing, yet most operate in an open-format that is susceptible to solvent evaporation and reagent contamination, causing poor signal stability under changing environments. Here, we present an equipment-free sealing strategy to construct closed µPADs by electrostatically adsorbing two polymer films onto open chips, forming an enclosed microenvironment. Using the Griess colorimetric reaction for nitrite, we benchmarked the closed-format against an open counterpart. At a standard condition, the closed µPAD produced a higher grayscale signal, reached a stable peak within 10 min, and remained stable for >60 min. It also demonstrated superior environmental robustness, yielding consistently smaller relative standard deviations (RSDs) across varying humidity levels and temperatures. With the optimized readout time, nitrite exhibited linear calibration over 2.0–10 mg/L (R² = 0.998), with a detection limit of 0.75 mg/L. In synthetic urine A, spike–recovery tests at 2.0, 5.0, and 9.0 mg/L gave acceptable recoveries and precision across temperature–humidity conditions (RSD < 10%). Additional verification in synthetic urine B at 5.0 mg/L under an uncontrolled environment further confirmed the practicality of this sealed µPAD for environment-tolerant quantitative nitrite analysis. Full article

DNA extraction is a critical prerequisite for reliable downstream analyses such as Polymerase Chain Reaction (PCR), sequencing, and genotyping. Conventional methods often require labor-intensive protocols, large sample volumes, or costly automation. Microfluidic approaches offer an alternative by reducing reagent consumption and enabling faster, more integrated workflows. Here, we present a passive lab-on-a-chip device that performs DNA extraction from complex biological media and enables subsequent on-chip single-molecule analysis. The chip integrates a magnetophoresis-based solid-phase extraction module with a fluorescence detection section capable of quantifying DNA molecules in microchannels and visualizing stretched molecules in nanochannels. The multi-level micro/nanofluidic architecture is fabricated in polymer using a single-step nanoimprinting process with a total manufacturing time of two minutes per chip, enabling scalable production. As a proof of concept, the device extracted DNA from samples spiked into buffer or plasma. On-chip transfer efficiency of DNA–bead complexes to the elution buffer reached 86%, and quantitative analysis of the recovered liquid showed an overall extraction efficiency of 40% (including DNA recovery off-chip), with intact 48 kbp DNA confirmed in both micro- and nanochannel measurements. This platform offers a promising foundation for point-of-care and point-of-interest applications, where integrated DNA extraction and analysis can reduce sample loss and support streamlined, automated workflows. Full article

RNA-based therapeutics are becoming increasingly important in oncology, particularly following the rapid development of mRNA technologies during the COVID-19 pandemic, but their success strongly depends on how efficiently they can be delivered to target cells. Microfluidic technologies have redefined the design and manufacturing of RNA-based nanocomplexes, as they enable precise control over physicochemical features that are critical for clinical translation in oncology. This review examines recent developments in microfluidic-assisted synthesis of RNA nanocarriers, with a focus on cancer applications. Through a detailed analysis of material systems, device architectures, and formulation strategies, we explore how laminar flow environments enable reproducible encapsulation, tunable particle size, and improved payload stability. We examine the microfluidic assembly of lipid nanoparticles and polymeric carriers for RNA delivery, highlighting strategies to enhance durability, bioavailability, and cellular uptake. Advancements in process optimization, including flow parameter refinement and inline monitoring, are discussed alongside the influence of device geometries on mixing dynamics and nucleation. Beyond formulation, we explore the integration of microfluidics with tumor-on-chip platforms to evaluate transport, penetration, and therapeutic response in physiologically relevant cancer models. By connecting technological innovation with preclinical application, this work outlines the trajectory toward next-generation, personalized RNA nanomedicines enabled by microfluidic precision. Full article

Poor vascularization is one of the basic obstacles to the regeneration of functioning tissues because an oxygen diffusion process and elimination of wastes are essential in preserving the grafts. Recently, biomaterials have allowed the invention of bioinspired polymer scaffolds and replicated the natural extracellular matrix (ECM) due to the mechanical tunability of the synthetic polymers with the biological signals of natural macromolecules. The review uses a mechanistic analysis of the strategies to improve angiogenesis by using surface topography modification, bioactive peptide incorporation and pre-vascularization. Another way to achieve complex, perfusable topologies is by using more sophisticated methods of fabrication, such as electrospinning, 3D/4D bioprinting, or microfluidics. Based on in vitro and in vivo results, we determine angiogenic effectiveness by using cellular assays and animal transfers, pointing towards the translational advances in patents and clinical uses of bone, cardiac, nervous, and skin tissues. In spite of the substantial improvements, large-scale production and high demands of the regulations still exist. The future directions include the incorporation of bioinspired designs and intelligent materials, nanotechnology, and AI-based optimization into developing patient-specific and adaptive scaffolds. The following innovations herald the advent of highly effective constructs that can be used to regenerate tissue and overcome the limitations of present tissue engineering therapies through the introduction of highly effective, vascularized constructs. Full article

The low signal-to-noise ratio (SNR) of existing magnetic sensors limits the detection of magnetic nanoparticles (MNPs) in microfluidic biosensing. We present a novel microfluidic coil-based impedance detection system for quantifying magnetic particles, including Fe filings and citrate-coated Fe₃O₄ MNPs, with potential applications in magnetically guided biosensing. Unlike conventional approaches that directly measure the magnetic properties of dispersed particles, our method employs an external collector magnet to concentrate particles within a copper coil detector. The accumulated particles alter the coil’s electromagnetic response through changes in the sample’s dielectric properties, producing an amplified impedance signal proportional to sample volume. We evaluated detection performance for 1–10 mg of ferromagnetic Fe filings and citrate-coated Fe₃O₄ MNPs across a broad frequency range. Results show a strong linear correlation between particle mass and impedance change, with SNR values from 25 dB to over 45 dB, demonstrating high sensitivity and precision. Coil sensitivity was further optimized by varying the number of turns (5, 10, and 15), enabling frequency-specific customization. This approach provides a scalable, low-cost platform adaptable to polymer-coated MNPs targeting biological analytes. Full article

Biomarker detection demands low cost, rapid turnaround, interference resistance, and wide dynamic range. However, traditional immunoassays and nucleic acid amplification methods remain constrained by complex matrices, batch stability, and portability limitations. Molecularly imprinted polymers (MIPs) exhibit “artificial antibody”-like specific recognition and high stability, while nanomaterials (NMs), depending on their composition, structure, and interfacial organization, can provide conductive pathways, catalytic activity, high-density loading sites, or mass-transfer-favorable architectures. Electrochemical biosensors synergistically constructed from these two components achieve complementary functions in recognition, mass transfer, and signal transduction. This paper systematically reviews key strategies and mechanisms for NM–MIP synergistic construction, focusing on six synergistic strategies that target key bottlenecks in mass transfer, signal generation, and interfacial stability: dynamic response regulation, hierarchical structural engineering, anti-fouling interfaces, multi-signal cross-validation, catalytic–recognition integration, and interfacial binding regulation. Representative biomarker cases are analyzed to illustrate how functional modules can coordinate across sample processing, signal generation, and recognition confirmation to improve analytical reliability and overall sensing performance. Finally, the review discusses challenges in clinical translation, including consistent manufacturing, matrix interference, long-term stability, and standardized validation, while outlining future directions toward mechanism-guided imprint design, intelligent data-assisted optimization, and integration with microfluidic and wearable platforms for multiplexed biomarker detection. Full article

Resin 3D-printed molds are being increasingly favored for PDMS microfluidics across many disciplines. However, resin diversity, as well as secret manufacturer formulations, leads to a lack of standardization when using 3D printing for microscale applications. The impact of physical resin properties, both in its monomeric concoction and polymerized lattices at 100 µm or lower scales, needs quantification. We tested the performance of locally available resin formulations, isolating the impact of resin pigments and how it impacted the resin’s properties and performance. Lower resin viscosity improved feature fidelity (edge filleting < 25 µm) and improved resolution limit for recessed features, while cured polymer mechanical strength impacted the limit for positive mold features. We combined our findings to fabricate quality negative and positive mold structures in the mold and determined the best protocols associated with limitations during the fabrication of such structures. The methodologies in this study are expected to be widely applicable across various resin types and simplify the adoption of 3D printing protocols for specific feature fabrication in microscale molds for PDMS devices. Full article

As the most abundant natural polymer on Earth, cellulose offers distinct advantages including renewability, biocompatibility, and modifiability. Among its various morphologies, spherical cellulose hydrogels (SCHs) represent a particularly versatile form ranging from micrometer to millimeter scales. They possess a unique hydrophilic 3D network, excellent flowability, high specific surface area, and outstanding mechanical stability, demonstrating great potential for biomedical applications. This mini-review highlights the primary bottom-up fabrication strategies for SCHs, including dripping, spraying, emulsion, and microfluidics, and the mechanisms by which different fabrication processes regulate their size, morphology, and structure are elucidated. On this basis, the recent advancements in SCHs across key biomedical domains, specifically in chromatographic separation, controlled drug delivery, tissue engineering, and wound healing, are discussed. Finally, the current challenges and future directions in this field are summarized and predicted, aiming to provide a reference for the development and application of high-performance cellulose-based biomaterials. Full article

Collagen, the most abundant extracellular matrix (ECM) protein, has emerged as a cornerstone biomaterial in drug delivery and regenerative medicine due to its intrinsic biocompatibility, biodegradability, and low immunogenicity. Engineering collagen into microspheres transforms its functionality beyond bulk scaffolds by increasing surface area, enabling minimally invasive delivery, and providing precise control over degradation, mechanical properties, and therapeutic release. This review provides a comprehensive analysis of collagen-based microspheres, with a particular focus on their dual role as biomimetic microenvironments and delivery systems. Recent advances in fabrication strategies, including emulsification, microfluidics, spray-drying, and electrospraying, are discussed in the context of scalability, size control, and payload encapsulation. Composite approaches that incorporate bioactive minerals, polysaccharides, or synthetic polymers are highlighted for their ability to enhance mechanical performance and biological function. We further examine characterization frameworks that link microscale structure and physicochemical properties to biological outcomes, with emphasis on how collagen microspheres replicate key structural, mechanical, and signaling features of native tissue microenvironments. Collagen microspheres have demonstrated broad utility as controlled delivery platforms, cell-instructive microcarriers, and injectable systems for tissue regeneration, including applications in bone, cartilage, skin, and nerve repair, as well as advanced wound care and localized cancer therapy. Finally, we critically assess current challenges related to scalable manufacturing, sterilization compatibility, and batch reproducibility, and outline emerging solutions such as recombinant collagen, advanced biofabrication, and stimuli-responsive systems. Collectively, collagen microspheres represent a powerful and adaptable platform poised to advance next-generation regenerative and therapeutic technologies. Full article

Polymerase chain reaction (PCR) is widely regarded as the gold standard for nucleic acid analysis; however, conventional thermal cycling limits its applicability in rapid and compact analytical systems. Here, we report an oscillating-flow microfluidic PCR method that enables rapid and flexible amplification by repeatedly shuttling the reaction mixture between two fixed-temperature zones. Unlike continuous-flow PCR, the proposed approach decouples PCR cycle number from microchannel geometry, allowing programmable cycling while reducing chip footprint. To enhance analytical reliability, polymer-assisted surface passivation using polyvinylpyrrolidone was employed to suppress nonspecific adsorption in polydimethylsiloxane (PDMS) microchannels, significantly improving amplification efficiency. Using Porphyromonas gingivalis and Treponema denticola as representative periodontal pathogens, 35-cycle amplification was completed within 20 min with reliable product yield. The proposed method advances oscillating-flow PCR toward a robust analytical strategy for rapid pathogen detection and related microfluidic nucleic acid analysis. Full article

This review deals with the development and progress of micro-electromechanical systems (MEMS) actuators, which are needed in microfluidic applications, such as lab-on-a-chip and diagnostics. In the last 10 years, there have been tremendous advances in materials, microfabrication and computational modeling that have increased the functionality and scope of MEMS-based microfluidic actuation. This study classifies MEMS actuators on the basis of the physical method of actuation, including electrostatic, piezoelectric, and pneumatic actuation designs, in comparison with their application in pumping, valving, and droplet control. It examines the suitability of emerging structural and functional materials, such as piezoelectric thin-films and electroactive polymers, paying special attention to their reliability and biocompatibility. It also highlights the progress in multiphysics modeling that incorporates electrical, thermal, mechanical, and fluidic models, which facilitates the efficient design and performance optimization procedures. Other trends are multifunctional actuators with built-in sensing capability and the use of artificial intelligence (AI)-assisted design in production. With these developments, however, there exist issues of power efficiency, thermal control, fabrication uniformity and operational durability, and also the absence of standardized benchmarking. Finally, future research directions are outlined, including hybrid MEMS actuation, intelligent microfluidic operations, to improve the performance of the system and enable the transfer of the lab demonstrations to the large scale application of the system. Full article

Fused Deposition Modeling (FDM) enables rapid, flexible production of polymer-based parts; however, because of additive manufacturing’s nature, it creates distinct microscale surface structures. These micro-scale surface morphologies directly affect the functional properties of the parts, such as surface roughness and wettability. In this study, the surface roughness and contact angle behavior of PLA, PETG, and ABS samples printed via FDM were investigated by varying layer thickness, print orientation, and infill density. The experimental design was created using a Taguchi L16 orthogonal array. Surface roughness was determined by optical profilometry, and wettability was measured by static contact angle tests. Surface topography was supported by scanning electron microscopy (SEM) and three-dimensional surface analyses. The findings revealed that surface roughness is predominantly dependent on layer thickness, whereas wettability is more strongly influenced by printing orientation, which determines the surface’s anisotropy. The developed artificial neural network (ANN) models successfully predicted the trends in surface roughness and contact angle outputs. This study reveals the effect of micro-scale surface structures formed in the FDM process on functional surface behavior, offering a fundamental framework for developing designable surfaces for micromechanical, microfluidic, and biomedical applications. Full article

Extracellular vesicles (EVs) have emerged as promising tools for cancer diagnosis and therapy owing to their excellent biocompatibility, low immunogenicity, and ability to transport diverse bioactive molecules. This review summarizes recent advances in EVs research, focusing on isolation and detection technologies, their diagnostic and therapeutic applications in oncology, and the key challenges limiting clinical translation. Conventional EVs isolation methods, including ultracentrifugation, density-gradient centrifugation, and polymer-based precipitation, are discussed alongside emerging strategies such as immunoaffinity enrichment, microfluidic separation, lipid-mediated isolation, and thermophoretic enrichment, with comparative evaluation of their yield, purity, cost, and scalability. In cancer diagnosis, EV-associated biomolecules, such as miRNAs, mRNAs, proteins, and lncRNAs, show strong potential as liquid biopsy biomarkers for noninvasive early detection and dynamic disease monitoring. In therapeutic contexts, EVs serve as versatile carriers for gene molecules, chemotherapeutic agents, and small-molecule drugs, and can enhance immunotherapy and RNA-based treatments. Importantly, EVs released from metabolically active tissues, particularly skeletal muscle, contribute to systemic immune regulation and metabolic homeostasis, and their biogenesis and molecular cargo can be influenced by physical activity and exercise-related nutritional status. These insights highlight the need to integrate microengineering technologies, biomolecular profiling, standardized manufacturing systems, and lifestyle-related factors such as exercise and nutrition to accelerate the clinical translation of EV-based strategies in precision oncology and regenerative medicine. Full article

Alginate-based hydrogels, derived from brown seaweed, represent biocompatible and biodegradable materials whose properties are systematically controlled through molecular structure (M/G composition), crosslinking strategy, and compositional modification. This review synthesizes recent advances in alginate hydrogel design, encompassing fundamental structural properties, three primary crosslinking approaches—ionic coordination with divalent cations (Ca²⁺, Ba²⁺, Sr²⁺), covalent chemical linkages, and hybrid multi-crosslinking systems—and strategic modification strategies including chemical derivatization, polymer blending, and nanoparticle incorporation. These modifications address inherent limitations of native alginate, namely insufficient mechanical strength and biological inertness, thereby expanding applicability. The review examines applications across biomedical domains (drug delivery, tissue engineering, wound healing), environmental remediation, food industry systems, and emerging technologies including flexible electronics and soft robotics. Advanced fabrication techniques—3D/4D printing, microfluidics, and electrospinning—enable improved architectural control. Current evidence from preclinical and clinical studies demonstrates feasibility in specific applications, while important challenges persist, including predictable degradation kinetics, mechanical property optimization, standardization of characterization protocols, regulatory compliance, and manufacturing scalability. This review aims to provide a systematic assessment of alginate-based hydrogel development and identify areas requiring further investigation to advance clinical translation. Full article

Microfluidics provides precise control of microscale fluid transport and has become central to biomedical, pharmaceutical, and industrial technologies. However, conventional fabrication methods such as photolithography and soft lithography require cleanroom facilities, use costly materials, and offer limited capability for constructing complex or multi-material architectures. This review highlights emerging manufacturing strategies, focusing on polymer-based micro-milling as an accessible and cost-effective alternative for microfluidic device production. Advances in micro-milling now enable the fabrication of microchannels and functional features with improved dimensional accuracy and surface quality, while additive manufacturing offers complementary rapid prototyping and design flexibility. Micro-milling is particularly promising for rapid prototyping of polymeric biosensor chips designed for point-of-care diagnostics. The technique supports diverse materials and eliminates reliance on cleanroom processing. Critical parameters, including tool geometry, spindle speed, and feeding rate, strongly influence fidelity and surface roughness, which directly affect biosensor sensitivity. Despite its advantages, challenges such as tool wear, burr formation, and limits on minimum feature size continue to hinder reproducibility. Recent progress in toolpath optimization, hybrid additive–subtractive methods, and real-time process monitoring shows the potential to overcome these barriers. Overall, micro-milling offers a scalable and economical route for fabricating accessible microfluidic and biosensing platforms, with future work needed to standardize processes and improve integration with surface functionalization methods. Full article