Search Results (79)

Microfluidic paper-based analytical devices (µPADs) convert ordinary cellulose into an active analytical platform where capillary gradients shape transport, surface chemistry guides recognition, and embedded electrodes or optical probes translate biochemical events into readable signals. Progress in fabrication—from wax and stencil barriers to laser-defined grooves, inkjet-printed conductive lattices, and 3D-structured multilayers—has expanded reaction capacity while preserving portability. Detection strategies span colorimetric fields that respond within porous fibers, fluorescence and ratiometric architectures tuned for low abundance biomarkers, and electrochemical interfaces resilient to turbidity, salinity, and biological noise. Applications now include diagnosing human body fluids, checking food safety, monitoring the environment, and testing for pesticides and illegal drugs, often in places with limited resources. Researchers are now using learning algorithms to read minute gradients or currents imperceptible to the human eye, effectively enhancing and assisting the measurement process. This perspective article focuses on the newest advancements in the design, fabrication, material selection, testing methods, and applications of µPADs, and it explains how they work, where they can be used, and what their future might hold. Full article

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

The convergence of 3D bioprinting and microfluidics has revolutionized the development of organ-on-a-chip platforms, offering unprecedented opportunities in biomedical research and tissue engineering. This comprehensive review delves into the latest advancements in these technologies, highlighting their significance and transformative potential. The introduction provides an overview of 3D bioprinting, microfluidics, and organ-on-a-chip systems, emphasizing their critical roles in replicating physiological conditions and enhancing the precision of biomedical studies. The review aims to move beyond fundamental concepts, focusing on recent innovations and applications that have propelled these technologies to the forefront of research. In the realm of 3D bioprinting, the review explores the evolution of bioprinting techniques, including extrusion-based, inkjet, and laser-assisted methods and polymer-based biomaterials as matrices for in vitro tissue modeling. Technological breakthroughs such as high-resolution bioprinting, multi-material printing, and advanced bioink development are discussed, showcasing their impact on creating complex tissue structures. Innovations in bioinks, including printable polymer-based hydrogels and decellularized matrix bioinks, are highlighted for their ability to replicate tissue microenvironments more accurately. The review also covers microfluidic innovations, detailing advances in design and fabrication, including 3D printing and sensor integration. Key innovations in fluid dynamics and tissue integration are examined, demonstrating how these advancements enhance tissue modeling and mimic physiological perfusion. Developing multi-organ-on-a-chip systems and connecting multiple tissue types for systemic studies are also explored. Hence, integrating 3D bioprinting and microfluidics is a focal point, with discussions on how their convergence enhances organ-on-a-chip platforms. The review concludes by examining current challenges, such as scalability and regulatory hurdles, and future directions, including emerging technologies like 4D bioprinting and AI-driven tissue design. Full article

Available models for mass transport in microfluidic electrochemical sensors fall short in capturing critical features of millimeter-scale devices 3D-printed using fused deposition modeling, including inherent porosity and non-flat electrode geometries, thereby reducing their predictive power and transferability. Meanwhile, growing interest in low-cost and accessible fabrication methodologies has driven the quantitative use of these devices without first understanding the effects of such structural features on current responses. Here, the quantitative electrochemical performance of millimeter-scale 3D-printed devices with channel band electrodes is studied through computational and theoretical methods aimed at understanding their fundamental behavior. Simulations and dimensionless analysis reveal the influence of electrode shape and porosity on current responses under laminar flow. An adjusted Levich model is proposed to incorporate non-flat electrode geometries, while two new analytical models—general and transition-specific—predict currents through all mass transport regimes (convection, diffusion, and transition) that can simultaneously emerge due to porosity effects. Moreover, we introduce a low-cost “print–pause–print” fabrication strategy for such systems, employing a desktop 3D printer and 3D pen, which allows electrode integration and activation through polishing and “in-channel” electrochemical treatment. These advances facilitate developing next-generation 3D-printed milli fluidic electrochemical platforms with improved performance and scalability. Full article

Hydrogel films have emerged as versatile platforms in biomedical engineering due to their unique physicochemical properties, biocompatibility, and adaptability to diverse therapeutic needs. This review provides a comprehensive overview of hydrogel film materials, including natural biopolymers, synthetic polymers, and multifunctional composites, highlighting their structural and functional diversity. We examine key fabrication techniques—ranging from solvent casting and photopolymerization to advanced methods like microfluidics and 3D printing—and discuss how these influence film architecture and performance. The biomedical applications of hydrogel films span wound healing, drug delivery, tissue engineering, ophthalmology, and implantable biosensors, with recent innovations enabling stimuli-responsive behavior, multi-drug loading, and integration with wearable electronics. Despite their promise, hydrogel films face persistent challenges in mechanical durability, sterilization, storage stability, regulatory approval, and scalable manufacturing. We conclude by identifying critical research gaps and outlining future directions, including AI-guided design, sustainable material development, and the establishment of standardized, regulatory-aligned, and industrially scalable fabrication strategies to accelerate clinical translation. Full article

Hydrogels derived from natural and synthetic polymers have emerged as versatile materials with wide applications in food science, biotechnology, and health-related sectors, providing unique opportunities to encapsulate, protect, and deliver bioactive compounds, as well as to create new textures and functional properties in food systems. This review summarizes the latest advances in the design and application of hydrogels, highlighting the critical relationship between polymer structure, crosslinking strategies, and functional performance. The analysis reveals that while significant progress has been achieved, challenges persist in scaling laboratory-scale hydrogel systems to industrially relevant processes, where stability, reproducibility, and regulatory acceptance remain major bottlenecks. Emerging directions in the field include the development of smart hydrogels that respond to environmental stimuli (pH, temperature, or enzymatic activity), sustainable fabrication routes using renewable biopolymers, integration with advanced processing technologies such as 3D printing or microfluidics, and biorefinery approaches emphasizing their role in valorizing agro-industrial by-products into high-value functional materials. Hydrogels represent a promising platform at the interface of polymer science, food technology, and biotechnology, whose continued development will depend on multidisciplinary innovation aiming to meet consumer demands for sustainable, safe, and health-promoting food systems. Full article

The female reproductive system represents a highly complex regulatory network governing critical physiological functions, encompassing reproductive capacity and endocrine regulation that maintains female physiological homeostasis. The in vitro simulation system provides a novel tool for biomedical research and can be used as physiological and pathological models to study the female reproductive system. Recent advances in this technology have evolved from 2D and 3D printing to organ-on-a-chip (OOC) and microfluidic systems, which has emerged as a transformative platform for modeling the female reproductive system. These microphysiological systems integrate microfluidics, 3D cell culture, and biomimetic scaffolds to replicate key functional aspects of reproductive organs and tissues. They have enabled precise simulation of hormonal regulation, embryo-endometrium interactions, and disease mechanisms such as endometriosis and gynecologic cancers. This review highlights the current state of female reproductive OOCs, including ovary-, uterus-, and fallopian tube-on-a-chip system, their applications in assisted reproduction and disease modeling, and the technological hurdles to their widespread application. Though significant barriers remain in scaling OOCs for high-throughput drug screening, standardizing protocols for clinical applications, and validating their predictive value against human patient outcomes, OOCs have emerged as a transformative platform to model complex pathologies, offering unprecedented insights into disease mechanisms and personalized therapeutic interventions. Future directions, including multi-organ integration for systemic reproductive modeling, incorporation of microbiome interactions, and clinical translation for mechanisms of drug action, will facilitate unprecedented insights into reproductive physiology and pathology. Full article

Tryptophan (Trp) and tryptamine (Tryp), critical biomarkers in mood regulation, immune function, and metabolic homeostasis, are increasingly recognized for their roles in both oral and systemic pathologies, including neurodegenerative disorders, cancers, and inflammatory conditions. Their rapid, sensitive detection in biofluids such as saliva—a non-invasive, real-time diagnostic medium—offers transformative potential for early disease identification and personalized health monitoring. This review synthesizes advancements in electrochemical sensor technologies tailored for Trp and Tryp quantification, emphasizing their clinical relevance in diagnosing conditions like oral squamous cell carcinoma (OSCC), Alzheimer’s disease (AD), and breast cancer, where dysregulated Trp metabolism reflects immune dysfunction or tumor progression. Electrochemical platforms have overcome the limitations of conventional techniques (e.g., enzyme-linked immunosorbent assays (ELISA) and mass spectrometry) by integrating innovative nanomaterials and smart engineering strategies. Carbon-based architectures, such as graphene (Gr) and carbon nanotubes (CNTs) functionalized with metal nanoparticles (Ni and Co) or nitrogen dopants, amplify electron transfer kinetics and catalytic activity, achieving sub-nanomolar detection limits. Synergies between doping and advanced functionalization—via aptamers (Apt), molecularly imprinted polymers (MIPs), or metal-oxide hybrids—impart exceptional selectivity, enabling the precise discrimination of Trp and Tryp in complex matrices like saliva. Mechanistically, redox reactions at the indole ring are optimized through tailored electrode interfaces, which enhance reaction kinetics and stability over repeated cycles. Translational strides include 3D-printed microfluidics and wearable sensors for continuous intraoral health surveillance, demonstrating clinical utility in detecting elevated Trp levels in OSCC and breast cancer. These platforms align with point-of-care (POC) needs through rapid response times, minimal fouling, and compatibility with scalable fabrication. However, challenges persist in standardizing saliva collection, mitigating matrix interference, and validating biomarkers across diverse populations. Emerging solutions, such as AI-driven analytics and antifouling coatings, coupled with interdisciplinary efforts to refine device integration and manufacturing, are critical to bridging these gaps. By harmonizing material innovation with clinical insights, electrochemical sensors promise to revolutionize precision medicine, offering cost-effective, real-time diagnostics for both localized oral pathologies and systemic diseases. As the field advances, addressing stability and scalability barriers will unlock the full potential of these technologies, transforming them into indispensable tools for early intervention and tailored therapeutic monitoring in global healthcare. Full article

Laser-induced forward transfer (LIFT) bioprinting enables precise deposition of biological materials for advanced biomedical applications. This study presents a parametric analysis of the donor–receiver distances (1.0, 1.5, 2.0, 2.5, and 3.0 mm) in LIFT bioprinting, investigated through high-speed video and image analysis of 4 × 4 spot arrays. Droplet velocity was quantified and jet trajectory characterized, revealing that increased distances reduced spatial resolution, with significant shape deterioration observed beyond 2.0 mm. Thus, a maximum 2.0 mm donor–receiver gap was determined as optimal for acceptable printing resolution. As an application, a microfluidic device was fabricated using LCD 3D printing with a biocompatible resin and glass-bottomed configuration. The chamber height was matched to the validated 2.0 mm distance, ensuring compatibility with LIFT printing. Computational fluid dynamics simulations were conducted to model fluid flow conditions within the device. Subsequently, LLC cells were successfully printed inside the microfluidic chamber, cultured under continuous flow for 24 h, and demonstrated normal proliferation. This work highlights LIFT bioprinting’s viability and precision for integrating cells within microfluidic platforms, presenting promising potential for organ-on-chip applications and future biomedical advancements. Full article

This study presents a microfluidic chip platform designed using a multiscale 3D printing strategy for fabricating microfluidic chips with integrated, high-resolution, and customizable membrane structures. By combining two-photon polymerization (2PP) for submicron membrane fabrication with liquid crystal display printing for rapid production of larger components, this approach addresses key challenges in membrane integration, including sealing reliability and the use of transparent materials. Compared to fully 2PP-based fabrication, the multiscale method achieved a 56-fold reduction in production time, reducing total fabrication time to approximately 7.2 h per chip and offering a highly efficient solution for integrating complex structures into fluidic chips. The fabricated chips demonstrated excellent mechanical integrity. Burst pressure testing showed that all samples withstood internal pressures averaging 1.27 ± 0.099 MPa, with some reaching up to 1.4 MPa. Flow testing from ~35 $\mathsf{\mu }$L/min to ~345 $\mathsf{\mu }$L/min confirmed stable operation in 75 $\mathsf{\mu }$m square channels, with no leakage and minimal flow resistance up to ~175 $\mathsf{\mu }$L/min without deviation from the predicted behavior in the 75 $\mathsf{\mu }$m. Membrane-integrated chips exhibited outlet flow asymmetries greater than 10%, indicating active fluid transfer across the membrane and highlighting flow-dependent permeability. Overall, this multiscale 3D printing approach offers a scalable and versatile solution for microfluidic device manufacturing. The method’s ability to integrate precise membrane structures enable advanced functionalities such as diffusion-driven particle sorting and molecular filtration, supporting a wide range of biomedical, environmental, and industrial lab-on-a-chip applications. Full article

Perfusable microvasculature is critical for advancing in vitro tissue models, particularly for neural applications where limited diffusion impairs organoid growth and fails to replicate neurovascular function. This study presents a versatile fabrication platform that integrates mesh-driven design, two-photon lithography (TPL), and modular interfacing to create multi-material, perfusable 3D microvasculatures. Various 2D and 3D capillary paths were test-printed using both polygonal and lattice support strategies. A double-layered capillary scaffold based on the Hilbert curve was used for comparative materials testing. Methods for printing rigid (OrmoComp), moderately stiff hydrogel (polyethylene glycol diacrylate, PEGDA 700), and soft elastomeric (photocurable polydimethylsiloxane, PDMS) materials were developed and evaluated. Cone support structures enabled high-fidelity printing of the softer materials. A compact heat-shrink tubing interface provided leak-free perfusion without bulky fittings. Physiologically relevant flow velocities and Dextran diffusion through the scaffold were successfully demonstrated. Cytocompatibility assays confirmed that all TPL-printed scaffold materials supported human neural stem cell viability. Among peripheral components, lids fabricated via fused deposition modeling designed to hold microfluidic needle adapters exhibited good biocompatibility, while those made using liquid crystal display-based photopolymerization showed significant cytotoxicity despite indirect exposure. Overall, this platform enables creation of multi-material microvascular systems facilitated by TPL technology for complex, 3D neurovascular modeling, blood–brain barrier studies, and integration into vascularized organ-on-chip applications. Full article

Hydroxychloroquine (HCQ), a cornerstone therapeutic agent for autoimmune diseases, requires precise serum concentration monitoring due to its narrow therapeutic window. Current HCQ monitoring methods such as HPLC and LC-MS/MS are sensitive but costly and complex. While electrochemical sensors offer rapid, cost-effective detection, their large chambers and high sample consumption hinder point-of-care use. To address these challenges, we developed a microfluidic electrochemical sensing platform based on a screen-printed carbon electrode (SPCE) modified with a hierarchical nanocomposite of gold nanoparticles (AuNPs), copper-based metal–organic frameworks (Cu-MOFs), and multi-walled carbon nanotubes (MWCNTs). The Cu-MOF provided high porosity and analyte enrichment, MWCNTs established a 3D conductive network to enhance electron transfer, and AuNPs further optimized catalytic activity through localized plasmonic effects. Structural characterization (SEM, XRD, FT-IR) confirmed the successful integration of these components via π-π stacking and metal–carboxylate coordination. Electrochemical analyses (CV, EIS, DPV) revealed exceptional performance, with a wide linear range (0.05–50 μM), a low detection limit (19 nM, S/N = 3), and a rapid response time (<5 min). The sensor exhibited outstanding selectivity against common interferents, high reproducibility (RSD = 3.15%), and long-term stability (98% signal retention after 15 days). By integrating the nanocomposite-modified SPCE into a microfluidic chip, we achieved accurate HCQ detection in 50 μL of serum, with recovery rates of 95.0–103.0%, meeting FDA validation criteria. This portable platform combines the synergistic advantages of nanomaterials with microfluidic miniaturization, offering a robust and practical tool for real-time therapeutic drug monitoring in clinical settings. Full article

Background/Objectives: Liver-on-a-chip (LiOC) technology is increasingly recognized as a transformative platform for modeling liver biology, disease mechanisms, drug metabolism, and toxicity screening. Traditional two-dimensional (2D) in vitro models lack the complexity needed to replicate the liver’s unique microenvironment. This review aims to summarize recent advancements in LiOC systems, emphasizing their potential in biomedical research and translational applications. Methods: This narrative review synthesizes findings from key studies on the development and application of LiOC platforms. We explored innovations in material science and bioengineering, including microfluidic design, 3D printing, stem cell– and tissue-derived liver organoid integration, and co-culture strategies. Commercially available LiOC systems and their regulatory relevance were also evaluated. Results: LiOC systems have evolved from simple PDMS-based chips to complex, multicellular constructs incorporating hepatocytes, endothelial cells, Kupffer cells, and hepatic stellate cells. Recent studies demonstrate their superior ability to replicate liver-specific architecture and functions. Applications span cancer research, drug toxicity assessment (e.g., drug-induced liver injury prediction with >85% sensitivity), disease modeling, and regenerative medicine. Several platforms have gained FDA recognition and are in active use for preclinical drug testing. Conclusions: LiOC technology offers a more physiologically relevant alternative to traditional models and holds promise for reducing reliance on animal studies. While challenges remain, such as vascularization and long-term function, ongoing advancements are paving the way toward clinical and pharmaceutical integration. The technology is poised to play a key role in personalized medicine and next-generation therapeutic development. Full article

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design and fabrication of organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores the applications of biomaterials in drug delivery, cell culture, and tissue engineering, and evaluates the potential of microfluidic systems in advancing personalized healthcare. We systematically analyze the evolution of microfluidic materials—from silicon and glass to polymers and paper—and highlight the advantages of 3D bioprinting over traditional fabrication methods. Currently, despite significant advances in microfluidics in medicine, challenges in scalability, stability, and clinical translation remain. The future of microfluidic biomaterials will depend on combining 3D bioprinting with dynamic functional design, developing hybrid strategies that combine traditional molds with bio-printed structures, and using artificial intelligence to monitor drug delivery or tissue response in real time. We believe that interdisciplinary collaborations between materials science, micromachining, and clinical medicine will accelerate the translation of organ-on-a-chip platforms into personalized therapies and high-throughput drug screening tools. Full article

Microfluidic technology is an emerging interdisciplinary field that uses micropipes to handle or manipulate tiny fluids in chemistry, fluid physics, and biomedical engineering. As one of the rapid prototyping methods, the three-dimensional (3D) printing technique, which is rapid and cost-effective and has integrated molding characteristics, has become an important manufacturing technology for microfluidic chips. Polymethyl-methacrylate (PMMA), as an exceptional thermoplastic material, has found widespread application in the field of microfluidics. This paper presents a comprehensive process study on the fabrication of fused deposition modeling (FDM) 3D-printed PMMA microfluidic chips (chips), encompassing finite element numerical analysis studies, orthogonal process parameter optimization experiments, and the application of 3D-printed integrated microfluidic reactors in the reaction between copper ions and ammonium hydroxide. In this work, a thermal stress finite element model shows that the printing platform temperature was a significant printing parameter to prevent warping and delamination in the 3D printing process. A single printing molding technique is employed to fabricate microfluidic chips with square cross-sectional dimensions reduced to 200 μm, and the microchannels exhibited no clogging or leakage. The orthogonal experimental method of 3D-printed PMMA microchannels was carried out, and the optimized printing parameter resulted in a reduction in the microchannel profile to Ra 1.077 μm. Finally, a set of chemical reaction experiments of copper ions and ammonium hydroxide are performed in a 3D-printed microreactor. Furthermore, a color data graph of copper hydroxide is obtained. This study provides a cheap and high-quality research method for future research in water quality detection and chemical engineering. Full article