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Keywords = microfluidic co-flow

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14 pages, 1522 KB  
Article
A Laminar Microfluidic Platform for Probing the Effects of Spatially Heterogeneous Drug Distributions
by Yang Zeng, Wenyan Liu, Jiahao Fu, Bingchen Che, Yonggang Liu, Xiaobo Gong, Dan Sun and Ce Zhang
Micromachines 2026, 17(6), 655; https://doi.org/10.3390/mi17060655 - 26 May 2026
Viewed by 328
Abstract
We herein designed a 64-chamber laminar-flow microfluidic chip with independently addressable culture units capable of establishing spatially heterogeneous chemical environments to mimic tissue microenvironments. Stable chemical gradients were successfully generated within the chip through controlled laminar flow, allowing precise spatial modulation of cellular [...] Read more.
We herein designed a 64-chamber laminar-flow microfluidic chip with independently addressable culture units capable of establishing spatially heterogeneous chemical environments to mimic tissue microenvironments. Stable chemical gradients were successfully generated within the chip through controlled laminar flow, allowing precise spatial modulation of cellular exposure. Using TNF-α as a model stimulus, we observed a clear time delay in NF-κB activation between cells directly exposed to the cytokine and those located on the medium-only side, confirming the establishment of spatially distinct chemical conditions. Notably, even cells not directly exposed to TNF-α eventually responded, indicating that molecular diffusion along the static solid–liquid interface serves as an effective delivery route for bioactive molecules. To further demonstrate the platform’s utility, we constructed a skin-mimetic co-culture model of HaCaT keratinocytes and human skin fibroblasts (HSFs) to assess the diffusion and cytotoxic effects of 5-fluorouracil (5-FU). The results revealed that fibroblasts provided protective effects against 5-FU-induced cytotoxicity, likely via paracrine signaling or direct cell–cell interactions. These findings highlight the platform’s capacity for probing not only spatial drug-delivery dynamics but also intercellular interactions under physiologically relevant conditions. This system offers a powerful and versatile tool for studying spatiotemporal signaling, drug screening, and topical therapeutic development. Full article
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23 pages, 5913 KB  
Review
A Review of Synergistic Acoustic Mechanisms in Porous Media: Microfluidic Insights for Geo-Energy Applications
by Han Ge, Ziling Teng, Shibo Liu, Xiulei Chen and Jiawang Chen
Appl. Sci. 2026, 16(10), 4949; https://doi.org/10.3390/app16104949 - 15 May 2026
Viewed by 238
Abstract
Geothermal energy extraction, hydrocarbon recovery, and CO2 geological sequestration are frequently hindered by interfacial barriers and slow mass transfer. While high-power ultrasound offers a sustainable, purely physical method for reservoir stimulation, its field effectiveness remains debated because traditional macroscopic experiments fail to [...] Read more.
Geothermal energy extraction, hydrocarbon recovery, and CO2 geological sequestration are frequently hindered by interfacial barriers and slow mass transfer. While high-power ultrasound offers a sustainable, purely physical method for reservoir stimulation, its field effectiveness remains debated because traditional macroscopic experiments fail to isolate mechanisms like acoustic streaming and cavitation. This review systematically examines acoustic mechanisms in porous media via microfluidic visualization, focusing on pore-scale fluid dynamics during enhanced oil recovery, hydrate dissociation, and CO2 sequestration. Microscopic evidence reveals that fluid transport mechanisms depend heavily on pore geometry and local acoustic intensity. In wider channels, nonlinear acoustic flow provides sustained, directed convection to strip away concentration boundary layers; in narrow throats, microjets and pulsed stresses generated by transient cavitation are responsible for physically breaking capillary barriers. The spatiotemporal synergy of these mechanisms is critical for multiphase fluid transport in tight porous networks. Pore geometry serves not only as the application context but also as a core physical variable. To translate microfluidic results into reservoir-scale applications, future research must address two-dimensional simplifications, thermodynamic discrepancies under high-temperature and high-pressure conditions, and bubble cluster interactions, alongside the development of adaptive frequency-modulated control and multiscale computational models. Full article
(This article belongs to the Section Fluid Science and Technology)
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29 pages, 2346 KB  
Review
Microfluidic Structuring Strategies for Edible Films and Coatings: Functional Design, Performance Implications, and Scale-Up Challenges
by Giovanna Rossi-Márquez, Cristian Aarón Dávalos-Saucedo, Sergio Rodríguez-Miranda, Edgardo Martínez-Orozco, Netzahualcóyotl Mayek-Pérez and Carlos E. Castañeda
Coatings 2026, 16(5), 553; https://doi.org/10.3390/coatings16050553 - 4 May 2026
Viewed by 473
Abstract
Microfluidic technologies are increasingly used as upstream structuring tools in the development of edible films and coatings. This review examines how flow-focusing, T-junction, co-flow, step-emulsification, and related microfluidic platforms generate emulsions, double emulsions, hydrogel microparticles, and multicompartment carriers that are relevant to coating [...] Read more.
Microfluidic technologies are increasingly used as upstream structuring tools in the development of edible films and coatings. This review examines how flow-focusing, T-junction, co-flow, step-emulsification, and related microfluidic platforms generate emulsions, double emulsions, hydrogel microparticles, and multicompartment carriers that are relevant to coating design. Rather than treating microfluidics as an end in itself, the review evaluates how microfluidically generated structures influence carrier protection, matrix compatibility, controlled release, and the final functionality of edible films and coatings. Particular attention is paid to whether carrier architecture survives matrix incorporation, deposition, drying, and end use, because these downstream steps determine whether structural advantages translate into barrier, mechanical, optical, and preservation-related performance. The review also discusses the principal factors that currently limit industrial implementation, including throughput, fouling, sanitation, thermoplastic manufacturing, bonding, and integration into hygienic food-processing environments. Overall, microfluidics offers a highly controlled route for mechanism-oriented formulation development, but its practical value for edible coatings depends on whether this structural control can be translated into robust, scalable, and food-compliant manufacturing routes. Full article
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22 pages, 3654 KB  
Article
Pulse Driven Injection in an Additive-Manufactured Microchannel for Rapid Mixing of Stratified Concurrent Flow and On-Demand Droplet Generation
by Faisal bin Nasser Sarbaland, Masashi Kobayashi, Daiki Tanaka, Risa Fujita, Nobuyuki Tanaka and Masahiro Furuya
Micromachines 2026, 17(5), 540; https://doi.org/10.3390/mi17050540 - 28 Apr 2026
Viewed by 515
Abstract
Laminar co-flow in microchannels typically results in stratified streams with diffusion-limited mixing. This work presents an additively manufactured microfluidic platform that integrates a pulse tank and a transverse injection nozzle into an otherwise straight channel, enabling pulse-driven mixing and droplet generation using air-pressure [...] Read more.
Laminar co-flow in microchannels typically results in stratified streams with diffusion-limited mixing. This work presents an additively manufactured microfluidic platform that integrates a pulse tank and a transverse injection nozzle into an otherwise straight channel, enabling pulse-driven mixing and droplet generation using air-pressure actuation alone. In Device A, transverse pulsed injection disrupted the stratified interface and significantly enhanced mixing compared with the no-pulse case, as confirmed by an entropy-based mixing index. In Device B, pulsed injection into a continuous oil phase enabled stable droplet-on-demand generation with pressure-tunable droplet diameter in a straight circular channel. The devices operated in a laminar regime, with representative Reynolds, Péclet, and capillary numbers confirming diffusion-limited baseline mixing and stable dripping-type droplet formation. The results demonstrate that pulse-driven injections in a simple, additively manufactured geometry provide an effective, low-complexity approach to mixing enhancement and droplet generation without external fields or complex channel designs. Full article
(This article belongs to the Special Issue Multiphase Microfluidics: Transport, Interfaces and Dynamics)
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30 pages, 453 KB  
Review
Biosurfactants as Antibiofilm Agents for Medical Devices: Mechanisms, Evidence and Integration into Infection Prevention and Control
by Sunday Stephen Abi and Ibrahim M. Banat
Microorganisms 2026, 14(4), 910; https://doi.org/10.3390/microorganisms14040910 - 17 Apr 2026
Cited by 1 | Viewed by 915
Abstract
Biofilms rapidly form on medical devices such as urinary catheters and surgical materials. These biofilms compromise patient safety and undermine infection prevention and control (IPC). Biofilms also reduce the effectiveness of antibiotics and disinfectants. As a result, they increase healthcare-associated infections and increase [...] Read more.
Biofilms rapidly form on medical devices such as urinary catheters and surgical materials. These biofilms compromise patient safety and undermine infection prevention and control (IPC). Biofilms also reduce the effectiveness of antibiotics and disinfectants. As a result, they increase healthcare-associated infections and increase costs through device failure and the need for maintenance or replacement. Researchers are increasingly exploring biosurfactants (BSs) as surface coatings and cleaning additives to prevent microbial attachment and disrupt early biofilm formation on medical devices and healthcare-related surfaces. This review examines the translational potential of biosurfactants as preventive, disruptive, and adjunctive antibiofilm agents for medical devices and healthcare-related surfaces. Literature evidence on glycolipids (rhamnolipids, sophorolipids) and lipopeptides (surfactin) from static, flow-based, and microfluidic in vitro models that used clinically relevant materials, such as silicone and polydimethylsiloxane (PDMS), were examined. In our literature search, we focused on pathogens central to IPC, such as Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., and Candida spp., and it was generally noted that BSs reduced microbial adhesion and delayed early biofilm formation on medical devices and healthcare-related surfaces. Significant evidence also suggests that they partially disrupt biofilms and improve antimicrobial penetration when co-applied, mainly through membrane disruption, destabilization of extracellular substances, interfering with quorum sensing, and synergistic and/or antagonistic interactions with other molecules. Their performance varied with class, formulation, hydrodynamic conditions, and microbial composition. BSs function better as preventive and adjunctive IPC tools than stand-alone antimicrobial agents and can help to reduce biofilm formation on devices and improve surface disinfection. However, translating this promise into practice demands more robust data on long-term safety, stability, and product quality. Full article
(This article belongs to the Special Issue Latest Review Papers in Antimicrobial Agents and Resistance 2026)
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21 pages, 4012 KB  
Article
Full Hematocrit–Viscosity Curve Identification Using Three-Dataset Krieger–Dougherty Regression
by Yang Jun Kang
Biosensors 2026, 16(4), 216; https://doi.org/10.3390/bios16040216 - 10 Apr 2026
Viewed by 516
Abstract
Blood viscosity is strongly dependent on hematocrit, and the hematocrit–viscosity relationship is an important determinant of blood rheology under physiological and pathological conditions. However, obtaining a full hematocrit–viscosity curve requires multiple measurements over a wide hematocrit range. In this study, a simple method [...] Read more.
Blood viscosity is strongly dependent on hematocrit, and the hematocrit–viscosity relationship is an important determinant of blood rheology under physiological and pathological conditions. However, obtaining a full hematocrit–viscosity curve requires multiple measurements over a wide hematocrit range. In this study, a simple method is proposed to reconstruct the full hematocrit–viscosity curve using only three-dataset Krieger–Dougherty (K–D) regression as μ=μ0(1ϕϕm)α ϕm. Based on suspended blood, RBC-rich blood and RBC-depleted blood are prepared after centrifugation. The hematocrit of each type of blood is measured using a micro-hemocytometer. Simultaneously, the blood viscosity of each type of blood is measured using the coflowing streams method. The proposed method is evaluated sequentially using reference datasets and hematocrit–viscosity datasets of control blood. According to results, the full hematocrit–viscosity curve obtained from three selected datasets is in good agreement with the experimental data and yields a lower root-mean-square error than conventional methods using all datasets. The exponent of the K–D model is strongly influenced by the midpoint dataset, whereas μ0 is mainly affected by the suspending medium (dextran solution). In contrast, GA-induced rigidified RBCs do not significantly affect μ0 within a 0.15% concentration. In conclusion, the proposed method provides a simple, efficient, and reliable approach for estimating the full hematocrit–viscosity curve. Full article
(This article belongs to the Special Issue Integrated Microfluidic Biosensing Systems: Designs and Applications)
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20 pages, 1352 KB  
Article
Lipid–Polymer Nanoparticles (LiPoNs) Mediated Codelivery of AntimiR-21 and Gadolinium Chelate in Triple Negative Breast Cancer Theranostics
by Felicia Roffo, Francesca Maria Orlandella, Neila Luciano, Giuliana Salvatore and Enza Torino
Bioengineering 2026, 13(2), 209; https://doi.org/10.3390/bioengineering13020209 - 12 Feb 2026
Cited by 1 | Viewed by 1014
Abstract
RNA-based interventions are particularly promising for next-generation therapeutic strategies and hold significant potential when integrated with diagnostic modalities. Among noncoding RNAs, microRNAs (miRNAs) regulate gene expression post-transcriptionally and represent compelling targets for cancer therapy. However, their clinical translation remains hindered by instability, off-target [...] Read more.
RNA-based interventions are particularly promising for next-generation therapeutic strategies and hold significant potential when integrated with diagnostic modalities. Among noncoding RNAs, microRNAs (miRNAs) regulate gene expression post-transcriptionally and represent compelling targets for cancer therapy. However, their clinical translation remains hindered by instability, off-target effects, and limited delivery efficiency. Here, we report the microfluidic synthesis of hybrid lipid–polymer nanoparticles (LiPoNs) that co-deliver an AntimiR-21 and the magnetic resonance imaging contrast agent gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA). The LiPoNs were obtained using coupled Hydrodynamic Flow Focusing (cHFF), enabling precise control over lipid–polymer self-assembly and surpassing the compositional limitations reported with conventional micromixers. The resulting AntimiR-21–Gd-DTPA–LiPoNs exhibited an average hydrodynamic diameter of 124 nm, narrow polydispersity (PDI < 0.2), and encapsulation efficiency up to 60%. In MDA-MB-231 breast cancer cells, treatment with AntimiR-21–LiPoNs induced suppression of miR-21 and a corresponding decrease in migratory capacity, demonstrating effective functional delivery and gene expression modulation. These findings establish a versatile microfluidic platform for engineering multifunctional lipid–polymer nanostructures whose hybrid architecture combines the biocompatibility and membrane fusion capability of lipids with the structural robustness and controlled release properties of polymers, thereby advancing RNA-based theranostic design for precision oncology and related applications. Full article
(This article belongs to the Special Issue Gene Delivery for Cancer Therapy)
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19 pages, 1037 KB  
Review
Cystic Fibrosis of the Pancreas: In Vitro Duct Models for CFTR-Targeted Translational Research
by Alessandra Ludovico, Martina Battistini and Debora Baroni
Int. J. Mol. Sci. 2026, 27(3), 1279; https://doi.org/10.3390/ijms27031279 - 27 Jan 2026
Cited by 1 | Viewed by 1295
Abstract
Cystic fibrosis (CF) is caused by loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride and bicarbonate channel and affects multiple organs, with pancreatic involvement showing very high penetrance. In pancreatic ducts, CFTR drives secretion of alkaline, bicarbonate-rich fluid that maintains [...] Read more.
Cystic fibrosis (CF) is caused by loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride and bicarbonate channel and affects multiple organs, with pancreatic involvement showing very high penetrance. In pancreatic ducts, CFTR drives secretion of alkaline, bicarbonate-rich fluid that maintains intraductal patency, neutralises gastric acid and permits safe delivery of digestive enzymes. Selective impairment of CFTR-dependent bicarbonate transport, even in the presence of residual chloride conductance, is strongly associated with exocrine pancreatic insufficiency, recurrent pancreatitis and cystic-fibrosis-related diabetes. These clinical manifestations are captured by pharmacodynamic anchors such as faecal elastase-1, steatorrhoea, pancreatitis burden and glycaemic control, providing clinically meaningful benchmarks for CFTR-targeted therapies. In this review, we summarise the principal mechanisms underlying pancreatic pathophysiology and the current approaches to clinical management. We then examine in vitro pancreatic duct models that are used to evaluate small molecules and emerging therapeutics targeting CFTR. These experimental systems include native tissue, primary cultures, organoids, co-cultures and microfluidic devices, each of which has its own advantages and limitations. Intact micro-perfused ducts provide the physiological benchmark for studying luminal pH control and bicarbonate (HCO3) secretion. Primary pancreatic duct epithelial cells (PDECs) and pancreatic ductal organoids (PDO) preserve ductal identity, patient-specific genotype and key regulatory networks. Immortalised ductal cell lines grown on permeable supports enable scalable screening and structure activity analyses. Co-culture models and organ-on-chip devices incorporate inflammatory, stromal and endocrine components together with flow and shear and provide system-level readouts, including duct-islet communication. Across this complementary toolkit, we prioritise bicarbonate-relevant endpoints, including luminal and intracellular pH and direct measures of HCO3 flux, to improve alignment between in vitro pharmacology and clinical pancreatic outcomes. The systematic use of complementary models should facilitate the discovery of next-generation CFTR modulators and adjunctive strategies with the greatest potential to protect both exocrine and endocrine pancreatic function in people with CF. Full article
(This article belongs to the Special Issue Molecular Mechanisms Underlying the Pathogenesis of Genetic Diseases)
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68 pages, 9076 KB  
Review
Collagen Type I as a Biological Barrier Interface in Biomimetic Microfluidic Devices: Properties, Applications, and Challenges
by Valentina Grumezescu and Liviu Duta
Biomimetics 2026, 11(1), 66; https://doi.org/10.3390/biomimetics11010066 - 13 Jan 2026
Cited by 2 | Viewed by 2359
Abstract
Collagen type I has become a practical cornerstone for constructing biologically meaningful barrier interfaces in microfluidic systems. Its fibrillar architecture, native ligand display, and susceptibility to cell-mediated remodeling support epithelial and endothelial polarization, tight junctions, and transport behaviors that are difficult to achieve [...] Read more.
Collagen type I has become a practical cornerstone for constructing biologically meaningful barrier interfaces in microfluidic systems. Its fibrillar architecture, native ligand display, and susceptibility to cell-mediated remodeling support epithelial and endothelial polarization, tight junctions, and transport behaviors that are difficult to achieve with purely synthetic barrier interfaces. Recent advances pair these biological strengths with tighter engineering control. For example, ultrathin collagen barriers (tens of micrometers or less) enable faster molecular exchange and short-range signaling; gentle crosslinking and composite designs limit gel compaction and delamination under flow; and patterning/bioprinting introduce alignment, graded porosity, and robust integration into device geometries. Applications now span intestine, vasculature, skin, airway, kidney, and tumor–stroma interfaces, with readouts including transepithelial/transendothelial electrical resistance (TEER), tracer permeability, and image-based quality control of fiber architecture. Persistent constraints include batch variability, long-term mechanical drift, limited standardization of fibrillogenesis conditions, and difficulties scaling fabrication without loss of bioactivity. Priorities include reporting standards for microstructure and residual crosslinker, chips for continuous monitoring, immune-competent co-cultures, and closer collaboration across materials science, microfabrication, computational modelling, and clinical pharmacology. Thus, this review synthesizes the state-of-the-art and offers practical guidance on technological readiness and future directions for using collagen type I as a biological barrier interface in biomimetic microfluidic systems. Full article
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19 pages, 1594 KB  
Article
Dual Core-Shell Loaded Lipid-Polymer Hybrid Nanoparticles as Combination Anti-Infective Delivery Platforms
by Valeria Carini, Giulia Scagnetti, Joanne Foulkes, Katie Evans, Imran Saleem and Sarah Gordon
Pharmaceutics 2026, 18(1), 13; https://doi.org/10.3390/pharmaceutics18010013 - 22 Dec 2025
Cited by 1 | Viewed by 1419
Abstract
Background/Objectives: The growing threat posed by antimicrobial resistance to worldwide public health highlights the urgent need not only for new anti-infective candidates, but also for innovative formulation strategies capable of mediating effective delivery of anti-infective compounds. The current study, therefore, aimed to demonstrate [...] Read more.
Background/Objectives: The growing threat posed by antimicrobial resistance to worldwide public health highlights the urgent need not only for new anti-infective candidates, but also for innovative formulation strategies capable of mediating effective delivery of anti-infective compounds. The current study, therefore, aimed to demonstrate the feasibility of formulating lipid-polymer hybrid nanoparticles (LPHNPs) with dual loading of both core and shell compartments for combination anti-infective delivery. Methods: LPHNPs containing the antibiotic cefotaxime within a chitosan polymer core and the novel antimicrobial peptide RN7IN6 within a bacteria-mimicking lipid shell were produced by microfluidic mixing, and optimized with respect to parameters including total flow rate, flow rate ratio, and lipid concentration. Minimum inhibitory concentrations of cefotaxime and RN7IN6 co-incorporated in LPHNPs were assessed as a preliminary indicator of antibacterial efficacy. Results: Uniformly nanosized LPHNPs were produced, with maximized loading of cefotaxime and RN7IN6 within particle cores and shells, respectively. Empty LPHNPs showed an appreciable antibacterial activity, particularly against the Gram-negative bacterium Escherichia coli, while RN7IN6 was indicated to enhance cefotaxime activity against E. coli when both actives were incorporated in LPHNPs. Conclusions: The current findings clearly demonstrate the feasibility of formulating LPHNPs for core-shell co-encapsulation and delivery of anti-infectives. The promising antibacterial efficacy of co-loaded LPHNPs warrants further in-depth investigation to determine the extent of co-loaded LPHNP applications as combination anti-infective delivery platforms. Full article
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15 pages, 3854 KB  
Article
Cascade Dielectrophoretic Separation for Selective Enrichment of Polyhydroxybutyrate (PHB)-Producing Cyanobacterium Synechocystis sp. PCC 6803
by Songyuan Yan, Sara Louise Pacheco, Asa K. Laskie, Cesar Raul Gonzalez Esquer and Lawrence Kulinsky
Micromachines 2025, 16(12), 1402; https://doi.org/10.3390/mi16121402 - 12 Dec 2025
Viewed by 765
Abstract
Maintaining favorable biological productivities in photosynthetic biomanufacturing systems, especially when the risk of contamination with competing microbes is high, remains a challenge to achieve while maintaining economic feasibility. This study presents a dielectrophoresis (DEP)-based microfluidic approach for isolating a desired strain within a [...] Read more.
Maintaining favorable biological productivities in photosynthetic biomanufacturing systems, especially when the risk of contamination with competing microbes is high, remains a challenge to achieve while maintaining economic feasibility. This study presents a dielectrophoresis (DEP)-based microfluidic approach for isolating a desired strain within a co-culture. The cyanobacterium Synechocystis sp. PCC 6803 (a strain capable of producing the bioplastic precursor polyhydroxybutyrate, or PHB) was enriched from mixed cultures containing the competing cyanobacterium Synechococcus elongatus PCC 7942 (which does not naturally produce PHB). A DEP cascade electrode system was established to increase purification efficiency through sequential enrichment, which leveraged inherent differences in cell morphology and dielectric properties, to achieve the selective separation of these strains under physiological conditions. A substantial increase in the relative abundance of PHB-producing cells was assessed by optical microscopy and flow cytometry characterization, confirming more than five-fold reduction of the Synechococcus fraction in the refined cell mix. The presented electrokinetic platform offers a scalable and effective approach for selectively enhancing desired microbial components within microbial biomanufacturing systems, leading towards improved product yields. Full article
(This article belongs to the Section C1: Micro/Nanoscale Electrokinetics)
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12 pages, 1913 KB  
Article
Characterization of PEG-Modified Composite Membranes for Microfluidic Oxygenator Applications
by Nicholas C. Higgins, David G. Blauvelt and Shuvo Roy
Micromachines 2025, 16(12), 1383; https://doi.org/10.3390/mi16121383 - 6 Dec 2025
Viewed by 869
Abstract
Microfluidic oxygenators promise to advance extracorporeal membrane oxygenation (ECMO) devices with enhanced hemodynamics and low prime volume. We are developing a silicon-based membrane oxygenator that will offer improved gas transfer and fluid flow control. Polyethylene glycol (PEG) has been used to improve hemocompatibility [...] Read more.
Microfluidic oxygenators promise to advance extracorporeal membrane oxygenation (ECMO) devices with enhanced hemodynamics and low prime volume. We are developing a silicon-based membrane oxygenator that will offer improved gas transfer and fluid flow control. Polyethylene glycol (PEG) has been used to improve hemocompatibility by providing excellent resistance to protein adsorption. Here, we characterized a polyethylene glycol surface modification of composite silicon–PDMS membranes to evaluate their effects on microfluidic oxygenator properties. X-ray photoelectron spectroscopy (XPS) and water contact angle goniometry confirmed successful PEG attachment, evidenced by the presence of characteristic C-O bonds and increased hydrophilicity, which was stable for 2 weeks. Oxygen flux tests demonstrated gas transfer rates as high as 89.6 ± 17.9 mL/min/m2 and 50.8 ± 11.7 mL/min/m2 for unmodified and PEG-coated membranes, respectively. Protein adsorption studies with human serum albumin (HSA) demonstrated a significant reduction in nonspecific protein binding on PEG-coated membranes with values as low as 14 ± 6 μg/cm2. These studies expand on the characterization of our engineered oxygenator membranes and provide insight for the development of future surface optimization strategies to enhance hemocompatibility. Full article
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19 pages, 1571 KB  
Review
From Spheroids to Tumor-on-a-Chip for Cancer Modeling and Therapeutic Testing
by Maria Veronica Lipreri, Marilina Tamara Totaro, Nicola Baldini and Sofia Avnet
Micromachines 2025, 16(12), 1343; https://doi.org/10.3390/mi16121343 - 27 Nov 2025
Cited by 7 | Viewed by 2100
Abstract
The high failure rate of anticancer drugs in clinical trials highlights the need for preclinical models that accurately reproduce the structural, biochemical, and mechanical complexity of human tumors. Conventional two-dimensional cultures and animal models often lack the physiological complexity required to predict clinical [...] Read more.
The high failure rate of anticancer drugs in clinical trials highlights the need for preclinical models that accurately reproduce the structural, biochemical, and mechanical complexity of human tumors. Conventional two-dimensional cultures and animal models often lack the physiological complexity required to predict clinical outcomes, driving the development of three-dimensional systems that better emulate the tumor microenvironment. Among these, microfluidic-based spheroid models have emerged as powerful tools for cancer research and drug screening. By integrating 3D spheroids with microfluidics, these platforms allow precise control of nutrient flow, oxygen gradients, shear stress, and interstitial pressure, while supporting co-culture with stromal, immune, and endothelial cells. Such systems enable the investigation of drug response, angiogenesis, metastasis, and immune interactions under dynamic and physiologically relevant conditions. This review summarizes recent advances in microfluidic spheroid models for cancer, covering both carcinomas and sarcomas, with an emphasis on device design, biomaterial integration, and translational validation. Key challenges remain, including technical complexity, scalability constraints, and the absence of standardized protocols. Overall, the merger of microfluidic technology with 3D spheroid culture provides a promising pathway toward predictive, ethical, and personalized preclinical testing, bridging the gap between in vitro modeling and clinical oncology. Full article
(This article belongs to the Special Issue Development of 3D Cancer Models in Microengineered Systems)
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20 pages, 2266 KB  
Article
Numerical Study of Pulsation-Controlled Droplet Generation in a Microfluidic T-Junction
by Alibek Kuljabekov, Darezhat Bolysbek, Zhibek Akasheva and Zhumabek Zhantayev
Processes 2025, 13(11), 3690; https://doi.org/10.3390/pr13113690 - 15 Nov 2025
Cited by 1 | Viewed by 1027
Abstract
Droplet generation in microfluidic T-junctions is a key process in various chemical and biomedical applications requiring precise size and frequency control. This study presents a numerical investigation of pulsation-controlled droplet formation using a two-phase incompressible laminar flow model with constant surface tension and [...] Read more.
Droplet generation in microfluidic T-junctions is a key process in various chemical and biomedical applications requiring precise size and frequency control. This study presents a numerical investigation of pulsation-controlled droplet formation using a two-phase incompressible laminar flow model with constant surface tension and defined wettability. Simulations were conducted in COMSOL Multiphysics employing the Level Set method, and the model was validated against the benchmark data of Bashir et al., accurately reproducing droplet pinch-off time and morphology under steady co-flow conditions. Pulsatile inlet velocity was then introduced to analyze its influence on droplet dynamics. Results show that at frequencies between 35 and 60 Hz, droplet generation becomes synchronized with the pulsation cycle, producing one droplet per period. Beyond 60 Hz, synchronization is lost, leading to irregular breakup and loss of droplet size control. The droplet length exhibited an approximately linear dependence on pulsation frequency, indicating predictable and tunable droplet formation. These findings demonstrate that simple modulation of the dispersed-phase velocity enables droplet-on-demand operation and robust control of droplet size and generation rate in standard microfluidic T-junctions. Full article
(This article belongs to the Section Process Control, Modeling and Optimization)
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13 pages, 977 KB  
Communication
Gel-Phase Microextraction Using Microfluidic-Directed Ultrashort Peptide Assemblies for the Determination of Drugs in Oral Fluids
by M. Laura Soriano, Ana M. Garcia, Juan A. Garcia-Romero, Pilar Prieto, Aldrik H. Velders and M. Victoria Gomez
Int. J. Mol. Sci. 2025, 26(20), 9982; https://doi.org/10.3390/ijms26209982 - 14 Oct 2025
Viewed by 932
Abstract
This study introduces an innovative microfluidic-based approach for extracting drugs from oral fluids using self-assembled tripeptide hydrogels as sorbents. Peptide microfiber derived from the heterochiral tripeptide DLeu-LPhe-LPhe was formed in situ within the 14 mm-long microchannel of a [...] Read more.
This study introduces an innovative microfluidic-based approach for extracting drugs from oral fluids using self-assembled tripeptide hydrogels as sorbents. Peptide microfiber derived from the heterochiral tripeptide DLeu-LPhe-LPhe was formed in situ within the 14 mm-long microchannel of a two-inlet microfluidic device. The methodology enables the laminar flow-driven mixing of buffer solutions, inducing hydrogel formation at their interface. The resulting fiber exhibited a well-defined morphology and β-sheet structure, confirmed by Raman spectroscopy and Thioflavin T fluorescence. The peptide fibers co-assembled successfully with 5-fluorouracil (5-FU) and naproxen (39.8 ± 1.4 nmol of 5-FU and 27.4 ± 6.6 nmol of naproxen per 112 nmol of peptide used to prepare the fiber), resulting in a molar ratio drug/peptide ratio of approximately 1:3 and 1:4, respectively, demonstrating versatility in drug entrapment. The use of the gel fiber as a sorbent phase was first assessed in buffer, and subsequently, the optimized method was applied to saliva. Adsorption studies under stopped-flow conditions showed a significant drug adsorption capability from buffered solutions by the pre-formed hydrogel (32.8 ± 0.9% of 5-FU and 36.4 ± 3.3% of naproxen per fiber preformed with 112 nmol of peptide), demonstrating their suitability as sorbent material. The extension of the methodology to simulated saliva samples allowed extraction of 36% of 5-FU by the fiber, as determined by 19F NMR spectroscopy on microcoils, which enabled us to work with the small volume of fluid extracted from the microfluidic device and provided clean spectra and quantitative results. These findings highlight the potential of this tripeptide hydrogel as a sorbent material for therapeutic drug monitoring and toxicological analysis via a simple, non-invasive and rapid approach for drug detection in oral fluids. Full article
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