{"title":"Spatial distribution and density of fibroblasts determine angiogenic response of endothelial cells","authors":"Pu Zhang, Melur K. Ramasubramanian, Li-Heng Cai","doi":"10.1007/s10404-026-02939-3","DOIUrl":"10.1007/s10404-026-02939-3","url":null,"abstract":"<div><p>Fibroblasts play indispensable roles in orchestrating revascularization and angiogenesis of endothelial cells. However, the specific conditions under which the influence of fibroblasts becomes important in modulating angiogenic formation remain to be determined. Here, we extend a previously established microfluidic co-culture system to enable precise manipulation of the density of human lung fibroblasts (HLF) and their distance to human umbilical vein endothelial cells (HUVECs) in a wide range within fibrin hydrogels. Using live cell imaging and image analysis, we quantify the effects of fibroblast density, HLF- HUVEC cell–cell distance, and culturing time on cell migration, morphology, microvasculature, and endothelial sprouting. We find that, within the system and parameter range explored here, for fibroblasts to have a significant positive impact in the angiogenesis of endothelial cells, the fibroblast density should be no less than ~3×10<sup>6</sup> cells/ml and the cell–cell distance should be no greater than ~2 mm. The experimental findings can be captured by a minimal model accounting for the concentration profile of pro-angiogenic factors secreted by fibroblasts. Our results provide insights into the remodeling of vasculature and the guidance for engineering vascularized tissue mimics.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10404-026-02939-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149176356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole Hintz, Christopher Johnson, Michael J. Vellekoop, Martina Hübner
{"title":"Fabrication and evaluation of self-aligned funnel inlets for DNA analysis in nanochannels","authors":"Nicole Hintz, Christopher Johnson, Michael J. Vellekoop, Martina Hübner","doi":"10.1007/s10404-026-02943-7","DOIUrl":"10.1007/s10404-026-02943-7","url":null,"abstract":"<div><p>A variety of DNA analysis techniques are enabled by linearization of the macromolecules through physical confinement in nanochannels. This work demonstrates the first nanolithography-free method for creating funneled inlets for nanochannels that are themselves fabricated without nanolithography. A self-aligning, anisotropic funnel etch step was introduced, which widens the entrance of the nanochannel by a factor of 10. Additionally, the shape of the funnel can be controlled by the etch parameters from an 8° inlet angle to 34°. Funneled inlets are suitable to reduce the entropic barrier and increase the amount of DNA molecules introduced into a nanochannel. The funnel etch can be done with XeF<sub>2</sub> when the nanochannels are surrounded by silicon nitride. Simulations of the electric field show how the introduced funnel can increase the capture rate of molecules by increasing the capture range by 20%. The funnels have been shown to bring DNA molecules into the nanochannels, where they are extended. This nanochannel and funnel etch method brings design freedom, while being a low-cost solution that is easily scalable for production of Lab-on-Chip DNA analysis systems.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10404-026-02943-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonlinear dynamics, hopf bifurcation, and optimal control of a pressure-driven microfluidic oscillator for lab-on-a-chip systems","authors":"Lakshmi N. Sridhar","doi":"10.1007/s10404-026-02944-6","DOIUrl":"10.1007/s10404-026-02944-6","url":null,"abstract":"<div><p>Microfluidic lab-on-a-chip systems have become indispensable in biomedical diagnostics, chemical analysis, and environmental monitoring owing to their ability to precisely manipulate minute fluid volumes within compact devices. However, the strong coupling between pressure, flow, and valve dynamics can introduce nonlinear oscillatory behavior that influences system performance and operational stability. In this study, a reduced-order nonlinear mathematical model of a pressure-driven microfluidic oscillator is developed to investigate the dynamic interactions among channel pressure, volumetric flow rate, and valve motion. Numerical continuation using MATCONT is employed to identify the stability characteristics of the system and to determine the onset of self-sustained oscillations. Two symmetry-induced supercritical Hopf bifurcation points are detected, and the associated stable limit cycles are computed to characterize the periodic operating regimes. The local stability of the equilibrium solutions is further examined through analytical Jacobian evaluation and eigenvalue analysis, confirming the transition from stable steady states to oscillatory behavior. To regulate these nonlinear dynamics, an optimal control problem is formulated and solved using PYOMO.DAE with IPOPT, where inlet pressure serves as the control variable. The control strategy minimizes overall system activity while reducing the actuation effort required for stable operation. The results demonstrate that incorporating bifurcation-aware constraints improves the control performance and reduces the objective function compared with conventional optimization. The proposed framework provides a systematic approach for analyzing and regulating nonlinear dynamics in pressure-driven microfluidic lab-on-a-chip systems, contributing to the development of stable, energy-efficient, and intelligent microfluidic devices.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrohydrodynamically driven liquid–liquid slug flow in a coaxial microreactor for intensified interfacial mass transfer and continuous extraction of rare-earth metals","authors":"Vahid Rafiei, Farshad Rahimi","doi":"10.1007/s10404-026-02945-5","DOIUrl":"10.1007/s10404-026-02945-5","url":null,"abstract":"<div><p>Rare-earth element (REE) recovery by solvent extraction is frequently constrained by slow interfacial mass transfer and the large footprint of conventional contactors. This work reports a coaxial microreactor in which liquid–liquid slug flow is actively controlled by an externally applied electrohydrodynamic (EHD) field to intensify Nd(III) extraction from an aqueous chloride solution into a di-(2-ethylhexyl)phosphoric acid (D2EHPA)–kerosene organic phase. A concentric capillary geometry with a needle electrode and a downstream ring electrode was energized with a DC voltage of up to 3 kV, generating a radial electric field across the aqueous–organic interface, promoting a measured reduction in interfacial tension (confirmed by direct pendant-drop tensiometry under the applied field, from 18.3 to 14.1 mN/m) and shorter slugs, with the specific interfacial area, calculated from the full end-cap-inclusive slug geometry, increasing from 1875 to 2222 m<sup>2</sup>/m<sup>3</sup>. Volumetric mass transfer coefficients increased nearly threefold, and extraction efficiency rose from 62.5% to 93.6% within a residence time of 82.8 s (full reactor length). A coupled computational fluid dynamics model of the electric field distribution was compared qualitatively with high-speed imaging of slug deformation. Dimensionless correlations relating the Sherwood number to Reynolds, capillary and Weber numbers were derived (R<sup>2</sup> = 0.96). Compared with mixer-settlers and conventional slug-flow microreactors, the EHD-assisted device achieved higher mass transfer rates at markedly shorter residence times.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Egor S. Goncharov, Artem V. Pripakhaylo, Lidia S. Foteeva, Rustam N. Magomedov
{"title":"Advanced microfluidic technologies in dispersion analysis of asphaltenes: a mini-review","authors":"Egor S. Goncharov, Artem V. Pripakhaylo, Lidia S. Foteeva, Rustam N. Magomedov","doi":"10.1007/s10404-026-02941-9","DOIUrl":"10.1007/s10404-026-02941-9","url":null,"abstract":"<div><p>This brief review analyzes existing microfluidic approaches for studying the precipitation and aggregation of petroleum asphaltenes under high-temperature and/or high-pressure conditions. Special focus is placed on instrumental designs suitable for reliably performing such studies, including microchip-based systems. Original contributions on the online visualization of asphaltene aggregation and precipitation processes are systematized, and the results are assessed for their potential to optimize technological processes for the processing and upgrading of heavy petroleum feedstocks.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in paper-based microfluidic devices fabrication techniques for rapid identification kits: a systematic literature review","authors":"Bondili Chiru Divya Bai, Reehana Shaik","doi":"10.1007/s10404-026-02940-w","DOIUrl":"10.1007/s10404-026-02940-w","url":null,"abstract":"<div><p>Paper-based microfluidic devices have surfaced as a potential rapid identification kit because of their affordability, portability and user-friendliness, making them vital for point-of-care diagnostics and monitoring of the environment. This review examines recent developments in paper-based microfluidic methods, focusing on fabrication techniques, applications in medical and biological diagnostics, environmental monitoring, and approaches to improve performance. Particular attention is given to nanomaterial integration and fluid control mechanisms, which are important to improve sensitivity and efficiency, and also study the current challenges faced and future trends in this domain. Key advancements highlighted include CRISPR-based integration for precise nucleic acid detection, optimization of point-of-care diagnostic applications for quick usability, hybrid nanostructures to enhance sensitivity, innovative signal amplification strategies, biodegradable materials for sustainability, and field-deployable designs customized for with low-resource areas. The review results reveal that paper-based microfluidics have been promisingly applied for the diagnosis of diseases, pollutant monitoring, and the detection of pathogens. Yet, limitations are persistent in signal amplification and reproducibility. To acknowledge these concerns, studies are conducted to fabricate the devices using hybrid materials, advancements in surface modification, and automation of fluid handling systems, which contribute to improving performance. The significance of this work lies in its ability to guide researchers and industry stakeholders toward designing next-generation paper-based microfluidic devices that maintain affordability with reliability, sensitivity, and accessibility. Through critical evaluation, this review offers information regarding future directions of paper-based microfluidic analytical devices, emphasizing the potential of this domain in point-of-care diagnostics and rapid identification kits in resource-limited areas.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chandra Bhushan, Amit Kumar, Ankit Shukla, Debayan Das
{"title":"Engineering passive flow control and hydrodynamic dispersion in paper-based microfluidics through thermal conditioning and residual saturation","authors":"Chandra Bhushan, Amit Kumar, Ankit Shukla, Debayan Das","doi":"10.1007/s10404-026-02942-8","DOIUrl":"10.1007/s10404-026-02942-8","url":null,"abstract":"<div><p>Paper-based microfluidic systems rely on capillary-driven flow through cellulose networks, where uncontrolled fluid spreading and hydrodynamic dispersion compromise reaction localization, analytical sensitivity, and assay reproducibility. Here, we demonstrate that thermal conditioning and residual saturation provide a simple passive strategy for regulating capillary flow and hydrodynamic dispersion without modifying membrane chemistry or device architecture. Four commercially available cellulose membranes (Dorsan 441, Dorsan 442, Whatman Grade 1, and Ashless) were systematically investigated under controlled thermal conditioning (30–80 °C) and prescribed residual saturation conditions obtained through membrane pre-drying (5–15 min). Time-resolved image analysis, integrated with wetting-front velocity, effective dispersion coefficient, Peclet number, capillary number and a Transport Quality Index (TQI), was used to quantify transport dynamics and flow localization. Moderate thermal conditioning (40 °C) and intermediate residual saturation (10 min drying) promoted synchronized pore filling, sharper reaction fronts, and improved flow confinement, while reducing hydrodynamic dispersion by up to 52% and substantially improving transport localization. Under controlled residual saturation, hydrodynamic dispersion was further regulated by up to 67% in Dorsan 442 and 53% in Ashless, demonstrating effective control of longitudinal spreading through passive substrate conditioning. Among the investigated membranes, Dorsan 442 exhibited the most robust transport performance, with TQI improving by 8.5-143.6% under thermal conditioning and 32.1–65.3% under varying residual saturation. These findings establish environmental conditioning as a practical passive flow control strategy for paper-based microfluidics and provide quantitative design guidelines for improving fluid handling, reaction localization, and assay reliability in capillary-driven microfluidic platforms.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149133280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of modified pump-free microfluidic system utilizing hydrostatic pressure on human cumulus cell culture: a model for long-term in vitro follicle growth","authors":"Thammawit Suwannaphan, Porntip Sirayapiwat, Alongkorn Pimpin, Akarawin Chaengsawang, Sadanan Summat, Paweena Thuwanut","doi":"10.1007/s10404-026-02938-4","DOIUrl":"10.1007/s10404-026-02938-4","url":null,"abstract":"<div><p>In this research, new design of modified pump-free microfluidic (MPFM) device was developed for long-term in vitro cell culture (IVC), serving as model for in vitro follicle growth (IVG). To evaluate device feasibility, mathematical model was developed to forecast media flow rate decrement driven by hydrostatic pressure. Implementation of designed MPFM achieved stable flow rate of approximately 0.0015 mL/min. For IVC study, cumulus cells were retrieved from six patients (35–39 years old) who present normal ovarian response to ovarian stimulation and undergoing in vitro fertilization. Pooled cumulus cells from each participant were equally divided into three groups; I) fresh, II) IVC under conventional culture system (control), and III) IVC under MPFM device. Cumulus cells, cultured for 10 d, were evaluated for total cell number, percentage of cell viability and relative gene expression levels (cell apoptotic marker: <i>Caspase−3</i>, <i>Caspase−9</i>, cell proliferation marker: <i>FOXL2</i> and follicle stimulating hormone receptor: <i>FSHR</i>). The major findings demonstrated that total cell number were increased by time of IVC <i>P</i> < 0.001). However, proportion of cell survival was decreased by culture period. Regarding relative gene expression levels, <i>Caspase−3</i> and <i>Caspase−9</i> expression levels in MPFM group were lower than control (<i>P</i> = 0.010 and <i>P</i> < 0.001, respectively). Additionally, relative expression levels of <i>FSHR</i> were comparable among cohorts. In conclusion, our current MPFM device could facilitate survival cascades and function of cumulus cells after 10 d of IVC. For extended culture period, next prototype should be developed as alternative model to improve reliability of long-term IVG.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design of metamodels of microcomponents to develop a microfluidic system and its optimization","authors":"Digvijay Ronge, Prashant Pawar, Ranjitsinha Gidde, Sachin Gavali","doi":"10.1007/s10404-026-02936-6","DOIUrl":"10.1007/s10404-026-02936-6","url":null,"abstract":"<div><p>This study presents a metamodel-based optimization framework specifically designed for a microfluidic system comprising two valveless micropumps and a T-shaped micromixer. Comprehensive high-fidelity simulations were conducted employing Computational Fluid Dynamics (CFD) grounded in the Finite Element Method to meticulously analyze the behavior of individual components. A regression-based metamodel was developed for the micromixer, while a Response Surface Methodology (RSM) was employed for the micropump. These component-level metamodels were subsequently integrated into a Simulink environment to establish a system-level model, facilitating efficient predictions of critical performance parameters, including flow rate, pressure drop, and mixing efficiency. Optimization of the system was executed utilizing a Genetic Algorithm, wherein the frequency and pressure amplitude of the micropump diaphragm were systematically varied. A collection of Pareto-optimal solutions was identified, with the optimal configuration achieving a mixing efficiency of 91.94% and a pressure drop of 3036.6 Pa at an actuation frequency of 25.3 Hz and an amplitude of 2.52 kPa. The results obtained from the Simulink-based model were validated against CFD simulations and further corroborated through experimental testing of a microfluidic prototype fabricated via soft lithography. This study underscores the efficacy of metamodeling and evolutionary algorithms in optimizing microfluidic systems at the system level and emphasizes the significant interdependence between micropump actuation and micromixing performance.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149034945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A lens-free wide-field microfluidic platform for blood cell counting: comparison of deterministic and deep learning methods","authors":"Deniz Dudukcu, Huseyin Kasci, Mehmet Yuksekkaya","doi":"10.1007/s10404-026-02937-5","DOIUrl":"10.1007/s10404-026-02937-5","url":null,"abstract":"<div><p>Complete blood count (CBC) testing is essential for clinical decision-making, but conventional analyzers are difficult to deploy in resource-limited and point-of-care settings. We present an in-house-developed, end-to-end lens-free wide-field microfluidic platform comprising an imaging module, a disposable laminated cartridge, and analysis software for red blood cell (RBC) enumeration from raw sensor-plane holograms. Cartridge characterization showed an 87.5% fabrication yield, 80.0% complete filling among successfully fabricated cartridges, and a mean filling time of 3.6 s. A deterministic image-processing pipeline and a YOLOv12 deep-learning detector were compared on the same holograms. Performance was evaluated using microscope-guided manual annotations of RBCs and visually confounding non-cell patterns directly on the holograms. Because true negatives are not naturally defined in instance-level detection, specificity is often omitted. Treating these patterns as hard negatives enabled specificity and accuracy to be reported alongside sensitivity, precision, and F1-score for both methods. Inter-observer agreement was high, with intraclass correlation coefficients of 0.962 for RBCs and 0.860 for hard negatives. YOLOv12 outperformed the deterministic pipeline (F1-score 0.882 vs. 0.834) and showed closer agreement with the clinical CBC reference (mean absolute percentage error [MAPE], 4.7% vs. 7.7%); manual counting yielded a MAPE of 1.3%. Without retraining, YOLOv12 retained lower MAPE on two additional independent samples (4.9% vs. 8.2% and 5.7% vs. 7.1%). These proof-of-concept findings support the technical feasibility of the lens-free microfluidic workflow and demonstrate the value of specificity-aware evaluation for distinguishing missed cells from spurious detections.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"30 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149034946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}