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Microfluidics in Biomedical Research

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A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B：Biology and Biomedicine".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 13474

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Prof. Dr. Nan Xiang

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Guest Editor

School of Mechanical Engineering, Southeast University, Nanjing 211189, China
Interests: microfluidics; cell separation and detection; dielectrophoresis; point-of-care testing (POCT) devices
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Special Issue Information

Dear Colleagues,

Microfluidics can precisely manipulate fluids or bioparticles by creating channels with dimensions of tens of micrometers using microfabrication. Over the past few decades, microfluidics has made important contributions to many subject areas, from chemical science and biomedical engineering to information science. Especially for the area of biomedical research, microfluidics has been widely employed for sample preparation, single-cell analysis, molecular detection, and disease diagnosis. For example, the enrichment and detection of rare cells (e.g., circulating tumor cells and fetal nucleated red blood cells) from complex background cells provide insightful techniques for the liquid biopsy of cancer and non-invasive prenatal diagnosis. In addition, microfluidics can be used to develop rapid and cost-effective point-of-care testing (POCT) devices for the early diagnosis and control of the transmission of plagues (e.g., COVID-19). With the development of modern science, various new technologies (e.g., artificial intelligence, internet of things, and quantum detection) can be integrated with microfluidics to achieve new functions and improved performances. Up until now, various microfluidic devices or instruments have been successfully commercialized, which has reformed biomedical research.

Scope of the Special Issue:

AI for microfluidics;
New functions realized by microfluidics;
Novel fabrication techniques for microfluidics;
Fundamentals of microfluidics for biomedical research;
Biomedical instruments and point-of-care testing (POCT) devices based on microfluidics;
New applications of microfluidics for biomedical research.

This Special Issue aims to highlight the most recent advances in microfluidics in biomedical research. Reviews and original research papers are all welcome.

Prof. Dr. Nan Xiang
Guest Editor

Manuscript Submission Information

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Keywords

microfluidics
artificial intelligence
point-of-care testing devices or instruments
biomedical research
emerging techniques

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Published Papers (11 papers)

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Research

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17 pages, 6590 KB

Open AccessArticle

Nanogroove-Induced Enhancement of Neural Spike Activity in Stem Cell-Derived Networks

by Rahman Sabahi-Kaviani, Marina A. Shiryaeva and Regina Luttge

Micromachines 2026, 17(5), 524; https://doi.org/10.3390/mi17050524 - 25 Apr 2026

Viewed by 278

Abstract

Nanogrooves provide instructive cues to cells in culture. Several nanofabrication techniques have been developed to create biomimetic substrates, advancing our understanding of cell adhesion. Their integration into nervous system models highlights the critical role of the extracellular matrix (ECM) in developing functional tissue constructs for in vitro platforms such as Brain-on-Chip (BoC) and Nervous System-on-Chip (NoC). This study presents a nanofabrication approach that integrates photolithography and microtransfer molding (μTM) to pattern nanogrooves using photocurable polymer NOA81 onto microelectrode array (MEA) plates. The resulting nanogrooves exhibited a pattern periodicity of 976 nm and a ridge width of 232 nm, as confirmed by scanning electron microscopy and atomic force microscopy. We assessed the biocompatibility and functional impact of these modified substrates using human induced pluripotent stem cell (hiPSC)-derived neuronal cultures. Neurons cultured on nanogroove-modified MEAs exhibited aligned neural processes due to the anisotropic surface features and expressed vivid spiking behavior and higher burst frequency compared to randomly cultured neuronal networks. In conclusion, the proposed fabrication technique integrates nanogrooves with commercial MEAs using a combination of microtransfer molding and photolithography, resulting in modified culture substrates that enhance spike activity and network organization, aiding in the development of more in vivo-like neural models. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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10 pages, 28956 KB

Open AccessCommunication

Fabrication of Paper Microfluidic Chips via Wax Soft Lithography

by Xinyi Chen, Jie Zhou, Jiahua Zhong, Zitong Ye, Qinghao He, Hao Chen and Weijin Guo

Micromachines 2026, 17(5), 512; https://doi.org/10.3390/mi17050512 - 23 Apr 2026

Viewed by 374

Abstract

Paper-based microfluidic devices (μPADs) have attracted significant attention for point-of-care testing (POCT), environmental monitoring, and food safety due to their low cost, ease of use, and minimal instrument dependence. However, fabricating high-resolution and reproducible microchannels on paper remains challenging. Conventional methods such as wax printing, photolithography, and inkjet printing are limited by resolution or equipment cost. Here, we present a low-cost, high-resolution fabrication method for μPADs, termed wax soft lithography, which combines wax printing with soft lithography. Through this method, microchannels with a minimum width of 234 ± 62 μm were consistently produced, and complex patterns were successfully fabricated, demonstrating high precision and reproducibility. As a proof-of-concept demonstration of device functionality, the fabricated μPADs were used to detect glucose in spiked urine samples, showing a concentration-dependent colorimetric response. This method provides an effective route for rapid production of high-resolution μPADs in resource-limited settings. With further validation before practical applications, this method shows promise for future development in POCT. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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20 pages, 13658 KB

Open AccessArticle

A Smartphone-Driven Acoustic Platform for Non-Invasive Modulation of Cellular Behavior in Microfluidic Channels

by Giulia Valenti, Emanuela Cutuli, Francesca Guarino and Maide Bucolo

Micromachines 2026, 17(3), 329; https://doi.org/10.3390/mi17030329 - 6 Mar 2026

Cited by 1 | Viewed by 593

Abstract

In recent years, passive cell manipulation in microfluidic devices has emerged as a crucial tool for biomedical and biotechnological applications, allowing control over cell positioning and behavior without the need for chemical labels or complex external forces. However, achieving precise and tunable modulation of cell dynamics remains a challenge, particularly with low-cost and non-invasive methods. In this work, we present a novel approach that leverages controlled acousto-mechanical perturbations (AMPs) to modulate cell arrangement and behavior in microchannels. By coupling a smartphone-driven audio speaker with a microfluidic device, acoustic signals are converted into mechanical vibrations of the tubing, generating AMPs that interact with hydrodynamically driven flows. Experiments with yeast cells and silica beads under different flow conditions revealed that acoustic stimulation induced periodic flow dynamics, with yeast cells showing tunable, flow-dependent responses while inert particles exhibited weak and stable modulation. Frequency-domain analysis highlighted a dominant response synchronized with the applied acoustic protocol, accompanied by higher-frequency components characteristic of acoustic actuation. These results demonstrate that simple, low-cost acoustic actuation revealed distinct dynamical responses between rigid inert particles and deformable biological cells and enable label-free cellular manipulation. The proposed platform offers a versatile, non-invasive, and accessible approach for controlled cell manipulation in microfluidics. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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16 pages, 2411 KB

Open AccessArticle

Single-Imaging Parasite-Quantification Microfluidic Device for Detection and Analysis of Schistosoma Eggs in Urine

by Heaven D. Chitemo, Vyacheslav R. Misko, Matthieu Briet, Jeffer Bhuko, Filip Legein, Humphrey D. Mazigo and Wim De Malsche

Micromachines 2026, 17(2), 270; https://doi.org/10.3390/mi17020270 - 22 Feb 2026

Viewed by 532

Abstract

The accurate diagnosis of schistosomiasis for effective disease surveillance, treatment, and follow-up is crucial to attain the World Health Organization’s 2030 goal to eliminate schistosomiasis as a public health problem. The current diagnostic tools for urinary schistosomiasis, including the gold standard urine filtration test, have been reported to show low sensitivity in detecting low-intensity infections, which, when missed, act as reservoirs for infections—an evident gap in endemic areas where preventive chemotherapy reduces infection intensities. This study assessed the laboratory-based performance of the newly developed urinary Single Imaging Parasite Quantification chip for Schistosoma haematobium egg detection across different infection intensities. Two designs of the urinary chips were evaluated using polystyrene particles as a model for Schistosoma haematobium eggs, where the prototype design effectively captured the particles in the field of view with 96.00% to 100% efficiency. The second-generation chip, while eliminating the need for the air-drying step that was necessary in the operation of the prototype chip, similarly showed high capture efficiencies (95.20% to 96.00%). Overall, the prototype chip slightly outperformed the second-generation chip, and this difference was statistically significant (unpaired t-test, p = 0.0319). Testing of the prototype chip with spiked goat urine maintained high efficiencies of 99.33% to 100%. Similarly, both chip designs could trap real Schistosoma haematobium eggs in their fields of view, demonstrating their potential as diagnostic platforms that can contribute to improved diagnostics, disease surveillance, and monitoring. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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17 pages, 2934 KB

Open AccessFeature PaperEditor’s ChoiceArticle

A Microfluidic Platform for Viscosity Testing of Non-Newtonian Fluids in Engineering and Biomedical Applications

by Yii-Nuoh Chang and Da-Jeng Yao

Micromachines 2026, 17(2), 201; https://doi.org/10.3390/mi17020201 - 1 Feb 2026

Viewed by 1117

Abstract

This study presents a microfluidic platform for non-Newtonian fluid viscosity sensing, integrating a high-flow-rate flow field stabilizer to mitigate flow uniformity limitations under elevated flow rate conditions. Building upon an established dual-phase laminar flow principle that determines relative viscosity via channel occupancy, this research aimed to extend the measurable viscosity range from 1–10 cP to 1–50 cP, which covers viscosity regimes relevant to biomedical fluids, dairy products during gelation, and low-to-moderate viscosity industrial liquids. A flow stabilizer was developed through computational fluid dynamics simulations, optimizing three key design parameters: blocker position, porosity, and the number of outlet paths. The N5 design proved most effective, providing over 50% reduction in standard deviation for asymmetric velocity distribution in high-flow simulations. The system was validated using simulated blood and dairy samples, achieving over 95% viscosity accuracy with less than 5% sample volume error compared to conventional viscometers. The chip successfully captured viscosity transitions during milk acidification and gelation, demonstrating excellent agreement with standard measurements. This low-volume, high-precision platform offers promising potential for applications in food engineering, biomedical diagnostics, and industrial fluid monitoring, enhancing microfluidic rheometry capabilities. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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20 pages, 28708 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Nervous System-on-Chip: Innovative Microfluidic Platform to Compartmentalize hiPSC-Derived Neural Networks

by Rahman Sabahi-Kaviani, Antigoni Gogolou, Celine Souilhol, Mark van der Kroeg, Steven A. Kushner, Femke M. S. de Vrij, Anestis Tsakiridis and Regina Luttge

Micromachines 2026, 17(2), 199; https://doi.org/10.3390/mi17020199 - 1 Feb 2026

Viewed by 1526

Abstract

This study presents the development of a Nervous System-on-Chip (NoC) using microfabrication techniques, focusing on the integration of human induced pluripotent stem cell (hiPSC)-derived neurons. We designed and fabricated NoCs based on microtunnel devices (MDs) with radial and linear configurations to facilitate the compartmentalized culture of cortical and enteric neural networks. Our findings demonstrate that these MDs allow axonal growth while restricting migration of somas and dendrites between compartments, thereby promoting the formation of organized neural networks. This creates a microfluidic platform capable of supporting the growth of different culture systems, which could potentially be combined to study interactions between the central and enteric nervous systems. The resulting neuronal networks exhibited viability, expression of key lineage markers, and synapse formation, highlighting the platform’s potential for advanced nervous system modeling. MD-based NoC models provide an innovative microfluidic platform for studying the biology of human neural networks, with implications for the investigation of neurodegenerative diseases such as Parkinson’s Disease and applications in pre-clinical research. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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23 pages, 5718 KB

Open AccessArticle

3D-Printed Microfluidic Chip System with Integrated Fluidic Breakers and Phaseguide Fluid Structures for Optimal Passive Mixing

by Christian Neubert, Tim Brauckhoff, Frank T. Hufert, Manfred Weidmann and Gregory Dame

Micromachines 2026, 17(2), 193; https://doi.org/10.3390/mi17020193 - 31 Jan 2026

Viewed by 711

Abstract

3D printing offers great potential for rapid and cost-effective fabrication of microfluidic lab-on-a-chip systems. Through a comparative approach, we implemented staggered herringbone mixer (SHM), Tesla mixer, and split and recombine mixer (SAR), along with a basic unperturbed channel into one chip and performed comparative mixing efficiency experiments. We also introduced a phaseguide-based, T-shaped stop structure at the Y-shaped inlets for bubble-free and parallel filling. The structures were analyzed with two poorly mixable dye solutions at flow rates ranging from 1 µL/min to 200 µL/min. The mixing efficiency was evaluated using optical gray value analysis and compared against diffusion-based mixing. The fluid-aligning phaseguides in the 3D-printed system were shown to work. Among the three different mixing structures tested, SHM exhibited the best mixing efficiency at all tested flow rates. Uniformly designed SHM structures contain a region of poor mixing between the two zones of turbulence. In a non-uniform design, fluid breakers were placed between two SHM units to redirect poorly mixed fluids to the edges, resulting in 100% mixing efficiency across all measured flow rates. These results, especially SHM with fluid breakers, support the development of cost-effective injection-molded lab-on-a-chip systems with improved mixing functionalities at close range instead of simple long-length meandric systems. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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24 pages, 12560 KB

Open AccessArticle

Impact of Magnetohydrodynamics on Thermal Mixing Efficiency and Entropy Generation Analysis Passing Through a Micromixer Using Non-Newtonian Nanofluid

by Naas Toufik Tayeb, Youcef Abdellah Ayoub Laouid, Ayache Lakhdar, Telha Mostefa, Sun Min Kim and Shakhawat Hossain

Micromachines 2026, 17(1), 66; https://doi.org/10.3390/mi17010066 - 31 Dec 2025

Viewed by 949

Abstract

The present paper investigates the steady laminar flow and thermal mixing performance of non-Newtonian Al₂O₃ nanofluids within a two-layer cross-channel micromixer, employing three-dimensional numerical simulations to solve the governing equations across a low Reynolds number range (0.1 to 50). It also addresses secondary flows and thermal mixing performance with two distinct inlet temperatures for thin nanofluids. Additionally, it explores how fluid properties and varying concentrations of Al₂O₃ nanoparticles impact thermal mixing efficiency and entropy generation. Simulations were conducted to optimize performance by adjusting the power law index (n) across different nanoparticle concentrations (1–5%). The findings show that magnetohydrodynamics can enhance mixing efficiency by generating vortices and altering flow behavior, providing important guidance for improving microfluidic system designs in practical applications. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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13 pages, 3501 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Channel-Free Micro-Well–Template-Assisted Magnetic Particle Trapping for Efficient Single-Particle Isolation

by Jin-Yeong Park, Kyeong-Taek Nam, Young-Ho Nam, Yong-Kweon Kim, Seung-Ki Lee and Jae-Hyoung Park

Micromachines 2025, 16(12), 1397; https://doi.org/10.3390/mi16121397 - 11 Dec 2025

Viewed by 1008

Abstract

This study presents a channel-free, micro-well–template-assisted magnetic particle trapping method for efficient single-particle isolation without the need for microfluidic channels. Dual-surface silicon micro-well arrays were fabricated using photolithography, PE-CVD, and DRIE processes, featuring hydrophilic well interiors and hydrophobic outer surfaces to enhance trapping performance. The proposed method combines magnet-assisted sedimentation with rotational sweeping of a glass slide placed above the micro-well array, enabling rapid and uniform particle confinement within a 250 × 250 well array. Experimental results showed that the trapping efficiency increased with the well width and depth, achieving over 93.8% within three trapping cycles for optimized structures. High single-particle occupancy was obtained for wells of comparable size to the particle diameter, while deeper wells enabled stable trapping with minimal loss. The entire trapping process was completed within five minutes per cycle, demonstrating a rapid, simple, and scalable approach applicable to digital immunoassay systems for ultrasensitive biomolecule detection. Full article

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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Review

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26 pages, 1113 KB

Open AccessReview

Organ-on-a-Chip Models of the Female Reproductive System: Current Progress and Future Perspectives

by Min Pan, Huike Chen, Kai Deng and Ke Xiao

Micromachines 2025, 16(10), 1125; https://doi.org/10.3390/mi16101125 - 30 Sep 2025

Cited by 9 | Viewed by 4423

Abstract

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

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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Other

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30 pages, 1982 KB

Open AccessPerspective

Microfluidic Paper-Based Devices at the Edge of Real Samples: Fabrication Limits, Hybrid Detection, and Perspectives

by Hsing-Meng Wang, Sheng-Zhuo Lee and Lung-Ming Fu

Micromachines 2026, 17(1), 105; https://doi.org/10.3390/mi17010105 - 13 Jan 2026

Cited by 3 | Viewed by 1148

Abstract

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

(This article belongs to the Special Issue Microfluidics in Biomedical Research)

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