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Micromachines
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Microfluidic Chips for Biomedical Applications
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Microfluidic Chips for Biomedical Applications

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

Deadline for manuscript submissions: 31 January 2026 | Viewed by 10710

Special Issue Editors

Prof. Dr. Yung-Shin Sun

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Guest Editor
Department of Physics, Fu Jen Catholic University, New Taipei City 242062, Taiwan
Interests: biosensors; microfluidics; surface plasmon resonance; surface coating
Dr. Paul Hsieh-Fu Tsai

E-Mail Website
Guest Editor
Department of Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan
Interests: microfluidics; biointerfaces; organ-on-chips
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microfluidics involves the manipulation of fluids in a very small volume, providing precise control over tiny amounts of chemicals, cells, and various biomaterials. Due to the small scale of microfluidic chips, significantly less sample and reagent volumes are required, resulting in cost savings and reduced waste. In addition, microfluidics can perform many experiments in parallel, increasing the throughput and efficiency. Due to these and other unique advantages compared to conventional techniques, microfluidics has been applied to a wide range of biomedical applications. This Special Issue focuses on the latest technical innovations and advancements in microfluidics, with a particular emphasis on biomedical applications. Topics of interest include (but are not limited to) the following:

  • Cell analysis: directed cell migrations such as electrotaxis and chemotaxis;
  • Organ-on-a-chip;
  • Tissue engineering and regenerative medicine;
  • Drug development and screening;
  • Diagnostics and point-of-care testing;
  • Gene sequencing and molecular biology.

We look forward to receiving your submissions.

Prof. Dr. Yung-Shin Sun
Dr. Paul Hsieh-Fu Tsai
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microfluidics
  • lab-on-a-chip
  • organ-on-a-chip
  • microfabrication
  • μTAS
  • MEMS

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Published Papers (7 papers)

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Research

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13 pages, 4027 KiB  
Article
A Dialysis Membrane-Integrated Microfluidic Device for Controlled Drug Retention and Nutrient Supply
by Hajime Miyashita, Yuya Ito, Kenta Shinha, Hiroko Nakamura and Hiroshi Kimura
Micromachines 2025, 16(7), 745; https://doi.org/10.3390/mi16070745 - 25 Jun 2025
Viewed by 330
Abstract
Traditional pre-clinical drug evaluation methods, including animal experiments and static cell cultures using human-derived cells, face critical limitations such as interspecies differences, ethical concerns, and poor physiological relevance. More recently, microphysiological systems (MPSs) that use microfluidic devices to mimic in vivo conditions have [...] Read more.
Traditional pre-clinical drug evaluation methods, including animal experiments and static cell cultures using human-derived cells, face critical limitations such as interspecies differences, ethical concerns, and poor physiological relevance. More recently, microphysiological systems (MPSs) that use microfluidic devices to mimic in vivo conditions have emerged as promising platforms. By enabling perfusion cell culture and incorporating human-derived cells, MPSs can evaluate drug efficacy and toxicity in a more human-relevant manner. However, standard MPS protocols rely on discrete medium changes, causing abrupt changes in drug concentrations that do not reflect the continuous pharmacokinetics seen in vivo. To overcome this limitation, we developed a Dialysis Membrane-integrated Microfluidic Device (DMiMD) which maintains continuous drug concentrations through selective medium change via a dialysis membrane. The membrane’s molecular weight cut-off (MWCO) enables the retention of high-molecular-weight drugs while facilitating the passage of essential low-molecular-weight nutrients such as glucose. We validated the membrane’s molecular selectivity and confirmed effective nutrient supply using cells. Additionally, anticancer drug efficacy was evaluated under continuously changing drug concentrations, demonstrating that the DMiMD successfully mimics in vivo drug exposure dynamics. These results indicate that the DMiMD offers a robust in vitro platform for accurate assessment of drug efficacy and toxicity, bridging the gap between conventional static assays and the physiological complexities of the human body. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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14 pages, 2324 KiB  
Article
An Organ-on-a-Chip Modular Platform with Integrated Immunobiosensors for Monitoring the Extracellular Environment
by Anastasia Kanioura, Myrto Kyriaki Filippidou, Dimitra Tsounidi, Panagiota S. Petrou, Stavros Chatzandroulis and Angeliki Tserepi
Micromachines 2025, 16(7), 740; https://doi.org/10.3390/mi16070740 - 25 Jun 2025
Viewed by 370
Abstract
OoC systems employing human cells mirror the functionality of human organs and faithfully simulate their physiological microfluidic environment. Despite the potential of OoC technology in emulating tissue complexity, a significant gap persists in the continuous real-time monitoring of cellular behaviors and their responses [...] Read more.
OoC systems employing human cells mirror the functionality of human organs and faithfully simulate their physiological microfluidic environment. Despite the potential of OoC technology in emulating tissue complexity, a significant gap persists in the continuous real-time monitoring of cellular behaviors and their responses to external stimuli, arising from the lack of biosensors integrated onto OoC microfluidic platforms. Addressing this limitation constitutes the primary objective of this study. By developing and incorporating biosensors onto a modular integrated OoC platform, we aim to enable the monitoring of changes taking place in the cellular environment under various stimuli in real time. An in-series modular integration of a biosensor array into an OoC platform is demonstrated herein, along with its potential to sustain human cell proliferation and accommodate the detection of IL-6, as an example of a mediator protein secreted as part of the immune response to inflammation. The implementation of commercially fabricated PCB components also addresses the issue of cost efficiency and manufacturing scaling-up of sensor-integrated OoCs. This advancement will not only enhance the accuracy and reliability of preclinical studies, but also pave the way for improved drug development and disease treatment. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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24 pages, 10324 KiB  
Article
A Versatile Platform for Designing and Fabricating Multi-Material Perfusable 3D Microvasculatures
by Nathaniel Harris, Charles Miller and Min Zou
Micromachines 2025, 16(6), 691; https://doi.org/10.3390/mi16060691 - 8 Jun 2025
Viewed by 1256
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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28 pages, 10258 KiB  
Article
Microfluidic Chip for Quantitatively Assessing Hemorheological Parameters
by Yang Jun Kang
Micromachines 2025, 16(5), 567; https://doi.org/10.3390/mi16050567 - 8 May 2025
Viewed by 737
Abstract
The biomechanical properties of blood are regarded as promising biomarkers for monitoring early-stage abnormalities and disease progression. To detect any changes in blood, it is necessary to measure as many rheological properties as possible. Herein, a novel method is proposed for measuring multiple [...] Read more.
The biomechanical properties of blood are regarded as promising biomarkers for monitoring early-stage abnormalities and disease progression. To detect any changes in blood, it is necessary to measure as many rheological properties as possible. Herein, a novel method is proposed for measuring multiple rheological properties of blood using a microfluidic chip. The syringe pump turns off for 5 min to induce RBC (red blood cell) sedimentation in the driving syringe. RBC aggregation is determined by analyzing the time-lapse blood image intensity at stasis: I(t) = I1 exp (−k1t) + I2 exp (−k2t). RBC-rich blood and RBC-depleted blood are sequentially infused into the microfluidic chip. Based on blood pressure estimated with time-lapse blood velocity, blood viscosity is acquired with the Hagen–Poiseuille law. RBC sedimentation is quantified as RBC sedimentation distance (Xesr) and erythrocyte sedimentation rate (ESR). The proposed method provides a consistent viscosity compared with previous methods. Two of the four variables (I1, I2) exhibited a strong correlation with the conventional RBC aggregation index (AI). The indices Xesr and ESR showed consistent trends with respect to the blood medium and hematocrit. In conclusion, the proposed method is then regarded as effective for monitoring multiple rheological properties. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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22 pages, 6265 KiB  
Article
Flow-Induced Shear Stress Combined with Microtopography Inhibits the Differentiation of Neuro-2a Cells
by Eleftheria Babaliari, Paraskevi Kavatzikidou, Dionysios Xydias, Sotiris Psilodimitrakopoulos, Anthi Ranella and Emmanuel Stratakis
Micromachines 2025, 16(3), 341; https://doi.org/10.3390/mi16030341 - 16 Mar 2025
Viewed by 1449
Abstract
Considering that neurological injuries cannot typically self-recover, there is a need to develop new methods to study neuronal outgrowth in a controllable manner in vitro. In this study, a precise flow-controlled microfluidic system featuring custom-designed chambers that integrate laser-microstructured polyethylene terephthalate (PET) substrates [...] Read more.
Considering that neurological injuries cannot typically self-recover, there is a need to develop new methods to study neuronal outgrowth in a controllable manner in vitro. In this study, a precise flow-controlled microfluidic system featuring custom-designed chambers that integrate laser-microstructured polyethylene terephthalate (PET) substrates comprising microgrooves (MGs) was developed to investigate the combined effect of shear stress and topography on Neuro-2a (N2a) cells’ behavior. The MGs were positioned parallel to the flow direction and the response of N2a cells was evaluated in terms of growth and differentiation. Our results demonstrate that flow-induced shear stress could inhibit the differentiation of N2a cells. This microfluidic system could potentially be used as a new model system to study the impact of shear stress on cell differentiation. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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13 pages, 2230 KiB  
Article
A Droplet-Based Microfluidic Platform for High-Throughput Culturing of Yeast Cells in Various Conditions
by Min-Chieh Yu and Yung-Shin Sun
Micromachines 2024, 15(8), 1034; https://doi.org/10.3390/mi15081034 - 15 Aug 2024
Cited by 1 | Viewed by 2278
Abstract
Yeast plays a significant role in a variety of fields. In particular, it is extensively used as a model organism in genetics and cellular biology studies, and is employed in the production of vaccines, pharmaceuticals, and biofuels. Traditional “bulk”-based studies on yeast growth [...] Read more.
Yeast plays a significant role in a variety of fields. In particular, it is extensively used as a model organism in genetics and cellular biology studies, and is employed in the production of vaccines, pharmaceuticals, and biofuels. Traditional “bulk”-based studies on yeast growth often overlook cellular variability, emphasizing the need for single-cell analysis. Micro-droplets, tiny liquid droplets with high surface-area-to-volume ratios, offer a promising platform for investigating single or a small number of cells, allowing precise control and monitoring of individual cell behaviors. Microfluidic devices, which facilitate the generation of micro-droplets, are advantageous due to their reduced volume requirements and ability to mimic in vivo micro-environments. This study introduces a custom-designed microfluidic device to encapsulate yeasts in micro-droplets under various conditions in a parallel manner. The results reveal that optimal glucose concentrations promoted yeast growth while cycloheximide and Cu2+ ions inhibited it. This platform enhances yeast cultivation strategies and holds potential for high-throughput single-cell investigations in more complex organisms. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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Review

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32 pages, 5584 KiB  
Review
Recent Advancements in Metal–Organic Framework-Based Microfluidic Chips for Biomedical Applications
by Alemayehu Kidanemariam and Sungbo Cho
Micromachines 2025, 16(7), 736; https://doi.org/10.3390/mi16070736 - 24 Jun 2025
Viewed by 830
Abstract
The integration of metal–organic frameworks (MOFs) with microfluidic technologies has opened new frontiers in biomedical diagnostics and therapeutics. Microfluidic chips offer precise fluid control, low reagent use, and high-throughput capabilities features further enhanced by MOFs’ ample surface area, adjustable porosity, and catalytic activity. [...] Read more.
The integration of metal–organic frameworks (MOFs) with microfluidic technologies has opened new frontiers in biomedical diagnostics and therapeutics. Microfluidic chips offer precise fluid control, low reagent use, and high-throughput capabilities features further enhanced by MOFs’ ample surface area, adjustable porosity, and catalytic activity. Together, they form powerful lab-on-a-chip platforms for sensitive biosensing, drug delivery, tissue engineering, and microbial detection. This review highlights recent advances in MOF-based microfluidic systems, focusing on material innovations, fabrication methods, and diagnostic applications. Particular emphasis is placed on MOF nanozymes, which enhance biochemical reactions for multiplexed testing and rapid pathogen identification. Challenges such as stability, biocompatibility, and manufacturing scalability are addressed, along with emerging trends like responsive MOFs, AI-assisted design, and clinical translation strategies. By bridging MOF chemistry and microfluidic engineering, these systems hold great promise for next-generation biomedical technologies. Full article
(This article belongs to the Special Issue Microfluidic Chips for Biomedical Applications)
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