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Micromachines
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Application of Microfluidic Technology in Bioengineering
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Application of Microfluidic Technology in Bioengineering

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

Deadline for manuscript submissions: 31 August 2025 | Viewed by 12225

Special Issue Editors

Dr. Shuli Wang

E-Mail Website
Guest Editor
School of Electronic Science and Engineering, Xiamen University, Xiamen 361005, China
Interests: microfluidics; nanofluidics; liquid gating technology; bioinspired materials; micro-LED
Dr. Yigang Shen

E-Mail Website
Guest Editor
College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
Interests: microfluidics; colloid and interface science; biosensors

Special Issue Information

Dear Colleagues,

Microfluidic technology, also known as lab-on-a-chip technology, is a cutting-edge field of research that focuses on the manipulation and control of small volumes of fluids within micrometer-sized channels. This innovative field has gained significant attention due to its unique features, including miniaturization, integration, precision, automation, and versatility, make it a powerful tool for manipulating fluids and analyzing samples in various applications, such as biomedical engineering, chemistry, material, and environmental sciences, etc. The Special Issue focuses on the application of microfluidic technology in bioengineering. This Special Issue invites manuscripts (research papers, perspectives, and review articles) related to fabrication of microfluidic systems and their applications in bioengineering, including, but not limited to, diagnostics, biodetection, biosensors, bioseparation, biomaterial synthesis, gene engineering, cell analysis, drug screening, tissue engineering, regenerative medicine, personalized healthcare, etc. We also encourage submissions on the advanced fabrication technology and integration of microfluidics devices. We invite researchers and practitioners from academia and industry to submit their work to the Special Issue. We look forward to receiving your contributions and sharing the latest advances of the application of microfluidic technology in bioengineering with our readers.

Dr. Shuli Wang
Dr. Yigang Shen
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
  • micro/nanofabrication
  • micro electrical mechanical systems
  • 3D-printing
  • diagnostics
  • biodetection
  • biosensors
  • bioseparation
  • biomaterial
  • genomics
  • cell analysis
  • Point-of-Care Testing
  • drug screening
  • tissue engineering
  • regenerative medicine
  • personalized healthcare

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Published Papers (9 papers)

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Research

Jump to: Review

21 pages, 6597 KiB  
Article
Effects of Fiber Arrangement on Flow Characteristics Along a Four-Fiber Element of Fiber Extractors
by Oluwaseyi O. Ayeni, Holly A. Stretz and Ahmad Vasel-Be-Hagh
Micromachines 2025, 16(4), 425; https://doi.org/10.3390/mi16040425 - 1 Apr 2025
Viewed by 263
Abstract
Fiber extractors, as process-intensified equipment, facilitate many applications, such as the purification of oils. The development of high-fidelity computational models is crucial to optimize the design. However, simulating microscale flows around tens of thousands of microfiber arrays is computationally unfeasible. Thus, it is [...] Read more.
Fiber extractors, as process-intensified equipment, facilitate many applications, such as the purification of oils. The development of high-fidelity computational models is crucial to optimize the design. However, simulating microscale flows around tens of thousands of microfiber arrays is computationally unfeasible. Thus, it is necessary to identify smaller elements, consisting of only a few fibers, that can represent flow within massively arrayed fiber extractors. This study employed computational fluid dynamics to investigate different configurations of four-fiber elements to achieve this aim. Following previous modeling featuring flow around only one fiber, the goal was to understand how variations in inter-fiber distances affect the phase structures of a corn oil/water mixture, the steady-state interfacial surface area per unit of fluid volume, and the pressure drop along the flow direction. The study explored various total and relative flow rates and contact angles. The research characterized the flow as semi-restricted annular, noting the influence of neighboring fibers on phase complexity. The inter-fiber distance played a crucial role in generating high interfacial areas and reducing pressure. The chaotic nature of the slug interfaces facilitated intermixing between flows along different fibers. Interestingly, the specific interfacial area reached an optimum when the inter-fiber distance was between 10 and 50 μm. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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14 pages, 4861 KiB  
Article
Pico-Scale Digital PCR on a Super-Hydrophilic Microarray Chip for Multi-Target Detection
by Qingyue Xian, Jie Zhang, Yu Ching Wong, Yibo Gao, Qi Song, Na Xu and Weijia Wen
Micromachines 2025, 16(4), 407; https://doi.org/10.3390/mi16040407 - 30 Mar 2025
Viewed by 297
Abstract
The technology of digital polymerase chain reaction (dPCR) is rapidly evolving, yet current devices often suffer from bulkiness and cumbersome sample-loading procedures. Moreover, challenges such as droplet merging and partition size limitations impede efficiency. In this study, we present a super-hydrophilic microarray chip [...] Read more.
The technology of digital polymerase chain reaction (dPCR) is rapidly evolving, yet current devices often suffer from bulkiness and cumbersome sample-loading procedures. Moreover, challenges such as droplet merging and partition size limitations impede efficiency. In this study, we present a super-hydrophilic microarray chip specifically designed for dPCR, featuring streamlined loading methods compatible with micro-electro-mechanical systems (MEMS) technology. Utilizing hydrodynamic principles, our platform enables the formation of a uniform array of 120-pL independent reaction units within a closed channel. The setup allows for rapid reactions facilitated by an efficient thermal cycler and real-time imaging. We achieved absolute quantitative detection of hepatitis B virus (HBV) plasmids at varying concentrations, alongside multiple targets, including cancer mutation gene fragments and reference genes. This work highlights the chip’s versatility and potential applications in point-of-care testing (POCT) for cancer diagnostics. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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13 pages, 3683 KiB  
Article
Automatic Single-Cell Harvesting for Fetal Nucleated Red Blood Cell Isolation on a Self-Assemble Cell Array (SACA) Chip
by Hsin-Yu Yang, Che-Hsien Lin, Yi-Wen Hu, Chih-Hsuan Chien, Mu-Chi Huang, Chun-Hao Lai, Jen-Kuei Wu and Fan-Gang Tseng
Micromachines 2024, 15(12), 1515; https://doi.org/10.3390/mi15121515 - 20 Dec 2024
Cited by 1 | Viewed by 1233
Abstract
(1) Background: Fetal chromosomal examination is a critical component of modern prenatal testing. Traditionally, maternal serum biomarkers such as free β-human chorionic gonadotropin (Free β-HCG) and pregnancy-associated plasma protein A (PAPPA) have been employed for screening, achieving a detection rate of approximately 90% [...] Read more.
(1) Background: Fetal chromosomal examination is a critical component of modern prenatal testing. Traditionally, maternal serum biomarkers such as free β-human chorionic gonadotropin (Free β-HCG) and pregnancy-associated plasma protein A (PAPPA) have been employed for screening, achieving a detection rate of approximately 90% for fetuses with Down syndrome, albeit with a false positive rate of 5%. While amniocentesis remains the gold standard for the prenatal diagnosis of chromosomal abnormalities, including Down syndrome and Edwards syndrome, its invasive nature carries a significant risk of complications, such as infection, preterm labor, or miscarriage, occurring at a rate of 7 per 1000 procedures. Beyond Down syndrome and Edwards syndrome, other chromosomal abnormalities, such as trisomy of chromosomes 9, 16, or Barr bodies, pose additional diagnostic challenges. Non-invasive prenatal testing (NIPT) has emerged as a powerful alternative for fetal genetic screening by leveraging maternal blood sampling. However, due to the extremely low abundance of fetal cells in maternal circulation, NIPT based on fetal cells faces substantial technical challenges. (2) Methods: Fetal nucleated red blood cells (FnRBCs) were first identified in maternal circulation in a landmark study published in The Lancet in 1959. Due to their fetal origin and presence in maternal peripheral blood, FnRBCs represent an ideal target for non-invasive prenatal testing (NIPT). In this study, we introduce a novel self-assembled cell array (SACA) chip system, a microfluidic-based platform designed to efficiently settle and align cells into a monolayer at the chip’s base within five minutes using lateral flow dynamics and gravity. This system is integrated with a fully automated, multi-channel fluorescence scanning module, enabling the real-time imaging and molecular profiling of fetal cells through fluorescence-tagged antibodies. By employing a combination of Hoechst+/CD71+/HbF+/CD45− markers, the platform achieves the precise enrichment and isolation of FnRBCs at the single-cell level from maternal peripheral blood. (3) Results: The SACA chip system effectively reduces the displacement of non-target cells by 31.2%, achieving a single-cell capture accuracy of 97.85%. This isolation and enrichment system for single cells is well suited for subsequent genetic analysis. Furthermore, the platform achieves a high purity of isolated cells, overcoming the concentration detection limit of short tandem repeat (STR) analysis, demonstrating its capability for reliable non-invasive prenatal testing. (4) Conclusions: This study demonstrates that the SACA chip, combined with an automated image positioning system, can efficiently isolate single fetal nucleated red blood cells (FnRBCs) from 50 million PBMCs in 2 mL of maternal blood, completing STR analysis within 120 min. With higher purification efficiency compared to existing NIPT methods, this platform shows great promise for prenatal diagnostics and potential applications in other clinical fields. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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10 pages, 3898 KiB  
Article
Rapid Construction of Liquid-like Surfaces via Single-Cycle Polymer Brush Grafting for Enhanced Antifouling in Microfluidic Systems
by Feng Wu, Jing Xu, Yuanyuan Liu, Hua Sun, Lishang Zhang, Yixuan Liu, Weiwei Wang, Fali Chong, Dan Zou and Shuli Wang
Micromachines 2024, 15(10), 1241; https://doi.org/10.3390/mi15101241 - 9 Oct 2024
Viewed by 1205
Abstract
Liquid-like surfaces have demonstrated immense potential in their ability to resist cell adhesion, a critical requirement for numerous applications across various domains. However, the conventional methodologies for preparing liquid-like surfaces often entail a complex multi-step polymer brush modification process, which is not only [...] Read more.
Liquid-like surfaces have demonstrated immense potential in their ability to resist cell adhesion, a critical requirement for numerous applications across various domains. However, the conventional methodologies for preparing liquid-like surfaces often entail a complex multi-step polymer brush modification process, which is not only time-consuming but also presents significant challenges. In this work, we developed a single-cycle polymer brush modification strategy to build liquid-like surfaces by leveraging high-molecular-weight bis(3-aminopropyl)-terminated polydimethylsiloxane, which significantly simplifies the preparation process. The resultant liquid-like surface is endowed with exceptional slipperiness, effectively inhibiting bacterial colonization and diminishing the adherence of platelets. Moreover, it offers promising implications for reducing the dependency on anticoagulants in microfluidic systems constructed from PDMS, all while sustaining its antithrombotic attributes. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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18 pages, 3074 KiB  
Article
Model-Based Optimization of Solid-Supported Micro-Hotplates for Microfluidic Cryofixation
by Daniel B. Thiem, Greta Szabo and Thomas P. Burg
Micromachines 2024, 15(9), 1069; https://doi.org/10.3390/mi15091069 - 24 Aug 2024
Cited by 1 | Viewed by 1327
Abstract
Cryofixation by ultra-rapid freezing is widely regarded as the gold standard for preserving cell structure without artefacts for electron microscopy. However, conventional cryofixation technologies are not compatible with live imaging, making it difficult to capture dynamic cellular processes at a precise time. To [...] Read more.
Cryofixation by ultra-rapid freezing is widely regarded as the gold standard for preserving cell structure without artefacts for electron microscopy. However, conventional cryofixation technologies are not compatible with live imaging, making it difficult to capture dynamic cellular processes at a precise time. To overcome this limitation, we recently introduced a new technology, called microfluidic cryofixation. The principle is based on micro-hotplates counter-cooled with liquid nitrogen. While the power is on, the sample inside a foil-embedded microchannel on top of the micro-hotplate is kept warm. When the heater is turned off, the thermal energy is drained rapidly and the sample freezes. While this principle has been demonstrated experimentally with small samples (<0.5 mm2), there is an important trade-off between the attainable cooling rate, sample size, and heater power. Here, we elucidate these connections by theoretical modeling and by measurements. Our findings show that cooling rates of 106 K s−1, which are required for the vitrification of pure water, can theoretically be attained in samples up to ∼1 mm wide and 5 μm thick by using diamond substrates. If a heat sink made of silicon or copper is used, the maximum thickness for the same cooling rate is reduced to ∼3 μm. Importantly, cooling rates of 104 K s−1 to 105 K s−1 can theoretically be attained for samples of arbitrary area. Such rates are sufficient for many real biological samples due to the natural cryoprotective effect of the cytosol. Thus, we expect that the vitrification of millimeter-scale specimens with thicknesses in the 10 μm range should be possible using micro-hotplate-based microfluidic cryofixation technology. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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16 pages, 7181 KiB  
Article
Elasticity of Carrier Fluid: A Key Factor Affecting Mechanical Phenotyping in Deformability Cytometry
by Hassan Pouraria and Jessica P. Houston
Micromachines 2024, 15(7), 822; https://doi.org/10.3390/mi15070822 - 25 Jun 2024
Viewed by 1752
Abstract
Recently, microfluidics deformability cytometry has emerged as a powerful tool for high-throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints by exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for [...] Read more.
Recently, microfluidics deformability cytometry has emerged as a powerful tool for high-throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints by exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label-free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids, such as methylcellulose dissolved in phosphate-buffered saline, is significantly influential to the resulting cellular deformation. We conducted CFD simulations conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e., HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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17 pages, 2946 KiB  
Article
The Utilization of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System for the Purification and Sorting of Circulating Tumor Cells (CTCs) with Different Sizes
by Po-Yu Chu, Thi Ngoc Anh Nguyen, Ai-Yun Wu, Po-Shuan Huang, Kai-Lin Huang, Chia-Jung Liao, Chia-Hsun Hsieh and Min-Hsien Wu
Micromachines 2023, 14(12), 2170; https://doi.org/10.3390/mi14122170 - 29 Nov 2023
Cited by 7 | Viewed by 1730
Abstract
The analysis of circulating tumor cells (CTCs) at the molecular level holds great promise for several clinical applications. For this goal, the harvest of high-purity, size-sorted CTCs with different subtypes from a blood sample are important. For this purpose, a two-step CTC isolation [...] Read more.
The analysis of circulating tumor cells (CTCs) at the molecular level holds great promise for several clinical applications. For this goal, the harvest of high-purity, size-sorted CTCs with different subtypes from a blood sample are important. For this purpose, a two-step CTC isolation protocol was proposed, by which the immunomagnetic beads-based cell separation was first utilized to remove the majority of blood cells. After that, an optically induced dielectrophoresis (ODEP) microfluidic system was developed to (1) purify the CTCs from the remaining magnetic microbeads-bound blood cells and to (2) sort and separate the CTCs with different sizes. In this study, the ODEP microfluidic system was designed and fabricated. Moreover, its optimum operation conditions and performance were explored. The results exhibited that the presented technique was able to purify and sort the cancer cells with two different sizes from a tested cell suspension in a high-purity (93.5% and 90.1% for the OECM 1 and HA22T cancer cells, respectively) manner. Overall, this study presented a technique for the purification and sorting of cancer cells with different sizes. Apart from this application, the technique is also useful for other applications in which the high-purity and label-free purification and sorting of cells with different sizes is required. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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Review

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25 pages, 5051 KiB  
Review
Advances in Microfluidic Single-Cell RNA Sequencing and Spatial Transcriptomics
by Yueqiu Sun, Nianzuo Yu, Junhu Zhang and Bai Yang
Micromachines 2025, 16(4), 426; https://doi.org/10.3390/mi16040426 - 2 Apr 2025
Viewed by 563
Abstract
The development of micro- and nano-fabrication technologies has greatly advanced single-cell and spatial omics technologies. With the advantages of integration and compartmentalization, microfluidic chips are capable of generating high-throughput parallel reaction systems for single-cell screening and analysis. As omics technologies improve, microfluidic chips [...] Read more.
The development of micro- and nano-fabrication technologies has greatly advanced single-cell and spatial omics technologies. With the advantages of integration and compartmentalization, microfluidic chips are capable of generating high-throughput parallel reaction systems for single-cell screening and analysis. As omics technologies improve, microfluidic chips can now integrate promising transcriptomics technologies, providing new insights from molecular characterization for tissue gene expression profiles and further revealing the static and even dynamic processes of tissues in homeostasis and disease. Here, we survey the current landscape of microfluidic methods in the field of single-cell and spatial multi-omics, as well as assessing their relative advantages and limitations. We highlight how microfluidics has been adapted and improved to provide new insights into multi-omics over the past decade. Last, we emphasize the contributions of microfluidic-based omics methods in development, neuroscience, and disease mechanisms, as well as further revealing some perspectives for technological advances in translational and clinical medicine. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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18 pages, 3473 KiB  
Review
Recent Advances in Microfluidic-Based Extracellular Vesicle Analysis
by Jiming Chen, Meiyu Zheng, Qiaoling Xiao, Hui Wang, Caixing Chi, Tahui Lin, Yulin Wang, Xue Yi and Lin Zhu
Micromachines 2024, 15(5), 630; https://doi.org/10.3390/mi15050630 - 8 May 2024
Cited by 6 | Viewed by 2943
Abstract
Extracellular vesicles (EVs) serve as vital messengers, facilitating communication between cells, and exhibit tremendous potential in the diagnosis and treatment of diseases. However, conventional EV isolation methods are labor-intensive, and they harvest EVs with low purity and compromised recovery. In addition, the drawbacks, [...] Read more.
Extracellular vesicles (EVs) serve as vital messengers, facilitating communication between cells, and exhibit tremendous potential in the diagnosis and treatment of diseases. However, conventional EV isolation methods are labor-intensive, and they harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as the limited sensitivity and specificity of traditional EV analysis methods, hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, and low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the distinct advantages of microfluidic technology in enhancing the capture efficiency and precise targeting of extracellular vesicles (EVs). We also explore its analytical role in targeted detection. Furthermore, this review highlights the transformative impact of microfluidic technology on EV analysis, with the potential to achieve automated and high-throughput EV detection in clinical samples. Full article
(This article belongs to the Special Issue Application of Microfluidic Technology in Bioengineering)
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