Microfluidics for Biomedical Applications (3rd Edition)

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 5318

Special Issue Editor


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Guest Editor
School of Mechanical Engineering, Southeast University, Nanjing 211189, China
Interests: inertial microfluidics; soft robotics; microfluidic cell separation; viscoelastic microfluidics; point-of-care testing devices; microflow cytometer; microfluidic valve; dielectrophoresis
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Special Issue Information

Dear Colleagues,

Microfluidics is a technique for controlling the behavior of fluids or bioparticles in microscale channels or spaces. The advent of microfluidics has provided new insights in the fields of biomedical research and clinical diagnosis. Compared with conventional techniques, microfluidics offers various advantages, such as low sample consumption, high efficiency, small device footprint, multifunction integration, and high manipulation resolution. To date, microfluidics has been employed for a range of biomedical applications, such as efficient sample pretreatment, single-cell analysis, high-throughput microflow cytometry, organ-on-a-chip, and biosensing. As a result, great improvements have been achieved in modern biomedical diagnosis and research. For example, the isolation and detection of rare circulating tumor cells (CTCs) from the peripheral blood have served as a noninvasive “virtual and real-time liquid biopsy” and are of great significance for the early diagnosis, personalized treatment, and therapeutic efficacy monitoring of cancers. On the basis of these applications, various point-of-care testing (POCT) devices have been invented, among which some have been successfully commercialized. This Special Issue is devoted to the most recent technical innovations and developments in the area of microfluidics, particularly for biomedical applications.

Scope of the Special Issue:

  • Fluid and cell manipulation via microfluidics;
  • Novel channel invention for new applications;
  • Fabrication methods for new functions;
  • Microfluidics-based point-of-care testing (POCT) devices;
  • Microfluidics for biotarget sensing and single-cell analysis;
  • Application of microfluidics in biomedical applications.

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

Prof. Dr. Nan Xiang
Guest Editor

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Keywords

  • microfluidics
  • cell manipulation and detection
  • point-of-care testing
  • lab on a chip
  • biomedical applications

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Published Papers (6 papers)

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Research

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13 pages, 2825 KiB  
Article
A Facile Surface Modification Strategy for Antibody Immobilization on 3D-Printed Surfaces
by Brandi Binkley and Peng Li
Biosensors 2025, 15(4), 211; https://doi.org/10.3390/bios15040211 - 25 Mar 2025
Viewed by 282
Abstract
3D-printed microdevices have become increasingly important to the advancement of point-of-care (POC) immunoassays. Despite its great potential, using 3D-printed surfaces on the solid support for immunorecognition has been limited due to the non-ideal adsorption properties for many photocurable resins. In this work, we [...] Read more.
3D-printed microdevices have become increasingly important to the advancement of point-of-care (POC) immunoassays. Despite its great potential, using 3D-printed surfaces on the solid support for immunorecognition has been limited due to the non-ideal adsorption properties for many photocurable resins. In this work, we report a simple surface modification protocol that works for diverse commercial photocurable resins, improving ELISAs performed directly on 3D-printed devices. This surface modification strategy involves surface activation via air plasma followed by the one-step incubation of GLYMO-labeled streptavidin. We successfully immobilized biotinylated anti-activin A antibodies on the 3D-printed surfaces and performed the complete ELISA protocol on the 3D-printed surfaces. We demonstrated that this protocol achieved an improved performance over passive adsorption for ELISAs. The present method is also compatible with diverse commercial resins and works with both microwells and microchannels. Finally, this method demonstrated a comparable limit of detection to the ELISA performed using commercial microwells. We believe the simplicity and broad compatibility of the present surface modification strategy will facilitate the development of 3D-printed POC ELISA devices. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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16 pages, 3209 KiB  
Article
Low-Cost, Open-Source, High-Precision Pressure Controller for Multi-Channel Microfluidics
by Mart Ernits, Olavi Reinsalu, Andreas Kyritsakis, Veikko Linko and Veronika Zadin
Biosensors 2025, 15(3), 154; https://doi.org/10.3390/bios15030154 - 2 Mar 2025
Viewed by 791
Abstract
Microfluidics is a technology that manipulates liquids on the scales ranging from microliters to femtoliters. Such low volumes require precise control over pressures that drive their flow into the microfluidic chips. This article describes a custom-built pressure controller for driving microfluidic chips. The [...] Read more.
Microfluidics is a technology that manipulates liquids on the scales ranging from microliters to femtoliters. Such low volumes require precise control over pressures that drive their flow into the microfluidic chips. This article describes a custom-built pressure controller for driving microfluidic chips. The pressure controller features piezoelectrically controlled pressure regulation valves. As an open-source system, it offers high customizability and allows users to modify almost every aspect. The cost is roughly a third of what similar, alternative, commercially available piezoelectrically controlled pressure regulators could be purchased for. The measured output pressure values of the device vary less than 0.7% from the device’s reported pressure values when the requested pressure is between −380 and 380 mbar. Importantly, the output pressure the device creates fluctuates only ±0.2 mbar when the pressure is cycled between 10 and 500 mbar. The pressure reading accuracy and stability validation suggest that the device is highly feasible for many advanced (low-pressure) microfluidic applications. Here, we compare the main features of our device to commercially and non-commercially available alternatives and further demonstrate the device’s performance and accessibility in successful microfluidic hydrodynamic focusing (MHF)-based synthesis of large unilamellar vesicles (LUVs). Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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13 pages, 2954 KiB  
Article
A Microfluidic Paper-Based Device for Monitoring Urease Activity in Saliva
by Francisca T. S. M. Ferreira, António O. S. S. Rangel and Raquel B. R. Mesquita
Biosensors 2025, 15(1), 48; https://doi.org/10.3390/bios15010048 - 15 Jan 2025
Viewed by 1027
Abstract
Chronic Kidney Disease (CKD) is a disorder that affects over 10% of the global population, and that would benefit from innovative methodologies that would provide early detection. Since it has been reported that there are high levels of urease in CKD patients’ saliva, [...] Read more.
Chronic Kidney Disease (CKD) is a disorder that affects over 10% of the global population, and that would benefit from innovative methodologies that would provide early detection. Since it has been reported that there are high levels of urease in CKD patients’ saliva, this sample is a promising non-invasive alternative to blood for CKD detection and monitoring. This work introduces a novel 3D µPAD for quantifying urease activity in saliva in a range of 0.041–0.750 U/mL, with limits of detection and quantification of 0.012 and 0.041 U/mL, respectively. The device uses the urease in the sample to convert urea into ammonia, causing a colorimetric change in the bromothymol blue. The accuracy of the developed device was evaluated by comparing the measurements of several saliva samples (#13) obtained with the μPAD and with a commercially available kit. Stability studies were also performed to assess its functionality as a point-of-care methodology, and the device was stable for 4 months when stored in a vacuum. After the sample placement, it could be scanned within 40 min without providing significantly different results. The developed device quantifies urease activity in saliva within 30 min, providing a simple, portable, lab-free alternative to existing methodologies. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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Review

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26 pages, 3050 KiB  
Review
Advancements in Circulating Tumor Cell Detection for Early Cancer Diagnosis: An Integration of Machine Learning Algorithms with Microfluidic Technologies
by Ling An, Yi Liu and Yaling Liu
Biosensors 2025, 15(4), 220; https://doi.org/10.3390/bios15040220 - 29 Mar 2025
Viewed by 656
Abstract
Circulating tumor cells (CTCs) are vital indicators of metastasis and provide a non-invasive method for early cancer diagnosis, prognosis, and therapeutic monitoring. However, their low prevalence and heterogeneity in the bloodstream pose significant challenges for detection. Microfluidic systems, or “lab-on-a-chip” devices, have emerged [...] Read more.
Circulating tumor cells (CTCs) are vital indicators of metastasis and provide a non-invasive method for early cancer diagnosis, prognosis, and therapeutic monitoring. However, their low prevalence and heterogeneity in the bloodstream pose significant challenges for detection. Microfluidic systems, or “lab-on-a-chip” devices, have emerged as a revolutionary tool in liquid biopsy, enabling efficient isolation and analysis of CTCs. These systems offer advantages such as reduced sample volume, enhanced sensitivity, and the ability to integrate multiple processes into a single platform. Several microfluidic techniques, including size-based filtration, dielectrophoresis, and immunoaffinity capture, have been developed to enhance CTC detection. The integration of machine learning (ML) with microfluidic systems has further improved the specificity and accuracy of CTC detection, significantly advancing the speed and efficiency of early cancer diagnosis. ML models have enabled more precise analysis of CTCs by automating detection processes and enhancing the ability to identify rare and heterogeneous cell populations. These advancements have already demonstrated their potential in improving diagnostic accuracy and enabling more personalized treatment approaches. In this review, we highlight the latest progress in the integration of microfluidic technologies and ML algorithms, emphasizing how their combination has changed early cancer diagnosis and contributed to significant advancements in this field. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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31 pages, 5720 KiB  
Review
The Latest Advances in Microfluidic DLD Cell Sorting Technology: The Optimization of Channel Design
by Dan Fan, Yi Liu and Yaling Liu
Biosensors 2025, 15(2), 126; https://doi.org/10.3390/bios15020126 - 19 Feb 2025
Viewed by 1176
Abstract
Cell sorting plays a crucial role in both medical and biological research. As a key passive sorting technique in the field of microfluidics, deterministic lateral displacement (DLD) has been widely applied to cell separation and sorting. This review aims to summarize the latest [...] Read more.
Cell sorting plays a crucial role in both medical and biological research. As a key passive sorting technique in the field of microfluidics, deterministic lateral displacement (DLD) has been widely applied to cell separation and sorting. This review aims to summarize the latest advances in the optimization of channel design for microfluidic DLD cell sorting. First, we provide an overview of the design elements of microfluidic DLD cell sorting channels, focusing on key factors that affect separation efficiency and accuracy, including channel geometry, fluid dynamics, and the interaction between cells and channel surfaces. Subsequently, we review recent innovations and progress in channel design for microfluidic DLD technology, exploring its applications in biomedical fields and its integration with machine learning. Additionally, we discuss the challenges currently faced in optimizing channel design for microfluidic DLD cell sorting. Finally, based on existing research, we make a summary and put forward prospective views on the further development of this field. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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16 pages, 10256 KiB  
Review
Microfluidic Assays for CD4 T Lymphocyte Counting: A Review
by Zhuolun Meng, Hassan Raji, Mahtab Kokabi, Deng Zou, James Chan, Qihao Liu, Ruifeng Zhang and Mehdi Javanmard
Biosensors 2025, 15(1), 33; https://doi.org/10.3390/bios15010033 - 9 Jan 2025
Viewed by 1153
Abstract
CD4 T lymphocytes play a key role in initiating the adaptive immune response, releasing cytokines that mediate numerous signal transduction pathways across the immune system. Therefore, CD4 T cell counts are widely used as an indicator of overall immunological health. HIV, one of [...] Read more.
CD4 T lymphocytes play a key role in initiating the adaptive immune response, releasing cytokines that mediate numerous signal transduction pathways across the immune system. Therefore, CD4 T cell counts are widely used as an indicator of overall immunological health. HIV, one of the leading causes of death in the developing world, specifically targets and gradually depletes CD4 cells, making CD4 counts a critical metric for monitoring disease progression. As a result, accurately counting CD4 cells represents a pressing challenge in global healthcare. Flow cytometry remains the gold standard for enumerating CD4 T cells; however, flow cytometers are expensive, difficult to transport, and require skilled medical staff to prepare samples, operate the equipment, and interpret results. This highlights the critical need for novel, rapid, cost-effective, and portable methods of CD4 enumeration that are suitable for deployment in resource-limited countries. This review will survey and analyze emerging research in CD4 counting, with a focus on microfluidic systems, which represent a promising area of investigation. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))
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