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Biosensors
Special Issues
Design, Fabrication, and Applications of Microfluidic Devices for Biosensing
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Design, Fabrication, and Applications of Microfluidic Devices for Biosensing

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

Deadline for manuscript submissions: closed (1 April 2025) | Viewed by 16583

Special Issue Editors

Dr. Lei Wu

E-Mail Website
Guest Editor
Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, China
Interests: lab on a chip; microfluidic chips
Dr. Xiang Qian

E-Mail Website
Guest Editor
Division of Advanced Manufacturing, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
Interests: microfluidic chips; flexible sensors and acuators

Special Issue Information

Dear Colleagues,

The main topic of this Special Issue is the design, fabrication, and applications of microfluidic devices for biosensing, and we aim to gather original articles and reviews showing research advances, fabrication, innovative applications, new challenges, and future perspectives in microfluidic devices for biosensing in biology, medicine, health, environmental monitoring, and more.

Microfluidic technology enables the automated pretreatment of samples, as well as the transportation of nanoliters or picoliters of solutions to designated biosensing sites. This facilitates high-throughput and automated detection in biosensors. Furthermore, the characteristics of microfluidics, such as the large specific surface area, can enhance the sensitivity of biosensors. Consequently, numerous biosensors incorporating microfluidic structures have been developed.

The objective of this Special Issue is to provide readers with an understanding of the potential of microfluidic technology in the development of biosensors, as well as an overview of the current challenges and opportunities in meeting application needs. The authors may include the fabrication processes for microfluidic devices. Indeed, the most conventional methods, e.g., PDMS on glass or SiO2, though successful in a laboratory setting, are not applicable on an industrial basis, which makes them very limited. Thus, reviews of alternative processes would be very interesting for readers.

Submissions may include, but are not limited to, the following topics:

  • sample-in–result-out  bioassay devices/point-of-care devices/diagnostic devices/healthcare medical devices;
  • devices for high-throughput, low-cost, and robust bioassays;
  • organ-on-a-chip models;
  • macro–micro interfaces for multiscale fluid handling, integration into experimental workflows, and coupling to analytical instruments;
  • reviews of fabrication processes that are more suitable for industrial production than conventional methods, e.g., PDMS on glass or SiO2;
  • microfluidic biosensing principles and devices for increased sensitivity.

Dr. Lei Wu
Dr. Xiang Qian
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. Biosensors 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 2200 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

  • microfluidic
  • biosensors
  • high-throughput
  • automation

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Published Papers (7 papers)

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Research

Jump to: Review

13 pages, 3541 KiB  
Article
Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
by Yuri M. Shlyapnikov and Elena A. Shlyapnikova
Biosensors 2025, 15(5), 316; https://doi.org/10.3390/bios15050316 - 15 May 2025
Viewed by 591
Abstract
The performance of heterophase immunoassays is often limited by the kinetics of analyte binding. This problem is partially solved by bead-based assays, which are characterized by rapid diffusion in the particle suspension. However, at low analyte concentrations, the binding rate is still low. [...] Read more.
The performance of heterophase immunoassays is often limited by the kinetics of analyte binding. This problem is partially solved by bead-based assays, which are characterized by rapid diffusion in the particle suspension. However, at low analyte concentrations, the binding rate is still low. Here, we demonstrate a further improvement of analyte binding kinetics in bead-based immunoassays by simultaneously concentrating both an analyte and magnetic beads in a compact spatial region where binding occurs. The analyte is electrophoretically concentrated in a flow cell where beads are magnetically retained and dragged along the channel by viscous force. The flow cell is integrated with a microarray-based signal detection module, where beads with bound analyte scan the microarray surface and are retained on it by single specific interactions, assuring ultra-high sensitivity of the method. Thus, a continuous flow assay system is formed. Its performance is demonstrated by simultaneous detection of model pathogen biomarkers, cholera toxin (CT) and staphylococcal enterotoxin B (SEB), with a detection limit of 0.1 fM and response time of under 10 min. The assay is capable of real-time online sample monitoring, as shown by a 12 h long continuous flow analysis of tap water for SEB and CT. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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12 pages, 2633 KiB  
Article
Rapid Microfluidic Ion-Exchange Optode System for Point-of-Care Determination of Sodium Concentration in Serum
by Kuan-Hsun Huang, Cheng-Xue Yu, Chia-Chun Lee, Chin-Chung Tseng and Lung-Ming Fu
Biosensors 2025, 15(2), 104; https://doi.org/10.3390/bios15020104 - 12 Feb 2025
Viewed by 1135
Abstract
A microfluidic system for detecting sodium ions (Na+) has been developed, incorporating a micro finger-pump chip and a micro-spectrometer platform to measure Na+ concentration in human serum. A small volume (10 μL) of serum sample is introduced into the microchip [...] Read more.
A microfluidic system for detecting sodium ions (Na+) has been developed, incorporating a micro finger-pump chip and a micro-spectrometer platform to measure Na+ concentration in human serum. A small volume (10 μL) of serum sample is introduced into the microchip and reacted with a preloaded reagent mixture through a two-step finger-pump actuation process. The resulting purple complex is directed into the detection area of the chip and analyzed using the micro-spectrometer at wavelengths of 555 and 666 nm. The Na+ concentration is then inversely derived from the measured A555/A666 absorbance ratio using self-written software installed on a Raspberry Pi. The entire detection process is completed in just 3 min, offering a significant advantage in meeting clinical needs compared to the traditional reporting turnaround time of several hours in medical institutions. The experimental results indicate a linear relationship between the measured absorbance ratio and Na+ concentration within the range of 1–200 mM, with a correlation coefficient of R2 = 0.9989. Additionally, the detection results from 60 serum samples collected from chronic kidney disease (CKD) patients showed a strong agreement with those obtained using the conventional indirect ion-selective electrode (ISE) method, achieving a correlation coefficient of R2 = 0.9885 and an average recovery rate of 99.4%. In summary, the proposed system provides a practical, affordable, and rapid alternative to conventional Na+ detection methods, making it highly promising for point-of-care (POC) testing applications. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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Graphical abstract

15 pages, 6331 KiB  
Article
Digital Melting Curve Analysis for Multiplex Quantification of Nucleic Acids on Droplet Digital PCR
by Xiaoqing Dai, Meng Cao and Zunliang Wang
Biosensors 2025, 15(1), 36; https://doi.org/10.3390/bios15010036 - 10 Jan 2025
Viewed by 1519
Abstract
We present a cost-effective and simple multiplex nucleic acid quantification method using droplet digital PCR (ddPCR) with digital melting curve analysis (MCA). This approach eliminates the need for complex fluorescent probe design, reducing both costs and dependence on fluorescence channels. We developed a [...] Read more.
We present a cost-effective and simple multiplex nucleic acid quantification method using droplet digital PCR (ddPCR) with digital melting curve analysis (MCA). This approach eliminates the need for complex fluorescent probe design, reducing both costs and dependence on fluorescence channels. We developed a convolutional neighborhood search algorithm to correct droplet displacement during heating, ensuring precise tracking and accurate extraction of melting curves. An experimental protocol for digital MCA on the ddPCR platform was established, enabling accurate quantification of six target pathogen genes using a single fluorescence channel, with an average accuracy of 85%. Our method overcomes the multiplexing limitations of ddPCR, facilitating its application in multi-target pathogen detection. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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12 pages, 2926 KiB  
Article
Rapid Microfluidic Biosensor for Point-of-Care Determination of Rheumatoid Arthritis via Anti-Cyclic Citrullinated Peptide Antibody Detection
by Wei-Yu Tai, To-Lin Chen, Hsing-Meng Wang and Lung-Ming Fu
Biosensors 2024, 14(11), 545; https://doi.org/10.3390/bios14110545 - 10 Nov 2024
Cited by 3 | Viewed by 1873
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes extensive damage to multiple organs and tissues and has no known cure. This study introduces a microfluidic detection platform that combines a microfluidic reaction chip with a micro-spectrometer to accurately detect the anti-cyclic [...] Read more.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes extensive damage to multiple organs and tissues and has no known cure. This study introduces a microfluidic detection platform that combines a microfluidic reaction chip with a micro-spectrometer to accurately detect the anti-cyclic citrullinated peptide antibody (anti-CCP Ab) biomarker, commonly associated with arthritis. The surface of the microfluidic reaction chip is functionalized using streptavidin to enable the subsequent immobilization of biotinylated-labeled cyclic citrullinated peptide (biotin–CCP) molecules through a streptavidin–biotin reaction. The modified chip is then exposed to anti-CCP Ab, second antibody conjugated with horseradish peroxidase (HRP) (2nd Ab-HRP), 3,3′,5,5′-tetramethylbenzidine (TMB), and a stop solution. Finally, the concentration of the anti-CCP Ab biomarker is determined by analyzing the optical density (OD) of the colorimetric reaction product at 450 nm using a micro-spectrometer. The detection platform demonstrated a strong correlation (R2 = 0.9966) between OD and anti-CCP Ab concentration. This was based on seven control samples with anti-CCP Ab concentrations ranging from 0.625 to 100 ng/mL. Moreover, for 30 artificial serum samples with unknown anti-CCP Ab concentrations, the biosensor achieves a correlation coefficient of (R2 = 0.9650). The proposed microfluidic detection platform offers a fast and effective method for accurately identifying and quantifying the anti-CCP Ab biomarker. Thus, it offers a valuable tool for the early diagnosis and monitoring of RA and its progression in point-of-care settings. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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15 pages, 2486 KiB  
Article
An Easy-to-Use Arrayed Brain–Heart Chip
by Xiyao Peng, Lei Wu, Qiushi Li, Yuqing Ge, Tiegang Xu and Jianlong Zhao
Biosensors 2024, 14(11), 517; https://doi.org/10.3390/bios14110517 - 22 Oct 2024
Viewed by 1945
Abstract
Multi-organ chips are effective at emulating human tissue and organ functions and at replicating the interactions among tissues and organs. An arrayed brain–heart chip was introduced whose configuration comprises open culture chambers and closed biomimetic vascular channels distributed in a horizontal pattern, separated [...] Read more.
Multi-organ chips are effective at emulating human tissue and organ functions and at replicating the interactions among tissues and organs. An arrayed brain–heart chip was introduced whose configuration comprises open culture chambers and closed biomimetic vascular channels distributed in a horizontal pattern, separated from each other by an endothelial barrier based on fibrin matrix. A 300 μm-high and 13.2 mm-long endothelial barrier surrounded each organoid culture chamber, thereby satisfying the material transport requirements. Numerical simulations were used to analyze the construction process of fibrin barriers in order to optimize the structural design and experimental manipulation, which exhibited a high degree of correlation with experiment results. In each interconnective unit, a cerebral organoid, a cardiac organoid, and endothelial cells were co-cultured stably for a minimum of one week. The permeability of the endothelial barrier and recirculating perfusion enabled cross talk between cerebral organoids and cardiac organoids, as well as between organoids and endothelial cells. This was corroborated by the presence of cardiac troponin I (cTnI) in the cerebral organoid culture chamber and the observation of cerebral organoid and endothelial cells invading the fibrin matrix after one week of co-culture. The arrayed chip was simple to manipulate, clearly visible under a microscope, and compatible with automated pipetting devices, and therefore had significant potential for application. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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14 pages, 5172 KiB  
Article
Fabrication of Patterned Magnetic Particles in Microchannels and Their Application in Micromixers
by Tianhao Li, Chen Yang, Zihao Shao, Ya Chen, Jiahui Zheng, Jun Yang and Ning Hu
Biosensors 2024, 14(9), 408; https://doi.org/10.3390/bios14090408 - 23 Aug 2024
Cited by 1 | Viewed by 1880
Abstract
Due to the extremely low Reynolds number, the mixing of substances in laminar flow within microfluidic channels primarily relies on slow intermolecular diffusion, whereas various rapid reaction and detection requirements in lab-on-a-chip applications often necessitate the efficient mixing of fluids within short distances. [...] Read more.
Due to the extremely low Reynolds number, the mixing of substances in laminar flow within microfluidic channels primarily relies on slow intermolecular diffusion, whereas various rapid reaction and detection requirements in lab-on-a-chip applications often necessitate the efficient mixing of fluids within short distances. This paper presents a magnetic pillar-shaped particle fabrication device capable of producing particles with planar shapes, which are then utilized to achieve the rapid mixing of multiple fluids within microchannels. During the particle fabrication process, a degassed PDMS chip provides self-priming capabilities, drawing in a UV-curable adhesive-containing magnetic powder and distributing it into distinct microwell structures. Subsequently, an external magnetic field is applied, and the chip is exposed to UV light, enabling the mass production of particles with specific magnetic properties through photo-curing. Without the need for external pumping, this chip-based device can fabricate hundreds of magnetic particles in less than 10 min. In contrast to most particle fabrication methods, the degassed PDMS approach enables self-priming and precise dispensing, allowing for precise control over particle shape and size. The fabricated dual-layer magnetic particles, featuring fan-shaped blades and disk-like structures, are placed within micromixing channels. By manipulating the magnetic field, the particles are driven into motion, altering the flow patterns to achieve fluid mixing. Under conditions where the Reynolds number in the chip ranges from 0.1 to 0.9, the mixing index for substances in aqueous solutions exceeds 0.9. In addition, experimental analyses of mixing efficiency for fluids with different viscosities, including 25 wt% and 50 wt% glycerol, reveal mixing indices exceeding 0.85, demonstrating the broad applicability of micromixers based on the rapid rotation of magnetic particles. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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Review

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16 pages, 2713 KiB  
Review
Machine Learning-Driven Innovations in Microfluidics
by Jinseok Park, Yang Woo Kim and Hee-Jae Jeon
Biosensors 2024, 14(12), 613; https://doi.org/10.3390/bios14120613 - 13 Dec 2024
Cited by 10 | Viewed by 3925
Abstract
Microfluidic devices have revolutionized biosensing by enabling precise manipulation of minute fluid volumes across diverse applications. This review investigates the incorporation of machine learning (ML) into the design, fabrication, and application of microfluidic biosensors, emphasizing how ML algorithms enhance performance by improving design [...] Read more.
Microfluidic devices have revolutionized biosensing by enabling precise manipulation of minute fluid volumes across diverse applications. This review investigates the incorporation of machine learning (ML) into the design, fabrication, and application of microfluidic biosensors, emphasizing how ML algorithms enhance performance by improving design accuracy, operational efficiency, and the management of complex diagnostic datasets. Integrating microfluidics with ML has fostered intelligent systems capable of automating experimental workflows, enabling real-time data analysis, and supporting informed decision-making. Recent advances in health diagnostics, environmental monitoring, and synthetic biology driven by ML are critically examined. This review highlights the transformative potential of ML-enhanced microfluidic systems, offering insights into the future trajectory of this rapidly evolving field. Full article
(This article belongs to the Special Issue Design, Fabrication, and Applications of Microfluidic Devices for Biosensing)
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