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Biosensors
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Microfluidics for Biomedical Applications (Volume II)
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Microfluidics for Biomedical Applications (Volume II)

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 8358

Special Issue Editors

Prof. Dr. Nan Xiang

E-Mail Website
Guest Editor
School of Mechanical Engineering, Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing 211189, China
Interests: inertial microfluidics; soft robotics; microfluidic cell separation; viscoelastic microfluidics; point-of-care testing device; microflow cytometer; microfluidic valve; dielectrophoresis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Zhonghua Ni

E-Mail Website
Guest Editor
School of Mechanical Engineering, Southeast University, Nanjing 211189, China
Interests: microfluidics; biomedical microdevices; biosensors
Special Issues, Collections and Topics in MDPI journals

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 are 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 of microfluidics for biomedical applications. Reviews and original research papers are welcome.

Prof. Dr. Nan Xiang
Prof. Dr. Zhonghua Ni
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 2700 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
  • cell manipulation and detection
  • point-of-care testing
  • lab on a chip
  • biomedical applications

Published Papers (6 papers)

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Research

17 pages, 3894 KiB  
Article
Analytical Validation of a Spiral Microfluidic Chip with Hydrofoil-Shaped Pillars for the Enrichment of Circulating Tumor Cells
by Begum Sen-Dogan, Mehmet Alper Demir, Buket Sahin, Ender Yildirim, Gizem Karayalcin, Sebnem Sahin, Ege Mutlu, Taylan Berkin Toral, Ebru Ozgur, Ozge Zorlu and Haluk Kulah
Biosensors 2023, 13(10), 938; https://doi.org/10.3390/bios13100938 - 19 Oct 2023
Viewed by 1550
Abstract
The isolation of circulating tumor cells (CTCs) from peripheral blood with high efficiency remains a challenge hindering the utilization of CTC enrichment methods in clinical practice. Here, we propose a microfluidic channel design for the size-based hydrodynamic enrichment of CTCs from blood in [...] Read more.
The isolation of circulating tumor cells (CTCs) from peripheral blood with high efficiency remains a challenge hindering the utilization of CTC enrichment methods in clinical practice. Here, we propose a microfluidic channel design for the size-based hydrodynamic enrichment of CTCs from blood in an epitope-independent and high-throughput manner. The microfluidic channel comprises a spiral-shaped part followed by a widening part, incorporating successive streamlined pillars, that improves the enrichment efficiency. The design was tested against two benchmark designs, a spiral microfluidic channel and a spiral microfluidic channel followed by a widening channel without the hydrofoils, by processing 5 mL of healthy blood samples spiked with 100 MCF-7 cells. The results proved that the design with hydrofoil-shaped pillars perform significantly better in terms of recovery (recovery rate of 67.9% compared to 23.6% in spiral and 56.7% in spiral with widening section), at a cost of slightly lower white blood cell (WBC) depletion (depletion rate of 94.2% compared to 98.6% in spiral and 94.2% in spiral with widening section), at 1500 µL/min flow rate. For analytical validation, the design was further tested with A549, SKOV-3, and BT-474 cell lines, yielding recovery rates of 62.3 ± 8.4%, 71.0 ± 6.5%, and 82.9 ± 9.9%, respectively. The results are consistent with the size and deformability variation in the respective cell lines, where the increasing size and decreasing deformability affect the recovery rate in a positive manner. The analysis before and after the microfluidic chip process showed that the process does not affect cell viability. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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12 pages, 4749 KiB  
Article
Establishment and Validation of an Integrated Microfluidic Step Emulsification Chip Supporting Droplet Digital Nucleic Acid Analysis
by Gangyin Luo, Ying Zhang, Shun Wang, Xinbei Lv, Tianhang Yang and Jinxian Wang
Biosensors 2023, 13(9), 888; https://doi.org/10.3390/bios13090888 - 18 Sep 2023
Viewed by 1047
Abstract
Uniform and stable droplet generation is critical for accurate and efficient digital nucleic acid analysis (dNAA). In this study, an integrated microfluidic step emulsification device with wide-range droplet generation capability, small device dimensions, convenient fabrication strategy, low contamination and high robustness was developed. [...] Read more.
Uniform and stable droplet generation is critical for accurate and efficient digital nucleic acid analysis (dNAA). In this study, an integrated microfluidic step emulsification device with wide-range droplet generation capability, small device dimensions, convenient fabrication strategy, low contamination and high robustness was developed. A tree-shaped droplet generation nozzle distribution design was proposed to increase the uniformity of droplet generation by equating flow rates, and the flow field in the design was numerically simulated. Theoretical analysis and comparative experiments on droplet size were performed regarding the influences of nozzle dimensions and surface properties. With incubation and hydrophobic reagent treatment, droplets as small as 73.1 μm were generated with multiplex nozzles of 18 μm (h) × 80 μm (w). The droplets were then collected into a standard PCR tube and an on-chip monolayer droplet collection chamber, without manual transfer and sample contamination. The oil-to-sample volume ratio in the PCR tube was recorded during collection. In the end, the droplets generated and collected using the microfluidic device proved to be stable and uniform for nucleic acid amplification and detection. This study provides reliable characteristic information for the design and fabrication of a micro-droplet generation device, and represents a promising approach for the realization of a three-in-one dNAA device under a step emulsification method. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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9 pages, 3986 KiB  
Communication
Development of a Microfluidic Chip System with Giant Magnetoresistance Sensor for High-Sensitivity Detection of Magnetic Nanoparticles in Biomedical Applications
by Tzong-Rong Ger, Pei-Sheng Wu, Wei-Jie Wang, Chiung-An Chen, Patricia Angela R. Abu and Shih-Lun Chen
Biosensors 2023, 13(8), 807; https://doi.org/10.3390/bios13080807 - 11 Aug 2023
Cited by 1 | Viewed by 1082
Abstract
Magnetic nanoparticles (MNPs) have been widely utilized in the biomedical field for numerous years, offering several advantages such as exceptional biocompatibility and diverse applications in biology. However, the existing methods for quantifying magnetic labeled sample assays are scarce. This research presents a novel [...] Read more.
Magnetic nanoparticles (MNPs) have been widely utilized in the biomedical field for numerous years, offering several advantages such as exceptional biocompatibility and diverse applications in biology. However, the existing methods for quantifying magnetic labeled sample assays are scarce. This research presents a novel approach by developing a microfluidic chip system embedded with a giant magnetoresistance (GMR) sensor. The system successfully detects low concentrations of MNPs with magnetic particle velocities of 20 mm/s. The stray field generated by the magnetic subject flowing through the microchannel above the GMR sensor causes variations in the signals. The sensor’s output signals are appropriately amplified, filtered, and processed to provide valuable indications. The integration of the GMR microfluidic chip system demonstrates notable attributes, including affordability, speed, and user-friendly operation. Moreover, it exhibits a high detection sensitivity of 10 μg/μL for MNPs, achieved through optimizing the vertical magnetic field to 100 Oe and the horizontal magnetic field to 2 Oe. Additionally, the study examines magnetic labeled RAW264.7 cells. This quantitative detection of magnetic nanoparticles can have applications in DNA concentration detection, protein concentration detection, and other promising areas of research. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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12 pages, 3081 KiB  
Article
Rapid Detection of Microparticles Using a Microfluidic Resistive Pulse Sensor Based on Bipolar Pulse-Width Multiplexing
by Ruiting Xu, Leixin Ouyang, Rubia Shaik, Heyi Chen, Ge Zhang and Jiang Zhe
Biosensors 2023, 13(7), 721; https://doi.org/10.3390/bios13070721 - 09 Jul 2023
Cited by 1 | Viewed by 1111
Abstract
Rapid and accurate analysis of micro/nano bio-objects (e.g., cells, biomolecules) is crucial in clinical diagnostics and drug discovery. While a traditional resistive pulse sensor can provide multiple kinds of information (size, count, surface charge, etc.) about analytes, it has low throughput. We present [...] Read more.
Rapid and accurate analysis of micro/nano bio-objects (e.g., cells, biomolecules) is crucial in clinical diagnostics and drug discovery. While a traditional resistive pulse sensor can provide multiple kinds of information (size, count, surface charge, etc.) about analytes, it has low throughput. We present a unique bipolar pulse-width, multiplexing-based resistive pulse sensor for high-throughput analysis of microparticles. Signal multiplexing is enabled by exposing the central electrode at different locations inside the parallel sensing channels. Together with two common electrodes, the central electrode encodes the electrical signal from each sensing channel, generating specific bipolar template waveforms with different pulse widths. Only one DC source is needed as input, and only one combined electrical output is collected. The combined signal can be demodulated using correlation analysis and a unique iterative cancellation scheme. The accuracy of particle counting and sizing was validated using mixtures of various sized microparticles. Results showed errors of 2.6% and 6.1% in sizing and counting, respectively. We further demonstrated its accuracy for cell analysis using HeLa cells. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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26 pages, 10732 KiB  
Article
Modeling of Paper-Based Bi-Material Cantilever Actuator for Microfluidic Biosensors
by Ashutosh Kumar, Hojat Heidari-Bafroui, Nassim Rahmani, Constantine Anagnostopoulos and Mohammad Faghri
Biosensors 2023, 13(6), 580; https://doi.org/10.3390/bios13060580 - 26 May 2023
Cited by 4 | Viewed by 1256
Abstract
This research explores the dynamics of a fluidically loaded Bi-Material cantilever (B-MaC), a critical component of μPADs (microfluidic paper-based analytical devices) used in point-of-care diagnostics. Constructed from Scotch Tape and Whatman Grade 41 filter paper strips, the B-MaC’s behavior under fluid imbibition is [...] Read more.
This research explores the dynamics of a fluidically loaded Bi-Material cantilever (B-MaC), a critical component of μPADs (microfluidic paper-based analytical devices) used in point-of-care diagnostics. Constructed from Scotch Tape and Whatman Grade 41 filter paper strips, the B-MaC’s behavior under fluid imbibition is examined. A capillary fluid flow model is formulated for the B-MaC, adhering to the Lucas–Washburn (LW) equation, and supported by empirical data. This paper further investigates the stress–strain relationship to estimate the modulus of the B-MaC at various saturation levels and to predict the behavior of the fluidically loaded cantilever. The study shows that the Young’s modulus of Whatman Grade 41 filter paper drastically decreases to approximately 20 MPa (about 7% of its dry-state value) upon full saturation. This significant decrease in flexural rigidity, in conjunction with the hygroexpansive strain and coefficient of hygroexpansion (empirically deduced to be 0.008), is essential in determining the B-MaC’s deflection. The proposed moderate deflection formulation effectively predicts the B-MaC’s behavior under fluidic loading, emphasizing the measurement of maximum (tip) deflection using interfacial boundary conditions for the B-MaC’s wet and dry regions. This knowledge of tip deflection will prove instrumental in optimizing the design parameters of B-MaCs. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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18 pages, 16982 KiB  
Article
Different Strategies for the Microfluidic Purification of Antibiotics from Food: A Comparative Study
by Lorenzo Lunelli, Martina Germanis, Lia Vanzetti and Cristina Potrich
Biosensors 2023, 13(3), 325; https://doi.org/10.3390/bios13030325 - 27 Feb 2023
Viewed by 1545
Abstract
The presence of residual antibiotics in food is increasingly emerging as a worrying risk for human health both for the possible direct toxicity and for the development of antibiotic-resistant bacteria. In the context of food safety, new methods based on microfluidics could offer [...] Read more.
The presence of residual antibiotics in food is increasingly emerging as a worrying risk for human health both for the possible direct toxicity and for the development of antibiotic-resistant bacteria. In the context of food safety, new methods based on microfluidics could offer better performance, providing improved rapidity, portability and sustainability, being more cost effective and easy to use. Here, a microfluidic method based on the use of magnetic microbeads specifically functionalized and inserted in polymeric microchambers is proposed. The microbeads are functionalized either with aptamers, antibodies or small functional groups able to interact with specific antibiotics. The setup of these different strategies as well as the performance of the different functionalizations are carefully evaluated and compared. The most promising results are obtained employing the functionalization with aptamers, which are able not only to capture and release almost all tetracycline present in the initial sample but also to deliver an enriched and simplified solution of antibiotic. These solutions of purified antibiotics are particularly suitable for further analyses, for example, with innovative methods, such as label-free detection. On the contrary, the on-chip process based on antibodies could capture only partially the antibiotics, as well as the protocol based on beads functionalized with small groups specific for sulfonamides. Therefore, the on-chip purification with aptamers combined with new portable detection systems opens new possibilities for the development of sensors in the field of food safety. Full article
(This article belongs to the Special Issue Microfluidics for Biomedical Applications (Volume II))
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