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Biosensors
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Application of Microfluidics in Cell Manipulation and Biosensing
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Application of Microfluidics in Cell Manipulation and Biosensing

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

Deadline for manuscript submissions: 31 July 2025 | Viewed by 20189

Special Issue Editors

Dr. Yupan Wu

E-Mail Website
Guest Editor
School of Microelectronics, Northwestern Polytechnical University, Xi’an 710072, China
Interests: lab on a chip; biochemical sensor; analytical chemistry; cell separation; microfluidics
Special Issues, Collections and Topics in MDPI journals
Dr. Ye Tian

E-Mail Website
Guest Editor
College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 02115-5005, China
Interests: microfluidics; soft materials; flexible electronics; sensors and probes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, point-of-care applications and high-throughput screening in the healthcare and pharmaceutical industries have resulted in the rapid development of microfluidic systems for cell biology and disease diagnostics. The microfluidic method has attracted significant attention in biological and chemical applications, especially in cell manipulation, mixing, and biosensing, due to its distinctive advantages.

Recent advances in microfluidics, such as the development of point-of-care devices for isolating bioparticles (cancer cells, exosomes, and nanoparticles), microfluidic systems for biosensing and mixing, and cell patterning and culturing using acoustic radiation force and the 3D characterization of cells, address many of the limitations of conventional methods.

In this Special Issue, we would like to invite, but not be limited to, the submission of research on the development of technologies and devices using the microfluidic method for bio/chemical analyses, such as cell manipulation, immunoassay sensors, cell rotating, cell sorting, cell patterning systems, and biosensing. Meanwile, immunoassay sensors and cell manipulation devices using acoustofluidic, electric, magnetic, and optofluidic approaches, as well as the discussion of potential opportunities and challenges of these fields, are also welcome. We encourage you to submit your manuscript with us and publish it.

Dr. Yupan Wu
Dr. Ye Tian
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

  • microfluidic chip
  • immunoassays
  • cell manipulation
  • biosensing
  • acoustofluidics

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Published Papers (9 papers)

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Research

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11 pages, 1982 KiB  
Article
Paper-Based Microfluidic Device for Extracellular Lactate Detection
by Yan Nan, Peng Zuo and Bangce Ye
Biosensors 2024, 14(9), 442; https://doi.org/10.3390/bios14090442 - 14 Sep 2024
Viewed by 1144
Abstract
Lactate is a critical regulatory factor secreted by tumors, influencing tumor development, metastasis, and clinical prognosis. Precise analysis of tumor-cell-secreted lactate is pivotal for early cancer diagnosis. This study describes a paper-based microfluidic chip to enable the detection of lactate levels secreted externally [...] Read more.
Lactate is a critical regulatory factor secreted by tumors, influencing tumor development, metastasis, and clinical prognosis. Precise analysis of tumor-cell-secreted lactate is pivotal for early cancer diagnosis. This study describes a paper-based microfluidic chip to enable the detection of lactate levels secreted externally by living cells. Under optimized conditions, the lactate biosensor can complete the assay in less than 30 min. In addition, the platform can be used to distinguish lactate secretion levels in different cell lines and can be applied to the screening of antitumor drugs. Through enzymatic chemical conversion, this platform generates fluorescent signals, enabling qualitative assessment under a handheld UV lamp and quantitative analysis via grayscale intensity measurements using ImageJ (Ver. 1.50i) software. The paper-based platform presented in this study is rapid and highly sensitive and does not necessitate other costly and intricate instruments, thus making it applicable in resource-constrained areas and serving as a valuable tool for investigating cell lactate secretion and screening various anti-cancer drugs. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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12 pages, 2744 KiB  
Article
Concentration of Microparticles/Cells Based on an Ultra-Fast Centrifuge Virtual Tunnel Driven by a Novel Lamb Wave Resonator Array
by Wei Wei, Zhaoxun Wang, Bingnan Wang, Wei Pang, Qingrui Yang and Xuexin Duan
Biosensors 2024, 14(6), 280; https://doi.org/10.3390/bios14060280 - 29 May 2024
Viewed by 1205
Abstract
The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and biomedical operations. Microfluidic centrifugation, a key component of LOC devices, enables rapid capture and enrichment of tiny objects in samples, improving sensitivity [...] Read more.
The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and biomedical operations. Microfluidic centrifugation, a key component of LOC devices, enables rapid capture and enrichment of tiny objects in samples, improving sensitivity and accuracy of detection and diagnosis. However, microfluidic systems face challenges due to viscosity dominance and difficulty in vortex formation. Acoustic-based centrifugation, particularly those using surface acoustic waves (SAWs), have shown promise in applications such as particle concentration, separation, and droplet mixing. However, challenges include accurate droplet placement, energy loss from off-axis positioning, and limited energy transfer from low-frequency SAW resonators, restricting centrifugal speed and sample volume. In this work, we introduce a novel ring array composed of eight Lamb wave resonators (LWRs), forming an Ultra-Fast Centrifuge Tunnel (UFCT) in a microfluidic system. The UFCT eliminates secondary vortices, concentrating energy in the main vortex and maximizing acoustic-to-streaming energy conversion. It enables ultra-fast centrifugation with a larger liquid capacity (50 μL), reduced power usage (50 mW) that is one order of magnitude smaller than existing devices, and greater linear speed (62 mm/s), surpassing the limitations of prior methods. We demonstrate successful high-fold enrichment of 2 μm and 10 μm particles and explore the UFCT’s potential in tissue engineering by encapsulating cells in a hydrogel-based micro-organ with a ring structure, which is of great significance for building more complex manipulation platforms for particles and cells in a bio-compatible and contactless manner. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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10 pages, 1857 KiB  
Communication
A Multi-Drug Concentration Gradient Mixing Chip: A Novel Platform for High-Throughput Drug Combination Screening
by Jiahao Fu, Yibo Feng, Yu Sun, Ruiya Yi, Jing Tian, Wei Zhao, Dan Sun and Ce Zhang
Biosensors 2024, 14(5), 212; https://doi.org/10.3390/bios14050212 - 23 Apr 2024
Viewed by 2015
Abstract
Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, [...] Read more.
Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors—epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)—on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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17 pages, 2738 KiB  
Article
Multi-Functional Nano-Doped Hollow Fiber from Microfluidics for Sensors and Micromotors
by Yanpeng Wang, Zhaoyang Wang, Haotian Sun, Tong Lyu, Xing Ma, Jinhong Guo and Ye Tian
Biosensors 2024, 14(4), 186; https://doi.org/10.3390/bios14040186 - 10 Apr 2024
Cited by 2 | Viewed by 1778
Abstract
Nano-doped hollow fiber is currently receiving extensive attention due to its multifunctionality and booming development. However, the microfluidic fabrication of nano-doped hollow fiber in a simple, smooth, stable, continuous, well-controlled manner without system blockage remains challenging. In this study, we employ a microfluidic [...] Read more.
Nano-doped hollow fiber is currently receiving extensive attention due to its multifunctionality and booming development. However, the microfluidic fabrication of nano-doped hollow fiber in a simple, smooth, stable, continuous, well-controlled manner without system blockage remains challenging. In this study, we employ a microfluidic method to fabricate nano-doped hollow fiber, which not only makes the preparation process continuous, controllable, and efficient, but also improves the dispersion uniformity of nanoparticles. Hydrogel hollow fiber doped with carbon nanotubes is fabricated and exhibits superior electrical conductivity (15.8 S m−1), strong flexibility (342.9%), and versatility as wearable sensors for monitoring human motions and collecting physiological electrical signals. Furthermore, we incorporate iron tetroxide nanoparticles into fibers to create magnetic-driven micromotors, which provide trajectory-controlled motion and the ability to move through narrow channels due to their small size. In addition, manganese dioxide nanoparticles are embedded into the fiber walls to create self-propelled micromotors. When placed in a hydrogen peroxide environment, the micromotors can reach a top speed of 615 μm s−1 and navigate hard-to-reach areas. Our nano-doped hollow fiber offers a broad range of applications in wearable electronics and self-propelled machines and creates promising opportunities for sensors and actuators. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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15 pages, 2644 KiB  
Article
A Novel Microfluidic Strategy for Efficient Exosome Separation via Thermally Oxidized Non-Uniform Deterministic Lateral Displacement (DLD) Arrays and Dielectrophoresis (DEP) Synergy
by Dayin Wang, Shijia Yang, Ning Wang, Han Guo, Shilun Feng, Yuan Luo and Jianlong Zhao
Biosensors 2024, 14(4), 174; https://doi.org/10.3390/bios14040174 - 4 Apr 2024
Cited by 2 | Viewed by 2375
Abstract
Exosomes, with diameters ranging from 30 to 150 nm, are saucer-shaped extracellular vesicles (EVs) secreted by various type of human cells. They are present in virtually all bodily fluids. Owing to their abundant nucleic acid and protein content, exosomes have emerged as promising [...] Read more.
Exosomes, with diameters ranging from 30 to 150 nm, are saucer-shaped extracellular vesicles (EVs) secreted by various type of human cells. They are present in virtually all bodily fluids. Owing to their abundant nucleic acid and protein content, exosomes have emerged as promising biomarkers for noninvasive molecular diagnostics. However, the need for exosome separation purification presents tremendous technical challenges due to their minuscule size. In recent years, microfluidic technology has garnered substantial interest as a promising alternative capable of excellent separation performance, reduced reagent consumption, and lower overall device and operation costs. In this context, we hereby propose a novel microfluidic strategy based on thermally oxidized deterministic lateral displacement (DLD) arrays with tapered shapes to enhance separation performance. We have achieved more than 90% purity in both polystyrene nanoparticle and exosome experiments. The use of thermal oxidation also significantly reduces fabrication complexity by avoiding the use of high-precision lithography. Furthermore, in a simulation model, we attempt to integrate the use of dielectrophoresis (DEP) to overcome the size-based nature of DLD and distinguish particles that are close in size but differ in biochemical compositions (e.g., lipoproteins, exomeres, retroviruses). We believe the proposed strategy heralds a versatile and innovative platform poised to enhance exosome analysis across a spectrum of biochemical applications. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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13 pages, 3068 KiB  
Article
A 3D Capillary-Driven Multi-Micropore Membrane-Based Trigger Valve for Multi-Step Biochemical Reaction
by Yijun Zhang, Yuang Li, Xiaofeng Luan, Xin Li, Jiahong Jiang, Yuanyuan Fan, Mingxiao Li, Chengjun Huang, Lingqian Zhang and Yang Zhao
Biosensors 2023, 13(1), 26; https://doi.org/10.3390/bios13010026 - 26 Dec 2022
Cited by 3 | Viewed by 2099
Abstract
Point-of-care testing (POCT) techniques based on microfluidic devices enabled rapid and accurate tests on-site, playing an increasingly important role in public health. As the critical component of capillary-driven microfluidic devices for POCT use, the capillary microfluidic valve could schedule multi-step biochemical operations, potentially [...] Read more.
Point-of-care testing (POCT) techniques based on microfluidic devices enabled rapid and accurate tests on-site, playing an increasingly important role in public health. As the critical component of capillary-driven microfluidic devices for POCT use, the capillary microfluidic valve could schedule multi-step biochemical operations, potentially being used for broader complex POCT tasks. However, owing to the reciprocal relationship between the capillary force and aperture in single-pore microchannels, it was challenging to achieve a high gating threshold and high operable liquid volume simultaneously with existing 2D capillary trigger valves. This paper proposed a 3D capillary-driven multi-microporous membrane-based trigger valve to address the issue. Taking advantage of the high gating threshold determined by micropores and the self-driven capillary channel, a 3D trigger valve composed of a microporous membrane for valving and a wedge-shaped capillary channel for flow pumping was implemented. Utilizing the capillary pinning effect of the multi-micropore membrane, the liquid above the membrane could be triggered by putting the drainage agent into the wedge-shaped capillary channel to wet the underside of the membrane, and it could also be cut off by taking away the agent. After theoretical analysis and performance characterizations, the 3D trigger valve performed a high gating threshold (above 1000 Pa) and high trigger efficiency with an operable liquid volume above 150 μL and a trigger-to-drain time below 6 s. Furthermore, the retention and trigger states of the valve could be switched for repeatable triggering for three cycles within 5 min. Finally, the microbead-based immunoreaction and live cell staining applications verified the valve’s ability to perform multi-step operations. The above results showed that the proposed 3D trigger valve could be expected to play a part in wide-ranging POCT application scenarios. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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16 pages, 6639 KiB  
Article
Development of an Open Microfluidic Platform for Oocyte One-Stop Vitrification with Cryotop Method
by Shu Miao, Chenxi Guo, Ze Jiang, Hao-Xiang Wei, Xin Jiang, Jingkai Gu, Zhuo Hai, Tianren Wang and Yun-Hui Liu
Biosensors 2022, 12(9), 766; https://doi.org/10.3390/bios12090766 - 19 Sep 2022
Cited by 7 | Viewed by 2954
Abstract
Oocyte vitrification technology is widely used for assisted reproduction and fertility preservation, which requires precise washing sequences and timings of cryoprotectant agents (CPAs) treatment to relieve the osmotic shock to cells. The gold standard Cryotop method is extensively used in oocyte vitrification and [...] Read more.
Oocyte vitrification technology is widely used for assisted reproduction and fertility preservation, which requires precise washing sequences and timings of cryoprotectant agents (CPAs) treatment to relieve the osmotic shock to cells. The gold standard Cryotop method is extensively used in oocyte vitrification and is currently the most commonly used method in reproductive centers. However, the Cryotop method requires precise and complex manual manipulation by an embryologist, whose proficiency directly determines the effect of vitrification. Therefore, in this study, an automatic microfluidic system consisting of a novel open microfluidic chip and a set of automatic devices was established as a standardized operating protocol to facilitate the conventional manual Cryotop method and minimize the osmotic shock applied to the oocyte. The proposed open microfluidic system could smoothly change the CPA concentration around the oocyte during vitrification pretreatment, and transferred the treated oocyte to the Cryotop with a tiny droplet. The system better conformed to the operating habits of embryologists, whereas the integration of commercialized Cryotop facilitates the subsequent freezing and thawing processes. With standardized operating procedures, our system provides consistent treatment effects for each operation, leading to comparable survival rate, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) level of oocytes to the manual Cryotop operations. The vitrification platform is the first reported microfluidic system integrating the function of cells transfer from the processing chip, which avoids the risk of cell loss or damage in a manual operation and ensures the sufficient cooling rate during liquid nitrogen (LN2) freezing. Our study demonstrates significant potential of the automatic microfluidic approach to serve as a facile and universal solution for the vitrification of various precious cells. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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Review

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38 pages, 8341 KiB  
Review
Single-Cell RNA Sequencing in Organ and Cell Transplantation
by Roozbeh Abedini-Nassab, Fatemeh Taheri, Ali Emamgholizadeh and Hossein Naderi-Manesh
Biosensors 2024, 14(4), 189; https://doi.org/10.3390/bios14040189 - 11 Apr 2024
Cited by 1 | Viewed by 2062
Abstract
Single-cell RNA sequencing is a high-throughput novel method that provides transcriptional profiling of individual cells within biological samples. This method typically uses microfluidics systems to uncover the complex intercellular communication networks and biological pathways buried within highly heterogeneous cell populations in tissues. One [...] Read more.
Single-cell RNA sequencing is a high-throughput novel method that provides transcriptional profiling of individual cells within biological samples. This method typically uses microfluidics systems to uncover the complex intercellular communication networks and biological pathways buried within highly heterogeneous cell populations in tissues. One important application of this technology sits in the fields of organ and stem cell transplantation, where complications such as graft rejection and other post-transplantation life-threatening issues may occur. In this review, we first focus on research in which single-cell RNA sequencing is used to study the transcriptional profile of transplanted tissues. This technology enables the analysis of the donor and recipient cells and identifies cell types and states associated with transplant complications and pathologies. We also review the use of single-cell RNA sequencing in stem cell implantation. This method enables studying the heterogeneity of normal and pathological stem cells and the heterogeneity in cell populations. With their remarkably rapid pace, the single-cell RNA sequencing methodologies will potentially result in breakthroughs in clinical transplantation in the coming years. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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25 pages, 6351 KiB  
Review
Photonic Microfluidic Technologies for Phytoplankton Research
by José Francisco Algorri, Pablo Roldán-Varona, María Gabriela Fernández-Manteca, José Miguel López-Higuera, Luis Rodriguez-Cobo and Adolfo Cobo-García
Biosensors 2022, 12(11), 1024; https://doi.org/10.3390/bios12111024 - 16 Nov 2022
Cited by 3 | Viewed by 2420
Abstract
Phytoplankton is a crucial component for the correct functioning of different ecosystems, climate regulation and carbon reduction. Being at least a quarter of the biomass of the world’s vegetation, they produce approximately 50% of atmospheric O2 and remove nearly a third of [...] Read more.
Phytoplankton is a crucial component for the correct functioning of different ecosystems, climate regulation and carbon reduction. Being at least a quarter of the biomass of the world’s vegetation, they produce approximately 50% of atmospheric O2 and remove nearly a third of the anthropogenic carbon released into the atmosphere through photosynthesis. In addition, they support directly or indirectly all the animals of the ocean and freshwater ecosystems, being the base of the food web. The importance of their measurement and identification has increased in the last years, becoming an essential consideration for marine management. The gold standard process used to identify and quantify phytoplankton is manual sample collection and microscopy-based identification, which is a tedious and time-consuming task and requires highly trained professionals. Microfluidic Lab-on-a-Chip technology represents a potential technical solution for environmental monitoring, for example, in situ quantifying toxic phytoplankton. Its main advantages are miniaturisation, portability, reduced reagent/sample consumption and cost reduction. In particular, photonic microfluidic chips that rely on optical sensing have emerged as powerful tools that can be used to identify and analyse phytoplankton with high specificity, sensitivity and throughput. In this review, we focus on recent advances in photonic microfluidic technologies for phytoplankton research. Different optical properties of phytoplankton, fabrication and sensing technologies will be reviewed. To conclude, current challenges and possible future directions will be discussed. Full article
(This article belongs to the Special Issue Application of Microfluidics in Cell Manipulation and Biosensing)
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