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Biosensors
Special Issues
Advanced Microfluidic Chips and Their Applications
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Advanced Microfluidic Chips and Their Applications

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 31410

Special Issue Editors

Dr. Shilun Feng

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Guest Editor
State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
Interests: microfluidics; droplet; deterministic lateral displacement; wearable devices; bacteria detection; on-chip imaging; POCT device
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jianlong Zhao

E-Mail Website
Guest Editor
State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China
Interests: integrated biochemical sensing technology; microelectronic technology

Special Issue Information

Dear Colleagues,

We are inviting contributions for this Special Issue covering advanced microfluidic lab-on-a-chip platforms and their wide range of applications.

Advanced microfluidic chips, with sampling, manipulation (mix, separation, purification, heating, reactions, etc.), and on-chip or off-chip detection functions, can be designed along with different integrated processing modules. These tools are useful for sample preparation, liquid handling, and cell/particle manipulation.

Along with relevant point-of-care testing (POCT) instruments, advanced microfluidic chips offer excellent and rapid, accurate, real-time, on-site, and multiplexed detections. Their applications have attracted increasing attention, especially for COVID-19 pathogen detection. Such instruments will be extensively adopted in both academic and industrial fields for healthcare, biochemistry, life science, food, water quality, etc.

This Special Issue aims to stimulate microfluidics development for POCT and provides the latest research results on microfluidic tools in the context of the COVID-19 pandemic.

Topics of interest include, but are not limited to:

  • Biomedical microfluidics;
  • Point-of-care testing (POCT);
  • Miniaturized systems for chemistry and life sciences (MicroTAS);
  • Pathogens;
  • Biosensors;
  • ddPCR and/or cdPCR;
  • Antibody and/or antigens;
  • Sampling;
  • Manipulation;
  • Separation and/or purification;
  • Imaging and other detection technologies.

Dr. Shilun Feng
Prof. Dr. Jianlong Zhao
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.

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Published Papers (10 papers)

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Research

12 pages, 2361 KiB  
Article
A Low-Cost Microfluidic-Based Detection Device for Rapid Identification and Quantification of Biomarkers-Based on a Smartphone
by Chonghui Yang, Yujing Yang, Gaozhen Zhao, Huan Wang, Yang Dai and Xiaowen Huang
Biosensors 2023, 13(7), 753; https://doi.org/10.3390/bios13070753 - 22 Jul 2023
Cited by 2 | Viewed by 2272
Abstract
The sensitive and rapid detection of microsamples is crucial for early diagnosis of diseases. The short response times and low sample volume requirements of microfluidic chips have shown great potential in early diagnosis, but there are still shortcomings such as complex preparation processes [...] Read more.
The sensitive and rapid detection of microsamples is crucial for early diagnosis of diseases. The short response times and low sample volume requirements of microfluidic chips have shown great potential in early diagnosis, but there are still shortcomings such as complex preparation processes and high costs. We developed a low-cost smartphone-based fluorescence detection device (Smartphone-BFDD) without precision equipment for rapid identification and quantification of biomarkers on glass capillary. The device combines microfluidic technology with RGB image analysis, effectively reducing the sample volume to 20 μL and detection time to only 30 min. For the sensitivity of the device, we constructed a standard sandwich immunoassay (antibody–antigen–antibody) in a glass capillary using the N-protein of SARS-CoV-2 as a biological model, realizing a low limit of detection (LOD, 40 ng mL−1). This device provides potential applications for different biomarkers and offers wide use for rapid biochemical analysis in biomedical research. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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13 pages, 3446 KiB  
Article
On-Chip Nucleic Acid Purification Followed by ddPCR for SARS-CoV-2 Detection
by Cong Ma, Yimeng Sun, Yuhang Huang, Zehang Gao, Yaru Huang, Ikshu Pandey, Chunping Jia, Shilun Feng and Jianlong Zhao
Biosensors 2023, 13(5), 517; https://doi.org/10.3390/bios13050517 - 5 May 2023
Cited by 3 | Viewed by 2065
Abstract
We developed a microfluidic chip integrated with nucleic acid purification and droplet-based digital polymerase chain reaction (ddPCR) modules to realize a ‘sample-in, result-out’ infectious virus diagnosis. The whole process involved pulling magnetic beads through drops in an oil-enclosed environment. The purified nucleic acids [...] Read more.
We developed a microfluidic chip integrated with nucleic acid purification and droplet-based digital polymerase chain reaction (ddPCR) modules to realize a ‘sample-in, result-out’ infectious virus diagnosis. The whole process involved pulling magnetic beads through drops in an oil-enclosed environment. The purified nucleic acids were dispensed into microdroplets by a concentric-ring, oil–water-mixing, flow-focusing droplets generator driven under negative pressure conditions. Microdroplets were generated with good uniformity (CV = 5.8%), adjustable diameters (50–200 μm), and controllable flow rates (0–0.3 μL/s). Further verification was provided by quantitative detection of plasmids. We observed a linear correlation of R2 = 0.9998 in the concentration range from 10 to 105 copies/μL. Finally, this chip was applied to quantify the nucleic acid concentrations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The measured nucleic acid recovery rate of 75 ± 8.8% and detection limit of 10 copies/μL proved its on-chip purification and accurate detection abilities. This chip can potentially be a valuable tool in point-of-care testing. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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11 pages, 3648 KiB  
Article
Wearable Microfluidic Sweat Chip for Detection of Sweat Glucose and pH in Long-Distance Running Exercise
by Dong Liu, Zhenyu Liu, Shilun Feng, Zehang Gao, Ran Chen, Gaozhe Cai and Shengtai Bian
Biosensors 2023, 13(2), 157; https://doi.org/10.3390/bios13020157 - 19 Jan 2023
Cited by 20 | Viewed by 5347
Abstract
Traditional exercise training monitoring is based on invasive blood testing methods. As sweat can reveal abundant blood-related physiological information about health, wearable sweat sensors have received significant research attention and become increasingly popular in the field of exercise training monitoring. However, most of [...] Read more.
Traditional exercise training monitoring is based on invasive blood testing methods. As sweat can reveal abundant blood-related physiological information about health, wearable sweat sensors have received significant research attention and become increasingly popular in the field of exercise training monitoring. However, most of these sensors are used to measure physical indicators such as heart rate, blood pressure, respiration, etc., demanding a versatile sensor that can detect relevant biochemical indicators in body fluids. In this work, we proposed a wearable microfluidic sweat chip combined with smartphone image processing to realize non-invasive in situ analysis of epidermal sweat for sports practitioners. The polydimethylsiloxane (PDMS) based chip was modified with nonionic surfactants to ensure good hydrophilicity for the automatic collection of sweat. Besides, a simple, reliable, and low-cost paper-based sensor was prepared for high-performance sensing of glucose concentration and pH in sweat. Under optimized conditions, this proposed chip can detect glucose with low concentrations from 0.05 mM to 0.40 mM, with a pH range of 4.0 to 6.5 for human sweat. The ability of this microfluidic chip for human sweat analysis was demonstrated by dynamically tracking the changes in glucose concentration and pH in long-distance running subjects. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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14 pages, 4770 KiB  
Article
A Compact Control System to Enable Automated Operation of Microfluidic Bioanalytical Assays
by Alan M. Gonzalez-Suarez, Alexander Long, XuHai Huang and Alexander Revzin
Biosensors 2022, 12(12), 1160; https://doi.org/10.3390/bios12121160 - 13 Dec 2022
Cited by 3 | Viewed by 2918
Abstract
We describe a control system for operating valve-enabled microfluidic devices and leverage this control system to carry out a complex workflow of plasma separation from 8 μL of whole blood followed by on-chip mixing of plasma with assay reagents for biomarker detection. The [...] Read more.
We describe a control system for operating valve-enabled microfluidic devices and leverage this control system to carry out a complex workflow of plasma separation from 8 μL of whole blood followed by on-chip mixing of plasma with assay reagents for biomarker detection. The control system incorporates pumps, digital pressure sensors, a microcontroller, solenoid valves and off-the-shelf components to deliver high and low air pressure in the desired temporal sequence to meter fluid flow and actuate microvalves. Importantly, our control system is portable, which is suitable for operating the microvalve-enabled microfluidic devices in the point-of-care setting. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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12 pages, 4384 KiB  
Article
A 3D-Printed Standardized Modular Microfluidic System for Droplet Generation
by Junyi Chen, Shaoqi Huang, Yan Long, Kan Wang, Yangtai Guan, Lianping Hou, Bo Dai, Songlin Zhuang and Dawei Zhang
Biosensors 2022, 12(12), 1085; https://doi.org/10.3390/bios12121085 - 28 Nov 2022
Cited by 5 | Viewed by 2873
Abstract
Droplet-based microfluidics has a variety of applications, such as material synthesis and single-cell analysis. In this paper, we propose a modular microfluidic system using projection micro-stereolithography three-dimensional (3D) printing technology for droplet generation. All modules are designed using a standard cubic structure with [...] Read more.
Droplet-based microfluidics has a variety of applications, such as material synthesis and single-cell analysis. In this paper, we propose a modular microfluidic system using projection micro-stereolithography three-dimensional (3D) printing technology for droplet generation. All modules are designed using a standard cubic structure with a specific leakage-free connection interface. Versatile droplets, including single droplets, alternating droplets, merged droplets, and Janus particles, have been successfully produced. The droplet size and the generation rate can be flexibly controlled by adjusting the flow rates. The influence of the flow rate fraction between the discrete phase and the continuous phase over the generation of the alternating and merged droplets is discussed. Furthermore, the ‘UV curing’ module can be employed to solidify the generated droplets to avoid coalescence and fix the status of the Janus particles. The proposed modular droplet generators are promising candidates for various chemical and biological applications, such as single-cell incubation, screening of protein crystallization conditions, synthesis of nanoparticles, and gene delivery. In addition, we envision that more functional modules, e.g., valve, microreactor, and detection modules, could be developed, and the 3D standardized modular microfluidics could be further applied to other complex systems, i.e., concentration gradient generators and clinical diagnostic systems. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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15 pages, 3501 KiB  
Article
Implementation of an Integrated Dielectrophoretic and Magnetophoretic Microfluidic Chip for CTC Isolation
by Kai Zhao, Penglu Zhao, Jianhong Dong, Yunman Wei, Bin Chen, Yanjuan Wang, Xinxiang Pan and Junsheng Wang
Biosensors 2022, 12(9), 757; https://doi.org/10.3390/bios12090757 - 14 Sep 2022
Cited by 16 | Viewed by 2966
Abstract
Identification of circulating tumor cells (CTCs) from a majority of various cell pools has been an appealing topic for diagnostic purposes. This study numerically demonstrates the isolation of CTCs from blood cells by the combination of dielectrophoresis and magnetophoresis in a microfluidic chip. [...] Read more.
Identification of circulating tumor cells (CTCs) from a majority of various cell pools has been an appealing topic for diagnostic purposes. This study numerically demonstrates the isolation of CTCs from blood cells by the combination of dielectrophoresis and magnetophoresis in a microfluidic chip. Taking advantage of the label-free property, the separation of red blood cells, platelets, T cells, HT-29, and MDA-231 was conducted in the microchannel. By using the ferromagnet structure with double segments and a relatively shorter distance in between, a strong gradient of the magnetic field, i.e., sufficiently large MAP forces acting on the cells, can be generated, leading to a high separation resolution. In order to generate strong DEP forces, the non-uniform electric field gradient is induced by applying the electric voltage through the microchannel across a pair of asymmetric orifices, i.e., a small orifice and a large orifice on the opposite wall of the channel sides. The distribution of the gradient of the magnetic field near the edge of ferromagnet segments, the gradient of the non-uniform electric field in the vicinity of the asymmetric orifices, and the flow field were investigated. In this numerical simulation, the effects of the ferromagnet structure on the magnetic field, the flow rate, as well as the strength of the electric field on their combined magnetophoretic and dielectrophoretic behaviors and trajectories are systemically studied. The simulation results demonstrate the potential of both property- and size-based cell isolation in the microfluidic device by implementing magnetophoresis and dielectrophoresis. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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15 pages, 2105 KiB  
Article
Portable Colorimetric Device with Commercial Microplates for Quantitative Detection of Urine Biomarkers: Design, Development, and Clinical Evaluation
by Anh Tran Tam Pham, Damian Tohl, Qi Hu, Jordan Li, Karen J. Reynolds and Youhong Tang
Biosensors 2022, 12(9), 723; https://doi.org/10.3390/bios12090723 - 4 Sep 2022
Cited by 2 | Viewed by 2195
Abstract
Urine biomarkers are important in monitoring diseases related to human kidney function. The current processes for measuring biomarker levels in urine samples require patients to regularly visit clinical facilities, which is inconvenient and sometimes impossible for patients in rural areas. Therefore, portable analysis [...] Read more.
Urine biomarkers are important in monitoring diseases related to human kidney function. The current processes for measuring biomarker levels in urine samples require patients to regularly visit clinical facilities, which is inconvenient and sometimes impossible for patients in rural areas. Therefore, portable analysis devices for the measurement of urine biomarkers are urgently requested. In this study, a portable platform using colorimetry, a common and simple-to-operate chemical analysis technique, was developed to measure urine biomarkers. The device, using commercial test kits as recognising reagents and a 96-well microplate as a solution container, provides quantitative measures of biomarker concentration. Moreover, the proposed device introduces a calibration method to minimise the dependence of regular maintenance. The device’s performance was evaluated with urine from 73 renal patients and its results matched with clinical results well. The device has the potential for measuring urine creatinine, in addition to performing a variety of commercial assays for biomarker detection in human body fluids in general. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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9 pages, 11057 KiB  
Article
Mxenes–Au NP Hybrid Plasmonic 2D Microplates in Microfluidics for SERS Detection
by Zhaoxian Chen, Anping Liu, Xiumei Zhang, Jiawei Jiao, Yuan Yuan, Yingzhou Huang and Sheng Yan
Biosensors 2022, 12(7), 505; https://doi.org/10.3390/bios12070505 - 10 Jul 2022
Cited by 2 | Viewed by 2117
Abstract
Combined with microfluidics, surface-enhanced Raman spectroscopy (SERS) exhibits huge application prospective in sensitive online detection. In current studies, the design and optimization of plasmonic enhanced structures in microfluidics for SERS detection could be an interesting challenge. In this work, hybrid plasmonic 2D microplates [...] Read more.
Combined with microfluidics, surface-enhanced Raman spectroscopy (SERS) exhibits huge application prospective in sensitive online detection. In current studies, the design and optimization of plasmonic enhanced structures in microfluidics for SERS detection could be an interesting challenge. In this work, hybrid plasmonic 2D microplates composed of Mxenes (Ti3C2Tx) microplates and in-situ synthesized Au nanoparticles (Au NPs) are fabricated in a microchannel for enhanced structures in SERS microfluidics. Benefiting from the 2D Mxenes microplates with complex distributions, the enhanced areas generated by Au NPs are quite enlarged in a microchannel, which exhibits high sensitivity in SERS detection at 10−10 M for Nile blue (NB) molecules in microfluidics. The mechanism of electromagnetic enhancement (EM) and chemical enhancement (CM) is analyzed. The experimental data indicate the ultrasonic times of Mxenes and the concentration of Au3+ play important roles in the sensitivity of SERS detection, which is confirmed by the simulated electric field distributions. Furthermore, a typical pesticide (thiram) at 100 ppm in water is detected on these SERS microfluidics with hybrid plasmonic enhanced structures, which demonstrates that our work not only strengthens the knowledge of plasmonics but also enlarges the application of SERS. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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13 pages, 2611 KiB  
Article
A High-Throughput MEMS-Based Differential Scanning Calorimeter for Direct Thermal Characterization of Antibodies
by Shifeng Yu, Yongjia Wu, Shuyu Wang, Michael Siedler, Peter M. Ihnat, Dana I. Filoti, Ming Lu and Lei Zuo
Biosensors 2022, 12(6), 422; https://doi.org/10.3390/bios12060422 - 16 Jun 2022
Cited by 3 | Viewed by 2808
Abstract
Calorimeters, which can be used for rapid thermal characterization of biomolecules, are getting intense attention in drug development. This paper presents a novel MEMS-based differential scanning calorimeter (DSC) for direct thermal characterization of protein samples. The DSC consisted of a pair of temperature [...] Read more.
Calorimeters, which can be used for rapid thermal characterization of biomolecules, are getting intense attention in drug development. This paper presents a novel MEMS-based differential scanning calorimeter (DSC) for direct thermal characterization of protein samples. The DSC consisted of a pair of temperature sensors made by vanadium oxide (VOx) film with a temperature coefficient of resistivity of −0.025/K at 300 K, a microfluidic device with high thermal insulation (2.8 K/mW), and a Peltier heater for linear temperature scanning. The DSC exhibited high sensitivity (6.1 µV/µW), low noise (0.4 µW), high scanning rate (45 K/min), and low sample consumption volume (0.63 µL). The MEMS DSC was verified by measuring the temperature-induced denaturation of lysozyme at different pH, and then used to study the thermal stability of a monoclonal antibody (mAb), an antigen-binding fragment (Fab), and a dual variable domain immunoglobulin (DVD-Ig) at pH = 6. The results showed that lysozyme is a stable protein in the pH range of 4.0–8.0. The protein stability study revealed that the transition temperatures of the intact Fab fragment, mAb, and DVD proteins were comparable with conformational stability results obtained using conventional commercial DSC. These studies demonstrated that the MEMS DSC is an effective tool for directly understanding the thermal stability of antibodies in a high-throughput and low-cost manner compared to conventional calorimeters. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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11 pages, 2082 KiB  
Article
All-in-One Digital Microfluidics System for Molecular Diagnosis with Loop-Mediated Isothermal Amplification
by Siyi Hu, Yuhan Jie, Kai Jin, Yifan Zhang, Tianjie Guo, Qi Huang, Qian Mei, Fuqiang Ma and Hanbin Ma
Biosensors 2022, 12(5), 324; https://doi.org/10.3390/bios12050324 - 11 May 2022
Cited by 24 | Viewed by 4133
Abstract
In this study, an “all-in-one” digital microfluidics (DMF) system was developed for automatic and rapid molecular diagnosis and integrated with magnetic bead-based nucleic acid extraction, loop-mediated isothermal amplification (LAMP), and real-time optical signal monitoring. First, we performed on- and off-chip comparison experiments for [...] Read more.
In this study, an “all-in-one” digital microfluidics (DMF) system was developed for automatic and rapid molecular diagnosis and integrated with magnetic bead-based nucleic acid extraction, loop-mediated isothermal amplification (LAMP), and real-time optical signal monitoring. First, we performed on- and off-chip comparison experiments for the magnetic bead nucleic acid extraction module and LAMP amplification function. The extraction efficiency for the on-chip test was comparable to that of conventional off-chip methods. The processing time for the automatic on-chip workflow was only 23 min, which was less than that of the conventional methods of 28 min 45 s. Meanwhile, the number of samples used in on-chip experiments was significantly smaller than that used in off-chip experiments; only 5 µL of E. coli samples was required for nucleic acid extraction, and 1 µL of the nucleic acid template was needed for the amplification reaction. In addition, we selected SARS-CoV-2 nucleic acid reference materials for the nucleic acid detection experiment, demonstrating a limit of detection of 10 copies/µL. The proposed “all-in-one” DMF system provides an on-site “sample to answer” time of approximately 60 min, which can be a powerful tool for point-of-care molecular diagnostics. Full article
(This article belongs to the Special Issue Advanced Microfluidic Chips and Their Applications)
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