Biosensors Based on Microfluidic Devices

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Nano- and Micro-Technologies in Biosensors".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 40130

Special Issue Editors


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Guest Editor
Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, China
Interests: microfluidics; surface plasmon resonance; electrochemical; lipid vesicle; cell electrofusion; electroporation; cell sorting; liquid crystal
Special Issues, Collections and Topics in MDPI journals
Bioengineering College, Chongqing University, Chongqing 400030, China
Interests: biomicrofluidics; fundamental and applications of cell electrofusion; implantable microdevices; microfluidics; nanofluidics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biosensors have been widely used in point-of-care testing (POCT) fields, such as clinical diagnosis, food safety, and environmental monitoring. A lot of efforts have been made recently on the development of portable, reliable, and rapid responsive biosensing platforms. Because of their easy integration, small sample consumption, precise manipulation of fluid, and high-throughput analysis, microfluidics offer significant advantages over traditional biosensing systems. Various microfluidic structures have been designed for analyte enrichment, target separation, multiplexed analysis, and sensing material fabrication. Based on the application scenarios, these microfluidic components integrated with signal transducers, such as surface-enhanced Raman scattering (SERS), surface plasma resonance (SPR), and electrochemical techniques, to form miniaturized devices, have gained increasing popularity in POCT applications.

This issue aims to focus on the biosensing methods and devices based on microfluidics. Original research articles, short communications, and reviews are all welcome.

Prof. Dr. Jun Yang
Dr. Ning Hu
Guest Editors

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Keywords

  • microfluidics
  • biosensing
  • surface plasmon resonance
  • electrochemical
  • surface ehanced Raman scattering
  • protable devices
  • point-of-care testing
  • liquid crystal

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Published Papers (9 papers)

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Research

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17 pages, 7338 KiB  
Article
Four-Channel Ultrasonic Sensor for Bulk Liquid and Biochemical Surface Interrogation
by Donatas Pelenis, Dovydas Barauskas, Mindaugas Dzikaras and Darius Viržonis
Biosensors 2024, 14(2), 66; https://doi.org/10.3390/bios14020066 - 26 Jan 2024
Viewed by 1768
Abstract
Custom electronics tailored for ultrasonic applications with four ultrasonic transmit-receive channels and a nominal 25 MHz single channel frequency were developed for ultrasound BAW and SAW biosensor uses. The designed integrated microcontroller, supported by Python with a SciPy library, and the developed system [...] Read more.
Custom electronics tailored for ultrasonic applications with four ultrasonic transmit-receive channels and a nominal 25 MHz single channel frequency were developed for ultrasound BAW and SAW biosensor uses. The designed integrated microcontroller, supported by Python with a SciPy library, and the developed system measured the time of flight (TOF) and other wave properties to characterize the acoustic properties of a bulk of the liquid in a microchannel or acoustic properties of biological species attached to an analytic surface in real time. The system can utilize both piezoelectric and capacitive micromachined ultrasound transducers. The device demonstrated a linear response to changes in water salinity. This response was primarily attributed to the time-of-flight (TOF) changes related to the varying solution density. Furthermore, real-time DNA oligonucleotide-based interactions between oligonucleotides immobilized on the device’s analytical area and oligonucleotides attached to gold nanoparticles (Au NPs) in the solution were demonstrated. The biological interaction led to an exponential decrease in the acoustic interfacial wave propagating across the interface between the solution and the solid surface of the sensor, the TOF signal. This decrease was attributed to the increase in the effective density of the solution in the vicinity of the sensor’s analytical area, as Au NPs modified by oligonucleotides were binding to the analytical area. The utilization of Au NPs in oligonucleotide surface binding yields a considerably stronger sensor signal than previously observed in earlier CMUT-based TOF biosensor prototypes. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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13 pages, 2177 KiB  
Article
Highly Sensitive Multiplex Detection of Molecular Biomarkers Using Hybridization Chain Reaction in an Encoded Particle Microfluidic Platform
by Iene Rutten, Devin Daems, Karen Leirs and Jeroen Lammertyn
Biosensors 2023, 13(1), 100; https://doi.org/10.3390/bios13010100 - 6 Jan 2023
Cited by 8 | Viewed by 2703
Abstract
In the continuous combat against diseases, there is the need for tools that enable an improved diagnostic efficiency towards higher information density combined with reduced time-to-result and cost. Here, a novel fully integrated microfluidic platform, the Evalution™, is evaluated as a potential solution [...] Read more.
In the continuous combat against diseases, there is the need for tools that enable an improved diagnostic efficiency towards higher information density combined with reduced time-to-result and cost. Here, a novel fully integrated microfluidic platform, the Evalution™, is evaluated as a potential solution to this need. Encoded microparticles combined with channel-based microfluidics allow a fast, sensitive and simultaneous detection of several disease-related biomarkers. Since the binary code is represented by physically present holes, 210 different codes can be created that will not be altered by light or chemically induced degradation. Exploiting the unique features of this multiplex platform, hybridization chain reaction (HCR) is explored as a generic approach to reach the desired sensitivity. Compared to a non-amplified reference system, the sensitivity was drastically improved by a factor of 104, down to low fM LOD values. Depending on the HCR duration, the assay can be tuned for sensitivity or total assay time, as desired. The huge potential of this strategy was further demonstrated by the successful detection of a multiplex panel of six different nucleic acid targets including viruses and bacteria. The ability to not only discriminate these two categories but, with the same effort, also virus strains (human adenovirus and human bocavirus), virus subtypes (human adenovirus type B and D) and antibiotic-resistant bacteria (Streptococcus pneumonia), exemplifies the specificity of the developed approach. The effective, yet highly simplified, isothermal and protein-enzyme-free signal amplification tool reaches an LOD ranging from as low as 33 ± 4 to 151 ± 12 fM for the different targets. Moreover, direct detection in a clinically relevant sample matrix was verified, resulting in a detection limit of 309 ± 80 fM, approximating the low fM levels detectable with the gold standard analysis method, PCR, without the drawbacks related to protein enzymes, thermal cycling and elaborate sample preparation steps. The reported strategy can be directly transferred as a generic approach for the sensitive and specific detection of various target molecules in multiplex. In combination with the high-throughput capacity and reduced reagent consumption, the Evalution™ demonstrates immense potential in the next generation of diagnostic tools towards more personalized medicine. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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13 pages, 3051 KiB  
Article
Nanogap Electrode-Enabled Versatile Electrokinetic Manipulation of Nanometric Species in Fluids
by Qiang Zhao, Yunjiao Wang, Bangyong Sun, Deqiang Wang and Gang Li
Biosensors 2022, 12(7), 451; https://doi.org/10.3390/bios12070451 - 24 Jun 2022
Cited by 2 | Viewed by 2454
Abstract
Noninvasive manipulation of nanoscopic species in liquids has attracted considerable attention due to its potential applications in diverse fields. Many sophisticated methodologies have been developed to control and study nanoscopic entities, but the low-power, cost-effective, and versatile manipulation of nanometer-sized objects in liquids [...] Read more.
Noninvasive manipulation of nanoscopic species in liquids has attracted considerable attention due to its potential applications in diverse fields. Many sophisticated methodologies have been developed to control and study nanoscopic entities, but the low-power, cost-effective, and versatile manipulation of nanometer-sized objects in liquids remains challenging. Here, we present a dielectrophoretic (DEP) manipulation technique based on nanogap electrodes, with which the on-demand capturing, enriching, and sorting of nano-objects in microfluidic systems can be achieved. The dielectrophoretic control unit consists of a pair of swelling-induced nanogap electrodes crossing a microchannel, generating a steep electric field gradient and thus strong DEP force for the effective manipulation of nano-objects microfluidics. The trapping, enriching, and sorting of nanoparticles and DNAs were performed with this device to demonstrate its potential applications in micro/nanofluidics, which opens an alternative avenue for the non-invasive manipulation and characterization of nanoparticles such as DNA, proteins, and viruses. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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12 pages, 3382 KiB  
Article
Bead Number Effect in a Magnetic-Beads-Based Digital Microfluidic Immunoassay
by Wensyang Hsu, Yu-Teng Shih, Meng-Shiue Lee, Hong-Yuan Huang and Wan-Ning Wu
Biosensors 2022, 12(5), 340; https://doi.org/10.3390/bios12050340 - 16 May 2022
Cited by 13 | Viewed by 4006
Abstract
In a biomedical diagnosis with a limited sample volume and low concentration, droplet-based microfluidics, also called digital microfluidics, becomes a very attractive approach. Previously, our group developed a magnetic-beads-based digital microfluidic immunoassay with a bead number of around 100, requiring less than 1 [...] Read more.
In a biomedical diagnosis with a limited sample volume and low concentration, droplet-based microfluidics, also called digital microfluidics, becomes a very attractive approach. Previously, our group developed a magnetic-beads-based digital microfluidic immunoassay with a bead number of around 100, requiring less than 1 μL of sample volume to achieve a pg/mL level limit of detection (LOD). However, the bead number in each measurement was not the same, causing an unstable coefficient of variation (CV) in the calibration curve. Here, we investigated whether a fixed number of beads in this bead-based digital microfluidic immunoassay could provide more stable results. First, the bead screening chips were developed to extract exactly 100, 49, and 25 magnetic beads with diameters of less than 6 μm. Then, four calibration curves were established. One calibration curve was constructed by using varying bead numbers (50–160) in the process. The other three calibration curves used a fixed number of beads, (100, 49, and 25). The results indicated that the CVs for a fixed number of beads were evidently smaller than the CVs for varying bead numbers, especially in the range of 1 pg/mL to 100 pg/mL, where the CVs for 100 beads were less than 10%. Furthermore, the calculated LOD, based on the composite calibration curves, could be reduced by three orders, from 3.0 pg/mL (for the unfixed bead number) to 0.0287 pg/mL (for 100 beads). However, when the bead numbers were too high (more than 500) or too low (25 or fewer), the bead manipulation for aggregation became more difficult in the magnetic-beads-based digital microfluidic immunoassay chip. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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15 pages, 1607 KiB  
Article
Design of an Integrated Microfluidic Paper-Based Chip and Inspection Machine for the Detection of Mercury in Food with Silver Nanoparticles
by Lung-Ming Fu, Ming-Kuei Shih, Chang-Wei Hsieh, Wei-Jhong Ju, You-Lin Tain, Kuan-Chen Cheng, Jia-Hong Hsu, Yu-Wei Chen and Chih-Yao Hou
Biosensors 2021, 11(12), 491; https://doi.org/10.3390/bios11120491 - 30 Nov 2021
Cited by 10 | Viewed by 3595
Abstract
For most of the fast screening test papers for detecting Hg2+, the obtained results are qualitative. This study developed an operation for the μPAD and combined it with the chemical colorimetric method. Silver nanoparticle (AgNP) colloids were adopted as the reactive [...] Read more.
For most of the fast screening test papers for detecting Hg2+, the obtained results are qualitative. This study developed an operation for the μPAD and combined it with the chemical colorimetric method. Silver nanoparticle (AgNP) colloids were adopted as the reactive color reagent to combine and react with the Hg standards on the paper-based chip. Then, the RGB values for the color change were used to establish the standard curve (R2 > 0.99). Subsequently, this detection system was employed for the detection tests of actual samples, and the detected RGB values of the samples were substituted back to the formula to calculate the Hg2+ contents in the food. In this study, the Hg2+ content and recovery rate in commercially available packaged water and edible salts were measured. The research results indicate that a swift, economical, and simple detection method for Hg2+ content in food has been successfully developed. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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Review

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20 pages, 3210 KiB  
Review
Point-of-Care Diagnostic Devices for Detection of Escherichia coli O157:H7 Using Microfluidic Systems: A Focused Review
by Naseem Abbas, Sehyeon Song, Mi-Sook Chang and Myung-Suk Chun
Biosensors 2023, 13(7), 741; https://doi.org/10.3390/bios13070741 - 17 Jul 2023
Cited by 9 | Viewed by 3599
Abstract
Bacterial infections represent a serious and global threat in modern medicine; thus, it is very important to rapidly detect pathogenic bacteria, such as Escherichia coli (E. coli) O157:H7. Once treatments are delayed after the commencement of symptoms, the patient’s health quickly [...] Read more.
Bacterial infections represent a serious and global threat in modern medicine; thus, it is very important to rapidly detect pathogenic bacteria, such as Escherichia coli (E. coli) O157:H7. Once treatments are delayed after the commencement of symptoms, the patient’s health quickly deteriorates. Hence, real-time detection and monitoring of infectious agents are highly critical in early diagnosis for correct treatment and safeguarding public health. To detect these pathogenic bacteria, many approaches have been applied by the biosensors community, for example, widely-used polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), culture-based method, and adenosine triphosphate (ATP) bioluminescence. However, these approaches have drawbacks, such as time-consumption, expensive equipment, and being labor-intensive, making it critical to develop ultra-sensitive and highly selective detection. The microfluidic platform based on surface plasmon resonance (SPR), electrochemical sensing, and rolling circle amplification (RCA) offers proper alternatives capable of supplementing the technological gap for pathogen detection. Note that the microfluidic biochip allows to develop rapid, sensitive, portable, and point-of-care (POC) diagnostic tools. This review focuses on recent studies regarding accurate and rapid detection of E. coli O157:H7, with an emphasis on POC methods and devices that complement microfluidic systems. We also examine the efficient whole-body detection by employing antimicrobial peptides (AMPs), which has attracted growing attention in many applications. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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24 pages, 2321 KiB  
Review
Microfluidic-Based Oxygen (O2) Sensors for On-Chip Monitoring of Cell, Tissue and Organ Metabolism
by Mostafa Azimzadeh, Patricia Khashayar, Meitham Amereh, Nishat Tasnim, Mina Hoorfar and Mohsen Akbari
Biosensors 2022, 12(1), 6; https://doi.org/10.3390/bios12010006 - 22 Dec 2021
Cited by 32 | Viewed by 8326
Abstract
Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cell culture is an important indicator of cell viability. Recent advances in microfluidics have made O2 sensing a crucial feature for organ-on-chip (OOC) devices for various biomedical [...] Read more.
Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cell culture is an important indicator of cell viability. Recent advances in microfluidics have made O2 sensing a crucial feature for organ-on-chip (OOC) devices for various biomedical applications. OOC O2 sensors can be categorized, based on their transducer type, into two main groups, optical and electrochemical. In this review, we provide an overview of on-chip O2 sensors integrated with the OOC devices and evaluate their advantages and disadvantages. Recent innovations in optical O2 sensors integrated with OOCs are discussed in four main categories: (i) basic luminescence-based sensors; (ii) microparticle-based sensors; (iii) nano-enabled sensors; and (iv) commercial probes and portable devices. Furthermore, we discuss recent advancements in electrochemical sensors in five main categories: (i) novel configurations in Clark-type sensors; (ii) novel materials (e.g., polymers, O2 scavenging and passivation materials); (iii) nano-enabled electrochemical sensors; (iv) novel designs and fabrication techniques; and (v) commercial and portable electrochemical readouts. Together, this review provides a comprehensive overview of the current advances in the design, fabrication and application of optical and electrochemical O2 sensors. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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18 pages, 3144 KiB  
Review
Applications of Microfluidics in Liquid Crystal-Based Biosensors
by Jinan Deng, Dandan Han and Jun Yang
Biosensors 2021, 11(10), 385; https://doi.org/10.3390/bios11100385 - 12 Oct 2021
Cited by 34 | Viewed by 3912
Abstract
Liquid crystals (LCs) with stimuli-responsive configuration transition and optical anisotropic properties have attracted enormous interest in the development of simple and label-free biosensors. The combination of microfluidics and the LCs offers great advantages over traditional LC-based biosensors including small sample consumption, fast analysis [...] Read more.
Liquid crystals (LCs) with stimuli-responsive configuration transition and optical anisotropic properties have attracted enormous interest in the development of simple and label-free biosensors. The combination of microfluidics and the LCs offers great advantages over traditional LC-based biosensors including small sample consumption, fast analysis and low cost. Moreover, microfluidic techniques provide a promising tool to fabricate uniform and reproducible LC-based sensing platforms. In this review, we emphasize the recent development of microfluidics in the fabrication and integration of LC-based biosensors, including LC planar sensing platforms and LC droplets. Fabrication and integration of LC-based planar platforms with microfluidics for biosensing applications are first introduced. The generation and entrapment of monodisperse LC droplets with different microfluidic structures, as well as their applications in the detection of chemical and biological species, are then summarized. Finally, the challenges and future perspectives of the development of LC-based microfluidic biosensors are proposed. This review will promote the understanding of microfluidic techniques in LC-based biosensors and facilitate the development of LC-based microfluidic biosensing devices with high performance. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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23 pages, 2874 KiB  
Review
Lab-on-Paper Devices for Diagnosis of Human Diseases Using Urine Samples—A Review
by Wei-Chun Tai, Yu-Chi Chang, Dean Chou and Lung-Ming Fu
Biosensors 2021, 11(8), 260; https://doi.org/10.3390/bios11080260 - 3 Aug 2021
Cited by 28 | Viewed by 8292
Abstract
In recent years, microfluidic lab-on-paper devices have emerged as a rapid and low-cost alternative to traditional laboratory tests. Additionally, they were widely considered as a promising solution for point-of-care testing (POCT) at home or regions that lack medical infrastructure and resources. This review [...] Read more.
In recent years, microfluidic lab-on-paper devices have emerged as a rapid and low-cost alternative to traditional laboratory tests. Additionally, they were widely considered as a promising solution for point-of-care testing (POCT) at home or regions that lack medical infrastructure and resources. This review describes important advances in microfluidic lab-on-paper diagnostics for human health monitoring and disease diagnosis over the past five years. The review commenced by explaining the choice of paper, fabrication methods, and detection techniques to realize microfluidic lab-on-paper devices. Then, the sample pretreatment procedure used to improve the detection performance of lab-on-paper devices was introduced. Furthermore, an in-depth review of lab-on-paper devices for disease measurement based on an analysis of urine samples was presented. The review concludes with the potential challenges that the future development of commercial microfluidic lab-on-paper platforms for human disease detection would face. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices)
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