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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 (15 September 2021) | Viewed by 60539

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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. Mohsen Asadnia

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Guest Editor

School of Engineering, Macquarie University, Sydney, NSW 2109, Australia
Interests: MEMS; sensors; biomimetics; microeletromechanical systems; pressure sensors; microfluidics; sensors arrays
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Dr. Ming Li

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Guest Editor

School of Engineering, Macquarie University, Sydney, NSW 2122, Australia
Interests: biomicrofluidics; plasmonic biosensors; droplet microfluidics; lab-on-a-chip devices; cytometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite contributions to this Special Issue covering biosensor development and biosensing in a wide range of fields using microfluidic lab-on-a-chip platforms. This Special Issue will report the latest innovative microfluidic devices and technologies for biosensing applications.

Rapid, accurate, real-time, on-site and multiplexed detection and characterization have been the requirements in current biosensor technology development, especially during the COVID-19 outbreak. The development of reliable and stable microfluidic biosensors, point-of-care biosensing platforms, and advanced detection methods have attracted increasing attention from both academia and industry.

Microfluidics offers excellent platforms for biosensor development and biosensing. The platforms are useful for sample preparation, liquid handling, and cell/particle manipulation. Multiple functions can be designed and achieved in microfluidic chips along with different on-chip and off-chip detection and processing modules. This has been extensively adopted in both academic and industrial applications for a wide range of applications in healthcare, biochemistry, life science, food, water quality, etc.

We therefore invite contributions to this Special Issue from different fields about biosensing and microfluidics. The list of potential topics is broad, but we are particularly interested in studies on the design, development, and applications of microfluidics-based technologies in point-of-care biosensing and testing.

We welcome high-quality publications with significant novelties that can potentially have high impacts on the abovementioned fields. The work should be thoughtfully organized and of great interest to the diverse microfluidics and biosensing community.

Dr. Shilun Feng
Dr. Mohsen Asadnia
Dr. Ming Li
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

biomedical microfluidics
lab on a chip
miniaturized systems for chemistry and life science (MicroTAS)
biosensor development and characteristics
imaging and other detection technologies
imaging and signal processing
point-of-care testing microdevices
food and water quality testing and control

Published Papers (12 papers)

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Research

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13 pages, 3052 KiB

Open AccessArticle

A 3D-Printed Microfluidic Device for qPCR Detection of Macrolide-Resistant Mutations of Mycoplasma pneumoniae

by Anyan Wang, Zhenhua Wu, Yuhang Huang, Hongbo Zhou, Lei Wu, Chunping Jia, Qiang Chen and Jianlong Zhao

Biosensors 2021, 11(11), 427; https://doi.org/10.3390/bios11110427 - 29 Oct 2021

Cited by 5 | Viewed by 2487

Abstract

Mycoplasma pneumonia (MP) is a common respiratory infection generally treated with macrolides, but resistance mutations against macrolides are often detected in mycoplasma pneumoniae in China. Rapid and accurate identification of mycoplasma pneumoniae and its mutant type is necessary for precise medication. This paper presents a 3D-printed microfluidic device to achieve this. By 3D printing, the stereoscopic structures such as microvalves, reservoirs, drainage tubes, and connectors were fabricated in one step. The device integrated commercial polymerase chain reaction (PCR) tubes as PCR chambers. The detection was a sample-to-answer procedure. First, the sample, a PCR mix, and mineral oil were respectively added to the reservoirs on the device. Next, the device automatically mixed the sample with the PCR mix and evenly dispensed the mixed solution and mineral oil into the PCR chambers, which were preloaded with the specified primers and probes. Subsequently, quantitative real-time PCR (qPCR) was carried out with the homemade instrument. Within 80 min, mycoplasma pneumoniae and its mutation type in the clinical samples were determined, which was verified by DNA sequencing. The easy-to-make and easy-to-use device provides a rapid and integrated detection approach for pathogens and antibiotic resistance mutations, which is urgently needed on the infection scene and in hospital emergency departments. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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21 pages, 3123 KiB

Open AccessArticle

OralDisk: A Chair-Side Compatible Molecular Platform Using Whole Saliva for Monitoring Oral Health at the Dental Practice

by Desirée Baumgartner, Benita Johannsen, Mara Specht, Jan Lüddecke, Markus Rombach, Sebastian Hin, Nils Paust, Felix von Stetten, Roland Zengerle, Christopher Herz, Johannes R. Peham, Pune N. Paqué, Thomas Attin, Joël S. Jenzer, Philipp Körner, Patrick R. Schmidlin, Thomas Thurnheer, Florian J. Wegehaupt, Wendy E. Kaman, Andrew Stubbs, John P. Hays, Viorel Rusu, Alex Michie, Thomas Binsl, David Stejskal, Michal Karpíšek, Kai Bao, Nagihan Bostanci, Georgios N. Belibasakis and Konstantinos Mitsakakis Show full author list Hide full author list

Biosensors 2021, 11(11), 423; https://doi.org/10.3390/bios11110423 - 28 Oct 2021

Cited by 12 | Viewed by 4177

Abstract

Periodontitis and dental caries are two major bacterially induced, non-communicable diseases that cause the deterioration of oral health, with implications in patients’ general health. Early, precise diagnosis and personalized monitoring are essential for the efficient prevention and management of these diseases. Here, we present a disk-shaped microfluidic platform (OralDisk) compatible with chair-side use that enables analysis of non-invasively collected whole saliva samples and molecular-based detection of ten bacteria: seven periodontitis-associated (Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and three caries-associated (oral Lactobacilli, Streptococcus mutans, Streptococcus sobrinus). Each OralDisk test required 400 µL of homogenized whole saliva. The automated workflow included bacterial DNA extraction, purification and hydrolysis probe real-time PCR detection of the target pathogens. All reagents were pre-stored within the disk and sample-to-answer processing took < 3 h using a compact, customized processing device. A technical feasibility study (25 OralDisks) was conducted using samples from healthy, periodontitis and caries patients. The comparison of the OralDisk with a lab-based reference method revealed a ~90% agreement amongst targets detected as positive and negative. This shows the OralDisk’s potential and suitability for inclusion in larger prospective implementation studies in dental care settings. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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11 pages, 2554 KiB

Open AccessArticle

Investigating the Regulation of Neural Differentiation and Injury in PC12 Cells Using Microstructure Topographic Cues

by Xindi Sun, Wei Li, Xiuqing Gong, Guohui Hu, Junyi Ge, Jinbo Wu and Xinghua Gao

Biosensors 2021, 11(10), 399; https://doi.org/10.3390/bios11100399 - 16 Oct 2021

Cited by 1 | Viewed by 2257

Abstract

In this study, we designed and manufactured a series of different microstructure topographical cues for inducing neuronal differentiation of cells in vitro, with different topography, sizes, and structural complexities. We cultured PC12 cells in these microstructure cues and then induced neural differentiation using nerve growth factor (NGF). The pheochromocytoma cell line PC12 is a validated neuronal cell model that is widely used to study neuronal differentiation. Relevant markers of neural differentiation and cytoskeletal F-actin were characterized. Cellular immunofluorescence detection and axon length analysis showed that the differentiation of PC12 cells was significantly different under different isotropic and anisotropic topographic cues. The expression differences of the growth cone marker growth-associated protein 43 (GAP-43) and sympathetic nerve marker tyrosine hydroxylase (TH) genes were also studied in different topographic cues. Our results revealed that the physical environment has an important influence on the differentiation of neuronal cells, and 3D constraints could be used to guide axon extension. In addition, the neurotoxin 6-hydroxydopamine (6-OHDA) was used to detect the differentiation and injury of PC12 cells under different topographic cues. Finally, we discussed the feasibility of combining the topographic cues and the microfluidic chip for neural differentiation research. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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18 pages, 5331 KiB

Open AccessArticle

Microfluidic Lab-on-a-Chip Based on UHF-Dielectrophoresis for Stemness Phenotype Characterization and Discrimination among Glioblastoma Cells

by Elisa Lambert, Rémi Manczak, Elodie Barthout, Sofiane Saada, Elena Porcù, Francesca Maule, Barbara Bessette, Giampietro Viola, Luca Persano, Claire Dalmay, Fabrice Lalloué and Arnaud Pothier

Biosensors 2021, 11(10), 388; https://doi.org/10.3390/bios11100388 - 13 Oct 2021

Cited by 13 | Viewed by 2301

Abstract

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Nowadays, the characterization of this cell type with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: f_x01 in the low-frequency range (below 500 kHz) and f_x02 in the ultra-high-frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. An U87-MG cell line was cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients’ primary cell culture were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low-frequency range DEP does not allow the discrimination of the undifferentiated GBM cells from the differentiated one. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetics of U87-MG phenotype transformation in a CSC enrichment medium and the cancer stem cells phenotype acquirement. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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13 pages, 4627 KiB

Open AccessArticle

VEGF Detection via Simplified FLISA Using a 3D Microfluidic Disk Platform

by Dong Hee Kang, Na Kyong Kim, Sang-Woo Park and Hyun Wook Kang

Biosensors 2021, 11(8), 270; https://doi.org/10.3390/bios11080270 - 11 Aug 2021

Cited by 2 | Viewed by 2624

Abstract

Fluorescence-linked immunosorbent assay (FLISA) is a commonly used, quantitative technique for detecting biochemical changes based on antigen–antibody binding reactions using a well-plate platform. As the manufacturing technology of microfluidic system evolves, FLISA can be implemented onto microfluidic disk platforms which allows the detection of trace biochemical reactions with high resolutions. Herein, we propose a novel microfluidic system comprising a disk with a three-dimensional incubation chamber, which can reduce the amount of the reagents to 1/10 and the required time for the entire process to less than an hour. The incubation process achieves an antigen–antibody binding reaction as well as the binding of fluorogenic substrates to target proteins. The FLISA protocol in the 3D incubation chamber necessitates performing the antibody-conjugated microbeads’ movement during each step in order to ensure sufficient binding reactions. Vascular endothelial growth factor as concentration with ng mL⁻¹ is detected sequentially using a benchtop process employing this 3D microfluidic disk. The 3D microfluidic disk works without requiring manual intervention or additional procedures for liquid control. During the incubation process, microbead movement is controlled by centrifugal force from the rotating disk and the sedimentation by gravitational force at the tilted floor of the chamber. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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19 pages, 3052 KiB

Open AccessArticle

Stochastic Time Response and Ultimate Noise Performance of Adsorption-Based Microfluidic Biosensors

by Ivana Jokić, Zoran Djurić, Katarina Radulović, Miloš Frantlović, Gradimir V. Milovanović and Predrag M. Krstajić

Biosensors 2021, 11(6), 194; https://doi.org/10.3390/bios11060194 - 12 Jun 2021

Cited by 2 | Viewed by 2425

Abstract

In order to improve the interpretation of measurement results and to achieve the optimal performance of microfluidic biosensors, advanced mathematical models of their time response and noise are needed. The random nature of adsorption–desorption and mass transfer (MT) processes that generate the sensor response makes the sensor output signal inherently stochastic and necessitates the use of a stochastic approach in sensor response analysis. We present a stochastic model of the sensor time response, which takes into account the coupling of adsorption–desorption and MT processes. It is used for the analysis of response kinetics and ultimate noise performance of protein biosensors. We show that slow MT not only decelerates the response kinetics, but also increases the noise and decreases the sensor’s maximal achievable signal-to-noise ratio, thus degrading the ultimate sensor performance, including the minimal detectable/quantifiable analyte concentration. The results illustrate the significance of the presented model for the correct interpretation of measurement data, for the estimation of sensors’ noise performance metrics important for reliable analyte detection/quantification, as well as for sensor optimization in terms of the lower detection/quantification limit. They are also incentives for the further investigation of the MT influence in nanoscale sensors, as a possible cause of false-negative results in analyte detection experiments. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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13 pages, 2783 KiB

Open AccessArticle

A Multichannel Microfluidic Sensing Cartridge for Bioanalytical Applications of Monolithic Quartz Crystal Microbalance

by María Calero, Román Fernández, Pablo García, José Vicente García, María García, Esther Gamero-Sandemetrio, Ilya Reviakine, Antonio Arnau and Yolanda Jiménez

Biosensors 2020, 10(12), 189; https://doi.org/10.3390/bios10120189 - 24 Nov 2020

Cited by 8 | Viewed by 3128

Abstract

Integrating acoustic wave sensors into lab-on-a-chip (LoC) devices is a well-known challenge. We address this challenge by designing a microfluidic device housing a monolithic array of 24 high-fundamental frequency quartz crystal microbalance with dissipation (HFF-QCMD) sensors. The device features six 6-µL channels of four sensors each for low-volume parallel measurements, a sealing mechanism that provides appropriate pressure control while assuring liquid confinement and maintaining good stability, and provides a mechanical, electrical, and thermal interface with the characterization electronics. We validate the device by measuring the response of the HFF-QCMD sensors to the air-to-liquid transition, for which the robust Kanazawa–Gordon–Mason theory exists, and then by studying the adsorption of model bioanalytes (neutravidin and biotinylated albumin). With these experiments, we show how the effects of the protein–surface interactions propagate within adsorbed protein multilayers, offering essentially new insight into the design of affinity-based bioanalytical sensors. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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13 pages, 3137 KiB

Open AccessEditor’s ChoiceArticle

Microfluidic-Based Electrochemical Immunosensing of Ferritin

by Mayank Garg, Martin Gedsted Christensen, Alexander Iles, Amit L. Sharma, Suman Singh and Nicole Pamme

Biosensors 2020, 10(8), 91; https://doi.org/10.3390/bios10080091 - 05 Aug 2020

Cited by 27 | Viewed by 6831

Abstract

Ferritin is a clinically important biomarker which reflects the state of iron in the body and is directly involved with anemia. Current methods available for ferritin estimation are generally not portable or they do not provide a fast response. To combat these issues, an attempt was made for lab-on-a-chip-based electrochemical detection of ferritin, developed with an integrated electrochemically active screen-printed electrode (SPE), combining nanotechnology, microfluidics, and electrochemistry. The SPE surface was modified with amine-functionalized graphene oxide to facilitate the binding of ferritin antibodies on the electrode surface. The functionalized SPE was embedded in the microfluidic flow cell with a simple magnetic clamping mechanism to allow continuous electrochemical detection of ferritin. Ferritin detection was accomplished via cyclic voltammetry with a dynamic linear range from 7.81 to 500 ng·mL⁻¹ and an LOD of 0.413 ng·mL⁻¹. The sensor performance was verified with spiked human serum samples. Furthermore, the sensor was validated by comparing its response with the response of the conventional ELISA method. The current method of microfluidic flow cell-based electrochemical ferritin detection demonstrated promising sensitivity and selectivity. This confirmed the plausibility of using the reported technique in point-of-care testing applications at a much faster rate than conventional techniques. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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Review

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26 pages, 3518 KiB

Open AccessReview

A Review of Capillary Pressure Control Valves in Microfluidics

by Shaoxi Wang, Xiafeng Zhang, Cong Ma, Sheng Yan, David Inglis and Shilun Feng

Biosensors 2021, 11(10), 405; https://doi.org/10.3390/bios11100405 - 19 Oct 2021

Cited by 17 | Viewed by 9451

Abstract

Microfluidics offer microenvironments for reagent delivery, handling, mixing, reaction, and detection, but often demand the affiliated equipment for liquid control for these functions. As a helpful tool, the capillary pressure control valve (CPCV) has become popular to avoid using affiliated equipment. Liquid can be handled in a controlled manner by using the bubble pressure effects. In this paper, we analyze and categorize the CPCVs via three determining parameters: surface tension, contact angle, and microchannel shape. Finally, a few application scenarios and impacts of CPCV are listed, which includes how CPVC simplify automation of microfluidic networks, work with other driving modes; make extensive use of microfluidics by open channel, and sampling and delivery with controlled manners. The authors hope this review will help the development and use of the CPCV in microfluidic fields in both research and industry. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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34 pages, 51903 KiB

Open AccessReview

Recent Progress in Wearable Biosensors: From Healthcare Monitoring to Sports Analytics

by Shun Ye, Shilun Feng, Liang Huang and Shengtai Bian

Biosensors 2020, 10(12), 205; https://doi.org/10.3390/bios10120205 - 15 Dec 2020

Cited by 58 | Viewed by 15321

Abstract

Recent advances in lab-on-a-chip technology establish solid foundations for wearable biosensors. These newly emerging wearable biosensors are capable of non-invasive, continuous monitoring by miniaturization of electronics and integration with microfluidics. The advent of flexible electronics, biochemical sensors, soft microfluidics, and pain-free microneedles have created new generations of wearable biosensors that explore brand-new avenues to interface with the human epidermis for monitoring physiological status. However, these devices are relatively underexplored for sports monitoring and analytics, which may be largely facilitated by the recent emergence of wearable biosensors characterized by real-time, non-invasive, and non-irritating sensing capacities. Here, we present a systematic review of wearable biosensing technologies with a focus on materials and fabrication strategies, sampling modalities, sensing modalities, as well as key analytes and wearable biosensing platforms for healthcare and sports monitoring with an emphasis on sweat and interstitial fluid biosensing. This review concludes with a summary of unresolved challenges and opportunities for future researchers interested in these technologies. With an in-depth understanding of the state-of-the-art wearable biosensing technologies, wearable biosensors for sports analytics would have a significant impact on the rapidly growing field—microfluidics for biosensing. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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34 pages, 6851 KiB

Open AccessReview

Modular and Integrated Systems for Nanoparticle and Microparticle Synthesis—A Review

by Hongda Lu, Shi-Yang Tang, Guolin Yun, Haiyue Li, Yuxin Zhang, Ruirui Qiao and Weihua Li

Biosensors 2020, 10(11), 165; https://doi.org/10.3390/bios10110165 - 03 Nov 2020

Cited by 17 | Viewed by 5121

Abstract

Nanoparticles (NPs) and microparticles (MPs) have been widely used in different areas of research such as materials science, energy, and biotechnology. On-demand synthesis of NPs and MPs with desired chemical and physical properties is essential for different applications. However, most of the conventional methods for producing NPs/MPs require bulky and expensive equipment, which occupies large space and generally need complex operation with dedicated expertise and labour. These limitations hinder inexperienced researchers to harness the advantages of NPs and MPs in their fields of research. When problems individual researchers accumulate, the overall interdisciplinary innovations for unleashing a wider range of directions are undermined. In recent years, modular and integrated systems are developed for resolving the ongoing dilemma. In this review, we focus on the development of modular and integrated systems that assist the production of NPs and MPs. We categorise these systems into two major groups: systems for the synthesis of (1) NPs and (2) MPs; systems for producing NPs are further divided into two sections based on top-down and bottom-up approaches. The mechanisms of each synthesis method are explained, and the properties of produced NPs/MPs are compared. Finally, we discuss existing challenges and outline the potentials for the development of modular and integrated systems. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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Other

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13 pages, 1531 KiB

Open AccessPerspective

Two-Phase Biocatalysis in Microfluidic Droplets

by Lanting Xiang, Felix Kaspar, Anett Schallmey and Iordania Constantinou

Biosensors 2021, 11(11), 407; https://doi.org/10.3390/bios11110407 - 21 Oct 2021

Cited by 3 | Viewed by 2454

Abstract

This Perspective discusses the literature related to two-phase biocatalysis in microfluidic droplets. Enzymes used as catalysts in biocatalysis are generally less stable in organic media than in their native aqueous environments; however, chemical and pharmaceutical compounds are often insoluble in water. The use of aqueous/organic two-phase media provides a solution to this problem and has therefore become standard practice for multiple biotransformations. In batch, two-phase biocatalysis is limited by mass transport, a limitation that can be overcome with the use of microfluidic systems. Although, two-phase biocatalysis in laminar flow systems has been extensively studied, microfluidic droplets have been primarily used for enzyme screening. In this Perspective, we summarize the limited published work on two-phase biocatalysis in microfluidic droplets and discuss the limitations, challenges, and future perspectives of this technology. Full article

(This article belongs to the Special Issue Microfluidics for Biosensing)

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