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Biosensors
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Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers
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Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers

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 December 2022) | Viewed by 21870

Special Issue Editors

Dr. András Dér

E-Mail Website
Guest Editor
HUN-REN Institute of Biophysics, Biological Research Centre, Temesvari krt 62, H-6726 Szeged, Hungary
Interests: integrated optics; electric properties of proteins and cells; lab-on-a-chip devices for photonic and biotechnological applications; statistical analysis of bioelectronics signals
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mária A. Deli

E-Mail Website
Guest Editor
HUN-REN Biological Research Centre, Institute of Biophysics, Szeged, Hungary
Interests: blood-brain barrier; blood-brain barrier dysfunction; brain endothelial protection; targeted drug delivery; targeted nanoparticle; BBB transporters; BBB transcytosis; organ-on-chip models
Special Issues, Collections and Topics in MDPI journals
Dr. András Kincses

E-Mail Website
Guest Editor
Institute of Biophysics, Biological Research Centre, 6726 Szeged, Hungary
Interests: lab-on-a-chip technologies
Dr. Fruzsina Walter

E-Mail Website
Guest Editor
Institute of Biophysics, Biological Research Centre, Temesvari krt 62, H-6726 Szeged, Hungary
Interests: biological barriers, brain pathologies, drug delivery, permeability studies, organoid and lab-on-a-chip devices; animal and human vascular endothelial cell culture models; co-culture models of the blood–brain barrier; protection of the biological barriers in pathologies; natural compounds as barrier-protecting agents; surface glycocalyx, surface potential measurements

Special Issue Information

Dear Colleagues,

The importance of integrated biochips for studying biological barriers in vitro has been increased in the last decade. With the possibility of the coculturing of multiple cell types and to integrate spheroids and organoids, these lab-on-a-chip devices offer effective ways to understand physiological functions, transport mechanisms, drug delivery and pathologies. Biological barriers include the skin, cornea, respiratory and gastrointestinal epithelial barriers, which are the first to come in contact with the outside environment. In the body, endothelial and epithelial cells form barriers in the testis, placenta and in the brain (blood–brain barrier, choroid plexus, blood–retina barrier). These protect the specific organ systems from outside damage and maintain ionic and nutritional homeostasis within the tissue. Integrated microelectronic biochips provide a complex hardware for multicellular barrier culture modelling, including several crucial parameters needed for effective translational studies. With the newly emerging concept of human stem cell-derived models and organoids, the field has never been more complex. This Special Issue provides a platform to feature novel developments on the miniaturized microfluidic biochip device family, integrating all types of measurements. This includes barrier integrity measurements, morphology characterizations, physiology and pathology investigations, protection in diseases, novel ways of drug targeting, and gene and protein expression studies.

Prof. Dr. András Dér
Prof. Dr. Mária A. Deli
Dr. András Kincses
Dr. Fruzsina Walter
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

  • lab-on-a-chip devices
  • microfluidics
  • microelectronics
  • endothelial and epithelial barriers
  • brain barriers
  • gastrointestinal barriers
  • respiratory barriers
  • skin barrier
  • cell culture, organoid and chip models
  • drug transport in chip models
  • biological barriers and pathological changes in chip devices
  • protection of biological barriers in diseases

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Published Papers (6 papers)

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Research

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17 pages, 2903 KiB  
Article
Co-Culture of Glomerular Endothelial Cells and Podocytes in a Custom-Designed Glomerulus-on-a-Chip Model Improves the Filtration Barrier Integrity and Affects the Glomerular Cell Phenotype
by Daan C. ‘t Hart, Dilemin Yildiz, Valentina Palacio-Castañeda, Lanhui Li, Burcu Gumuscu, Roland Brock, Wouter P. R. Verdurmen, Johan van der Vlag and Tom Nijenhuis
Biosensors 2023, 13(3), 339; https://doi.org/10.3390/bios13030339 - 3 Mar 2023
Cited by 8 | Viewed by 3801
Abstract
Crosstalk between glomerular endothelial cells and glomerular epithelial cells (podocytes) is increasingly becoming apparent as a crucial mechanism to maintain the integrity of the glomerular filtration barrier. However, in vitro studies directly investigating the effect of this crosstalk on the glomerular filtration barrier [...] Read more.
Crosstalk between glomerular endothelial cells and glomerular epithelial cells (podocytes) is increasingly becoming apparent as a crucial mechanism to maintain the integrity of the glomerular filtration barrier. However, in vitro studies directly investigating the effect of this crosstalk on the glomerular filtration barrier are scarce because of the lack of suitable experimental models. Therefore, we developed a custom-made glomerulus-on-a-chip model recapitulating the glomerular filtration barrier, in which we investigated the effects of co-culture of glomerular endothelial cells and podocytes on filtration barrier function and the phenotype of these respective cell types. The custom-made glomerulus-on-a-chip model was designed using soft lithography. The chip consisted of two parallel microfluidic channels separated by a semi-permeable polycarbonate membrane. The glycocalyx was visualized by wheat germ agglutinin staining and the barrier integrity of the glomerulus-on-a-chip model was determined by measuring the transport rate of fluorescently labelled dextran from the top to the bottom channel. The effect of crosstalk on the transcriptome of glomerular endothelial cells and podocytes was investigated via RNA-sequencing. Glomerular endothelial cells and podocytes were successfully cultured on opposite sides of the membrane in our glomerulus-on-a-chip model using a polydopamine and collagen A double coating. Barrier integrity of the chip model was significantly improved when glomerular endothelial cells were co-cultured with podocytes compared to monocultures of either glomerular endothelial cells or podocytes. Co-culture enlarged the surface area of podocyte foot processes and increased the thickness of the glycocalyx. RNA-sequencing analysis revealed the regulation of cellular pathways involved in cellular differentiation and cellular adhesion as a result of the interaction between glomerular endothelial cells and podocytes. We present a novel custom-made glomerulus-on-a-chip co-culture model and demonstrated for the first time using a glomerulus-on-a-chip model that co-culture affects the morphology and transcriptional phenotype of glomerular endothelial cells and podocytes. Moreover, we showed that co-culture improves barrier function as a relevant functional readout for clinical translation. This model can be used in future studies to investigate specific glomerular paracrine pathways and unravel the role of glomerular crosstalk in glomerular (patho) physiology. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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14 pages, 3075 KiB  
Article
Liver Acinus Dynamic Chip for Assessment of Drug-Induced Zonal Hepatotoxicity
by Dohyung Kwon, Geonho Choi, Song-A Park, Sungwoo Cho, Sihun Cho and Sungho Ko
Biosensors 2022, 12(7), 445; https://doi.org/10.3390/bios12070445 - 23 Jun 2022
Cited by 7 | Viewed by 3179
Abstract
Zonation along the liver acinus is considered a key feature of liver physiology. Here, we developed a liver acinus dynamic (LADY) chip that recapitulates a key functional structure of the liver acinus and hepatic zonation. Corresponding to the blood flow from portal triads [...] Read more.
Zonation along the liver acinus is considered a key feature of liver physiology. Here, we developed a liver acinus dynamic (LADY) chip that recapitulates a key functional structure of the liver acinus and hepatic zonation. Corresponding to the blood flow from portal triads to the central vein in vivo, gradual flow of oxygen and glucose–carrying culture medium into the HepG2 cell chamber of the LADY chip generated zonal protein expression patterns in periportal (PP) zone 1 and perivenous (PV) zone 3. Higher levels of albumin secretion and urea production were obtained in a HepG2/HUVECs co-culture LADY chip than in HepG2 mono-culture one. Zonal expression of PEPCK as a PP marker and CYP2E1 as a PV marker was successfully generated. Cell death rate of the PV cells was higher than that of the PP cells since zonal factors responsible for metabolic activation of acetaminophen (APAP) were highly expressed in the PV region. We also found the co-culture enhanced metabolic capacity to process APAP, thus improving resistance to APAP toxicity, in comparison with HepG2 mono-culture. These results indicate that our LADY chip successfully represents liver zonation and could be useful in drug development studies as a drug-induced zonal hepatotoxicity testing platform. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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15 pages, 38640 KiB  
Article
Malignant Melanoma-Derived Exosomes Induce Endothelial Damage and Glial Activation on a Human BBB Chip Model
by Peng Wang, Yunsong Wu, Wenwen Chen, Min Zhang and Jianhua Qin
Biosensors 2022, 12(2), 89; https://doi.org/10.3390/bios12020089 - 31 Jan 2022
Cited by 16 | Viewed by 4598
Abstract
Malignant melanoma is a type of highly aggressive tumor, which has a strong ability to metastasize to brain, and 60–70% of patients die from the spread of the tumor into the central nervous system. Exosomes are a type of nano-sized vesicle secreted by [...] Read more.
Malignant melanoma is a type of highly aggressive tumor, which has a strong ability to metastasize to brain, and 60–70% of patients die from the spread of the tumor into the central nervous system. Exosomes are a type of nano-sized vesicle secreted by most living cells, and accumulated studies have reported that they play crucial roles in brain tumor metastasis, such as breast cancer and lung cancer. However, it is unclear whether exosomes also participate in the brain metastasis of malignant melanoma. Here, we established a human blood–brain barrier (BBB) model by co-culturing human brain microvascular endothelial cells, astrocytes and microglial cells under a biomimetic condition, and used this model to explore the potential roles of exosomes derived from malignant melanoma in modulating BBB integrity. Our findings showed that malignant melanoma-derived exosomes disrupted BBB integrity and induced glial activation on the BBB chip. Transcriptome analyses revealed dys-regulation of autophagy and immune responses following tumor exosome treatment. These studies indicated malignant melanoma cells might modulate BBB integrity via exosomes, and verified the feasibility of a BBB chip as an ideal platform for studies of brain metastasis of tumors in vitro. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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8 pages, 1632 KiB  
Communication
Sensing of C-Reactive Protein Using an Extended-Gate Field-Effect Transistor with a Tungsten Disulfide-Doped Peptide-Imprinted Conductive Polymer Coating
by Kai-Hsi Liu, Hung-Yin Lin, James L. Thomas, Chen-Yuan Chen, Yen-Ting Chen, Chuen-Yau Chen, Chien-Hsin Yang and Mei-Hwa Lee
Biosensors 2022, 12(1), 31; https://doi.org/10.3390/bios12010031 - 7 Jan 2022
Cited by 6 | Viewed by 2593
Abstract
C-reactive protein (CRP) is a non-specific biomarker of inflammation and may be associated with cardiovascular disease. In recent studies, systemic inflammatory responses have also been observed in cases of coronavirus disease 2019 (COVID-19). Molecularly imprinted polymers (MIPs) have been developed to replace natural [...] Read more.
C-reactive protein (CRP) is a non-specific biomarker of inflammation and may be associated with cardiovascular disease. In recent studies, systemic inflammatory responses have also been observed in cases of coronavirus disease 2019 (COVID-19). Molecularly imprinted polymers (MIPs) have been developed to replace natural antibodies with polymeric materials that have low cost and high stability and could thus be suitable for use in a home-care system. In this work, a MIP-based electrochemical sensing system for measuring CRP was developed. Such a system can be integrated with microfluidics and electronics for lab-on-a-chip technology. MIP composition was optimized using various imprinting template (CRP peptide) concentrations. Tungsten disulfide (WS2) was doped into the MIPs. Doping not only enhances the electrochemical response accompanying the recognition of the template molecules but also raises the top of the sensing range from 1.0 pg/mL to 1.0 ng/mL of the imprinted peptide. The calibration curve of the WS2-doped peptide-imprinted polymer-coated electrodes in the extended-gate field-effect transistor platform was obtained and used for the measurement of CRP concentration in real human serum. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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Review

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21 pages, 5027 KiB  
Review
miRNAs as Predictors of Barrier Integrity
by Judit Bovari-Biri, Kitti Garai, Krisztina Banfai, Veronika Csongei and Judit E. Pongracz
Biosensors 2023, 13(4), 422; https://doi.org/10.3390/bios13040422 - 26 Mar 2023
Cited by 3 | Viewed by 2621
Abstract
The human body has several barriers that protect its integrity and shield it from mechanical, chemical, and microbial harm. The various barriers include the skin, intestinal and respiratory epithelia, blood–brain barrier (BBB), and immune system. In the present review, the focus is on [...] Read more.
The human body has several barriers that protect its integrity and shield it from mechanical, chemical, and microbial harm. The various barriers include the skin, intestinal and respiratory epithelia, blood–brain barrier (BBB), and immune system. In the present review, the focus is on the physical barriers that are formed by cell layers. The barrier function is influenced by the molecular microenvironment of the cells forming the barriers. The integrity of the barrier cell layers is maintained by the intricate balance of protein expression that is partly regulated by microRNAs (miRNAs) both in the intracellular space and the extracellular microenvironment. The detection of changes in miRNA patterns has become a major focus of diagnostic, prognostic, and disease progression, as well as therapy-response, markers using a great variety of detection systems in recent years. In the present review, we highlight the importance of liquid biopsies in assessing barrier integrity and challenges in differential miRNA detection. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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17 pages, 1601 KiB  
Review
The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions
by András Kincses, Judit P. Vigh, Dániel Petrovszki, Sándor Valkai, Anna E. Kocsis, Fruzsina R. Walter, Hung-Yin Lin, Jeng-Shiung Jan, Mária A. Deli and András Dér
Biosensors 2023, 13(3), 357; https://doi.org/10.3390/bios13030357 - 8 Mar 2023
Cited by 10 | Viewed by 3688
Abstract
The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier [...] Read more.
The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach. The BBB represents the tightest endothelial barrier within the vasculature with high electric resistance and low passive permeability, providing a controlled interface between the circulation and the brain. The multi-cell type dynamic BBB-on-chip models are in demand in several fields as alternatives to expensive animal studies or static culture inserts methods. Their combination with integrated biosensors provides real-time and noninvasive monitoring of the integrity of the BBB and of the presence and concentration of agents contributing to the physiological and metabolic functions and pathologies. In this review, we describe built-in sensors to characterize BBB models via quasi-direct current and electrical impedance measurements, as well as the different types of biosensors for the detection of metabolites, drugs, or toxic agents. We also give an outlook on the future of the field, with potential combinations of existing methods and possible improvements of current techniques. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices and Biosensors to Model Biological Barriers)
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