Micro/Nanofluidic and Lab-on-a-Chip Devices for Biomedical Applications

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B:Biology and Biomedicine".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 60615

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Guest Editor
Department of Mechanical Engineering, University of Minho, 4800-058 Guimarães, Portugal
Interests: numerical modeling; hemodynamics; in vitro tests; biosensing; organ-on-a-chips

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Guest Editor
Department of Mechanical Technology, School of Technology and Management, Polytechnic Institute of Bragança, Santa Apolónia Campus, 5300-253 Bragança, Portugal
Interests: prosthetic materials; design, control, and biomechanics of prosthesis; manufacturing processes of prosthesis
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Special Issue Information

Dear Colleagues,

Recently, microfluidic, nanofluidic and lab-on-a-chip devices have gained particular attention in biomedical applications. Due to their advantages, such as miniaturization, versatility, ease of use, cost-effectiveness, and the potential to replace animal models for drug development and testing, these devices hold tremendous potential to revolutionize the research of more effective treatments for several diseases that threaten human life. With integrated biosensors, these devices allow the development and design of micro- and nanoparticles to be studied in detail, modelling human physiology, investigating the molecular and cellular mechanisms underlying disease formation and progression, and gaining insights into the performance and long-term effects of responsive drug delivery nanocarriers.

This Special Issue seeks to gather research papers, and review articles focusing on novel microfluidic, nanofluidic and lab-on-a-chip devices for biomedical applications, addressing all steps related to fabrication, biosensor integration and development, characterization, numerical simulations and validation of the devices, optimization and, if possible, the translation of these devices from research labs to industry settings.

We look forward to receiving your submissions.

Dr. Violeta Carvalho
Prof. Dr. Senhorinha Teixeira
Prof. Dr. João Eduardo P. Castro Ribeiro
Guest Editors

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Keywords

  • Micro- and nanofluidics
  • Lab-on-a-Chip
  • Biosensing
  • Nanoparticles
  • Drug delivery systems
  • 3D organ models
  • Nanotechnology
  • Numerical simulations

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Related Special Issue

Published Papers (15 papers)

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Editorial

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3 pages, 198 KiB  
Editorial
Editorial for the Special Issue on Micro/Nanofluidic and Lab-on-a-Chip Devices for Biomedical Applications
by Violeta Meneses Carvalho, Senhorinha Teixeira and João E. Ribeiro
Micromachines 2022, 13(10), 1718; https://doi.org/10.3390/mi13101718 - 12 Oct 2022
Cited by 1 | Viewed by 1394
Abstract
Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [...] Full article

Research

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13 pages, 4527 KiB  
Article
A Poly-(ethylene glycol)-diacrylate 3D-Printed Micro-Bioreactor for Direct Cell Biological Implant-Testing on the Developing Chicken Chorioallantois Membrane
by Eric Lutsch, Andreas Struber, Georg Auer, Thomas Fessmann and Günter Lepperdinger
Micromachines 2022, 13(8), 1230; https://doi.org/10.3390/mi13081230 - 31 Jul 2022
Cited by 3 | Viewed by 2344
Abstract
Advancements in biomaterial manufacturing technologies calls for improved standards of fabrication and testing. Currently 3D-printable resins are being formulated which exhibit the potential to rapidly prototype biocompatible devices. For validation purposes, 3D-printed materials were subjected to a hierarchical validation onto the chorioallantoic membrane [...] Read more.
Advancements in biomaterial manufacturing technologies calls for improved standards of fabrication and testing. Currently 3D-printable resins are being formulated which exhibit the potential to rapidly prototype biocompatible devices. For validation purposes, 3D-printed materials were subjected to a hierarchical validation onto the chorioallantoic membrane of the developing chicken, better known as the HET CAM assay. Working along these lines, prints made from poly-(ethylene glycol)-diacrylate (PEGDA), which had undergone appropriate post-print processing, outperformed other commercial resins. This material passed all tests without displaying adverse effects, as experienced with other resin types. Based on this finding, the micro bioreactors (MBR) design, first made of PDMS and that also passed with cell tests on the HET-CAM, was finally printed in PEGDA, and applied in vivo. Following this workflow shows the applicability of 3D-printable resins for biomedical device manufacturing, consents to adherence to the present standards of the 3R criteria in material research and development, and provides flexibility and fast iteration of design and test cycles for MBR adaptation and optimization. Full article
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12 pages, 3191 KiB  
Article
Stimulus-Evoked Activity Modulation of In Vitro Engineered Cortical and Hippocampal Networks
by Francesca Callegari, Martina Brofiga, Fabio Poggio and Paolo Massobrio
Micromachines 2022, 13(8), 1212; https://doi.org/10.3390/mi13081212 - 29 Jul 2022
Cited by 12 | Viewed by 2072
Abstract
The delivery of electrical stimuli is crucial to shape the electrophysiological activity of neuronal populations and to appreciate the response of the different brain circuits involved. In the present work, we used dissociated cortical and hippocampal networks coupled to Micro-Electrode Arrays (MEAs) to [...] Read more.
The delivery of electrical stimuli is crucial to shape the electrophysiological activity of neuronal populations and to appreciate the response of the different brain circuits involved. In the present work, we used dissociated cortical and hippocampal networks coupled to Micro-Electrode Arrays (MEAs) to investigate the features of their evoked response when a low-frequency (0.2 Hz) electrical stimulation protocol is delivered. In particular, cortical and hippocampal neurons were topologically organized to recreate interconnected sub-populations with a polydimethylsiloxane (PDMS) mask, which guaranteed the segregation of the cell bodies and the connections among the sub-regions through microchannels. We found that cortical assemblies were more reactive than hippocampal ones. Despite both configurations exhibiting a fast (<35 ms) response, this did not uniformly distribute over the MEA in the hippocampal networks. Moreover, the propagation of the stimuli-evoked activity within the networks showed a late (35–500 ms) response only in the cortical assemblies. The achieved results suggest the importance of the neuronal target when electrical stimulation experiments are performed. Not all neuronal types display the same response, and in light of transferring stimulation protocols to in vivo applications, it becomes fundamental to design realistic in vitro brain-on-a-chip devices to investigate the dynamical properties of complex neuronal circuits. Full article
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14 pages, 1124 KiB  
Article
The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts
by Job Komen, Sanne M. van Neerven, Elsbeth G. B. M. Bossink, Nina E. de Groot, Lisanne E. Nijman, Albert van den Berg, Louis Vermeulen and Andries D. van der Meer
Micromachines 2022, 13(5), 739; https://doi.org/10.3390/mi13050739 - 6 May 2022
Cited by 2 | Viewed by 3681
Abstract
The cancer xenograft model in which human cancer cells are implanted in a mouse is one of the most used preclinical models to test the efficacy of novel cancer drugs. However, the model is imperfect; animal models are ethically burdened, and the imperfect [...] Read more.
The cancer xenograft model in which human cancer cells are implanted in a mouse is one of the most used preclinical models to test the efficacy of novel cancer drugs. However, the model is imperfect; animal models are ethically burdened, and the imperfect efficacy predictions contribute to high clinical attrition of novel drugs. If microfluidic cancer-on-chip models could recapitulate key elements of the xenograft model, then these models could substitute the xenograft model and subsequently surpass the xenograft model by reducing variation, increasing sensitivity and scale, and adding human factors. Here, we exposed HCT116 colorectal cancer spheroids to dynamic, in vivo-like, concentrations of oxaliplatin, including a 5 day drug-free period, on-chip. Growth inhibition on-chip was comparable to existing xenograft studies. Furthermore, immunohistochemistry showed a similar response in proliferation and apoptosis markers. While small volume changes in xenografts are hard to detect, in the chip-system, we could observe a temporary growth delay. Lastly, histopathology and a pharmacodynamic model showed that the cancer spheroid-on-chip was representative of the proliferating outer part of a HCT116 xenograft, thereby capturing the major driver of the drug response of the xenograft. Hence, the cancer-on-chip model recapitulated the response of HCT116 xenografts to oxaliplatin and provided additional drug efficacy information. Full article
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15 pages, 4627 KiB  
Article
Optimization and Fabrication of Multi-Level Microchannels for Long-Term Imaging of Bacterial Growth and Expansion
by Hsieh-Fu Tsai, Daniel W. Carlson, Anzhelika Koldaeva, Simone Pigolotti and Amy Q. Shen
Micromachines 2022, 13(4), 576; https://doi.org/10.3390/mi13040576 - 7 Apr 2022
Cited by 1 | Viewed by 3334
Abstract
Bacteria are unicellular organisms whose length is usually around a few micrometers. Advances in microfabrication techniques have enabled the design and implementation of microdevices to confine and observe bacterial colony growth. Microstructures hosting the bacteria and microchannels for nutrient perfusion usually require separate [...] Read more.
Bacteria are unicellular organisms whose length is usually around a few micrometers. Advances in microfabrication techniques have enabled the design and implementation of microdevices to confine and observe bacterial colony growth. Microstructures hosting the bacteria and microchannels for nutrient perfusion usually require separate microfabrication procedures due to different feature size requirements. This fact increases the complexity of device integration and assembly process. Furthermore, long-term imaging of bacterial dynamics over tens of hours requires stability in the microscope focusing mechanism to ensure less than one-micron drift in the focal axis. In this work, we design and fabricate an integrated multi-level, hydrodynamically-optimized microfluidic chip to study long-term Escherichia coli population dynamics in confined microchannels. Reliable long-term microscopy imaging and analysis has been limited by focus drifting and ghost effect, probably caused by the shear viscosity changes of aging microscopy immersion oil. By selecting a microscopy immersion oil with the most stable viscosity, we demonstrate successful captures of focally stable time-lapse bacterial images for ≥72 h. Our fabrication and imaging methodology should be applicable to other single-cell studies requiring long-term imaging. Full article
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12 pages, 3326 KiB  
Article
Single Red Blood Cell Hydrodynamic Traps via the Generative Design
by Georgii V. Grigorev, Nikolay O. Nikitin, Alexander Hvatov, Anna V. Kalyuzhnaya, Alexander V. Lebedev, Xiaohao Wang, Xiang Qian, Georgii V. Maksimov and Liwei Lin
Micromachines 2022, 13(3), 367; https://doi.org/10.3390/mi13030367 - 26 Feb 2022
Cited by 4 | Viewed by 2799
Abstract
This paper describes a generative design methodology for a micro hydrodynamic single-RBC (red blood cell) trap for applications in microfluidics-based single-cell analysis. One key challenge in single-cell microfluidic traps is to achieve desired through-slit flowrates to trap cells under implicit constraints. In this [...] Read more.
This paper describes a generative design methodology for a micro hydrodynamic single-RBC (red blood cell) trap for applications in microfluidics-based single-cell analysis. One key challenge in single-cell microfluidic traps is to achieve desired through-slit flowrates to trap cells under implicit constraints. In this work, the cell-trapping design with validation from experimental data has been developed by the generative design methodology with an evolutionary algorithm. L-shaped trapping slits have been generated iteratively for the optimal geometries to trap living-cells suspended in flow channels. Without using the generative design, the slits have low flow velocities incapable of trapping single cells. After a search with 30,000 solutions, the optimized geometry was found to increase the through-slit velocities by 49%. Fabricated and experimentally tested prototypes have achieved 4 out of 4 trapping efficiency of RBCs. This evolutionary algorithm and trapping design can be applied to cells of various sizes. Full article
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17 pages, 2689 KiB  
Article
Osmotically Enabled Wearable Patch for Sweat Harvesting and Lactate Quantification
by Tamoghna Saha, Jennifer Fang, Sneha Mukherjee, Charles T. Knisely, Michael D. Dickey and Orlin D. Velev
Micromachines 2021, 12(12), 1513; https://doi.org/10.3390/mi12121513 - 4 Dec 2021
Cited by 21 | Viewed by 5092
Abstract
Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in [...] Read more.
Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in humans at rest), and do not provide adequate information about the relationship between sweat and blood lactate levels. Here, we discuss the on-skin operation of our recently developed wearable sweat sampling patch. The patch combines osmosis (using hydrogel discs) and capillary action (using paper microfluidic channel) for long-term sweat withdrawal and management. When subjects are at rest, the hydrogel disc can withdraw fluid from the skin via osmosis and deliver it to the paper. The lactate amount in the fluid is determined using a colorimetric assay. During active sweating (e.g., exercise), the paper can harvest sweat even in the absence of the hydrogel patch. The captured fluid contains lactate, which we quantify using a colorimetric assay. The measurements show the that the total number of moles of lactate in sweat is correlated to sweat rate. Lactate concentrations in sweat and blood correlate well only during high-intensity exercise. Hence, sweat appears to be a suitable biofluid for lactate quantification. Overall, this wearable patch holds the potential of providing a comprehensive analysis of sweat lactate trends in the human body. Full article
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14 pages, 30722 KiB  
Article
Development of an Automated, Non-Enzymatic Nucleic Acid Amplification Test
by Zackary A. Zimmers, Alexander D. Boyd, Hannah E. Stepp, Nicholas M. Adams and Frederick R. Haselton
Micromachines 2021, 12(10), 1204; https://doi.org/10.3390/mi12101204 - 30 Sep 2021
Cited by 3 | Viewed by 2548
Abstract
Among nucleic acid diagnostic strategies, non-enzymatic tests are the most promising for application at the point of care in low-resource settings. They remain relatively under-utilized, however, due to inadequate sensitivity. Inspired by a recent demonstration of a highly-sensitive dumbbell DNA amplification strategy, we [...] Read more.
Among nucleic acid diagnostic strategies, non-enzymatic tests are the most promising for application at the point of care in low-resource settings. They remain relatively under-utilized, however, due to inadequate sensitivity. Inspired by a recent demonstration of a highly-sensitive dumbbell DNA amplification strategy, we developed an automated, self-contained assay for detection of target DNA. In this new diagnostic platform, called the automated Pi-powered looping oligonucleotide transporter, magnetic beads capture the target DNA and are then loaded into a microfluidic reaction cassette along with the other reaction solutions. A stepper motor controls the motion of the cassette relative to an external magnetic field, which moves the magnetic beads through the reaction solutions automatically. Real-time fluorescence is used to measure the accumulation of dumbbells on the magnetic bead surface. Left-handed DNA dumbbells produce a distinct signal which reflects the level of non-specific amplification, acting as an internal control. The autoPiLOT assay detected as little as 5 fM target DNA, and was also successfully applied to the detection of S. mansoni DNA. The autoPiLOT design is a novel step forward in the development of a sensitive, user-friendly, low-resource, non-enzymatic diagnostic test. Full article
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11 pages, 3776 KiB  
Article
Microfluidic Device Using Mouse Small Intestinal Tissue for the Observation of Fluidic Behavior in the Lumen
by Satoru Kuriu, Naoyuki Yamamoto and Tadashi Ishida
Micromachines 2021, 12(6), 692; https://doi.org/10.3390/mi12060692 - 13 Jun 2021
Cited by 4 | Viewed by 3656
Abstract
The small intestine has the majority of a host’s immune cells, and it controls immune responses. Immune responses are induced by a gut bacteria sampling process in the small intestine. The mechanism of immune responses in the small intestine is studied by genomic [...] Read more.
The small intestine has the majority of a host’s immune cells, and it controls immune responses. Immune responses are induced by a gut bacteria sampling process in the small intestine. The mechanism of immune responses in the small intestine is studied by genomic or histological techniques after in vivo experiments. While the distribution of gut bacteria, which can be decided by the fluid flow field in the small intestinal tract, is important for immune responses, the fluid flow field has not been studied due to limits in experimental methods. Here, we propose a microfluidic device with chemically fixed small intestinal tissue as a channel. A fluid flow field in the small intestinal tract with villi was observed and analyzed by particle image velocimetry. After the experiment, the distribution of microparticles on the small intestinal tissue was histologically analyzed. The result suggests that the fluid flow field supports the settlement of microparticles on the villi. Full article
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15 pages, 2686 KiB  
Article
Toward Development of a Label-Free Detection Technique for Microfluidic Fluorometric Peptide-Based Biosensor Systems
by Nikita Sitkov, Tatiana Zimina, Alexander Kolobov, Vladimir Karasev, Alexander Romanov, Viktor Luchinin and Dmitry Kaplun
Micromachines 2021, 12(6), 691; https://doi.org/10.3390/mi12060691 - 13 Jun 2021
Cited by 17 | Viewed by 3233
Abstract
The problems of chronic or noncommunicable diseases (NCD) that now kill around 40 million people each year require multiparametric combinatorial diagnostics for the selection of effective treatment tactics. This could be implemented using the biosensor principle based on peptide aptamers for spatial recognition [...] Read more.
The problems of chronic or noncommunicable diseases (NCD) that now kill around 40 million people each year require multiparametric combinatorial diagnostics for the selection of effective treatment tactics. This could be implemented using the biosensor principle based on peptide aptamers for spatial recognition of corresponding protein markers of diseases in biological fluids. In this paper, a low-cost label-free principle of biomarker detection using a biosensor system based on fluorometric registration of the target proteins bound to peptide aptamers was investigated. The main detection principle considered includes the re-emission of the natural fluorescence of selectively bound protein markers into a longer-wavelength radiation easily detectable by common charge-coupled devices (CCD) using a specific luminophore. Implementation of this type of detection system demands the reduction of all types of stray light and background fluorescence of construction materials and aptamers. The latter was achieved by careful selection of materials and design of peptide aptamers with substituted aromatic amino acid residues and considering troponin T, troponin I, and bovine serum albumin as an example. The peptide aptamers for troponin T were designed in silico using the «Protein 3D» (SPB ETU, St. Petersburg, Russia) software. The luminophore was selected from the line of ZnS-based solid-state compounds. The test microfluidic system was arranged as a flow through a massive of four working chambers for immobilization of peptide aptamers, coupled with the optical detection system, based on thick film technology. The planar optical setup of the biosensor registration system was arranged as an excitation-emission cascade including 280 nm ultraviolet (UV) light-emitting diode (LED), polypropylene (PP) UV transparent film, proteins layer, glass filter, luminophore layer, and CCD sensor. A laboratory sample has been created. Full article
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12 pages, 2133 KiB  
Article
A Portable Microfluidic System for Point-of-Care Detection of Multiple Protein Biomarkers
by Nan Li, Minjie Shen and Youchun Xu
Micromachines 2021, 12(4), 347; https://doi.org/10.3390/mi12040347 - 24 Mar 2021
Cited by 10 | Viewed by 3442
Abstract
Protein biomarkers are indicators of many diseases and are commonly used for disease diagnosis and prognosis prediction in the clinic. The urgent need for point-of-care (POC) detection of protein biomarkers has promoted the development of automated and fully sealed immunoassay platforms. In this [...] Read more.
Protein biomarkers are indicators of many diseases and are commonly used for disease diagnosis and prognosis prediction in the clinic. The urgent need for point-of-care (POC) detection of protein biomarkers has promoted the development of automated and fully sealed immunoassay platforms. In this study, a portable microfluidic system was established for the POC detection of multiple protein biomarkers by combining a protein microarray for a multiplex immunoassay and a microfluidic cassette for reagent storage and liquid manipulation. The entire procedure for the immunoassay was automatically conducted, which included the antibody–antigen reaction, washing and detection. Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carcinoma antigen 125 (CA125) were simultaneously detected in this system within 40 min with limits of detection of 0.303 ng/mL, 1.870 ng/mL, and 18.617 U/mL, respectively. Five clinical samples were collected and tested, and the results show good correlations compared to those measured by the commercial instrument in the hospital. The immunoassay cassette system can function as a versatile platform for the rapid and sensitive multiplexed detection of biomarkers; therefore, it has great potential for POC diagnostics. Full article
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Review

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17 pages, 1234 KiB  
Review
Diagnosis Methods for COVID-19: A Systematic Review
by Renata Maia, Violeta Carvalho, Bernardo Faria, Inês Miranda, Susana Catarino, Senhorinha Teixeira, Rui Lima, Graça Minas and João Ribeiro
Micromachines 2022, 13(8), 1349; https://doi.org/10.3390/mi13081349 - 19 Aug 2022
Cited by 25 | Viewed by 5312
Abstract
At the end of 2019, the coronavirus appeared and spread extremely rapidly, causing millions of infections and deaths worldwide, and becoming a global pandemic. For this reason, it became urgent and essential to find adequate tests for an accurate and fast diagnosis of [...] Read more.
At the end of 2019, the coronavirus appeared and spread extremely rapidly, causing millions of infections and deaths worldwide, and becoming a global pandemic. For this reason, it became urgent and essential to find adequate tests for an accurate and fast diagnosis of this disease. In the present study, a systematic review was performed in order to provide an overview of the COVID-19 diagnosis methods and tests already available, as well as their evolution in recent months. For this purpose, the Science Direct, PubMed, and Scopus databases were used to collect the data and three authors independently screened the references, extracted the main information, and assessed the quality of the included studies. After the analysis of the collected data, 34 studies reporting new methods to diagnose COVID-19 were selected. Although RT-PCR is the gold-standard method for COVID-19 diagnosis, it cannot fulfill all the requirements of this pandemic, being limited by the need for highly specialized equipment and personnel to perform the assays, as well as the long time to get the test results. To fulfill the limitations of this method, other alternatives, including biological and imaging analysis methods, also became commonly reported. The comparison of the different diagnosis tests allowed to understand the importance and potential of combining different techniques, not only to improve diagnosis but also for a further understanding of the virus, the disease, and their implications in humans. Full article
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25 pages, 4369 KiB  
Review
Engineering Organ-on-a-Chip to Accelerate Translational Research
by Jihoon Ko, Dohyun Park, Somin Lee, Burcu Gumuscu and Noo Li Jeon
Micromachines 2022, 13(8), 1200; https://doi.org/10.3390/mi13081200 - 28 Jul 2022
Cited by 27 | Viewed by 6405
Abstract
We guide the use of organ-on-chip technology in tissue engineering applications. Organ-on-chip technology is a form of microengineered cell culture platform that elaborates the in-vivo like organ or tissue microenvironments. The organ-on-chip platform consists of microfluidic channels, cell culture chambers, and stimulus sources [...] Read more.
We guide the use of organ-on-chip technology in tissue engineering applications. Organ-on-chip technology is a form of microengineered cell culture platform that elaborates the in-vivo like organ or tissue microenvironments. The organ-on-chip platform consists of microfluidic channels, cell culture chambers, and stimulus sources that emulate the in-vivo microenvironment. These platforms are typically engraved into an oxygen-permeable transparent material. Fabrication of these materials requires the use of microfabrication strategies, including soft lithography, 3D printing, and injection molding. Here we provide an overview of what is an organ-on-chip platform, where it can be used, what it is composed of, how it can be fabricated, and how it can be operated. In connection with this topic, we also introduce an overview of the recent applications, where different organs are modeled on the microscale using this technology. Full article
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19 pages, 2767 KiB  
Review
Microfluidic Organ-on-a-Chip Devices for Liver Disease Modeling In Vitro
by Perizat Kanabekova, Adina Kadyrova and Gulsim Kulsharova
Micromachines 2022, 13(3), 428; https://doi.org/10.3390/mi13030428 - 10 Mar 2022
Cited by 36 | Viewed by 8370
Abstract
Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have significant potential for the study of the pathophysiology of liver [...] Read more.
Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have significant potential for the study of the pathophysiology of liver diseases in vitro. Different liver-on-a-chip microphysiological platforms have been reported to study cell-signaling pathways such as those activating stellate cells within liver diseases. Moreover, the drug efficacy for liver conditions might be evaluated on a cellular metabolic level. Here, we present a comprehensive review of microphysiological platforms used for modelling liver diseases. First, we briefly introduce the concept and importance of organs-on-a-chip in studying liver diseases in vitro, reflecting on existing reviews of healthy liver-on-a-chip platforms. Second, the techniques of cell cultures used in the microfluidic devices, including 2D, 3D, and spheroid cells, are explained. Next, the types of liver diseases (NAFLD, ALD, hepatitis infections, and drug injury) on-chip are explained for a further comprehensive overview of the design and methods of developing liver diseases in vitro. Finally, some challenges in design and existing solutions to them are reviewed Full article
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14 pages, 2675 KiB  
Review
Computational Simulations in Advanced Microfluidic Devices: A Review
by Violeta Carvalho, Raquel O. Rodrigues, Rui A. Lima and Senhorinha Teixeira
Micromachines 2021, 12(10), 1149; https://doi.org/10.3390/mi12101149 - 23 Sep 2021
Cited by 22 | Viewed by 4269
Abstract
Numerical simulations have revolutionized research in several engineering areas by contributing to the understanding and improvement of several processes, being biomedical engineering one of them. Due to their potential, computational tools have gained visibility and have been increasingly used by several research groups [...] Read more.
Numerical simulations have revolutionized research in several engineering areas by contributing to the understanding and improvement of several processes, being biomedical engineering one of them. Due to their potential, computational tools have gained visibility and have been increasingly used by several research groups as a supporting tool for the development of preclinical platforms as they allow studying, in a more detailed and faster way, phenomena that are difficult to study experimentally due to the complexity of biological processes present in these models—namely, heat transfer, shear stresses, diffusion processes, velocity fields, etc. There are several contributions already in the literature, and significant advances have been made in this field of research. This review provides the most recent progress in numerical studies on advanced microfluidic devices, such as organ-on-a-chip (OoC) devices, and how these studies can be helpful in enhancing our insight into the physical processes involved and in developing more effective OoC platforms. In general, it has been noticed that in some cases, the numerical studies performed have limitations that need to be improved, and in the majority of the studies, it is extremely difficult to replicate the data due to the lack of detail around the simulations carried out. Full article
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