Special Issue "Biomedical Microfluidic Devices 2019"

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

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editor

Prof. Dr. Kwang W. Oh
Website
Guest Editor
Director of SMALL (Sensors and MicroActuators Learning Lab) Department of Electrical Engineering and Department of Biomedical Engineering State University of New York at Buffalo (SUNY-Buffalo), Buffalo, NY 14260 USA
Interests: bioMEMS; lab-on-a-chip (LOC); microfluidics; droplet-based microfluidics; blood separation; micro PCR; micro SERS; sensors for LOC
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Special Issue Information

Dear Colleagues,

One of the greatest challenges of researchers using microfluidics is to develop novel microfluidic devices for the enhancement of their capabilities in biology and medical research. Many biomedical microfluidic devices have been miniaturized to replace conventional bioassays and diagnostics, featuring high bioassay performance, high system integration, improved potential for automation and control, small volume of samples and reagents, reduced cost, greater reliability and sensitivity, disposability and shorter bioassay times.

In this Special Issue, we solicit review articles and original research papers addressing technical challenges on developing microfluidic devices for biomedical and diagnostics applications. The papers can cover all aspects of biomedical microfluidic devices including, but not limited to, recent developments in the following areas: biomedical microfluidic devices; DNA, protein, cell, organism, tissue and organ on chip; diagnostics and theranostics; drug discovery and delivery; lab on chip (LOC); manipulation of biomolecules and biofluids; micro total analysis (mTAS); miniaturization of bioassays; and point of care (POC) devices.
Authors are invited to contact the guest editors prior to submission if they are uncertain whether their work falls within the general scope of this Special Issue on "Biomedical Microfluidic Devices 2019".

Prof. Dr. Kwang W. Oh
Guest Editor

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 papers will be 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. Micromachines 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 1600 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 microfluidic devices
  • diagnostics
  • DNA, protein, cell, organism, tissue and organ on chip
  • drug discovery and delivery
  • lab on chip (LOC)
  • manipulation of biomolecules and biofluids
  • micro total analysis (mTAS)
  • miniaturization of bioassays
  • point
  • theranostics

Published Papers (10 papers)

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Editorial

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Open AccessEditorial
Microfluidic Devices for Biomedical Applications: Biomedical Microfluidic Devices 2019
Micromachines 2020, 11(4), 370; https://doi.org/10.3390/mi11040370 - 01 Apr 2020
Abstract
Microfluidic devices and systems are well-suited for the manipulation of biomolecules, cells, or particles [...] Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)

Research

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Open AccessArticle
Measurement of the Imaginary Part of the Clausius-Mossotti Factor of Particle/Cell via Dual Frequency Electrorotation
Micromachines 2020, 11(3), 329; https://doi.org/10.3390/mi11030329 - 22 Mar 2020
Cited by 1
Abstract
A simple and inexpensive method using planar electrodes was proposed for the measurement of the imaginary part of the Clausius-Mossotti factor, K i , of particle/cell for electrorotation (ER) and travelling wave dielectrophoresis (twDEP). It is based on the balance between the dielectrophoretic [...] Read more.
A simple and inexpensive method using planar electrodes was proposed for the measurement of the imaginary part of the Clausius-Mossotti factor, K i , of particle/cell for electrorotation (ER) and travelling wave dielectrophoresis (twDEP). It is based on the balance between the dielectrophoretic and viscous torques on a particle undergoing ER subject to dual frequency operation in an ER chamber. A four-phase ac voltage signal with a given frequency is applied for generating ER for measurement, and another two-phase signal is applied at a selected frequency for generating a negative dielectrophoretic force for confining the particle motion, instead of using laser tweezer or three-dimensional electrodes in the literature. Both frequencies can be applied to the same electrodes in a four-electrode ER system and to alternative different electrodes in an eight-electrode ER system, and both systems are capable for providing accurate measurement. The measurements were validated by comparing with the theoretical result using sephadex particles in KCl solution, and with the existing experimental results for various human cancer cells in medium with conductivity from 0.01–1.2 S/m, using ER with optical tweezer and dual frequency twDEP. Contrast between the ER and the twDEP methods (the current two available methods) was discussed and commented. The present method could provide measurement for wider frequency range and more accurate result near K i = 0, in comparison with the results using the twDEP method. However, the twDEP method could perform much more rapid measurement. Detailed forces and torque were calculated inside the ER chamber for understanding the physics and assessing the characteristics of the dual frequency ER method. This study is of academic interest as the torque in ER and the force in twDEP can be calculated only when K i is known. It also finds biomedical applications as the K i -spectra can be served as physical phenotypes for different cells, and can be applied for deriving dielectric properties of cells. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessFeature PaperArticle
Digital Microfluidics for Single Bacteria Capture and Selective Retrieval Using Optical Tweezers
Micromachines 2020, 11(3), 308; https://doi.org/10.3390/mi11030308 - 15 Mar 2020
Cited by 1
Abstract
When screening microbial populations or consortia for interesting cells, their selective retrieval for further study can be of great interest. To this end, traditional fluorescence activated cell sorting (FACS) and optical tweezers (OT) enabled methods have typically been used. However, the former, although [...] Read more.
When screening microbial populations or consortia for interesting cells, their selective retrieval for further study can be of great interest. To this end, traditional fluorescence activated cell sorting (FACS) and optical tweezers (OT) enabled methods have typically been used. However, the former, although allowing cell sorting, fails to track dynamic cell behavior, while the latter has been limited to complex channel-based microfluidic platforms. In this study, digital microfluidics (DMF) was integrated with OT for selective trapping, relocation, and further proliferation of single bacterial cells, while offering continuous imaging of cells to evaluate dynamic cell behavior. To enable this, magnetic beads coated with Salmonella Typhimurium-targeting antibodies were seeded in the microwell array of the DMF platform, and used to capture single cells of a fluorescent S. Typhimurium population. Next, OT were used to select a bead with a bacterium of interest, based on its fluorescent expression, and to relocate this bead to a different microwell on the same or different array. Using an agar patch affixed on top, the relocated bacterium was subsequently allowed to proliferate. Our OT-integrated DMF platform thus successfully enabled selective trapping, retrieval, relocation, and proliferation of bacteria of interest at single-cell level, thereby enabling their downstream analysis. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessArticle
An Interphase Microfluidic Culture System for the Study of Ex Vivo Intestinal Tissue
Micromachines 2020, 11(2), 150; https://doi.org/10.3390/mi11020150 - 30 Jan 2020
Cited by 1
Abstract
Ex vivo explant culture models offer unique properties to study complex mechanisms underlying tissue growth, renewal, and disease. A major weakness is the short viability depending on the biopsy origin and preparation protocol. We describe an interphase microfluidic culture system to cultivate full [...] Read more.
Ex vivo explant culture models offer unique properties to study complex mechanisms underlying tissue growth, renewal, and disease. A major weakness is the short viability depending on the biopsy origin and preparation protocol. We describe an interphase microfluidic culture system to cultivate full thickness murine colon explants which keeps morphological structures of the tissue up to 192 h. The system was composed of a central well on top of a porous membrane supported by a microchannel structure. The microfluidic perfusion allowed bathing the serosal side while preventing immersion of the villi. After eight days, up to 33% of the samples displayed no histological abnormalities. Numerical simulation of the transport of oxygen and glucose provided technical solutions to improve the functionality of the microdevice. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessFeature PaperArticle
Miniaturized Platform for Individual Coral Polyps Culture and Monitoring
Micromachines 2020, 11(2), 127; https://doi.org/10.3390/mi11020127 - 23 Jan 2020
Cited by 1
Abstract
Methodologies for coral polyps culture and real-time monitoring are important in investigating the effects of the global environmental changes on coral reefs and marine biology. However, the traditional cultivation method is limited in its ability to provide a rapid and dynamic microenvironment to [...] Read more.
Methodologies for coral polyps culture and real-time monitoring are important in investigating the effects of the global environmental changes on coral reefs and marine biology. However, the traditional cultivation method is limited in its ability to provide a rapid and dynamic microenvironment to effectively exchange the chemical substances and simulate the natural environment change. Here, an integrated microdevice with continuous perfusion and temperature-control in the microenvironment was fabricated for dynamic individual coral polyps culture. For a realistic mimicry of the marine ecological environment, we constructed the micro-well based microfluidics platform that created a fluid flow environment with a low shear rate and high substance transfer, and developed a sensitive temperature control system for the long-term culture of individual coral polyps. This miniaturized platform was applied to study the individual coral polyps in response to the temperature change for evaluating the coral death caused by El Nino. The experimental results demonstrated that the microfluidics platform could provide the necessary growth environment for coral polyps as expected so that in turn the biological activity of individual coral polyps can quickly be recovered. The separation between the algae and host polyp cells were observed in the high culture temperature range and the coral polyp metabolism was negatively affected. We believe that our culture platform for individual coral polyps can provide a reliable analytical approach for model and mechanism investigations of coral bleaching and reef conservation. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessArticle
Investigation of Leukocyte Viability and Damage in Spiral Microchannel and Contraction-Expansion Array
Micromachines 2019, 10(11), 772; https://doi.org/10.3390/mi10110772 - 12 Nov 2019
Cited by 2
Abstract
Inertial separation techniques in a microfluidic system have been widely employed in the field of medical diagnosis for a long time. Despite no requirement of external forces, it requires strong hydrodynamic forces that could potentially cause cell damage or loss during the separation [...] Read more.
Inertial separation techniques in a microfluidic system have been widely employed in the field of medical diagnosis for a long time. Despite no requirement of external forces, it requires strong hydrodynamic forces that could potentially cause cell damage or loss during the separation process. This might lead to the wrong interpretation of laboratory results since the change of structures and functional characteristics of cells due to the hydrodynamic forces that occur are not taken into account. Therefore, it is important to investigate the cell viability and damage along with the separation efficacy of the device in the design process. In this study, two inertial separation techniques—spiral microchannel and contraction-expansion array (CEA)—were examined to evaluate cell viability, morphology and intracellular structures using a trypan blue assay (TB), Scanning Electron Microscopy (SEM) and Wright-Giemsa stain. We discovered that cell loss was not significantly found in a feeding system, i.e., syringe, needle and tube, but mostly occurred in the inertial separation devices while the change of cell morphology and intracellular structures were found in the feeding system and inertial separation devices. Furthermore, percentage of cell loss was not significant in both devices (7–10%). However, the change of cell morphology was considerably increased (30%) in spiral microchannel (shear stress dominated) rather than in CEA (12%). In contrast, the disruption of intracellular structures was increased (14%) in CEA (extensional and shear stress dominated equally) rather than spiral microchannel (2%). In these experiments, leukocytes of canine were used as samples because their sizes are varied in a range between 7–12 µm, and they are commonly used as a biomarker in many clinical and medical applications. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessArticle
A Compact, Syringe-Assisted, Vacuum-Driven Micropumping Device
Micromachines 2019, 10(8), 543; https://doi.org/10.3390/mi10080543 - 17 Aug 2019
Cited by 1
Abstract
In this paper, a simple syringe‑assisted pumping method is introduced. The proposed fluidic micropumping system can be used instead of a conventional pumping system which tends to be large, bulky, and expensive. The micropump was designed separately from the microfluidic channels and directly [...] Read more.
In this paper, a simple syringe‑assisted pumping method is introduced. The proposed fluidic micropumping system can be used instead of a conventional pumping system which tends to be large, bulky, and expensive. The micropump was designed separately from the microfluidic channels and directly bonded to the outlet of the microfluidic device. The pump components were composed of a dead‑end channel which was surrounded by a microchamber. A syringe was then connected to the pump structure by a short tube, and the syringe plunger was manually pulled out to generate low pressure inside the microchamber. Once the sample was loaded in the inlet, air inside the channel diffused into the microchamber through the PDMS (polydimethylsiloxane) wall, acting as a dragging force and pulling the sample toward the outlet. A constant flow with a rate that ranged from 0.8 nl · s 1 to 7.5 nl · s 1 was achieved as a function of the geometry of the pump, i.e., the PDMS wall thickness and the diffusion area. As a proof-of-concept, microfluidic mixing was demonstrated without backflow. This method enables pumping for point-of-care testing (POCT) with greater flexibility in hand-held PDMS microfluidic devices. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessArticle
Hemostasis-On-a-Chip: Impedance Spectroscopy Meets Microfluidics for Hemostasis Evaluation
Micromachines 2019, 10(8), 534; https://doi.org/10.3390/mi10080534 - 14 Aug 2019
Cited by 3
Abstract
In the case of vascular injury, a complex process (of clotting) starts, involving mainly platelets and coagulation factors. This process in healthy humans is known as hemostasis, but when it is deregulated (thrombosis), it can be the cause of important cardiovascular diseases. Nowadays, [...] Read more.
In the case of vascular injury, a complex process (of clotting) starts, involving mainly platelets and coagulation factors. This process in healthy humans is known as hemostasis, but when it is deregulated (thrombosis), it can be the cause of important cardiovascular diseases. Nowadays, the aging of the population and unhealthy lifestyles increase the impact of thrombosis, and therefore there is a need for tools to provide a better understanding of the hemostasis mechanisms, as well as more cost-effective diagnosis and control devices. This study proposes a novel microflow chamber, with interchangeable biomimetic surfaces to evaluate global hemostasis, using reduced amounts of blood sample and reagents, and also a minimized time required to do the test. To validate the performance of this novel device, a study on the new oral anticoagulant Apixaban (APIX) has been performed and compared to previous conventional techniques. The test shows an excellent agreement, while the amount of the required sample has been reduced (only 100 µL is used), and the amount of reagent as well. An imprinted electrode embedded in the chamber in order to measure the impedance during the coagulation process. This approach distinguishes the impedance behavior of plasma poor in platelets (PPP) and plasma rich in platelets (PRP) for the first time. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Open AccessArticle
A Low-Cost, Rapidly Integrated Debubbler (RID) Module for Microfluidic Cell Culture Applications
Micromachines 2019, 10(6), 360; https://doi.org/10.3390/mi10060360 - 30 May 2019
Cited by 1
Abstract
Microfluidic platforms use controlled fluid flows to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. Undisturbed flows are critical in these systems, and air bubbles entering microfluidic channels can lead to device delamination or cell [...] Read more.
Microfluidic platforms use controlled fluid flows to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. Undisturbed flows are critical in these systems, and air bubbles entering microfluidic channels can lead to device delamination or cell damage. To prevent bubble entry into microfluidic channels, we report a low-cost, Rapidly Integrated Debubbler (RID) module that is simple to fabricate, inexpensive, and easily combined with existing experimental systems. We demonstrate successful removal of air bubbles spanning three orders of magnitude with a maximum removal rate (dV/dt)max = 1.5 mL min−1, at flow rates required to apply physiological wall shear stress (1–200 dyne cm−2) to mammalian cells cultured in microfluidic channels. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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Review

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Open AccessReview
Microfluidic Systems Applied in Solid-State Nanopore Sensors
Micromachines 2020, 11(3), 332; https://doi.org/10.3390/mi11030332 - 23 Mar 2020
Cited by 1
Abstract
Microfluidic system, as a kind of miniature integrated operating platform, has been applied to solid-state nanopore sensors after many years of experimental study. In the process of introducing microfluidic into solid-state nanopore sensors, many novel device structures are designed due to the abundance [...] Read more.
Microfluidic system, as a kind of miniature integrated operating platform, has been applied to solid-state nanopore sensors after many years of experimental study. In the process of introducing microfluidic into solid-state nanopore sensors, many novel device structures are designed due to the abundance of analytes and the diversity of detection methods. Here we review the fundamental setup of nanopore-based microfluidic systems and the developments and advancements that have been taking place in the field. The microfluidic systems with a multichannel strategy to elevate the throughput and efficiency of nanopore sensors are then presented. Multifunctional detection represented by optical-electrical detection, which is realized by microfluidic integration, is also described. A high integration microfluidic system with nanopore is further discussed, which shows the prototype of commercialization. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices 2019)
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