Special Issue "Advances in Microfluidics for Quantifying Cell Mechanics and Biotransport"

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

Deadline for manuscript submissions: closed (20 August 2021) | Viewed by 4978

Special Issue Editors

Dr. Hiroaki Ito
E-Mail Website
Guest Editor
Department of Physics, Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba, Japan
Interests: non-equilibrium interfacial phenomena; structure and function of soft interfaces in meso-scale;soft matter physics; biophysics; physics of diseases; medical application; control engineering; robotics
Dr. Naoki Takeishi
E-Mail Website
Guest Editor
Department of Mechanical Science & Bioengineering, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan
Interests: fluid mechanics; computational biomechanics; microcirculation; (hemo)rheology; capsule; red blood cell (RBC); margination; leukocyte; platlets; circulating tumor cell (CTC); cell adhesion; drug delivery; cancer metastasis; active cell migration; brain development; GPGPU

Special Issue Information

Dear Colleagues,

Microfluidics is a fundamental but practical way to precisely manipulate and control fluids and small particles and has been widely used in various fields, including physics, engineering, medicine, biology, and chemistry. Due to recent advancements, this technology enables us to perform automated, high-throughput, and precisely controlled assays even with extremely small amounts of reagent. Quantification of the mechanical properties or microscopic responses of biological cells has led to the development of appropriate mathematical models and also to systematic computational studies, which have revealed their underlying mechanics, e.g., relationships between the stress field and cell deformation. Thus, for clarifying mechanisms or developing a deeper understanding of the microscopic biological phenomena, more detailed and statistically reliable quantification in microfluidic devices is necessary. Based on this idea, we hope that such studies will provide insight not only into cell biology but also into the precise diagnosis of, e.g., hematologic disorders.

In this Special Issue, we highlight recent advances in microfluidics for quantifying cell mechanics and biotransport phenomena, with original research papers and review papers that focus on single-cell mechanics, suspension rheology, the collective behaviors of microswimmers, the mechanical responses of cells in confined fluid flow, fundamental technologies in micro-electro-mechanical systems (MEMS), and mathematical models. We look forward to receiving your submissions.

Dr. Hiroaki Ito
Dr. Naoki Takeishi
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 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

  • microfluidics
  • confined flow
  • cell mechanics
  • cell physiology
  • mechanotransduction
  • biotransport
  • biorheology
  • microswimmer
  • microrobotics
  • cell manipulation
  • diagnostics
  • mathematical model
  • computational fluid mechanics

Published Papers (7 papers)

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Research

Article
Accumulation of Tetrahymena pyriformis on Interfaces
Micromachines 2021, 12(11), 1339; https://doi.org/10.3390/mi12111339 - 30 Oct 2021
Viewed by 525
Abstract
The behavior of ciliates has been studied for many years through environmental biology and the ethology of microorganisms, and recent hydrodynamic studies of microswimmers have greatly advanced our understanding of the behavioral dynamics at the single-cell level. However, the association between single-cell dynamics [...] Read more.
The behavior of ciliates has been studied for many years through environmental biology and the ethology of microorganisms, and recent hydrodynamic studies of microswimmers have greatly advanced our understanding of the behavioral dynamics at the single-cell level. However, the association between single-cell dynamics captured by microscopic observation and pattern dynamics obtained by macroscopic observation is not always obvious. Hence, to bridge the gap between the two, there is a need for experimental results on swarming dynamics at the mesoscopic scale. In this study, we investigated the spatial population dynamics of the ciliate, Tetrahymena pyriformis, based on quantitative data analysis. We combined the image processing of 3D micrographs and machine learning to obtain the positional data of individual cells of T. pyriformis and examined their statistical properties based on spatio-temporal data. According to the 3D spatial distribution of cells and their temporal evolution, cells accumulated both on the solid wall at the bottom surface and underneath the air–liquid interface at the top. Furthermore, we quantitatively clarified the difference in accumulation levels between the bulk and the interface by creating a simple behavioral model that incorporated quantitative accumulation coefficients in its solution. The accumulation coefficients can be compared under different conditions and between different species. Full article
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Article
Pattern Transition on Inertial Focusing of Neutrally Buoyant Particles Suspended in Rectangular Duct Flows
Micromachines 2021, 12(10), 1242; https://doi.org/10.3390/mi12101242 - 14 Oct 2021
Viewed by 411
Abstract
The continuous separation and filtration of particles immersed in fluid flows are important interests in various applications. Although the inertial focusing of particles suspended in a duct flow is promising in microfluidics, predicting the focusing positions depending on the parameters, such as the [...] Read more.
The continuous separation and filtration of particles immersed in fluid flows are important interests in various applications. Although the inertial focusing of particles suspended in a duct flow is promising in microfluidics, predicting the focusing positions depending on the parameters, such as the shape of the duct cross-section and the Reynolds number (Re) has not been achieved owing to the diversity of the inertial-focusing phenomena. In this study, we aimed to elucidate the variation of the inertial focusing depending on Re in rectangular duct flows. We performed a numerical simulation of the lift force exerted on a spherical particle flowing in a rectangular duct and determined the lift-force map within the duct cross-section over a wide range of Re. We estimated the particle trajectories based on the lift map and Stokes drag, and identified the particle-focusing points appeared in the cross-section. For an aspect ratio of the duct cross-section of 2, we found that the blockage ratio changes transition structure of particle focusing. For blockage ratios smaller than 0.3, particles focus near the centres of the long sides of the cross-section at low Re and near the centres of both the long and short sides at relatively higher Re. This transition is expressed as a subcritical pitchfork bifurcation. For blockage ratio larger than 0.3, another focusing pattern appears between these two focusing regimes, where particles are focused on the centres of the long sides and at intermediate positions near the corners. Thus, there are three regimes; the transition between adjacent regimes at lower Re is found to be expressed as a saddle-node bifurcation and the other transition as a supercritical pitchfork bifurcation. Full article
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Article
The Effect of the Layered Internal Structure of Fibrous Beds on the Hydrodynamic Diffusive Behavior of Microparticles
Micromachines 2021, 12(10), 1241; https://doi.org/10.3390/mi12101241 - 13 Oct 2021
Viewed by 443
Abstract
To separate and collect microparticles such as cells, the behavior of particles in fibrous filters was investigated. It is essential to understand, in detail, the motion of particles in microscale flows, because Re is often small, and particles exhibit complex behaviors such as [...] Read more.
To separate and collect microparticles such as cells, the behavior of particles in fibrous filters was investigated. It is essential to understand, in detail, the motion of particles in microscale flows, because Re is often small, and particles exhibit complex behaviors such as changes in relative position and spreading owing to hydrodynamic interactions. We calculated the motion of microparticles passing through the fibrous bed using the Stokesian dynamics method, in which hydrodynamic interaction is considered, theoretically. The fibrous bed was modeled by particles and five types of structures (a monolayer with fiber volume fractions φ of 3%, 4%, and 5%, and a bilayer with φ = 3%−5% and 5%−3%) were considered. Our numerical results showed that the particles moved in a complicated manner, and spread throughout the fibrous bed. It was found that the behavior of individual microparticles varied depending on the internal structure, although the average permeation velocity was primarily determined by the fiber volume fraction. This great dependence of the behavior of particle assemblage on the internal structure of the fibrous bed was caused by the individual particle motion under the influence of the layers in front of and behind them, owing to the hydrodynamic interaction. Full article
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Article
Margination of Platelet-Sized Particles in the Red Blood Cell Suspension Flow through Square Microchannels
Micromachines 2021, 12(10), 1175; https://doi.org/10.3390/mi12101175 - 29 Sep 2021
Cited by 1 | Viewed by 563
Abstract
In the blood flow through microvessels, platelets show high concentrations near the vessel wall. This phenomenon is called margination of platelets and is closely associated with hemostasis and thrombosis. In the present study, we conducted in vitro experiments using platelet-sized fluorescent particles as [...] Read more.
In the blood flow through microvessels, platelets show high concentrations near the vessel wall. This phenomenon is called margination of platelets and is closely associated with hemostasis and thrombosis. In the present study, we conducted in vitro experiments using platelet-sized fluorescent particles as platelet substitutes to investigate the cross-sectional distribution of these particles in the red blood cell suspension flowing through microchannels with a square cross section. Fluorescence observations were performed to measure the transverse distribution of particles at various heights from the bottom face with the use of a confocal laser scanning microscope system. In downstream cross sections of the channel, particles showed focusing near the four corners rather than uniform margination along the entire circumference of the cross section. The focusing of particles near the corners was more enhanced for higher hematocrits. On the other hand, particles in circular channel flows showed nearly axisymmetric uniform accumulation adjacent to the channel wall. The present result suggests that the segregation of suspended particles in the flow of multicomponent suspensions could have such heterogeneous 2D features of particle distribution in the cross section of channels, especially for rectangular channels often used in microfluidics. Full article
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Article
Axial and Nonaxial Migration of Red Blood Cells in a Microtube
Micromachines 2021, 12(10), 1162; https://doi.org/10.3390/mi12101162 - 28 Sep 2021
Cited by 1 | Viewed by 697
Abstract
Human red blood cells (RBCs) are subjected to high viscous shear stress, especially during microcirculation, resulting in stable deformed shapes such as parachute or slipper shape. Those unique deformed RBC shapes, accompanied with axial or nonaxial migration, cannot be fully described according to [...] Read more.
Human red blood cells (RBCs) are subjected to high viscous shear stress, especially during microcirculation, resulting in stable deformed shapes such as parachute or slipper shape. Those unique deformed RBC shapes, accompanied with axial or nonaxial migration, cannot be fully described according to traditional knowledge about lateral movement of deformable spherical particles. Although several experimental and numerical studies have investigated RBC behavior in microchannels with similar diameters as RBCs, the detailed mechanical characteristics of RBC lateral movement—in particular, regarding the relationship between stable deformed shapes, equilibrium radial RBC position, and membrane load—has not yet been fully described. Thus, we numerically investigated the behavior of single RBCs with radii of 4 μm in a circular microchannel with diameters of 15 μm. Flow was assumed to be almost inertialess. The problem was characterized by the capillary number, which is the ratio between fluid viscous force and membrane elastic force. The power (or energy dissipation) associated with membrane deformations was introduced to quantify the state of membrane loads. Simulations were performed with different capillary numbers, viscosity ratios of the internal to external fluids of RBCs, and initial RBC centroid positions. Our numerical results demonstrated that axial or nonaxial migration of RBC depended on the stable deformed RBC shapes, and the equilibrium radial position of the RBC centroid correlated well with energy expenditure associated with membrane deformations. Full article
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Article
Fabrication of Microparticles with Front–Back Asymmetric Shapes Using Anisotropic Gelation
Micromachines 2021, 12(9), 1121; https://doi.org/10.3390/mi12091121 - 17 Sep 2021
Cited by 1 | Viewed by 797
Abstract
Droplet-based microfluidics is a powerful tool for producing monodispersed micrometer-sized droplets with controlled sizes and shapes; thus, it has been widely applied in diverse fields from fundamental science to industries. Toward a simpler method for fabricating microparticles with front–back asymmetry in their shapes, [...] Read more.
Droplet-based microfluidics is a powerful tool for producing monodispersed micrometer-sized droplets with controlled sizes and shapes; thus, it has been widely applied in diverse fields from fundamental science to industries. Toward a simpler method for fabricating microparticles with front–back asymmetry in their shapes, we studied anisotropic gelation of alginate droplets, which occurs inside a flow-focusing microfluidic device. In the proposed method, sodium alginate (NaAlg) aqueous phase fused with a calcium chloride (CaCl2) emulsion dispersed in the organic phase just before the aqueous phase breaks up into the droplets. The fused droplet with a front–back asymmetric shape was generated, and the asymmetric shape was kept after geometrical confinement by a narrow microchannel was removed. The shape of the fused droplet depended on the size of prefused NaAlg aqueous phase and a CaCl2 emulsion, and the front–back asymmetry appeared in the case of the smaller emulsion size. The analysis of the velocity field inside and around the droplet revealed that the stagnation point at the tip of the aqueous phase also played an important role. The proposed mechanism will be potentially applicable as a novel fabrication technique of microparticles with asymmetric shapes. Full article
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Article
Driving a Microswimmer with Wall-Induced Flow
Micromachines 2021, 12(9), 1025; https://doi.org/10.3390/mi12091025 - 27 Aug 2021
Cited by 3 | Viewed by 742
Abstract
Active walls such as cilia and bacteria carpets generate background flows that can influence the trajectories of microswimmers moving nearby. Recent advances in artificial magnetic cilia carpets offer the potentiality to use a similar wall-generated background flow to steer bio-hybrid microrobots. In this [...] Read more.
Active walls such as cilia and bacteria carpets generate background flows that can influence the trajectories of microswimmers moving nearby. Recent advances in artificial magnetic cilia carpets offer the potentiality to use a similar wall-generated background flow to steer bio-hybrid microrobots. In this paper, we provide some ground theoretical and numerical work assessing the viability of this novel means of swimmer guidance by setting up a simple model of a spherical swimmer in an oscillatory flow and analysing it from the control theory viewpoint. We show a property of local controllability around the reference free trajectories and investigate the bang–bang structure of the control for time-optimal trajectories, with an estimation of the minimal time for suitable objectives. By direct simulation, we have demonstrated that the wall actuation can improve the wall-following transport by nearly 50%, which can be interpreted by synchronous flow structure. Although an open-loop control with a periodic bang–bang actuation loses some robustness and effectiveness, a feedback control is found to improve its robustness and effective transport, even with hydrodynamic wall-swimmer interactions. The results shed light on the potentialities of flow control and open the way to future experiments on swimmer guidance. Full article
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