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2 pages, 161 KiB

Open AccessEditorial

Editorial for the Special Issue on Microfluidics for Soft Matter and Mechanobiology

by Sung Sik Lee

Micromachines 2020, 11(4), 372; https://doi.org/10.3390/mi11040372 - 02 Apr 2020

Cited by 3 | Viewed by 1526

Abstract

Microfluidics has proven to be a useful platform to understand the material properties and technical applications of soft matter, including emulsions, polymer solutions, hydrogels, and cellulose papers [...] Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

Research

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13 pages, 3436 KiB

Open AccessFeature PaperArticle

On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures

by Tao Yue, Na Liu, Yuanyuan Liu, Yan Peng, Shaorong Xie, Jun Luo, Qiang Huang, Masaru Takeuchi and Toshio Fukuda

Micromachines 2019, 10(12), 840; https://doi.org/10.3390/mi10120840 - 01 Dec 2019

Cited by 11 | Viewed by 3246

Abstract

Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based [...] Read more.

Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based on direct fabrication and assembly inside a microfluidic device. This four-layer microfluidic device has two separate inlets for fabricating various microstructures. We have achieved alternating-layered microtubes by controlling the fabrication, flow, and assembly time of each microstructure, and as well, double-layered microtubes have been built by a two-step assembly method. Modifications of both the inner and outer layers was successfully demonstrated, and the flow conditions during the on-chip assembly were evaluated and optimized. Each microtube was successfully constructed within several minutes, showing the potential applications of the presented method for building engineered vascular-like microstructures with high efficiency. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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14 pages, 2774 KiB

Open AccessArticle

Sheathless Shape-Based Separation of Candida Albicans Using a Viscoelastic Non-Newtonian Fluid

by Jeonghun Nam, Hyunseul Jee, Woong Sik Jang, Jung Yoon, Borae G. Park, Seong Jae Lee and Chae Seung Lim

Micromachines 2019, 10(12), 817; https://doi.org/10.3390/mi10120817 - 26 Nov 2019

Cited by 18 | Viewed by 2935

Abstract

Rapid and accurate identification of Candida albicans from among other candida species is critical for cost-effective treatment and antifungal drug assays. Shape is a critical biomarker indicating cell type, cell cycle, and environmental conditions; however, most microfluidic techniques have been focused only on [...] Read more.

Rapid and accurate identification of Candida albicans from among other candida species is critical for cost-effective treatment and antifungal drug assays. Shape is a critical biomarker indicating cell type, cell cycle, and environmental conditions; however, most microfluidic techniques have been focused only on size-based particle/cell manipulation. This study demonstrates a sheathless shape-based separation of particles/cells using a viscoelastic non-Newtonian fluid. The size of C. albicans was measured at 37 °C depending on the incubation time (0 h, 1 h, and 2 h). The effects of flow rates on the flow patterns of candida cells with different shapes were examined. Finally, 2-h-incubated candida cells with germ tube formations (≥26 μm) were separated from spherical candida cells and shorter candida cells with a separation efficiency of 80.9% and a purity of 91.2% at 50 μL/min. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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8 pages, 2373 KiB

Open AccessArticle

Prediction of Droplet Production Speed by Measuring the Droplet Spacing Fluctuations in a Flow-Focusing Microdroplet Generator

by Wen Zeng, Dong Xiang and Hai Fu

Micromachines 2019, 10(12), 812; https://doi.org/10.3390/mi10120812 - 25 Nov 2019

Cited by 5 | Viewed by 3092

Abstract

In a flow-focusing microdroplet generator, by changing the flow rates of the two immiscible fluids, production speed can be increased from tens to thousands of droplets per second. However, because of the nonlinearity of the flow-focusing microdroplet generator, the production speed of droplets [...] Read more.

In a flow-focusing microdroplet generator, by changing the flow rates of the two immiscible fluids, production speed can be increased from tens to thousands of droplets per second. However, because of the nonlinearity of the flow-focusing microdroplet generator, the production speed of droplets is difficult to quantitatively study for the typical flow-focusing geometry. In this paper, we demonstrate an efficient method that can precisely predict the droplet production speed for a wide range of fluid flow rates. While monodisperse droplets are formed in the flow-focusing microchannel, droplet spacing as a function of time was measured experimentally. We discovered that droplet spacing changes periodically with time during each process of droplet generation. By comparing the frequency of droplet spacing fluctuations with the droplet production speed, precise predictions of droplet production speed can be obtained for different flow conditions in the flow-focusing microdroplet generator. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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15 pages, 3775 KiB

Open AccessArticle

CO₂ Laser Fabrication of PMMA Microfluidic Double T-Junction Device with Modified Inlet-Angle for Cost-Effective PCR Application

by Gamal A. Nasser, Ahmed M.R. Fath El-Bab, Ahmed L. Abdel-Mawgood, Hisham Mohamed and Abdelatty M. Saleh

Micromachines 2019, 10(10), 678; https://doi.org/10.3390/mi10100678 - 09 Oct 2019

Cited by 19 | Viewed by 3947

Abstract

The formation of uniform droplets and the control of their size, shape and monodispersity are of utmost importance in droplet-based microfluidic systems. The size of the droplets is precisely tuned by the channel geometry, the surface interfacial tension, the shear force and fluid [...] Read more.

The formation of uniform droplets and the control of their size, shape and monodispersity are of utmost importance in droplet-based microfluidic systems. The size of the droplets is precisely tuned by the channel geometry, the surface interfacial tension, the shear force and fluid velocity. In addition, the fabrication technique and selection of materials are essential to reduce the fabrication cost and time. In this paper, for reducing the fabrication cost Polymethyl methacrylate (PMMA) sheet is used with direct write laser technique by VERSA CO₂ laser VLS3.5. This laser writing technique gives minimum channel width of about

160 μ m

, which limit miniaturizing the droplet. To overcome this, modification on double T-junction (DTJ) channel geometry has been done by modifying the channel inlets angles. First, a two-dimensional (2D) simulation has been done to study the effect of the new channel geometry modification on droplet size, droplets distribution inside the channel, and its throughput. The fabricated modified DTJ gives the minimum droplet diameter of

39 \pm 2 μ m

, while DTJ channel produced droplet diameter of

48 \pm 4 μ m

at the same conditions. Moreover, the modified double T-junction (MDTJ) decreases the variation in droplets diameter at the same flow rates by

4.5 - 13 %

than DTJ. This low variation in the droplet diameter is suitable for repeatability of the DNA detection results. The MDTJ also enhanced the droplet generation frequency by

8 - 25 %

more than the DTJ channel. The uniformity of droplet distribution inside the channel was enhanced by

3 - 20 %

compared to the DTJ channel geometry. This fabrication technique eliminates the need for a photomask and cleanroom environment in addition shortening the cost and time. It takes only

20 \min

for fabrication. The minimum generated droplet diameter is within

40 μ m

with more than

1000

droplets per second (at

10 mL / h

. oil flow rate). The device is a high-throughput and low-cost micro-droplet formation aimed to be as a front-end to a dynamic droplet digital PCR (ddPCR) platform for use in resource-limited environment. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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13 pages, 2230 KiB

Open AccessFeature PaperArticle

Scalable Production of Monodisperse Functional Microspheres by Multilayer Parallelization of High Aspect Ratio Microfluidic Channels

by Casper Ho Yin Chung, Binbin Cui, Ruyuan Song, Xin Liu, Xiaonan Xu and Shuhuai Yao

Micromachines 2019, 10(9), 592; https://doi.org/10.3390/mi10090592 - 10 Sep 2019

Cited by 17 | Viewed by 4037

Abstract

Droplet microfluidics enables the generation of highly uniform emulsions with excellent stability, precise control over droplet volume, and morphology, which offer superior platforms over conventional technologies for material synthesis and biological assays. However, it remains a challenge to scale up the production of [...] Read more.

Droplet microfluidics enables the generation of highly uniform emulsions with excellent stability, precise control over droplet volume, and morphology, which offer superior platforms over conventional technologies for material synthesis and biological assays. However, it remains a challenge to scale up the production of the microfluidic devices due to their complicated geometry and long-term reliability. In this study, we present a high-throughput droplet generator by parallelization of high aspect ratio rectangular structures, which enables facile and scalable generation of uniform droplets without the need to precisely control external flow conditions. A multilayer device is formed by stacking layer-by-layer of the polydimethylsiloxane (PDMS) replica patterned with parallelized generators. By feeding the sample fluid into the device immersed in the carrying fluid, we used the multilayer device with 1200 parallelized generators to generate monodisperse droplets (~45 μm in diameter with a coefficient of variation <3%) at a frequency of 25 kHz. We demonstrate this approach is versatile for a wide range of materials by synthesis of polyacrylamide hydrogel and Poly (l-lactide-co-glycolide) (PLGA) through water-in-oil (W/O) and oil-in-water (O/W) emulsion templates, respectively. The combined scalability and robustness of such droplet emulsion technology is promising for production of monodisperse functional materials for large-scale applications. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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13 pages, 3149 KiB

Open AccessFeature PaperCommunication

A Toolbox for Organelle Mechanobiology Research—Current Needs and Challenges

by Qian Feng, Sung Sik Lee and Benoît Kornmann

Micromachines 2019, 10(8), 538; https://doi.org/10.3390/mi10080538 - 16 Aug 2019

Cited by 10 | Viewed by 4913

Abstract

Mechanobiology studies from the last decades have brought significant insights into many domains of biological research, from development to cellular signaling. However, mechano-regulation of subcellular components, especially membranous organelles, are only beginning to be unraveled. In this paper, we take mitochondrial mechanobiology as [...] Read more.

Mechanobiology studies from the last decades have brought significant insights into many domains of biological research, from development to cellular signaling. However, mechano-regulation of subcellular components, especially membranous organelles, are only beginning to be unraveled. In this paper, we take mitochondrial mechanobiology as an example to discuss recent advances and current technical challenges in this field. In addition, we discuss the needs for future toolbox development for mechanobiological research of intracellular organelles. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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12 pages, 3040 KiB

Open AccessArticle

Effects of Ionic Strength on Lateral Particle Migration in Shear-Thinning Xanthan Gum Solutions

by Mira Cho, Sun Ok Hong, Seung Hak Lee, Kyu Hyun and Ju Min Kim

Micromachines 2019, 10(8), 535; https://doi.org/10.3390/mi10080535 - 15 Aug 2019

Cited by 8 | Viewed by 3733

Abstract

Viscoelastic fluids, including particulate systems, are found in various biological and industrial systems including blood flow, food, cosmetics, and electronic materials. Particles suspended in viscoelastic fluids such as polymer solutions migrate laterally, forming spatially segregated streams in pressure-driven flow. Viscoelastic particle migration was [...] Read more.

Viscoelastic fluids, including particulate systems, are found in various biological and industrial systems including blood flow, food, cosmetics, and electronic materials. Particles suspended in viscoelastic fluids such as polymer solutions migrate laterally, forming spatially segregated streams in pressure-driven flow. Viscoelastic particle migration was recently applied to microfluidic technologies including particle counting and sorting and the micromechanical measurement of living cells. Understanding the effects on equilibrium particle positions of rheological properties of suspending viscoelastic fluid is essential for designing microfluidic applications. It has been considered that the shear-thinning behavior of viscoelastic fluid is a critical factor in determining the equilibrium particle positions. This work presents the lateral particle migration in two different xanthan gum-based viscoelastic fluids with similar shear-thinning viscosities and the linear viscoelastic properties. The flexibility and contour length of the xanthan gum molecules were tuned by varying the ionic strength of the solvent. Particles suspended in flexible and short xanthan gum solution, dissolved at high ionic strength, migrated toward the corners in a square channel, whereas particles in the rigid and long xanthan gum solutions in deionized water migrated toward the centerline. This work suggests that the structural properties of polymer molecules play significant roles in determining the equilibrium positions in shear-thinning fluids, despite similar bulk rheological properties. The current results are expected to be used in a wide range of applications such as cell counting and sorting. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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14 pages, 2348 KiB

Open AccessArticle

Direct Patterning of a Carbon Nanotube Thin Layer on a Stretchable Substrate

by Eunji Lee, Hye Jin Kim, Yejin Park, Seungjun Lee, Sae Youn Lee, Taewon Ha, Hyun-Joon Shin, Youngbaek Kim and Jinsik Kim

Micromachines 2019, 10(8), 530; https://doi.org/10.3390/mi10080530 - 11 Aug 2019

Cited by 7 | Viewed by 4243

Abstract

Solution-based direct patterning on an elastomer substrate with meniscus-dragging deposition (MDD) enables fabrication of very thin carbon nanotube (CNT) layers in the nanometer scale (80–330 nm). To fabricate the CNT pattern with CNT solution, contact angle, electrical variation, mechanical stress, and surface cracks [...] Read more.

Solution-based direct patterning on an elastomer substrate with meniscus-dragging deposition (MDD) enables fabrication of very thin carbon nanotube (CNT) layers in the nanometer scale (80–330 nm). To fabricate the CNT pattern with CNT solution, contact angle, electrical variation, mechanical stress, and surface cracks of elastomer substrate were analyzed to identify the optimal conditions of O₂ treatment (treatment for 30 s with RF power of 50 W in O₂ atmosphere of 50 sccm) and mixture ratio between Ecoflex and polydimethylsiloxane (PDMS) (Ecoflex:PDMS = 5:1). The type of mask for patterning of the CNT layer was determined through quantitative analysis for sharpness and uniformity of the fabricated CNT pattern. Through these optimization processes, the CNT pattern was produced on the elastomer substrate with selected mask (30 μm thick oriented polypropylene). The thickness of CNT pattern was also controlled to have hundreds nanometer and 500 μm wide rectangular and circular shapes were demonstrated. Furthermore, the change in the current and resistance of the CNT layer according to the applied strain on the elastomer substrate was analyzed. Our results demonstrated the potential of the MDD method for direct CNT patterning with high uniformity and the possibility to fabricate a stretchable sensor. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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9 pages, 3310 KiB

Open AccessArticle

Microfluidic Generation of Amino-Functionalized Hydrogel Microbeads Capable of On-Bead Bioassay

by Seongsoo Kim, Sang-Myung Lee, Sung Sik Lee and Dong-Sik Shin

Micromachines 2019, 10(8), 527; https://doi.org/10.3390/mi10080527 - 09 Aug 2019

Cited by 4 | Viewed by 4548

Abstract

Microfluidic generation of hydrogel microbeads is a highly efficient and reproducible approach to create various functional hydrogel beads. Here, we report a method to prepare crosslinked amino-functionalized polyethylene glycol (PEG) microbeads using a microfluidic channel. The microbeads generated from a microfluidic device were [...] Read more.

Microfluidic generation of hydrogel microbeads is a highly efficient and reproducible approach to create various functional hydrogel beads. Here, we report a method to prepare crosslinked amino-functionalized polyethylene glycol (PEG) microbeads using a microfluidic channel. The microbeads generated from a microfluidic device were evaluated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and confocal laser scanning microscopy, respectively. We found that the microbeads were monodisperse and the amino groups were localized on the shell region of the microbeads. A swelling test exhibited compatibility with various solvents. A cell binding assay was successfully performed with RGD peptide-coupled amino-functionalized hydrogel microbeads. This strategy will enable the large production of the various functional microbeads, which can be used for solid phase peptide synthesis and on-bead bioassays. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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12 pages, 2252 KiB

Open AccessArticle

Sheathless High-Throughput Circulating Tumor Cell Separation Using Viscoelastic non-Newtonian Fluid

by Hyunjung Lim, Seung Min Back, Min Ho Hwang, Dae-Hee Lee, Hyuk Choi and Jeonghun Nam

Micromachines 2019, 10(7), 462; https://doi.org/10.3390/mi10070462 - 10 Jul 2019

Cited by 24 | Viewed by 3523

Abstract

Circulating tumor cells (CTCs) have attracted increasing attention as important biomarkers for clinical and biological applications. Several microfluidic approaches have been demonstrated to separate CTCs using immunoaffinity or size difference from other blood cells. This study demonstrates a sheathless, high-throughput separation of CTCs [...] Read more.

Circulating tumor cells (CTCs) have attracted increasing attention as important biomarkers for clinical and biological applications. Several microfluidic approaches have been demonstrated to separate CTCs using immunoaffinity or size difference from other blood cells. This study demonstrates a sheathless, high-throughput separation of CTCs from white blood cells (WBCs) using a viscoelastic fluid. To determine the fluid viscoelasticity and the flow rate for CTC separation, and to validate the device performance, flow characteristics of 6, 13, and 27 μm particles in viscoelastic fluids with various concentrations were estimated at different flow rates. Using 0.2% hyaluronic acid (HA) solution, MCF-7 (Michigan Cancer Foundation-7) cells mimicking CTCs in this study were successfully separated from WBCs at 500 μL/min with a separation efficiency of 94.8%. Small amounts of MCF-7 cells (~5.2%) were found at the center outlet due to the size overlap with WBCs. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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Review

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30 pages, 6526 KiB

Open AccessReview

Recent Advances of Fluid Manipulation Technologies in Microfluidic Paper-Based Analytical Devices (μPADs) toward Multi-Step Assays

by Taehoon H. Kim, Young Ki Hahn and Minseok S. Kim

Micromachines 2020, 11(3), 269; https://doi.org/10.3390/mi11030269 - 04 Mar 2020

Cited by 39 | Viewed by 6333

Abstract

Microfluidic paper-based analytical devices (μPADs) have been suggested as alternatives for developing countries with suboptimal medical conditions because of their low diagnostic cost, high portability, and disposable characteristics. Recently, paper-based diagnostic devices enabling multi-step assays have been drawing attention, as they allow complicated [...] Read more.

Microfluidic paper-based analytical devices (μPADs) have been suggested as alternatives for developing countries with suboptimal medical conditions because of their low diagnostic cost, high portability, and disposable characteristics. Recently, paper-based diagnostic devices enabling multi-step assays have been drawing attention, as they allow complicated tests, such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), which were previously only conducted in the laboratory, to be performed on-site. In addition, user convenience and price of paper-based diagnostic devices are other competitive points over other point-of-care testing (POCT) devices, which are more critical in developing countries. Fluid manipulation technologies in paper play a key role in realizing multi-step assays via μPADs, and the expansion of biochemical applications will provide developing countries with more medical benefits. Therefore, we herein aimed to investigate recent fluid manipulation technologies utilized in paper-based devices and to introduce various approaches adopting several principles to control fluids on papers. Fluid manipulation technologies are classified into passive and active methods. While passive valves are structurally simple and easy to fabricate, they are difficult to control in terms of flow at a specific spatiotemporal condition. On the contrary, active valves are more complicated and mostly require external systems, but they provide much freedom of fluid manipulation and programmable operation. Both technologies have been revolutionized in the way to compensate for their limitations, and their advances will lead to improved performance of μPADs, increasing the level of healthcare around the world. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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25 pages, 5049 KiB

Open AccessReview

Recent Advances in Droplet-based Microfluidic Technologies for Biochemistry and Molecular Biology

by Joel Sánchez Barea, Juhwa Lee and Dong-Ku Kang

Micromachines 2019, 10(6), 412; https://doi.org/10.3390/mi10060412 - 20 Jun 2019

Cited by 60 | Viewed by 11557

Abstract

Recently, droplet-based microfluidic systems have been widely used in various biochemical and molecular biological assays. Since this platform technique allows manipulation of large amounts of data and also provides absolute accuracy in comparison to conventional bioanalytical approaches, over the last decade a range [...] Read more.

Recently, droplet-based microfluidic systems have been widely used in various biochemical and molecular biological assays. Since this platform technique allows manipulation of large amounts of data and also provides absolute accuracy in comparison to conventional bioanalytical approaches, over the last decade a range of basic biochemical and molecular biological operations have been transferred to drop-based microfluidic formats. In this review, we introduce recent advances and examples of droplet-based microfluidic techniques that have been applied in biochemistry and molecular biology research including genomics, proteomics and cellomics. Their advantages and weaknesses in various applications are also comprehensively discussed here. The purpose of this review is to provide a new point of view and current status in droplet-based microfluidics to biochemists and molecular biologists. We hope that this review will accelerate communications between researchers who are working in droplet-based microfluidics, biochemistry and molecular biology. Full article

(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)

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