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Micromachines
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Design, Optimization, Fabrication and Applications of Microfluidic Devices
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Design, Optimization, Fabrication and Applications of Microfluidic Devices

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "E：Engineering and Technology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 23533

Special Issue Editors

Dr. Bobby Mathew

E-Mail Website
Guest Editor
Department of Mechanical Engineering, United Arab Emirates University, Al Ain 17666, United Arab Emirates
Interests: BioMEMS; mathematical modeling; microfabrication
Dr. Nien-Tsu Huang

E-Mail Website
Guest Editor
Department of Electrical Engineering, National Taiwan University, Taipei 106, Taiwan
Interests: Bio-MEMS; optical-MEMS; microfluidics; biosensing; cell manipulation in microenvironment; micro/nano fabrication techniques
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sherif M. Karam

E-Mail Website
Guest Editor
Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates
Interests: stem cells; 3D culture models; tissue engineering; carcinogenesis

Special Issue Information

Dear Colleagues,

This special issue of Micromachines deals with design, optimization and fabrication of microfluidic devices particularly those with biomedical applications. Microfluidic devices are being increasingly proposed, developed and employed for applications in medicine as tools for diagnosis and regenerative therapy. These devices execute operations like heating/cooling, mixing, focusing, and separation. The microfluidic devices have single or multiple flow passages with hydraulic diameter less than 1000 μm and have continuous or intermittent flow of single or multiple fluids achieved using passive or active techniques. Traditional and newer fabrication techniques such as microfabrication, micromachining, soft lithography, and additive manufacturing are employed for realizing these microfluidic devices. You are cordially invited to submit original research as well as review manuscripts related to microfluidic devices developed for biomedical applications to this special issue of Micromachines. Original research and review related to the design and optimization, based on analytical equations and numerical solutions, of operations executed in microfluidic devices are welcomed to consider for this special issue. Manuscripts demonstrating the application of traditional or novel fabrication techniques for creating microfluidic devices for stem cells and tissue engineering are of particular interest to this special issue. Please feel free to contact us if you have any questions related to this special issue.

Dr. Bobby Mathew
Dr. Nien-Tsu Huang
Prof. Dr. Sherif M. Karam
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. 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 2600 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

  • acoustophoresis
  • additive manufacturing
  • dielectrophoresis
  • droplets
  • focusing
  • lab on a chip
  • organs-on-chips
  • magnetophoresis
  • mathematical modeling
  • microfabrication
  • micromachining
  • multiphase
  • micropumps
  • mixing
  • separation
  • soft lithography

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Published Papers (9 papers)

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Research

12 pages, 2275 KiB  
Article
3D-Printed Microfluidic Chip for Real-Time Glucose Monitoring in Liquid Analytes
by Ivana Podunavac, Miroslav Djocos, Marija Vejin, Slobodan Birgermajer, Zoran Pavlovic, Sanja Kojic, Bojan Petrovic and Vasa Radonic
Micromachines 2023, 14(3), 503; https://doi.org/10.3390/mi14030503 - 21 Feb 2023
Cited by 5 | Viewed by 3708
Abstract
The connection of macrosystems with microsystems for in-line measurements is important in different biotechnological processes as it enables precise and accurate monitoring of process parameters at a small scale, which can provide valuable insights into the process, and ultimately lead to improved process [...] Read more.
The connection of macrosystems with microsystems for in-line measurements is important in different biotechnological processes as it enables precise and accurate monitoring of process parameters at a small scale, which can provide valuable insights into the process, and ultimately lead to improved process control and optimization. Additionally, it allows continuous monitoring without the need for manual sampling and analysis, leading to more efficient and cost-effective production. In this paper, a 3D printed microfluidic (MF) chip for glucose (Glc) sensing in a liquid analyte is proposed. The chip made in Poly(methyl methacrylate) (PMMA) contains integrated serpentine-based micromixers realized via stereolithography with a slot for USB-like integration of commercial DropSens electrodes. After adjusting the sample’s pH in the first micromixer, small volumes of the sample and enzyme are mixed in the second micromixer and lead to a sensing chamber where the Glc concentration is measured via chronoamperometry. The sensing potential was examined for Glc concentrations in acetate buffer in the range of 0.1–100 mg/mL and afterward tested for Glc sensing in a cell culturing medium. The proposed chip showed great potential for connection with macrosystems, such as bioreactors, for direct in-line monitoring of a quality parameter in a liquid sample. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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15 pages, 6113 KiB  
Article
Designing a Microfluidic Chip Driven by Carbon Dioxide for Separation and Detection of Particulate Matter
by Ruofei Wang, Heng Zhao, Xingbo Wang and Jiaqi Li
Micromachines 2023, 14(1), 183; https://doi.org/10.3390/mi14010183 - 11 Jan 2023
Cited by 4 | Viewed by 1759
Abstract
Atmospheric particulate pollution poses a great danger to the environment and human health, and there is a strong need to develop equipment for collecting and separating particulate matter of different particle sizes to study the effects of particulate matter on human health. A [...] Read more.
Atmospheric particulate pollution poses a great danger to the environment and human health, and there is a strong need to develop equipment for collecting and separating particulate matter of different particle sizes to study the effects of particulate matter on human health. A virtual impactor is a particle separation device based on the principle of inertial separation which provides scientific guidance for identifying the composition characteristics of particles. Much existing virtual impactor research focuses on the design of structural dimensions with little exploration of the effect of fluid properties on performance. In this paper, a microfluidic chip with a cutoff diameter of 1.85 µm was designed based on computational fluid dynamics and numerically simulated via finite element analysis to analyze important parameters such as inlet flow rate, splitting ratio and fluid properties. By numerical simulation of the split ratio, we found that the obtained collection efficiency curves could not be combined into one characteristic curve by the Stk0.5 scaling method. We therefore propose a modified Stokes number equation for predicting the cutoff diameter at different splitting ratios. The collection efficiency curves of different fluids as microfluidic chip media were plotted, and the results show that the cut particle size was reduced from 2.5 µm to 1.85 µm after replacing conventional fluid air with CO2 formed by dry ice sublimation. This is a decrease of approximately 26%, which is superior to other existing methods for reducing the cutoff diameter. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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13 pages, 1908 KiB  
Article
Pulsation Reduction Using Dual Sidewall-Driven Micropumps
by Takuto Atsumi, Toshio Takayama and Makoto Kaneko
Micromachines 2023, 14(1), 19; https://doi.org/10.3390/mi14010019 - 21 Dec 2022
Viewed by 1932
Abstract
Single-cell manipulation in microfluidic channels at the micrometer scale has recently become common. However, the current mainstream method using a syringe pump and a piezoelectric actuator is not suitable for long-term experiments. Some methods incorporate a pump mechanism into a microfluidic channel, but [...] Read more.
Single-cell manipulation in microfluidic channels at the micrometer scale has recently become common. However, the current mainstream method using a syringe pump and a piezoelectric actuator is not suitable for long-term experiments. Some methods incorporate a pump mechanism into a microfluidic channel, but they are not suitable for mass production owing to their complex structures. Here, we propose a sidewall-driven micropump integrated into a microfluidic device as well as a method for reducing the pulsation of flow. This sidewall-driven micropump consists of small chambers lined up on both sides along the main flow path, with a wall separating the flow path and each chamber being deformed by air pressure. The chambers are pressurized to make the peristaltic motion of the wall possible, which generates flow in the main flow path. This pump can be created in a single layer, which allows a simplified structure to be achieved, although pulsation can occur when the pump is used alone. We created two types of chips with two micropumps placed in the flow path and attempted to reduce pulsation by driving them in different phases. The proposed dually driven micropump reduced pulsation when compared with the single pump. This device enables precise particle control and is expected to contribute to less costly and easier cell manipulation experiments. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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11 pages, 1996 KiB  
Article
RGB-Detector: A Smart, Low-Cost Device for Reading RGB Indexes of Microfluidic Paper-Based Analytical Devices
by Bianca Maria Pazzi, Dario Pistoia and Giancarla Alberti
Micromachines 2022, 13(10), 1585; https://doi.org/10.3390/mi13101585 - 23 Sep 2022
Cited by 5 | Viewed by 2373
Abstract
A user-friendly, low-cost detector able to read the RGB indexes of microfluidic paper-based analytical devices (µPADs) was developed. The RGB-detector was built with 3D printing using PLA+ and reused Li-ion batteries. It is Arduino-based, which provides an easy interface between the sensor TCS3200, [...] Read more.
A user-friendly, low-cost detector able to read the RGB indexes of microfluidic paper-based analytical devices (µPADs) was developed. The RGB-detector was built with 3D printing using PLA+ and reused Li-ion batteries. It is Arduino-based, which provides an easy interface between the sensor TCS3200, which reads the quadratic wave of the times corresponding to the RGB numbers, the Arduino itself, whose software translates the times into RGB values, and the touchscreen display, NX3224T028, which shows the results. This detector permits multi-sample analysis since it has a sample holder that can keep up to six µPADs simultaneously and rotate after the display’s request. This work shows how the readings of the RGB indexes by the proposed RGB-detector implement the measurements’ reproducibility. As a proof-of-concept, the RGB-detector application to a green array of µPADs for pH measurement coupled with chemometric analysis allowed us to achieve good results in terms of precision and agreement with the pH values measured by a classical pH-meter. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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8 pages, 2977 KiB  
Article
Fabrication of Multilayer Molds by Dry Film Photoresist
by Narek E. Koucherian, Shijun Yan and Elliot E. Hui
Micromachines 2022, 13(10), 1583; https://doi.org/10.3390/mi13101583 - 23 Sep 2022
Cited by 1 | Viewed by 2136
Abstract
Dry film photoresists are widely employed to fabricate high-aspect-ratio microstructures, such as molds for microfluidic devices. Unlike liquid resists, such as SU-8, dry films do not require a cleanroom facility, and it is straightforward to prepare uniform and reproducible films as thick as [...] Read more.
Dry film photoresists are widely employed to fabricate high-aspect-ratio microstructures, such as molds for microfluidic devices. Unlike liquid resists, such as SU-8, dry films do not require a cleanroom facility, and it is straightforward to prepare uniform and reproducible films as thick as 500 µm. Multilayer patterning, however, can be problematic with dry film resists even though it is critical for a number of microfluidic devices. Layer-to-layer mask alignment typically requires the first layer to be fully developed, making the pattern visible, before applying and patterning the second layer. While a liquid resist can flow over the topography of previous layers, this is not the case with dry film lamination. We found that post-exposure baking of dry film photoresists can preserve a flat topography while revealing an image of the patterned features that is suitable for alignment to the next layer. We demonstrate the use of this technique with two different types of dry film resist to fabricate master molds for a hydrophoresis size-sorting device and a cell chemotaxis device. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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22 pages, 5778 KiB  
Article
Oil Displacement in Calcite-Coated Microfluidic Chips via Waterflooding at Elevated Temperatures and Long Times
by Duy Le-Anh, Ashit Rao, Amy Z. Stetten, Subhash C. Ayirala, Mohammed B. Alotaibi, Michel H. G. Duits, Han Gardeniers, Ali A. AlYousef and Frieder Mugele
Micromachines 2022, 13(8), 1316; https://doi.org/10.3390/mi13081316 - 14 Aug 2022
Cited by 4 | Viewed by 3428
Abstract
In microfluidic studies of improved oil recovery, mostly pore networks with uniform depth and surface chemistry are used. To better mimic the multiple porosity length scales and surface heterogeneity of carbonate reservoirs, we coated a 2.5D glass microchannel with calcite particles. After aging [...] Read more.
In microfluidic studies of improved oil recovery, mostly pore networks with uniform depth and surface chemistry are used. To better mimic the multiple porosity length scales and surface heterogeneity of carbonate reservoirs, we coated a 2.5D glass microchannel with calcite particles. After aging with formation water and crude oil (CRO), high-salinity Water (HSW) was flooded at varying temperatures and durations. Time-resolved microscopy revealed the CRO displacements. Precise quantification of residual oil presented some challenges due to calcite-induced optical heterogeneity and brine–oil coexistence at (sub)micron length scales. Both issues were addressed using pixel-wise intensity calibration. During waterflooding, most of the ultimately produced oil gets liberated within the first pore volume (similar to glass micromodels). Increasing temperature from 22 °C to 60 °C and 90 °C produced some more oil. Waterflooding initiated directly at 90 °C produced significantly more oil than at 22 °C. Continuing HSW exposure at 90 °C for 8 days does not release additional oil; although, a spectacular growth of aqueous droplets is observed. The effect of calcite particles on CRO retention is weak on flat surfaces, where the coverage is ~20%. The calcite-rich pore edges retain significantly more oil suggesting that, in our micromodel wall roughness is a stronger determinant for oil retention than surface chemistry. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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14 pages, 6327 KiB  
Article
Sensitivity Enhancement and Probiotic Detection of Microfluidic Chips Based on Terahertz Radiation Combined with Metamaterial Technology
by Yen-Shuo Lin, Shih-Ting Huang, Shen-Fu Steve Hsu, Kai-Yuan Tang, Ta-Jen Yen and Da-Jeng Yao
Micromachines 2022, 13(6), 904; https://doi.org/10.3390/mi13060904 - 7 Jun 2022
Cited by 3 | Viewed by 2048
Abstract
Terahertz (THz) radiation has attracted wide attention in recent years due to its non-destructive properties and ability to sense molecular structures. In applications combining terahertz radiation with metamaterial technology, the interaction between the terahertz radiation and the metamaterials causes resonance reactions; different analytes [...] Read more.
Terahertz (THz) radiation has attracted wide attention in recent years due to its non-destructive properties and ability to sense molecular structures. In applications combining terahertz radiation with metamaterial technology, the interaction between the terahertz radiation and the metamaterials causes resonance reactions; different analytes have different resonance performances in the frequency domain. In addition, a microfluidic system is able to provide low volume reagents for detection, reduce noise from the environment, and concentrate the sample on the detection area. Through simulation, a cruciform metamaterial pattern was designed; the proportion, periodicity, and width of the metamaterial were adjusted to improve the sensing capability of the chip. In the experiments, the sensing capabilities of Type A, B, and C chips were compared. The Type C chip had the most significant resonant effect; its maximum shift could be increased to 89 GHz. In the probiotic experiment, the cruciform chip could have a 0.72 GHz shift at a concentration of 0.025 mg/50 μL, confirming that terahertz radiation combined with a metamaterial microfluidic chip can perform low-concentration detection. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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12 pages, 3651 KiB  
Article
A Cost-Effective Nucleic Acid Detection System Using a Portable Microscopic Device
by Chengzhuang Yu, Shanshan Li, Chunyang Wei, Shijie Dai, Xinyi Liang and Junwei Li
Micromachines 2022, 13(6), 869; https://doi.org/10.3390/mi13060869 - 31 May 2022
Cited by 5 | Viewed by 2491
Abstract
A fluorescence microscope is one of the most important tools for biomedical research and laboratory diagnosis. However, its high cost and bulky size hinder the application of laboratory microscopes in space-limited and low-resource applications. Here, in this work, we proposed a portable and [...] Read more.
A fluorescence microscope is one of the most important tools for biomedical research and laboratory diagnosis. However, its high cost and bulky size hinder the application of laboratory microscopes in space-limited and low-resource applications. Here, in this work, we proposed a portable and cost-effective fluorescence microscope. Assembled from a set of 3D print components and a webcam, it consists of a three-degree-of-freedom sliding platform and a microscopic imaging system. The microscope is capable of bright-field and fluorescence imaging with micron-level resolution. The resolution and field of view of the microscope were evaluated. Compared with a laboratory-grade inverted fluorescence microscope, the portable microscope shows satisfactory performance, both in the bright-field and fluorescence mode. From the configurations of local resources, the microscope costs around USD 100 to assemble. To demonstrate the capability of the portable fluorescence microscope, we proposed a quantitative polymerase chain reaction experiment for meat product authenticating applications. The portable and low-cost microscope platform demonstrates the benefits in space-constrained environments and shows high potential in telemedicine, point-of-care testing, and more. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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26 pages, 11190 KiB  
Article
Rational Design and Numerical Analysis of a Hybrid Floating cIDE Separator for Continuous Dielectrophoretic Separation of Microparticles at High Throughput
by Yalin Li, Yan Wang, Georg R. Pesch, Michael Baune, Fei Du and Xiaomin Liu
Micromachines 2022, 13(4), 582; https://doi.org/10.3390/mi13040582 - 8 Apr 2022
Cited by 6 | Viewed by 2289
Abstract
Dielectrophoresis (DEP) enables continuous and label-free separation of (bio)microparticles with high sensitivity and selectivity, whereas the low throughput issue greatly confines its clinical application. Herein, we report a novel design of the DEP separator embedded with cylindrical interdigitated electrodes that incorporate hybrid floating [...] Read more.
Dielectrophoresis (DEP) enables continuous and label-free separation of (bio)microparticles with high sensitivity and selectivity, whereas the low throughput issue greatly confines its clinical application. Herein, we report a novel design of the DEP separator embedded with cylindrical interdigitated electrodes that incorporate hybrid floating electrode layout for (bio)microparticle separation at favorable throughput. To better predict microparticle trajectory in the scaled-up DEP platform, a theoretical model based on coupling of electrostatic, fluid and temperature fields is established, in which the effects of Joule heating-induced electrothermal and buoyancy flows on particles are considered. Size-based fractionation of polystyrene microspheres and dielectric properties-based isolation of MDA-MB-231 from blood cells are numerically realized, respectively, by the proposed separator with sample throughputs up to 2.6 mL/min. Notably, the induced flows can promote DEP discrimination of heterogeneous cells. This work provides a reference on tailoring design of enlarged DEP platforms for highly efficient separation of (bio)samples at high throughput. Full article
(This article belongs to the Special Issue Design, Optimization, Fabrication and Applications of Microfluidic Devices)
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