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Micromachines
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Microfluidic Cell Assay Chips
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Microfluidic Cell Assay Chips

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

Deadline for manuscript submissions: closed (10 December 2018) | Viewed by 41097

Special Issue Editors

Dr. Yu-Chih Chen

E-Mail Website
Guest Editor
1. UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
2. Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA
3. CMU-Pitt Ph.D. Program in Computational Biology, Pittsburgh, PA 15213, USA
4. Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15260, USA
Interests: single-cell analysis; cancer precision medicine; microfluidics; machine learning; gene sequencing
Special Issues, Collections and Topics in MDPI journals
Prof. Euisik Yoon

E-Mail Website
Guest Editor
1. Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA
2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
Interests: microfluidic; neurotechnology; MEMS; integrated circuits

Special Issue Information

Dear Colleagues,

Microfluidic technology has emerged as a state-of-the-art approach for cell biology because of precise micro-environment manipulation, minimal reagent usage, and high potential in scaling and automation. Recently, microfluidic cell assay chips have demonstrated the capabilities of drug screening, 3D cell culture, cell migration and invasion, cell-cell interaction, single cell analysis, transcriptomic and proteomic profiling, and clinical diagnostics. Though core functions were developed as prototypes, there is a recognized need to provide low-cost and reliable manufacturing methods for dissemination of the technology. Further development in automation and system integration will be required to realize full potential of high-throughput assays and readouts. In addition, the smart interface between microfluidics and conventional bulk machines is critical for handling small sample volumes and saving reagents. In light of these prevailing challenges, this Special Issue seeks to collect research papers, short communications, and review articles that focus on, but are not limited to, novel microfluidic cell assays, low-cost and reliable micro-manufacturing methods, 3D printed microfluidics, high-throughput experimentation, automation, and smart interface for microfluidic cell analysis.

Dr. Yu-Chih Chen
Prof. Euisik Yoon
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

  • Microfluidic cell assays
  • Lab on a chip
  • Micro-total analysis systems
  • High-throughput screening
  • Micro-manufacturing
  • Micro-machining
  • 3D printing
  • Microfluidic interface
  • Microfluidic system integration
  • Clinical diagnostics

Related Special Issue

Published Papers (7 papers)

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11 pages, 2291 KiB  
Article
Multiplexed PCR-Free Detection of MicroRNAs in Single Cancer Cells Using a DNA-Barcoded Microtrough Array Chip
by Nayi Wang, Yao Lu, Zhuo Chen and Rong Fan
Micromachines 2019, 10(4), 215; https://doi.org/10.3390/mi10040215 - 27 Mar 2019
Cited by 4 | Viewed by 4205
Abstract
MicroRNAs are a class of small RNA molecules that regulate the expression of mRNAs in a wide range of biological processes and are implicated in human health and disease such as cancers. How to measure microRNA profiles in single cells with high throughput [...] Read more.
MicroRNAs are a class of small RNA molecules that regulate the expression of mRNAs in a wide range of biological processes and are implicated in human health and disease such as cancers. How to measure microRNA profiles in single cells with high throughput is essential to the development of cell-based assays for interrogating microRNA-mediated intratumor heterogeneity and the design of new lab tests for diagnosis and monitoring of cancers. Here, we report on an in situ hybridization barcoding workflow implemented in a sub-nanoliter microtrough array chip for high-throughput and multiplexed microRNA detection at the single cell level. The microtroughs are used to encapsulate single cells that are fixed, permeabilized, and pre-incubated with microRNA detection probes, each of which consists of a capture strand complementary to specific microRNA and a unique reporter strand that can be photocleaved in the microtroughs and subsequently detected by an array of DNA barcodes patterned on the bottom of the microtroughs. In this way, the measurement of reporter strands released from single cells is a surrogate for detecting single-cell microRNA profiles. This approach permits direct measurement of microRNAs without PCR amplification owing to the small volume (<1 nL) of microtroughs. It offers high throughput and high multiplexing capability for evaluating microRNA heterogeneity in single cells, representing a new approach toward microRNA-based diagnosis and monitoring of complex human diseases. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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12 pages, 2930 KiB  
Article
Patterning Perfluorinated Surface with Graphene Oxide and the Microarray Applications
by Liang Wu, Baishu Liu, Meiling Zhu, Dameng Guo, Han Wu, Liming Bian and Bo Zheng
Micromachines 2019, 10(3), 173; https://doi.org/10.3390/mi10030173 - 01 Mar 2019
Cited by 2 | Viewed by 3462
Abstract
A method was developed to pattern the surface of perfluorinated materials with graphene oxide thin film, and various biological applications of the patterned perfluorinated surface were illustrated. Perfluorinated surfaces such as Teflon, Cytop, and other perfluorinated materials are known to be both hydrophobic [...] Read more.
A method was developed to pattern the surface of perfluorinated materials with graphene oxide thin film, and various biological applications of the patterned perfluorinated surface were illustrated. Perfluorinated surfaces such as Teflon, Cytop, and other perfluorinated materials are known to be both hydrophobic and oleophobic, with low adhesion for most materials. Modifying the perfluorinated surfaces has been difficult due to the extraordinary chemical inertness, which limits the applications of perfluorinated materials as anti-fouling substrates. Herein we successfully patterned Cytop surfaces with graphene oxide. Patterns of the graphene oxide thin film with feature dimension down to 40 microns were formed and remained stable on the Cytop surface against washing with water, ethanol and acetone. The graphene oxide thin film on the Cytop surface allowed non-specific protein adsorption. To illustrate the applications of the patterned Cytop surface, we used the patterned Cytop surface as the substrate to study the protein-protein interactions, stem cell culture, and stem cell proliferation. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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17 pages, 4102 KiB  
Article
The Effect of Microfluidic Geometry on Myoblast Migration
by Rahul Atmaramani, Bryan J. Black, Kevin H. Lam, Vinit M. Sheth, Joseph J. Pancrazio, David W. Schmidtke and Nesreen Zoghoul Alsmadi
Micromachines 2019, 10(2), 143; https://doi.org/10.3390/mi10020143 - 21 Feb 2019
Cited by 7 | Viewed by 5370
Abstract
In vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels—from the [...] Read more.
In vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels—from the proximal to the distal chamber. Myoblast migration was examined in microfluidic devices with varying microchannel widths of 1.5–20 µm, and in chips with uniform microchannel widths over time spans that are relevant for myoblast-to-myofiber differentiation in vitro. We found that the likelihood of spontaneous myoblast migration was microchannel width dependent and that a width of 3 µm was necessary to limit spontaneous migration below 5% of cells in the seeded well after 48 h. These results inform the future design of Polydimethylsiloxane (PDMS) microchannel-based co-culture platforms as well as future in vitro studies of myoblast migration. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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12 pages, 1674 KiB  
Article
Development of Microfluidic Stretch System for Studying Recovery of Damaged Skeletal Muscle Cells
by Wanho Kim, Jaesang Kim, Hyung-Soon Park and Jessie S. Jeon
Micromachines 2018, 9(12), 671; https://doi.org/10.3390/mi9120671 - 18 Dec 2018
Cited by 16 | Viewed by 5544
Abstract
The skeletal muscle occupies about 40% mass of the human body and plays a significant role in the skeletal movement control. Skeletal muscle injury also occurs often and causes pain, discomfort, and functional impairment in daily living. Clinically, most studies observed the recovery [...] Read more.
The skeletal muscle occupies about 40% mass of the human body and plays a significant role in the skeletal movement control. Skeletal muscle injury also occurs often and causes pain, discomfort, and functional impairment in daily living. Clinically, most studies observed the recovery phenomenon of muscle by massage or electrical stimulation, but there are limitations on quantitatively analyzing the effects on recovery. Although additional efforts have been made within in vitro biochemical research, some questions still remain for effects of the different cell microenvironment for recovery. To overcome these limitations, we have developed a microfluidic system to investigate appropriate conditions for repairing skeletal muscle injury. First, the muscle cells were cultured in the microfluidic chip and differentiated to muscle fibers. After differentiation, we treated hydrogen peroxide and 18% axial stretch to cause chemical and physical damage to the muscle fibers. Then the damaged muscle fibers were placed under the cyclic stretch condition to allow recovery. Finally, we analyzed the damage and recovery by quantifying morphological change as well as the intensity change of intracellular fluorescent signals and showed the skeletal muscle fibers recovered better in the cyclic stretched condition. In total, our in situ generation of muscle damage and induction recovery platform may be a key system for investigating muscle recovery and rehabilitation. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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8 pages, 3386 KiB  
Article
Etching-Assisted Ablation of the UV-Transparent Fluoropolymer CYTOP Using Various Laser Pulse Widths and Subsequent Microfluidic Applications
by Keisuke Nemoto and Yasutaka Hanada
Micromachines 2018, 9(12), 662; https://doi.org/10.3390/mi9120662 - 15 Dec 2018
Cited by 4 | Viewed by 3323
Abstract
This work demonstrated the surface microfabrication of the UV-transparent fluoropolymer CYTOP (perfluoro 1-butenyl vinyl ether), by etching-assisted ablation using lasers with different pulse widths. In previous studies, we developed a technique for CYTOP microfluidic fabrication using laser ablation followed by etching and annealing. [...] Read more.
This work demonstrated the surface microfabrication of the UV-transparent fluoropolymer CYTOP (perfluoro 1-butenyl vinyl ether), by etching-assisted ablation using lasers with different pulse widths. In previous studies, we developed a technique for CYTOP microfluidic fabrication using laser ablation followed by etching and annealing. However, this technique was not suitable for some industrial applications due to the requirement for prolonged etching of the irradiated areas. The present work developed a faster etching-assisted ablation method in which the laser ablation of CYTOP took place in fluorinated etching solvent and investigated into the fabrication mechanism of ablated craters obtained from various pulse width lasers. The mechanism study revealed that the efficient CYTOP microfabrication can be achieved with a longer pulse width laser using this technique. Therefore, the rapid, high-quality surface microfabrication of CYTOP was demonstrated using a conventional nanosecond laser. Additionally, Microfluidic systems were produced on a CYTOP substrate via the new etching-assisted laser ablation process followed by annealing within 1 h, which is faster than the prior work of the microfluidic chip fabrication. Subsequently, CYTOP and polydimethylsiloxane substrates were bonded to create a 3D microfluidic chip that allowed for a clear microscopic image of the fluid boundary. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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10 pages, 2933 KiB  
Article
Microfabrication of Micropore Array for Cell Separation and Cell Assay
by Yaoping Liu, Han Xu, Lingqian Zhang and Wei Wang
Micromachines 2018, 9(12), 620; https://doi.org/10.3390/mi9120620 - 24 Nov 2018
Cited by 1 | Viewed by 4122
Abstract
Micropore arrays have attracted a substantial amount of attention due to their strong capability to separate specific cell types, such as rare tumor cells, from a heterogeneous sample and to perform cell assays on a single cell level. Micropore array filtration has been [...] Read more.
Micropore arrays have attracted a substantial amount of attention due to their strong capability to separate specific cell types, such as rare tumor cells, from a heterogeneous sample and to perform cell assays on a single cell level. Micropore array filtration has been widely used in rare cell type separation because of its potential for a high sample throughput, which is a key parameter for practical clinical applications. However, most of the present micropore arrays suffer from a low throughput, resulting from a low porosity. Therefore, a robust microfabrication process for high-porosity micropore arrays is urgently demanded. This study investigated four microfabrication processes for micropore array preparation in parallel. The results revealed that the Parylene-C molding technique with a silicon micropillar array as the template is the optimized strategy for the robust preparation of a large-area and high-porosity micropore array, along with a high size controllability. The Parylene-C molding technique is compatible with the traditional micromechanical system (MEMS) process and ready for scale-up manufacture. The prepared Parylene-C micropore array is promising for various applications, such as rare tumor cell separation and cell assays in liquid biopsy for cancer precision medicine. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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12 pages, 2025 KiB  
Perspective
Engineering Microfluidic Organoid-on-a-Chip Platforms
by Fang Yu, Walter Hunziker and Deepak Choudhury
Micromachines 2019, 10(3), 165; https://doi.org/10.3390/mi10030165 - 27 Feb 2019
Cited by 142 | Viewed by 14521
Abstract
In vitro cell culture models are emerging as promising tools to understand human development, disease progression, and provide reliable, rapid and cost-effective results for drug discovery and screening. In recent years, an increasing number of in vitro models with complex organization and controlled [...] Read more.
In vitro cell culture models are emerging as promising tools to understand human development, disease progression, and provide reliable, rapid and cost-effective results for drug discovery and screening. In recent years, an increasing number of in vitro models with complex organization and controlled microenvironment have been developed to mimic the in vivo organ structure and function. The invention of organoids, self-organized organ-like cell aggregates that originate from multipotent stem cells, has allowed a whole new level of biomimicry to be achieved. Microfluidic organoid-on-a-chip platforms can facilitate better nutrient and gas exchange and recapitulate 3D tissue architecture and physiology. They have the potential to transform the landscape of drug development and testing. In this review, we discuss the challenges in the current organoid models and describe the recent progress in the field of organoid-on-a-chip. Full article
(This article belongs to the Special Issue Microfluidic Cell Assay Chips)
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