Microfluidics Technologies for Cell-based Assays

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

Deadline for manuscript submissions: closed (1 February 2020) | Viewed by 16598

Special Issue Editors


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Guest Editor
School of Engineering, RMIT University, City Campus, Melbourne, VIC 3001, Australia
Interests: microfluidics; lab-on-a-chip; organ-on-a-chip; mechanobiology; soft matter
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Guest Editor
School of Health and Biomedical Sciences, RMIT University, Bundoora Campus, Melbourne, VIC 3083, Australia
Interests: mechanobiology; bio-microfluidics; cell biology; atherosclerosis; super-resolution microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microfluidic systems are increasingly used for conducting cell-based assays. Such systems enable monitoring cellular responses under well-controlled physical (mechanical, shear stress, thermal, optical) and chemical (drugs, chemicals, nanomaterials) stimuli to mimic various physiological and pathological cues, allowing for more realistic in vitro models. Furthermore, advancement of micro-fabrication technologies has facilitated highly integrated and multi-functional organ-on-chip systems that can replace the lengthy and expensive ex vivo and in vivo models. This Special Issue seeks to showcase research papers, short communications, and review articles reporting the latest developments in this exciting and multi-disciplinary field. The topics include but are not limited to (i) studying the viability, proliferation, metabolism, signaling, migration, and morphology of cells, (ii) sorting and patterning of cells, and (iii) development of disease-on-chip, organ-on-chip models using microfluidic technologies.  

Dr. Khashayar Khoshmanesh
Dr. Sara Baratchi
Guest Editors

Manuscript Submission Information

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Keywords

  • Microfluidics
  • Lab-on-a-Chip
  • Cellular assays
  • Cell stimulation
  • Mechanobiology
  • Disease-on-Chip
  • Organ-on-Chip

Published Papers (5 papers)

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Research

14 pages, 2193 KiB  
Article
Label-Free, High-Throughput Assay of Human Dendritic Cells from Whole-Blood Samples with Microfluidic Inertial Separation Suitable for Resource-Limited Manufacturing
by Mohamed Yousuff Caffiyar, Kue Peng Lim, Ismail Hussain Kamal Basha, Nor Hisham Hamid, Sok Ching Cheong and Eric Tatt Wei Ho
Micromachines 2020, 11(5), 514; https://doi.org/10.3390/mi11050514 - 19 May 2020
Cited by 11 | Viewed by 3299
Abstract
Microfluidics technology has not impacted the delivery and accessibility of point-of-care health services, like diagnosing infectious disease, monitoring health or delivering interventions. Most microfluidics prototypes in academic research are not easy to scale-up with industrial-scale fabrication techniques and cannot be operated without complex [...] Read more.
Microfluidics technology has not impacted the delivery and accessibility of point-of-care health services, like diagnosing infectious disease, monitoring health or delivering interventions. Most microfluidics prototypes in academic research are not easy to scale-up with industrial-scale fabrication techniques and cannot be operated without complex manipulations of supporting equipment and additives, such as labels or reagents. We propose a label- and reagent-free inertial spiral microfluidic device to separate red blood, white blood and dendritic cells from blood fluid, for applications in health monitoring and immunotherapy. We demonstrate that using larger channel widths, in the range of 200 to 600 µm, allows separation of cells into multiple focused streams, according to different size ranges, and we utilize a novel technique to collect the closely separated focused cell streams, without constricting the channel. Our contribution is a method to adapt spiral inertial microfluidic designs to separate more than two cell types in the same device, which is robust against clogging, simple to operate and suitable for fabrication and deployment in resource-limited populations. When tested on actual human blood cells, 77% of dendritic cells were separated and 80% of cells remained viable after our assay. Full article
(This article belongs to the Special Issue Microfluidics Technologies for Cell-based Assays)
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11 pages, 1550 KiB  
Article
Nitric Oxide and a Conditioned Medium Affect the Hematopoietic Development in a Microfluidic Mouse Embryonic Stem Cell/OP9 Co-Cultivation System
by Kae Sato, Momoko Maeda, Eriko Kamata, Sayaka Ishii, Kanako Yanagisawa, Kenji Kitajima and Takahiko Hara
Micromachines 2020, 11(3), 305; https://doi.org/10.3390/mi11030305 - 14 Mar 2020
Cited by 4 | Viewed by 2376
Abstract
A microfluidic co-culture system, consisting of mouse embryonic stem cells (mESCs)/OP9 cells, was evaluated as a platform for studying hematopoietic differentiation mechanisms in vitro. mESC differentiation into blood cells was achieved in a microchannel that had the minimum size necessary to culture cells. [...] Read more.
A microfluidic co-culture system, consisting of mouse embryonic stem cells (mESCs)/OP9 cells, was evaluated as a platform for studying hematopoietic differentiation mechanisms in vitro. mESC differentiation into blood cells was achieved in a microchannel that had the minimum size necessary to culture cells. The number of generated blood cells increased or decreased based on the nitric oxide (NO) donor or inhibitor used. Conditioned medium from OP9 cell cultures also promoted an increase in the number of blood cells. The number of generated blood cells under normal medium flow conditions was lower than that observed under the static condition. However, when using a conditioned medium, the number of generated blood cells under flow conditions was the same as that observed under the static condition. We conclude that secreted molecules from OP9 cells have a large influence on the differentiation of mESCs into blood cells. This is the first report of a microfluidic mESC/OP9 co-culture system that can contribute to highly detailed hematopoietic research studies by mimicking the cellular environment. Full article
(This article belongs to the Special Issue Microfluidics Technologies for Cell-based Assays)
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16 pages, 3251 KiB  
Article
Centrifugal Microfluidics Traps for Parallel Isolation and Imaging of Single Cells
by Adam Snider, Ileana Pirozzi and Anubhav Tripathi
Micromachines 2020, 11(2), 149; https://doi.org/10.3390/mi11020149 - 29 Jan 2020
Cited by 4 | Viewed by 3067
Abstract
Analysis at the single cell level has becoming an increasingly important procedure to diagnose cancer tissue biopsies. These tissue samples are often heterogeneous and consist of 1000–15,000 cells. We study the use of centrifugal microfluidics to isolate single cells into micro chambers. We [...] Read more.
Analysis at the single cell level has becoming an increasingly important procedure to diagnose cancer tissue biopsies. These tissue samples are often heterogeneous and consist of 1000–15,000 cells. We study the use of centrifugal microfluidics to isolate single cells into micro chambers. We describe the optimization of our microfluidics flow device, characterize its performance using both polystyrene beads as a cell analogue and MCF-7 breast cancer cells, and discuss potential applications for the device. Our results show rapid isolation of ~2000 single cell aliquots in ~20 min. We were able to occupy 65% of available chambers with singly occupied cancer cells, and observed capture efficiencies as high as 80% using input samples ranging from 2000 to 15,000 cells in 20 min. We believe our device is a valuable research tool that addresses the unmet need for massively parallel single cell level analysis of cell populations. Full article
(This article belongs to the Special Issue Microfluidics Technologies for Cell-based Assays)
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9 pages, 1410 KiB  
Article
A Microfluidic Detection System for Bladder Cancer Tumor Cells
by Shuxing Lv, Jinwei Yu, Yan Zhao, Hongxiang Li, Fang Zheng, Ning Liu, Dahua Li and Xuguo Sun
Micromachines 2019, 10(12), 871; https://doi.org/10.3390/mi10120871 - 11 Dec 2019
Cited by 8 | Viewed by 3257
Abstract
The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine [...] Read more.
The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine interferes with the recognition of tumor cells. In this paper, a technique for detecting cancer cells in urine based on microfluidics provides a novel approach to bladder cancer diagnosis. The bladder cancer cell line (T24) and MeT-5A were used as positive bladder tumor cells and non-tumor cells, respectively. The practicality of the tumor cell detection system based on microfluidic cell chip detection technology is discussed. The tumor cell (T24) concentration was around 1 × 104 to 300 × 104 cells/mL. When phosphate buffer saline (PBS) was the diluted solution, the tumor cell detected rate was 63–71% and the detection of tumor cell number stability (coefficient of variation, CV%) was 6.7–4.1%, while when urine was the diluted solution, the tumor cell detected rate was 64–72% and the detection of tumor cell number stability (CV%) was 6.3–3.9%. In addition, both PBS and urine are tumor cell dilution fluid solutions. The sample was analyzed at a speed of 750 microns per hour. Based on the above experiments, a system for detecting bladder cancer cells in urine by microfluidic analysis chip technology was reported. The rate of recognizing bladder cancer cells reached 68.4%, and the speed reached 2 mL/h. Full article
(This article belongs to the Special Issue Microfluidics Technologies for Cell-based Assays)
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13 pages, 3168 KiB  
Article
Selective Detection of Human Lung Adenocarcinoma Cells Based on the Aptamer-Conjugated Self-Assembled Monolayer of Gold Nanoparticles
by Ngoc-Viet Nguyen and Chun-Ping Jen
Micromachines 2019, 10(3), 195; https://doi.org/10.3390/mi10030195 - 19 Mar 2019
Cited by 22 | Viewed by 4163
Abstract
This study established a microfluidic chip for the capture of A549 human lung circulating tumor cells via the aptamer-conjugated self-assembled monolayer (SAM) of gold nanoparticles (AuNPs) in the channel. AuNPs are among the most attractive nanomaterials for the signal enhancement of biosensors owing [...] Read more.
This study established a microfluidic chip for the capture of A549 human lung circulating tumor cells via the aptamer-conjugated self-assembled monolayer (SAM) of gold nanoparticles (AuNPs) in the channel. AuNPs are among the most attractive nanomaterials for the signal enhancement of biosensors owing to their unique chemical, physical, and mechanical properties. The microchip was fabricated using soft photolithography and casting and molding techniques. A self-assembly method was designed to attach AuNPs, cell-specific aptamers, and target cells onto the desired area (i.e., SAM area). In this study, the gold microelectrode configuration was characterized by fluorescence microscopy and impedance measurements to confirm the important modification steps. Subsequently, several investigations with the proposed assay were conducted with different cell samples to determine the specific binding ability of the device for A549 adenocarcinoma cancer cells. This work has ensured a simple, convenient, selective, and sensitive approach for the development of biosensors for lung cancer detection during the early stages. Full article
(This article belongs to the Special Issue Microfluidics Technologies for Cell-based Assays)
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