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Micromachines
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Microfluidics for Cell-Based Assays
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Microfluidics 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 (15 October 2018) | Viewed by 21081

Special Issue Editor

Dr. Francis Lin

E-Mail Website
Guest Editor
Department of Physics and Astronomy & Immunology, University of Manitoba, Winnipeg, MB, Canada
Interests: microfluidic devices; cell migration; biomedical diagnostic assays; organ-on-chip models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Owing to miniaturization, microfluidic devices provide useful tools for a wide range of research areas in life sciences. In particular, many microfluidics-based cell assays have been developed to enable advanced studies of various cell functions such as cell growth, differentiation, adhesion and migration under well-controlled microenvironments. With the recent rapid development of organ-on-chip approach, microfluidic devices have been increasingly employed to configure complex multicellular environments and to study cell-cell and cell-extracellular matrix (ECM) interactions. Finally, various microfluidics-based cell assays have been developed for biomedical diagnostic applications. Through this Special Issue, we aim to highlight the development of novel cell assays based on microfluidic devices. In particular, we are interested in research articles that demonstrate the unique ability of microfluidic devices for controlling complex cellular microenvironments and for dynamic visualization and quantification of cellular functions and intercellular interactions. In addition, we are interested in research papers of microfluidics-based cell assays with clinical relevance. Review papers that highlight recent research development in the directions described above are also welcomed.

Dr. Francis Lin
Guest Editor

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

  • Microfluidics
  • Lab-on-Chip
  • Cell assays
  • Biological research
  • Clinical applications

Published Papers (5 papers)

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Research

11 pages, 2566 KiB  
Article
A Fluidic Device for Immunomagnetic Separation of Foodborne Bacteria Using Self-Assembled Magnetic Nanoparticle Chains
by Gaozhe Cai, Siyuan Wang, Lingyan Zheng and Jianhan Lin
Micromachines 2018, 9(12), 624; https://doi.org/10.3390/mi9120624 - 27 Nov 2018
Cited by 32 | Viewed by 4629
Abstract
Immunomagnetic separation has been widely used for the separation and concentration of foodborne pathogens from complex food samples, however it can only handle a small volume of samples. In this paper, we presented a novel fluidic device for the specific and efficient separation [...] Read more.
Immunomagnetic separation has been widely used for the separation and concentration of foodborne pathogens from complex food samples, however it can only handle a small volume of samples. In this paper, we presented a novel fluidic device for the specific and efficient separation and concentration of salmonella typhimurium using self-assembled magnetic nanoparticle chains. The laminated sawtooth-shaped iron foils were first mounted in the 3D-printed matrix and magnetized by a strong magnet to generate dot-array high gradient magnetic fields in the fluidic channel, which was simulated using COMSOL (5.3a, Burlington, MA, USA). Then, magnetic nanoparticles with a diameter of 150 nm, which were modified with the anti-salmonella polyclonal antibodies, were injected into the channel, and the magnetic nanoparticle chains were vertically formed at the dots and verified using a fluorescence inverted microscope. Finally, the bacterial sample was continuous-flow injected, and the target bacteria could be captured by the antibodies on the chains, followed by gold standard culture plating to determine the amount of the target bacteria. Under the optimal conditions, the target bacteria could be separated with a separation efficiency of 80% in 45 min. This fluidic device could be further improved using thinner sawtooth-shaped iron foils and stronger magnets to obtain a better dot-array magnetic field with larger magnetic intensity and denser dot distribution, and has the potential to be integrated with the existing biological assays for rapid and sensitive detection of foodborne bacteria. Full article
(This article belongs to the Special Issue Microfluidics for Cell-Based Assays)
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12 pages, 2035 KiB  
Article
On-Chip Isoniazid Exposure of Mycobacterium smegmatis Penicillin-Binding Protein (PBP) Mutant Using Time-Lapse Fluorescent Microscopy
by Meltem Elitas
Micromachines 2018, 9(11), 561; https://doi.org/10.3390/mi9110561 - 31 Oct 2018
Cited by 4 | Viewed by 2973
Abstract
Antibiotic resistance has been one of the biggest threats to global health. Despite the available prevention and control strategies and efforts in developing new antibiotics, the need remains for effective approaches against antibiotic resistance. Efficient strategies to cope with antimicrobial resistance require a [...] Read more.
Antibiotic resistance has been one of the biggest threats to global health. Despite the available prevention and control strategies and efforts in developing new antibiotics, the need remains for effective approaches against antibiotic resistance. Efficient strategies to cope with antimicrobial resistance require a quantitative and deeper understanding of microbial behavior, which can be obtained using different techniques to provide the missing pieces of the current antibiotic-resistance puzzle. Microfluidic-microscopy techniques are among the most promising methods that contribute modernization of traditional assays in microbiology. They provide monitoring and manipulation of cells at micro-scale volumes. Here, we combined population-level, culture-based assays with single-cell resolution, microfluidic-microscopy systems to investigate isoniazid response of Mycobacterium smegmatis penicillin-binding protein (PBP) mutant. This mutant exhibited normal growth in plain medium and sensitivity to stress responses when treated with thermal stress (45 °C), detergent stress (0.1% sodium dodecyl sulfate), acid stress (pH 4.5), and nutrient starvation (1XPBS). The impact of msm0031 transposon insertion on drug-mediated killing was determined for isoniazid (INH, 50 µg/mL), rifampicin (RIF, 200 µg/mL), ethionamide (ETH, 200 µg/mL), and ethambutol (EMB, 5 µg/mL). The PBP mutant demonstrated remarkable isoniazid-killing phenotype in batch culture. Therefore, we hypothesized that single-cell analysis will show increased lysis kinetics and fewer intact cells after drug treatment. However, the single-cell analysis data showed that upon isoniazid exposure, the percentage of the intact PBP mutant cells was 24%, while the percentage of the intact wild-type cells was 4.6%. The PBP mutant cells exhibited decreased cell-lysis profile. Therefore, the traditional culture-based assays were not sufficient to provide insights about the subpopulation of viable but non-culture cells. Consequently, we need more adequate tools to be able to comprehend and fight the antibiotic resistance of bacteria. Full article
(This article belongs to the Special Issue Microfluidics for Cell-Based Assays)
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18 pages, 3152 KiB  
Article
Microfluidic-Based Technique for Measuring RBC Aggregation and Blood Viscosity in a Continuous and Simultaneous Fashion
by Yang Jun Kang
Micromachines 2018, 9(9), 467; https://doi.org/10.3390/mi9090467 - 14 Sep 2018
Cited by 18 | Viewed by 3577
Abstract
Hemorheological properties such as viscosity, deformability, and aggregation have been employed to monitor or screen patients with cardiovascular diseases. To effectively evaluate blood circulating within an in vitro closed circuit, it is important to quantify its hemorheological properties consistently and accurately. A simple [...] Read more.
Hemorheological properties such as viscosity, deformability, and aggregation have been employed to monitor or screen patients with cardiovascular diseases. To effectively evaluate blood circulating within an in vitro closed circuit, it is important to quantify its hemorheological properties consistently and accurately. A simple method for measuring red blood cell (RBC) aggregation and blood viscosity is proposed for analyzing blood flow in a microfluidic device, especially in a continuous and simultaneous fashion. To measure RBC aggregation, blood flows through three channels: the left wide channel, the narrow channel and the right wide channel sequentially. After quantifying the image intensity of RBCs aggregated in the left channel (<IRA>) and the RBCs disaggregated in the right channel (<IRD>), the RBC aggregation index (AIPM) is obtained by dividing <IRA> by <IRD>. Simultaneously, based on a modified parallel flow method, blood viscosity is obtained by detecting the interface between two fluids in the right wide channel. RBC aggregation and blood viscosity were first evaluated under constant and pulsatile blood flows. AIPM varies significantly with respect to blood flow rate (for both its amplitude and period) and the concentration of the dextran solution used. According to our quantitative comparison between the proposed aggregation index (AIPM) and the conventional aggregation index (AICM), it is found that AIPM provides consistent results. Finally, the suggested method is employed to obtain the RBC aggregation and blood viscosity of blood circulating within an in vitro fluidic circuit. The experimental results lead to the conclusion that the proposed method can be successfully used to measure RBC aggregation and blood viscosity, especially in a continuous and simultaneous fashion. Full article
(This article belongs to the Special Issue Microfluidics for Cell-Based Assays)
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12 pages, 2864 KiB  
Article
Nanoliter Centrifugal Liquid Dispenser Coupled with Superhydrophobic Microwell Array Chips for High-Throughput Cell Assays
by Yuyi Wang, Yushuai Wu, Yue Chen, Jianxiong Zhang, Xiaofang Chen and Peng Liu
Micromachines 2018, 9(6), 286; https://doi.org/10.3390/mi9060286 - 06 Jun 2018
Cited by 10 | Viewed by 4942
Abstract
Microfluidic systems have been regarded as a potential platform for high-throughput screening technology in drug discovery due to their low sample consumption, high integration, and easy operation. The handling of small-volume liquid is an essential operation in microfluidic systems, especially in investigating large-scale [...] Read more.
Microfluidic systems have been regarded as a potential platform for high-throughput screening technology in drug discovery due to their low sample consumption, high integration, and easy operation. The handling of small-volume liquid is an essential operation in microfluidic systems, especially in investigating large-scale combination conditions. Here, we develop a nanoliter centrifugal liquid dispenser (NanoCLD) coupled with superhydrophobic microwell array chips for high-throughput cell-based assays in the nanoliter scale. The NanoCLD consists of a plastic stock block with an array of drilled through holes, a reagent microwell array chip (reagent chip), and an alignment bottom assembled together in a fixture. A simple centrifugation at 800 rpm can dispense ~160 nL reagents into microwells in 5 min. The dispensed reagents are then delivered to cells by sandwiching the reagent chip upside down with another microwell array chip (cell chip) on which cells are cultured. A gradient of doxorubicin is then dispensed to the cell chip using the NanoCLD for validating the feasibility of performing drug tests on our microchip platform. This novel nanoliter-volume liquid dispensing method is simple, easy to operate, and especially suitable for repeatedly dispensing many different reagents simultaneously to microwells. Full article
(This article belongs to the Special Issue Microfluidics for Cell-Based Assays)
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13 pages, 28099 KiB  
Article
A Microfluidic Chip with Double-Slit Arrays for Enhanced Capture of Single Cells
by Jingyi Xu, Shulei Chen, Dongyang Wang, Yue Jiang, Ming Hao, Guangyu Du, Dechun Ba, Qiao Lin, Qi Mei, Yingchao Ning, Da Su and Kun Liu
Micromachines 2018, 9(4), 157; https://doi.org/10.3390/mi9040157 - 01 Apr 2018
Cited by 9 | Viewed by 4455
Abstract
The application of microfluidic technology to manipulate cells or biological particles is becoming one of the rapidly growing areas, and various microarray trapping devices have recently been designed for high throughput single-cell analysis and manipulation. In this paper, we design a double-slit microfluidic [...] Read more.
The application of microfluidic technology to manipulate cells or biological particles is becoming one of the rapidly growing areas, and various microarray trapping devices have recently been designed for high throughput single-cell analysis and manipulation. In this paper, we design a double-slit microfluidic chip for hydrodynamic cell trapping at the single-cell level, which maintains a high capture ability. The geometric effects on flow behaviour are investigated in detail for optimizing chip architecture, including the flow velocity, the fluid pressure, and the equivalent stress of cells. Based on the geometrical parameters optimized, the double-slit chip enhances the capture of HeLa cells and the drug experiment verifies the feasibility of the drug delivery. Full article
(This article belongs to the Special Issue Microfluidics for Cell-Based Assays)
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