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Micromachines
Special Issues
Micro/Nanofluidic Devices for Single Cell Analysis, Volume III
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Micro/Nanofluidic Devices for Single Cell Analysis, Volume III

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 16733

Special Issue Editors

Dr. Tuhin Subhra Santra

E-Mail Website
Guest Editor
Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India
Interests: MEMS; Bio-NEMS; single- cell technology; biomedical micro/nano devices; micro/nanofluidics; nanomedicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Fan-Gang Tseng

E-Mail Website
Guest Editor
Distinguished Professor, Department of Engineering and System Science, National Tsing Hua University (NTHU), Affiliated Research Fellow, Academia Sinica, Hsinchu, Taiwan
Interests: organ on a chip; microfluidic systems; biosensors; CTCs/CTM diagnosis; single cell analysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cells are the most fundamental building blocks for most life forms and play a significant role in coordinating with one another to perform systematic functions in living creatures. However, the cell-to-cell or cell-to-environment behaviors of cells with their organelles and their intracellular physical/biochemical/biological effects are still unknown. To gain insight into these interactions, the ensemble measurement of millions of cells together cannot provide proper information, such as stem cell proliferation and differentiation, neural network coordination, and cardiomyocyte synchronization. Thus, single-cell analysis has emerged in frontier research in the last few decades. To analyze cellular functions, single-cell analysis (SCA) can be conducted by employing miniaturized devices, whose dimension is similar to that of single cells. Micro-/nanofluidic devices with the power to manipulate and detect biosamples, reagents, or biomolecules at the micro-/nano-scale can well fulfill this requirement for SCA. This analysis can be performed by combining capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection methods, electrochemical detection (ED), flow cytometry, mass spectrometry, etc., thereby providing specific information about cell interactions with high spatial and temporal resolution. Micro-/nanofluidic devices are not only useful for cell manipulation, cell lysis, and cell separation, but also for easily controlling biochemical, electrical, and mechanical parameters for SCA.

This Special Issue invites manuscripts conducting research on integrated micro- or nanosystems dealing with single-cell manipulation, injection, separation, lysis of single cells, and dynamics of single cells using micro-/nanofluidic devices combined with various detection schemes. The role of SCA is recognized as one of the most important pathways for system biology, proteomics, genomics, metabolomics, and fluxomics and can potentially lead to a paradigm shift. Discussions on the application of SCA for biocatalysis, metabolics, and bioprocess engineering, as well as on the future challenges for SCA and its advantages and limitations, are also welcome.

Dr. Tuhin Subhra Santra
Prof. Dr. Fan-Gang Tseng
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

  • Lab on a chip
  • Life on a chip
  • Organ on a chip
  • Lab in a cell
  • Cell chip
  • Micro total analysis (µTAS)
  • Microfluidics
  • Nanofluidics
  • Single-cell perturbation
  • Single-cell cultivation
  • Single-cell proteomics
  • Single-cell interaction
  • Dielectrophoresis
  • Electrophoresis
  • Optical trapping
  • Capillary electrophoresis
  • Electroporation
  • Flow cytometry
  • Heterogeneity
  • Mechanical characterization
  • Optical characterization
  • Biochemical characterization
  • System biology

Published Papers (5 papers)

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Research

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14 pages, 7221 KiB  
Article
Individual Microparticle Manipulation Using Combined Electroosmosis and Dielectrophoresis through a Si3N4 Film with a Single Micropore
by Chenang Lyu, Leo Lou, Matthew J. Powell-Palm, Gideon Ukpai, Xing Li and Boris Rubinsky
Micromachines 2021, 12(12), 1578; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12121578 - 18 Dec 2021
Viewed by 1870
Abstract
Porous dielectric membranes that perform insulator-based dielectrophoresis or electroosmotic pumping are commonly used in microchip technologies. However, there are few fundamental studies on the electrokinetic flow patterns of single microparticles around a single micropore in a thin dielectric film. Such a study would [...] Read more.
Porous dielectric membranes that perform insulator-based dielectrophoresis or electroosmotic pumping are commonly used in microchip technologies. However, there are few fundamental studies on the electrokinetic flow patterns of single microparticles around a single micropore in a thin dielectric film. Such a study would provide fundamental insights into the electrokinetic phenomena around a micropore, with practical applications regarding the manipulation of single cells and microparticles by focused electric fields. We have fabricated a device around a silicon nitride film with a single micropore (2–4 µm in diameter) which has the ability to locally focus electric fields on the micropore. Single microscale polystyrene beads were used to study the electrokinetic flow patterns. A mathematical model was developed to support the experimental study and evaluate the electric field distribution, fluid motion, and bead trajectories. Good agreement was found between the mathematic model and the experimental data. We show that the combination of electroosmotic flow and dielectrophoretic force induced by direct current through a single micropore can be used to trap, agglomerate, and repel microparticles around a single micropore without an external pump. The scale of our system is practically relevant for the manipulation of single mammalian cells, and we anticipate that our single-micropore approach will be directly employable in applications ranging from fundamental single cell analyses to high-precision single cell electroporation or cell fusion. Full article
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume III)
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14 pages, 8767 KiB  
Article
Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study
by Yugyung Jung, Minkook Son, Yu Ri Nam, Jongchan Choi, James R. Heath and Sung Yang
Micromachines 2021, 12(10), 1147; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12101147 - 23 Sep 2021
Cited by 1 | Viewed by 3051
Abstract
Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need [...] Read more.
Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need to be analyzed at the single-cell level by monitoring various proteins and investigating their heterogeneity. We propose a microfluidic chip for a single-cell proteomics assay that is capable of analyzing complex cellular signaling systems to reveal the heterogeneity of cancer cells. The single-cell assay chip comprises (i) microchambers (n = 1376) for manipulating single cancer cells, (ii) micropumps for rapid single-cell lysis, and (iii) barcode immunosensors for detecting nine different secretory and intracellular proteins to reveal the correlation among cancer-related proteins. Using this chip, the single-cell proteomics of a lung cancer cell line, which may be easily masked in bulk analysis, were evaluated. By comparing changes in the level of protein secretion and heterogeneity in response to combinations of four anti-cancer drugs, this study suggests a new method for selecting the best combination of anti-cancer drugs. Subsequent preclinical and clinical trials should enable this platform to become applicable for patient-customized therapies. Full article
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume III)
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12 pages, 1963 KiB  
Article
Deformation of an Encapsulated Leukemia HL60 Cell through Sudden Contractions of a Microfluidic Channel
by Mohammad Nooranidoost and Ranganathan Kumar
Micromachines 2021, 12(4), 355; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12040355 - 25 Mar 2021
Viewed by 1790
Abstract
Migration of an encapsulated leukemia HL60 cell through sudden contractions in a capillary tube is investigated. An HL60 cell is initially encapsulated in a viscoelastic shell fluid. As the cell-laden droplet moves through the sudden contraction, shear stresses are experienced around the cell. [...] Read more.
Migration of an encapsulated leukemia HL60 cell through sudden contractions in a capillary tube is investigated. An HL60 cell is initially encapsulated in a viscoelastic shell fluid. As the cell-laden droplet moves through the sudden contraction, shear stresses are experienced around the cell. These stresses along with the interfacial force and geometrical effects cause mechanical deformation which may result in cell death. A parametric study is done to investigate the effects of shell fluid relaxation time, encapsulating droplet size and contraction geometries on cell mechanical deformation. It is found that a large encapsulating droplet with a high relaxation time will undergo low cell mechanical deformation. In addition, the deformation is enhanced for capillary tubes with narrow and long contraction. This study can be useful to characterize cell deformation in constricted microcapillaries and to improve cell viability in bio-microfluidics. Full article
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume III)
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Review

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36 pages, 8285 KiB  
Review
Microfluidic Based Physical Approaches towards Single-Cell Intracellular Delivery and Analysis
by Kiran Kaladharan, Ashish Kumar, Pallavi Gupta, Kavitha Illath, Tuhin Subhra Santra and Fan-Gang Tseng
Micromachines 2021, 12(6), 631; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12060631 - 28 May 2021
Cited by 12 | Viewed by 6309
Abstract
The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have [...] Read more.
The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great interest. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. This review article aims to cover various microfluidic-based physical methods for single-cell intracellular delivery such as electroporation, mechanoporation, microinjection, sonoporation, optoporation, magnetoporation, and thermoporation and their analysis. The mechanisms of various physical methods, their applications, limitations, and prospects are also elaborated. Full article
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume III)
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Other

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8 pages, 1010 KiB  
Perspective
Multi-Modal Microfluidics (M3) for Sample Preparation of Liquid Biopsy: Bridging the Gap between Proof-of-Concept Demonstrations and Practical Applications
by Yaoping Liu and Wei Wang
Micromachines 2022, 13(2), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/mi13020209 - 28 Jan 2022
Cited by 1 | Viewed by 2089
Abstract
Liquid biopsy, the technique used to shed light on diseases via liquid samples, has displayed various advantages, including minimal invasiveness, low risk, and ease of multiple sampling for dynamic monitoring, and has drawn extensive attention from multidisciplinary fields in the past decade. With [...] Read more.
Liquid biopsy, the technique used to shed light on diseases via liquid samples, has displayed various advantages, including minimal invasiveness, low risk, and ease of multiple sampling for dynamic monitoring, and has drawn extensive attention from multidisciplinary fields in the past decade. With the rapid development of microfluidics, it has been possible to manipulate targets of interest including cells, microorganisms, and exosomes at a single number level, which dramatically promotes the characterization and analysis of disease-related markers, and thus improves the capability of liquid biopsy. However, when lab-ready techniques transfer into hospital-applicable tools, they still face a big challenge in processing raw clinical specimens, which are usually of a large volume and consist of rare targets drowned in complex backgrounds. Efforts toward the sample preparation of clinical specimens (i.e., recovering/concentrating the rare targets among complex backgrounds from large-volume liquids) are required to bridge the gap between the proof-of-concept demonstrations and practical applications. The throughput, sensitivity, and purity (TSP performance criteria) in sample preparation, i.e., the volume speed in processing liquid samples and the efficiencies of recovering rare targets and depleting the backgrounds, are three key factors requiring careful consideration when implementing microfluidic-based liquid biopsy for clinical practices. Platforms based on a single microfluidic module (single-modal microfluidics) can hardly fulfill all the aforementioned TSP performance criteria in clinical practices, which puts forward an urgent need to combine/couple multiple microfluidic modules into one working system (i.e., multi-modal microfluidics, M3) to realize practically applicable techniques for the sample preparation of liquid biopsy. This perspective briefly summarizes the typical microfluidic-based liquid biopsy techniques and discusses potential strategies to develop M3 systems for clinical practices of liquid biopsy from the aspect of sample preparation. Full article
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume III)
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