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Special Issue "Microdevices and Microsystems for Cell Manipulation"

A special issue of Micromachines (ISSN 2072-666X).

Deadline for manuscript submissions: closed (31 March 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Aaron T. Ohta

Department of Electrical Engineering, University of Hawai'i at Manoa, 2540 Dole Street, Holmes Hall 483, Honolulu, HI 96822, USA
Website | E-Mail
Phone: +1 808 956 8196
Fax: +1 808 956 3427
Interests: MEMS; biomedical microdevices; microfluidics, and optofluidics; microrobotics and cell manipulation; single-cell patterning and assembly; molecular delivery; reconfigurable electronics using liquid metals; optically induced dielectrophoresis (optoelectronic tweezers)
Guest Editor
Dr. Wenqi Hu

Department of Physical Intelligence, Max-Planck-Institut für Intelligente Systeme, Room No. 4P08 Heisenbergstraße 3, 70569 Stuttgart, Germany
E-Mail
Phone: +49-711-689-3430
Interests: medical robotics; reconfigurable mechanical systems in millimeter scale; automation in bio-medical analysis; MEMS; microfluidics

Special Issue Information

Dear Colleagues,

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest.

Prof. Dr. Aaron T. Ohta
Dr. Wenqi Hu
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 papers will be 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 1000 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
  • optofluidics
  • lab-on-a-chip
  • single-cell manipulation
  • single-cell analysis
  • cell trapping
  • cell sorting
  • molecular delivery
  • transfection
  • cell lysis
  • automation

Published Papers (10 papers)

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Research

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Open AccessArticle Three-Dimensional Calcium Alginate Hydrogel Assembly via TiOPc-Based Light-Induced Controllable Electrodeposition
Micromachines 2017, 8(6), 192; doi:10.3390/mi8060192
Received: 31 March 2017 / Revised: 12 June 2017 / Accepted: 15 June 2017 / Published: 19 June 2017
PDF Full-text (3480 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Artificial reconstruction of three-dimensional (3D) hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based
[...] Read more.
Artificial reconstruction of three-dimensional (3D) hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based 3D hydrogel fabrication methods have enabled the formation of 3D tissue constructs. However, they still lack flexibility and high efficiency, which restrict their application in 3D tissue constructs. Alternatively, we report a feasible method for the fabrication and reconstruction of customized 3D hydrogel blocks. Arbitrary hydrogel microstructures were fabricated in situ via flexible and rapid light-addressable electrodeposition. To demonstrate the versatility of this method, the higher-order assembly of 3D hydrogel blocks was investigated using a constant direct current (DC) voltage (6 V) applied between two electrodes for 20–120 s. In addition to the plane-based two-dimensional (2D) assembly, hierarchical structures—including multi-layer 3D hydrogel structures and vessel-shaped structures—could be assembled using the proposed method. Overall, we developed a platform that enables researchers to construct complex 3D hydrogel microstructures efficiently and simply, which has the potential to facilitate research on drug screening and 3D tissue constructs. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle Dynamical Modeling and Analysis of Viscoelastic Properties of Single Cells
Micromachines 2017, 8(6), 171; doi:10.3390/mi8060171
Received: 14 April 2017 / Revised: 13 May 2017 / Accepted: 22 May 2017 / Published: 1 June 2017
PDF Full-text (3726 KB) | HTML Full-text | XML Full-text
Abstract
A single cell can be regarded as a complex network that contains thousands of overlapping signaling pathways. The traditional methods for describing the dynamics of this network are extremely complicated. The mechanical properties of a cell reflect the cytoskeletal structure and composition and
[...] Read more.
A single cell can be regarded as a complex network that contains thousands of overlapping signaling pathways. The traditional methods for describing the dynamics of this network are extremely complicated. The mechanical properties of a cell reflect the cytoskeletal structure and composition and are closely related to the cellular biological functions and physiological activities. Therefore, modeling the mechanical properties of single cells provides the basis for analyzing and controlling the cellular state. In this study, we developed a dynamical model with cellular viscoelasticity properties as the system parameters to describe the stress-relaxation phenomenon of a single cell indented by an atomic force microscope (AFM). The system order and parameters were identified and analyzed. Our results demonstrated that the parameters identified using this model represent the cellular mechanical elasticity and viscosity and can be used to classify cell types. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle A Micromanipulator and Transporter Based on Vibrating Bubbles in an Open Chip Environment
Micromachines 2017, 8(4), 130; doi:10.3390/mi8040130
Received: 13 January 2017 / Revised: 22 March 2017 / Accepted: 7 April 2017 / Published: 18 April 2017
PDF Full-text (12379 KB) | HTML Full-text | XML Full-text
Abstract
A novel micromanipulation technique of multi-objectives based on vibrating bubbles in an open chip environment is described in this paper. Bubbles were created in an aqueous medium by the thermal energy converted from a laser. When the piezoelectric stack fixed under the chip
[...] Read more.
A novel micromanipulation technique of multi-objectives based on vibrating bubbles in an open chip environment is described in this paper. Bubbles were created in an aqueous medium by the thermal energy converted from a laser. When the piezoelectric stack fixed under the chip vibrated the bubbles, micro-objects (microparticles, cells, etc.) rapidly moved towards the bubbles. Results from numerical simulation demonstrate that convective flow around the bubbles can provide forces to capture objects. Since bubbles can be generated at arbitrary destinations in the open chip environment, they can act as both micromanipulators and transporters. As a result, micro- and bio-objects could be collected and transported effectively as masses in the open chip environment. This makes it possible for scientific instruments, such as atomic force microscopy (AFM) and scanning ion conductive microscopy (SICM), to operate the micro-objects directly in an open chip environment. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle Localized Single-Cell Lysis and Manipulation Using Optothermally-Induced Bubbles
Micromachines 2017, 8(4), 121; doi:10.3390/mi8040121
Received: 3 March 2017 / Revised: 30 March 2017 / Accepted: 7 April 2017 / Published: 11 April 2017
PDF Full-text (5536 KB) | HTML Full-text | XML Full-text
Abstract
Localized single cells can be lysed precisely and selectively using microbubbles optothermally generated by microsecond laser pulses. The shear stress from the microstreaming surrounding laser-induced microbubbles and direct contact with the surface of expanding bubbles cause the rupture of targeted cell membranes. High-resolution
[...] Read more.
Localized single cells can be lysed precisely and selectively using microbubbles optothermally generated by microsecond laser pulses. The shear stress from the microstreaming surrounding laser-induced microbubbles and direct contact with the surface of expanding bubbles cause the rupture of targeted cell membranes. High-resolution single-cell lysis is demonstrated: cells adjacent to targeted cells are not lysed. It is also shown that only a portion of the cell membrane can be punctured using this method. Both suspension and adherent cell types can be lysed in this system, and cell manipulation can be integrated for cell–cell interaction studies. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle Cell Migration According to Shape of Graphene Oxide Micropatterns
Micromachines 2016, 7(10), 186; doi:10.3390/mi7100186
Received: 26 August 2016 / Revised: 5 October 2016 / Accepted: 7 October 2016 / Published: 14 October 2016
PDF Full-text (3551 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Photolithography is a unique process that can effectively manufacture micro/nano-sized patterns on various substrates. On the other hand, the meniscus-dragging deposition (MDD) process can produce a uniform surface of the substrate. Graphene oxide (GO) is the oxidized form of graphene that has high
[...] Read more.
Photolithography is a unique process that can effectively manufacture micro/nano-sized patterns on various substrates. On the other hand, the meniscus-dragging deposition (MDD) process can produce a uniform surface of the substrate. Graphene oxide (GO) is the oxidized form of graphene that has high hydrophilicity and protein absorption. It is widely used in biomedical fields such as drug delivery, regenerative medicine, and tissue engineering. Herein, we fabricated uniform GO micropatterns via MDD and photolithography. The physicochemical properties of the GO micropatterns were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), and Raman spectroscopy. Furthermore, cell migration on the GO micropatterns was investigated, and the difference in cell migration on triangle and square GO micropatterns was examined for their effects on cell migration. Our results demonstrated that the GO micropatterns with a desired shape can be finely fabricated via MDD and photolithography. Moreover, it was revealed that the shape of GO micropatterns plays a crucial role in cell migration distance, speed, and directionality. Therefore, our findings suggest that the GO micropatterns can serve as a promising biofunctional platform and cell-guiding substrate for applications to bioelectric devices, cell-on-a-chip, and tissue engineering scaffolds. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle A Robot-Assisted Cell Manipulation System with an Adaptive Visual Servoing Method
Micromachines 2016, 7(6), 104; doi:10.3390/mi7060104
Received: 10 May 2016 / Revised: 6 June 2016 / Accepted: 15 June 2016 / Published: 20 June 2016
Cited by 1 | PDF Full-text (7783 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Robot-assisted cell manipulation is gaining attention for its ability in providing high throughput and high precision cell manipulation for the biological industry. This paper presents a visual servo microrobotic system for cell microinjection. We investigated the automatic cell autofocus method that reduced the
[...] Read more.
Robot-assisted cell manipulation is gaining attention for its ability in providing high throughput and high precision cell manipulation for the biological industry. This paper presents a visual servo microrobotic system for cell microinjection. We investigated the automatic cell autofocus method that reduced the complexity of the system. Then, we produced an adaptive visual processing algorithm to detect the location of the cell and micropipette toward the uneven illumination problem. Fourteen microinjection experiments were conducted with zebrafish embryos. A 100% success rate was achieved either in autofocus or embryo detection, which verified the robustness of the proposed automatic cell manipulation system. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Review

Jump to: Research, Other

Open AccessReview Microfluidic Technology for the Generation of Cell Spheroids and Their Applications
Micromachines 2017, 8(4), 94; doi:10.3390/mi8040094
Received: 11 January 2017 / Revised: 13 March 2017 / Accepted: 15 March 2017 / Published: 23 March 2017
Cited by 1 | PDF Full-text (1433 KB) | HTML Full-text | XML Full-text
Abstract
A three-dimensional (3D) tissue model has significant advantages over the conventional two-dimensional (2D) model. A 3D model mimics the relevant in-vivo physiological conditions, allowing a cell culture to serve as an effective tool for drug discovery, tissue engineering, and the investigation of disease
[...] Read more.
A three-dimensional (3D) tissue model has significant advantages over the conventional two-dimensional (2D) model. A 3D model mimics the relevant in-vivo physiological conditions, allowing a cell culture to serve as an effective tool for drug discovery, tissue engineering, and the investigation of disease pathology. The present reviews highlight the recent advances and the development of microfluidics based methods for the generation of cell spheroids. The paper emphasizes on the application of microfluidic technology for tissue engineering including the formation of multicellular spheroids (MCS). Further, the paper discusses the recent technical advances in the integration of microfluidic devices for MCS-based high-throughput drug screening. The review compares the various microfluidic techniques and finally provides a perspective for the future opportunities in this research area. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessReview A Review on Macroscale and Microscale Cell Lysis Methods
Micromachines 2017, 8(3), 83; doi:10.3390/mi8030083
Received: 21 January 2017 / Revised: 26 February 2017 / Accepted: 3 March 2017 / Published: 8 March 2017
PDF Full-text (15397 KB) | HTML Full-text | XML Full-text
Abstract
The lysis of cells in order to extract the nucleic acids or proteins inside it is a crucial unit operation in biomolecular analysis. This paper presents a critical evaluation of the various methods that are available both in the macro and micro scale
[...] Read more.
The lysis of cells in order to extract the nucleic acids or proteins inside it is a crucial unit operation in biomolecular analysis. This paper presents a critical evaluation of the various methods that are available both in the macro and micro scale for cell lysis. Various types of cells, the structure of their membranes are discussed initially. Then, various methods that are currently used to lyse cells in the macroscale are discussed and compared. Subsequently, popular methods for micro scale cell lysis and different microfluidic devices used are detailed with their advantages and disadvantages. Finally, a comparison of different techniques used in microfluidics platform has been presented which will be helpful to select method for a particular application. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessReview Microfluidic Platform for Cell Isolation and Manipulation Based on Cell Properties
Micromachines 2017, 8(1), 15; doi:10.3390/mi8010015
Received: 28 July 2016 / Revised: 8 November 2016 / Accepted: 8 November 2016 / Published: 4 January 2017
PDF Full-text (5590 KB) | HTML Full-text | XML Full-text
Abstract
In molecular and cellular biological research, cell isolation and sorting are required for accurate investigation of a specific cell types. By employing unique cell properties to distinguish between cell types, rapid and accurate sorting with high efficiency is possible. Though conventional methods can
[...] Read more.
In molecular and cellular biological research, cell isolation and sorting are required for accurate investigation of a specific cell types. By employing unique cell properties to distinguish between cell types, rapid and accurate sorting with high efficiency is possible. Though conventional methods can provide high efficiency sorting using the specific properties of cell, microfluidics systems pave the way to utilize multiple cell properties in a single pass. This improves the selectivity of target cells from multiple cell types with increased purity and recovery rate while maintaining higher throughput comparable to conventional systems. This review covers the breadth of microfluidic platforms for isolation of cellular subtypes based on their intrinsic (e.g., electrical, magnetic, and compressibility) and extrinsic properties (e.g., size, shape, morphology and surface markers). The review concludes by highlighting the advantages and limitations of the reviewed techniques which then suggests future research directions. Addressing these challenges will lead to improved purity, throughput, viability and recovery of cells and be an enabler for novel downstream analysis of cells. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Other

Jump to: Research, Review

Open AccessLetter Fabrication of a Cell Fixation Device for Robotic Cell Microinjection
Micromachines 2016, 7(8), 131; doi:10.3390/mi7080131
Received: 21 June 2016 / Revised: 28 July 2016 / Accepted: 29 July 2016 / Published: 4 August 2016
PDF Full-text (4605 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Automation of cell microinjection greatly reduces operational difficulty, but cell fixation remains a challenge. Here, we describe an innovative device that solves the fixation problem without single-cell operation. The microarray cylinder is designed with a polydimethylsiloxane (PDMS) material surface to control the contact
[...] Read more.
Automation of cell microinjection greatly reduces operational difficulty, but cell fixation remains a challenge. Here, we describe an innovative device that solves the fixation problem without single-cell operation. The microarray cylinder is designed with a polydimethylsiloxane (PDMS) material surface to control the contact force between cells and the material. Data show that when the injection velocity exceeds 1.5 mm/s, microinjection success rate is over 80%. The maximum value of the adhesion force between the PDMS plate and the cell is 0.0138 N, and the need can be met in practical use of the robotic microinjection. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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