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Micromachines
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Advances in Nanofluidics
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Advances in Nanofluidics

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

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 42049

Special Issue Editors

Dr. Yutaka Kazoe

E-Mail Website
Guest Editor
Department of System Design Engineering, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan
Interests: nanofluidics; microfluidics; fluid mechanics; flow measurements; biomimetics; single-cell analysis; mass spectrometry
Special Issues, Collections and Topics in MDPI journals
Dr. Yan Xu

E-Mail Website
Guest Editor
Department of Chemical Engineering, Graduate School of Engineering, Osaka Prefecture University, Osaka 599-8570, Japan
Interests: nanofluidics; single-molecule manipulation; single-molecule regulated chemistry; nano-optofluidics; single-cell omics; nanobio interfaces; nanomedicine　
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanofluidics has developed to open a new frontier of fluid science and engineering at the 1–1000 nm scale with contributions to the fields of chemistry, biology, materials sciences, bioengineering, medicine, drug discovery, energy, and environmental engineering. Device platforms such as nanochannels, nanopillars, nanopores, and nanotubes have been realized through recent progress in top–down and bottom–up nanofabrication technologies. Single-phase or multiphase fluids in these nanospaces, which are often smaller than light wavelengths, are controlled by capillary flows, pressure-driven flows, and electrokinetic flows. To measure nanoparticles, molecules, and ions contained in such an ultrasmall amount of fluid, advanced detection methods have been developed. Based on these fundamental technologies, various operations at volumes smaller than picoliter have been achieved, and currently novel applications are expected, such as single-molecule analysis, single-cell omics, high-efficient ion conductor/separator, high-efficient heat exchanger, and nanomaterial synthesis. Simultaneously, nanofluidics have provided research tools and knowledge for the elucidation of phenomena of nanoscale confined fluids, which are important in various fields; e.g., physical chemistry, separation science, biophysics, and membrane engineering. The use of nanofluidic platforms has allowed basic experimental research under well-regulated conditions, to elucidate unique fluid properties and specific transport phenomena resulting from dominant surface effects owing to significantly increased surface-to-volume ratios. According to state-of-the-art research, this Special Issue seeks to showcase research papers, short communications, and review articles that focus on all aspects of nanofluidics, including fundamental technologies, sciences, and applications

Dr. Yutaka Kazoe
Dr. Yan Xu
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

  • Nanofluidics
  • Nanochannel
  • Nanopillar
  • Nanopore
  • Nanotube
  • Single molecule
  • Nanomedicine
  • Lab-on-a-Chip

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Published Papers (11 papers)

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11 pages, 2180 KiB  
Article
Size Sorting of Exosomes by Tuning the Thicknesses of the Electric Double Layers on a Micro-Nanofluidic Device
by Satoko Fujiwara, Kyojiro Morikawa, Tatsuro Endo, Hideaki Hisamoto and Kenji Sueyoshi
Micromachines 2020, 11(5), 458; https://doi.org/10.3390/mi11050458 - 28 Apr 2020
Cited by 14 | Viewed by 4282
Abstract
Exosomes, a type of extracellular vesicle with a diameter of 30–150 nm, perform key biological functions such as intercellular communication. Recently, size sorting of exosomes has received increasing attention in order to clarify the correlation between their size and components. However, such sorting [...] Read more.
Exosomes, a type of extracellular vesicle with a diameter of 30–150 nm, perform key biological functions such as intercellular communication. Recently, size sorting of exosomes has received increasing attention in order to clarify the correlation between their size and components. However, such sorting remains extremely difficult. Here, we propose to sort their size by controlling their electrokinetic migration in nanochannels in a micro-nanofluidic device, which is achieved by tuning the thickness of the electric double layers in the nanochannels. This approach was demonstrated experimentally for exosomes smaller than 250 nm. Using different running buffer concentrations (1 × 10−3, 1 × 10−4, and 1 × 10−5 M), most of the exosomes larger than 140, 110, and 80 nm were successfully cut off at the downstream of the nanochannels, respectively. Therefore, it is clarified that the proposed method is applicable for the size sorting of exosomes. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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12 pages, 2137 KiB  
Article
Mechanical Rupture-Based Antibacterial and Cell-Compatible ZnO/SiO2 Nanowire Structures Formed by Bottom-Up Approaches
by Taisuke Shimada, Takao Yasui, Akihiro Yonese, Takeshi Yanagida, Noritada Kaji, Masaki Kanai, Kazuki Nagashima, Tomoji Kawai and Yoshinobu Baba
Micromachines 2020, 11(6), 610; https://doi.org/10.3390/mi11060610 - 24 Jun 2020
Cited by 19 | Viewed by 4391
Abstract
There are growing interests in mechanical rupture-based antibacterial surfaces with nanostructures that have little toxicity to cells around the surfaces; however, current surfaces are fabricated via top-down nanotechnologies, which presents difficulties to apply for bio-surfaces with hierarchal three-dimensional structures. Herein, we developed ZnO/SiO [...] Read more.
There are growing interests in mechanical rupture-based antibacterial surfaces with nanostructures that have little toxicity to cells around the surfaces; however, current surfaces are fabricated via top-down nanotechnologies, which presents difficulties to apply for bio-surfaces with hierarchal three-dimensional structures. Herein, we developed ZnO/SiO2 nanowire structures by using bottom-up approaches and demonstrated to show mechanical rupture-based antibacterial activity and compatibility with human cells. When Escherichia coli were cultured on the surface for 24 h, over 99% of the bacteria were inactivated, while more than 80% of HeLa cells that were cultured on the surface for 24 h were still alive. This is the first demonstration of mechanical rupture-based bacterial rupture via the hydrothermally synthesized nanowire structures with antibacterial activity and cell compatibility. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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12 pages, 2194 KiB  
Article
A Simple Low-Temperature Glass Bonding Process with Surface Activation by Oxygen Plasma for Micro/Nanofluidic Devices
by Koki Shoda, Minori Tanaka, Kensuke Mino and Yutaka Kazoe
Micromachines 2020, 11(9), 804; https://doi.org/10.3390/mi11090804 - 25 Aug 2020
Cited by 24 | Viewed by 5684
Abstract
The bonding of glass substrates is necessary when constructing micro/nanofluidic devices for sealing micro- and nanochannels. Recently, a low-temperature glass bonding method utilizing surface activation with plasma was developed to realize micro/nanofluidic devices for various applications, but it still has issues for general [...] Read more.
The bonding of glass substrates is necessary when constructing micro/nanofluidic devices for sealing micro- and nanochannels. Recently, a low-temperature glass bonding method utilizing surface activation with plasma was developed to realize micro/nanofluidic devices for various applications, but it still has issues for general use. Here, we propose a simple process of low-temperature glass bonding utilizing typical facilities available in clean rooms and applied it to the fabrication of micro/nanofluidic devices made of different glasses. In the process, the substrate surface was activated with oxygen plasma, and the glass substrates were placed in contact in a class ISO 5 clean room. The pre-bonded substrates were heated for annealing. We found an optimal concentration of oxygen plasma and achieved a bonding energy of 0.33–0.48 J/m2 in fused-silica/fused-silica glass bonding. The process was applied to the bonding of fused-silica glass and borosilicate glass, which is generally used in optical microscopy, and revealed higher bonding energy than fused-silica/fused-silica glass bonding. An annealing temperature lower than 200 °C was necessary to avoid crack generation by thermal stress due to the different thermal properties of the glasses. A fabricated micro/nanofluidic device exhibited a pressure resistance higher than 600 kPa. This work will contribute to the advancement of micro/nanofluidics. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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14 pages, 3318 KiB  
Article
Electrochemical Performance of Micropillar Array Electrodes in Microflows
by Bo Liu, Chuanwen Lv, Chaozhan Chen, Bin Ran, Minbo Lan, Huaying Chen and Yonggang Zhu
Micromachines 2020, 11(9), 858; https://doi.org/10.3390/mi11090858 - 17 Sep 2020
Cited by 12 | Viewed by 3623
Abstract
The microchip-based electrochemical detection system (μEDS) has attracted plenty of research attention due to its merits including the capability in high-density integration, high sensitivity, fast analysis time, and reduced reagent consumption. The miniaturized working electrode is usually regarded as the core component of [...] Read more.
The microchip-based electrochemical detection system (μEDS) has attracted plenty of research attention due to its merits including the capability in high-density integration, high sensitivity, fast analysis time, and reduced reagent consumption. The miniaturized working electrode is usually regarded as the core component of the μEDS, since its characteristic directly determines the performance of the whole system. Compared with the microelectrodes with conventional shapes such as the band, ring and disk, the three-dimensional (3D) micropillar array electrode (μAE) has demonstrated significant potential in improving the current response and decreasing the limits of detection due to its much larger reaction area. In this study, the numerical simulation method was used to investigate the performance of the μEDS, and both the geometrical and hydrodynamic parameters, including the micropillars shape, height, arrangement form and the flow rate of the reactant solution, were taken into consideration. The tail effect in μAEs was also quantitatively analyzed based on a pre-defined parameter of the current density ratio. In addition, a PDMS-based 3D μAE was fabricated and integrated into the microchannel for the electrochemical detection. The experiments of cyclic voltammetry (CV) and chronoamperometry (CA) were conducted, and a good agreement was found between the experimental and simulation results. This study would be instructive for the configuration and parameters design of the μEDS, and the presented method can be adopted to analyze and optimize the performance of nanochip-based electrochemical detection system (nEDS). Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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21 pages, 3226 KiB  
Review
Advances in Label-Free Detections for Nanofluidic Analytical Devices
by Thu Hac Huong Le, Hisashi Shimizu and Kyojiro Morikawa
Micromachines 2020, 11(10), 885; https://doi.org/10.3390/mi11100885 - 23 Sep 2020
Cited by 19 | Viewed by 4368
Abstract
Nanofluidics, a discipline of science and engineering of fluids confined to structures at the 1–1000 nm scale, has experienced significant growth over the past decade. Nanofluidics have offered fascinating platforms for chemical and biological analyses by exploiting the unique characteristics of liquids and [...] Read more.
Nanofluidics, a discipline of science and engineering of fluids confined to structures at the 1–1000 nm scale, has experienced significant growth over the past decade. Nanofluidics have offered fascinating platforms for chemical and biological analyses by exploiting the unique characteristics of liquids and molecules confined in nanospaces; however, the difficulty to detect molecules in extremely small spaces hampers the practical applications of nanofluidic devices. Laser-induced fluorescence microscopy with single-molecule sensitivity has been so far a major detection method in nanofluidics, but issues arising from labeling and photobleaching limit its application. Recently, numerous label-free detection methods have been developed to identify and determine the number of molecules, as well as provide chemical, conformational, and kinetic information of molecules. This review focuses on label-free detection techniques designed for nanofluidics; these techniques are divided into two groups: optical and electrical/electrochemical detection methods. In this review, we discuss on the developed nanofluidic device architectures, elucidate the mechanisms by which the utilization of nanofluidics in manipulating molecules and controlling light–matter interactions enhances the capabilities of biological and chemical analyses, and highlight new research directions in the field of detections in nanofluidics. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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13 pages, 10249 KiB  
Article
Pore Structures for High-Throughput Nanopore Devices
by Sou Ryuzaki, Rintaro Matsuda and Masateru Taniguchi
Micromachines 2020, 11(10), 893; https://doi.org/10.3390/mi11100893 - 26 Sep 2020
Cited by 1 | Viewed by 2889
Abstract
Nanopore devices are expected to advance the next-generation of nanobiodevices because of their strong sensing and analyzing capabilities for single molecules and bioparticles. However, the device throughputs are not sufficiently high. Although analytes pass through a nanopore by electrophoresis, the electric field gradient [...] Read more.
Nanopore devices are expected to advance the next-generation of nanobiodevices because of their strong sensing and analyzing capabilities for single molecules and bioparticles. However, the device throughputs are not sufficiently high. Although analytes pass through a nanopore by electrophoresis, the electric field gradient is localized inside and around a nanopore structure. Thus, analytes located far from a nanopore cannot be driven by electrophoresis. Here, we report nanopore structures for high-throughput sensing, namely, inverted pyramid (IP)-shaped nanopore structures. Silicon-based IP-shaped nanopore structures create a homogeneous electric field gradient within a nanopore device, indicating that most of the analytes can pass through a nanopore by electrophoresis, even though the analytes are suspended far from the nanopore entrance. In addition, the nanostructures can be fabricated only by photolithography. The present study suggests a high potential for inverted pyramid shapes to serve as nanopore devices for high-throughput sensing. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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14 pages, 1902 KiB  
Article
Single-Molecule Counting of Nucleotide by Electrophoresis with Nanochannel-Integrated Nano-Gap Devices
by Takahito Ohshiro, Yuki Komoto and Masateru Taniguchi
Micromachines 2020, 11(11), 982; https://doi.org/10.3390/mi11110982 - 31 Oct 2020
Cited by 9 | Viewed by 2915
Abstract
We utilized electrophoresis to control the fluidity of sample biomolecules in sample aqueous solutions inside the nanochannel for single-molecule detection by using a nanochannel-integrated nanogap electrode, which is composed of a nano-gap sensing electrode, nanochannel, and tapered focusing channel. In order to suppress [...] Read more.
We utilized electrophoresis to control the fluidity of sample biomolecules in sample aqueous solutions inside the nanochannel for single-molecule detection by using a nanochannel-integrated nanogap electrode, which is composed of a nano-gap sensing electrode, nanochannel, and tapered focusing channel. In order to suppress electro-osmotic flow and thermal convection inside this nanochannel, we optimized the reduction ratios of the tapered focusing channel, and the ratio of inlet 10 μm to outlet 0.5 μm was found to be high performance of electrophoresis with lower concentration of 0.05 × TBE (Tris/Borate/EDTA) buffer containing a surfactant of 0.1 w/v% polyvinylpyrrolidone (PVP). Under the optimized conditions, single-molecule electrical measurement of deoxyguanosine monophosphate (dGMP) was performed and it was found that the throughput was significantly improved by nearly an order of magnitude compared to that without electrophoresis. In addition, it was also found that the long-duration signals that could interfere with discrimination were significantly reduced. This is because the strong electrophoresis flow inside the nanochannels prevents the molecules’ adsorption near the electrodes. This single-molecule electrical measurement with nanochannel-integrated nano-gap electrodes by electrophoresis significantly improved the throughput of signal detection and identification accuracy. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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11 pages, 2767 KiB  
Article
Advanced Top-Down Fabrication for a Fused Silica Nanofluidic Device
by Kyojiro Morikawa, Yutaka Kazoe, Yuto Takagi, Yoshiyuki Tsuyama, Yuriy Pihosh, Takehiko Tsukahara and Takehiko Kitamori
Micromachines 2020, 11(11), 995; https://doi.org/10.3390/mi11110995 - 9 Nov 2020
Cited by 39 | Viewed by 3666
Abstract
Nanofluidics have recently attracted significant attention with regard to the development of new functionalities and applications, and producing new functional devices utilizing nanofluidics will require the fabrication of nanochannels. Fused silica nanofluidic devices fabricated by top-down methods are a promising approach to realizing [...] Read more.
Nanofluidics have recently attracted significant attention with regard to the development of new functionalities and applications, and producing new functional devices utilizing nanofluidics will require the fabrication of nanochannels. Fused silica nanofluidic devices fabricated by top-down methods are a promising approach to realizing this goal. Our group previously demonstrated the analysis of a living single cell using such a device, incorporating nanochannels having different sizes (102–103 nm) and with branched and confluent structures and surface patterning. However, fabrication of geometrically-controlled nanochannels on the 101 nm size scale by top-down methods on a fused silica substrate, and the fabrication of micro-nano interfaces on a single substrate, remain challenging. In the present study, the smallest-ever square nanochannels (with a size of 50 nm) were fabricated on fused silica substrates by optimizing the electron beam exposure time, and the absence of channel breaks was confirmed by streaming current measurements. In addition, micro-nano interfaces between 103 nm nanochannels and 101 μm microchannels were fabricated on a single substrate by controlling the hydrophobicity of the nanochannel surfaces. A micro-nano interface for a single cell analysis device, in which a nanochannel was connected to a 101 μm single cell chamber, was also fabricated. These new fabrication procedures are expected to advance the basic technologies employed in the field of nanofluidics. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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12 pages, 3312 KiB  
Article
Joule Heating Effects on Transport-Induced-Charge Phenomena in an Ultrathin Nanopore
by Zhixuan Wang, Wei-Lun Hsu, Shuntaro Tsuchiya, Soumyadeep Paul, Amer Alizadeh and Hirofumi Daiguji
Micromachines 2020, 11(12), 1041; https://doi.org/10.3390/mi11121041 - 26 Nov 2020
Cited by 10 | Viewed by 3835
Abstract
Transport-induced-charge (TIC) phenomena, in which the concentration imbalance between cations and anions occurs when more than two chemical potential gradients coexist within an ultrathin dimension, entail numerous nanofluidic systems. Evidence has indicated that the presence of TIC produces a nonlinear response of electroosmotic [...] Read more.
Transport-induced-charge (TIC) phenomena, in which the concentration imbalance between cations and anions occurs when more than two chemical potential gradients coexist within an ultrathin dimension, entail numerous nanofluidic systems. Evidence has indicated that the presence of TIC produces a nonlinear response of electroosmotic flow to the applied voltage, resulting in complex fluid behavior. In this study, we theoretically investigate thermal effects due to Joule heating on TIC phenomena in an ultrathin nanopore by computational fluid dynamics simulation. Our modeling results show that the rise of local temperature inside the nanopore significantly enhances TIC effects and thus has a significant influence on electroosmotic behavior. A local maximum of the solution conductivity occurs near the entrance of the nanopore at the high salt concentration end, resulting in a reversal of TIC across the nanopore. The Joule heating effects increase the reversal of TIC with the synergy of the negatively charged nanopore, and they also enhance the electroosmotic flow regardless of whether the nanopore is charged. These theoretical observations will improve our knowledge of nonclassical electrokinetic phenomena for flow control in nanopore systems. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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11 pages, 2549 KiB  
Article
Fabrication of Infrared-Compatible Nanofluidic Devices for Plasmon-Enhanced Infrared Absorption Spectroscopy
by Thu Hac Huong Le, Takumi Matsushita, Ryoichi Ohta, Yuta Shimoda, Hiroaki Matsui and Takehiko Kitamori
Micromachines 2020, 11(12), 1062; https://doi.org/10.3390/mi11121062 - 30 Nov 2020
Cited by 4 | Viewed by 2546
Abstract
Nanofluidic devices have offered us fascinating analytical platforms for chemical and bioanalysis by exploiting unique properties of liquids and molecules confined in nanospaces. The increasing interests in nanofluidic analytical devices have triggered the development of new robust and sensitive detection techniques, especially label-free [...] Read more.
Nanofluidic devices have offered us fascinating analytical platforms for chemical and bioanalysis by exploiting unique properties of liquids and molecules confined in nanospaces. The increasing interests in nanofluidic analytical devices have triggered the development of new robust and sensitive detection techniques, especially label-free ones. IR absorption spectroscopy is one of the most powerful biochemical analysis methods for identification and quantitative measurement of chemical species in the label-free and non-invasive fashion. However, the low sensitivity and the difficulties in fabrication of IR-compatible nanofluidic devices are major obstacles that restrict the applications of IR spectroscopy in nanofluidics. Here, we realized the bonding of CaF2 and SiO2 at room temperature and demonstrated an IR-compatible nanofluidic device that allowed the IR spectroscopy in a wide range of mid-IR regime. We also performed the integration of metal-insulator-metal perfect absorber metamaterials into nanofluidic devices for plasmon-enhanced infrared absorption spectroscopy with ultrahigh sensitivity. This study also shows a proof-of-concept of the multi-band absorber by combining different types of nanostructures. The results indicate the potential of implementing metamaterials in tracking several characteristic molecular vibrational modes simultaneously, making it possible to identify molecular species in mixture or complex biological entities. Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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3 pages, 159 KiB  
Editorial
Advances in Nanofluidics
by Yutaka Kazoe and Yan Xu
Micromachines 2021, 12(4), 427; https://doi.org/10.3390/mi12040427 - 14 Apr 2021
Cited by 5 | Viewed by 2459
Abstract
Recently, a new frontier in fluid science and engineering at the 1 to 1000 nm scale, called nanofluidics, has developed and provided new methodologies and applications to the fields of chemistry, biology, material sciences, bioengineering, medicine, drug discovery, energy, and environmental engineering [...] [...] Read more.
Recently, a new frontier in fluid science and engineering at the 1 to 1000 nm scale, called nanofluidics, has developed and provided new methodologies and applications to the fields of chemistry, biology, material sciences, bioengineering, medicine, drug discovery, energy, and environmental engineering [...] Full article
(This article belongs to the Special Issue Advances in Nanofluidics)
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