Special Issue "Micro- and Nanofluidics for Bionanoparticle Analysis"

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

Deadline for manuscript submissions: closed (30 April 2019)

Special Issue Editors

Guest Editor
Dr. Xuanhong Cheng

Materials Science and Engineering/Bioengineering, Lehigh University, 5 E. Packer Ave, Bethlehem, PA 18015, USA
Website | E-Mail
Phone: 610-758-2002
Interests: microfluidics; biosensor; bioseparation; lab-on-a-chip; bioMEMS
Guest Editor
Dr. Yong Zeng

Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA
Website | E-Mail
Interests: microfluidics; lab-on-a-chip; nanomaterials; cancer biomarker; liquid biopsy; exosome

Special Issue Information

Dear Colleagues,

Bionanoparticles such as microorganisms and exosomes are recoganized as important targets for clinical applications, food safety, and environmental monitoring. Other nanoscale biological particles, includeing liposomes, micelles, and functionalized polymeric particles are widely used in nanomedicines. The recent deveopment of microfluidic and nanofluidic technologies has enabled the separation and anslysis of these species in a lab-on-a-chip platform, while there are still many challenges to address before these analytical tools can be adopted in practice. For example, the complex matrices within which these species reside in create a high background for their detection. Their small dimension and often low concentration demand creative strategies to amplify the sensing signal and enhance the detection speed. This Special Issue aims to recruit recent discoveries and developments of micro- and nanofluidic strategies for the processing and analysis of biological nanoparticles. The collection of papers will hopefully bring out more innovative ideas and fundamental insights to overcome the hurdles faced in the separation and detection of bionanoparticles.

Dr. Xuanhong Cheng
Dr. Yong Zeng
Guest Editors

Manuscript Submission Information

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Keywords

  • Microfluidics
  • Nanofluidics
  • Biological nanoparticles
  • Virus
  • Exosome
  • Liposome
  • Micelle
  • Lab-on-a-chip
  • Biosensing
  • Bioseparation

Published Papers (7 papers)

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Research

Open AccessArticle
Tangential Flow Microfiltration for Viral Separation and Concentration
Micromachines 2019, 10(5), 320; https://doi.org/10.3390/mi10050320
Received: 26 April 2019 / Revised: 7 May 2019 / Accepted: 9 May 2019 / Published: 12 May 2019
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Abstract
Microfluidic devices that allow biological particle separation and concentration have found wide applications in medical diagnosis. Here we present a viral separation polydimethylsiloxane (PDMS) device that combines tangential flow microfiltration and affinity capture to enrich HIV virus in a single flow-through fashion. The [...] Read more.
Microfluidic devices that allow biological particle separation and concentration have found wide applications in medical diagnosis. Here we present a viral separation polydimethylsiloxane (PDMS) device that combines tangential flow microfiltration and affinity capture to enrich HIV virus in a single flow-through fashion. The set-up contains a filtration device and a tandem resistance channel. The filtration device consists of two parallel flow channels separated by a polycarbonate nanoporous membrane. The resistance channel, with dimensions design-guided by COMSOL simulation, controls flow permeation through the membrane in the filtration device. A flow-dependent viral capture efficiency is observed, which likely reflects the interplay of several processes, including specific binding of target virus, physical deposition of non-specific particles, and membrane cleaning by shear flow. At the optimal flow rate, nearly 100% of viral particles in the permeate are captured on the membrane with various input viral concentrations. With its easy operation and consistent performance, this microfluidic device provides a potential solution for HIV sample preparation in resource-limited settings. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessArticle
Portable Rice Disease Spores Capture and Detection Method Using Diffraction Fingerprints on Microfluidic Chip
Micromachines 2019, 10(5), 289; https://doi.org/10.3390/mi10050289
Received: 3 April 2019 / Revised: 25 April 2019 / Accepted: 25 April 2019 / Published: 28 April 2019
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Abstract
Crop diseases cause great harm to food security, 90% of these are caused by fungal spores. This paper proposes a crop diseases spore detection method, based on the lensfree diffraction fingerprint and microfluidic chip. The spore diffraction images are obtained by a designed [...] Read more.
Crop diseases cause great harm to food security, 90% of these are caused by fungal spores. This paper proposes a crop diseases spore detection method, based on the lensfree diffraction fingerprint and microfluidic chip. The spore diffraction images are obtained by a designed large field of view lensless diffraction detection platform which contains the spore enrichment microfluidic chip and lensless imaging module. By using the microfluidic chip to enrich and isolate spores in advance, the required particles can be captured in the chip enrichment area, and other impurities can be filtered to reduce the interference of impurities on spore detection. The light source emits partially coherent light and irradiates the target to generate diffraction fingerprints, which can be used to distinguish spores and impurities. According to the theoretical analysis, two parameters, Peak to Center ratio (PCR) and Peak to Valley ratio (PVR), are found to quantify these spores. The correlation coefficient between the detection results of rice blast spores by the constructed device and the results of microscopic artificial identification was up to 0.99, and the average error rate of the proposed device was only 5.91%. The size of the device is only 4 cm × 4 cm × 5 cm, and the cost is less than $150, which is one thousandth of the existing equipment. Therefore, it may be widely used as an early detection method for crop disease caused by spores. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Graphical abstract

Open AccessFeature PaperArticle
Detection of Cigarette Smoke Using a Surface-Acoustic-Wave Gas Sensor with Non-Polymer-Based Oxidized Hollow Mesoporous Carbon Nanospheres
Micromachines 2019, 10(4), 276; https://doi.org/10.3390/mi10040276
Received: 31 March 2019 / Revised: 22 April 2019 / Accepted: 22 April 2019 / Published: 24 April 2019
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Abstract
The objective of this research was to develop a surface-acoustic-wave (SAW) sensor of cigarette smoke to prevent tobacco hazards and to detect cigarette smoke in real time through the adsorption of an ambient tobacco marker. The SAW sensor was coated with oxidized hollow [...] Read more.
The objective of this research was to develop a surface-acoustic-wave (SAW) sensor of cigarette smoke to prevent tobacco hazards and to detect cigarette smoke in real time through the adsorption of an ambient tobacco marker. The SAW sensor was coated with oxidized hollow mesoporous carbon nanospheres (O-HMC) as a sensing material of a new type, which replaced a polymer. O-HMC were fabricated using nitric acid to form carboxyl groups on carbon frameworks. The modified conditions of O-HMC were analyzed with Scanning Electron Microscopy (SEM), Fourier transform infrared spectrometry (FTIR), and X-ray diffraction (XRD). The appropriately modified O-HMC are more sensitive than polyacrylic acid and hollow mesoporous carbon nanospheres (PAA-HMC), which is proven by normalization. This increases the sensitivity of a standard tobacco marker (3-ethenylpyridine, 3-EP) from 37.8 to 51.2 Hz/ppm and prevents the drawbacks of a polymer-based sensing material. On filtering particles above 1 μm and using tar to prevent tar adhesion, the SAW sensor detects cigarette smoke with sufficient sensitivity and satisfactory repeatability. Tests, showing satisfactory selectivity to the cigarette smoke marker (3-EP) with interfering gases CH4, CO, and CO2, show that CO and CO2 have a negligible role during the detection of cigarette smoke. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessArticle
A Microfluidic Split-Flow Technology for Product Characterization in Continuous Low-Volume Nanoparticle Synthesis
Micromachines 2019, 10(3), 179; https://doi.org/10.3390/mi10030179
Received: 29 January 2019 / Revised: 26 February 2019 / Accepted: 5 March 2019 / Published: 9 March 2019
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Abstract
A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily [...] Read more.
A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily block or alter the flow. Online analysis of the product stream can alleviate this problem by providing a feedback signal. When this signal exceeds a pre-defined range, the process can be re-adjusted or interrupted to prevent contamination. Here we demonstrate the feasibility of this concept by implementing a microfluidic detector downstream of a segmented-flow system for the synthesis of lipid nanoparticles. To match the flow rate through the detector to the measurement bandwidth independent of the synthesis requirements, a small stream is sidelined from the original product stream and routed through a measuring channel with 2 × 2 µm cross-section. The small size of the measuring channel prevents the entry of air plugs, which are inherent to our segmented flow synthesis device. Nanoparticles passing through the small channel were detected and characterized by quantitative fluorescence measurements. With this setup, we were able to count single nanoparticles. This way, we were able to detect changes in the particle synthesis affecting the size, concentration, or velocity of the particles in suspension. We envision that the flow-splitting scheme demonstrated here can be transferred to detection methods other than fluorescence for continuous monitoring and feedback control of microfluidic nanoparticle synthesis. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessFeature PaperArticle
Affordable Fabrication of Conductive Electrodes and Dielectric Films for a Paper-Based Digital Microfluidic Chip
Micromachines 2019, 10(2), 109; https://doi.org/10.3390/mi10020109
Received: 3 January 2019 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 7 February 2019
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Abstract
In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the [...] Read more.
In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the electrodes. For precise and programmable printing of the patterned electrodes, we used a digital plotter with a ballpoint pen filled with a silver nanoparticle (AgNP) ink. Instead of using conventional material deposition methods, such as chemical vapor deposition, printing, and spin coating, for fabricating the thin dielectric layer, we used a simple method in which we prepared a thin dielectric layer using pre-made linear, low-density polyethylene (LLDPE) plastic (17-μm thick) by simple wrapping. We then sealed it tightly with thin silicone oil layers so that it could be used as a DMF chip. Such a treated dielectric layer showed good electrowetting performance for a sessile drop without contact angle hysteresis under an applied voltage of less than 170 V. By using this straightforward fabrication method, we quickly and affordably fabricated a paper-based DMF chip and demonstrated the digital electrofluidic actuation and manipulation of drops. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessArticle
Magnetically Induced Flow Focusing of Non-Magnetic Microparticles in Ferrofluids under Inclined Magnetic Fields
Micromachines 2019, 10(1), 56; https://doi.org/10.3390/mi10010056
Received: 30 December 2018 / Revised: 11 January 2019 / Accepted: 14 January 2019 / Published: 15 January 2019
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Abstract
The ability to focus biological particles into a designated position of a microchannel is vital for various biological applications. This paper reports particle focusing under vertical and inclined magnetic fields. We analyzed the effect of the angle of rotation (θ) of [...] Read more.
The ability to focus biological particles into a designated position of a microchannel is vital for various biological applications. This paper reports particle focusing under vertical and inclined magnetic fields. We analyzed the effect of the angle of rotation (θ) of the permanent magnets and the critical Reynolds number (Rec) on the particle focusing in depth. We found that a rotation angle of 10° is preferred; a particle loop has formed when Re < Rec and Rec of the inclined magnetic field is larger than that of the vertical magnetic field. We also conducted experiments with polystyrene particles (10.4 μm in diameter) to prove the calculations. Experimental results show that the focusing effectiveness improved with increasing applied magnetic field strength or decreasing inlet flow rate. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessFeature PaperArticle
An Optically Induced Dielectrophoresis (ODEP)-Based Microfluidic System for the Isolation of High-Purity CD45neg/EpCAMneg Cells from the Blood Samples of Cancer Patients—Demonstration and Initial Exploration of the Clinical Significance of These Cells
Micromachines 2018, 9(11), 563; https://doi.org/10.3390/mi9110563
Received: 14 October 2018 / Revised: 28 October 2018 / Accepted: 30 October 2018 / Published: 31 October 2018
PDF Full-text (2191 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Circulating tumour cells (CTCs) in blood circulation play an important role in cancer metastasis. CTCs are generally defined as the cells in circulating blood expressing the surface antigen EpCAM (epithelial cell adhesion molecule). Nevertheless, CTCs with a highly metastatic nature might undergo an [...] Read more.
Circulating tumour cells (CTCs) in blood circulation play an important role in cancer metastasis. CTCs are generally defined as the cells in circulating blood expressing the surface antigen EpCAM (epithelial cell adhesion molecule). Nevertheless, CTCs with a highly metastatic nature might undergo an epithelial-to-mesenchymal transition (EMT), after which their EpCAM expression is downregulated. In current CTC-related studies, however, these clinically important CTCs with high relevance to cancer metastasis could be missed due to the use of the conventional CTC isolation methodologies. To precisely explore the clinical significance of these cells (i.e., CD45neg/EpCAMneg cells), the high-purity isolation of these cells from blood samples is required. To achieve this isolation, the integration of fluorescence microscopic imaging and optically induced dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system was proposed. In this study, an ODEP microfluidic system was developed. The optimal ODEP operating conditions and the performance of live CD45neg/EpCAMneg cell isolation were evaluated. The results demonstrated that the proposed system was capable of isolating live CD45neg/EpCAMneg cells with a purity as high as 100%, which is greater than the purity attainable using the existing techniques for similar tasks. As a demonstration case, the cancer-related gene expression of CD45neg/EpCAMneg cells isolated from the blood samples of healthy donors and cancer patients was successfully compared. The initial results indicate that the CD45neg/EpCAMneg nucleated cell population in the blood samples of cancer patients might contain cancer-related cells, particularly EMT-transformed CTCs, as suggested by the high detection rate of vimentin gene expression. Overall, this study presents an ODEP microfluidic system capable of simply and effectively isolating a specific, rare cell species from a cell mixture. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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