Special Issue "Liquid Biopsy in a Microfluidic Chip for Rapid and Non-Invasive Point-of-Care Diagnostics"

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

Deadline for manuscript submissions: closed (30 April 2018).

Special Issue Editor

Prof. Dr. Yong-Ak (Rafael) Song
E-Mail Website
Guest Editor
Division of Engineering, New York University Abu Dhabi (NYUAD), Abu Dhabi, UAE;
Tandon School of Engineering, Department of Chemical and Biomolecular Engineering, New York University, Brooklyn, NY, USA
Tel. +971-2-628-4781
Interests: micro- and nanofluidics; point-of-care diagnostics; liquid biopsy; electrokinetics

Special Issue Information

Dear Colleagues,

“Liquid biopsy” has gained a tremendous amount of interest in clinical diagnostics, as well as in patient care, due to its non-invasive nature compared to traditional tissue biopsy. Circulating tumor cells (CTC), cell-free circulating tumor DNA (ctDNA), and exosomes that can be isolated from blood and other body fluids without removing tissues, which are sometimes difficult to access, offer exciting new opportunities for early cancer diagnostics. Several studies have already indicated that CTC cells, ctDNA and vesicles can be linked to specific disease states and can potentially be used as biomarkers for early detection, as well as for continuous monitoring of the progress of a treatment. To conduct liquid biopsy in a rapid manner, preferably at the point-of-care, the microfluidic chip format offers an integrated solution for sample processing and detection. Compared to other detection platforms, it provides unique advantages with regards to the required sample volume, speed, sensitivity and the possibility for high-throughput screening.  In this Special Issue, we invite research groups from diverse disciplines to submit original research works related to liquid biopsy on a microfluidic chip.  Potential topics, but not limited to, are new microfluidic devices for efficient and rapid isolation of biomarkers from various types of body fluid sources for sample preparation and rapid analysis of biomolecular contents. Clinical studies using microfluidic devices for liquid biopsy are especially welcome. This Special Issue will highlight the progress that has been made in liquid biopsy-on-a-chip, as well as show new opportunities of “liquid-biopsy-on-a-chip” in clinical applications.

Prof. Dr. Yong-Ak (Rafael) Song
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 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 1400 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-a-Chip
  • Liquid Biopsy
  • Circulating Tumor Cells (CTC)
  • Circulating Tumor DNA (ctDNA)
  • Exosomes
  • Exosomal RNA
  • Point-of-Care Diagnostics
  • Cancer Detection

Published Papers (7 papers)

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Research

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Open AccessArticle
Rapid Detection and Trapping of Extracellular Vesicles by Electrokinetic Concentration for Liquid Biopsy on Chip
Micromachines 2018, 9(6), 306; https://doi.org/10.3390/mi9060306 - 19 Jun 2018
Cited by 3
Abstract
Exosomes have gained immense importance since their proteomic and genetic contents could potentially be used for disease diagnostics, monitoring of cancer progression, metastasis, and drug efficacy. However, establishing the clinical utility of exosomes has been restricted due to small sizes and high sample [...] Read more.
Exosomes have gained immense importance since their proteomic and genetic contents could potentially be used for disease diagnostics, monitoring of cancer progression, metastasis, and drug efficacy. However, establishing the clinical utility of exosomes has been restricted due to small sizes and high sample loss from extensive sample preparation. Sample loss is particularly critical for body fluids limited in volume and difficult to access, e.g., cerebrospinal fluid. We present a microfluidic technique that locally enhances the concentration of extracellular vesicles extracted from MDA-MB-231 human breast cancer cell lines by using an ion concentration polarization (ICP)-based electrokinetic concentrator. Our design incorporates a trapping mechanism near the conductive polymer membrane; therefore, we can preconcentrate and capture extracellular vesicles simultaneously. Compared with standard fluorescence detection, our method increased the limit of detection (LOD) of extracellular vesicles by two orders of magnitude in 30 min. Our concentrator increased the extracellular vesicle concentration for 5.0 × 107 particles/1 mL (LOD), 5.0 × 108 particles/1 mL, and 5.0 × 109 particles/1 mL by ~100-fold each within 30 min using 45 V. This study demonstrates an alternative platform to simultaneously preconcentrate and capture extracellular vesicles that can be incorporated as part of a liquid biopsy-on-a-chip system for the detection of exosomal biomarkers and analysis of their contents for early cancer diagnosis. Full article
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Open AccessFeature PaperArticle
PDMS-Parylene Hybrid, Flexible Microfluidics for Real-Time Modulation of 3D Helical Inertial Microfluidics
Micromachines 2018, 9(6), 255; https://doi.org/10.3390/mi9060255 - 23 May 2018
Cited by 4
Abstract
Inertial microfluidics has drawn much attention for its applications for circulating tumor cell separations from blood. The fluid flows and the inertial particle focusing in inertial microfluidic systems are highly dependent on the channel geometry and structure. Flexible microfluidic systems can have adjustable [...] Read more.
Inertial microfluidics has drawn much attention for its applications for circulating tumor cell separations from blood. The fluid flows and the inertial particle focusing in inertial microfluidic systems are highly dependent on the channel geometry and structure. Flexible microfluidic systems can have adjustable 3D channel geometries by curving planar 2D channels into 3D structures, which will enable tunable inertial separation. We present a poly(dimethylsiloxane) (PDMS)-parylene hybrid thin-film microfluidic system that can provide high flexibility for 3D channel shaping while maintaining the channel cross-sectional shape. The PDMS-parylene hybrid microfluidic channels were fabricated by a molding and bonding technique using initiated chemical vapor deposition (iCVD) bonding. We constructed 3D helical inertial microfluidic channels by coiling a straight 2D channel and studied the inertial focusing while varying radius of curvature and Reynolds number. This thin film structure allows for high channel curvature and high Dean numbers which leads to faster inertial particle focusing and shorter channel lengths than 2D spiral channels. Most importantly, the focusing positions of particles and cells in the microchannel can be tuned in real time by simply modulating the channel curvature. The simple mechanical modulation of these 3D structure microfluidic systems is expected to provide unique advantages of convenient tuning of cell separation thresholds with a single device. Full article
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Open AccessArticle
Continuous-Flow Cell Dipping and Medium Exchange in a Microdevice using Dielectrophoresis
Micromachines 2018, 9(5), 223; https://doi.org/10.3390/mi9050223 - 08 May 2018
Cited by 6
Abstract
Medium exchange is the process of changing the suspension medium of cells/particles, and has applications in washing, surface modifications, nutrient replenishment, or simply changing the environment of the target entities. Dipping involves diverting the path of target cells in the carrying fluid to [...] Read more.
Medium exchange is the process of changing the suspension medium of cells/particles, and has applications in washing, surface modifications, nutrient replenishment, or simply changing the environment of the target entities. Dipping involves diverting the path of target cells in the carrying fluid to immerse them in another fluid for a short duration, and pushing them again into the original medium. In this paper, a simple microfluidic platform is introduced that employs dielectrophoresis to achieve medium exchange and dipping of micro-objects in a continuous manner. The essential feature of the platform is a microchannel that includes two arrays of microelectrodes that partly enter the bottom surface from both sides. In the first step, numerous finite element-based parametric studies are carried out to obtain the optimized geometrical and operational parameters ensuring successful dipping and medium exchange processes. The results of those studies are utilized to fabricate the platform using standard photolithography techniques. The electrodes are patterned on a glass substrate, while the channel, made out of polydimethylsiloxane, is bonded on top of the glass. Trajectories of blood cells from numerical studies and experimentations are reported, and both results exhibited close agreement. Full article
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Open AccessArticle
Spiral Microchannels with Trapezoidal Cross Section Fabricated by Femtosecond Laser Ablation in Glass for the Inertial Separation of Microparticles
Micromachines 2018, 9(4), 171; https://doi.org/10.3390/mi9040171 - 09 Apr 2018
Cited by 4
Abstract
The fabrication and testing of spiral microchannels with a trapezoidal cross section for the passive separation of microparticles is reported in this article. In contrast to previously reported fabrication methods, the fabrication of trapezoidal spiral channels in glass substrates using a femtosecond laser [...] Read more.
The fabrication and testing of spiral microchannels with a trapezoidal cross section for the passive separation of microparticles is reported in this article. In contrast to previously reported fabrication methods, the fabrication of trapezoidal spiral channels in glass substrates using a femtosecond laser is reported for the first time in this paper. Femtosecond laser ablation has been proposed as an accurate and fast prototyping method with the ability to create 3D features such as slanted-base channels. Moreover, the fabrication in borosilicate glass substrates can provide high optical transparency, thermal resistance, dimensional stability, and chemical inertness. Post-processing steps of the laser engraved glass substrate are also detailed in this paper including hydrogen fluoride (HF) dipping, chemical cleaning, surface activation, and thermal bonding. Optical 3D images of the fabricated chips confirmed a good fabrication accuracy and acceptable surface roughness. To evaluate the particle separation function of the microfluidic chip, 5 μm, 10 μm, and 15 μm particles were focused and recovered from the two outlets of the spiral channel. In conclusion, the new chemically inert separation chip can be utilized in biological or chemical processes where different sizes of cells or particles must be separated, i.e., red blood cells, circulating tumor cells, and technical particle suspensions. Full article
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Review

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Open AccessFeature PaperReview
Toward Exosome-Based Neuronal Diagnostic Devices
Micromachines 2018, 9(12), 634; https://doi.org/10.3390/mi9120634 - 29 Nov 2018
Cited by 1
Abstract
Targeting exosome for liquid biopsy has gained significant attention for its diagnostic and therapeutic potential. For detecting neuronal disease diagnosis such as Alzheimer’s disease (AD), the main technique for identifying AD still relies on positron-emission tomography (PET) imaging to detect the presence of [...] Read more.
Targeting exosome for liquid biopsy has gained significant attention for its diagnostic and therapeutic potential. For detecting neuronal disease diagnosis such as Alzheimer’s disease (AD), the main technique for identifying AD still relies on positron-emission tomography (PET) imaging to detect the presence of amyloid-β (Aβ). While the detection of Aβ in cerebrospinal fluid has also been suggested as a marker for AD, the lack of quantitative measurements has compromised existing assays. In cerebrospinal fluid, in addition to Aβ, T-Tau, and P-Tau, alpha-synuclein has been considered a biomarker of neurodegeneration. This review suggests that and explains how the exosome can be used as a neuronal diagnostic component. To this end, we summarize current progress in exosome preparation/isolation and quantification techniques and comment on the outlooks for neuronal exosome-based diagnostic techniques. Full article
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Open AccessReview
The Use of Microfluidic Technology for Cancer Applications and Liquid Biopsy
Micromachines 2018, 9(8), 397; https://doi.org/10.3390/mi9080397 - 10 Aug 2018
Cited by 3
Abstract
There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to sample a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor [...] Read more.
There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to sample a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor biomarkers is needed. Liquid biopsy has gained attention due to its non-invasive sampling of tumor tissue and ability to serially assess disease via a simple blood draw over the course of treatment. Among the leading technologies developing liquid biopsy solutions, microfluidics has recently come to the fore. Microfluidic platforms offer cellular separation and analysis platforms that allow for high throughout, high sensitivity and specificity, low sample volumes and reagent costs and precise liquid controlling capabilities. These characteristics make microfluidic technology a promising tool in separating and analyzing circulating tumor biomarkers for diagnosis, prognosis and monitoring. In this review, the characteristics of three kinds of circulating tumor markers will be described in the context of cancer, circulating tumor cells (CTCs), exosomes, and circulating tumor DNA (ctDNA). The review will focus on how the introduction of microfluidic technologies has improved the separation and analysis of these circulating tumor markers. Full article
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Open AccessReview
Liquid Biopsy in Colorectal Cancer-Current Status and Potential Clinical Applications
Micromachines 2018, 9(6), 300; https://doi.org/10.3390/mi9060300 - 15 Jun 2018
Cited by 2
Abstract
Colorectal cancer is one of the most frequent solid malignancies worldwide. The treatment is either surgical or multimodal and depends on the stage of the disease at diagnosis. Accurate disease assessment is thus of great importance for choosing the most optimal treatment strategy. [...] Read more.
Colorectal cancer is one of the most frequent solid malignancies worldwide. The treatment is either surgical or multimodal and depends on the stage of the disease at diagnosis. Accurate disease assessment is thus of great importance for choosing the most optimal treatment strategy. However, the standard means of disease assessment by radiological imaging or histopathological analysis of the removed tumor tissue lack the sensitivity in detecting the early systemic spread of the disease. To overcome this deficiency, the concept of liquid biopsy from the peripheral blood of patients has emerged as a new, very promising diagnostic tool. In this article, we provide an overview of the current status of clinical research on liquid biopsy in colorectal cancer. We also highlight the clinical situations in which the concept might be of the greatest benefit for the management of colorectal cancer patients in the future. Full article
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