Advances in Microfluidics Technology for Diagnostics and Detection

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Manufacturing Processes and Systems".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 29561

Special Issue Editors


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Guest Editor
School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin 9, Ireland
Interests: point-of-care diagnostics; point-of-use testing; centrifugal microfluidics; microfabrication; 3D printing

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Guest Editor
Institute of Microstructure Technology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
Interests: low-cost MEMS devices; extreme point-of-care systems; embedded systems in PoC
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
MiNaLab, Microsystems and Nanotechnology Department, SINTEF Digital, SINTEF AS, NO-7465 Trondheim, Norway
Interests: biomedical MEMS; microsystems design and technology; medical sensors; biomicrofluidics; centrifugal microfluidics

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Guest Editor
Federal University of São Carlos, Sorocaba, São Carlos, SP 13565-905, Brazil
Interests: materials for sensing; surface functionalization; biosensors; centrifugal microfluidics

Special Issue Information

Dear Colleagues,

Microfluidics and lab-on-a-chip have, in recent years, come to the forefront in diagnostics and detection. At point-of-care, in the emergency room, and at the hospital bed or GP clinic, lab-on-a-chip offers the potential to rapidly detect time-critical and life-threatening diseases such as sepsis and bacterial meningitis. Furthermore, portable and user-friendly diagnostic platforms can enable disease diagnostics and detection to occur in resource-poor setting where centralised laboratory facilities may not be available. At point-of-use, microfluidics and lab-on-chip can be applied in the field to rapidly identify plant pathogens, thus reducing the need for damaging broad spectrum pesticides while also reducing food losses. Microfluidics can also be applied to the continuous monitoring of water quality and can support policy-makers and protection agencies in protecting the environment. Perhaps most excitingly, microfluidics also offers the potential to enable entirely new diagnostic tests that cannot be implemented using conventional laboratory tools. Examples of microfluidics at the frontier of new medical diagnostic tests include early detection of cancers through circulating tumour cells (CTCs) and highly sensitive genetic tests using droplet-based digital PCR.

This Special Issue on “Advances in Microfluidics Technology for Diagnostics and Detection” aims to gather outstanding research and carry out comprehensive coverage of all aspects related to microfluidics in diagnostics and detection. Topics include but not are limited to the following:

  • Microfluidics technology and lab-on-a-chip for point-of-care (medical) and point-of-use (environmental) testing;
  • Integration of embedded systems with lab-on-a-chip for enhanced diagnostic testing;
  • Addressing the challenges of applying microfluidic technology to diagnostics (micro-fabrication, sensitive detection, surface treatments, etc.);
  • New diagnostic tests enabled by microfluidic phenomena.

Dr. David Kinahan
Dr. Dario Mager
Dr. Elizaveta Vereshchagina
Dr. Celina Miyazaki
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. Processes 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 2400 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

  • point-of-care diagnostics
  • point-of-use testing
  • embedded systems in diagnostisc
  • lab-on-a-chip
  • microfluidics
  • microfabrication

Published Papers (8 papers)

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Editorial

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2 pages, 157 KiB  
Editorial
Special Issue on “Advances in Microfluidics Technology for Diagnostics and Detection”
by David J. Kinahan, Dario Mager, Elizaveta Vereshchagina and Celina M. Miyazaki
Processes 2021, 9(5), 854; https://doi.org/10.3390/pr9050854 - 13 May 2021
Viewed by 1514
Abstract
In recent years microfluidics and lab-on-a-chip havecome to the forefront in diagnostics and detection [...] Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)

Research

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15 pages, 4640 KiB  
Article
Dissolvable Film-Controlled Buoyancy Pumping and Aliquoting on a Lab-On-A-Disc
by Niamh A. Kilcawley, Toni C. Voebel, Philip L. Early, Niamh A. McArdle, Marine Renou, Jeanne Rio, Godefroi Saint-Martin, Macdara T. Glynn, Daniel Zontar, Christian Brecher, Jens Ducrée and David J. Kinahan
Processes 2023, 11(1), 128; https://doi.org/10.3390/pr11010128 - 01 Jan 2023
Cited by 4 | Viewed by 1597
Abstract
Lab-on-a-Disc (LoaD) has great potential for applications in decentralised bioanalytical testing where speed and robustness are critical. Here, a disc-shaped microfluidic chip is rotated to pump liquid radially outwards; thus, all microfluidic structures must be fitted into the available radial length. To overcome [...] Read more.
Lab-on-a-Disc (LoaD) has great potential for applications in decentralised bioanalytical testing where speed and robustness are critical. Here, a disc-shaped microfluidic chip is rotated to pump liquid radially outwards; thus, all microfluidic structures must be fitted into the available radial length. To overcome this limitation, several centripetal pumping technologies have been developed. In this work, we combine buoyancy pumping, enabled by displacing aqueous samples and reagents centripetally inwards by a dense liquid (fluorocarbon FC-40), with dissolvable film (DF) to automate a multi-step assay. The DF dissolves in the presence of water but is not in contact with the FC-40. Therefore, the FC-40 can be stored behind the DF membranes and is autonomously released by contact with the arriving aqueous sample. Using this technology, tasks such as blood centrifugation can be located on the disc periphery where ‘disc real estate’ is less valuable and centrifugal forces are higher. To demonstrate this, we use the combination of the buoyancy-driven centripetal pumping with DF barriers to implement a fully automated multi-parameter diagnostic assay on the LoaD platform. The implemented steps include plasma extraction from a structure, automatically triggered metering/aliquoting, and the management of five onboard stored liquid reagents. Critically, we also demonstrate highly accurate aliquoting of reagents using centripetal pumping. We also provide a mathematical model to describe the pumping mechanism and apply lumped-element modelling and Monte Carlo simulation to estimate errors in the aliquoting volumes caused by manufacturing deviations. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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16 pages, 4265 KiB  
Article
Controlling Nanoparticle Formulation: A Low-Budget Prototype for the Automation of a Microfluidic Platform
by Dominik M. Loy, Rafał Krzysztoń, Ulrich Lächelt, Joachim O. Rädler and Ernst Wagner
Processes 2021, 9(1), 129; https://doi.org/10.3390/pr9010129 - 08 Jan 2021
Cited by 8 | Viewed by 2599
Abstract
Active pharmaceutical ingredients (API) with suboptimal pharmacokinetic properties may require formulation into nanoparticles. In addition to the quality of the excipients, production parameters are crucial for producing nanoparticles which reliably deliver APIs to their target. Microfluidic platforms promise increased control over the formulation [...] Read more.
Active pharmaceutical ingredients (API) with suboptimal pharmacokinetic properties may require formulation into nanoparticles. In addition to the quality of the excipients, production parameters are crucial for producing nanoparticles which reliably deliver APIs to their target. Microfluidic platforms promise increased control over the formulation process due to the decreased degrees of freedom at the micro- and nanoscale. Publications about these platforms usually provide only limited information about the soft- and hardware required to integrate the microfluidic chip seamlessly into an experimental set-up. We describe a modular, low-budget prototype for microfluidic mixing in detail. The prototype consists of four modules. The control module is a raspberry pi executing customizable python scripts to control the syringe pumps and the fraction collector. The feeding module consists of up to three commercially available, programable syringe pumps. The formulation module can be any macro- or microfluidic chip connectable to syringe pumps. The collection module is a custom-built fraction collector. We describe each feature of the working prototype and demonstrate its power with polyplexes formulated from siRNA and two different oligomers that are fed to the chip at two different stages during the assembly of the nanoparticles. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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10 pages, 2260 KiB  
Article
Centrifugal Microfluidic Integration of 4-Plex ddPCR Demonstrated by the Quantification of Cancer-Associated Point Mutations
by Franziska Schlenker, Elena Kipf, Nadine Borst, Nils Paust, Roland Zengerle, Felix von Stetten, Peter Juelg and Tobias Hutzenlaub
Processes 2021, 9(1), 97; https://doi.org/10.3390/pr9010097 - 05 Jan 2021
Cited by 15 | Viewed by 3897
Abstract
We present the centrifugal microfluidic implementation of a four-plex digital droplet polymerase chain reaction (ddPCR). The platform features 12 identical ddPCR units on a LabDisk cartridge, each capable of generating droplets with a diameter of 82.7 ± 9 µm. By investigating different oil–surfactant [...] Read more.
We present the centrifugal microfluidic implementation of a four-plex digital droplet polymerase chain reaction (ddPCR). The platform features 12 identical ddPCR units on a LabDisk cartridge, each capable of generating droplets with a diameter of 82.7 ± 9 µm. By investigating different oil–surfactant concentrations, we identified a robust process for droplet generation and stabilization. We observed high droplet stability during thermocycling and endpoint fluorescence imaging, as is required for ddPCRs. Furthermore, we introduce an automated process for four-color fluorescence imaging using a commercial cell analysis microscope, including a customized software pipeline for ddPCR image evaluation. The applicability of ddPCRs is demonstrated by the quantification of three cancer-associated KRAS point mutations (G12D, G12V and G12A) in a diagnostically relevant wild type DNA background. The four-plex assay showed high sensitivity (3.5–35 mutant DNA copies in 15,000 wild type DNA copies) and linear performance (R² = 0.99) across all targets in the LabDisk. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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16 pages, 915 KiB  
Article
Characterization of a Wireless Vacuum Sensor Prototype Based on the SAW-Pirani Principle
by Sofia Toto, Mazin Jouda, Jan G. Korvink, Suparna Sundarayyan, Achim Voigt, Hossein Davoodi and Juergen J. Brandner
Processes 2020, 8(12), 1685; https://doi.org/10.3390/pr8121685 - 21 Dec 2020
Cited by 2 | Viewed by 2499
Abstract
A prototype of a wireless vacuum microsensor combining the Pirani principle and surface acoustic waves (SAW) with extended range and sensitivity was designed, modelled, manufactured and characterised under different conditions. The main components of the prototype are a sensing SAW chip, a heating [...] Read more.
A prototype of a wireless vacuum microsensor combining the Pirani principle and surface acoustic waves (SAW) with extended range and sensitivity was designed, modelled, manufactured and characterised under different conditions. The main components of the prototype are a sensing SAW chip, a heating coil and an interrogation antenna. All the components were assembled on a 15 mm × 11 mm × 3 mm printed circuit board (PCB). The behaviour of the PCB was characterised under ambient conditions and in vacuum. The quality of the SAW interrogation signal, the frequency shift and the received current of the coil were measured for different configurations. Pressures between 0.9 and 100,000 Pa were detected with sensitivities between 2.8 GHz/Pa at 0.9 Pa and 1 Hz/Pa close to atmospheric pressure. This experiment allowed us to determine the optimal operating conditions of the sensor and the integration conditions inside a vacuum chamber in addition to obtaining a pressure-dependent signal. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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16 pages, 3395 KiB  
Article
VectorDisk: A Microfluidic Platform Integrating Diagnostic Markers for Evidence-Based Mosquito Control
by Sebastian Hin, Desirée Baumgartner, Mara Specht, Jan Lüddecke, Ehsan Mahmodi Arjmand, Benita Johannsen, Larissa Schiedel, Markus Rombach, Nils Paust, Felix von Stetten, Roland Zengerle, Nadja Wipf, Pie Müller, Konstantinos Mavridis, John Vontas and Konstantinos Mitsakakis
Processes 2020, 8(12), 1677; https://doi.org/10.3390/pr8121677 - 18 Dec 2020
Cited by 7 | Viewed by 2683
Abstract
Effective mosquito monitoring relies on the accurate identification and characterization of the target population. Since this process requires specialist knowledge and equipment that is not widely available, automated field-deployable systems are highly desirable. We present a centrifugal microfluidic cartridge, the VectorDisk, which integrates [...] Read more.
Effective mosquito monitoring relies on the accurate identification and characterization of the target population. Since this process requires specialist knowledge and equipment that is not widely available, automated field-deployable systems are highly desirable. We present a centrifugal microfluidic cartridge, the VectorDisk, which integrates TaqMan PCR assays in two feasibility studies, aiming to assess multiplexing capability, specificity, and reproducibility in detecting disk-integrated vector-related assays. In the first study, pools of 10 mosquitoes were used as samples. We tested 18 disks with 27 DNA and RNA assays each, using a combination of multiple microfluidic chambers and detection wavelengths (geometric and color multiplexing) to identify mosquito and malaria parasite species as well as insecticide resistance mechanisms. In the second study, purified nucleic acids served as samples to test arboviral and malaria infective mosquito assays. Nine disks were tested with 14 assays each. No false positive results were detected on any of the disks. The coefficient of variation in reproducibility tests was <10%. The modular nature of the platform, the easy adaptation of the primer/probe panels, the cold chain independence, the rapid (2–3 h) analysis, and the assay multiplexing capacity are key features, rendering the VectorDisk a potential candidate for automated vector analysis. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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12 pages, 2334 KiB  
Article
Microfluidic Nano-Scale qPCR Enables Ultra-Sensitive and Quantitative Detection of SARS-CoV-2
by Xin Xie, Tamara Gjorgjieva, Zaynoun Attieh, Mame Massar Dieng, Marc Arnoux, Mostafa Khair, Yasmine Moussa, Fatima Al Jallaf, Nabil Rahiman, Christopher A. Jackson, Lobna El Messery, Khristine Pamplona, Zyrone Victoria, Mohammed Zafar, Raghib Ali, Fabio Piano, Kristin C. Gunsalus and Youssef Idaghdour
Processes 2020, 8(11), 1425; https://doi.org/10.3390/pr8111425 - 09 Nov 2020
Cited by 19 | Viewed by 13452
Abstract
A major challenge in controlling the COVID-19 pandemic is the high false-negative rate of the commonly used RT-PCR methods for SARS-CoV-2 detection in clinical samples. Accurate detection is particularly challenging in samples with low viral loads that are below the limit of detection [...] Read more.
A major challenge in controlling the COVID-19 pandemic is the high false-negative rate of the commonly used RT-PCR methods for SARS-CoV-2 detection in clinical samples. Accurate detection is particularly challenging in samples with low viral loads that are below the limit of detection (LoD) of standard one- or two-step RT-PCR methods. In this study, we implemented a three-step approach for SARS-CoV-2 detection and quantification that employs reverse transcription, targeted cDNA preamplification, and nano-scale qPCR based on a commercially available microfluidic chip. Using SARS-CoV-2 synthetic RNA and plasmid controls, we demonstrate that the addition of a preamplification step enhances the LoD of this microfluidic RT-qPCR by 1000-fold, enabling detection below 1 copy/µL. We applied this method to analyze 182 clinical NP swab samples previously diagnosed using a standard RT-qPCR protocol (91 positive, 91 negative) and demonstrate reproducible and quantitative detection of SARS-CoV-2 over five orders of magnitude (<1 to 106 viral copies/µL). Crucially, we detect SARS-CoV-2 with relatively low viral load estimates (<1 to 40 viral copies/µL) in 17 samples with negative clinical diagnosis, indicating a potential false-negative rate of 18.7% by clinical diagnostic procedures. In summary, this three-step nano-scale RT-qPCR method can robustly detect SARS-CoV-2 in samples with relatively low viral loads (<1 viral copy/µL) and has the potential to reduce the false-negative rate of standard RT-PCR-based diagnostic tests for SARS-CoV-2 and other viral infections. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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Review

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44 pages, 12898 KiB  
Review
Biosensing on the Centrifugal Microfluidic Lab-on-a-Disc Platform
by Celina M. Miyazaki, Eadaoin Carthy and David J. Kinahan
Processes 2020, 8(11), 1360; https://doi.org/10.3390/pr8111360 - 28 Oct 2020
Cited by 31 | Viewed by 7826
Abstract
Lab-on-a-Disc (LoaD) biosensors are increasingly a promising solution for many biosensing applications. In the search for a perfect match between point-of-care (PoC) microfluidic devices and biosensors, the LoaD platform has the potential to be reliable, sensitive, low-cost, and easy-to-use. The present global pandemic [...] Read more.
Lab-on-a-Disc (LoaD) biosensors are increasingly a promising solution for many biosensing applications. In the search for a perfect match between point-of-care (PoC) microfluidic devices and biosensors, the LoaD platform has the potential to be reliable, sensitive, low-cost, and easy-to-use. The present global pandemic draws attention to the importance of rapid sample-to-answer PoC devices for minimising manual intervention and sample manipulation, thus increasing the safety of the health professional while minimising the chances of sample contamination. A biosensor is defined by its ability to measure an analyte by converting a biological binding event to tangible analytical data. With evolving manufacturing processes for both LoaDs and biosensors, it is becoming more feasible to embed biosensors within the platform and/or to pair the microfluidic cartridges with low-cost detection systems. This review considers the basics of the centrifugal microfluidics and describes recent developments in common biosensing methods and novel technologies for fluidic control and automation. Finally, an overview of current devices on the market is provided. This review will guide scientists who want to initiate research in LoaD PoC devices as well as providing valuable reference material to researchers active in the field. Full article
(This article belongs to the Special Issue Advances in Microfluidics Technology for Diagnostics and Detection)
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