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Micromachines
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Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing
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Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B4: Point-of-Care Devices".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 16579

Special Issue Editor

Dr. Chunxiao Hu

E-Mail Website
Guest Editor
James Watt School of Engineering, University of Glasgow, Glasgow, Scotland G12 8QQ, UK
Interests: microsystems; nano-devices; microfluidics; surface functionalization; biosensors; platform integration

Special Issue Information

Dear Colleagues,

Diagnostics are the first line of defense towards better health and fitness. Although conventional laboratory testing and microscopy will still be needed, it is expected that faster and more accurate point-of-care diagnostic tests that do not require laboratory infrastructure will play an increasing role in expanding health care, especially in low- and middle-income countries. Advances in engineering and innovation in diagnostic technologies are enabling miniaturized devices (e.g., lab-on-a-chip) at the micro- or nanoscale, and these devices may eventually provide most of the current range of central laboratory clinical tests at the point-of-care setting. Different types of micro-technologies (e.g., lithography, laser ablation, micromolding, reactive ion etching) have been used to fabricate a variety of analyzers and analytical devices. At a much smaller scale, nanotechnology (1–100 nm scale) is providing both nanomaterials and nanodevices that have analytical potential. Micro/nanotechnology, a series of methods for design and manipulation materials at the micrometer and nanometer scales, which perfectly covers the key building blocks of life including cells, organelles, proteins, nucleic acids, and other components, has unique advantages over current diagnostic methods.

This Special Issue of Micromachines collects research papers, technical notes, communications, and review articles that discuss the latest advancements and future perspectives in Micro/Nanosystems for diagnostic applications in the point-of-care (PoC) setting. Contributions related to the development, design, fabrication, characterization, and especially applications of PoC diagnostic devices are highly welcome.

We look forward to receiving your submissions.

Dr. Chunxiao Hu
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 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

  • micro/nano systems
  • point-of-care
  • diagnostic technology
  • biosensing
  • microfluidics

Published Papers (5 papers)

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Research

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19 pages, 5042 KiB  
Article
Closed-Loop Microreactor on PCB for Ultra-Fast DNA Amplification: Design and Thermal Validation
by Panagiotis Skaltsounis, George Kokkoris, Theodoros G. Papaioannou and Angeliki Tserepi
Micromachines 2023, 14(1), 172; https://doi.org/10.3390/mi14010172 - 10 Jan 2023
Cited by 2 | Viewed by 2170
Abstract
Polymerase chain reaction (PCR) is the most common method used for nucleic acid (DNA) amplification. The development of PCR-performing microfluidic reactors (μPCRs) has been of major importance, due to their crucial role in pathogen detection applications in medical diagnostics. Closed loop (CL) is [...] Read more.
Polymerase chain reaction (PCR) is the most common method used for nucleic acid (DNA) amplification. The development of PCR-performing microfluidic reactors (μPCRs) has been of major importance, due to their crucial role in pathogen detection applications in medical diagnostics. Closed loop (CL) is an advantageous type of μPCR, which uses a circular microchannel, thus allowing the DNA sample to pass consecutively through the different temperature zones, in order to accomplish a PCR cycle. CL μPCR offers the main advantages of the traditional continuous-flow μPCR, eliminating at the same time most of the disadvantages associated with the long serpentine microchannel. In this work, the performance of three different CL μPCRs designed for fabrication on a printed circuit board (PCB) was evaluated by a computational study in terms of the residence time in each thermal zone. A 3D heat transfer model was used to calculate the temperature distribution in the microreactor, and the residence times were extracted by this distribution. The results of the computational study suggest that for the best-performing microreactor design, a PCR of 30 cycles can be achieved in less than 3 min. Subsequently, a PCB chip was fabricated based on the design that performed best in the computational study. PCB constitutes a great substrate as it allows for integrated microheaters inside the chip, permitting at the same time low-cost, reliable, reproducible, and mass-amenable fabrication. The fabricated chip, which, at the time of this writing, is the first CL μPCR chip fabricated on a PCB, was tested by measuring the temperatures on its surface with a thermal camera. These results were then compared with the ones of the computational study, in order to evaluate the reliability of the latter. The comparison of the calculated temperatures with the measured values verifies the accuracy of the developed model of the microreactor. As a result of that, a total power consumption of 1.521 W was experimentally measured, only ~7.3% larger than the one calculated (1.417 W). Full validation of the realized CL μPCR chip will be demonstrated in future work. Full article
(This article belongs to the Special Issue Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing)
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16 pages, 3236 KiB  
Article
Microfluidic Paper-Based Blood Plasma Separation Device as a Potential Tool for Timely Detection of Protein Biomarkers
by Francisco Burgos-Flórez, Alexander Rodríguez, Eliana Cervera, Marcio De Ávila, Marco Sanjuán and Pedro J. Villalba
Micromachines 2022, 13(5), 706; https://doi.org/10.3390/mi13050706 - 29 Apr 2022
Cited by 9 | Viewed by 3532
Abstract
A current challenge regarding microfluidic paper-based analytical devices (µPAD) for blood plasma separation (BPS) and electrochemical immunodetection of protein biomarkers is how to achieve a µPAD that yields enough plasma to retain the biomarker for affinity biosensing in a functionalized electrode system. This [...] Read more.
A current challenge regarding microfluidic paper-based analytical devices (µPAD) for blood plasma separation (BPS) and electrochemical immunodetection of protein biomarkers is how to achieve a µPAD that yields enough plasma to retain the biomarker for affinity biosensing in a functionalized electrode system. This paper describes the development of a BPS µPAD to detect and quantify the S100B biomarker from peripheral whole blood. The device uses NaCl functionalized VF2 filter paper as a sample collection pad, an MF1 filter paper for plasma retention, and an optimized microfluidic channel geometry. An inverted light microscope, scanning electron microscope (SEM), and image processing software were used for visualizing BPS efficiency. A design of experiments (DOE) assessed the device’s efficacy using an S100B ELISA Kit to measure clinically relevant S100B concentrations in plasma. The BPS device obtained 50 μL of plasma from 300 μL of whole blood after 3.5 min. The statistical correlation of S100B concentrations obtained using plasma from standard centrifugation and the BPS device was 0.98. The BPS device provides a simple manufacturing protocol, short fabrication time, and is capable of S100B detection using ELISA, making one step towards the integration of technologies aimed at low-cost POC testing of clinically relevant biomarkers. Full article
(This article belongs to the Special Issue Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing)
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15 pages, 3815 KiB  
Article
Schistoscope: An Automated Microscope with Artificial Intelligence for Detection of Schistosoma haematobium Eggs in Resource-Limited Settings
by Prosper Oyibo, Satyajith Jujjavarapu, Brice Meulah, Tope Agbana, Ingeborg Braakman, Angela van Diepen, Michel Bengtson, Lisette van Lieshout, Wellington Oyibo, Gleb Vdovine and Jan-Carel Diehl
Micromachines 2022, 13(5), 643; https://doi.org/10.3390/mi13050643 - 19 Apr 2022
Cited by 12 | Viewed by 4755
Abstract
For many parasitic diseases, the microscopic examination of clinical samples such as urine and stool still serves as the diagnostic reference standard, primarily because microscopes are accessible and cost-effective. However, conventional microscopy is laborious, requires highly skilled personnel, and is highly subjective. Requirements [...] Read more.
For many parasitic diseases, the microscopic examination of clinical samples such as urine and stool still serves as the diagnostic reference standard, primarily because microscopes are accessible and cost-effective. However, conventional microscopy is laborious, requires highly skilled personnel, and is highly subjective. Requirements for skilled operators, coupled with the cost and maintenance needs of the microscopes, which is hardly done in endemic countries, presents grossly limited access to the diagnosis of parasitic diseases in resource-limited settings. The urgent requirement for the management of tropical diseases such as schistosomiasis, which is now focused on elimination, has underscored the critical need for the creation of access to easy-to-use diagnosis for case detection, community mapping, and surveillance. In this paper, we present a low-cost automated digital microscope—the Schistoscope—which is capable of automatic focusing and scanning regions of interest in prepared microscope slides, and automatic detection of Schistosoma haematobium eggs in captured images. The device was developed using widely accessible distributed manufacturing methods and off-the-shelf components to enable local manufacturability and ease of maintenance. For proof of principle, we created a Schistosoma haematobium egg dataset of over 5000 images captured from spiked and clinical urine samples from field settings and demonstrated the automatic detection of Schistosoma haematobium eggs using a trained deep neural network model. The experiments and results presented in this paper collectively illustrate the robustness, stability, and optical performance of the device, making it suitable for use in the monitoring and evaluation of schistosomiasis control programs in endemic settings. Full article
(This article belongs to the Special Issue Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing)
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16 pages, 2117 KiB  
Article
Uniform Tumor Spheroids on Surface-Optimized Microfluidic Biochips for Reproducible Drug Screening and Personalized Medicine
by Neda Azizipour, Rahi Avazpour, Michael H. Weber, Mohamad Sawan, Abdellah Ajji and Derek H. Rosenzweig
Micromachines 2022, 13(4), 587; https://doi.org/10.3390/mi13040587 - 9 Apr 2022
Cited by 9 | Viewed by 3094
Abstract
Spheroids are recognized for resembling the important characteristics of natural tumors in cancer research. However, the lack of controllability of the spheroid size, form, and density in conventional spheroid culture methods reduces the reproducibility and precision of bioassay results and the assessment of [...] Read more.
Spheroids are recognized for resembling the important characteristics of natural tumors in cancer research. However, the lack of controllability of the spheroid size, form, and density in conventional spheroid culture methods reduces the reproducibility and precision of bioassay results and the assessment of drug-dose responses in spheroids. Nonetheless, the accurate prediction of cellular responses to drug compounds is crucial for developing new efficient therapeutic agents and optimizing existing therapeutic strategies for personalized medicine. We developed a surface-optimized PDMS microfluidic biochip to produce uniform and homogenous multicellular spheroids in a reproducible manner. This platform is surface optimized with 10% bovine serum albumin (BSA) to provide cell-repellent properties. Therefore, weak cell-surface interactions lead to the promotion of cell self-aggregations and the production of compact and uniform spheroids. We used a lung cancer cell line (A549), a co-culture model of lung cancer cells (A549) with (primary human osteoblasts, and patient-derived spine metastases cells (BML, bone metastasis secondary to lung). We observed that the behavior of cells cultured in three-dimensional (3D) spheroids within this biochip platform more closely reflects in vivo-like cellular responses to a chemotherapeutic drug, Doxorubicin, rather than on 24-well plates (two-dimensional (2D) model). It was also observed that the co-culture and patient-derived spheroids exhibited resistance to anti-cancer drugs more than the mono-culture spheroids. The repeatability of drug test results in this optimized platform is the hallmark of the reproducibility of uniform spheroids on a chip. This surface-optimized biochip can be a reliable platform to generate homogenous and uniform spheroids to study and monitor the tumor microenvironment and for drug screening. Full article
(This article belongs to the Special Issue Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing)
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Review

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17 pages, 8739 KiB  
Review
Integrating Microfluidics and Electronics in Point-of-Care Diagnostics: Current and Future Challenges
by Valerio Francesco Annese and Chunxiao Hu
Micromachines 2022, 13(11), 1923; https://doi.org/10.3390/mi13111923 - 7 Nov 2022
Cited by 5 | Viewed by 2193
Abstract
Point-of-Care (POC) diagnostics have gained increasing attention in recent years due to its numerous advantages over conventional diagnostic approaches. As proven during the recent COVID-19 pandemic, the rapidity and portability of POC testing improves the efficiency of healthcare services and reduces the burden [...] Read more.
Point-of-Care (POC) diagnostics have gained increasing attention in recent years due to its numerous advantages over conventional diagnostic approaches. As proven during the recent COVID-19 pandemic, the rapidity and portability of POC testing improves the efficiency of healthcare services and reduces the burden on healthcare providers. There are hundreds of thousands of different applications for POC diagnostics, however, the ultimate requirement for the test is the same: sample-in and result-out. Many technologies have been implemented, such as microfluidics, semiconductors, and nanostructure, to achieve this end. The development of even more powerful POC systems was also enabled by merging multiple technologies into the same system. One successful example is the integration of microfluidics and electronics in POC diagnostics, which has simplified the sample handling process, reduced sample usage, and reduced the cost of the test. This review will analyze the current development of the POC diagnostic systems with the integration of microfluidics and electronics and discuss the future challenges and perspectives that researchers might have. Full article
(This article belongs to the Special Issue Innovation in Diagnostic Technologies—Applications of Micro/Nanosystems in Point-of-Care Testing)
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