Research

14 pages, 5633 KiB

Open AccessArticle

Improved Enumeration of Weakly Fluorescent CD4+ T-lymphocytes by Confining Cells in a Spinning Sample Cartridge with a Helical Minichannel

by Subin Kim, Jakir Hossain Imran, Mohiuddin Khan Shourav and Jung Kyung Kim

Micromachines 2020, 11(6), 618; https://doi.org/10.3390/mi11060618 - 25 Jun 2020

Cited by 1 | Viewed by 1908

Abstract

The CD4 (cluster of differentiation 4) counting method is used to measure the number of CD4+ T-lymphocytes per microliter of blood and to evaluate the timing of the initiation of antiretroviral therapy as well as the effectiveness of treatment in patients with human [...] Read more.

The CD4 (cluster of differentiation 4) counting method is used to measure the number of CD4+ T-lymphocytes per microliter of blood and to evaluate the timing of the initiation of antiretroviral therapy as well as the effectiveness of treatment in patients with human immunodeficiency virus. We developed a three-dimensional helical minichannel-based sample cartridge in which a thread-like microgroove formed in the cylindrical surface and configured a particle-positioning and imaging system equipped with a single DC (direct current) motor that can be controlled by a smartphone application. Confinement and enrichment of CD4 cells within a sharp focal depth along the helical minichannel is accomplished by spinning the cylindrical sample cartridge at high speed before acquiring cell images and thus CD4+ cells with weak fluorescence intensity can be detected even in a channel much deeper than existing two-dimensional flat chambers without an autofocusing module. By detecting more cells in a larger sample volume, the accuracy of the CD4 cell count is improved by a factor of 5.8 with a channel of 500 μm depth and the precision is enhanced by a factor of 1.5 with a coefficient of variation of 2.6%. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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8 pages, 1907 KiB

Open AccessArticle

Impedance-Based Biosensing of Pseudomonas putida via Solution Blow Spun PLA: MWCNT Composite Nanofibers

by Craig Miller, Madison Stiglich, Mark Livingstone and Jordon Gilmore

Micromachines 2019, 10(12), 876; https://doi.org/10.3390/mi10120876 - 13 Dec 2019

Cited by 7 | Viewed by 3192

Abstract

Quantifiable sensing of common microbes in chronic wounds has the potential to enable an objective assessment of wound healing for diagnostic applications. Sensing platforms should be robust, simple, and flexible to provide clinicians with a point-of-care tool. In this work, solution blow spun [...] Read more.

Quantifiable sensing of common microbes in chronic wounds has the potential to enable an objective assessment of wound healing for diagnostic applications. Sensing platforms should be robust, simple, and flexible to provide clinicians with a point-of-care tool. In this work, solution blow spun poly (lactic acid)/multiwalled carbon nanotube nanofiber composites are used to detect the presence and concentration of Pseudomonas putida in vitro using changes in impedance. Impedance microbiology (IM) is a well-documented diagnostic technique used in many applications, including cancer detection, tuberculosis screening and pregnancy tests. Twenty-four hour real-time measurements of the equivalent circuit of three culture media were taken with an inductance, capacitance, and resistance (LCR) meter. Variations in impedance were calculated to correspond to the growth of P. putida. Additionally, instantaneous measurements of bacterial cultures were taken over a one-minute time point to display the fast sensing of bacterial load via IM. This proof-of-concept shows that conductive solution blow spun fiber mats is a valid fabrication technique to develop in situ wound dressing impedance sensors. Study results indicate successful measurement and quantification of bacterial growth in this proof-of-concept study. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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13 pages, 2453 KiB

Open AccessFeature PaperArticle

Automated Pre-Analytic Processing of Whole Saliva Using Magnet-Beating for Point-of-Care Protein Biomarker Analysis

by Benita Johannsen, Lara Müller, Desirée Baumgartner, Lena Karkossa, Susanna M. Früh, Nagihan Bostanci, Michal Karpíšek, Roland Zengerle, Nils Paust and Konstantinos Mitsakakis

Micromachines 2019, 10(12), 833; https://doi.org/10.3390/mi10120833 - 30 Nov 2019

Cited by 18 | Viewed by 4647

Abstract

Saliva offers many advantages for point-of-care (PoC) diagnostic applications due to non-invasive, easy, and cost-effective methods of collection. However, the complex matrix with its non-Newtonian behavior and high viscosity poses handling challenges. Several tedious and long pre-analytic steps, incompatible with PoC use, are [...] Read more.

Saliva offers many advantages for point-of-care (PoC) diagnostic applications due to non-invasive, easy, and cost-effective methods of collection. However, the complex matrix with its non-Newtonian behavior and high viscosity poses handling challenges. Several tedious and long pre-analytic steps, incompatible with PoC use, are required to liquefy and homogenize saliva samples before protein analysis can be performed. We apply magnet-beating to reduce hands-on time and to simplify sample preparation. A magnet in a chamber containing the whole saliva is actuated inside a centrifugal microfluidic cartridge by the interplay of centrifugal and magnetic forces. Rigorous mixing, which homogenizes the saliva sample, is then initiated. Consequently, fewer manual steps are required to introduce the whole saliva into the cartridge. After 4 min of magnet-beating, the processed sample can be used for protein analysis. The viscosity of whole saliva has been reduced from 10.4 to 2.3 mPa s. Immunoassay results after magnet-beating for three salivary periodontal markers (MMP-8, MMP-9, TIMP-1) showed a linear correlation with a slope of 0.99 when compared to results of reference method treated samples. Conclusively, magnet-beating has been shown to be a suitable method for the pre-analytic processing of whole saliva for fully automated PoC protein analysis. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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Graphical abstract

11 pages, 1950 KiB

Open AccessArticle

Fast and Parallel Detection of Four Ebola Virus Species on a Microfluidic-Chip-Based Portable Reverse Transcription Loop-Mediated Isothermal Amplification System

by Xue Lin, Xiangyu Jin, Bin Xu, Ruliang Wang, Rongxin Fu, Ya Su, Kai Jiang, Han Yang, Ying Lu, Yong Guo and Guoliang Huang

Micromachines 2019, 10(11), 777; https://doi.org/10.3390/mi10110777 - 14 Nov 2019

Cited by 20 | Viewed by 3588

Abstract

Considering the lack of official vaccines and medicines for Ebola virus infection, reliable diagnostic methods are necessary for the control of the outbreak and the spread of the disease. We developed a microfluidic-chip-based portable system for fast and parallel detection of four Ebola [...] Read more.

Considering the lack of official vaccines and medicines for Ebola virus infection, reliable diagnostic methods are necessary for the control of the outbreak and the spread of the disease. We developed a microfluidic-chip-based portable system for fast and parallel detection of four Ebola virus species. The system is based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and consists of four specific LAMP primers, a disc microfluidic chip, and a portable real-time fluorescence detector. It could specifically and parallelly distinguish four species of the Ebola virus after only one sampling, including the Zaire Ebola virus, the Sudan Ebola virus, the Bundibugyo Ebola virus, and the Tai Forest Ebola virus, without cross-contamination. The limit of detection was as small as 10 copies per reaction, while the total consumption of sample and reagent was 0.94 μL per reaction. The final results could be obtained in 50 min after one addition of sample and reagent mixture. This approach provides simplicity, high sensitivity, and multi-target parallel detection at a low cost, which could enable convenient and effective on-site detections of the Ebola virus in the outdoors, remote areas, and modern hospitals. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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Review

Jump to: Research, Other

23 pages, 559 KiB

Open AccessReview

Quantum Dots: An Emerging Tool for Point-of-Care Testing

by Suchita Singh, Aksha Dhawan, Sonali Karhana, Madhusudan Bhat and Amit Kumar Dinda

Micromachines 2020, 11(12), 1058; https://doi.org/10.3390/mi11121058 - 29 Nov 2020

Cited by 30 | Viewed by 6479

Abstract

Quantum dots (QDs) are semiconductor crystals in the nanodimension having unique optical and electronic properties that differ from bulk material due to quantum mechanics. The QDs have a narrow emission peak, size-dependent emission wavelength, and broad excitation range which can be utilized for [...] Read more.

Quantum dots (QDs) are semiconductor crystals in the nanodimension having unique optical and electronic properties that differ from bulk material due to quantum mechanics. The QDs have a narrow emission peak, size-dependent emission wavelength, and broad excitation range which can be utilized for diverse biomedical applications such as molecular imaging, biosensing, and diagnostic systems. This article reviews the current developments of biomedical applications of QDs with special reference to point-of-care testing. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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31 pages, 1245 KiB

Open AccessReview

Biomarkers for Point-of-Care Diagnosis of Sepsis

by Andrew Teggert, Harish Datta and Zulfiqur Ali

Micromachines 2020, 11(3), 286; https://doi.org/10.3390/mi11030286 - 10 Mar 2020

Cited by 49 | Viewed by 11367

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to [...] Read more.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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Other

Jump to: Research, Review

7 pages, 1011 KiB

Open AccessOpinion

2019 Novel Coronavirus Disease (COVID-19): Paving the Road for Rapid Detection and Point-of-Care Diagnostics

by Trieu Nguyen, Dang Duong Bang and Anders Wolff

Micromachines 2020, 11(3), 306; https://doi.org/10.3390/mi11030306 - 14 Mar 2020

Cited by 215 | Viewed by 39595

Abstract

We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well [...] Read more.

We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well as factors for the preparedness and response to the outbreak of the COVID-19. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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28 pages, 1835 KiB

Open AccessFeature PaperOpinion

How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development

by Sara Graziadio, Amanda Winter, B. Clare Lendrem, Jana Suklan, William S. Jones, Samuel G. Urwin, Rachel A. O’Leary, Rachel Dickinson, Anna Halstead, Kasia Kurowska, Kile Green, Andrew Sims, A. John Simpson, H. Michael Power and A. Joy Allen

Micromachines 2020, 11(3), 291; https://doi.org/10.3390/mi11030291 - 10 Mar 2020

Cited by 17 | Viewed by 6173

Abstract

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence [...] Read more.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system. We highlight the importance of articulating the value propositions and documenting the care pathway. We provide guidance on how to conduct care pathway analysis as little has been published on this. We summarize the clinical, economic and qualitative studies to be considered for developing evidence, and provide useful links to relevant software, on-line applications, websites, and give practical advice. We also provide advice on patient and public involvement and engagement (PPIE), and on product management. Our aim is to help device manufacturers to understand the concepts and terminology used in evaluation of in vitro diagnostics (IVDs) so that they can communicate effectively with evaluation methodologists, statisticians, and health economists. Manufacturers of medical tests and devices can use the proposed framework to plan their evidence development strategy in alignment with device development, applications for regulatory approval, and publication. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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12 pages, 1396 KiB

Open AccessFeature PaperConcept Paper

Efficient Development of Integrated Lab-On-A-Chip Systems Featuring Operational Robustness and Manufacturability

by Jens Ducrée

Micromachines 2019, 10(12), 886; https://doi.org/10.3390/mi10120886 - 17 Dec 2019

Cited by 20 | Viewed by 3789

Abstract

The majority of commercially oriented microfluidic technologies provide novel point-of-use solutions for laboratory automation with important areas in the context of the life sciences such as health care, biopharma, veterinary medicine and agrifood as well as for monitoring of the environment, infrastructures and [...] Read more.

The majority of commercially oriented microfluidic technologies provide novel point-of-use solutions for laboratory automation with important areas in the context of the life sciences such as health care, biopharma, veterinary medicine and agrifood as well as for monitoring of the environment, infrastructures and industrial processes. Such systems are often composed of a modular setup exhibiting an instrument accommodating rather conventional actuation, detection and control units which interfaces with a fluidically integrated “Lab-on-a-Chip” device handling (bio-)sample(s) and reagents. As the complex network of tiny channels, chambers and surface-functionalised zones can typically not be properly cleaned and regenerated, these microfluidic chips are mostly devised as single-use disposables. The availability of cost-efficient materials and associated structuring, functionalisation and assembly schemes thus represents a key ingredient along the commercialisation pipeline and will be a first focus of this work. Furthermore, and owing to their innate variability, investigations on biosamples mostly require the acquisition of statistically relevant datasets. Consequently, intermediate numbers of consistently performing chips are already needed during application development; to mitigate the potential pitfalls of technology migration and to facilitate regulatory compliance of the end products, manufacture of such pilot series should widely follow larger-scale production schemes. To expedite and de-risk the development of commercially relevant microfluidic systems towards high Technology Readiness Levels (TRLs), we illustrate a streamlined, manufacturing-centric platform approach employing the paradigms of tolerance-forgiving Design-for-Manufacture (DfM) and Readiness for Scale-up (RfS) from prototyping to intermediate pilot series and eventual mass fabrication. Learning from mature industries, we further propose pursuing a platform approach incorporating aspects of standardisation in terms of specification, design rules and testing methods for materials, components, interfaces, and operational procedures; this coherent strategy will foster the emergence of dedicated commercial supply chains and also improve the economic viability of Lab-on-a-Chip systems often targeting smaller niche markets by synergistically bundling technology development. Full article

(This article belongs to the Special Issue Microsystems for Point-of-Care Testing)

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