Miniaturized Technologies for Point-of-Care

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Point-of-Care Diagnostics and Devices".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 31137

Special Issue Editor


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Guest Editor
North Dakota State University, Fargo, ND, USA
Interests: biosensing; lab-on-a-chip technologies; biomanufacuring

Special Issue Information

Dear Colleagues,

The technologies used in point-of-care settings such as clinics, hospitals, and medical centers play a vital role in delivering quality healthcare at an affordable cost. Recent developments in lab-on-a-chip technologies have a great potential to address the critical limitations in the technologies needed in the point-of-care. This Special Issue is dedicated to technical papers that address some of the current barriers. Authors should clearly identify the technical problem that they are addressing, as well as its significance. Appropriate articles to this Issue will be basic proof-of-concept studies that could lead to the development of novel miniaturized capabilities in point-of-care, or studies related to the translation of developed technologies towards point-of-care applications.

Dr. Keerthi Nawarathna
Guest Editor

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Keywords

  • Microfluidics
  • Biomarkers
  • Diagnostics
  • Screening
  • Point-of-care

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Published Papers (4 papers)

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Research

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14 pages, 4465 KiB  
Article
Thromboinflammation Model-on-A-Chip by Whole Blood Microfluidics on Fixed Human Endothelium
by Alexander Dupuy, Lejla Hagimola, Neil S. A. Mgaieth, Callum B. Houlahan, Renee E. Preketes-Tardiani, Paul R. Coleman and Freda H. Passam
Diagnostics 2021, 11(2), 203; https://doi.org/10.3390/diagnostics11020203 - 29 Jan 2021
Cited by 14 | Viewed by 3722
Abstract
Microfluidic devices have an established role in the study of platelets and coagulation factors in thrombosis, with potential diagnostic applications. However, few microfluidic devices have assessed the contribution of neutrophils to thrombus formation, despite increasing knowledge of neutrophils’ importance in cardiovascular thrombosis. We [...] Read more.
Microfluidic devices have an established role in the study of platelets and coagulation factors in thrombosis, with potential diagnostic applications. However, few microfluidic devices have assessed the contribution of neutrophils to thrombus formation, despite increasing knowledge of neutrophils’ importance in cardiovascular thrombosis. We describe a thromboinflammation model which uses straight channels, lined with fixed human umbilical vein endothelial cells, after treatment with tumour necrosis factor-alpha. Re-calcified whole blood is perfused over the endothelium at venous and arterial shear rate. Neutrophil adhesion, platelet and fibrin thrombus formation, is measured over time by the addition of fluorescent antibodies to a whole blood sample. Fixed endothelium retains surface expression of adhesion molecules ICAM-1 and E-Selectin. Neutrophils adhere preferentially to platelet thrombi on the endothelium. Inhibitors of neutrophil adhesion and anti-inflammatory agents, such as isoquercetin, decrease neutrophil adhesion. Our model offers the advantage of the use of (1) fixed endothelium, (2) whole blood, instead of isolated neutrophils, and (3) a small amount of blood (1 mL). The characteristics of this thromboinflammation model provide the potential for further development for drug screening and point-of-care applications. Full article
(This article belongs to the Special Issue Miniaturized Technologies for Point-of-Care)
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15 pages, 3953 KiB  
Article
Enhanced Colorimetric Signal for Accurate Signal Detection in Paper-Based Biosensors
by Dorin Harpaz, Evgeni Eltzov, Timothy S. E. Ng, Robert S. Marks and Alfred I. Y. Tok
Diagnostics 2020, 10(1), 28; https://doi.org/10.3390/diagnostics10010028 - 7 Jan 2020
Cited by 27 | Viewed by 14218
Abstract
Paper-based colorimetric biosensors combine the use of paper with colorimetric signal detection. However, they usually demonstrate lower sensitivities because a signal amplification procedure has not been used. Stopping the reaction of colorimetric signal generation is often used in lab-based assays in order to [...] Read more.
Paper-based colorimetric biosensors combine the use of paper with colorimetric signal detection. However, they usually demonstrate lower sensitivities because a signal amplification procedure has not been used. Stopping the reaction of colorimetric signal generation is often used in lab-based assays in order to amplify and stabilize the colorimetric signal for detection. In this study, the generation of a stopped colorimetric signal was examined for accurate and enhanced signal detection in paper-based biosensors. The colorimetric reaction in biosensors is usually based on the interaction between the enzyme horseradish peroxidase (HRP) and a selected chromogenic substrate. The two most commonly used HRP substrates, 3,3’,5,5’-tetramethylbenzidine (TMB) and 2’-azinobis (3-ethylbenzothiazoline-6-sulfonic-acid) (ABTS), were compared in terms of their ability to generate a stopped colorimetric signal on membrane. The stopped colorimetric signal was visible for TMB but not for ABTS. Moreover, the generation of stopped colorimetric signal was dependent on the presence of polyvinylidene-difluoride (PVDF) membrane as the separation layer. With PVDF the colorimetric signal (color intensity) was higher (TMB: 126 ± 6 and ABTS: 121 ± 9) in comparison to without PVDF (TMB: 110 ± 2 and ABTS: 102 ± 4). The TMB stopped colorimetric signal demonstrated a more stable signal detection with lower standard deviation values. To conclude, a stopped colorimetric signal can be generated in paper-based biosensors for enhanced and accurate signal detection. Full article
(This article belongs to the Special Issue Miniaturized Technologies for Point-of-Care)
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18 pages, 2662 KiB  
Article
Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
by Rama S. Sista, Rainer Ng, Miriam Nuffer, Michael Basmajian, Jacob Coyne, Jennifer Elderbroom, Daniel Hull, Kathryn Kay, Maithri Krishnamurthy, Christopher Roberts, Daniel Wu, Adam D. Kennedy, Rajendra Singh, Vijay Srinivasan and Vamsee K. Pamula
Diagnostics 2020, 10(1), 21; https://doi.org/10.3390/diagnostics10010021 - 1 Jan 2020
Cited by 36 | Viewed by 7984
Abstract
“Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is an excellent [...] Read more.
“Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is an excellent example of clinical care that is not yet customized to the needs of children, especially newborns. Cumulative blood loss resulting from clinical testing does not typically impact critically ill adult patients, but can quickly escalate in children, leading to iatrogenic anemia and related comorbidities. Moreover, the tests prioritized for rapid, near-patient testing in adults are not always the most clinically relevant tests for children or newborns. This report describes the development of a digital microfluidic testing platform and associated clinical assays purposely curated to address current shortcomings in pediatric laboratory testing by using microliter volumes (<50 µL) of samples. The automated platform consists of a small instrument and single-use cartridges, which contain all reagents necessary to prepare the sample and perform the assay. Electrowetting technology is used to precisely manipulate nanoliter-sized droplets of samples and reagents inside the cartridge. To date, we have automated three disparate types of assays (biochemical assays, immunoassays, and molecular assays) on the platform and have developed over two dozen unique tests, each with important clinical application to newborns and pediatric patients. Cell lysis, plasma preparation, magnetic bead washing, thermocycling, incubation, and many other essential functions were all performed on the cartridge without any user intervention. The resulting assays demonstrate performance comparable to standard clinical laboratory assays and are economical due to the reduced hands-on effort required for each assay and lower overall reagent consumption. These capabilities allow a wide range of assays to be run simultaneously on the same cartridge using significantly reduced sample volumes with results in minutes. Full article
(This article belongs to the Special Issue Miniaturized Technologies for Point-of-Care)
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Review

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18 pages, 359 KiB  
Review
Blood-Based Biomarkers Are Associated with Different Ischemic Stroke Mechanisms and Enable Rapid Classification between Cardioembolic and Atherosclerosis Etiologies
by Dorin Harpaz, Raymond C. S. Seet, Robert S. Marks and Alfred I. Y. Tok
Diagnostics 2020, 10(10), 804; https://doi.org/10.3390/diagnostics10100804 - 9 Oct 2020
Cited by 17 | Viewed by 4733
Abstract
Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main [...] Read more.
Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main value of subtyping ischemic stroke patients is for a better therapeutic decision-making process. The current classification methods are complex and time-consuming (hours to days). Specific blood-based biomarker measurements have promising potential to improve ischemic stroke mechanism classification. Over the past decades, the hypothesis that different blood-based biomarkers are associated with different ischemic stroke mechanisms is increasingly investigated. This review presents the recent studies that investigated blood-based biomarker characteristics differentiation between ischemic stroke mechanisms. Different blood-based biomarkers are specifically discussed (b-type natriuretic peptide, d-dimer, c-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1β, neutrophil–lymphocyte ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and apolipoprotein A), as well as the different cut-off values that may be useful in specific classifications for cardioembolic and atherosclerosis etiologies. Lastly, the structure of a point-of-care biosensor device is presented, as a measuring tool on-site. The information presented in this review will hopefully contribute to the major efforts to improve the care for stroke patients. Full article
(This article belongs to the Special Issue Miniaturized Technologies for Point-of-Care)
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