Special Issue "Point-of-Care Diagnostics"

A special issue of Biosensors (ISSN 2079-6374).

Deadline for manuscript submissions: closed (31 July 2017) | Viewed by 59478

Special Issue Editors

Dr. Ioannis Raptis
E-Mail Website
Guest Editor
Optical Sensors Lab, Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 15310 Aghia Paraskevi, Greece
Interests: integrated photonic devices & systems for chem & bio applications; electronic micro-devices & systems for gas sensing applications; lithography simulation for the realization of structures in the nano scale; patterning technologies for the realization of structures in the micro & nano scale
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pangiota S. Petrou
E-Mail Website
Guest Editor
Immunoassays/Immunosensors Lab, Institute of Nuclear & Radiological Science & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Agia Paraskevi, 15341 Athens, Greece
Interests: optical biosensors; electrochemical biosensors; immunosensors; analytical microsystems; nanomaterials application in immunoanalysis
Special Issues, Collections and Topics in MDPI journals
Prof. B.S. Satyanarayana
E-Mail Website
Guest Editor
BML Munjal University, Kapriwas, Haryana 122413, India
Interests: low temperature nanocarbons, vacuum nanoelectronics, large area & felxible electronics, sensors & medical instrumentation

Special Issue Information

Dear Colleagues,

The last decade has witnessed tremendous advances in point-of-care (POC) diagnostics, which are paving the way to next-generation of bioanalytical testing. In addition to a wide range of rapid assay formats, such as those based on lateral flow, a wide range of rapid assay chemistries have been developed and successfully commercialized. These procedures have played a prominent role in critically reducing the assay duration and complexity. Many new biosensing concepts, such as those based on label-free sensing and fluorescence resonance energy transfer, have provided the desired bioanalytical tools for prospective applications. This is further supplemented by the development of fully integrated lab-on-a-chip platforms and technologies, which are facilitating the development of fully-automated POC diagnostic systems. The other prospective advances include the development of multiplex assays and wash-free assays. The low-cost paper-based assays have always been a long vision of researchers for POC diagnostics. The current trend has drifted significantly towards smartphone based assays and devices, which have been demonstrated with remarkable analytical features and capabilities for a very wide range of POC bioanalytical applications. Similarly, there have been significant advances in the field of mobile Healthcare and Telemedicine. The growing need for POC diagnostics, the emerging complementary technologies, the evolving trend towards smartphone based POC devices equipped with mobile healthcare tools, and the POC bioanalytical applications target the central theme of this Special Issue.

Dr. Sandeep K. Vashist
Dr. Ioannis Raptis
Dr. Panagiota Petrou
Prof. B.S. Satyanarayana
Guest Editor

Manuscript Submission Information

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Published Papers (11 papers)

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Editorial

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Editorial
Point-of-Care Diagnostics: Recent Advances and Trends
Biosensors 2017, 7(4), 62; https://doi.org/10.3390/bios7040062 - 18 Dec 2017
Cited by 81 | Viewed by 5870
Abstract
Recent years have witnessed tremendous advances in point-of-care diagnostics (POCD), which are a result of continuous developments in biosensors, microfluidic, bioanalytical platforms, assay formats, lab-on-a-chip technologies, and complementary technologies. This special issue targets the critical advances in POCD and provides guided insights and [...] Read more.
Recent years have witnessed tremendous advances in point-of-care diagnostics (POCD), which are a result of continuous developments in biosensors, microfluidic, bioanalytical platforms, assay formats, lab-on-a-chip technologies, and complementary technologies. This special issue targets the critical advances in POCD and provides guided insights and directions for future research. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)

Research

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Article
A Gal-MµS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields
Biosensors 2017, 7(4), 54; https://doi.org/10.3390/bios7040054 - 21 Nov 2017
Cited by 9 | Viewed by 3872
Abstract
Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent [...] Read more.
Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS), spinal cord repair and tumor treating fields (TTF). The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, restoration of vision via cellular replacement therapies has been limited by low numbers of motile cells post-transplantation. Here, the combinatory application of electrical fields with other stimuli to direct cells within transplantable biomaterials and/or host tissues has been understudied. In this work, we developed the Gal-MµS device, a novel microfluidics device capable of examining cell migratory behavior in response to single and combinatory stimuli of electrical and chemical fields. The formation of steady-state, chemical concentration gradients and electrical fields within the Gal-MµS were modeled computationally and verified experimentally within devices fabricated via soft lithography. Further, we utilized real-time imaging within the device to capture cell trajectories in response to electric fields and chemical gradients, individually, as well as in combinatory fields of both. Our data demonstrated that neural cells migrated longer distances and with higher velocities in response to combined galvanic and chemical stimuli than to either field individually, implicating cooperative behavior. These results reveal a biological response to galvano-chemotactic fields that is only partially understood, as well as point towards novel migration-targeted treatments to improve cell-based regenerative therapies. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
CFD Modeling of Chamber Filling in a Micro-Biosensor for Protein Detection
Biosensors 2017, 7(4), 45; https://doi.org/10.3390/bios7040045 - 03 Oct 2017
Cited by 5 | Viewed by 4529
Abstract
Tuberculosis (TB) remains one of the main causes of human death around the globe. The mortality rate for patients infected with active TB goes beyond 50% when not diagnosed. Rapid and accurate diagnostics coupled with further prompt treatment of the disease is the [...] Read more.
Tuberculosis (TB) remains one of the main causes of human death around the globe. The mortality rate for patients infected with active TB goes beyond 50% when not diagnosed. Rapid and accurate diagnostics coupled with further prompt treatment of the disease is the cornerstone for controlling TB outbreaks. To reduce this burden, the existing gap between detection and treatment must be addressed, and dedicated diagnostic tools such as biosensors should be developed. A biosensor is a sensing micro-device that consists of a biological sensing element and a transducer part to produce signals in proportion to quantitative information about the binding event. The micro-biosensor cell considered in this investigation is designed to operate based on aptamers as recognition elements against Mycobacterium tuberculosis secreted protein MPT64, combined in a microfluidic-chamber with inlet and outlet connections. The microfluidic cell is a miniaturized platform with valuable advantages such as low cost of analysis with low reagent consumption, reduced sample volume, and shortened processing time with enhanced analytical capability. The main purpose of this study is to assess the flooding characteristics of the encapsulated microfluidic cell of an existing micro-biosensor using Computational Fluid Dynamics (CFD) techniques. The main challenge in the design of the microfluidic cell lies in the extraction of entrained air bubbles, which may remain after the filling process is completed, dramatically affecting the performance of the sensing element. In this work, a CFD model was developed on the platform ANSYS-CFX using the finite volume method to discretize the domain and solving the Navier–Stokes equations for both air and water in a Eulerian framework. Second-order space discretization scheme and second-order Euler Backward time discretization were used in the numerical treatment of the equations. For a given inlet–outlet diameter and dimensions of an in-house built cell chamber, different inlet liquid flow rates were explored to determine an appropriate flow condition to guarantee an effective venting of the air while filling the chamber. The numerical model depicted free surface waves as promoters of air entrainment that ultimately may explain the significant amount of air content in the chamber observed in preliminary tests after the filling process is completed. Results demonstrated that for the present design, against the intuition, the chamber must be filled with liquid at a modest flow rate to minimize free surface waviness during the flooding stage of the chamber. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
Substituting Sodium Hydrosulfite with Sodium Metabisulfite Improves Long-Term Stability of a Distributable Paper-Based Test Kit for Point-of-Care Screening for Sickle Cell Anemia
Biosensors 2017, 7(3), 39; https://doi.org/10.3390/bios7030039 - 20 Sep 2017
Cited by 8 | Viewed by 4277
Abstract
Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness [...] Read more.
Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness of laboratory-based SCA screening programs. To address this limitation our laboratory previously developed a low-cost, equipment-free, point-of-care, paper-based SCA test. Here, we improved the stability and performance of the test by replacing sodium hydrosulfite (HS), a key reducing agent in the hemoglobin solubility buffer which is not stable in aqueous solutions, with sodium metabisulfite (MS). The MS formulation of the test was compared to the HS formulation in a laboratory setting by inexperienced users (n = 3), to determine visual limit of detection (LOD), readout time, diagnostic accuracy, intra- and inter-observer agreement, and shelf life. The MS test was found to have a 10% sickle hemoglobin LOD, 21-min readout time, 97.3% sensitivity and 99.5% specificity for SCA, almost perfect intra- and inter-observer agreement, at least 24 weeks of shelf stability at room temperature, and could be packaged into a self-contained, distributable test kits comprised of off-the-shelf disposable components and food-grade reagents with a total cost of only $0.21 (USD). Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
A Novel Surface Plasmon Resonance Biosensor for the Rapid Detection of Botulinum Neurotoxins
Biosensors 2017, 7(3), 32; https://doi.org/10.3390/bios7030032 - 07 Aug 2017
Cited by 15 | Viewed by 5070
Abstract
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD [...] Read more.
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD50 of 1–2 ng/kg body weight), cause fatal flaccid paralysis by blocking neurotransmitter release. The current gold standard detection method, the mouse-bioassay, often takes days to confirm botulism. Furthermore, there are no effective antidotes known to reverse the symptoms of botulism, and as a result, patients with severe botulism often require meticulous care during the prolonged paralytic illness. To combat potential bio-terrorism incidents of botulinum neurotoxins, their rapid detection is paramount. Surface plasmon resonance (SPR) is a very sensitive technique to examine bio-molecular interactions. The label-free, real-time analysis, with high sensitivity and low sample consumption makes this technology particularly suitable for detection of the toxin. In this study, we demonstrated the feasibility in an assay with a newly designed SPR instrument for the rapid detection of botulinum neurotoxins. The LOD (limit of detection) of the Newton Photonics (NP) SPR based assay is 6.76 pg/mL for Botulinum Neurotoxin type A Light Chain (BoNT/A LC). We established that the detection sensitivity of the system is comparable to the traditional mouse LD50 bioassay in BoNT/A using this SPR technology. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
A Label-Free, Quantitative Fecal Hemoglobin Detection Platform for Colorectal Cancer Screening
Biosensors 2017, 7(2), 19; https://doi.org/10.3390/bios7020019 - 05 May 2017
Cited by 8 | Viewed by 4797
Abstract
The early detection of colorectal cancer is vital for disease management and patient survival. Fecal hemoglobin detection is a widely-adopted method for screening and early diagnosis. Fecal Immunochemical Test (FIT) is favored over the older generation chemical based Fecal Occult Blood Test (FOBT) [...] Read more.
The early detection of colorectal cancer is vital for disease management and patient survival. Fecal hemoglobin detection is a widely-adopted method for screening and early diagnosis. Fecal Immunochemical Test (FIT) is favored over the older generation chemical based Fecal Occult Blood Test (FOBT) as it does not require dietary or drug restrictions, and is specific to human blood from the lower digestive tract. To date, no quantitative FIT platforms are available for use in the point-of-care setting. Here, we report proof of principle data of a novel low cost quantitative fecal immunochemical-based biosensor platform that may be further developed into a point-of-care test in low-resource settings. The label-free prototype has a lower limit of detection (LOD) of 10 µg hemoglobin per gram (Hb/g) of feces, comparable to that of conventional laboratory based quantitative FIT diagnostic systems. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
Rapid Detection of Bacillus anthracis Spores Using Immunomagnetic Separation and Amperometry
Biosensors 2016, 6(4), 61; https://doi.org/10.3390/bios6040061 - 20 Dec 2016
Cited by 10 | Viewed by 4907
Abstract
Portable detection and quantitation methods for Bacillus anthracis (anthrax) spores in pure culture or in environmental samples are lacking. Here, an amperometric immunoassay has been developed utilizing immunomagnetic separation to capture the spores and remove potential interferents from test samples followed by amperometric [...] Read more.
Portable detection and quantitation methods for Bacillus anthracis (anthrax) spores in pure culture or in environmental samples are lacking. Here, an amperometric immunoassay has been developed utilizing immunomagnetic separation to capture the spores and remove potential interferents from test samples followed by amperometric measurement on a field-portable instrument. Antibody-conjugated magnetic beads and antibody-conjugated glucose oxidase were used in a sandwich format for the capture and detection of target spores. Glucose oxidase activity of spore pellets was measured indirectly via amperometry by applying a bias voltage after incubation with glucose, horseradish peroxidase, and the electron mediator 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid). Target capture was mediated by polyclonal antisera, whereas monoclonal antibodies were used for signal generation. This strategy maximized sensitivity (500 target spores, 5000 cfu/mL), while also providing a good specificity for Bacillus anthracis spores. Minimal signal deviation occurs in the presence of environmental interferents including soil and modified pH conditions, demonstrating the strengths of immunomagnetic separation. The simultaneous incubation of capture and detection antibodies and rapid substrate development (5 min) result in short sample-to-signal times (less than an hour). With attributes comparable or exceeding that of ELISA and LFDs, amperometry is a low-cost, low-weight, and practical method for detecting anthrax spores in the field. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Article
TERMA Framework for Biomedical Signal Analysis: An Economic-Inspired Approach
Biosensors 2016, 6(4), 55; https://doi.org/10.3390/bios6040055 - 02 Nov 2016
Cited by 15 | Viewed by 5200
Abstract
Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers [...] Read more.
Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers have difficulty detecting these peaks to investigate, interpret and analyze their corresponding events. To date, there is no generic framework that captures these events in a robust, efficient and consistent manner. A new method referred to for the first time as two event-related moving averages (“TERMA”) involves event-related moving averages and detects events in biomedical signals. The TERMA framework is flexible and universal and consists of six independent LEGO building bricks to achieve high accuracy detection of biomedical events. Results recommend that the window sizes for the two moving averages ( W 1 and W 2 ) have to follow the inequality ( 8 × W 1 ) W 2 ( 2 × W 1 ) . Moreover, TERMA is a simple yet efficient event detector that is suitable for wearable devices, point-of-care devices, fitness trackers and smart watches, compared to more complex machine learning solutions. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Review

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Review
Development and Bioanalytical Applications of a White Light Reflectance Spectroscopy Label-Free Sensing Platform
Biosensors 2017, 7(4), 46; https://doi.org/10.3390/bios7040046 - 13 Oct 2017
Cited by 10 | Viewed by 5043
Abstract
The development of a sensing platform based on white light reflectance spectroscopy (WLRS) is presented. The evolution of the system, from polymer film characterization and sensing of volatile organic compounds to biosensor for the label-free determination of either high (e.g., proteins) or low [...] Read more.
The development of a sensing platform based on white light reflectance spectroscopy (WLRS) is presented. The evolution of the system, from polymer film characterization and sensing of volatile organic compounds to biosensor for the label-free determination of either high (e.g., proteins) or low molecular weight analytes (e.g., pesticides), is described. At the same time, the passage from single to multi-analyte determinations, and from a laboratory prototype set-up to a compact device appropriate for on-site determination, is outlined. The improvements made on both the sensor and the optical set-up, and the concomitant advances in the analytical characteristics and the robustness of the assays performed with the different layouts, are also presented. Finally, the future perspectives of the system, aiming for the creation of a standalone instrument to be used by non-experts, will be discussed. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Review
Point-of-Care-Testing in Acute Stroke Management: An Unmet Need Ripe for Technological Harvest
Biosensors 2017, 7(3), 30; https://doi.org/10.3390/bios7030030 - 03 Aug 2017
Cited by 32 | Viewed by 8151
Abstract
Stroke, the second highest leading cause of death, is caused by an abrupt interruption of blood to the brain. Supply of blood needs to be promptly restored to salvage brain tissues from irreversible neuronal death. Existing assessment of stroke patients is based largely [...] Read more.
Stroke, the second highest leading cause of death, is caused by an abrupt interruption of blood to the brain. Supply of blood needs to be promptly restored to salvage brain tissues from irreversible neuronal death. Existing assessment of stroke patients is based largely on detailed clinical evaluation that is complemented by neuroimaging methods. However, emerging data point to the potential use of blood-derived biomarkers in aiding clinical decision-making especially in the diagnosis of ischemic stroke, triaging patients for acute reperfusion therapies, and in informing stroke mechanisms and prognosis. The demand for newer techniques to deliver individualized information on-site for incorporation into a time-sensitive work-flow has become greater. In this review, we examine the roles of a portable and easy to use point-of-care-test (POCT) in shortening the time-to-treatment, classifying stroke subtypes and improving patient’s outcome. We first examine the conventional stroke management workflow, then highlight situations where a bedside biomarker assessment might aid clinical decision-making. A novel stroke POCT approach is presented, which combines the use of quantitative and multiplex POCT platforms for the detection of specific stroke biomarkers, as well as data-mining tools to drive analytical processes. Further work is needed in the development of POCTs to fulfill an unmet need in acute stroke management. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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Review
Carbon Nanotubes as an Effective Opportunity for Cancer Diagnosis and Treatment
Biosensors 2017, 7(1), 9; https://doi.org/10.3390/bios7010009 - 15 Feb 2017
Cited by 68 | Viewed by 7113
Abstract
Despite the current progresses of modern medicine, the resistance of malignant tumors to present medical treatments points to the necessity of developing new therapeutic approaches. In recent years, numerous studies have focused their attention on the promising use of nanomaterials, like iron oxide [...] Read more.
Despite the current progresses of modern medicine, the resistance of malignant tumors to present medical treatments points to the necessity of developing new therapeutic approaches. In recent years, numerous studies have focused their attention on the promising use of nanomaterials, like iron oxide nanowires, zinc oxide or mesoporous silica nanoparticles, for cancer and metastasis treatment with the advantage of operating directly at the bio-molecular scale. Among them, carbon nanotubes emerged as valid candidates not only for drug delivery, but also as a valuable tool in cancer imaging and physical ablation. Nevertheless, deep investigations about carbon nanotubes’ potential bio-compatibility and cytotoxicity limits should be also critically addressed. In the present review, after introducing carbon nanotubes and their promising advantages and drawbacks for fighting cancer, we want to focus on the numerous and different ways in which they can assist to reach this goal. Specifically, we report on how they can be used not only for drug delivery purposes, but also as a powerful ally to develop effective contrast agents for tumors’ medical or photodynamic imaging, to perform direct physical ablation of metastasis, as well as gene therapy. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics)
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