Biomedicines

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13 pages, 2191 KiB

Open AccessEditor’s ChoiceArticle

Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing

by Dániel Petrovszki, Fruzsina R. Walter, Judit P. Vigh, Anna Kocsis, Sándor Valkai, Mária A. Deli and András Dér

Biomedicines 2022, 10(1), 188; https://doi.org/10.3390/biomedicines10010188 - 17 Jan 2022

Cited by 25 | Viewed by 9791

Abstract

Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing [...] Read more.

Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing multiple neurological symptoms with increased neuroinflammation and blood–brain barrier (BBB) damage. The viral spike protein disseminates via circulation during infection, and when reaching the brain could possibly cross the BBB, which was demonstrated in mice. Therefore, its medical relevance is of high importance. The aim of this study was to evaluate the barrier penetration of the S1 subunit of spike protein in model systems of human organs highly exposed to the infection. For this purpose, in vitro human BBB and intestinal barrier cell–culture systems were investigated by an optical biosensing method. We found that spike protein crossed the human brain endothelial cell barrier effectively. Additionally, spike protein passage was found in a lower amount for the intestinal barrier cell layer. These observations were corroborated with parallel specific ELISAs. The findings on the BBB model could provide a further basis for studies focusing on the mechanism and consequences of spike protein penetration across the BBB to the brain. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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13 pages, 1756 KiB

Open AccessArticle

Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model

by Míriam Illa, Laura Pla, Sergio Berdún, Mònica Mir, Lourdes Rivas, Samuel Dulay, Nicole Picard-Hagen, Josep Samitier, Eduard Gratacós and Elisenda Eixarch

Biomedicines 2021, 9(10), 1344; https://doi.org/10.3390/biomedicines9101344 - 28 Sep 2021

Viewed by 2395

Abstract

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized [...] Read more.

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO₂ and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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19 pages, 2636 KiB

Open AccessArticle

Cardioluminescence in Transgenic Zebrafish Larvae: A Calcium Imaging Tool to Study Drug Effects and Pathological Modeling

by Manuel Vicente, Jussep Salgado-Almario, Michelle M. Collins, Antonio Martínez-Sielva, Masafumi Minoshima, Kazuya Kikuchi, Beatriz Domingo and Juan Llopis

Biomedicines 2021, 9(10), 1294; https://doi.org/10.3390/biomedicines9101294 - 22 Sep 2021

Cited by 11 | Viewed by 3739

Abstract

Zebrafish embryos and larvae have emerged as an excellent model in cardiovascular research and are amenable to live imaging with genetically encoded biosensors to study cardiac cell behaviours, including calcium dynamics. To monitor calcium ion levels in three to five days post-fertilization larvae, [...] Read more.

Zebrafish embryos and larvae have emerged as an excellent model in cardiovascular research and are amenable to live imaging with genetically encoded biosensors to study cardiac cell behaviours, including calcium dynamics. To monitor calcium ion levels in three to five days post-fertilization larvae, we have used bioluminescence. We generated a transgenic line expressing GFP-aequorin in the heart, Tg(myl7:GA), and optimized a reconstitution protocol to boost aequorin luminescence. The analogue diacetylh-coelenterazine enhanced light output and signal-to-noise ratio. With this cardioluminescence model, we imaged the time-averaged calcium levels and beat-to-beat calcium oscillations continuously for hours. As a proof-of-concept of the transgenic line, changes in ventricular calcium levels were observed by Bay K8644, an L-type calcium channel activator and with the blocker nifedipine. The β-adrenergic blocker propranolol decreased calcium levels, heart rate, stroke volume, and cardiac output, suggesting that larvae have a basal adrenergic tone. Zebrafish larvae treated with terfenadine for 24 h have been proposed as a model of heart failure. Tg(myl7:GA) larvae treated with terfenadine showed bradycardia, 2:1 atrioventricular block, decreased time-averaged ventricular calcium levels but increased calcium transient amplitude, and reduced cardiac output. As alterations of calcium signalling are involved in the pathogenesis of heart failure and arrhythmia, the GFP-aequorin transgenic line provides a powerful platform for understanding calcium dynamics. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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10 pages, 1805 KiB

Open AccessArticle

Fabrication of an Electrochemical Aptasensor Composed of Multifunctional DNA Three-Way Junction on Au Microgap Electrode for Interferon Gamma Detection in Human Serum

by Seungwoo Noh, Jinmyeong Kim, Chulhwan Park, Junhong Min and Taek Lee

Biomedicines 2021, 9(6), 692; https://doi.org/10.3390/biomedicines9060692 - 18 Jun 2021

Cited by 10 | Viewed by 4775

Abstract

Interferon gamma (IFN-γ) is an important cytokine with antiviral, antibacterial, and immunosuppressive properties. It has been used as a biomarker for the early detection of several diseases, including cancer, human immunodeficiency virus (HIV), tuberculosis, and paratuberculosis. In this study, we developed an electrochemical [...] Read more.

Interferon gamma (IFN-γ) is an important cytokine with antiviral, antibacterial, and immunosuppressive properties. It has been used as a biomarker for the early detection of several diseases, including cancer, human immunodeficiency virus (HIV), tuberculosis, and paratuberculosis. In this study, we developed an electrochemical biosensor composed of multifunctional DNA 3WJ to detect IFN-γ level with high sensitivity. Each multifunctional triple-stranded aptamer (MF-3WJ) was designed to have an IFN-γ aptamer sequence, anchoring region (thiol group), and 4C–C (cytosine–cytosine) mismatch sequence (signal generation), which could introduce silver ions. To generate the electrochemical signal, four Ag⁺ ions were intercalated (3wj b-3wj c) in the 4C–C mismatch sequence. MF-3WJ was assembled through the annealing step, and the assembly of MF-3WJ was confirmed by 8% tris–boric–EDTA native polyacrylamide gel electrophoresis. The Au microgap electrode was manufactured to load sample volumes of 5 µL. The reliability of electrochemical biosensor measurement was established by enabling the measurement of seven samples from one Au microgap electrode. MF-3WJ was immobilized on the Au microgap electrode. Then, cyclic voltammetry and electrochemical impedance spectroscopy were performed to confirm the electrochemical properties of MF-3WJ. To test the electrochemical biosensor’s ability to detect IFN-γ, the limit of detection (LOD) and selectivity tests were performed by square wave voltammetry. A linear region was observed in the concentration range of 1 pg/mL–10 ng/mL of IFN-γ. The LOD of the fabricated electrochemical biosensor was 0.67 pg/mL. In addition, for the clinical test, the LOD test was carried out for IFN-γ diluted in 10% human serum samples in the concentration range of 1 pg/mL–10 ng/mL, and the LOD was obtained at 0.42 pg/mL. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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12 pages, 1349 KiB

Open AccessArticle

Fluorescence Based on Surface Plasmon Coupled Emission for Ultrahigh Sensitivity Immunoassay of Cardiac Troponin I

by Vien Thi Tran and Heongkyu Ju

Biomedicines 2021, 9(5), 448; https://doi.org/10.3390/biomedicines9050448 - 21 Apr 2021

Cited by 15 | Viewed by 2979

Abstract

This work demonstrates the quantitative assay of cardiac Troponin I (cTnI), one of the key biomarkers for acute cardiovascular diseases (the leading cause of death worldwide) using the fluorescence-based sandwich immune reaction. Surface plasmon coupled emission (SPCE) produced by non-radiative coupling of dye [...] Read more.

This work demonstrates the quantitative assay of cardiac Troponin I (cTnI), one of the key biomarkers for acute cardiovascular diseases (the leading cause of death worldwide) using the fluorescence-based sandwich immune reaction. Surface plasmon coupled emission (SPCE) produced by non-radiative coupling of dye molecules with surface plasmons being excitable via the reverse Kretschmann format is exploited for fluorescence-based sandwich immunoassay for quantitative detection of cTnI. The SPCE fluorescence chip utilizes the gold (2 nm)-silver (50 nm) bimetallic thin film, with which molecules of the dye Alexa 488 (conjugated with detection antibodies) make a near field coupling with the plasmonic film for SPCE. The experimental results find that the SPCE greatly improves the sensitivity via enhancing the fluorescence signal (up to 50-fold) while suppressing the photo-bleaching, permitting markedly enhanced signal-to-noise ratio. The limit of detection of 21.2 ag mL⁻¹ (atto-gram mL⁻¹) is obtained, the lowest ever reported to date amid those achieved by optical technologies such as luminescence and label-free optical sensing techniques. The features discovered such as ultrahigh sensitivity may prompt the presented technologies to be applied for early diagnosis of cTnI in blood, particularly for emergency medical centers overloaded with patients with acute myocardial infarction who would suffer from time-delayed diagnosis due to insufficient assay device sensitivity. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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8 pages, 1381 KiB

Open AccessArticle

Label-Free Assay of Protein Kinase A Activity and Inhibition Using a Peptide-Based Electrochemical Sensor

by Hyunju Cho, Chang-Seuk Lee and Tae Hyun Kim

Biomedicines 2021, 9(4), 423; https://doi.org/10.3390/biomedicines9040423 - 13 Apr 2021

Cited by 9 | Viewed by 2880

Abstract

We propose a simple label-free electrochemical biosensor for monitoring protein kinase activity and inhibition using a peptide-modified electrode. The biosensor employs cys-kemptide (CLRRASLG) as a substrate peptide which was immobilized on the surface of a gold electrode via the self-assembly of the thiol [...] Read more.

We propose a simple label-free electrochemical biosensor for monitoring protein kinase activity and inhibition using a peptide-modified electrode. The biosensor employs cys-kemptide (CLRRASLG) as a substrate peptide which was immobilized on the surface of a gold electrode via the self-assembly of the thiol terminals in cysteine (C) residues. The interaction between protein kinase A (PKA) and adenosine 5′-triphosphate (ATP) on the cys-kemptide immobilized electrode can cause the transfer of ATP terminal phosphates to the peptide substrates at serine (S) residues, which alters the surface charge of the electrode, thus enabling monitoring of the PKA activity via measuring the interfacial electron transfer resistance with electrochemical impedance spectroscopy. The proposed sensor showed reliable, sensitive, and selective detection of PKA activity with a wide dynamic range of 0.1–100 U/mL and a detection limit of 56 mU/mL. The sensor also exhibited high selectivity, rendering it possible to screen PKA inhibitors. Moreover, the sensor can be employed to evaluate the activity and inhibition of PKA in real samples. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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17 pages, 3010 KiB

Open AccessArticle

Electrochemical Determination of Hydroxyurea in a Complex Biological Matrix Using MoS₂-Modified Electrodes and Chemometrics

by Remi Cazelles, Rajendra P. Shukla, Russell E. Ware, Alexander A. Vinks and Hadar Ben-Yoav

Biomedicines 2021, 9(1), 6; https://doi.org/10.3390/biomedicines9010006 - 24 Dec 2020

Cited by 8 | Viewed by 4417

Abstract

Hydroxyurea, an oral medication with important clinical benefits in the treatment of sickle cell anemia, can be accurately determined in plasma with a transition metal dichalcogenide-based electrochemical sensor. We used a two-dimensional molybdenum sulfide material (MoS₂) selectively electrodeposited on a polycrystalline [...] Read more.

Hydroxyurea, an oral medication with important clinical benefits in the treatment of sickle cell anemia, can be accurately determined in plasma with a transition metal dichalcogenide-based electrochemical sensor. We used a two-dimensional molybdenum sulfide material (MoS₂) selectively electrodeposited on a polycrystalline gold electrode via tailored waveform polarization in the gold electrical double layer formation region. The electro-activity of the modified electrode depends on the electrical waveform parameters used to electro-deposit MoS₂. The concomitant oxidation of the MoS₂ material during its electrodeposition allows for the tuning of the sensor’s specificity. Chemometrics, utilizing mathematical procedures such as principal component analysis and multivariable partial least square regression, were used to process the electrochemical data generated at the bare and the modified electrodes, thus allowing the hydroxyurea concentrations to be predicted in human plasma. A limit-of-detection of 22 nM and a sensitivity of 37 nA cm⁻² µM⁻¹ were found to be suitable for pharmaceutical and clinical applications. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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11 pages, 2936 KiB

Open AccessArticle

Efficient Portable Urea Biosensor Based on Urease Immobilized Membrane for Monitoring of Physiological Fluids

by Jee Young Kim, Gun Yong Sung and Min Park

Biomedicines 2020, 8(12), 596; https://doi.org/10.3390/biomedicines8120596 - 11 Dec 2020

Cited by 23 | Viewed by 4054

Abstract

Numerous studies have addressed the utilization of glutaraldehyde (GA) as a homobifunctional cross-linker. However, its applicability has been impeded due to several issues, including the tendency of GA molecules to undergo polymerization. Herein, a portable urea biosensor was developed for the real-time monitoring [...] Read more.

Numerous studies have addressed the utilization of glutaraldehyde (GA) as a homobifunctional cross-linker. However, its applicability has been impeded due to several issues, including the tendency of GA molecules to undergo polymerization. Herein, a portable urea biosensor was developed for the real-time monitoring of the flow of physiological fluids; this was achieved by using disuccinimidyl cross-linker-based urease immobilization. Urease was immobilized on a porous polytetrafluoroethylene (PTFE) solid support using different disuccinimidyl cross-linkers, namely disuccinimidyl glutarate (DSG), disuccinimidyl suberate (DSS) and bis-N-succinimidyl-(pentaethylene glycol) ester (BS(PEG)₅). A urease activity test revealed that DSS exhibited the highest urease immobilizing efficiency, whereas FT-IR analysis confirmed that urease was immobilized on the PTFE membrane via DSS cross-linking. The membrane was inserted in a polydimethylsiloxane (PDMS) fluidic chamber that generated an electrochemical signal in the presence of a flowing fluid containing urea. Urea samples were allowed to flow into the urea biosensor (1.0 mL/min) and the signal was measured using chronoamperometry. The sensitivity of the DSS urea biosensor was the highest of all the trialed biosensors and was found to be superior to the more commonly used GA cross-linker. To simulate real-time monitoring in a human patient, flowing urea-spiked human serum was measured and the effective urease immobilization of the DSS urea biosensor was confirmed. The repeatability and interference of the urea biosensor were suitable for monitoring urea concentrations typically found in human patients. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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Review

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60 pages, 36217 KiB

Open AccessReview

Label-Free Physical Techniques and Methodologies for Proteins Detection in Microfluidic Biosensor Structures

by Georgii Konoplev, Darina Agafonova, Liubov Bakhchova, Nikolay Mukhin, Marharyta Kurachkina, Marc-Peter Schmidt, Nikolay Verlov, Alexander Sidorov, Aleksandr Oseev, Oksana Stepanova, Andrey Kozyrev, Alexander Dmitriev and Soeren Hirsch

Biomedicines 2022, 10(2), 207; https://doi.org/10.3390/biomedicines10020207 - 18 Jan 2022

Cited by 18 | Viewed by 6173

Abstract

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices [...] Read more.

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices for point-of-care (POC) analysis based on microfluidic technology as an alternative to conventional laboratory protein assays. In contrast to universally accepted analytical methods involving protein labeling, label-free approaches often allow the development of biosensors with minimal requirements for sample preparation by omitting expensive labelling reagents. The aim of the present work is to review the variety of physical label-free techniques of protein detection and characterization which are suitable for application in micro-fluidic structures and analyze the technological and material aspects of label-free biosensors that implement these methods. The most widely used optical and impedance spectroscopy techniques: absorption, fluorescence, surface plasmon resonance, Raman scattering, and interferometry, as well as new trends in photonics are reviewed. The challenges of materials selection, surfaces tailoring in microfluidic structures, and enhancement of the sensitivity and miniaturization of biosensor systems are discussed. The review provides an overview for current advances and future trends in microfluidics integrated technologies for label-free protein biomarkers detection and discusses existing challenges and a way towards novel solutions. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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56 pages, 19063 KiB

Open AccessReview

Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation

by Beatrix Péter, Imre Boldizsár, Gábor M. Kovács, Anna Erdei, Zsuzsa Bajtay, Alexandra Vörös, Jeremy J. Ramsden, Ildikó Szabó, Szilvia Bősze and Robert Horvath

Biomedicines 2021, 9(12), 1781; https://doi.org/10.3390/biomedicines9121781 - 26 Nov 2021

Cited by 5 | Viewed by 4299

Abstract

Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and [...] Read more.

Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and migration via various signaling pathways and by directly inactivating key cell adhesion surface receptor sites. The evidence for this proposition is reviewed (by summarizing the natural metabolites and their effects influencing cellular adhesion and migration), along with the classical measuring techniques used to gain such evidence. We systematize existing knowledge concerning the mechanisms of how natural metabolites affect adhesion and movement, and their role in gene expression as well. We conclude by highlighting the possibilities to screen natural compounds faster and more easily by applying new label-free methods, which also enable a far greater degree of quantification than the conventional methods used hitherto. We have systematically classified recent studies regarding the effects of natural compounds on cellular adhesion and movement, characterizing the active substances according to their organismal origin (plants, animals or fungi). Finally, we also summarize the results of recent studies and experiments on SARS-CoV-2 treatments by natural extracts affecting mainly the adhesion and entry of the virus. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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23 pages, 3182 KiB

Open AccessReview

Non-Coding RNA-Based Biosensors for Early Detection of Liver Cancer

by Sedigheh Falahi, Hossain-Ali Rafiee-Pour, Mashaalah Zarejousheghani, Parvaneh Rahimi and Yvonne Joseph

Biomedicines 2021, 9(8), 964; https://doi.org/10.3390/biomedicines9080964 - 5 Aug 2021

Cited by 15 | Viewed by 4160

Abstract

Primary liver cancer is an aggressive, lethal malignancy that ranks as the fourth leading cause of cancer-related death worldwide. Its 5-year mortality rate is estimated to be more than 95%. This significant low survival rate is due to poor diagnosis, which can be [...] Read more.

Primary liver cancer is an aggressive, lethal malignancy that ranks as the fourth leading cause of cancer-related death worldwide. Its 5-year mortality rate is estimated to be more than 95%. This significant low survival rate is due to poor diagnosis, which can be referred to as the lack of sufficient and early-stage detection methods. Many liver cancer-associated non-coding RNAs (ncRNAs) have been extensively examined to serve as promising biomarkers for precise diagnostics, prognostics, and the evaluation of the therapeutic progress. For the simple, rapid, and selective ncRNA detection, various nanomaterial-enhanced biosensors have been developed based on electrochemical, optical, and electromechanical detection methods. This review presents ncRNAs as the potential biomarkers for the early-stage diagnosis of liver cancer. Moreover, a comprehensive overview of recent developments in nanobiosensors for liver cancer-related ncRNA detection is provided. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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26 pages, 8936 KiB

Open AccessReview

Near-Infrared-Triggered Upconverting Nanoparticles for Biomedicine Applications

by Manoj Kumar Mahata, Ranjit De and Kang Taek Lee

Biomedicines 2021, 9(7), 756; https://doi.org/10.3390/biomedicines9070756 - 29 Jun 2021

Cited by 60 | Viewed by 7967

Abstract

Due to the unique properties of lanthanide-doped upconverting nanoparticles (UCNP) under near-infrared (NIR) light, the last decade has shown a sharp progress in their biomedicine applications. Advances in the techniques for polymer, dye, and bio-molecule conjugation on the surface of the nanoparticles has [...] Read more.

Due to the unique properties of lanthanide-doped upconverting nanoparticles (UCNP) under near-infrared (NIR) light, the last decade has shown a sharp progress in their biomedicine applications. Advances in the techniques for polymer, dye, and bio-molecule conjugation on the surface of the nanoparticles has further expanded their dynamic opportunities for optogenetics, oncotherapy and bioimaging. In this account, considering the primary benefits such as the absence of photobleaching, photoblinking, and autofluorescence of UCNPs not only facilitate the construction of accurate, sensitive and multifunctional nanoprobes, but also improve therapeutic and diagnostic results. We introduce, with the basic knowledge of upconversion, unique properties of UCNPs and the mechanisms involved in photon upconversion and discuss how UCNPs can be implemented in biological practices. In this focused review, we categorize the applications of UCNP-based various strategies into the following domains: neuromodulation, immunotherapy, drug delivery, photodynamic and photothermal therapy, bioimaging and biosensing. Herein, we also discuss the current emerging bioapplications with cutting edge nano-/biointerfacing of UCNPs. Finally, this review provides concluding remarks on future opportunities and challenges on clinical translation of UCNPs-based nanotechnology research. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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27 pages, 5177 KiB

Open AccessReview

Biosensors Designed for Clinical Applications

by James F. Rusling and Robert J. Forster

Biomedicines 2021, 9(7), 702; https://doi.org/10.3390/biomedicines9070702 - 22 Jun 2021

Cited by 19 | Viewed by 3903

Abstract

Emerging and validated biomarkers promise to revolutionize clinical practice, shifting the emphasis away from the management of chronic disease towards prevention, early diagnosis and early intervention. The challenge of detecting these low abundance protein and nucleic acid biomarkers within the clinical context demands [...] Read more.

Emerging and validated biomarkers promise to revolutionize clinical practice, shifting the emphasis away from the management of chronic disease towards prevention, early diagnosis and early intervention. The challenge of detecting these low abundance protein and nucleic acid biomarkers within the clinical context demands the development of highly sensitive, even single molecule, assays that are also capable of selectively measuring a small number of defined analytes in complex samples such as whole blood, interstitial fluid, saliva or urine. Success relies on significant innovations in nanomaterials, bioreceptor engineering, transduction strategies and microfluidics. Primarily using examples from our work, this article discusses some recent advance in the selective and sensitive detection of disease biomarkers, highlights key innovations in sensor materials and identifies issues and challenges that need to be carefully considered especially for researchers entering the field. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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32 pages, 4358 KiB

Open AccessReview

Advanced Signal-Amplification Strategies for Paper-Based Analytical Devices: A Comprehensive Review

by Thi Xoan Hoang, Le Minh Tu Phan, Thuy Anh Thu Vo and Sungbo Cho

Biomedicines 2021, 9(5), 540; https://doi.org/10.3390/biomedicines9050540 - 12 May 2021

Cited by 15 | Viewed by 6729

Abstract

Paper-based analytical devices (PADs) have emerged as a promising approach to point-of-care (POC) detection applications in biomedical and clinical diagnosis owing to their advantages, including cost-effectiveness, ease of use, and rapid responses as well as for being equipment-free, disposable, and user-friendly. However, the [...] Read more.

Paper-based analytical devices (PADs) have emerged as a promising approach to point-of-care (POC) detection applications in biomedical and clinical diagnosis owing to their advantages, including cost-effectiveness, ease of use, and rapid responses as well as for being equipment-free, disposable, and user-friendly. However, the overall sensitivity of PADs still remains weak, posing a challenge for biosensing scientists exploiting them in clinical applications. This review comprehensively summarizes the current applicable potential of PADs, focusing on total signal-amplification strategies that have been applied widely in PADs involving colorimetry, luminescence, surface-enhanced Raman scattering, photoacoustic, photothermal, and photoelectrochemical methods as well as nucleic acid-mediated PAD modifications. The advances in signal-amplification strategies in terms of signal-enhancing principles, sensitivity, and time reactions are discussed in detail to provide an overview of these approaches to using PADs in biosensing applications. Furthermore, a comparison of these methods summarizes the potential for scientists to develop superior PADs. This review serves as a useful inside look at the current progress and prospective directions in using PADs for clinical diagnostics and provides a better source of reference for further investigations, as well as innovations, in the POC diagnostics field. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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20 pages, 4877 KiB

Open AccessReview

Recent Advances in Electrochemical Sensors for the Detection of Biomolecules and Whole Cells

by Intan Rosalina Suhito, Kyeong-Mo Koo and Tae-Hyung Kim

Biomedicines 2021, 9(1), 15; https://doi.org/10.3390/biomedicines9010015 - 26 Dec 2020

Cited by 60 | Viewed by 10989

Abstract

Electrochemical sensors are considered an auspicious tool to detect biomolecules (e.g., DNA, proteins, and lipids), which are valuable sources for the early diagnosis of diseases and disorders. Advances in electrochemical sensing platforms have enabled the development of a new type of biosensor, enabling [...] Read more.

Electrochemical sensors are considered an auspicious tool to detect biomolecules (e.g., DNA, proteins, and lipids), which are valuable sources for the early diagnosis of diseases and disorders. Advances in electrochemical sensing platforms have enabled the development of a new type of biosensor, enabling label-free, non-destructive detection of viability, function, and the genetic signature of whole cells. Numerous studies have attempted to enhance both the sensitivity and selectivity of electrochemical sensors, which are the most critical parameters for assessing sensor performance. Various nanomaterials, including metal nanoparticles, carbon nanotubes, graphene and its derivatives, and metal oxide nanoparticles, have been used to improve the electrical conductivity and electrocatalytic properties of working electrodes, increasing sensor sensitivity. Further modifications have been implemented to advance sensor platform selectivity and biocompatibility using biomaterials such as antibodies, aptamers, extracellular matrix (ECM) proteins, and peptide composites. This paper summarizes recent electrochemical sensors designed to detect target biomolecules and animal cells (cancer cells and stem cells). We hope that this review will inspire researchers to increase their efforts to accelerate biosensor progress—enabling a prosperous future in regenerative medicine and the biomedical industry. Full article

(This article belongs to the Special Issue Biosensors at the Aid of Medicine)

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