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Biosensors
Volume 15
Issue 3
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Biosensors, Volume 15, Issue 3 (March 2025) – 72 articles

Cover Story (view full-size image): The advancement of personalized medicine and digital health has significantly accelerated the development of wearable and implantable biosensors. However, the effective use of these sensors is often limited by issues such as biofouling and foreign body responses, which can severely impact sensor performance and longevity. In this featured paper, the authors present a novel nanocomposite coating made from cross-linked bovine serum albumin, pentaamine-functionalized reduced graphene, and covalently bound antibiotics, which prevents non-specific protein, microbial, and fibroblast attachment while remaining non-toxic to primary human cells. This nanocomposite coating has the potential to greatly improve the longevity and clinical translatability of implantable biosensors, enabling continuous monitoring of multiple diseases and real-time therapeutic responses. View this paper
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26 pages, 7293 KiB  
Review
Advances in Virus Biorecognition and Detection Techniques for the Surveillance and Prevention of Infectious Diseases
by Shuwen Luo, Lihong Yin, Xiaohui Liu and Xuemei Wang
Biosensors 2025, 15(3), 198; https://doi.org/10.3390/bios15030198 - 20 Mar 2025
Viewed by 217
Abstract
Viral infectious diseases pose a serious threat to global public health due to their high transmissibility, rapid mutation rates, and limited treatment options. Recent outbreaks of diseases such as plague, monkeypox, avian influenza, and coronavirus disease 2019 (COVID-19) have underscored the urgent need [...] Read more.
Viral infectious diseases pose a serious threat to global public health due to their high transmissibility, rapid mutation rates, and limited treatment options. Recent outbreaks of diseases such as plague, monkeypox, avian influenza, and coronavirus disease 2019 (COVID-19) have underscored the urgent need for efficient diagnostic and surveillance technologies. Focusing on viral infectious diseases that seriously threaten human health, this review summarizes and analyzes detection techniques from the perspective of combining viral surveillance and prevention advice, and discusses applications in improving diagnostic sensitivity and specificity. One of the major innovations of this review is the systematic integration of advanced biorecognition and detection technologies, such as bionanosensors, rapid detection test strips, and microfluidic platforms, along with the exploration of artificial intelligence in virus detection. These technologies address the limitations of traditional methods and enable the real-time monitoring and early warning of viral outbreaks. By analyzing the application of these technologies in the detection of pathogens, new insights are provided for the development of next-generation diagnostic tools to address emerging and re-emerging viral threats. In addition, we analyze the current progress of developed vaccines, combining virus surveillance with vaccine research to provide new ideas for future viral disease prevention and control and vaccine development, and call for global attention and the development of new disease prevention and detection technologies. Full article
(This article belongs to the Special Issue Nanosensors for Bioanalysis)
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19 pages, 885 KiB  
Review
Piezoelectric Chemosensors and Biosensors in Medical Diagnostics
by Miroslav Pohanka
Biosensors 2025, 15(3), 197; https://doi.org/10.3390/bios15030197 - 20 Mar 2025
Viewed by 158
Abstract
This article explores the development and application of innovative piezoelectric sensors in point-of-care diagnostics. It highlights the significance of bedside tests, such as lateral flow and electrochemical tests, in providing rapid and accurate results directly at the patient’s location. This paper delves into [...] Read more.
This article explores the development and application of innovative piezoelectric sensors in point-of-care diagnostics. It highlights the significance of bedside tests, such as lateral flow and electrochemical tests, in providing rapid and accurate results directly at the patient’s location. This paper delves into the principles of piezoelectric assays, emphasizing their ability to detect disease-related biomarkers through mechanical stress-induced electrical signals. Various applications of piezoelectric chemosensors and biosensors are discussed, including their use in the detection of cancer biomarkers, pathogens, and other health-related analytes. This article also addresses the integration of piezoelectric materials with advanced sensing technologies to improve diagnostic accuracy and efficiency, offering a comprehensive overview of current advances and future directions in medical diagnostics. Full article
(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)
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19 pages, 2283 KiB  
Article
A Platform for the Glucose Biosensor Based on Dendritic Gold Nanostructures and Polyaniline-Gold Nanoparticles Nanocomposite
by Natalija German, Anton Popov, Arunas Ramanavicius and Almira Ramanaviciene
Biosensors 2025, 15(3), 196; https://doi.org/10.3390/bios15030196 - 19 Mar 2025
Viewed by 126
Abstract
Diabetes mellitus is a pathological condition that requires continuous measurement of glucose concentration in human blood. In this study, two enzymatic mediator-free glucose biosensors based on premodified graphite rod (GR) electrodes were developed and compared. GR electrode modified with electrochemically synthesized dendritic gold [...] Read more.
Diabetes mellitus is a pathological condition that requires continuous measurement of glucose concentration in human blood. In this study, two enzymatic mediator-free glucose biosensors based on premodified graphite rod (GR) electrodes were developed and compared. GR electrode modified with electrochemically synthesized dendritic gold nanostructures (DGNS), a cystamine (Cys) self-assembled monolayer (SAM), and glucose oxidase (GOx) (GR/DGNS/Cys/GOx) and GR electrode modified with DGNS, Cys SAM, enzymatically obtained polyaniline (PANI) nanocomposites with embedded 6 nm gold nanoparticles (AuNPs) and GOx (GR/DGNS/Cys/PANI-AuNPs-GOx/GOx) were investigated electrochemically. Biosensors based on GR/DGNS/Cys/GOx and GR/DGNS/Cys/PANI-AuNPs-GOx/GOx electrodes were characterized by a linear range (LR) of up to 1.0 mM of glucose, storage stability of over 71 days, sensitivity of 93.7 and 72.0 μA/(mM cm2), limit of detection (LOD) of 0.027 and 0.034 mM, reproducibility of 13.6 and 9.03%, and repeatability of 8.96 and 8.01%, respectively. The GR/DGNS/Cys/PANI-AuNPs-GOx/GOx electrode was proposed as more favorable for glucose concentration determination in serum due to its better stability and resistance to interfering electrochemically active species. The technological solutions presented in this paper are expected to enable the development of innovative mediator-free enzymatic glucose biosensors, offering advantages for clinical assays, particularly for controlling blood glucose concentration in individuals with diabetes. Full article
(This article belongs to the Special Issue Recent Advances in Glucose Biosensors)
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17 pages, 2651 KiB  
Article
Magnetically Localized Detection of Amplified DNA Using Biotinylated and Fluorescent Primers and Magnetic Nanoparticles
by Etienne Orsini, Franz Bruckert, Marianne Weidenhaupt, Orphée Cugat, Paul Kauffmann and Sarah Delshadi
Biosensors 2025, 15(3), 195; https://doi.org/10.3390/bios15030195 - 18 Mar 2025
Viewed by 277
Abstract
Quantitative nucleic acid detection is widely used in molecular diagnostics for infectious diseases. Here, we demonstrate that the previously developed MLFIA (magnetically localized fluorescent immunoassay) has the potential to detect Polymerase Chain Reaction (PCR) and loop-mediated isothermal amplification (LAMP) products using biotinylated and [...] Read more.
Quantitative nucleic acid detection is widely used in molecular diagnostics for infectious diseases. Here, we demonstrate that the previously developed MLFIA (magnetically localized fluorescent immunoassay) has the potential to detect Polymerase Chain Reaction (PCR) and loop-mediated isothermal amplification (LAMP) products using biotinylated and fluorescent primers and streptavidin-coated magnetic nanoparticles. The functionalized nanoparticles separate amplified DNA from non-incorporated primers in situ, allowing the quantification of DNA products. We compare magnetically localized fluorescence detection to commercial technologies based on the DNA intercalation of fluorescent dyes. Our system allows the detection of PCR and LAMP products but is approximately 10 times less sensitive than standard commercial assays. Future optimizations, such as enhancing the signal-to-noise ratio and improving nanoparticle functionalization, could significantly increase sensitivity and bring it closer to current diagnostic standards. This work highlights the potential of magnetically localized fluorescence detection to detect DNA. Full article
(This article belongs to the Special Issue Nanoparticle-Based Biosensors for Detection)
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15 pages, 3686 KiB  
Article
A Wearable Molecularly Imprinted Electrochemical Sensor for Cortisol Stable Monitoring in Sweat
by Yitao Chen, Zidong He, Yuanzhao Wu, Xinyu Bai, Yuancheng Li, Weiwei Yang, Yiwei Liu and Run-Wei Li
Biosensors 2025, 15(3), 194; https://doi.org/10.3390/bios15030194 - 18 Mar 2025
Viewed by 304
Abstract
Cortisol, a steroid hormone, is closely associated with human mental stress. The rapid, real-time, and continuous detection of cortisol using wearable devices offers a promising approach for individual mental health. These devices must exhibit high sensitivity and long-term stability to ensure reliable performance. [...] Read more.
Cortisol, a steroid hormone, is closely associated with human mental stress. The rapid, real-time, and continuous detection of cortisol using wearable devices offers a promising approach for individual mental health. These devices must exhibit high sensitivity and long-term stability to ensure reliable performance. This study developed a wearable electrochemical sensor based on molecularly imprinted polymer (MIP) technology for real-time and dynamic monitoring of cortisol in sweat. A flexible gold (Au) electrode with interfacial hydrophilic treatment was employed to construct a highly stable electrode. The integration of a silk fibroin/polyvinylidene fluoride (SF/PVDF) composite membrane facilitates directional sweat transport, while liquid metal bonding enhances electrode flexibility and mechanical anti-delamination capability. The sensor exhibits an ultrawide detection range (0.1 pM to 5 μM), high selectivity (over 100-fold against interferents such as glucose and lactic acid), and long-term stability (less than 3.76% signal attenuation over 120 cycles). Additionally, a gradient modulus design was implemented to mitigate mechanical deformation interference under wearable conditions. As a flexible wearable device for cortisol monitoring in human sweat, the sensor’s response closely aligns with the diurnal cortisol rhythm, offering a highly sensitive and interference-resistant wearable solution for mental health monitoring and advancing personalized dynamic assessment of stress-related disorders. Full article
(This article belongs to the Special Issue Advanced Biosensors and Bioelectronics: From Liquid Metal-Based to Flexible Devices)
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54 pages, 9948 KiB  
Review
The Versatility of Biological Field-Effect Transistor-Based Biosensors (BioFETs) in Point-of-Care Diagnostics: Applications and Future Directions for Peritoneal Dialysis Monitoring
by Quan Wang, Zi-An Zhao, Ke-Yu Yao, Yuk-Lun Cheng, Dexter Siu-Hong Wong, Duo Wai-Chi Wong and James Chung-Wai Cheung
Biosensors 2025, 15(3), 193; https://doi.org/10.3390/bios15030193 - 18 Mar 2025
Viewed by 425
Abstract
Peritoneal dialysis (PD) is a vital treatment for end-stage renal disease patients, but its efficacy is often compromised by complications such as infections and peritoneal fibrosis. Biological field-effect transistors (BioFETs) present a promising solution for rapid, sensitive, and non-invasive detection of indicators and [...] Read more.
Peritoneal dialysis (PD) is a vital treatment for end-stage renal disease patients, but its efficacy is often compromised by complications such as infections and peritoneal fibrosis. Biological field-effect transistors (BioFETs) present a promising solution for rapid, sensitive, and non-invasive detection of indicators and biomarkers associated with these complications, potentially enabling early intervention. However, BioFETs are yet to be adopted for PD monitoring. This review presents a forward-looking analysis of the capacity and potential integration of BioFETs into PD management systems, highlighting their capacity to monitor both routine indicators of dialysis efficiency and metabolic status, as well as specific biomarkers for complications such as inflammation and fibrosis. We examine the challenges in adapting BioFETs for PD applications, focusing on key areas for improvement, including sensitivity, specificity, stability, reusability, and clinical integration. Furthermore, we discuss various approaches to address these challenges, which are crucial for developing point-of-care (PoC) and multiplexed wearable devices. These advancements could facilitate continuous, precise, and user-friendly monitoring, potentially revolutionizing PD complication management and enhancing patient care. Full article
(This article belongs to the Special Issue Microelectronics and MEMS-Based Biosensors for Healthcare Application)
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17 pages, 5360 KiB  
Article
A Portable Smartphone-Based 3D-Printed Biosensing Platform for Kidney Function Biomarker Quantification
by Sangeeta Palekar, Sharayu Kalambe, Jayu Kalambe, Madhusudan B. Kulkarni and Manish Bhaiyya
Biosensors 2025, 15(3), 192; https://doi.org/10.3390/bios15030192 - 18 Mar 2025
Viewed by 243
Abstract
Detecting kidney function biomarkers is critical for the early diagnosis of kidney diseases and monitoring treatment efficacy. In this work, a portable, 3D-printed colorimetric sensor platform was developed to detect key kidney biomarkers: uric acid, creatinine, and albumin. The platform features a 3D-printed [...] Read more.
Detecting kidney function biomarkers is critical for the early diagnosis of kidney diseases and monitoring treatment efficacy. In this work, a portable, 3D-printed colorimetric sensor platform was developed to detect key kidney biomarkers: uric acid, creatinine, and albumin. The platform features a 3D-printed enclosure with integrated diffused LED lighting to ensure a controlled environment for image acquisition. A disposable 3D-printed flow cell holds samples, ensuring precision and minimizing contamination. The sensor relies on colorimetric analysis, where a reagent reacts with blood serum to produce a color shift proportional to the biomarker concentration. Using a smartphone, the color change is captured, and RGB values are normalized to calculate concentrations based on the Beer-Lambert Law. The system adapts to variations in smartphones, reagent brands, and lighting conditions through an adaptive calibration algorithm, ensuring flexibility and accuracy. The sensor demonstrated good linear detection ranges for uric acid (1–30 mg/dL), creatinine (0.1–20 mg/dL), and albumin (0.1–8 g/dL), with detection limits of 1.15 mg/dL, 0.15 mg/dL, and 0.11 g/dL, respectively. These results correlated well with commercial biochemistry analyzers. Additionally, an Android application was developed to handle image processing and database management, providing a user-friendly interface for real-time blood analysis. This portable, cost-effective platform shows significant potential for point-of-care diagnostics and remote health monitoring. Full article
(This article belongs to the Special Issue Innovative Biosensing Technologies for Sustainable Healthcare)
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37 pages, 2063 KiB  
Review
Analysis of Personalized Cardiovascular Drug Therapy: From Monitoring Technologies to Data Integration and Future Perspectives
by Runxing Lin, Ziyu Huang, Yu Liu and Yinning Zhou
Biosensors 2025, 15(3), 191; https://doi.org/10.3390/bios15030191 - 17 Mar 2025
Viewed by 306
Abstract
Cardiovascular diseases have long been a major challenge to human health, and the treatment differences caused by individual variability remain unresolved. In recent years, personalized cardiovascular drug therapy has attracted widespread attention. This paper reviews the strategies for achieving personalized cardiovascular drug therapy [...] Read more.
Cardiovascular diseases have long been a major challenge to human health, and the treatment differences caused by individual variability remain unresolved. In recent years, personalized cardiovascular drug therapy has attracted widespread attention. This paper reviews the strategies for achieving personalized cardiovascular drug therapy through traditional dynamic monitoring and multidimensional data integration and analysis. It focuses on key technologies for dynamic monitoring, dynamic monitoring based on individual differences, and multidimensional data integration and analysis. By systematically reviewing the relevant literature, the main challenges in current research and the proposed potential directions for future studies were summarized. Full article
(This article belongs to the Section Biosensors and Healthcare)
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16 pages, 2353 KiB  
Article
The Usefulness of the Glucose Management Indicator in Evaluating the Quality of Glycemic Control in Patients with Type 1 Diabetes Using Continuous Glucose Monitoring Sensors: A Cross-Sectional, Multicenter Study
by Sandra Lazar, Ovidiu Potre, Ioana Ionita, Delia-Viola Reurean-Pintilei, Romulus Timar, Andreea Herascu, Vlad Florian Avram and Bogdan Timar
Biosensors 2025, 15(3), 190; https://doi.org/10.3390/bios15030190 - 16 Mar 2025
Viewed by 374
Abstract
The Glucose Management Indicator (GMI) is a biomarker of glycemic control which estimates hemoglobin A1c (HbA1c) based on the average glycemia recorded by continuous glucose monitoring sensors (CGMS). The GMI provides an immediate overview of the patient’s glycemic control, but it might be [...] Read more.
The Glucose Management Indicator (GMI) is a biomarker of glycemic control which estimates hemoglobin A1c (HbA1c) based on the average glycemia recorded by continuous glucose monitoring sensors (CGMS). The GMI provides an immediate overview of the patient’s glycemic control, but it might be biased by the patient’s sensor wear adherence or by the sensor’s reading errors. This study aims to evaluate the GMI’s performance in the assessment of glycemic control and to identify the factors leading to erroneous estimates. In this study, 147 patients with type 1 diabetes, users of CGMS, were enrolled. Their GMI was extracted from the sensor’s report and HbA1c measured at certified laboratories. The median GMI value overestimated the HbA1c by 0.1 percentage points (p = 0.007). The measurements had good reliability, demonstrated by a Cronbach’s alpha index of 0.74, an inter-item correlation coefficient of 0.683 and an inter-item covariance between HbA1c and GMI of 0.813. The HbA1c and the difference between GMI and HbA1c were reversely associated (Spearman’s r = −0.707; p < 0.001). The GMI is a reliable tool in evaluating glycemic control in patients with diabetes. It tends to underestimate the HbA1c in patients with high HbA1c values, while it tends to overestimate the HbA1c in patients with low HbA1c. Full article
(This article belongs to the Section Biosensors and Healthcare)
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43 pages, 9263 KiB  
Review
Biosensor Technologies for Water Quality: Detection of Emerging Contaminants and Pathogens
by Antía Fdez-Sanromán, Nuria Bernárdez-Rodas, Emilio Rosales, Marta Pazos, Elisa González-Romero and Maria Ángeles Sanromán
Biosensors 2025, 15(3), 189; https://doi.org/10.3390/bios15030189 - 15 Mar 2025
Viewed by 984
Abstract
This review explores the development, technological foundations, and applications of biosensor technologies across various fields, such as medicine for disease diagnosis and monitoring, and the food industry. However, the primary focus is on their use in detecting contaminants and pathogens, as well as [...] Read more.
This review explores the development, technological foundations, and applications of biosensor technologies across various fields, such as medicine for disease diagnosis and monitoring, and the food industry. However, the primary focus is on their use in detecting contaminants and pathogens, as well as in environmental monitoring for water quality assessment. The review classifies different types of biosensors based on their bioreceptor and transducer, highlighting how they are specifically designed for the detection of emerging contaminants (ECs) and pathogens in water. Key innovations in this technology are critically examined, including advanced techniques such as systematic evolution of ligands by exponential enrichment (SELEX), molecularly imprinted polymers (MIPs), and self-assembled monolayers (SAMs), which enable the fabrication of sensors with improved sensitivity and selectivity. Additionally, the integration of microfluidic systems into biosensors is analyzed, demonstrating significant enhancements in performance and detection speed. Through these advancements, this work emphasizes the fundamental role of biosensors as key tools for safeguarding public health and preserving environmental integrity. Full article
(This article belongs to the Section Environmental Biosensors and Biosensing)
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27 pages, 3044 KiB  
Review
Heavy Metal–Gut Microbiota Interactions: Probiotics Modulation and Biosensors Detection
by Liliana Anchidin-Norocel, Oana C. Iatcu, Andrei Lobiuc and Mihai Covasa
Biosensors 2025, 15(3), 188; https://doi.org/10.3390/bios15030188 - 14 Mar 2025
Viewed by 344
Abstract
This study provides a comprehensive analysis of the complex interaction between heavy metals (HMs) and the gut microbiota, adopting a bidirectional approach that explores both the influence of HMs on the gut microbiota populations and the potential role of probiotics in modulating these [...] Read more.
This study provides a comprehensive analysis of the complex interaction between heavy metals (HMs) and the gut microbiota, adopting a bidirectional approach that explores both the influence of HMs on the gut microbiota populations and the potential role of probiotics in modulating these changes. By examining these interconnected aspects, the study aims to offer a deeper understanding of how HMs disrupt microbial balance and how probiotic interventions may mitigate or reverse these effects, promoting detoxification processes and overall gut health. In addition, the review highlights innovative tools, such as biosensors, for the rapid, precise, and non-invasive detection of HMs in urine. These advanced technologies enable the real-time monitoring of the effectiveness of probiotic-based interventions, offering critical insights into their role in promoting the elimination of HMs from the body and improving detoxification. Full article
(This article belongs to the Special Issue Biophysical Sensors for Biomedical/Health Monitoring Applications (2nd Edition))
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20 pages, 10507 KiB  
Article
Bioaggregachromism of Asymmetric Monomethine Cyanine Dyes as Noncovalent Binders for Nucleic Acids
by Sonia Ilieva, Nikolay Petkov, Raimundo Gargallo, Christo Novakov, Miroslav Rangelov, Nadezhda Todorova, Aleksey Vasilev and Diana Cheshmedzhieva
Biosensors 2025, 15(3), 187; https://doi.org/10.3390/bios15030187 - 14 Mar 2025
Viewed by 188
Abstract
Two new asymmetric monomethine cyanine dyes, featuring dimethoxy quinolinium or methyl quinolinium end groups and benzothiazole or methyl benzothiazole end groups were synthesized. The chemical structures of the two dyes—(E)-6,7-dimethoxy-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium iodide (3a) and (E)-4-((3,5-dimethylbenzo[d]thiazol-2(3H)-ylidene)methyl)-1,2-dimethylquinolin-1-ium iodide (3b [...] Read more.
Two new asymmetric monomethine cyanine dyes, featuring dimethoxy quinolinium or methyl quinolinium end groups and benzothiazole or methyl benzothiazole end groups were synthesized. The chemical structures of the two dyes—(E)-6,7-dimethoxy-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium iodide (3a) and (E)-4-((3,5-dimethylbenzo[d]thiazol-2(3H)-ylidene)methyl)-1,2-dimethylquinolin-1-ium iodide (3b)—were confirmed through NMR spectroscopy and MALDI-TOF mass spectrometry. A new methodology was developed to study monocationic dyes in the absence of a matrix and cationizing compounds in MALDI-TOF mass experiments. The newly synthesized dyes contain hydrophobic functional groups attached to the chromophore, enhancing their affinity for the hydrophobic regions of nucleic acids within the biological matrix. The dyes’ photophysical properties were investigated in aqueous solutions and DMSO, as well as in the presence of nucleic acids. The dyes exhibit notable aggregachromism in both pure aqueous and buffered solutions. The observed aggregation phenomena were further elucidated using computational methods. Fluorescence titration experiments revealed that upon contact with nucleic acids, the dyes exhibit bioaggregachromism–aggregachromism on the surfaces of the respective biomolecular matrix (RNA or DNA). This bioaggregachromism was further confirmed by CD spectroscopy. Given the pronounced aggregachromism detected, we conclude that the dyes investigated in this study are highly suitable for use as fluorogenic probes in biomolecular recognition techniques. The unique absorption and fluorescence spectra of these dyes make them promising fluorogenic markers for various bioanalytical methods related to biomolecular recognition. Full article
(This article belongs to the Special Issue Advanced Fluorescence Biosensors)
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15 pages, 3033 KiB  
Article
Surface Functionalization of ITO for Dual-Mode Hypoxia-Associated Cancer Biomarker Detection
by Edmunds Zutis, Gunita Paidere, Rihards Ruska, Toms Freimanis, Janis Cipa, Raivis Zalubovskis, Maira Elksne, Kaspars Tars, Andris Kazaks, Janis Leitans, Anatolijs Sarakovskis and Andris Anspoks
Biosensors 2025, 15(3), 186; https://doi.org/10.3390/bios15030186 - 14 Mar 2025
Viewed by 245
Abstract
Indium tin oxide (ITO) is a transparent conducting material with exceptional electrical and optical properties, widely used in biosensing and bioelectronics. Functionalization of ITO with linker molecules enables covalent attachment of biomolecules, allowing for dual-mode optical and electrochemical detection. Carbonic anhydrase IX (CA [...] Read more.
Indium tin oxide (ITO) is a transparent conducting material with exceptional electrical and optical properties, widely used in biosensing and bioelectronics. Functionalization of ITO with linker molecules enables covalent attachment of biomolecules, allowing for dual-mode optical and electrochemical detection. Carbonic anhydrase IX (CA IX), a transmembrane enzyme overexpressed in hypoxic tumors, is a promising biomarker for cancer diagnostics due to its restricted expression in normal tissues. However, conventional detection methods are time-intensive and unsuitable for point-of-care applications. In this study, ITO surfaces were functionalized using silane-based chemistry to immobilize CA IX-specific antibodies, creating a novel biosensing platform. The biosensor utilized a secondary horseradish peroxidase (HRP)-conjugated antibody to catalyze the oxidation of luminol in the presence of hydrogen peroxide, producing a chemiluminescent and electrochemical signal. Characterization of the biosensor via a dual-mode optical and electrochemical approach revealed efficient antibody immobilization. Due to the high variation observed in the optical approach, limit of detection (LOD) experiments were conducted exclusively with electrochemistry, yielding an LOD of 266.4 ng/mL. These findings demonstrate the potential of ITO-based electrochemical biosensors for sensitive and selective CA IX detection, highlighting their applicability in cancer diagnostics and other biomedical fields. Full article
(This article belongs to the Special Issue Biosensors for Biomedical Diagnostics)
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19 pages, 18304 KiB  
Article
Amplitude of Intracranial Induced Electric Fields Does Not Linearly Decrease with Age: A Computational Study of Anatomical Effects in Adults
by Jianxu Zhang, Zilong Yan, Anshun Kang, Jian Ouyang, Lihua Ma, Xinyue Wang, Jinglong Wu, Dingjie Suo, Shintaro Funahashi, Wei Meng, Li Wang and Jian Zhang
Biosensors 2025, 15(3), 185; https://doi.org/10.3390/bios15030185 - 13 Mar 2025
Viewed by 281
Abstract
Transcranial electrical stimulation, as a means of neural modulation, is increasingly favored by researchers. The distribution and magnitude of the electric field generated within the brain may directly affect the results of neural modulation. Therefore, it is important to clarify the change trend [...] Read more.
Transcranial electrical stimulation, as a means of neural modulation, is increasingly favored by researchers. The distribution and magnitude of the electric field generated within the brain may directly affect the results of neural modulation. Therefore, it is important to clarify the change trend of the cortical electric field and the determinants of the induced electric field in the endodermis at different ages during the adult life cycle. In this study, we used SimNIBS software to perform MR image segmentation and realistic head model reconstruction on 476 individuals (aged 18 to 88 years old) and calculated the cortical electric field of four electrode montages commonly used in cognitive tasks. We divided all participants into groups by age with a span of 10 years for each group and compared the electric field distribution patterns, electric field intensities, and focalities of the cortexes and regions of interest related to cognitive tasks within groups. The degree of influence of global and local anatomical parameters on the electric field was analyzed using a stepwise regression model. The results showed that, in the cortexes and regions of interest, the variability of electric field distribution patterns was highest in adolescents (<20 years old) and elderly individuals (>80 years old). Moreover, throughout the adult lifespan, the electric field induced by transcranial electrical stimulation did not decrease linearly with age but rather presented a U-shaped pattern. In terms of the entire adult life cycle, compared with global anatomical parameters (intracranial brain tissue volume), local anatomical parameters (such as scalp or skull thickness below the electrode) have a greater impact on the amplitude of the intracranial electric field. Our research results indicated that it is necessary to consider the effects caused by different brain tissues when using transcranial electrical stimulation to modulate or treat individuals of different ages. Full article
(This article belongs to the Special Issue Implantable, Wireless Biosensors and Biodevices for Neuroscience Research)
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16 pages, 5848 KiB  
Article
Molecularly Imprinted Electrochemical Sensor Based on MWCNTs/GQDs for the Detection of Sulfamethazine in Aquaculture Seawater
by Jianlei Chen, Tianruo Zhang, Yong Xu, Hao Li, Hongwu Cui, Xinguo Zhao, Yun Zhou, Keming Qu and Zhengguo Cui
Biosensors 2025, 15(3), 184; https://doi.org/10.3390/bios15030184 - 13 Mar 2025
Viewed by 312
Abstract
In this work, a novel molecularly imprinted electrochemical sensor was proposed based on molecular imprinting technology for the detection of sulfamethazine. A glassy carbon electrode was modified with a composite material of carbon nanotubes and graphene quantum dots to effectively improve sensitivity. The [...] Read more.
In this work, a novel molecularly imprinted electrochemical sensor was proposed based on molecular imprinting technology for the detection of sulfamethazine. A glassy carbon electrode was modified with a composite material of carbon nanotubes and graphene quantum dots to effectively improve sensitivity. The molecularly imprinted electrochemical sensor was then prepared by electropolymerization using sulfamethazine as the template and o-phenylenediamine as the functional monomer on the modified electrode. Under optimal measurement conditions, electrochemical tests of different sulfamethazine concentrations (0.5 μM–200 μM) showed excellent linearity and a detection limit of 0.068 μM. In addition, the sensor demonstrated satisfactory selectivity, stability, and reusability. Furthermore, the sensor was applied to the spiked analysis of sulfamethazine in grouper aquaculture water, achieving recovery rates between 95.4% and 104.8%, with a relative standard deviation (RSD) of less than 4.14%. These results indicated that the developed method was effective for the analysis of sulfamethazine in aquaculture seawater, providing a new approach for the detection of antibiotic residues in seawater samples. Full article
(This article belongs to the Special Issue Application of Biosensors in Environmental Monitoring)
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35 pages, 3811 KiB  
Review
Nanobody-Based Immunoassays for the Detection of Food Hazards—A Review
by Wenkai Li, Zhihao Xu, Qiyi He, Junkang Pan, Yijia Zhang, El-Sayed A. El-Sheikh, Bruce D. Hammock and Dongyang Li
Biosensors 2025, 15(3), 183; https://doi.org/10.3390/bios15030183 - 13 Mar 2025
Viewed by 308
Abstract
Food safety remains a significant global challenge that affects human health. Various hazards, including microbiological and chemical threats, can compromise food safety throughout the supply chain. To address food safety issues and ensure public health, it is necessary to adopt rapid, accurate, and [...] Read more.
Food safety remains a significant global challenge that affects human health. Various hazards, including microbiological and chemical threats, can compromise food safety throughout the supply chain. To address food safety issues and ensure public health, it is necessary to adopt rapid, accurate, and highly specific detection methods. Immunoassays are considered to be an effective method for the detection of highly sensitive biochemical indicators and provide an efficient platform for the identification of food hazards. In immunoassays, antibodies function as the primary recognition elements. Nanobodies have significant potential as valuable biomolecules in diagnostic applications. Their distinctive physicochemical and structural characteristics make them excellent candidates for the development of reliable diagnostic assays, and as promising alternatives to monoclonal and polyclonal antibodies. Herein, we summarize a comprehensive overview of the status and prospects of nanobody-based immunoassays in ensuring food safety. First, we begin with a historical perspective on the development of nanobodies and their unique characteristics. Subsequently, we explore the definitions and boundaries of immunoassays and immunosensors, before discussing the potential applications of nanobody-based immunoassays in food safety testing that have emerged over the past five years, and follow the different immunoassays, highlighting their advantages over traditional detection methods. Finally, the directions and challenges of nanobody-based immunoassays in food safety are discussed. Due to their remarkable sensitivity, specificity and versatility, nanobody-based immunoassays hold great promise in revolutionizing food safety testing and ensuring public health and well-being. Full article
(This article belongs to the Special Issue Immunoassays and Biosensing (2nd Edition))
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14 pages, 3539 KiB  
Article
First Vibrational Fingerprint of Parietaria judaica Protein via Surface-Enhanced Raman Spectroscopy
by Dario Morganti, Valeria Longo, Antonio Alessio Leonardi, Alessia Irrera, Paolo Colombo and Barbara Fazio
Biosensors 2025, 15(3), 182; https://doi.org/10.3390/bios15030182 - 13 Mar 2025
Viewed by 139
Abstract
Accurate identification and characterization of allergenic proteins at the molecular level are essential for pinpointing the specific protein structures responsible for allergic reactions, thus advancing the development of precise diagnostic tests. Significant efforts have been focused on novel experimental techniques aimed at deepening [...] Read more.
Accurate identification and characterization of allergenic proteins at the molecular level are essential for pinpointing the specific protein structures responsible for allergic reactions, thus advancing the development of precise diagnostic tests. Significant efforts have been focused on novel experimental techniques aimed at deepening the understanding of the underlying molecular mechanisms of these reactions. In this work, we show, for the first time to our knowledge, the unique Raman fingerprint of three Parietaria judaica (Par j) allergenic proteins. These proteins are typically present in pollen and are known to trigger severe respiratory diseases. In our research, we further exploited the surface-enhanced Raman scattering (SERS) effect from an Ag dendrite substrate. This approach provided better discrimination and a comprehensive analysis of the proteins Par j 1, 2, and 4 in hydration conditions, enabling rapid differentiation between them through a spectroscopic study. Full article
(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)
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13 pages, 5460 KiB  
Article
Dynamic Plasmonic Coupling in Gold Nanosphere Oligomers: Mechanically Tuned Red and Blue Shifts for SERS/SEF
by István Tóth and Cosmin Farcău
Biosensors 2025, 15(3), 181; https://doi.org/10.3390/bios15030181 - 13 Mar 2025
Viewed by 188
Abstract
Controlling the surface plasmon resonances of metal nanostructures is crucial for advancing numerous high-sensitivity optical (bio)sensing applications. Furthermore, dynamically adjusting these resonances enables real-time tuning of the spectrum of enhanced electromagnetic fields in the near field, thereby regulating the optical interactions between molecules [...] Read more.
Controlling the surface plasmon resonances of metal nanostructures is crucial for advancing numerous high-sensitivity optical (bio)sensing applications. Furthermore, dynamically adjusting these resonances enables real-time tuning of the spectrum of enhanced electromagnetic fields in the near field, thereby regulating the optical interactions between molecules and the metal surface. In this study, we investigate the plasmonic behavior of linear oligomers composed of gold nanospheres using finite-difference time-domain electromagnetic simulations. The extinction spectra of linear arrangements such as dimers, trimers, and quadrumers are obtained for different sphere sizes, interparticle gaps, and polarization of the incident light. In view of (bio)sensing applications based on plasmon-enhanced optical spectroscopy such as surface-enhanced Raman/fluorescence (SERS/SEF), the sensitivity of various coupled plasmon modes to the variation of the interparticle gap is evaluated. The achievement of both red-shifting and blue-shifting plasmon modes offers ways to mechanically control the optical response of the linear oligomers in real-time and design new optical sensing protocols. Based on these findings, both an approach for trapping molecules into SERS hotspots and an approach for dual-mode SERS/SEF using a single excitation wavelength are proposed, contributing to the future development of (bio)sensing protocols. Full article
(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)
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13 pages, 1462 KiB  
Article
Attention Affecting Response Inhibition in Overweight Adults with Food Addiction
by Xiaotong Liu, Guangying Pei, Jiayuan Zhao, Mengzhou Xu, Lizhi Cao, Jian Zhang, Tiantian Liu, Jinglong Wu, Shintaro Funahashi, Lei Ding and Li Wang
Biosensors 2025, 15(3), 180; https://doi.org/10.3390/bios15030180 - 13 Mar 2025
Viewed by 270
Abstract
Food addiction is associated with attention bias and response inhibition deficits, while the relationship between these two domains is unclear. Participants with body mass index (BMI) ≥ 25 and exhibiting food addiction behaviors (FA group, n = 20) were compared with healthy controls [...] Read more.
Food addiction is associated with attention bias and response inhibition deficits, while the relationship between these two domains is unclear. Participants with body mass index (BMI) ≥ 25 and exhibiting food addiction behaviors (FA group, n = 20) were compared with healthy controls (HC group, n = 23). We examined attention-inhibition mechanisms using resting EEG microstate analysis, food-cue-evoked event-related potentials (ERPs), and non-food Go/No-Go tasks. Overweight individuals with food addiction behaviors demonstrated attentional deficits, as indicated by abnormalities in microstate D and the P100 component. Importantly, both microstate D and the P100 component significantly predicted No-Go performance, linking neurophysiological markers to behavioral inhibition. This study suggests that attention bias may be an important interaction factor of response inhibition, providing novel mechanistic insights into food addiction. Full article
(This article belongs to the Special Issue Artificial Intelligence (AI) and Machine Learning (ML) in Biosensors: Innovation, Application, and Challenge)
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14 pages, 3468 KiB  
Article
Pathway-like Activation of 3D Neuronal Constructs with an Optical Interface
by Saeed Omidi and Yevgeny Berdichevsky
Biosensors 2025, 15(3), 179; https://doi.org/10.3390/bios15030179 - 12 Mar 2025
Viewed by 215
Abstract
Three-dimensional neuronal organoids, spheroids, and tissue mimics are increasingly used to model cognitive processes in vitro. These 3D constructs are also used to model the effects of neurological and psychiatric disorders and to perform computational tasks. The brain’s complex network of neurons is [...] Read more.
Three-dimensional neuronal organoids, spheroids, and tissue mimics are increasingly used to model cognitive processes in vitro. These 3D constructs are also used to model the effects of neurological and psychiatric disorders and to perform computational tasks. The brain’s complex network of neurons is activated via feedforward sensory pathways. Therefore, an interface to 3D constructs that models sensory pathway-like inputs is desirable. In this work, an optical interface for 3D neuronal constructs was developed. Dendrites and axons extended by cortical neurons within the 3D constructs were guided into microchannel-confined bundles. These neurite bundles were then optogenetically stimulated, and evoked responses were evaluated by calcium imaging. Optical stimulation was designed to deliver distinct input patterns to the network in the 3D construct, mimicking sensory pathway inputs to cortical areas in the intact brain. Responses of the network to the stimulation possessed features of neuronal population code, including separability by input pattern and mixed selectivity of individual neurons. This work represents the first demonstration of a pathway-like activation of networks in 3D constructs. Another innovation of this work is the development of an all-optical interface to 3D neuronal constructs, which does not require the use of expensive microelectrode arrays. This interface may enable the use of 3D neuronal constructs for investigations into cortical information processing. It may also enable studies into the effects of neurodegenerative or psychiatric disorders on cortical computation. Full article
(This article belongs to the Special Issue Advanced Microfluidic Devices and Lab-on-Chip (Bio)sensors)
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11 pages, 1957 KiB  
Article
Evaluation of Preferential Cytokine Adsorption onto Biosensing Surface Modified with Glycopolymer
by Yuhei Terada, Masayuki Futamata, Kaori Tsutsui and Hiroshi Aoki
Biosensors 2025, 15(3), 178; https://doi.org/10.3390/bios15030178 - 12 Mar 2025
Viewed by 217
Abstract
For the improvement of biosensor performance, the development of a molecular recognition material as well as a sensor platform is necessary. A glycopolymer is a molecular recognition material capable of recognizing specific proteins as natural glycans. However, the target molecules for biosensors using [...] Read more.
For the improvement of biosensor performance, the development of a molecular recognition material as well as a sensor platform is necessary. A glycopolymer is a molecular recognition material capable of recognizing specific proteins as natural glycans. However, the target molecules for biosensors using glycopolymers are limited to lectins that are already known for their specific interactions with glycan residues. The aim of this study is to investigate a glycopolymer-modified (GM) surface capable of recognizing non-lectin proteins. As non-lectin proteins, we focused on cytokines, in which the interaction preference to glycopolymers is unknown. The cytokine adsorption onto the GM surfaces was evaluated using a surface plasmon resonance imaging technique as a biosensing tool. Differences in cytokine adsorption onto the different glycan residues were revealed, which will be important for selective cytokine detection. This study indicates the possibility of a biosensing surface modified with glycopolymers for the detection of non-lectin proteins. The results are beneficial for expanding the use of glycopolymers as a molecular recognition material for future applications such as cell analysis and diagnostic devices. Full article
(This article belongs to the Special Issue Biomaterials for Biosensing Applications)
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19 pages, 5866 KiB  
Article
A Low-Cost Hydrogel Electrode for Multifunctional Sensing: Strain, Temperature, and Electrophysiology
by Junjie Zheng, Jinli Zhou, Yixin Zhao, Chenxiao Wang, Mengzhao Fan, Yunfei Li, Chaoran Yang and Hongying Yang
Biosensors 2025, 15(3), 177; https://doi.org/10.3390/bios15030177 - 11 Mar 2025
Viewed by 237
Abstract
With the rapid development of wearable technology, multifunctional sensors have demonstrated immense application potential. However, the limitations of traditional rigid materials restrict the flexibility and widespread adoption of such sensors. Hydrogels, as flexible materials, provide an effective solution to this challenge due to [...] Read more.
With the rapid development of wearable technology, multifunctional sensors have demonstrated immense application potential. However, the limitations of traditional rigid materials restrict the flexibility and widespread adoption of such sensors. Hydrogels, as flexible materials, provide an effective solution to this challenge due to their excellent stretchability, biocompatibility, and adaptability. This study developed a multifunctional flexible sensor based on a composite hydrogel of polyvinyl alcohol (PVA) and sodium alginate (SA), using poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT:PSS) as the conductive material to achieve multifunctional detection of strain, temperature, and physiological signals. The sensor features a simple fabrication process, low cost, and low impedance. Experimental results show that the prepared hydrogel exhibits outstanding mechanical properties and conductivity, with a strength of 118.8 kPa, an elongation of 334%, and a conductivity of 256 mS/m. In strain sensing, the sensor demonstrates a rapid response to minor strains (4%), high sensitivity (gauge factors of 0.39 for 0–120% and 0.73 for 120–200% strain ranges), short response time (2.2 s), low hysteresis, and excellent cyclic stability (over 500 cycles). For temperature sensing, the sensor achieves high sensitivities of −27.43 Ω/K (resistance mode) and 0.729 mV/K (voltage mode), along with stable performance across varying temperature ranges. Furthermore, the sensor has been successfully applied to monitor human motion (e.g., finger bending, wrist movement) and physiological signals such as electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG), highlighting its significant potential in wearable health monitoring. By employing a simple and efficient fabrication method, this study presents a high-performance multifunctional flexible sensor, offering novel insights and technical support for the advancement of wearable devices. Full article
(This article belongs to the Special Issue Wearable and Implantable Bioelectronics for Advanced Biosensing and Human Health Monitoring)
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43 pages, 7519 KiB  
Review
Bone-on-a-Chip Systems for Hematological Cancers
by Gül Kozalak and Ali Koşar
Biosensors 2025, 15(3), 176; https://doi.org/10.3390/bios15030176 - 9 Mar 2025
Viewed by 408
Abstract
Hematological malignancies originating from blood, bone marrow, and lymph nodes include leukemia, lymphoma, and myeloma, which necessitate the use of a distinct chemotherapeutic approach. Drug resistance frequently complicates their treatment, highlighting the need for predictive tools to guide therapeutic decisions. Conventional 2D/3D cell [...] Read more.
Hematological malignancies originating from blood, bone marrow, and lymph nodes include leukemia, lymphoma, and myeloma, which necessitate the use of a distinct chemotherapeutic approach. Drug resistance frequently complicates their treatment, highlighting the need for predictive tools to guide therapeutic decisions. Conventional 2D/3D cell cultures do not fully encompass in vivo criteria, and translating disease models from mice to humans proves challenging. Organ-on-a-chip technology presents an avenue to surmount genetic disparities between species, offering precise design, concurrent manipulation of various cell types, and extrapolation of data to human physiology. The development of bone-on-a-chip (BoC) systems is crucial for accurately representing the in vivo bone microenvironment, predicting drug responses for hematological cancers, mitigating drug resistance, and facilitating personalized therapeutic interventions. BoC systems for modeling hematological cancers and drug research can encompass intricate designs and integrated platforms for analyzing drug response data to simulate disease scenarios. This review provides a comprehensive examination of BoC systems applicable to modeling hematological cancers and visualizing drug responses within the intricate context of bone. It thoroughly discusses the materials pertinent to BoC systems, suitable in vitro techniques, the predictive capabilities of BoC systems in clinical settings, and their potential for commercialization. Full article
(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening (2nd Edition))
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13 pages, 1739 KiB  
Article
Regulatory Effects of RNA–Protein Interactions Revealed by Reporter Assays of Bacteria Grown on Solid Media
by Guillermo Pérez-Ropero, Roswitha Dolcemascolo, Anna Pérez-Ràfols, Karl Andersson, U. Helena Danielson, Guillermo Rodrigo and Jos Buijs
Biosensors 2025, 15(3), 175; https://doi.org/10.3390/bios15030175 - 8 Mar 2025
Viewed by 287
Abstract
Reporter systems are widely used to study biomolecular interactions and processes in vivo, representing one of the basic tools used to characterize synthetic regulatory circuits. Here, we developed a method that enables the monitoring of RNA–protein interactions through a reporter system in bacteria [...] Read more.
Reporter systems are widely used to study biomolecular interactions and processes in vivo, representing one of the basic tools used to characterize synthetic regulatory circuits. Here, we developed a method that enables the monitoring of RNA–protein interactions through a reporter system in bacteria with high temporal resolution. For this, we used a Real-Time Protein Expression Assay (RT-PEA) technology for real-time monitoring of a fluorescent reporter protein, while having bacteria growing on solid media. Experimental results were analyzed by fitting a three-variable Gompertz growth model. To validate the method, the interactions between a set of RNA sequences and the RNA-binding protein (RBP) Musashi-1 (MSI1) were evaluated, as well as the allosteric modulation of the interaction by a small molecule (oleic acid). This new approach proved to be suitable to quantitatively characterize RNA–RBP interactions, thereby expanding the toolbox to study molecular interactions in living bacteria, including allosteric modulation, with special relevance for systems that are not suitable to be studied in liquid media. Full article
(This article belongs to the Special Issue Microbial Biosensor: From Design to Applications)
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12 pages, 2648 KiB  
Article
Development of a Rapid-Response Fluorescent Probe for H2S: Mechanism Elucidation and Biological Applications
by Trevor Dvorak, Haley Hernandez-Sandoval, Sunayn Cheku, Marijose Mora Valencia González, Linus Borer, Riley Grieser, Kimberly A. Carlson and Haishi Cao
Biosensors 2025, 15(3), 174; https://doi.org/10.3390/bios15030174 - 7 Mar 2025
Viewed by 420
Abstract
Hydrogen sulfide (H2S) is an important signaling molecule involved in various physiological and pathological processes, making its accurate detection in biological systems highly desirable. In this study, two fluorescent probes (M1 and M2) based on 1,8-naphthalimide were developed for [...] Read more.
Hydrogen sulfide (H2S) is an important signaling molecule involved in various physiological and pathological processes, making its accurate detection in biological systems highly desirable. In this study, two fluorescent probes (M1 and M2) based on 1,8-naphthalimide were developed for H2S detection via a nucleophilic aromatic substitution. M1 demonstrated high sensitivity and selectivity for H2S in aqueous media, with a detection limit of 0.64 µM and a strong linear fluorescence response in the range of 0–22 µM of NaHS. The reaction kinetics revealed a rapid response, with a reaction rate constant of 7.56 × 102 M−1 s−1, and M1 was most effective in the pH range of 6–10. Mechanism studies using 1H NMR titration confirmed the formation of 4-hydroxyphenyl-1,8-naphthalimide as the product of H2S-triggered nucleophilic substitution. M1 was applied in MDA-MB-231 cells for cell imaging, in which M1 provided significant fluorescence enhancement upon NaHS treatment, confirming its applicability for detecting H2S in biological environments. In comparison, M2, designed with extended conjugation for red-shifted emission, exhibited weaker sensitivity due to the reduced stability of its naphtholate product and lower solubility. These results demonstrate that M1 is a highly effective and selective fluorescent probe for detecting H2S, providing a valuable resource for investigating the biological roles of H2S in health and disease. Full article
(This article belongs to the Special Issue Fluorescent Materials with Excellent Biocompatibility and Their Application in Bio-Sensing, Bio-Imaging (Volume II))
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15 pages, 12854 KiB  
Article
Non-Invasive and Long-Term Electrophysiological Monitoring Sensors for Cerebral Organoids Differentiation
by Yan Jin, Yixun Guo, Qiushi Li, Lei Wu, Yuqing Ge and Jianlong Zhao
Biosensors 2025, 15(3), 173; https://doi.org/10.3390/bios15030173 - 7 Mar 2025
Viewed by 406
Abstract
Cerebral organoids derived from human induced pluripotent stem cells (iPSCs) have emerged as powerful in vitro models for studying human brain development and neurological disorders. Understanding the electrophysiological properties of these organoids is crucial for evaluating their functional maturity and potential applications. However, [...] Read more.
Cerebral organoids derived from human induced pluripotent stem cells (iPSCs) have emerged as powerful in vitro models for studying human brain development and neurological disorders. Understanding the electrophysiological properties of these organoids is crucial for evaluating their functional maturity and potential applications. However, the differentiation and maturation of stem cells into cerebral organoids is a long, slow, and error-prone process. Hence, it is vitally crucial to establish a non-invasive method of monitoring the process over a long period of time. In this study, a planar microelectrode array (MEA) with platinum (Pt) black electroplating is designed to monitor the electrophysiological activities and pharmacological responses of cerebral organoids using an external neural signal acquisition system interfaced with the MEA. The planar MEA with Pt black electroplating has a significantly reduced electrode impedance and exhibits a robust capability for the real-time detection of spontaneous neural activities, including extracellular spikes and local field potentials. Distinct electrophysiological signal strengths in cerebral organoids were observed at early and late developmental stages. Further pharmacological stimulations showed that 30 mM KCl would induce a marked increase in spike rate, indicating an enhancement of neuronal depolarization and an elevation of network excitability. This robust response to KCl stimulation in mature networks serves as a reliable indicator of neural maturity in cerebral organoids and underscores the platform’s potential for drug screening applications. This work highlights the integration of MEA technology with cerebral organoids, offering a powerful platform for real-time electrophysiological monitoring. It provides new insights into the functional maturation of neural networks and establishes a reliable system for drug screening and disease modeling, facilitating future research into human brain physiology and pathology. Full article
(This article belongs to the Special Issue Microelectrode Array for Biomedical Applications)
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19 pages, 3453 KiB  
Article
Microfluidic Device on Fused Silica for Raman Spectroscopy of Liquid Samples
by Celia Gómez-Galdós, Andrea Perez-Asensio, María Gabriela Fernández-Manteca, Borja García García, José Francisco Algorri, José Miguel López-Higuera, Luis Rodríguez-Cobo and Adolfo Cobo
Biosensors 2025, 15(3), 172; https://doi.org/10.3390/bios15030172 - 6 Mar 2025
Viewed by 344
Abstract
Water testing is becoming increasingly important due to dangerous phenomena such as Harmful Algal Blooms (HABs). Commonly, the content of a water sample is measured for the detection, monitoring and control of these events. Raman spectroscopy is a technique for the molecular characterization [...] Read more.
Water testing is becoming increasingly important due to dangerous phenomena such as Harmful Algal Blooms (HABs). Commonly, the content of a water sample is measured for the detection, monitoring and control of these events. Raman spectroscopy is a technique for the molecular characterization of materials in solid, liquid or gaseous form, which makes it an attractive method for analysing materials’ components. However, Raman scattering is a weak optical process and requires an accurate system for detection. In our work, we present, from design to fabrication, a microfluidic device on fused silica adapted to optimise the Raman spectrum of liquid samples when using a Raman probe. The device features a portable design for rapid on-site continuous flow measurements avoiding the use of large, costly and complex laboratory equipment. The main manufacturing technique used was ultrafast laser-assisted etching (ULAE). Finally, the effectiveness of the microfluidic device was demonstrated by comparing the Raman spectra of a known species of cyanobacteria with those obtained using other conventional substrates in laboratory analysis. The results demonstrate that the microfluidic device, under continuous flow conditions, exhibited a lower standard deviation of the Raman signal, reduced background noise and avoided signal variations caused by sample drying in static measurements. Full article
(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices—2nd Edition)
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19 pages, 2617 KiB  
Article
An Antimicrobial and Antifibrotic Coating for Implantable Biosensors
by Sofia Wareham-Mathiassen, Pawan Jolly, Nandhinee Radha Shanmugam, Badrinath Jagannath, Pranav Prabhala, Yunhao Zhai, Alican Ozkan, Arash Naziripour, Rohini Singh, Henrik Bengtsson, Thomas Bjarnsholt and Donald E. Ingber
Biosensors 2025, 15(3), 171; https://doi.org/10.3390/bios15030171 - 6 Mar 2025
Viewed by 622
Abstract
Biofouling and foreign body responses have deleterious effects on the functionality and longevity of implantable biosensors, seriously impeding their implementation for long-term monitoring. Here, we describe a nanocomposite coating composed of a cross-linked lattice of bovine serum albumin and pentaamine-functionalized reduced graphene that [...] Read more.
Biofouling and foreign body responses have deleterious effects on the functionality and longevity of implantable biosensors, seriously impeding their implementation for long-term monitoring. Here, we describe a nanocomposite coating composed of a cross-linked lattice of bovine serum albumin and pentaamine-functionalized reduced graphene that is covalently coupled to antibody ligands for analyte detection as well as antibiotic drugs (gentamicin or ceftriaxone), which actively combats biofouling while retaining high electroconductivity and excellent electrochemical immunosensor behavior. Sensors overlaid with this coating inhibit the proliferation of Pseudomonas aeruginosa bacteria and adhesion of primary human fibroblasts while not having any significant effects on fibroblast viability or on the immune function of primary human monocytes. Under these conditions, the sensor maintains its electrochemical stability for at least 3 weeks after exposure to soluble proteins that interfere with the activity of uncoated sensors. Proof-of-concept for the coating’s applicability is demonstrated by integrating the antimicrobial coating within an immunosensor and demonstrating the detection of cytokines in both culture medium and complex human plasma. This new coating technology holds the potential to substantially increase the lifespan of implanted biosensors and widen their application areas, potentially enabling continuous monitoring of analytes in complex biofluids for weeks in vivo. Full article
(This article belongs to the Special Issue Recent Developments in Nanomaterial-Based Electrochemical Biosensors)
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14 pages, 6225 KiB  
Article
Development of a Brain Catheter for Optical Coherence Tomography in Advanced Cerebrovascular Diagnostics
by Tae-Mi Jung, Tahsin Nairuz, Chang-Hyun Kim and Jong-Ha Lee
Biosensors 2025, 15(3), 170; https://doi.org/10.3390/bios15030170 - 6 Mar 2025
Viewed by 381
Abstract
Optical coherence tomography (OCT) has been extensively utilized in cardiovascular diagnostics due to its high resolution, rapid imaging capabilities; however, its adaptation for cerebrovascular applications remains constrained by the narrow, tortuous anatomical structure of cerebral vessels. To address these limitations, this study introduces [...] Read more.
Optical coherence tomography (OCT) has been extensively utilized in cardiovascular diagnostics due to its high resolution, rapid imaging capabilities; however, its adaptation for cerebrovascular applications remains constrained by the narrow, tortuous anatomical structure of cerebral vessels. To address these limitations, this study introduces a cerebrovascular-specific OCT (bOCT) catheter, an advanced adaptation of the cardiovascular OCT (cOCT) catheter, with significant structural modifications for improved access to brain blood vessels. The bOCT catheter incorporates a braided wire within a braided tube, strategically reinforcing axial strength. The distal shaft was reconfigured as a single-lumen structure, facilitating unified movement of the rotating fiber optic core and guidewire, thereby reducing guidewire bending and augmenting force transmission stability. Additionally, the anterior protrusion was removed and replaced with a dual-lumen configuration, significantly enhancing lesion accessibility. The bOCT catheter’s performance was validated in a 3D physical model and an animal model, demonstrating pronounced enhancements in flexibility, pushability, and navigability. Notably, the pushability through curved flow paths significantly improved, enhancing access to cerebral blood vessels. Therefore, this innovation promises to revolutionize cerebrovascular diagnostics with high-resolution imaging suited to the complex brain vasculature, setting a new standard in intravascular imaging technology. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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15 pages, 7264 KiB  
Article
High-Frequency 64-Element Ring-Annular Array Transducer: Development and Preclinical Validation for Intravascular Ultrasound Imaging
by Xi Liu, Yuanlong Li, Haiguo Qin and Chang Peng
Biosensors 2025, 15(3), 169; https://doi.org/10.3390/bios15030169 - 5 Mar 2025
Viewed by 442
Abstract
Intravascular ultrasound (IVUS) imaging has become an essential method for diagnosing coronary artery disease. However, traditional mechanically rotational IVUS catheters encounter issues such as mechanical wear and imaging distortions in curved vessels. The ring-annular IVUS array has gained attention because it offers superior [...] Read more.
Intravascular ultrasound (IVUS) imaging has become an essential method for diagnosing coronary artery disease. However, traditional mechanically rotational IVUS catheters encounter issues such as mechanical wear and imaging distortions in curved vessels. The ring-annular IVUS array has gained attention because it offers superior imaging performance without the need for mechanical rotational parts, thereby avoiding rotational imaging distortion. An optimized mechanical micromachining process employing precision dicing technology is proposed in this study, with the objective of achieving higher operating frequencies and minimized outer diameters for a 64-element ring-annular array. This method broadens the range of fabrication options and improves the imaging sensitivity of ring-annular IVUS arrays, as well as eliminating imaging distortion in rotational IVUS catheters, particularly in curved vessels. The probe has a 7.5 Fr (2.5 mm) outer diameter, with key fabrication steps including precision dicing, flexible circuit integration, and Parylene C encapsulation. The ring-annular array has a center frequency of 21.51 MHz with 67.87% bandwidth, with a 56 µm axial resolution and a 276 µm lateral resolution. The imaging performance is further validated by in vitro phantom imaging and ex vivo imaging. Full article
(This article belongs to the Special Issue Biosensors for Biomedical Diagnostics)
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