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Biosensors, Volume 15, Issue 6 (June 2025) – 43 articles

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15 pages, 6302 KiB  
Article
Fluorescent–Electrochemical–Colorimetric Triple-Model Immunoassays with Multifunctional Metal–Organic Frameworks for Signal Amplification
by Ning Xia, Chuye Zheng and Gang Liu
Biosensors 2025, 15(6), 376; https://doi.org/10.3390/bios15060376 (registering DOI) - 11 Jun 2025
Abstract
Multimode immunoassays based on multiple response mechanisms have received great attention due to their capacity to effectively improve the accuracy and reliability of biosensing platforms. However, few strategies have been reported for triple-mode immunoassays due to the shortage of multifunctional sensing materials and [...] Read more.
Multimode immunoassays based on multiple response mechanisms have received great attention due to their capacity to effectively improve the accuracy and reliability of biosensing platforms. However, few strategies have been reported for triple-mode immunoassays due to the shortage of multifunctional sensing materials and the incompatibility of signal transduction methods in different detection modes. In this work, a fluorescent–electrochemical–colorimetric triple-mode immunoassay platform was proposed with Cu-based metal–organic frameworks (MOFs) as the signal labels. The captured Cu-MOFs were successfully decomposed under an acidic condition, leading to the release of numerous Cu2+ ions and 2-aminobenzene-1,4-dicarboxylic acid (NH2-BDC) ligands. The released NH2-BDC were determined by fluorescence titration. Meanwhile, the released Cu2+ were readily quantified by differential pulse voltammetry (DPV) and simply detected through the catalytic oxidation of chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB). Taking alpha-fetoprotein (AFP) as a model analyte, the designed triple-mode immunoassays showed good performances with the linear range of 10–200 pg/mL, 10–200 pg/mL, and 1–100 pg/mL for the fluorescent, electrochemical, and colorimetric modes, respectively. The proposed triple-mode biosensing platforms show great potential for the applications in disease diagnosis, since they can be easily extended to other bioassays by changing the targets and recognition elements. Full article
(This article belongs to the Special Issue Signal Amplification in Biosensing)
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27 pages, 2382 KiB  
Review
Advances of Nanozyme-Driven Multimodal Sensing Strategies in Point-of-Care Testing
by Ziyi Chang, Qingjie Fu, Mengke Wang and Demin Duan
Biosensors 2025, 15(6), 375; https://doi.org/10.3390/bios15060375 - 10 Jun 2025
Abstract
Point-of-care testing (POCT) has garnered widespread attention due to its rapid, convenient, and efficient detection capabilities, particularly playing an increasingly pivotal role in medical diagnostics and significantly improving the efficiency and quality of healthcare services. Nanozymes, as novel enzyme-mimicking materials, have emerged as [...] Read more.
Point-of-care testing (POCT) has garnered widespread attention due to its rapid, convenient, and efficient detection capabilities, particularly playing an increasingly pivotal role in medical diagnostics and significantly improving the efficiency and quality of healthcare services. Nanozymes, as novel enzyme-mimicking materials, have emerged as a research hotspot owing to their superior catalytic performance, low cost, and robust stability. This review provides a systematic overview of the fundamental characteristics and classifications of nanozymes, along with various sensing strategies employed in POCT applications, colorimetric, electrochemical, fluorescent, chemiluminescent, and surface-enhanced Raman scattering (SERS)-based approaches. Furthermore, this review highlights innovative designs that enhance the sensitivity and accuracy of POCT across multiple domains, such as biomarker detection, environmental monitoring, and food safety analysis, thereby offering novel perspectives for the practical implementation of nanozymes in point-of-care diagnostics. Finally, this review analyzes current challenges in nanozyme-based POCT systems, including limitations in optimizing catalytic activity, ensuring nanozyme homogeneity, and achieving large-scale production, while proposing future development trajectories. Full article
(This article belongs to the Special Issue Advances in Nanozyme-Based Biosensors)
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21 pages, 2609 KiB  
Article
Assessing the Role of EEG Biosignal Preprocessing to Enhance Multiscale Fuzzy Entropy in Alzheimer’s Disease Detection
by Pasquale Arpaia, Maria Cacciapuoti, Andrea Cataldo, Sabatina Criscuolo, Egidio De Benedetto, Antonio Masciullo, Marisa Pesola and Raissa Schiavoni
Biosensors 2025, 15(6), 374; https://doi.org/10.3390/bios15060374 - 10 Jun 2025
Abstract
Quantitative electroencephalography (QEEG) has emerged as a promising tool for detecting Alzheimer’s disease (AD). Among QEEG measures, Multiscale Fuzzy Entropy (MFE) shows great potential in identifying AD-related changes in EEG complexity. However, MFE is intrinsically linked to signal amplitude, which can vary substantially [...] Read more.
Quantitative electroencephalography (QEEG) has emerged as a promising tool for detecting Alzheimer’s disease (AD). Among QEEG measures, Multiscale Fuzzy Entropy (MFE) shows great potential in identifying AD-related changes in EEG complexity. However, MFE is intrinsically linked to signal amplitude, which can vary substantially among EEG systems, and this hinders the adoption of this metric for AD detection. To overcome this issue, this study investigates different preprocessing strategies to make the calculation of MFE less dependent on the specific amplitude characteristics of the EEG signals at hand. This contributes to generalizing and making more robust the adoption of MFE for AD detection. To demonstrate the robustness of the proposed preprocessing methods, binary classification tasks with Support Vector Machines (SVMs), Random Forest (RF), and K-Nearest Neighbor (KNN) classifiers are used. Performance metrics, such as classification accuracy and Matthews Correlation Coefficient (MCC), are employed to assess the results. The methodology is validated on two public EEG datasets. Results show that amplitude transformation, particularly normalization, significantly enhances AD detection, achieving mean classification accuracy values exceeding 80% with an uncertainty of 10% across all classifiers. These results highlight the importance of preprocessing in improving the accuracy and the reliability of EEG-based AD diagnostic tools, offering potential advancements in patient management and treatment planning. Full article
(This article belongs to the Section Biosensors and Healthcare)
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17 pages, 2881 KiB  
Article
Biological Sensing Using Vertical MoS2-Graphene Heterostructure-Based Field-Effect Transistor Biosensors
by Ying Chen, Nataly Vicente, Tung Pham and Ashok Mulchandani
Biosensors 2025, 15(6), 373; https://doi.org/10.3390/bios15060373 - 10 Jun 2025
Abstract
Our study develops two configurations of MoS2 and graphene heterostructures—MoS2 on graphene (MG) and graphene on MoS2 (GM)—to investigate biomolecule sensing in field-effect transistor (FET) biosensors. Leveraging MoS2 and graphene’s distinctive properties, we employ specialized functionalization techniques for each [...] Read more.
Our study develops two configurations of MoS2 and graphene heterostructures—MoS2 on graphene (MG) and graphene on MoS2 (GM)—to investigate biomolecule sensing in field-effect transistor (FET) biosensors. Leveraging MoS2 and graphene’s distinctive properties, we employ specialized functionalization techniques for each configuration: graphene with MoS2 on top uses a silane-based method with triethoxysilylbutyraldehyde (TESBA), and MoS2 with graphene on top utilizes 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE). Our research explores the application of MoS2–Graphene heterostructures in biosensors, emphasizing the roles of synthesis, fabrication, and material functionalization in optimizing sensor performance. Through our experimental investigations, we have observed that doping MoS2 and graphene leads to noticeable changes in the Raman spectrum and shifts in transfer curves. Techniques such as XPS, Raman, and AFM have successfully confirmed the biofunctionalization. Transfer curves were instrumental in characterizing the biosensing performance, revealing that GM configurations exhibit higher sensitivity and a lower limit of detection (LOD) compared to MG configurations. We demonstrate that GM heterostructures offer superior sensitivity and specificity in biosensing, highlighting their significant potential to advance biosensor technologies. This research contributes to the field by detailing the creation process of vertical MoS2–graphene heterostructures and evaluating their effectiveness in accurate biomolecule detection, advancing biosensing technology. Full article
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12 pages, 694 KiB  
Article
Sudomotor Dysfunction as an Early Marker of Autonomic and Cardiovascular Risk in Diabetes: Insights from a Cross-Sectional Study Using SUDOSCAN
by Larisa Anghel, Claudiu Cobuz, Laura-Cătălina Benchea, Vasile Maciuc, Maricela Cobuz, Radu-Andy Sascău and Cristian Stătescu
Biosensors 2025, 15(6), 372; https://doi.org/10.3390/bios15060372 - 10 Jun 2025
Abstract
Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to [...] Read more.
Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to measure ESC in the hands and feet. Clinical and laboratory parameters, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, lipid profile, and cardiovascular risk, were analyzed for correlations with ESC. Neuropathy status was evaluated, and ROC analysis was performed to assess diagnostic accuracy. Results: Sudomotor dysfunction was prevalent, particularly in patients with a diabetes duration exceeding 20 years (p < 0.05). Men showed significantly higher right foot ESC than women (76.5 ± 13.1 vs. 74.0 ± 13.5 µS, p = 0.041). A strong inverse correlation was found between cardiovascular risk score and right foot ESC (r = −0.455, p < 0.001). Left foot ESC also correlated inversely with cardiovascular risk (r = −0.401, p < 0.001) and HbA1c (r = −0.150, p = 0.049), while a weak positive correlation was seen with BMI (r = 0.145, p = 0.043). ROC analysis showed the highest area under the curve (AUC) in right foot ESC for autonomic neuropathy (AUC = 0.750, 95% CI: 0.623–0.877, p < 0.001). Conclusions: This study is among the few to systematically correlate ESC with validated cardiovascular risk scores in a diabetic outpatient cohort, highlighting its potential as a novel early screening biomarker for autonomic and cardiovascular complications. Full article
(This article belongs to the Section Biosensors and Healthcare)
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47 pages, 1518 KiB  
Review
Advances in MoS2-Based Biosensors: From Material Fabrication and Characterization to Biomedical, Environmental, and Industrial Applications
by Chun-Liang Lai, Arvind Mukundan, Riya Karmakar, Roopmeet Kaur, Kuo-Liang Huang and Hsiang-Chen Wang
Biosensors 2025, 15(6), 371; https://doi.org/10.3390/bios15060371 - 10 Jun 2025
Abstract
The growing demand for low-cost biosensors has stimulated the study of new technologies and materials like molybdenum disulfide (MoS2). Due to its electroconductive nature and high surface-to-volume ratio, it allows for the ultra-sensitive detection of biomarkers. The crystal structure of MoS [...] Read more.
The growing demand for low-cost biosensors has stimulated the study of new technologies and materials like molybdenum disulfide (MoS2). Due to its electroconductive nature and high surface-to-volume ratio, it allows for the ultra-sensitive detection of biomarkers. The crystal structure of MoS2 provides it with a unique micrometer thickness, making it appropriate for biosensing in healthcare, environmental monitoring, and food safety. As compared to traditional materials, MoS2 can work without labels (through field-effect transduction or plasmonic shifts) while maintaining biocompatibility and low-cost fabrication, which fill significant voids in the early diagnosis of diseases. This paper provides an overview of the recent advancements in MoS2-based biosensors, which are primarily focused on the field-effect transistors and surface plasmon resonance techniques and fabrication methods for MoS2-based biosensors like mechanical exfoliation, liquid-phase exfoliation, physical vapor deposition, chemical vapor deposition, and chemical exfoliation, applications in various industries, and their characterization techniques to evaluate the quality and functionality of MoS2 nanosheets in biosensors. While certain challenges remain like improving conductivity and scalability, MoS2-based biosensors serve as a powerful tool for the precise and reliable detection of biomarkers in environmental, food, and healthcare industries. Full article
(This article belongs to the Collection Novel Sensing System for Biomedical Applications)
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11 pages, 1351 KiB  
Article
Improving the Enrichment of Submicron-Sized Particles by Size Decreasing of Cruciform Cross-Sectional Microchannel in Viscoelastic Microfluidics
by Jaekyeong Jang, Eunjin Kim, Sungdong Kim, Ok-Chan Jeong, Sangwook Lee and Younghak Cho
Biosensors 2025, 15(6), 370; https://doi.org/10.3390/bios15060370 - 9 Jun 2025
Abstract
The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating [...] Read more.
The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating the separation and focusing of various cell types, including blood cells, circulating tumor cells (CTCs), and microalgae. However, the viscoelastic nature of the particles imposes limitations in the handling of submicron-sized particles, due to a significant decrease in the viscoelastic force acting on the particle. In this study, we propose a microfluidic device featuring a cruciform cross-sectional microchannel with 45 µm and 45 µm of its vertical and horizontal size, respectively. The cruciform microchannel, which has a 270° reflex angle on four corners, can increase the viscoelastic force on the particles, allowing the device to focus submicron-sized particles down to 180 nm in a single-stream manner. It is important to note that the single-stream formation was maintained, while the channel width at the outlet region was drastically increased, allowing for the enrichment of submicron-sized particles. For biological feasibility, the proposed device also demonstrates the single-stream focusing on biological particles such as bacteria. The presented microfluidic device would have great potential for the focusing and enrichment of nanoparticles including bacteria in a highly robust manner, expecting its use in the various fields such as diverse biological analysis and biomedical research. Full article
(This article belongs to the Section Nano- and Micro-Technologies in Biosensors)
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12 pages, 1925 KiB  
Article
Large-Area Nanogap Platforms for Surface-Enhanced Raman Spectroscopy Toward Sensing Applications: Comparison Between Ag and Au
by Arunkumar Alagurasu, Satyabrat Behera, Joon-Mo Yang, Dai-Sik Kim and Seon Namgung
Biosensors 2025, 15(6), 369; https://doi.org/10.3390/bios15060369 - 9 Jun 2025
Abstract
Sub-wavelength metallic nanostructures allow the squeezing of light within nanoscale regions, called plasmonic hotspots. Squeezed near-field light has been demonstrated to detect, modulate, and generate light in more effective ways. The enhanced electric field in the plasmonic hotspots are also utilized for identifying [...] Read more.
Sub-wavelength metallic nanostructures allow the squeezing of light within nanoscale regions, called plasmonic hotspots. Squeezed near-field light has been demonstrated to detect, modulate, and generate light in more effective ways. The enhanced electric field in the plasmonic hotspots are also utilized for identifying molecular fingerprints in a more sensitive manner, i.e., surface-enhanced Raman spectroscopy (SERS). SERS is a versatile tool used to characterize chemicals and biomolecules with the advantages of label-free detection, specificity, and high sensitivity compared to fluorescence and colorimetric sensing methods. With its practical and diverse applications such as biomedical sensing, the evaluation of SERS on diverse nano-structure platforms and materials is highly in demand. Nanogap structures are promising SERS platforms which can be fabricated over a large area with uniform nanoscale gap size. Here, we demonstrate the fabrication of large-area metal–insulator–metal nanogap structures with different metals (i.e., Au and Ag) and analyze material dependence on SERS. While both nanometer-sized gap structures exhibit a large enhancement factor for Raman spectroscopy, Ag-based structures exhibit 58- and 15-times-larger enhancement factors for bottom and top plasmonic hotspots, respectively. The enhanced detection on a silver nanogap platform is attributed to enhanced electric field in the gap, as confirmed by simulation. Our findings provide not only a way to better understand SERS in different metallic nano platforms but also insights for designing highly sensitive nanoscale chemical and biomedical sensors. Full article
(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)
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10 pages, 1763 KiB  
Communication
Multi-Mode Coupling Enabled Broadband Coverage for Terahertz Biosensing Applications
by Dongyu Hu, Mengya Pan, Yanpeng Shi and Yifei Zhang
Biosensors 2025, 15(6), 368; https://doi.org/10.3390/bios15060368 - 7 Jun 2025
Viewed by 200
Abstract
Terahertz (THz) biosensing faces critical challenges in balancing high sensitivity and broadband spectral coverage, particularly under miniaturized device constraints. Conventional quasi-bound states in the continuum (QBIC) metasurfaces achieve high quality factor (Q) but suffer from narrow bandwidth, while angle-scanning strategies for broadband detection [...] Read more.
Terahertz (THz) biosensing faces critical challenges in balancing high sensitivity and broadband spectral coverage, particularly under miniaturized device constraints. Conventional quasi-bound states in the continuum (QBIC) metasurfaces achieve high quality factor (Q) but suffer from narrow bandwidth, while angle-scanning strategies for broadband detection require complex large-angle illumination. Here, we propose a symmetry-engineered, all-dielectric metasurface that leverages multipolar interference coupling to overcome this limitation. By introducing angular perturbation, the metasurface transforms the original magnetic dipole (MD)-dominated QBIC resonance into hybridized, multipolar modes. It arises from the interference coupling between MD, toroidal dipole (TD), and magnetic quadrupole (MQ). This mechanism induces dual counter-directional, frequency-shifted, resonance branches within angular variations below 16°, achieving simultaneous 0.42 THz broadband coverage and high Q of 499. Furthermore, a derived analytical model based on Maxwell equations and mode coupling theory rigorously validates the linear relationship between frequency splitting interval and incident angle with the Relative Root Mean Square Error (RRMSE) of 1.4% and the coefficient of determination (R2) of 0.99. This work establishes a paradigm for miniaturized THz biosensors, advancing applications in practical molecular diagnostics and multi-analyte screening. Full article
(This article belongs to the Special Issue Photonics for Bioapplications: Sensors and Technology—2nd Edition)
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11 pages, 425 KiB  
Article
Influence of Gait Speed on Inter-Joint Coordination in People with and Without Parkinson’s Disease
by Patrick Ippersiel, Philippe C. Dixon, Elke Warmerdam, Robbin Romijnders, Walter Maetzler and Clint Hansen
Biosensors 2025, 15(6), 367; https://doi.org/10.3390/bios15060367 - 6 Jun 2025
Viewed by 182
Abstract
Background: The influence of gait speed on lower-extremity coordination while walking in people with Parkinson’s disease (pwPD) is poorly understood. This study sought to investigate the relationship between gait speed and hip–knee coordination and coordination variability in older adults and pwPD. Methods: A [...] Read more.
Background: The influence of gait speed on lower-extremity coordination while walking in people with Parkinson’s disease (pwPD) is poorly understood. This study sought to investigate the relationship between gait speed and hip–knee coordination and coordination variability in older adults and pwPD. Methods: A total of 27 pwPD and 21 healthy older adults were recruited. Participants walked in a straight line at slow, preferred, and fast walking speeds. Gait data were collected using inertial measurement units, and the kinematics of the hip and knee were calculated. Coordination and coordination variability at the hip–knee joint pair were determined using continuous relative phase. A repeated measures two-way ANCOVA tested the impact of gait speed on coordination and coordination variability, while group differences were evaluated using statistical parametric mapping (SPM). Results: Neither the healthy older adults nor the pwPD adjusted their hip–knee coordination in response to changes in gait speed. pwPD also displayed a trend towards restricted hip and knee joint excursion compared to older adults, which may further limit their ability to adapt gait strategies. Conclusions: These findings suggest that interventions addressing both joint excursion and motor adaptability may be important for improving gait function in individuals with Parkinson’s disease. Real-world applicability can be found in the potential of wearable sensors to become a valuable tool in routine clinical practice for both diagnosis and ongoing management. Trial registration: The study is registered in the German Clinical Trials Register (DRKS00022998). Full article
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15 pages, 3593 KiB  
Article
Polypyrrole Coatings as Possible Solutions for Sensing and Stimulation in Bioelectronic Medicines
by Cristian Sevcencu, Izabella Crăciunescu, Alin-Alexandru Andrei, Maria Suciu, Sergiu Macavei and Lucian Barbu-Tudoran
Biosensors 2025, 15(6), 366; https://doi.org/10.3390/bios15060366 - 6 Jun 2025
Viewed by 169
Abstract
Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of [...] Read more.
Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of the present work was to investigate whether the electroconductive polymer polypyrrole (PPy) could be used for fabricating such electrodes, as PPy is several orders softer than metals. For this purpose, we here investigated if electrodes made using coatings and films of PPy doped with naphthalin-2-sulfonic acid (PPy/N) are capable to record and elicit by stimulation cardiac monophasic action potentials (MAPs) and if PPy/N is also biocompatible. The results of this study showed that the tested PPy/N electrodes are capable of recording MAPs almost identical to the MAPs recorded with platinum electrodes and eliciting stimulation-evoked MAPs almost identical to the spontaneous MAPs. In addition, we show here that the cell cultures that we used for biocompatibility tests grew in a similar manner on PPy/N and platinum substrates. We, therefore, conclude that PPy/N coatings and films have recording and electrical stimulation capabilities that are similar to those of platinum electrodes and that PPy/N substrates are as biocompatible as the platinum substrates. Full article
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24 pages, 1476 KiB  
Article
Wearable Ultrasound-Imaging-Based Visual Feedback (UVF) Training for Ankle Rehabilitation of Chronic Stroke Survivors: A Proof-of-Concept Randomized Crossover Study
by Yu-Yan Luo, Chen Huang, Zhen Song, Vaheh Nazari, Arnold Yu-Lok Wong, Lin Yang, Mingjie Dong, Mingming Zhang, Yong-Ping Zheng, Amy Siu-Ngor Fu and Christina Zong-Hao Ma
Biosensors 2025, 15(6), 365; https://doi.org/10.3390/bios15060365 - 6 Jun 2025
Viewed by 106
Abstract
This study investigated the effect of wearable ultrasound-imaging-based visual feedback (UVF) on assisting paretic ankle dorsiflexion training of chronic stroke survivors. Thirty-three participants with unilateral hemiplegia performed maximal isometric contractions on an isokinetic dynamometer in randomized conditions with and without UVF that provided [...] Read more.
This study investigated the effect of wearable ultrasound-imaging-based visual feedback (UVF) on assisting paretic ankle dorsiflexion training of chronic stroke survivors. Thirty-three participants with unilateral hemiplegia performed maximal isometric contractions on an isokinetic dynamometer in randomized conditions with and without UVF that provided by a wearable ultrasound imaging system. Torque parameters (mean, peak, percentage of maximal voluntary contraction) and tibialis anterior muscle thickness were analyzed across different contraction phases. Statistical comparisons were conducted using paired t-tests or Wilcoxon tests. Correlation analyses were performed using Pearson’s or Spearman’s tests. Results demonstrated that UVF significantly improved torque output, as evidence by the increased percentage of maximal voluntary contraction (%MVC) during entire contractions (p = 0.007), increased mean (p ≤ 0.022) and peak (p ≤ 0.044) torque and the %MVC (p ≤ 0.004) during mid and end phases, and larger muscle thickness during mid contraction (p = 0.045). Moderate correlations were found between torque and muscle thickness (r ≥ 0.30, p ≤ 0.049). These findings preliminarily supported the positive outcomes of real-time wearable UVFs in enhancing paretic ankle dorsiflexion strength and force control during isometric contractions in chronic stroke survivors. While the developed and validated new training protocol may potentially serve as a practical adjunct to existing rehabilitation approaches, further investigations emphasizing the functional outcomes and clinical translations are still needed to verify the clinical utility. Full article
(This article belongs to the Special Issue Innovative Biosensing Technologies for Sustainable Healthcare)
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13 pages, 1960 KiB  
Article
Electrochemical Detection of Prostate Cancer—Associated miRNA-141 Using a Low-Cost Disposable Biosensor
by Alexander Hunt and Gymama Slaughter
Biosensors 2025, 15(6), 364; https://doi.org/10.3390/bios15060364 - 6 Jun 2025
Viewed by 173
Abstract
Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. The early detection of aggressive forms is critical. Current diagnostic methods, including PSA testing and biopsies, are invasive and often yield false results. MicroRNA-141 (miRNA-141) has emerged [...] Read more.
Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. The early detection of aggressive forms is critical. Current diagnostic methods, including PSA testing and biopsies, are invasive and often yield false results. MicroRNA-141 (miRNA-141) has emerged as a promising non-invasive biomarker due to its elevated levels in the urine of patients with metastatic prostate cancer. Here, a low-cost, paper-based electrochemical biosensor for the sensitive detection of miRNA-141 in synthetic urine is reported. The device employs inkjet-printed gold electrodes on photopaper, functionalized with thiolated single-stranded DNA-141 capture probes for specific target recognition. The biosensor achieves a sensitivity of 78.66 fM µA−1 cm−2 and a linear detection range of 1 fM to 100 nM, encompassing clinically relevant concentrations of miRNA-141 found in patients with metastatic prostate cancer. A low limit of detection of 2.15 fM, strong selectivity against non-target sequences, and a rapid response time of 15 min further highlight the diagnostic potential of the device. This platform represents a significant advancement in the development of point-of-care diagnostic tools for prostate cancer and is readily adaptable for detecting other disease-specific miRNAs through simple probe modification. As such, it holds broad promise for accessible, early-stage cancer detection and longitudinal disease monitoring in diverse clinical settings. Full article
(This article belongs to the Special Issue Innovative Strategies for Cancer Biosensing)
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43 pages, 9912 KiB  
Review
Advances in Hydrogel-Integrated SERS Platforms: Innovations, Applications, Challenges, and Future Prospects in Food Safety Detection
by Xorlali Nunekpeku, Huanhuan Li, Ayesha Zahid, Chenhui Li and Wei Zhang
Biosensors 2025, 15(6), 363; https://doi.org/10.3390/bios15060363 - 5 Jun 2025
Viewed by 166
Abstract
Background: Food safety remains a global concern due to biological and chemical contaminants, including adulterants, pathogens, antibiotic residues, and pesticides. Traditional detection methods are accurate but limited by time requirements, complex sample preparation, high costs, and poor field applicability. Surface-Enhanced Raman Spectroscopy [...] Read more.
Background: Food safety remains a global concern due to biological and chemical contaminants, including adulterants, pathogens, antibiotic residues, and pesticides. Traditional detection methods are accurate but limited by time requirements, complex sample preparation, high costs, and poor field applicability. Surface-Enhanced Raman Spectroscopy (SERS) offers non-destructive analysis with low detection limits and high specificity, yet conventional SERS substrates face challenges with reproducibility, nanoparticle aggregation, and sensitivity in food matrices. Hydrogels have emerged as supporting materials for SERS due to their water content, tunable porosity, flexibility, and ability to entrap plasmonic nanostructures. Scope and Approach: This review examines recent advances in hydrogel-integrated SERS platforms for food safety applications. The three-dimensional structure of hydrogels enables homogeneous distribution of metal nanoparticles, prevents aggregation, and offers analyte enrichment. We analyze material design, functionalization strategies, and how hydrogel properties—crosslinking density, porosity, surface charge, and nanoparticle distribution—influence SERS performance in food matrices. Key Findings and Conclusions: Hydrogel-integrated SERS platforms demonstrate superior performance in detecting various food contaminants—including pesticides, adulterants, and additives—in real food matrices, often achieving detection limits in the nanomolar to picomolar range, depending on the analyte and substrate design. Current limitations include storage stability concerns, batch-to-batch variability, and regulatory acceptance hurdles. Future research directions should focus on multiplex detection capabilities, integration with smart sensing technologies, and industrial scalability to facilitate practical deployment in global food safety monitoring across diverse supply chains. Full article
(This article belongs to the Special Issue Advanced SERS Biosensors for Detection and Analysis)
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32 pages, 5494 KiB  
Review
Colorimetric Biosensors: Advancements in Nanomaterials and Cutting-Edge Detection Strategies
by Yubeen Lee, Izzati Haizan, Sang Baek Sim and Jin-Ha Choi
Biosensors 2025, 15(6), 362; https://doi.org/10.3390/bios15060362 - 5 Jun 2025
Viewed by 249
Abstract
Colorimetric-based biosensors are practical detection devices that can detect the presence and concentration of biomarkers through simple color changes. Conventional laboratory-based tests are highly sensitive but require long processing times and expensive equipment, which makes them difficult to apply for on-site diagnostics. In [...] Read more.
Colorimetric-based biosensors are practical detection devices that can detect the presence and concentration of biomarkers through simple color changes. Conventional laboratory-based tests are highly sensitive but require long processing times and expensive equipment, which makes them difficult to apply for on-site diagnostics. In contrast, the colorimetric method offers advantages for point-of-care testing and real-time monitoring due to its flexibility, simple operation, rapid results, and versatility across many applications. In order to enhance the color change reactions in colorimetric techniques, functional nanomaterials are often integrated due to their desirable intrinsic properties. In this review, the working principles of nanomaterial-based detection strategies in colorimetric systems are introduced. In addition, current signal amplification methods for colorimetric biosensors are comprehensively outlined and evaluated. Finally, the latest trends in artificial intelligence (AI) and machine learning integration into colorimetric-based biosensors, including their potential for technological advancements in the near future, are discussed. Future research is expected to develop highly sensitive and multifunctional colorimetric methods, which will serve as powerful alternatives for point-of-care testing and self-testing. Full article
(This article belongs to the Special Issue Functional Materials for Biosensing Applications)
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11 pages, 1139 KiB  
Article
Electrochemical Sensor Platform for Rapid Detection of Foodborne Toxins
by Kundan Kumar Mishra, Krupa M. Thakkar, Vikram Narayanan Dhamu, Sriram Muthukumar and Shalini Prasad
Biosensors 2025, 15(6), 361; https://doi.org/10.3390/bios15060361 - 4 Jun 2025
Viewed by 276
Abstract
Zearalenone (ZEA), a potent mycotoxin commonly found in contaminated grains, presents a serious threat to food safety and public health. Conventional detection methods, including culture-based assays and laboratory-bound analytical tools, are often time-consuming, require specialized infrastructure, and lack portability, limiting their utility for [...] Read more.
Zearalenone (ZEA), a potent mycotoxin commonly found in contaminated grains, presents a serious threat to food safety and public health. Conventional detection methods, including culture-based assays and laboratory-bound analytical tools, are often time-consuming, require specialized infrastructure, and lack portability, limiting their utility for rapid, on-site screening. In response, this study introduces a compact, real-time electrochemical sensing platform for the swift and selective detection of ZEA in corn flour matrices. Utilizing a non-faradaic, label-free approach based on Electrochemical Impedance Spectroscopy (EIS), the sensor leverages ZEA-specific antibodies to achieve rapid detection within 5 min. The platform demonstrates a low detection limit of 0.05 ng/mL, with a broad dynamic range from 0.1 ng/mL to 25.6 ng/mL. Reproducibility tests confirm consistent performance, with both inter- and intra-assay variation remaining under a 20% coefficient of variation (%CV). Comparative evaluation with standard benchtop systems underscores its accuracy and field applicability. This portable and user-friendly device provides a powerful tool for real-time mycotoxin monitoring, offering significant potential for improving food safety practices and enabling point-of-need testing in resource-limited settings. Full article
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20 pages, 1022 KiB  
Review
CRISPR/Cas12a-Based Biosensing: Advances in Mechanisms and Applications for Nucleic Acid Detection
by Kun Du, Qinlong Zeng, Mingjun Jiang, Zhiqing Hu, Miaojin Zhou and Kun Xia
Biosensors 2025, 15(6), 360; https://doi.org/10.3390/bios15060360 - 4 Jun 2025
Viewed by 358
Abstract
Nucleic acid detection technology is crucial for molecular diagnosis. The advent of CRISPR/Cas12a-based nucleic acid detection has considerably broadened its scope, from the identification of infectious disease-causing microorganisms to the detection of disease-associated biomarkers. This innovative system capitalizes on the non-specific single-strand cleavage [...] Read more.
Nucleic acid detection technology is crucial for molecular diagnosis. The advent of CRISPR/Cas12a-based nucleic acid detection has considerably broadened its scope, from the identification of infectious disease-causing microorganisms to the detection of disease-associated biomarkers. This innovative system capitalizes on the non-specific single-strand cleavage activity of Cas12a upon target DNA recognition. By employing a fluorescent probe in the form of a single-stranded DNA/RNA, this technology enables the observation of fluorescence changes resulting from nonspecific cleavage, thereby facilitating detection. CRISPR/Cas12a-based detection systems can be regarded as a new type of biosensor, offering a practical and efficient approach for nucleic acid analysis in various diagnostic settings. CRISPR/Cas12a-based biosensors outperform conventional nucleic acid detection methods in terms of portability, simplicity, speed, and efficiency. In this review, we elucidate the detection principle of CRISPR/Cas12a-based biosensors and their application in disease diagnostics and discuss recent innovations and technological challenges, aiming to provide insights for the research and further development of CRISPR/Cas12a-based biosensors in personalized medicine. Our findings show that although CRISPR/Cas12a-based biosensors have considerable potential for various applications and theoretical research, certain challenges remain. These include simplifying the reaction process, enhancing precision, broadening the scope of disease detection, and facilitating the translation of research findings into clinical practice. We anticipate that ongoing advancements in CRISPR/Cas12a-based biosensors will address these challenges. Full article
(This article belongs to the Section Biosensors and Healthcare)
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30 pages, 3363 KiB  
Review
Surface Plasmon Resonance Aptasensors: Emerging Design and Deployment Landscape
by Fahd Khalid-Salako, Hasan Kurt and Meral Yüce
Biosensors 2025, 15(6), 359; https://doi.org/10.3390/bios15060359 - 4 Jun 2025
Viewed by 176
Abstract
SPR biosensors operate on the principle of evanescent wave propagation at metal–dielectric interfaces in total internal reflection conditions, with consequent photonic energy attenuation. This plasmonic excitation occurs in specific conditions of incident light wavelength, angle, and the dielectric refractive index. This principle has [...] Read more.
SPR biosensors operate on the principle of evanescent wave propagation at metal–dielectric interfaces in total internal reflection conditions, with consequent photonic energy attenuation. This plasmonic excitation occurs in specific conditions of incident light wavelength, angle, and the dielectric refractive index. This principle has been the basis for SPR-based biosensor setups wherein mass/concentration-induced changes in the refractive indices of dielectric media reflect as plasmonic resonance condition changes quantitatively reported as arbitrary response units. SPR biosensors operating on this conceptual framework have been designed to study biomolecular interactions with real-time readout and in label-free setups, providing key kinetic characterization that has been valuable in various applications. SPR biosensors often feature antibodies as target affinity probes. Notably, the operational challenges encountered with antibodies have led to the development of aptamers—oligonucleotide biomolecules rationally designed to adopt tertiary structures, enabling high affinity and specific binding to a wide range of targets. Aptamers have been extensively adopted in SPR biosensor setups with promising clinical and industrial prospects. In this paper, we explore the growing literature on SPR setups featuring aptamers, specifically providing expert commentary on the current state and future implications of these SPR aptasensors for drug discovery as well as disease diagnosis and monitoring. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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27 pages, 7352 KiB  
Article
Sensing of Volatile Organic Compounds by Haller’s Structure in Ixodidae Tick: Electroscutumography and Olfactometric Bioassay
by Alivia Mandal, Bishwajeet Paul, Biswanath Bhowmik, Raja Reddy Gundreddy, Adolat U. Mirzaieva and Kakali Bhadra
Biosensors 2025, 15(6), 358; https://doi.org/10.3390/bios15060358 - 4 Jun 2025
Viewed by 283
Abstract
Background: Chemosensation in ticks opens a novel and unique field for scientific research. This study highlights ticks’ chemosensory system to comprehend its host-searching behavior and other integrated chemistry and biology involving Haller’s structure. Methodology: This study combines microanatomical, electrophysiological, and behavioral experiments to [...] Read more.
Background: Chemosensation in ticks opens a novel and unique field for scientific research. This study highlights ticks’ chemosensory system to comprehend its host-searching behavior and other integrated chemistry and biology involving Haller’s structure. Methodology: This study combines microanatomical, electrophysiological, and behavioral experiments to investigate the role of Haller’s organ in adult ticks in response to different classes of organic compounds. Results: We showed the microscopic anatomy of Haller’s organ in Haemaphysalis darjeeling, present at the terminal segment of the first pair of appendages. Haller’s structure serves a vital function in perceiving odor. The electrophysiological activity of adult ticks to different classes of organic compounds via electroscutumography was explored at five different concentrations: w/v 0.001, 0.01, 0.1, 1.0, and 2.0%. Among 55 organic compounds, moderate to high stimulation was recorded with pyruvate (13.28 mv at 2%), ammonia (12.26 mv at 2%), benzoic acid (1.99 mv at 0.001%), isobutyric acid (1.39 mv at 0.001%), 2,6-dichlorophenol (1.34 mv at 0.001%), p-Tolualdehyde (1.26 mv at 2%), tetradecane (1.23 mv at 2%), docosane (1.17 mv at 2%), citronellal (1.13 mv at 0.1%), isopropyl acetate (1.05 mv at 0.01%), cyclohexanol (1.03 mv at 2%), 1-octane-3-ol (1.02 mv at 2%), and 1-octanol (1.01 mv at 0.001%). Olfactometric bioassays at w/v 2.0% concentration further confirmed that ammonia, pyruvate, 1-octane-3-ol, hematin porcine, p-Tolualdehyde, methyl salicylate, uric acid, tetradecane, carbon dioxide, propanoic acid, 3-hexanol, hexanoic acid, adenine, 2,6-dichlorophenol, hexadecane, heptanoic acid, pentanoic acid, octadecane, guanine, and nonanoic acid acted as strong attractants, while citronellal, eugenol, butyric acid, geraniol, benzaldehyde, and tiglic aldehyde showed an active repellent effect against the tick species. Conclusions: This investigation provides knowledge of the olfactory sensilla of Haller’s structure as biosensors behind tick olfaction and the possibility for chemical detection of diverse attractants and repellents for future development of anti-tick compounds. Full article
(This article belongs to the Section Environmental Biosensors and Biosensing)
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16 pages, 4359 KiB  
Article
Nonlinear Imaging Detection of Organ Fibrosis in Minute Samples for Early Stage Utilizing Dual-Channel Two-Photon and Second-Harmonic Excitation
by Bo-Song Yu, Qing-Di Cheng, Yi-Zhou Liu, Rui Zhang, Da-Wei Li, Ai-Min Wang, Li-Shuang Feng and Xiao Jia
Biosensors 2025, 15(6), 357; https://doi.org/10.3390/bios15060357 - 4 Jun 2025
Viewed by 209
Abstract
Histopathological staining remains the fibrosis diagnostic gold standard yet suffers from staining artifacts and variability. Nonlinear optical techniques (e.g., spontaneous fluorescence, Second Harmonic Generation) enhance accuracy but struggle with rapid trace-level detection of fibrosis. To address these limitations, a dual-channel nonlinear optical imaging [...] Read more.
Histopathological staining remains the fibrosis diagnostic gold standard yet suffers from staining artifacts and variability. Nonlinear optical techniques (e.g., spontaneous fluorescence, Second Harmonic Generation) enhance accuracy but struggle with rapid trace-level detection of fibrosis. To address these limitations, a dual-channel nonlinear optical imaging system with excitation wavelengths at 780 nm and 820 nm was developed, enabling simultaneous spontaneous fluorescence and second-harmonic generation imaging through grid localization. This study applies dual-modality nonlinear imaging to achieve label-free, high-resolution visualization of pulmonary and renal fibrosis at the ECM microstructure scale. Through leveraging this system, it is demonstrated that collagen can be rapidly detected via spontaneous fluorescence at 780 nm, whereas the spatial distribution of collagen fibrils is precisely mapped using Second Harmonic Generation at 820 nm. This approach allows for the rapid and sensitive detection of trace fibrosis in a 5-day unilateral ureteral obstruction mouse model. Additionally, we identify that the elastic fibers, which can also be visualized, provide a foundation for staging diagnosis and delivering accurate and quantitative data for pathological studies and analysis. The research findings underscore the potential of this dual-channel nonlinear optical imaging system as a powerful tool for rapid, precise, and noninvasive fibrosis detection and staging. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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19 pages, 7961 KiB  
Article
A Gait Sub-Phase Switching-Based Active Training Control Strategy and Its Application in a Novel Rehabilitation Robot
by Junyu Wu, Ran Wang, Zhuoqi Man, Yubin Liu, Jie Zhao and Hegao Cai
Biosensors 2025, 15(6), 356; https://doi.org/10.3390/bios15060356 - 4 Jun 2025
Viewed by 259
Abstract
This research study proposes a heuristic hybrid deep neural network (DNN) gait sub-phase recognition model based on multi-source heterogeneous motion data fusion which quantifies gait phases and is applied in balance disorder rehabilitation control, achieving a recognition accuracy exceeding 99%. Building upon this [...] Read more.
This research study proposes a heuristic hybrid deep neural network (DNN) gait sub-phase recognition model based on multi-source heterogeneous motion data fusion which quantifies gait phases and is applied in balance disorder rehabilitation control, achieving a recognition accuracy exceeding 99%. Building upon this model, a motion control strategy for a novel rehabilitation training robot is designed and developed. For patients with some degree of independent movement, an active training strategy is introduced; it combines gait recognition with a variable admittance control strategy. This strategy provides assistance during the stance phase and moderate support during the swing phase, effectively enhancing the patient’s autonomous movement capabilities and increasing engagement in the rehabilitation process. The gait phase recognition system not only provides rehabilitation practitioners with a comprehensive tool for patient assessment but also serves as a theoretical foundation for collaborative control in rehabilitation robots. Through the innovative active–passive training control strategy and its application in the novel rehabilitation robot, this research study overcomes the limitations of traditional rehabilitation robots, which typically operate in a single functional mode, thereby expanding their functional boundaries and enabling more precise, personalized rehabilitation training programs tailored to the needs of patients in different stages of recovery. Full article
(This article belongs to the Special Issue Wearable Sensors for Precise Exercise Monitoring and Analysis)
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31 pages, 4568 KiB  
Review
Stimuli-Responsive DNA Hydrogel Design Strategies for Biomedical Applications
by Minhyuk Lee, Minjae Lee, Sungjee Kim and Nokyoung Park
Biosensors 2025, 15(6), 355; https://doi.org/10.3390/bios15060355 - 4 Jun 2025
Viewed by 289
Abstract
Hydrogels are three-dimensional network structures composed of hydrophilic polymers that can swell in water and are very similar to soft tissues such as connective tissue or the extracellular matrix. DNA hydrogels are particularly notable for biomedical applications due to their high biocompatibility, physiological [...] Read more.
Hydrogels are three-dimensional network structures composed of hydrophilic polymers that can swell in water and are very similar to soft tissues such as connective tissue or the extracellular matrix. DNA hydrogels are particularly notable for biomedical applications due to their high biocompatibility, physiological stability, molecular recognition, biodegradability, easy functionalization, and low immunogenicity. Based on these advantages, stimuli-responsive DNA hydrogels that have the property of reversibly changing their structure in response to various microenvironments or molecules are attracting attention as smart nanomaterials that can be applied to biosensing and material transfer, such as in the case of cells and drugs. As DNA nanotechnology advances, DNA can be hybridized with a variety of nanomaterials, from inorganic nanomaterials such as gold nanoparticles (AuNPs) and quantum dots (QDs) to synthetic polymers such as polyacrylamide (PAAm) and poly(N-isopropylacrylamide) (pNIPAM). These hybrid structures exhibit various optical and chemical properties. This review discusses recent advances and remaining challenges in biomedical applications of stimuli-responsive smart DNA hydrogel-based systems. It also highlights various types of hybridized DNA hydrogel, explores various response mechanism strategies of stimuli-responsive DNA hydrogel, and provides insights and prospects for biomedical applications such as biosensing and drug delivery. Full article
(This article belongs to the Special Issue Hydrogel-Based Biosensors: From Design to Applications)
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14 pages, 1793 KiB  
Article
A Metal–Organic Hybrid Composed of Dual Quenching Cofactors as a Nanoquencher for the Fluorescent Determination of Protease Caspase-3
by Fengli Gao, Lin Liu, Cancan He, Yong Chang and Weiqiang Wang
Biosensors 2025, 15(6), 354; https://doi.org/10.3390/bios15060354 - 4 Jun 2025
Viewed by 244
Abstract
Nanoquenchers with a single quenching cofactor exhibit limited fluorescence quenching efficiency. In this work, a metal–organic hybrid with dual quenching cofactors (Cu2+ and pyrroloquinoline quinone or PQQ) was prepared by metal-coordinated assembly and used as a nanoquencher for a protease assay with [...] Read more.
Nanoquenchers with a single quenching cofactor exhibit limited fluorescence quenching efficiency. In this work, a metal–organic hybrid with dual quenching cofactors (Cu2+ and pyrroloquinoline quinone or PQQ) was prepared by metal-coordinated assembly and used as a nanoquencher for a protease assay with enhanced quenching efficiency. The peptide substrate with an oligohistidine (His6) tag was labeled with a fluorophore. Caspase-3 was determined as a protease example. The substrate was attached onto the surface of the Cu-PQQ nanoquencher by a metal coordination interaction between the unsaturated Cu2+ on the nanoparticle surface and the His6 tag in the peptide. The cleavage of the peptide substrate by enzymatic hydrolysis led to the release of a fluorophore-conjugated segment from the nanoquencher surface, thus turning on the fluorescence. The nanoprobe was used to determine caspase-3 with a linear range of 0.01–5 ng/mL and a detection limit of 7 pg/mL. Furthermore, the method was used to evaluate inhibition efficiency and monitor drug-induced cell apoptosis. In contrast to other means of peptide immobilization, such as physical adsorption and covalent coupling, the strategy based on the metal coordination interaction is simple and powerful, thereby achieving assays of caspase-3 activity in lysates with a satisfactory result. The work should be valuable for the design of nanoquenchers with multiple quenching cofactors and the development of novel biosensors. Full article
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14 pages, 2190 KiB  
Article
Flow-Based Dielectrophoretic Biosensor for Detection of Bacteriophage MS2 as a Foodborne Virus Surrogate
by Inae Lee, Heejin So, Kacie K. H. Y. Ho, Yong Li and Soojin Jun
Biosensors 2025, 15(6), 353; https://doi.org/10.3390/bios15060353 - 3 Jun 2025
Viewed by 255
Abstract
Norovirus, a foodborne pathogen, causes a significant economic and health burden globally. Although detection methods exist, they are expensive and non-field deployable. A flow-based dielectrophoretic biosensor was designed for the detection of foodborne pathogenic viruses and was tested using bacteriophage MS2 as a [...] Read more.
Norovirus, a foodborne pathogen, causes a significant economic and health burden globally. Although detection methods exist, they are expensive and non-field deployable. A flow-based dielectrophoretic biosensor was designed for the detection of foodborne pathogenic viruses and was tested using bacteriophage MS2 as a norovirus surrogate. The flow-based MS2 sensor comprises a concentrator and a detector. The concentrator is an interdigitated electrode array designed to impart dielectrophoretic effects to manipulate viral particles toward the detector in a fluidic channel. The detector is made of a silver electrode conjugated with anti-MS2 IgG to allow for antibody–antigen biorecognition events and is supplied with the electrical current for the purpose of measurement. Serially diluted MS2 suspensions were continuously injected into the fluidic channel at 0.1 mL/min. A cyclic voltammogram indicated that current measurements from single-walled carbon nanotube (SWCNT)-coated electrodes increased compared to uncoated electrodes. Additionally, a drop in the current measurements after antibody immobilization and MS2 capture was observed with the developed electrodes. Antibody immobilization at the biorecognition site provided greater current changes with the antibody-MS2 complexes vs. the assays without antibodies. The electric field applied to the fluidic channel at 10 Vpp and 1 MHz contributed to an increase in current changes in response to MS2 bound on the detector and was dependent on the MS2 concentrations in the sample. The developed biosensor was able to detect MS2 with a sensitivity of 102 PFU/mL within 15 min. Overall, this work demonstrates a proof of concept for a rapid and field-deployable strategy to detect foodborne pathogens. Full article
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12 pages, 1598 KiB  
Article
Autofluorescence Imaging of Parathyroid and Thyroid Under Visible and Near-IR Light Excitation
by Zhenguo Wu, Sam M. Wiseman and Haishan Zeng
Biosensors 2025, 15(6), 352; https://doi.org/10.3390/bios15060352 - 3 Jun 2025
Viewed by 188
Abstract
Identifying parathyroid glands during surgery is challenging and time-consuming due to their small size (3–5 mm) and camouflaged appearance in the background of the thyroid, lymph nodes, fat, and other neck structures. For the gland itself, it is also important to differentiate abnormal [...] Read more.
Identifying parathyroid glands during surgery is challenging and time-consuming due to their small size (3–5 mm) and camouflaged appearance in the background of the thyroid, lymph nodes, fat, and other neck structures. For the gland itself, it is also important to differentiate abnormal ones from normal ones. Accidental damage or removal of the normal glands can result in complications like hypocalcemia, which may necessitate lifelong medication dependence, and, in extreme cases, lead to death. The study of autofluorescence optical properties of normal and abnormal parathyroid glands and the surrounding tissue will be helpful for developing non-invasive detection devices. The near-infrared (NIR) autofluorescence characteristics of parathyroid and thyroid tissues have been studied extensively and are now used for parathyroid gland detection during surgery. Additionally, there have been a few reports on the UV-visible light-excited autofluorescence characteristics of these tissues with a focus on spectroscopy. However, there is a lack of high-resolution, side-by-side autofluorescence imaging comparisons of both tissue types under various excitation wavelengths, ranging from visible to NIR. We developed a standalone tabletop autofluorescence imaging system to acquire images of ex vivo specimens in the operating room under different excitation wavelengths: visible 405 nm, 454 nm, 520 nm, 628 nm, and NIR 780 nm. Autofluorescence imaging features of parathyroid adenomas for each excitation wavelength were described and compared. It was found that visible light excites much stronger autofluorescence from parathyroid adenoma tissue compared to NIR light. However, NIR excitation provides the best intensity difference/contrast between parathyroid adenoma and thyroid tissue, making it optimal for differentiating these two tissue types, and detecting parathyroid adenoma during surgery. The high fluorescent site under the NIR 780 nm excitation also generates high fluorescence under visible excitation wavelengths. Heterogeneous fluorescence patterns were observed in most of the parathyroid adenoma cases across all the excitation wavelengths. Full article
(This article belongs to the Special Issue Advanced Optical Methods for Biosensing)
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25 pages, 4644 KiB  
Review
Non-Invasive Wearables in Inflammation Monitoring: From Biomarkers to Biosensors
by Tingting Wu and Guozhen Liu
Biosensors 2025, 15(6), 351; https://doi.org/10.3390/bios15060351 - 1 Jun 2025
Viewed by 512
Abstract
Quantifying inflammation plays a critical role in understanding the progression and development of various diseases. Non-invasive or minimally invasive wearable biosensors have garnered significant attention in recent years due to their convenience, comfort, and ability to provide continuous monitoring of biomarkers, particularly in [...] Read more.
Quantifying inflammation plays a critical role in understanding the progression and development of various diseases. Non-invasive or minimally invasive wearable biosensors have garnered significant attention in recent years due to their convenience, comfort, and ability to provide continuous monitoring of biomarkers, particularly in infectious diseases and chronic diseases. However, there are still areas for improvement in developing reliable biosensing devices to detect key inflammatory biomarkers in clinically relevant biofluids. This review first introduces common biofluids with a focus on the most clinically significant inflammatory biomarkers. Specifically, it discusses the challenges encountered in extracting and detecting analytes in these biofluids. Subsequently, we review three popular types of non-invasive wearable biosensors for inflammation monitoring (microneedle patches, flexible electronic skins, and textile-based sensors). The design and operational considerations of these devices are analyzed, followed by an exploration of the information processing approaches employed during data processing. Finally, we envision future opportunities by guiding the development and refinement of non-invasive or minimally invasive wearable biosensors for continuous inflammation monitoring in chronic diseases. Full article
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29 pages, 7096 KiB  
Review
Recent Progress on the Application of Microneedles for In Situ Sampling in Surface-Enhanced Raman Scattering Detection
by Weiqing Yang, Ying Chen, Xingliang Cheng, Shuojiang Liu, Huiqi Zhu and Yuling Hu
Biosensors 2025, 15(6), 350; https://doi.org/10.3390/bios15060350 - 1 Jun 2025
Viewed by 466
Abstract
The efficient and non-invasive collection of biological samples has become a critical challenge for the continued development of surface-enhanced Raman scattering (SERS). When integrated with minimally invasive microneedle (MN) sampling technology, SERS enhances its applicability in real-time, non-invasive molecular detection. This review focuses [...] Read more.
The efficient and non-invasive collection of biological samples has become a critical challenge for the continued development of surface-enhanced Raman scattering (SERS). When integrated with minimally invasive microneedle (MN) sampling technology, SERS enhances its applicability in real-time, non-invasive molecular detection. This review focuses on the latest advances in MN-based SERS sensors. Firstly, a comprehensive summary is presented of MN types and research progress in the design and engineering of SERS-active MNs. Then, the sampling method of SERS MNs and the MN-based SERS detection mode are also described in detail. Finally, the applications of SERS MNs in fields such as disease diagnosis, drug monitoring, and food safety are highlighted. Additionally, current challenges are discussed and future development prospects are prospected with the aim of contributing to the design of MN-based SERS sensors for diverse applications. Full article
(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)
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19 pages, 1121 KiB  
Review
Betalain Pigments: Isolation and Application as Reagents for Colorimetric Methods and Biosensors
by Rimadani Pratiwi, Devita Salsa Maharani and Sarah Gustia Redjeki
Biosensors 2025, 15(6), 349; https://doi.org/10.3390/bios15060349 - 1 Jun 2025
Viewed by 307
Abstract
Betalains are hydrophilic natural pigments commonly found in plants of the Caryophyllales order, as well as in specific species and genera of fungi, such as Hygrocybe, Hygrophorus, and Amanita muscaria. Betalains are sorted into two groups: betacyanins, which form red-violet [...] Read more.
Betalains are hydrophilic natural pigments commonly found in plants of the Caryophyllales order, as well as in specific species and genera of fungi, such as Hygrocybe, Hygrophorus, and Amanita muscaria. Betalains are sorted into two groups: betacyanins, which form red-violet pigments, and betaxanthins, which form yellow-orange pigments. These compounds can be employed as colorimetric sensors and biosensors. This paper provides a review of the isolation methods of betalains and the various applications of betalains as colorimetric sensors and biosensors. The review was conducted by collecting publications over the last decade. The results show that betalains can be used as a colorimetric sensor to identify metal compounds in water and nonmetal compounds that indicate the quality of food. In addition, betaxanthin has been used for developing cell-based biosensors from yeast and bacteria. Furthermore, betalain as a colorimetric sensor and biosensor is developed by using an innovative digital detector, such as a smartphone. Nevertheless, the fragile stability of betalains presents a significant barrier during the extraction. As a result, future studies could focus on adding innovative technologies for optimizing extraction and also developing betalain as novel bio-indicators for specific analytes. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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13 pages, 7042 KiB  
Article
Electrochemical Sensor Capable of Enhancing Dopamine Sensitivity Based on Micron-Sized Metal–Organic Frameworks
by Ruhui Yan, Yuewu Zhao, Huaixiao Geng, Mengxia Yan, Jine Wang and Shuang Han
Biosensors 2025, 15(6), 348; https://doi.org/10.3390/bios15060348 - 30 May 2025
Viewed by 226
Abstract
Micron-sized, ultrathin metal–organic framework (MOF) sheet is a two-dimensional (2D) hybrid material with a large specific surface area, which can be used not only in the fields of energy and biomedicine, but also in electrode modification to improve the electrochemical detection effect. In [...] Read more.
Micron-sized, ultrathin metal–organic framework (MOF) sheet is a two-dimensional (2D) hybrid material with a large specific surface area, which can be used not only in the fields of energy and biomedicine, but also in electrode modification to improve the electrochemical detection effect. In this work, the 2D-structured Co-TCPP(Fe) MOF sheets were synthesized from porphyrin molecules and cobalt ions and then combined with reduced graphene oxide (rGO) and perfluorosulfonic acid polymer (Nafion) solution to construct Co-TCPP(Fe)/rGO/Nafion-modified electrodes capable of sensitively capturing dopamine (DA). The 2D ultrathin lamellar structure of this electrode-modified material is beneficial to the formation of π-π stacking effect with DA molecules, and the oxygen-containing groups carried on its surface can also form electrostatic attraction with the amino groups of DA molecules. Therefore, the Co-TCPP(Fe)/rGO/Nafion-modified electrode under the synergistic effect shows a specific adsorption effect on DA molecules, resulting in high anti-interference ability and a low detection limit of 0.014 µM in the concentration range of 0.1–100 µM. Furthermore, the Co-TCPP(Fe)/rGO/Nafion composite material composed of micron-sized, ultrathin lamellar structures also shows high reusability due to the stability of its coordination structure and can demonstrate good results when applied to the actual sample detection of human urine. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Framework Materials)
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11 pages, 2484 KiB  
Communication
Novel Device for Intraoperative Quantitative Measurements of Extraocular Muscle Tensile Strength
by Hyun Jin Shin, Minung Park, Hyunkyoo Kang and Andrew G. Lee
Biosensors 2025, 15(6), 347; https://doi.org/10.3390/bios15060347 - 30 May 2025
Viewed by 253
Abstract
Understanding the tensile properties of extraocular muscles (EOMs) is crucial for successful strabismus surgery and accurate predictions of surgical outcomes. Assessments of EOM tensile strength are traditionally highly dependent on the expertise of the ophthalmic surgeon, since they involve manually pulling the EOM [...] Read more.
Understanding the tensile properties of extraocular muscles (EOMs) is crucial for successful strabismus surgery and accurate predictions of surgical outcomes. Assessments of EOM tensile strength are traditionally highly dependent on the expertise of the ophthalmic surgeon, since they involve manually pulling the EOM in opposite directions. This approach only provides subjective measurements that are not quantifiable. Previous quantitative approaches have utilized various devices such as implanted force transducers or dial tension gauges connected to muscle tendons with nylon sutures, but these methods are complex and so are rarely used outside of research settings. Consequently, the goal of this study was to create a quantitative and clinically applicable device for assessing EOM tensile strength. This developed device uses a strabismus hook connected to a strain gauge load cell that measures the tensile force and includes a tilting sensor to ensure that the hook is pulled at a consistent angle when a force is applied. The performance of the device was tested on 22 EOMs in 11 patients with intermittent exotropia during surgery for resecting the medial rectus (MR) and recessing the lateral rectus (LR) under general anesthesia. The measured tensile strengths of the MR and LR were 284.9 ± 58.3 and 278.3 ± 64.6 g (mean ± SD), respectively. In conclusion, the novel device developed in this study for quantitative measurements of EOM tensile strength in clinical settings will facilitate understanding of the pathophysiology of strabismus, as well as of the mechanical properties of the EOMs, and enhance the precision of surgical interventions. Full article
(This article belongs to the Section Biosensors and Healthcare)
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