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Journal Description

Biosensors

Biosensors is an international, peer-reviewed, open access journal on the technology and science of biosensors published monthly online by MDPI.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, CAPlus / SciFinder, Inspec, and other databases.
Journal Rank: JCR - Q1 (Chemistry, Analytical) / CiteScore - Q1 (Instrumentation)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.9 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.

Impact Factor: 4.9 (2023); 5-Year Impact Factor: 5.2 (2023)

Imprint Information Journal Flyer Open Access ISSN: 2079-6374

Latest Articles

12 pages, 1925 KiB

Open AccessArticle

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 (registering DOI) - 9 Jun 2025

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

Open AccessCommunication

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 (registering DOI) - 7 Jun 2025

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 (

R^{2}

) 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

Open AccessArticle

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

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

(This article belongs to the Special Issue Advances in Flexible Bioelectronics and Intelligent Biosensing Systems)

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15 pages, 3593 KiB

Open AccessArticle

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

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

(This article belongs to the Special Issue Wearable and Implantable Bioelectronics for Advanced Biosensing and Human Health Monitoring)

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24 pages, 898 KiB

Open AccessArticle

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

This study investigated the effect of wearable ultrasound-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 provided by [...] Read more.

This study investigated the effect of wearable ultrasound-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 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)

13 pages, 1960 KiB

Open AccessArticle

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

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

Open AccessReview

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

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

Open AccessReview

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

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

Open AccessArticle

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

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

(This article belongs to the Special Issue Electrochemical (Bio)Sensors as Promising Analytical Tools in the Analysis of Soils, Plants and Environmental Monitoring)

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20 pages, 1022 KiB

Open AccessReview

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

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

Open AccessReview

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

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

Open AccessArticle

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

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

Open AccessArticle

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

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

Open AccessArticle

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

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

Open AccessReview

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

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

Open AccessArticle

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

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

(This article belongs to the Special Issue Nanosensors for the Detection and Characterization of Food, Environmental and Medical Samples—2nd Edition)

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14 pages, 2190 KiB

Open AccessArticle

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

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 V_pp 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

(This article belongs to the Special Issue Cell-Based Biosensors for Rapid Detection and Monitoring (2nd Edition))

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12 pages, 1598 KiB

Open AccessArticle

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

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

Open AccessReview

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

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

(This article belongs to the Special Issue Wearable and Implantable Bioelectronics for Advanced Biosensing and Human Health Monitoring)

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29 pages, 7096 KiB

Open AccessReview

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

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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