Biosensors

10 pages, 4315 KiB

Open AccessArticle

Point-of-Care NSE Biosensor for Objective Assessment of Stroke Risk

by Cheng Hsu Chen, Erick Wang, Tsung-Han Lee, Cheng-Chieh Huang, Chun-San Tai, Yan-Ren Lin and Wen-Liang Chen

Biosensors 2025, 15(4), 264; https://doi.org/10.3390/bios15040264 - 20 Apr 2025

Abstract

The rapid identification of stroke is critical to improving stroke patient outcomes. Existing protocols for assessing the risk of stroke are subjective and may be further complicated by nonspecific symptoms, increasing the risk of misdiagnosis. Neuron-specific enolase (NSE) has emerged as a promising [...] Read more.

The rapid identification of stroke is critical to improving stroke patient outcomes. Existing protocols for assessing the risk of stroke are subjective and may be further complicated by nonspecific symptoms, increasing the risk of misdiagnosis. Neuron-specific enolase (NSE) has emerged as a promising stroke biomarker. However, current detection methods such as the electrochemiluminescence immunoassay (ECLIA) are time-consuming and costly. In this research, we developed an electrochemical biosensor for the rapid quantification of NSE in whole blood. Mouse stroke models were established, and blood samples collected were analyzed using both hospital-standard ECLIA as well as the biosensor. The biosensor limit of detection was 1.15 ng/mL. NSE measurements were highly correlated between the two methods and were obtained in 5 min using 20 μL of unprocessed whole blood samples. Notably, the biosensor could accurately quantify elevated blood NSE blood that was associated with more severe stroke. Our results demonstrate the utility of the proposed biosensor in pre-hospital settings. Combined with existing stroke assessment methods, the biosensor may enable emergency personnel to identify stroke risk with greater accuracy to optimize the chances of receiving necessary treatment within the effective window. Full article

(This article belongs to the Special Issue Applications of Cutting-Edge Biosensors in Environment, Food and Healthcare Field)

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16 pages, 1263 KiB

Open AccessArticle

Smart Prussian Blue Analog Decorated with Zinc Oxide Nanohybrid: Fluorescent Sensing and Sustainability of Sunset Yellow in Food and Environment

by Hany A. Batakoushy, Amr K. A. Bass, Hassanien Gomaa, Sami El Deeb and Adel Ehab Ibrahim

Biosensors 2025, 15(4), 263; https://doi.org/10.3390/bios15040263 - 20 Apr 2025

Abstract

In the current study, the Prussian blue analog decorated with zinc oxide (PBA@ZnO) was produced using a simple chemical co-precipitation method. The nanohybrid was examined using XRD, EDX, SEM, and TEM techniques, where it exhibited a polycrystalline structure with highly intense broadening peaks. [...] Read more.

In the current study, the Prussian blue analog decorated with zinc oxide (PBA@ZnO) was produced using a simple chemical co-precipitation method. The nanohybrid was examined using XRD, EDX, SEM, and TEM techniques, where it exhibited a polycrystalline structure with highly intense broadening peaks. The surface morphology was observed as thin nanosheets decorated with tiny spheres. Following excitation at 360 nm, the fluorescence spectra of PBA@ZnO showed fluorescence emission at 455 nm. The developed PBA@ZnO was used to qualitatively and quantitatively assess sunset yellow (SY), where its native fluorescence was selectively quenched as SY concentrations increased. For the first time, PBA@ZnO was used as a turn-off nano-sensor for the spectrofluorimetric measurement of SY. The method’s markable sensitivity was demonstrated within an SY linearity range of 50–500 ng/mL, where the limit of detection was calculated as 9.77 ng/mL. Real sample analysis in the food industry, including samples from real food, soft drinks, and sun cream, was made possible by the detection of tiny amounts of SY. Analytical Greenness (AGREE), AGREEprep, and the complementing Green Analytical Procedure Index (Complex MoGAPI) were used to illustrate the new approach’s exceptional eco-friendliness and greenness. The RGB 12 algorithm worked to demonstrate that the suggested approach is less costly, more environmentally friendly, more sustainable, analytically sound, and whiter than the ones that were previously published. In accordance with ICH principles, the suggested method was validated. This approach offers a promising way to rapidly and accurately identify and measure SY in the food industry, helping to guarantee food safety and maintain the health of customers. Full article

(This article belongs to the Special Issue Innovative Biosensing Technologies for Sustainable Healthcare)

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15 pages, 3266 KiB

Open AccessArticle

Distinct Neural Activities in Hippocampal Subregions Revealed Using a High-Performance Wireless Microsystem with PtNPs/PEDOT:PSS-Enhanced Microelectrode Arrays

by Peiyao Jiao, Qianli Jia, Shuqi Li, Jin Shan, Wei Xu, Yu Wang, Yu Liu, Mingchuan Wang, Yilin Song, Yulian Zhang, Yanbing Yu, Mixia Wang and Xinxia Cai

Biosensors 2025, 15(4), 262; https://doi.org/10.3390/bios15040262 - 18 Apr 2025

Viewed by 104

Abstract

Wireless microsystems for neural signal recording have emerged as a solution to overcome the limitations of tethered systems, which restrict the mobility of subjects and introduce noise interference. However, existing microsystems often face data throughput, signal processing, and long-distance wireless transmission challenges. This [...] Read more.

Wireless microsystems for neural signal recording have emerged as a solution to overcome the limitations of tethered systems, which restrict the mobility of subjects and introduce noise interference. However, existing microsystems often face data throughput, signal processing, and long-distance wireless transmission challenges. This study presents a high-performance wireless microsystem capable of 32-channel, 30 kHz real-time recording, featuring Field Programmable Gate Array (FPGA)-based signal processing to reduce transmission load. The microsystem is integrated with platinum nanoparticles/poly (3,4-ethylenedioxythiophene) polystyrene sulfonate-enhanced microelectrode arrays for improved signal quality. A custom NeuroWireless platform was developed for seamless data reception and storage. Experimental validation in rats demonstrated the microsystem’s ability to detect spikes and local field potentials from the hippocampal CA1 and CA2 subregions. Comparative analysis of the neural signals revealed distinct activity patterns between these subregions. The wireless microsystem achieves high accuracy and throughput over distances up to 30 m, demonstrating its resilience and potential for neuroscience research. This work provides a compact, adaptable solution for multi-channel neural signal detection and offers a foundation for future applications in brain–computer interfaces. Full article

(This article belongs to the Special Issue Implantable, Wireless Biosensors and Biodevices for Neuroscience Research, 2nd Edition)

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11 pages, 3253 KiB

Open AccessArticle

Development of a Smartphone-Linked Immunosensing System for Oxytocin Determination

by Miku Sarubo, Yoka Suzuki, Yuka Numazaki and Hiroyuki Kudo

Biosensors 2025, 15(4), 261; https://doi.org/10.3390/bios15040261 - 18 Apr 2025

Viewed by 94

Abstract

We report an optical immunosensing system for oxytocin (OXT) based on image analysis of color reactions in an enzyme-linked immunosorbent assay (ELISA). We employed a miniaturized optical immunosensing unit that was functionally connected to an LED and a smartphone camera. Our system measures [...] Read more.

We report an optical immunosensing system for oxytocin (OXT) based on image analysis of color reactions in an enzyme-linked immunosorbent assay (ELISA). We employed a miniaturized optical immunosensing unit that was functionally connected to an LED and a smartphone camera. Our system measures OXT levels using a metric called the RGBscore, which is derived from the red, green, and blue (RGB) information in the captured images. By calculating the RGBscore regressively using the brute-force method, this approach can be applied to smartphones with various CMOS image sensors and firmware. The lower detection limit was determined to be 5.26 pg/mL, and the measurement results showed a higher correlation (r = 0.972) with those obtained from conventional ELISA. These results suggest the potential for its application in a simplified health management system for individuals. Full article

(This article belongs to the Special Issue Biosensors Based on Microfluidic Devices—2nd Edition)

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16 pages, 4048 KiB

Open AccessReview

Challenges of Using Whole-Cell Bioreporter for Assessment of Heavy Metal Bioavailability in Soil/Sediment

by Shanshan Bai, Zhipeng Liu, Jiazhi Xu, Yongshuo Li, Zirun Zhang, Zefeng Huang, Williamson Gustave, Boling Li, Xiaokai Zhang and Feng He

Biosensors 2025, 15(4), 260; https://doi.org/10.3390/bios15040260 - 18 Apr 2025

Viewed by 100

Abstract

Soil and sediment contamination with heavy metals (HMs) is a critical environmental issue, posing significant risks to both ecosystems and human health. Whole-cell bioreporter (WCB) technology offers a promising alternative to traditional detection techniques due to its ability to rapidly assess the bioavailability [...] Read more.

Soil and sediment contamination with heavy metals (HMs) is a critical environmental issue, posing significant risks to both ecosystems and human health. Whole-cell bioreporter (WCB) technology offers a promising alternative to traditional detection techniques due to its ability to rapidly assess the bioavailability of pollutants. Specifically, lights-on WCBs quantify pollutant bioavailability by measuring bioluminescence or fluorescence in response to pollutant exposure, demonstrating comparable accuracy to traditional methods for quantitative pollutant detection. However, when applied to soil and sediment, the signal intensity directly measured by WCBs is often attenuated due to interference from solid particles, leading to the underestimation of bioavailability. Currently, no standardized method exists to correct for this signal attenuation. This review provides a critical analysis of the benefits and limitations of traditional detection methods and WCB technology in assessing HM bioavailability in soil and sediment. Based on the approaches used to address WCB signal attenuation, correction methods are categorized into four types: the assumed negligible method, the non-inducible luminescent control method, the addition of a standard to a reference soil, and a pre-exposure bioreporter. We provide a comprehensive analysis of each method’s applicability, benefits, and limitations. Lastly, potential future directions for advancing WCB technology are proposed. This review seeks to establish a theoretical foundation for researchers and environmental professionals utilizing WCB technology for pollutant bioavailability assessment in soil and sediment. Full article

(This article belongs to the Special Issue Application of Biosensors in Environmental Monitoring)

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16 pages, 4084 KiB

Open AccessArticle

Movement Recognition and Muscle Force Estimation of Wrist Based on Electromyographic Signals of Forearm

by Leiyu Zhang, Zhenxing Jiao, Yongzhen Li and Yawei Chang

Biosensors 2025, 15(4), 259; https://doi.org/10.3390/bios15040259 - 17 Apr 2025

Viewed by 95

Abstract

To enhance wrist impairment rehabilitation efficiency, self-rehabilitation training using healthy-side forearm sEMG was introduced, improving patient engagement and proprioception. A sEMG-based movement recognition and muscle force estimation algorithm was proposed to transmit the estimated results to a wrist rehabilitation robot. Dominant eigenvalues of [...] Read more.

To enhance wrist impairment rehabilitation efficiency, self-rehabilitation training using healthy-side forearm sEMG was introduced, improving patient engagement and proprioception. A sEMG-based movement recognition and muscle force estimation algorithm was proposed to transmit the estimated results to a wrist rehabilitation robot. Dominant eigenvalues of raw forearm EMG signals were selected to construct a movement recognition model that included a BPNN, a voting decision, and an intensified algorithm. An experimental platform for muscle force estimation was established to measure sEMG under various loads. The linear fitting was performed between mean absolute values (MAVs) and external loads to derive static muscle force estimation models. A dynamic muscle force estimation model was established through linear fitting average MAVs. Volunteers wore EMG sensors and performed six typical movements to complete the verification experiment. The average accuracy of only BPNN was 90.7%, and after the addition of the voting decision and intensified algorithm, it was improved to 98.7%. In the resistance training, the measured and estimated muscle forces exhibited similar trends, with RMSE of 4.2 N for flexion/extension and 5.8 N for ulnar/radial deviation. Under two different speeds and loads, the theoretical and estimated values of dynamic muscle forces showed similar trends with almost no phase difference, and the estimation accuracy was better during flexion movements compared to radial deviations. The proposed algorithms had strong versatility and practicality, aiming to realize the self-rehabilitation trainings of patients. Full article

(This article belongs to the Section Wearable Biosensors)

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15 pages, 3390 KiB

Open AccessArticle

Achievement of 15-Minute Adaptive PCR Benchmark with 1370 nm Laser Heating

by Nicholas Spurlock, Rosana Alfaro, William E. Gabella, Kunal Chugh, Megan E. Pask, Franz Baudenbacher and Frederick R. Haselton

Biosensors 2025, 15(4), 258; https://doi.org/10.3390/bios15040258 - 17 Apr 2025

Viewed by 128

Abstract

In low-resource and point-of-care settings, traditional PCR often faces challenges of poor sample preparation, adverse environmental conditions, and long assay times. We have previously described a laboratory-based instrument to achieve “adaptive” PCR, a PCR thermocycling control system that replaces preset cycling times and [...] Read more.

In low-resource and point-of-care settings, traditional PCR often faces challenges of poor sample preparation, adverse environmental conditions, and long assay times. We have previously described a laboratory-based instrument to achieve “adaptive” PCR, a PCR thermocycling control system that replaces preset cycling times and temperatures with the optical monitoring of added L-DNA stereoisomers matching the sequences of the reaction primers and target. These L-DNA biosensors directly monitor DNA hybridization, compensating for ambient environmental conditions and poor sample preparation. This report describes instrument simplifications and a comparative evaluation of both direct photothermal and plasmonic laser heating to reduce the assay time to 15 min. Instrument performance was assessed using a split sample design to compare reaction performances of 1370 and 808 nm adaptive PCR heating modalities to a standard PCR instrument. Both the novel 1370 nm direct heating and the 808 nm plasmonic method achieved target amplification similar to the traditional PCR system within 15 min. However, a major disadvantage of 808 nm heating was nanorod optical interference that reduced the fluorescence signal from PCR probes and optical cycling components. Further characterization of the 1370 nm direct heating method found comparable limits of detection of 10⁰ copies/µL and reaction efficiencies of approximately 2 for both the 1370 nm system and the traditional PCR instrument. These results suggest that a field-deployable PCR instrument design incorporating both adaptive optical control and 1370 nm laser heating can achieve 15 min sample assay times without sacrificing analytical sensitivity. Full article

(This article belongs to the Special Issue Feature Paper in Biosensor and Bioelectronic Devices 2025)

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24 pages, 1661 KiB

Open AccessReview

Innovative Methodologies for the Early Detection of Breast Cancer: A Review Categorized by Target Biological Samples

by Antonella Grasso, Vittorio Altomare, Giulia Fiorini, Alessandro Zompanti, Giorgio Pennazza and Marco Santonico

Biosensors 2025, 15(4), 257; https://doi.org/10.3390/bios15040257 - 17 Apr 2025

Viewed by 82

Abstract

Innovative biosensor technologies are revolutionizing cancer detection by offering non-invasive, sensitive, and rapid diagnostic tools, addressing the limitations of conventional screening. Non-invasive samples like breath, saliva, urine, and sweat, analyzed using advanced technologies like electronic nose systems and AI, show promise for early [...] Read more.

Innovative biosensor technologies are revolutionizing cancer detection by offering non-invasive, sensitive, and rapid diagnostic tools, addressing the limitations of conventional screening. Non-invasive samples like breath, saliva, urine, and sweat, analyzed using advanced technologies like electronic nose systems and AI, show promise for early detection and frequent monitoring, though validation is needed. AI integration enhances data analysis and personalization. While blood-based methods remain the gold standard, combining them with less invasive sample types like saliva or sweat, and using sensitive techniques, is a promising direction. Conventional methods (mammography, MRI, etc.) offer proven efficacy, but are costly and invasive. Innovative methods using biosensors offer reduced infrastructure needs, lower costs, and patient-friendly sampling. However, challenges remain in validation, standardization, and low biomarker concentrations. Integrating both methodologies could create a comprehensive framework, combining reliability with accessibility. Future research should focus on robust biosensor development, standardization, expanding application to other cancers, exploring less-studied samples like sweat, and improving affordability for wider adoption, especially in resource-limited settings. The future lies in integrating diverse approaches for more sensitive, specific, and patient-friendly screening, improving early detection and outcomes. Full article

(This article belongs to the Special Issue Innovative Strategies for Cancer Biosensing)

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21 pages, 9099 KiB

Open AccessArticle

Polymerized Alizarin Red–Inorganic Hybrid Nanoarchitecture (PARIHN) as a Novel Fluorogenic Label for the Immunosorbent Assay of COVID-19

by Fatema Kaladari, Mahmoud El-Maghrabey, Naoya Kishikawa, Rania El-Shaheny and Naotaka Kuroda

Biosensors 2025, 15(4), 256; https://doi.org/10.3390/bios15040256 - 16 Apr 2025

Viewed by 133

Abstract

This study seeks to develop and implement a non-enzymatic fluorescent labeling for immunoassay and immunochromatographic assay (ICAs) targeting SARS-CoV-2, to meet the extensive interest and need for effective COVID-19 diagnosis. In this manuscript, we delineate the development, synthesis, and evaluation of a novel [...] Read more.

This study seeks to develop and implement a non-enzymatic fluorescent labeling for immunoassay and immunochromatographic assay (ICAs) targeting SARS-CoV-2, to meet the extensive interest and need for effective COVID-19 diagnosis. In this manuscript, we delineate the development, synthesis, and evaluation of a novel quinone polymer zinc hybrid nanoarchitecture, referred to as polymerized alizarin red–inorganic hybrid nanoarchitecture (PARIHN), which integrates an antibody for direct use in fluorescent immunoassays, offering enhanced sensitivity, reduced costs, and improved environmental sustainability. The designed nanoarchitecture can enhance the sensitivity of the immunoassay and enable rapid results without the complexities associated with enzymes, such as their low stability and high cost. At first, a chitosan–alizarin polymer was synthesized utilizing quinone–chitosan conjugation chemistry (QCCC). Then, the chitosan–alizarin polymer was embedded with the detection antibody using zinc ion, forming PARIHN, which was proven to be a stable label with the ability to enhance the assay stability and sensitivity of the immunoassay. PARIHN can react with phenylboronic acid (PBA) or boric acid through its alizarin content to produce fluorescence signals with an LOD of 15.9 and 2.6 pm for PBA and boric acid, respectively, which is the first use of a boric acid derivative in signal generation in the immunoassay. Furthermore, PARIHN demonstrated high practicality in detecting SARS-CoV-2 nucleoprotein in fluorescence (PBA and boric acid) systems with an LOD of 0.76 and 10.85 pm, respectively. Furthermore, owing to the high brightness of our PARIHN fluorogenic reaction, our labeling approach was extended to immunochromatographic assays for SARS-CoV-2 with high sensitivity down to 9.45 pg/mL. Full article

(This article belongs to the Special Issue Novel Nanomaterials and Nanotechnology: From Fabrication Methods and Improvement Strategies to Applications in Biosensing and Biomedicine (2nd Edition))

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27 pages, 7099 KiB

Open AccessArticle

Diabetes: Non-Invasive Blood Glucose Monitoring Using Federated Learning with Biosensor Signals

by Narmatha Chellamani, Saleh Ali Albelwi, Manimurugan Shanmuganathan, Palanisamy Amirthalingam and Anand Paul

Biosensors 2025, 15(4), 255; https://doi.org/10.3390/bios15040255 - 16 Apr 2025

Viewed by 200

Abstract

Diabetes is a growing global health concern, affecting millions and leading to severe complications if not properly managed. The primary challenge in diabetes management is maintaining blood glucose levels (BGLs) within a safe range to prevent complications such as renal failure, cardiovascular disease, [...] Read more.

Diabetes is a growing global health concern, affecting millions and leading to severe complications if not properly managed. The primary challenge in diabetes management is maintaining blood glucose levels (BGLs) within a safe range to prevent complications such as renal failure, cardiovascular disease, and neuropathy. Traditional methods, such as finger-prick testing, often result in low patient adherence due to discomfort, invasiveness, and inconvenience. Consequently, there is an increasing need for non-invasive techniques that provide accurate BGL measurements. Photoplethysmography (PPG), a photosensitive method that detects blood volume variations, has shown promise for non-invasive glucose monitoring. Deep neural networks (DNNs) applied to PPG signals can predict BGLs with high accuracy. However, training DNN models requires large and diverse datasets, which are typically distributed across multiple healthcare institutions. Privacy concerns and regulatory restrictions further limit data sharing, making conventional centralized machine learning (ML) approaches less effective. To address these challenges, this study proposes a federated learning (FL)-based solution that enables multiple healthcare organizations to collaboratively train a global model without sharing raw patient data, thereby enhancing model performance while ensuring data privacy and security. In the data preprocessing stage, continuous wavelet transform (CWT) is applied to smooth PPG signals and remove baseline drift. Adaptive cycle-based segmentation (ACBS) is then used for signal segmentation, followed by particle swarm optimization (PSO) for feature selection, optimizing classification accuracy. The proposed system was evaluated on diverse datasets, including VitalDB and MUST, under various conditions with data collected during surgery and anesthesia. The model achieved a root mean square error (RMSE) of 19.1 mg/dL, demonstrating superior predictive accuracy. Clarke error grid analysis (CEGA) confirmed the model’s clinical reliability, with 99.31% of predictions falling within clinically acceptable limits. The FL-based approach outperformed conventional deep learning models, making it a promising method for non-invasive, privacy-preserving glucose monitoring. Full article

(This article belongs to the Section Biosensors and Healthcare)

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14 pages, 4011 KiB

Open AccessArticle

The Optimization of a T-Cell Resonator: Towards Highly Sensitive Photoacoustic Spectroscopy for Noninvasive Blood Glucose Detection

by Thasin Mohammad Zaman, Md Rejvi Kaysir, Shazzad Rassel and Dayan Ban

Biosensors 2025, 15(4), 254; https://doi.org/10.3390/bios15040254 - 16 Apr 2025

Viewed by 152

Abstract

Noninvasive blood glucose monitoring is crucial for diabetes management, and photoacoustic spectroscopy (PAS) offers a promising solution by detecting glucose levels through human skin. However, weak acoustic signals in PAS systems require optimized resonator designs for enhanced detection sensitivity. Designing such resonators physically [...] Read more.

Noninvasive blood glucose monitoring is crucial for diabetes management, and photoacoustic spectroscopy (PAS) offers a promising solution by detecting glucose levels through human skin. However, weak acoustic signals in PAS systems require optimized resonator designs for enhanced detection sensitivity. Designing such resonators physically is complex, requiring the precise identification of critical parameters before practical implementation. This study focused on optimizing a T-shaped photoacoustic resonator using finite element modeling in a COMSOL Multiphysics environment. By systematically varying the geometric design parameters of the T-cell resonator, a maximum increase in the pressure amplitude of 12.76 times with a quality factor (Q-factor) of 47.5 was achieved compared to the previously designed reference acoustic resonator. This study took a significant step forward by identifying key geometric parameters that influence resonator performance, paving the way for more sensitive and reliable noninvasive glucose monitoring systems. Full article

(This article belongs to the Section Optical and Photonic Biosensors)

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46 pages, 3258 KiB

Open AccessReview

Organic Bioelectronics in Microphysiological Systems: Bridging the Gap Between Biological Systems and Electronic Technologies

by Pauline Coquart, Andrea El Haddad, Dimitrios A. Koutsouras and Johanna Bolander

Biosensors 2025, 15(4), 253; https://doi.org/10.3390/bios15040253 - 16 Apr 2025

Viewed by 427

Abstract

The growing burden of degenerative, cardiovascular, neurodegenerative, and cancerous diseases necessitates innovative approaches to improve our pathophysiological understanding and ability to modulate biological processes. Organic bioelectronics has emerged as a powerful tool in this pursuit, offering a unique ability to interact with biology [...] Read more.

The growing burden of degenerative, cardiovascular, neurodegenerative, and cancerous diseases necessitates innovative approaches to improve our pathophysiological understanding and ability to modulate biological processes. Organic bioelectronics has emerged as a powerful tool in this pursuit, offering a unique ability to interact with biology due to the mixed ionic–electronic conduction and tissue-mimetic mechanical properties of conducting polymers (CPs). These materials enable seamless integration with biological systems across different levels of complexity, from monolayers to complex 3D models, microfluidic chips, and even clinical applications. CPs can be processed into diverse formats, including thin films, hydrogels, 3D scaffolds, and electrospun fibers, allowing the fabrication of advanced bioelectronic devices such as multi-electrode arrays, transistors (EGOFETs, OECTs), ion pumps, and photoactuators. This review examines the integration of CP-based bioelectronics in vivo and in in vitro microphysiological systems, focusing on their ability to monitor key biological events, including electrical activity, metabolic changes, and biomarker concentrations, as well as their potential for electrical, mechanical, and chemical stimulation. We highlight the versatility and biocompatibility of CPs and their role in advancing personalized medicine and regenerative therapies and discuss future directions for organic bioelectronics to bridge the gap between biological systems and electronic technologies. Full article

(This article belongs to the Special Issue Bioelectronics and Biosensors Using Novel Metal-Oxide and Semiconductor Materials)

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16 pages, 4957 KiB

Open AccessReview

Recent Advances of Fluorescent Aptasensors for the Detection of Antibiotics in Food

by Zheng Liu, Wenyi Yang, Huikai Lin, Mingdi Zhang and Chunyan Sun

Biosensors 2025, 15(4), 252; https://doi.org/10.3390/bios15040252 - 16 Apr 2025

Viewed by 170

Abstract

Antibiotics can accumulate in the body via ingestion, presenting serious health and safety risks to humans, and have garnered extensive international attention in recent years. Meanwhile, aptamers have been applied in the detection of antibiotics, mainly because of their good stability, high specificity, [...] Read more.

Antibiotics can accumulate in the body via ingestion, presenting serious health and safety risks to humans, and have garnered extensive international attention in recent years. Meanwhile, aptamers have been applied in the detection of antibiotics, mainly because of their good stability, high specificity, easy synthesis, and low cost. Among various kinds of aptasensors, fluorescent dye-based or nanomaterial-based fluorescent aptasensors serve as highly efficient tools for the rapid quantification of antibiotics owing to their remarkable sensitivity, specificity, and selectivity. In addition, some novel techniques such as aptamer tailoring, signal amplification, and artificial intelligence for aptasensors are also presented. This paper provides a detailed and comprehensive review of fluorescent aptasensors for antibiotic detection. Moreover, it pinpoints the challenges encountered during the development of the aforesaid fluorescent aptasensors and puts forward future research directions. Full article

(This article belongs to the Special Issue Advancements in Molecular Diagnostics and Biosensing: Harnessing the Power of FRET Technology)

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20 pages, 2497 KiB

Open AccessArticle

White Light Spectroscopy Characteristics and Expansion Dynamic Behavior of Primary T-Cells: A Possibility of Online, Real-Time, and Sampling-Less CAR T-Cell Production Monitoring

by Bruno Wacogne, Maxime Brito, Clémentine Gamonet, Alain Rouleau and Annie Frelet-Barrand

Biosensors 2025, 15(4), 251; https://doi.org/10.3390/bios15040251 - 15 Apr 2025

Viewed by 119

Abstract

The production of advanced therapy medicinal products (ATMP) is a long and highly technical process, resulting in a high cost per dose, which reduces the number of eligible patients. There is a critical need for a closed and sample-free monitoring system to perform [...] Read more.

The production of advanced therapy medicinal products (ATMP) is a long and highly technical process, resulting in a high cost per dose, which reduces the number of eligible patients. There is a critical need for a closed and sample-free monitoring system to perform the numerous quality controls required. Current monitoring methods are not optimal, mainly because they require the system to be opened up for sampling and result in material losses. White light spectroscopy has emerged as a technique for sample-free control compatible with closed systems. We have recently proposed its use to monitor cultures of CEM-C1 cell lines. In this paper, we apply this method to T-cells isolated from healthy donor blood samples. The main differences between cell lines and human primary T-cells lie in the slightly different shape of their absorption spectra and in the dynamics of cell expansion. T-cells do not multiply exponentially, resulting in a non-constant generation time. Cell expansion is described by a power-law model, which allows for the definition of instantaneous generation times. A correlation between the linear asymptotic behavior of these generation times and the initial cell concentration leads to the hypothesis that this could be an early predictive marker of the final culture concentration. To the best of our knowledge, this is the first time that such concepts have been proposed. Full article

(This article belongs to the Special Issue Photonics for Bioapplications: Sensors and Technology—2nd Edition)

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27 pages, 6659 KiB

Open AccessArticle

Blood Glucose Monitoring Biosensor Based on Multiband Split-Ring Resonator Monopole Antenna

by Dalia N. Elsheakh, EL-Hawary Mohamed and Angie R. Eldamak

Biosensors 2025, 15(4), 250; https://doi.org/10.3390/bios15040250 - 15 Apr 2025

Viewed by 188

Abstract

This paper introduces a novel-shaped, compact, multiband monopole antenna sensor incorporating an irregular curved split-ring resonator (SRR) design for non-invasive, continuous monitoring of human blood glucose levels (BGL). The sensor operates at multiple resonance frequencies: 0.94, 1.5, 3, 4.6, and 6.3 GHz, achieving [...] Read more.

This paper introduces a novel-shaped, compact, multiband monopole antenna sensor incorporating an irregular curved split-ring resonator (SRR) design for non-invasive, continuous monitoring of human blood glucose levels (BGL). The sensor operates at multiple resonance frequencies: 0.94, 1.5, 3, 4.6, and 6.3 GHz, achieving coefficient reflection impedance bandwidths ≤ −10 dB of 4%, 1%, 3.5%, 65%, and 50%, respectively. Additionally, novel shapes of two SRR metamaterial cells create notches at 1.7 GHz and 4.4 GHz. The antenna is fabricated on an economical FR4 substrate with compact dimensions of 35 × 50 × 1.6 mm³. The sensor’s performance is evaluated using 3D electromagnetic software, incorporating a human finger phantom model and applying the Cole–Cole model to mimic the blood layer’s sensitivity to blood glucose variations. The phantom model is positioned at different angles relative to the biosensor to detect frequency shifts corresponding to different glucose levels. Experimental validation involves placing a real human finger around the sensor to measure resonant frequency, magnitude, and phase changes. The fabricated sensor demonstrates a superior sensitivity of 24 MHz/mg/dL effectiveness compared to existing methods. This emphasizes its potential for practical, non-invasive glucose monitoring applications. Full article

(This article belongs to the Special Issue Advances in Glucose Biosensors Toward Continuous Glucose Monitoring)

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15 pages, 2947 KiB

Open AccessArticle

Biofuel Cells Based on Oxidoreductases and Electroactive Nanomaterials: Development and Characterization

by Olha Demkiv, Nataliya Stasyuk, Galina Gayda, Oksana Zakalska, Mykhailo Gonchar and Marina Nisnevitch

Biosensors 2025, 15(4), 249; https://doi.org/10.3390/bios15040249 - 14 Apr 2025

Viewed by 229

Abstract

Amperometric biosensors (ABSs) and enzymatic biofuel cells (BFCs) share several fundamental principles in their functionality, despite serving different primary purposes. Both devices rely on biorecognition, redox reactions, electron transfer (ET), and advanced electrode materials, including innovative nanomaterials (NMs). ABSs and BFCs, utilizing microbial [...] Read more.

Amperometric biosensors (ABSs) and enzymatic biofuel cells (BFCs) share several fundamental principles in their functionality, despite serving different primary purposes. Both devices rely on biorecognition, redox reactions, electron transfer (ET), and advanced electrode materials, including innovative nanomaterials (NMs). ABSs and BFCs, utilizing microbial oxidoreductases in combination with electroactive NMs, are both efficient and cost-effective. In the current study, several laboratory prototypes of BFCs have been developed with bioanodes based on yeast flavocytochrome b₂ (Fcb₂) and alcohol oxidase (AO), and a cathode based on fungal laccase. For the first time, BFCs have been developed featuring anodes based on Fcb₂ co-immobilized with redox NMs on a glassy carbon electrode (GCE), and cathode-utilizing laccase combined with gold–cerium–platinum nanoparticles (nAuCePt). The most effective lactate BFC, which contains gold–hexacyanoferrate (AuHCF), exhibited a specific power density of 1.8 µW/cm². A series of BFCs were developed with an AO-containing anode and a laccase/nAuCePt/GCE cathode. The optimal configuration featured a bioanode architecture of AO/nCoPtCu/GCE, achieving a specific power density of 3.2 µW/cm². The constructed BFCs were tested using lactate-containing food product samples as fuels. Full article

(This article belongs to the Special Issue Advances in Biosensing and Bioanalysis Based on Nanozymes)

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18 pages, 3599 KiB

Open AccessArticle

FRET Visualization of High Mechanosensation of von Willebrand Factor to Hydrodynamic Force

by Mingxing Ouyang, Yao Gao, Binqian Zhou, Jia Guo, Lei Lei, Yingxiao Wang and Linhong Deng

Biosensors 2025, 15(4), 248; https://doi.org/10.3390/bios15040248 - 14 Apr 2025

Viewed by 106

Abstract

von Willebrand factor (vWF) is a large glycoprotein in the circulation system, which senses hydrodynamic force at vascular injuries and then recruits platelets in assembling clots. How vWF mechanosenses shear flow for molecular unfolding is an important topic. Here, a Förster resonance energy [...] Read more.

von Willebrand factor (vWF) is a large glycoprotein in the circulation system, which senses hydrodynamic force at vascular injuries and then recruits platelets in assembling clots. How vWF mechanosenses shear flow for molecular unfolding is an important topic. Here, a Förster resonance energy transfer (FRET) biosensor was developed to monitor vWF conformation change to hydrodynamic force. The vWF-based biosensor is anchored on the cell surface, in which the A2 domain is flanked with a FRET pair. With 293T cells seeded into microfluidic channels, 2.8 dyn/cm² of shear force (i.e., 28 μN/cm², or 264.1/s in shear rate) induced a remarkable FRET change (~60%) in 30 min. A gradient micro-shear below 2.8 dyn/cm² demonstrated FRET responses positively related to flow magnitudes, with 0.14 dyn/cm² (1.4 μN/cm²) inducing an obvious change (~16%). The FRET increases indicate closer positioning of A2’s two terminals in vWF or the addition of a more parallel orientation of the FRET pair, supported with the high FRET of the A2-only-based biosensor, which probably resulted from flow-induced A2 dissociation from vWF intramolecular binding such as that in A1/A3 domains. Interestingly, gradient flow increases from 2.8 to 28 dyn/cm² led to decreasing FRET changes, suggesting the second-level unfolding in the A2 domain. The LOCK-vWF biosensor with bridged A2 two terminals or an A2-only biosensor could not sense the shear, indicating a structure-flexible A2 and large vWF molecules that are important in the mechanosensation. In conclusion, the developed vWF-based biosensor demonstrated the high mechanosensation of vWF with two-level unfolding to shear force: the dissociation of the A2 domain from vWF intramolecular binding under a micro-shear, and then the unfolding of A2 in vWF under a higher shear; the FRET response to shear force at a very low scale may support the observed clot formation at microvascular wounds. This study provides new insights into the vWF’s mechanosensitive feature for its physiological functions and implicated disorders. Full article

(This article belongs to the Special Issue Advancements in Molecular Diagnostics and Biosensing: Harnessing the Power of FRET Technology)

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15 pages, 5398 KiB

Open AccessArticle

Design and In Vivo Evaluation of an Intraocular Electrode for Ciliary Muscle Biopotential Measurement in a Non-Human Primate Model of Human Accommodation

by Sven Schumayer, Esmaeil Ghadiri Zahrani, Bahman Azarhoushang, Volker Bucher and Torsten Straßer

Biosensors 2025, 15(4), 247; https://doi.org/10.3390/bios15040247 - 13 Apr 2025

Viewed by 310

Abstract

The measurement of electrical potentials in the human body is becoming increasingly important in healthcare as a valuable diagnostic parameter. In ophthalmology, while these signals are primarily used to assess retinal function, other applications, such as recording accommodation-related biopotentials from the ciliary muscle, [...] Read more.

The measurement of electrical potentials in the human body is becoming increasingly important in healthcare as a valuable diagnostic parameter. In ophthalmology, while these signals are primarily used to assess retinal function, other applications, such as recording accommodation-related biopotentials from the ciliary muscle, remain poorly understood. Here, we present the development and evaluation of a novel implantable ring electrode for recording biopotentials from the ciliary muscle. Inspired by capsular tension rings, the electrode was fabricated using laser cutting, wiring, and physical vapor deposition coating. The constant impedance and weight over a simulated aging period of 391 days, demonstrated the electrode’s stability. In vivo testing in non-human primates further validated the electrode’s surgical handling and long-term stability, with no delamination or tissue ingrowth after 100 days of implantation. Recorded biopotentials from the ciliary muscle (up to 700 µV) exceeded amplitudes reported in the literature. While the results are promising, further research is needed to investigate the signal quality and origin as well as the correlation between these signals and ciliary muscle activity. Ultimately, this electrode will be used in an implanted device to record ciliary muscle biopotentials to control an artificial lens designed to restore accommodation in individuals with presbyopia. Full article

(This article belongs to the Section Biosensors and Healthcare)

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15 pages, 3378 KiB

Open AccessArticle

Dendritic Gold Nanoparticles Loaded on 3D Graphene-like Surface and Layer-by-Layer Assembly for Enhanced Glucose Biosensing

by Zifeng Zhu, Yiming Zhao, Yongming Ruan, Xuexiang Weng and Gesmi Milcovich

Biosensors 2025, 15(4), 246; https://doi.org/10.3390/bios15040246 - 12 Apr 2025

Viewed by 208

Abstract

Background/Objectives: In this study, AuDNs/EPLE composite electrodes with hierarchical dendritic nanogold structures were fabricated using the in situ electrodeposition of gold nanoparticles through the i-t method. Methods: A conductive polymer composite membrane, PEDOT, was synthesized via the electropolymerization of EDOT and [...] Read more.

Background/Objectives: In this study, AuDNs/EPLE composite electrodes with hierarchical dendritic nanogold structures were fabricated using the in situ electrodeposition of gold nanoparticles through the i-t method. Methods: A conductive polymer composite membrane, PEDOT, was synthesized via the electropolymerization of EDOT and the negatively charged PSS⁻. The negatively charged SO₃⁻ groups on the surface of the PEDOT membrane were electrostatically adsorbed with the glucose oxidase (GOD) enzyme and a positively charged chitosan co-solution (GOD/chit⁺). Using a layer-by-layer self-assembly approach, GOD was incorporated into the multilayers of the composite electrode to create the composite GOD/chit⁺/PEDOT/AuDNs/EPLE. Results: Electrochemical analysis revealed a GOD surface coverage of 8.5 × 10⁻¹⁰ mol cm⁻² and an electron transfer rate of 1.394 ± 0.02 s⁻¹. The composite electrode exhibited a linear response to glucose in the concentration range of 6.923 × 10⁻² mM to 1.54 mM, with an apparent Michaelis constant of 0.352 ± 0.02 mM. Furthermore, the GOD/chit⁺/PEDOT/AuDNs/EPLE also showed good accuracy of glucose determination in human serum samples. Conclusions: These findings highlight the potential of the GOD/chit⁺/PEDOT/AuDNs/EPLE composite electrode in the development of efficient enzymatic biofuel cells for glucose sensing and energy harvesting applications. Full article

(This article belongs to the Special Issue Nanosensors for Bioanalysis)

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20 pages, 2342 KiB

Open AccessSystematic Review

Trends and Challenges of SPR Aptasensors in Viral Diagnostics: A Systematic Review and Meta-Analysis

by Elba Mauriz

Biosensors 2025, 15(4), 245; https://doi.org/10.3390/bios15040245 - 12 Apr 2025

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Abstract

Surface plasmon resonance (SPR) aptasensors benefit from the SPR phenomenon in measuring aptamer interactions with specific targets. Integrating aptamers into SPR detection enables extensive applications in clinical analysis. Specifically, virus aptasensing platforms are highly desirable to face the ongoing challenges of virus outbreaks. [...] Read more.

Surface plasmon resonance (SPR) aptasensors benefit from the SPR phenomenon in measuring aptamer interactions with specific targets. Integrating aptamers into SPR detection enables extensive applications in clinical analysis. Specifically, virus aptasensing platforms are highly desirable to face the ongoing challenges of virus outbreaks. This study systematically reviews the latest advances in SPR aptasensors for virus detection according to PRISMA guidelines. The literature search recovered 322 original articles from the Scopus (n = 152), Web of Science (n = 83), and PubMed (n = 87) databases. The selected articles (29) deal with the binding events between the aptamers immobilized on the sensor surface and their target molecule: virus proteins or intact viruses according to different SPR configurations. The methodological quality of each study was assessed using QUADAS-2, and a meta-analysis was conducted with the CochReview Manager (RevMan) Edition7.12.0 Data were analyzed, focusing on the types of viruses, the virus target, and the reference method. The pooled sensitivity was 1.89 (95%, CI 1.29, 2.78, I² = 49%). The analysis of different types of plasmonic sensors showed the best diagnostic results with the least heterogeneity for SPR conventional configurations: 3.23 (95% CI [1.80, 5.79]; I² = 0%, p = 0.65). These findings show that even though plasmonic biosensors effectively analyze viruses through aptamer approaches, there are still big challenges to using them regularly for diagnostics. Practical considerations for measuring label-free interactions revealed functional capabilities, technological boundaries, and future outlooks of SPR virus aptasensing. Full article

(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)

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15 pages, 3701 KiB

Open AccessReview

Single-Cell Endoscopy for Multifunctional Live-Cell Molecular Analysis

by Haoze Xue, Li Wang, Han Yao, Shuwei Shen, Xu Zhao, Chenxi Yuan, Luting Yu, Guoguang Chen and Jia Liu

Biosensors 2025, 15(4), 244; https://doi.org/10.3390/bios15040244 - 11 Apr 2025

Viewed by 115

Abstract

Molecular analyses of individual cells with high resolution, specificity, and sensitivity can not only reveal cellular heterogeneity but also provide a better understanding of diseases and accelerate drug discoveries. Single-cell endoscopy is an advanced live-cell technique that relies on a smart endoscope that [...] Read more.

Molecular analyses of individual cells with high resolution, specificity, and sensitivity can not only reveal cellular heterogeneity but also provide a better understanding of diseases and accelerate drug discoveries. Single-cell endoscopy is an advanced live-cell technique that relies on a smart endoscope that allows minimally invasive probing of the interiors of individual cells. Compared with other single-cell analysis techniques, single-cell endoscopy has shown great promise in applications such as flexible single-cell manipulation, ultrasensitive sensing, and precise intracellular delivery. In this review, we aim to map out the landscape of recent advances in single-cell endoscopy techniques by focusing on both fundamental considerations and significant progress over the past decade. Specifically, we summarize the predominant live-cell endoscopes, including their fabrication and characterization. Furthermore, a series of valuable intracellular molecular sensing events, such as nucleic acids, proteins, ions, etc., are introduced with a main emphasis on how single-cell endoscopy can solve these issues and what merits single-cell endoscopy can provide. Finally, we briefly outline the remaining challenges and directions for the future development of single-cell endoscopy techniques. Full article

(This article belongs to the Section Biosensors and Healthcare)

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18 pages, 7033 KiB

Open AccessArticle

A Novel Adaptive Independent Component Analysis Method for Multi-Channel Optically Pumped Magnetometers’ Magnetocardiography Signals

by Shuang Liang, Jiahe Qi, Junhuai He, Yikang Jia, Aimin Wang, Ting Zhao, Chaoliang Wei, Hongchen Jiao, Lishuang Feng and Heping Cheng

Biosensors 2025, 15(4), 243; https://doi.org/10.3390/bios15040243 - 11 Apr 2025

Viewed by 135

Abstract

With the gradual maturation of optically pumped magnetometer (OPM) technology, the use of OPMs to acquire weak magnetocardiography (MCG) signals has started to gain widespread application. Due to the complexity of magnetic environments, MCG signals are often subject to interference from various unknown [...] Read more.

With the gradual maturation of optically pumped magnetometer (OPM) technology, the use of OPMs to acquire weak magnetocardiography (MCG) signals has started to gain widespread application. Due to the complexity of magnetic environments, MCG signals are often subject to interference from various unknown sources. Independent component analysis (ICA) is one of the most widely used methods for blind source separation. However, in practical applications, the numbers of retained components and filtering components are often selected manually, relying on subjective experience. This study proposes an adaptive ICA method that estimates the signal-to-noise ratio (SNR) before processing to determine the number of components and selects heartbeat-related components based on their characteristic indicators. The method was validated using phantom experiments and MCG data in a 128-channel OPM-MCG system. In the human subject experiment, the array output SNR reached 31.8 dB, and the processing time was significantly reduced to 1/38 of the original. The proposed method outperformed traditional techniques in terms of its ability to identify artifacts and efficiency in this regard, providing strong support for the broader clinical application of OPM-MCG. Full article

(This article belongs to the Special Issue Innovative Technologies of Acquiring, Processing, Modeling, or Utilizing Biomedical and Physiological Signals from Biosensing)

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30 pages, 5618 KiB

Open AccessReview

High-Resolution Tracking of Aging-Related Small Molecules: Bridging Pollutant Exposure, Brain Aging Mechanisms, and Detection Innovations

by Keying Yu, Sirui Yang, Hongxu Song, Zhou Sun, Kaichao Wang, Yuqi Zhu, Chengkai Yang, Rongzhang Hao and Yuanyuan Cao

Biosensors 2025, 15(4), 242; https://doi.org/10.3390/bios15040242 - 11 Apr 2025

Viewed by 288

Abstract

Brain aging is a complex process regulated by genetic, environmental, and metabolic factors, and increasing evidence suggests that environmental pollutants can significantly accelerate this process by interfering with oxidative stress, neuroinflammation, and mitochondrial function-related signaling pathways. Traditional studies have focused on the direct [...] Read more.

Brain aging is a complex process regulated by genetic, environmental, and metabolic factors, and increasing evidence suggests that environmental pollutants can significantly accelerate this process by interfering with oxidative stress, neuroinflammation, and mitochondrial function-related signaling pathways. Traditional studies have focused on the direct damage of pollutants on macromolecules (e.g., proteins, DNA), while the central role of senescence-associated small molecules (e.g., ROS, PGE2, lactate) in early regulatory mechanisms has been long neglected. In this study, we innovatively proposed a cascade framework of “small molecule metabolic imbalance-signaling pathway dysregulation-macromolecule collapse”, which reveals that pollutants exacerbate the dynamics of brain aging through activation of NLRP3 inflammatory vesicles and inhibition of HIF-1α. Meanwhile, to address the technical bottleneck of small molecule spatiotemporal dynamics monitoring, this paper systematically reviews the cutting-edge detection tools such as electrochemical sensors, genetically encoded fluorescent probes and antioxidant quantum dots (AQDs). Among them, AQDs show unique advantages in real-time monitoring of ROS fluctuations and intervention of oxidative damage by virtue of their ultra-high specific surface area, controllable surface modification, and free radical scavenging ability. By integrating multimodal detection techniques and mechanism studies, this work provides a new perspective for analyzing pollutant-induced brain aging and lays a methodological foundation for early intervention strategies based on small molecule metabolic networks. Full article

(This article belongs to the Special Issue Novel Designs and Applications for Electrochemical Biosensors)

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17 pages, 12096 KiB

Open AccessArticle

Real-Time Precise Prediction Dispersion Turning Point of Optical Microfiber Coupler Biosensor with Ultra-High Sensitivity and Wide Linear Dynamic Range

by Haiyang Yu, Yue Wang, Yang Xu, Wenchao Zhou and Yihui Wu

Biosensors 2025, 15(4), 241; https://doi.org/10.3390/bios15040241 - 10 Apr 2025

Viewed by 208

Abstract

Optical microfiber biosensors demonstrate exceptionally ultra-high sensitivity at the dispersion turning point (DTP). However, the DTP is highly susceptible to variations in dimensional and external environmental factors, and the spectral response is mismatched from preparation in air to application in a liquid environment, [...] Read more.

Optical microfiber biosensors demonstrate exceptionally ultra-high sensitivity at the dispersion turning point (DTP). However, the DTP is highly susceptible to variations in dimensional and external environmental factors, and the spectral response is mismatched from preparation in air to application in a liquid environment, making the DTP difficult to control effectively. In this work, we propose a method that bridges the relationship between the interference spectra of air and aqueous environments. By counting the interference peaks in air, we can accurately predict the DTP position in liquids. Meanwhile, it provides a new balance between sensitivity and wide linear dynamic range, achieving wide dynamic range detection across various concentrations. The optical microfiber coupler (OMC) is fabricated using the hydrogen–oxygen flame melting tapering method. In addition, the concentration, temperature, and solvent used for the sensor’s biofunctional layer are optimized. Finally, in refractive index sensing, a maximum sensitivity of 1.17 × 105 ± 0.038 × 105 nm/RIU is achieved. For biosensing, a wide dynamic range detection of cardiac troponin I (cTnI) is realized at concentrations of 12–48 ng/mL, 120–480 pg/mL, and 120–480 fg/mL. Full article

(This article belongs to the Special Issue Micro-nano Optic-Based Biosensing Technology and Strategy)

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23 pages, 2928 KiB

Open AccessArticle

Intra- and Inter-Regional Complexity in Multi-Channel Awake EEG Through Multivariate Multiscale Dispersion Entropy for Assessing Sleep Quality and Aging

by Ahmad Zandbagleh, Saeid Sanei, Lucía Penalba-Sánchez, Pedro Miguel Rodrigues, Mark Crook-Rumsey and Hamed Azami

Biosensors 2025, 15(4), 240; https://doi.org/10.3390/bios15040240 - 9 Apr 2025

Viewed by 363

Abstract

Aging and poor sleep quality are associated with altered brain dynamics, yet current electroencephalography (EEG) analyses often overlook regional complexity. This study addresses this gap by introducing a novel integration of intra- and inter-regional complexity analysis using multivariate multiscale dispersion entropy (mvMDE) from [...] Read more.

Aging and poor sleep quality are associated with altered brain dynamics, yet current electroencephalography (EEG) analyses often overlook regional complexity. This study addresses this gap by introducing a novel integration of intra- and inter-regional complexity analysis using multivariate multiscale dispersion entropy (mvMDE) from awake resting-state EEG for the first time. Moreover, assessing both intra- and inter-regional complexity provides a comprehensive perspective on the dynamic interplay between localized neural activity and its coordination across brain regions, which is essential for understanding the neural substrates of aging and sleep quality. Data from 58 participants—24 young adults (mean age = 24.7 ± 3.4) and 34 older adults (mean age = 72.9 ± 4.2)—were analyzed, with each age group further divided based on Pittsburgh Sleep Quality Index (PSQI) scores. To capture inter-regional complexity, mvMDE was applied to the most informative group of sensors, with one sensor selected from each brain region using four methods: highest average correlation, highest entropy, highest mutual information, and highest principal component loading. This targeted approach reduced computational cost and enhanced the effect sizes (ESs), particularly at large scale factors (e.g., 25) linked to delta-band activity, with the PCA-based method achieving the highest ESs (1.043 for sleep quality in older adults). Overall, we expect that both inter- and intra-regional complexity will play a pivotal role in elucidating neural mechanisms as captured by various physiological data modalities—such as EEG, magnetoencephalography, and magnetic resonance imaging—thereby offering promising insights for a range of biomedical applications. Full article

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

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18 pages, 4658 KiB

Open AccessArticle

Atomic Pt-Layer-Coated Au Peroxidase Nanozymes with Enhanced Activity for Ultrasensitive Colorimetric Immunoassay of Interleukin-12

by Han Zhang, Xiang Peng, Hao Song, Yongfeng Tan, Jianglian Xu, Qunfang Li and Zhuangqiang Gao

Biosensors 2025, 15(4), 239; https://doi.org/10.3390/bios15040239 - 9 Apr 2025

Viewed by 258

Abstract

Interleukin-12 (IL-12), a crucial biomarker for immune and inflammatory responses, plays a pivotal role in diagnosing and managing diverse pathological conditions. Although colorimetric enzyme-linked immunosorbent assays (CELISAs) have been extensively employed to detect IL-12 in biological samples, their sensitivity is inherently limited by [...] Read more.

Interleukin-12 (IL-12), a crucial biomarker for immune and inflammatory responses, plays a pivotal role in diagnosing and managing diverse pathological conditions. Although colorimetric enzyme-linked immunosorbent assays (CELISAs) have been extensively employed to detect IL-12 in biological samples, their sensitivity is inherently limited by the catalytic efficiency of enzyme labels, presenting substantial challenges in achieving ultrasensitive detection and enabling pre-symptomatic diagnosis of diseases. In this study, we address this limitation by developing a novel peroxidase nanozyme, featuring ultrathin Pt skins consisting of only ~4 atomic layers, coated on Au nanoparticles (denoted as Au@Pt_4LNPs). These Au@Pt_4LNPs exhibit remarkable catalytic performance, achieving a ~1063-fold enhancement in peroxidase-like activity compared to horseradish peroxidase (HRP), while minimizing Pt consumption, thereby improving Pt utilization efficiency and reducing costs. This advancement facilitates the construction of an ultrasensitive CELISA capable of detecting IL-12 at femtomolar concentrations. Using Au@Pt_4LNPs as the signal labels, the developed CELISA demonstrates a quantitative detection range from 0.1 to 100 pg mL⁻¹, with a limit of detection (LOD) as low as 0.084 pg mL⁻¹ (1.1 fM), offering ~10 times greater sensitivity than the HRP-based CELISA. This study highlights the potential of Au@Pt_4LNP nanozymes as advanced signal labels, opening new avenues for next-generation ultrasensitive bioassays. Full article

(This article belongs to the Special Issue Nano Biosensors and Their Applications for In Vivo/Vitro Diagnosis—2nd Edition)

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32 pages, 2877 KiB

Open AccessReview

New Frontiers for the Early Diagnosis of Cancer: Screening miRNAs Through the Lateral Flow Assay Method

by Afsaneh Emamiamin, Seyedeh Rojin Shariati Pour, Thea Serra, Donato Calabria, Marta Varone, Fabio Di Nardo, Massimo Guardigli, Laura Anfossi, Claudio Baggiani, Martina Zangheri and Mara Mirasoli

Biosensors 2025, 15(4), 238; https://doi.org/10.3390/bios15040238 - 8 Apr 2025

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Abstract

MicroRNAs (miRNAs), which circulate in the serum and plasma, play a role in several biological processes, and their levels in body fluids are associated with the pathogenesis of various diseases, including different types of cancer. For this reason, miRNAs are considered promising candidates [...] Read more.

MicroRNAs (miRNAs), which circulate in the serum and plasma, play a role in several biological processes, and their levels in body fluids are associated with the pathogenesis of various diseases, including different types of cancer. For this reason, miRNAs are considered promising candidates as biomarkers for diagnostic purposes, enabling the early detection of pathological onset and monitoring drug responses during therapy. However, current methods for miRNA quantification, such as northern blotting, isothermal amplification, RT-PCR, microarrays, and next-generation sequencing, are limited by their reliance on centralized laboratories, high costs, and the need for specialized personnel. Consequently, the development of sensitive, simple, and one-step analytical techniques for miRNA detection is highly desirable, particularly given the importance of early diagnosis and prompt treatment in cases of cancer. Lateral flow assays (LFAs) are among the most attractive point-of-care (POC) devices for healthcare applications. These systems allow for the rapid and straightforward detection of analytes using low-cost setups that are accessible to a wide audience. This review focuses on LFA-based methods for detecting and quantifying miRNAs associated with the diagnosis of various cancers, with particular emphasis on sensitivity enhancements achieved through the application of different labels and detection systems. Early, non-invasive detection of these diseases through the quantification of tailored biomarkers can significantly reduce mortality, improve survival rates, and lower treatment costs. Full article

(This article belongs to the Special Issue Advanced Biosensors for Disease Screening, Monitoring, Diagnosis and Treatment)

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13 pages, 3781 KiB

Open AccessArticle

Nanoparticulate Copper Cluster-Mediated Biosensing of Cardiac Biomolecular Markers

by Lakshmi V. Nair, Jarred Wheeler, Yaelyn Ha, Kimberly M. Jones, Jesse Jones and Vinoy Thomas

Biosensors 2025, 15(4), 237; https://doi.org/10.3390/bios15040237 - 8 Apr 2025

Viewed by 239

Abstract

Being a leading cause of death, heart diseases across the globe need special attention to enable early diagnosis. Metal nanoparticle-mediated biosensors are useful clinical tools for the early detection of bio-analytes. The size-dependent surface plasmon resonance (SPR) of metal nanoparticles can be effectively [...] Read more.

Being a leading cause of death, heart diseases across the globe need special attention to enable early diagnosis. Metal nanoparticle-mediated biosensors are useful clinical tools for the early detection of bio-analytes. The size-dependent surface plasmon resonance (SPR) of metal nanoparticles can be effectively utilized for the same purpose. The early detection of heart diseases can be evaluated by monitoring the troponin level. A copper nanoparticle-mediated troponin biosensor was developed through antibody conjugation for troponin I and troponin T. The copper nanosensor shows a concentration-dependent SPR change towards troponin T and troponin I. Full article

(This article belongs to the Special Issue Nanomaterial-Enhanced Biosensing for Point-of-Care Diagnostics)

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16 pages, 2711 KiB

Open AccessArticle

Ultrasensitive Peptide-Based Electrochemical Biosensor for Universal Diagnostic of Dengue

by Isis Campos Prado, João Pedro Rangel da Silva Carvalho, André Souza Araujo, Paloma Napoleão-Pêgo and Salvatore Giovanni De-Simone

Biosensors 2025, 15(4), 236; https://doi.org/10.3390/bios15040236 - 8 Apr 2025

Viewed by 310

Abstract

Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, [...] Read more.

Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, there is still a huge demand for new diagnostic methods that provide rapid, low-cost, easy-to-use confirmation. Thus, in this study, we developed an affordable electrochemical biosensor for rapidly detecting immunoglobulin G (IgG) serological antibodies in the sera of DENV-infected patients. An identified linear B-cell epitope (DENV/18) specific for DENV 1–4 serotypes recognized by IgG in patient sera was selected as a target molecule after a microarray of peptides using the SPOT-synthesis methodology. After chemical synthesis, the DENV/18-peptide was immobilized on the surface of the working electrode of a commercially available screen-printed gold electrode (SPGE). The capture of DENV-specific IgG allowed for the formation of an immunocomplex that was measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using a potassium ferrocyanide/ferricyanide ([Fe(CN)₆]^3−/4−) electrochemical probe. An evaluation of the biosensor’s performance showed a detection limit of 100 µg mL⁻¹ for the synthetic peptides (DENV/18) and 1.21 ng mL⁻¹ in CV and 0.43 ng mL⁻¹ in DPV for human serum, with a sensitivity of 7.21 µA in CV and 8.79 µA in DPV. The differentiation of infected and uninfected individuals was possible even at a high dilution factor that reduced the required sample volumes to a few microliters. The final device proved suitable for diagnosing DENV by analyzing real serum samples, and the results showed good agreement with molecular biology diagnostics. The flexibility to conjugate other antigenic peptides to SPEs suggests that this technology could be rapidly adapted to diagnose other pathogens. Full article

(This article belongs to the Special Issue Biosensing and Diagnosis—2nd Edition)

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15 pages, 9907 KiB

Open AccessArticle

A Facile Method for Synthesizing Cobalt Oxide Nanoparticles to Create a Highly Sensitive Non-Enzyme Glucose Sensor

by Zhanar K. Kalkozova, Ulpan A. Balgimbayeva, Maratbek T. Gabdullin, Lesya V. Gritsenko, Guoquan Suo and Khabibulla A. Abdullin

Biosensors 2025, 15(4), 235; https://doi.org/10.3390/bios15040235 - 7 Apr 2025

Viewed by 304

Abstract

In this study, an electrochemical non-enzymatic glucose sensor based on cobalt oxide was developed using a simple chemical bath deposition method. The as-synthesized material exhibited no significant sensitivity; the latter emerged only after subsequent electrochemical activation. To the best of our knowledge, this [...] Read more.

In this study, an electrochemical non-enzymatic glucose sensor based on cobalt oxide was developed using a simple chemical bath deposition method. The as-synthesized material exhibited no significant sensitivity; the latter emerged only after subsequent electrochemical activation. To the best of our knowledge, this is the first report demonstrating the successful application of electrochemical activation to achieve enhanced sensitivity. An X-ray diffraction analysis confirmed that a single-phase Co₂(OH)₂(CO₃) material was obtained immediately after synthesis, which was subsequently transformed into Co₃O₄ nanoparticles during electrochemical activation. SEM and TEM analyses revealed that the synthesized particles initially exhibited a nanorod structure, which evolved into a highly dispersed form after activation. The non-enzymatic glucose sensor based on the electrochemically activated material demonstrated excellent glucose sensitivity of 33,245 µA mM⁻¹ cm⁻² within the linear range of 0–0.5 mM, with a detection limit (LOD) of 5 µM. The starting material remained stable for over 12 months under ambient storage conditions and regained its high sensitivity following electrochemical activation. Full article

(This article belongs to the Section Biosensor Materials)

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