Biosensors

21 pages, 1566 KiB

Open AccessArticle

A Multi-Domain Feature Fusion CNN for Myocardial Infarction Detection and Localization

by Yunfan Chen, Jinxing Ye, Yuting Li, Zhe Luo, Jieqiang Luo and Xiangkui Wan

Biosensors 2025, 15(6), 392; https://doi.org/10.3390/bios15060392 - 17 Jun 2025

Myocardial infarction (MI) is a critical cardiovascular disease characterized by extensive myocardial necrosis occurring within a short timeframe. Traditional MI detection and localization techniques predominantly utilize single-domain features as input. However, relying solely on single-domain features of the electrocardiogram (ECG) proves challenging for [...] Read more.

Myocardial infarction (MI) is a critical cardiovascular disease characterized by extensive myocardial necrosis occurring within a short timeframe. Traditional MI detection and localization techniques predominantly utilize single-domain features as input. However, relying solely on single-domain features of the electrocardiogram (ECG) proves challenging for accurate MI detection and localization due to the inability of these features to fully capture the complexity and variability in cardiac electrical activity. To address this, we propose a multi-domain feature fusion convolutional neural network (MFF–CNN) that integrates the time domain, frequency domain, and time-frequency domain features of ECG for automatic MI detection and localization. Initially, we generate 2D frequency domain and time-frequency domain images to combine with single-dimensional time domain features, forming multi-domain input features to overcome the limitations inherent in single-domain approaches. Subsequently, we introduce a novel MFF–CNN comprising a 1D CNN and two 2D CNNs for multi-domain feature learning and MI detection and localization. The experimental results demonstrate that in rigorous inter-patient validation, our method achieves 99.98% detection accuracy and 84.86% localization accuracy. This represents a 3.43% absolute improvement in detection and a 16.97% enhancement in localization over state-of-the-art methods. We believe that our approach will greatly benefit future research on cardiovascular disease. Full article

(This article belongs to the Special Issue Portable Bioelectronic Devices for Telemedicine, Healthcare and Sports Applications)

14 pages, 1049 KiB

Open AccessArticle

MyμAlbumin: A Cutting-Edge Immunoturbidity-Based Device with Real-time and Seamless Data Transmission for Early Detection of Chronic Kidney Disease at the Point of Care

by Wanna Chaijaroenkul, Napaporn Youngvises, Artitaya Thiengsusuk, Tullayakorn Plengsuriyakarn, Jakkrapong Suwanboriboon, Kridsada Sirisabhabhorn, Wanchai Meesiri and Kesara Na-Bangchang

Biosensors 2025, 15(6), 391; https://doi.org/10.3390/bios15060391 - 17 Jun 2025

Abstract

Microalbuminemia, characterized by a urinary albumin concentration between 20 and 200 mg/L, is a critical marker in assessing the risk of chronic kidney disease (CKD), diabetic nephropathy, and various other chronic conditions. Previously, we developed and validated the MyACR point-of-care (PoC) device, which [...] Read more.

Microalbuminemia, characterized by a urinary albumin concentration between 20 and 200 mg/L, is a critical marker in assessing the risk of chronic kidney disease (CKD), diabetic nephropathy, and various other chronic conditions. Previously, we developed and validated the MyACR point-of-care (PoC) device, which facilitates the monitoring of CKD progression through real-time data transmission, thus enhancing patient management. This device utilizes a spectrophotometric dye-binding assay to measure albumin and creatinine concentrations in urine samples, providing an albumin-to-creatinine ratio (ACR) result. In the present study, we introduced a refined version of the PoC device, MyμAlbumin, designed to offer a simple, accurate, specific, sensitive, and rapid method for detecting microalbumin in urine as an early indicator of CKD and related diseases. The measurement is based on a specific immunoturbidimetric assay in a microcuvette, using a total solution volume of 125 µL (n = 5 for each validation test). The MyμAlbumin device demonstrated excellent performance, achieving high accuracy (%DMV < 4.67) and precision (%CV < 5) and a strong correlation (R² > 0.995) with laboratory spectrophotometry (dye-binding assay) and reference hospital-based immunoturbidimetric assay. Its high sensitivity (LOQ = 5 mg/L) positions MyμAlbumin as a highly viable and cost-effective tool for clinical use. Additionally, the device supports real-time, seamless data transmission, making it ideal for integration into remote healthcare settings. Full article

(This article belongs to the Section Biosensors and Healthcare)

13 pages, 3820 KiB

Open AccessArticle

Cellulose-Based Colorimetric Test Strips for SARS-CoV-2 Antibody Detection

by Mariana P. Sousa, Ana Cláudia Pereira, Bárbara Correia, Anália do Carmo, Ana Miguel Matos, Maria Teresa Cruz and Felismina T. C. Moreira

Biosensors 2025, 15(6), 390; https://doi.org/10.3390/bios15060390 - 17 Jun 2025

Abstract

The COVID-19 pandemic highlighted the need for rapid, cost-effective tools to monitor transmission and immune response. We developed two novel paper-based colorimetric biosensors using glutaraldehyde as a protein dye—its first use in this context. Glutaraldehyde reacts with amino groups to generate a brown [...] Read more.

The COVID-19 pandemic highlighted the need for rapid, cost-effective tools to monitor transmission and immune response. We developed two novel paper-based colorimetric biosensors using glutaraldehyde as a protein dye—its first use in this context. Glutaraldehyde reacts with amino groups to generate a brown color, enabling detection of SARS-CoV-2 antibodies. Wathman filter paper was functionalized with (3-aminopropyl)triethoxysilane (APTES) to immobilize virus-like particles (VLPs) and nucleocapsid protein (N-protein) as biorecognition elements. Upon incubation with antibody-containing samples, glutaraldehyde enabled colorimetric detection using RGB analysis in ImageJ software. Both sensors showed a linear correlation between antibody concentration and RGB values in buffer and serum. The VLP sensor responded linearly within the range of 1.0–20 µg/mL (green coordinate) in 500-fold diluted serum and the N-protein sensor from 1.0–40 µg/mL (blue coordinate) in 250-fold diluted serum. Both sensors demonstrated good selectivity, with glucose causing up to 18% interference. These biosensors represent a paradigm shift, as they provide a sensitive, user-friendly, and cost-effective option for semi-quantitative serological analysis. Furthermore, their versatility goes beyond the detection of SARS-CoV-2 antibodies and suggests broader applicability for various molecular targets. Full article

(This article belongs to the Special Issue Material-Based Biosensors and Biosensing Strategies)

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Graphical abstract

13 pages, 5000 KiB

Open AccessArticle

Comprehensive Analysis of Shear Deformation Cytometry Based on Numerical Simulation Method

by Jun Wang, Jiahe Chen, Wenlai Tang and Shu Zhu

Biosensors 2025, 15(6), 389; https://doi.org/10.3390/bios15060389 - 17 Jun 2025

Abstract

The deformability of cells reflects their capacity for shape changes under external forces; however, the systematic investigation of deformation-influencing factors remains conspicuously underdeveloped. In this work, by using an incompressible neo-Hookean viscoelastic solid model, coupled with the Kelvin–Voigt model, the effects of flow [...] Read more.

The deformability of cells reflects their capacity for shape changes under external forces; however, the systematic investigation of deformation-influencing factors remains conspicuously underdeveloped. In this work, by using an incompressible neo-Hookean viscoelastic solid model, coupled with the Kelvin–Voigt model, the effects of flow rate, fluid viscosity, cell diameter, and shear modulus on cell deformability were systematically calculated and simulated. Additionally, the relationship between cell deformability and relaxation time within a dissipative process was also simulated. The results indicate that cell deformation is positively correlated with flow rate, with an approximate linear relationship between the deformation index and flow velocity. Fluid viscosity also significantly affects cell deformation, as an approximate linear relationship with the deformation index is observed. Cell diameter has a more prominent impact on cell deformability than do flow rate or fluid viscosity, with the deformation index increasing more rapidly than the cell diameter. As the Young’s modulus increases, cell deformation decreases non-linearly. Cell deformation in the channel also gradually decreases with the increase in relaxation time. These findings enhance the understanding of cell biophysical characteristics and provide a basis for the precise control of cell deformation in deformability cytometry. This research holds significant implications for cell analysis-based animal health monitoring in the field of agriculture, as well as for other related areas. Full article

(This article belongs to the Section Nano- and Micro-Technologies in Biosensors)

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19 pages, 2667 KiB

Open AccessCommunication

Parylene-C Modified OSTE Molds for PDMS Microfluidic Chip Fabrication and Applications in Plasma Separation and Polymorphic Crystallization

by Muyang Zhang, Haonan Li, Xionghui Li, Zitong Ye, Qinghao He, Jie Zhou, Jiahua Zhong, Hao Chen, Xinyi Chen, Yixi Shi, Huiru Zhang, Lok Ting Chu and Weijin Guo

Biosensors 2025, 15(6), 388; https://doi.org/10.3390/bios15060388 - 16 Jun 2025

Abstract

This work presents a novel microfabrication process that addresses the interference of thiol groups on off-stoichiometry thiolene (OSTE) surfaces with the curing of polydimethylsiloxane (PDMS) by integrating the high-performance polymer Parylene-C. The process utilizes a Parylene-C coating to encapsulate the active thiol groups [...] Read more.

This work presents a novel microfabrication process that addresses the interference of thiol groups on off-stoichiometry thiolene (OSTE) surfaces with the curing of polydimethylsiloxane (PDMS) by integrating the high-performance polymer Parylene-C. The process utilizes a Parylene-C coating to encapsulate the active thiol groups on the OSTE surface, enabling precise replication of PDMS microstructures. Based on this method, PDMS micropillar arrays and microwell arrays were successfully fabricated and applied in passive plasma separation and polymorphic crystal formation, respectively. The experimental results demonstrate that the plasma-separation chip efficiently isolates plasma from whole-blood samples with varying hematocrit (HCT) levels, achieving a separation efficiency of up to 57.5%. Additionally, the microwell array chip exhibits excellent stability and controllability in the growth of salt and protein crystals. This study not only provides a new approach for microfabricating microfluidic chips, but also highlights its potential applications in biomedical diagnostics and materials science. Full article

(This article belongs to the Special Issue Microfluidics and MEMS for Diagnostics and Biomedical Applications—2nd Edition)

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15 pages, 1911 KiB

Open AccessArticle

Aptamer-Functionalized Gold Nanoparticle Assay for Rapid Visual Detection of Norovirus in Stool Samples

by Maytawan Thanunchai, Sirikwan Sangboonruang, Natthawat Semakul, Kattareeya Kumthip, Niwat Maneekarn and Khajornsak Tragoolpua

Biosensors 2025, 15(6), 387; https://doi.org/10.3390/bios15060387 - 16 Jun 2025

Abstract

Norovirus (NoV), a leading cause of acute gastroenteritis worldwide, imposes significant morbidity and economic burdens across all age groups. Timely and accurate laboratory diagnosis is crucial for effective outbreak control and patient management. However, current diagnostic methods often require specialized equipment, technical expertise, [...] Read more.

Norovirus (NoV), a leading cause of acute gastroenteritis worldwide, imposes significant morbidity and economic burdens across all age groups. Timely and accurate laboratory diagnosis is crucial for effective outbreak control and patient management. However, current diagnostic methods often require specialized equipment, technical expertise, and considerable time. To address these challenges, we developed a visual detection method utilizing gold nanoparticles (AuNPs) functionalized with the SMV25 aptamer specific to the NoV capsid protein. Detection relies on MgCl₂-induced changes in the color and absorbance of these aptamer-functionalized AuNPs. The assay exhibited a good linear relationship between the A630/A520 absorbance ratio and NoV capsid protein concentration. Specifically, in a buffer system, this linearity (R² = 0.9026) was observed over a 0–32 ng/µL range with a limit of detection (LOD) of 9.65 ng/µL. Similarly, for NoV spiked into stool suspensions, a strong linear correlation (R² = 0.9170) was found across a 0–100 ng/µL range, with an LOD of 37.11 ng/µL. Evaluation with real stool samples yielded 77% sensitivity and 65% specificity. Notably, the assay demonstrated the highest sensitivity towards NoV GII.2 (100%), followed by GII.4 (78%). Scanning transmission electron microscopy confirmed the underlying aggregation and dispersion patterns of the aptamer-functionalized AuNPs. This colorimetric assay provides a simple, rapid, and visual method for NoV detection. Nevertheless, further enhancements are necessary to improve its performance in the direct testing of complex specimens, paving the way for future on-site detection applications, especially in resource-limited settings. Full article

(This article belongs to the Section Biosensors and Healthcare)

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13 pages, 1792 KiB

Open AccessArticle

A High-Sensitivity, Bluetooth-Enabled PCB Biosensor for HER2 and CA15-3 Protein Detection in Saliva: A Rapid, Non-Invasive Approach to Breast Cancer Screening

by Hsiao-Hsuan Wan, Chao-Ching Chiang, Fan Ren, Cheng-Tse Tsai, Yu-Siang Chou, Chun-Wei Chiu, Yu-Te Liao, Dan Neal, Coy D. Heldermon, Mateus G. Rocha and Josephine F. Esquivel-Upshaw

Biosensors 2025, 15(6), 386; https://doi.org/10.3390/bios15060386 - 15 Jun 2025

Viewed by 48

Abstract

Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive [...] Read more.

Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive biopsies and time-intensive laboratory procedures. In this study, we present a biosensor integrated with a reusable printed circuit board (PCB) and functionalized glucose test strips designed for rapid and non-invasive HER2 detection in saliva. The biosensor achieved a limit of detection of 10⁻¹⁵ g/mL, 4 to 5 orders of magnitude more sensitive than the enzyme-linked immunosorbent assay (ELISA), with a sensitivity of 95/dec and a response time of 1 s. In addition to HER2, the biosensor also detects cancer antigen 15-3 (CA15-3), another clinically relevant breast cancer biomarker. The CA15-3 test demonstrated an equally low limit of detection, 10⁻¹⁵ g/mL, and a higher sensitivity, 190/dec, further validated using human saliva samples. Clinical validation using 29 saliva samples confirmed our biosensor’s ability to distinguish between healthy, in situ breast cancer, and invasive breast cancer patients. The system, which integrates a Bluetooth Low-Energy (BLE) module, enables remote monitoring, reduces hospital visits, and enhances accessibility for point-of-care and mobile screening applications. This ultra-sensitive, rapid, and portable biosensor can serve as a promising alternative for breast cancer detection and monitoring, particularly in rural and underserved communities. Full article

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

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22 pages, 2249 KiB

Open AccessArticle

Impedimetric DNA Sensor Based on a Composite of Electrochemically Reduced Graphene Oxide and Polyproflavine Electropolymerized from Natural Deep Eutectic Solvent for Anthracycline Medications Determination

by Anastasia Goida, Tatiana Krasnova, Rezeda Shamagsumova, Vladimir Evtugyn, Anatoly Saveliev and Anna Porfireva

Biosensors 2025, 15(6), 385; https://doi.org/10.3390/bios15060385 - 14 Jun 2025

Viewed by 28

Abstract

A novel nanocomposite based on electrochemically reduced graphene oxide (ERGO) and electropolymerized polyproflavine (PPFL) was obtained within a “one-pot” synthesis from natural deep eutectic solvent (NADES). NADES consisted of citric acid, glucose, and water in a molar ratio of 1:1:6. The synthesis was [...] Read more.

A novel nanocomposite based on electrochemically reduced graphene oxide (ERGO) and electropolymerized polyproflavine (PPFL) was obtained within a “one-pot” synthesis from natural deep eutectic solvent (NADES). NADES consisted of citric acid, glucose, and water in a molar ratio of 1:1:6. The synthesis was carried out in potentiostatic mode by consequent potential application in cathodic and anodic areas. The composite was applied to develop the impedimetric DNA sensor for anthracycline determination. The sensor has provided linear range from 10 nM to 0.1 mM for doxorubicin, from 1 pM to 10 nM for epirubicin, and from 10 pM to 10 nM for idarubicin, with the limit of detection 3 nM, 1 pM, and 5 pM, respectively. The concentrations of doxorubicin below 10 nM did not have any other influence on epirubicin and idarubicin determination despite their molecular structure similarity. The sensor developed was used for the determination of anticancer medications, such as doxorubicin, epirubicin, and idarubicin, in their standard solutions, pharmaceuticals, artificial, and human urine samples. It is worth noting that the additions of mannitol and lactose, which are the stabilizers of the pharmaceuticals, exhibited an interfering effect on the sensor response. Full article

(This article belongs to the Special Issue Application of Nanocomposites for Biosensors)

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15 pages, 3820 KiB

Open AccessArticle

Gold Nanoparticle-Enhanced Molecularly Imprinted Polymer Electrode for Non-Enzymatic Lactate Sensing

by Christopher Animashaun, Abdellatif Ait Lahcen and Gymama Slaughter

Biosensors 2025, 15(6), 384; https://doi.org/10.3390/bios15060384 - 13 Jun 2025

Viewed by 155

Abstract

We are reporting the development of a high-performance, non-enzymatic electrochemical biosensor for selective lactate detection, integrating laser-induced graphene (LIG), gold nanoparticles (AuNPs), and a molecularly imprinted polymer (MIP) synthesized from poly(3,4-ethylenedioxythiophene) (PEDOT). The LIG electrode offers a highly porous, conductive scaffold, while electrodeposited [...] Read more.

We are reporting the development of a high-performance, non-enzymatic electrochemical biosensor for selective lactate detection, integrating laser-induced graphene (LIG), gold nanoparticles (AuNPs), and a molecularly imprinted polymer (MIP) synthesized from poly(3,4-ethylenedioxythiophene) (PEDOT). The LIG electrode offers a highly porous, conductive scaffold, while electrodeposited AuNPs enhance catalytic activity and signal amplification. The PEDOT-based MIP layer, electropolymerized via cyclic voltammetry, imparts molecular specificity by creating lactate-specific binding sites. Cyclic voltammetry confirmed successful molecular imprinting and enhanced interfacial electron transfer. The resulting LIG/AuNPs/MIP biosensor demonstrated a wide linear detection range from 0.1 µM to 2500 µM, with a sensitivity of 22.42 µA/log(µM) and a low limit of detection (0.035 µM). The sensor showed excellent selectivity against common electroactive interferents such as glucose and uric acid, long-term stability, and accurate recovery in artificial saliva (>95.7%), indicating strong potential for practical application. This enzyme-free platform offers a robust and scalable strategy for continuous lactate monitoring, particularly suited for wearable devices in sports performance monitoring and critical care diagnostics. Full article

(This article belongs to the Special Issue Advanced Nanomaterials for Electrochemical Biosensing Application)

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13 pages, 2158 KiB

Open AccessArticle

A Smart Nanoprobe for Visually Investigating the Activation Effect of Cyclical DOX Release on the p53 Pathway and Pathway-Related Molecules

by Ping Sun, Chunlei Gao, Zhe Chen, Siyu Wang, Gang Li, Mingming Luan and Yaoguang Wang

Biosensors 2025, 15(6), 383; https://doi.org/10.3390/bios15060383 - 13 Jun 2025

Viewed by 160

Abstract

Developing appropriate methods for real-time in situ investigation of how drugs influence signaling pathways and related biomolecules holds enormous potential for helping to provide an understanding of how anticancer drugs exert their effects. Herein, we report a smart nanoprobe, PDA-MB (DOX)-Pep, constructed on [...] Read more.

Developing appropriate methods for real-time in situ investigation of how drugs influence signaling pathways and related biomolecules holds enormous potential for helping to provide an understanding of how anticancer drugs exert their effects. Herein, we report a smart nanoprobe, PDA-MB (DOX)-Pep, constructed on the basis of polydopamine nanoparticles (PDA NPs) modified with a dense shell of molecular beacon (MB) with embedded doxorubicin (DOX) and peptide, which can respond specifically to miRNA-34a and Caspase-3 targets. Intracellular experiments demonstrated that, in comparison to the control nanoprobe PDA-MB-Pep, the smart nanoprobe could selectively respond to miRNA-34a, facilitating the release of the embedded DOX. The released DOX subsequently activated the p53 pathway, which further upregulated miRNA-34a expression, leading to additional DOX release. This initiated a cyclical process involving the probe’s response to miRNA-34a, DOX release, p53 activation, and miRNA-34a upregulation, ultimately enhancing cell apoptosis and increasing Caspase-3 expression. The designed smart nanoprobe offers a visual approach to explore how anticancer drugs influence signaling pathways and related molecules at the cellular level. Full article

(This article belongs to the Special Issue Application of Functional Nanomaterials in Photo/Electrical Biosensing)

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16 pages, 3643 KiB

Open AccessArticle

Sensing Protein Structural Transitions with Microfluidic Modulation Infrared Spectroscopy

by Lathan Lucas, Phoebe S. Tsoi, Ananya Nair, Allan Chris M. Ferreon and Josephine C. Ferreon

Biosensors 2025, 15(6), 382; https://doi.org/10.3390/bios15060382 - 13 Jun 2025

Viewed by 206

Abstract

Microfluidic modulation spectroscopy-infrared (MMS) offers a label-free, high-sensitivity approach for quantifying changes in protein secondary structures under native solution conditions. MMS subtracts the solvent backgrounds from sample signals by alternately flowing proteins and matched buffers through a microfluidic chamber, yielding clear amide I [...] Read more.

Microfluidic modulation spectroscopy-infrared (MMS) offers a label-free, high-sensitivity approach for quantifying changes in protein secondary structures under native solution conditions. MMS subtracts the solvent backgrounds from sample signals by alternately flowing proteins and matched buffers through a microfluidic chamber, yielding clear amide I spectra from microliter volumes. In this study, we validated MMS on canonical globular proteins, bovine serum albumin, mCherry, and lysozyme, demonstrating accurate detection and resolution of α-helix, β-sheet, and mixed-fold structures. Applying MMS to the intrinsically disordered protein Tau, we detected environment-driven shifts in transient conformers: both the acidic (pH 2.5) and alkaline (pH 10) conditions increased the turn/unordered structures and decreased the α-helix content relative to the neutral pH, highlighting the charge-mediated destabilization of the labile motifs. Hyperphosphorylation of Tau yielded a modest decrease in the α-helical fraction and an increase in the turn/unordered structures. Comparison of monomeric and aggregated hyperphosphorylated Tau revealed a dramatic gain in β-sheet and a loss in turn/unordered structures upon amyloid fibril formation, confirming MMS’s ability to distinguish disordered monomers from amyloids. These findings establish MMS as a robust platform for detecting protein secondary structures and monitoring aggregation pathways in both folded and disordered systems. The sensitive detection of structural transitions offers opportunities for probing misfolding mechanisms and advancing our understanding of aggregation-related diseases. Full article

(This article belongs to the Special Issue Design and Application of Microfluidic Biosensors in Biomedicine)

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14 pages, 1649 KiB

Open AccessArticle

Evaluation of Smartphones Equipped with Light Detection and Ranging Technology for Circumferential and Volumetric Measurements in Lower Extremity Lymphedema

by Masato Tsuchiya, Kanako Abe, Satoshi Kubo and Ryuichi Azuma

Biosensors 2025, 15(6), 381; https://doi.org/10.3390/bios15060381 - 12 Jun 2025

Viewed by 170

Abstract

Lower extremity lymphedema (LEL) requires precise limb measurements for treatment evaluation and compression garment design. Tape measurement (TM) is the standard method but is time-consuming. Smartphones with light detection and ranging (LiDAR) technology may offer fast and efficient alternatives for three-dimensional imaging and [...] Read more.

Lower extremity lymphedema (LEL) requires precise limb measurements for treatment evaluation and compression garment design. Tape measurement (TM) is the standard method but is time-consuming. Smartphones with light detection and ranging (LiDAR) technology may offer fast and efficient alternatives for three-dimensional imaging and measurement. This study evaluated the accuracy, reliability, and time efficiency of LiDAR measurements compared with those of TM in patients with LEL. A healthy volunteer and 55 patients were included. Circumferences of the foot, ankle, calf, knee, and thigh and the volume were measured using TM and smartphones with LiDAR. The water displacement method was used to validate volume measurements. The measurement time, reliability, correlation, agreement, and systematic differences between the methods were assessed. LiDAR showed excellent reliability in the healthy volunteer (inter-rater intraclass correlation coefficients: 0.960–0.988) and significantly reduced the measurement time compared with TM (64.0 ± 15.1 vs. 115.3 ± 30.6 s). In patients with LEL, strong correlations and agreements were observed for ankle, calf, and knee measurements. However, foot and thigh measurements showed lower correlations and larger discrepancies. LiDAR has excellent accuracy and reliability in measuring the circumference and volume of the lower leg and has the potential to reduce the time required to acquire data. Limitations include lower accuracy for foot and thigh measurements and the current workflow complexity, which requires the use of multiple software tools. Full article

(This article belongs to the Special Issue Smart, Connected, and Portable Biosensors and Bioelectronics for Advancing Human Healthcare, Disease Diagnosis, and Therapeutics (2nd Edition))

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36 pages, 3955 KiB

Open AccessReview

Electrochemical Microneedles for Real-Time Monitoring in Interstitial Fluid: Emerging Technologies and Future Directions

by Suhyeon Cha, Min Yu Choi, Min Jung Kim, Sang Baek Sim, Izzati Haizan and Jin-Ha Choi

Biosensors 2025, 15(6), 380; https://doi.org/10.3390/bios15060380 - 12 Jun 2025

Viewed by 238

Abstract

Conventional blood-based detection methods for biomarkers and analytes face significant limitations, including complex processing, variability in blood components, and the inability to provide continuous monitoring. These challenges hinder the early diagnosis and effective management of various health conditions. Electrochemical microneedles (MNs) have emerged [...] Read more.

Conventional blood-based detection methods for biomarkers and analytes face significant limitations, including complex processing, variability in blood components, and the inability to provide continuous monitoring. These challenges hinder the early diagnosis and effective management of various health conditions. Electrochemical microneedles (MNs) have emerged as a minimally invasive and highly efficient platform to overcome these barriers, enabling continuous molecular monitoring by directly accessing the interstitial fluid. Electrochemical MNs offer several advantages, including reduced patient discomfort, real-time data acquisition, enhanced specificity, and potential applications in wearable, long-term monitoring. In this review, we first analyze material selection and fabrication techniques to optimize sensor performance, stability, and biocompatibility. We then examine diverse detection strategies utilized in electrochemical MNs, including enzyme-based, aptamer-based, and antibody-based sensing mechanisms, each offering unique benefits in sensitivity and selectivity. Finally, we highlight the integration of electrochemical MN technology with multi-target detection, AI-driven analytics, and theragnostic capabilities. This convergence offers strong potential for smart healthcare and precision medicine. Through these technological innovations, electrochemical MNs are expected to play an important role in advancing continuous, noninvasive health monitoring and personalized medical care. Full article

(This article belongs to the Special Issue Recent Advancements in Nanomaterials for Biomolecular Monitoring in Miniaturized Sensing Platforms)

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30 pages, 4440 KiB

Open AccessSystematic Review

The Use of CRISPR-Cas Systems for Viral Detection: A Bibliometric Analysis and Systematic Review

by Othmane Jeddoub, Nadia Touil, Omar Nyabi, Elmostafa El Fahime, Khalid Ennibi, Jean-Luc Gala, Abdelaziz Benjouad and Lamiae Belayachi

Biosensors 2025, 15(6), 379; https://doi.org/10.3390/bios15060379 - 12 Jun 2025

Viewed by 256

Abstract

Viral infections impose a significant burden on global public health and the economy. This study examines the current state of CRISPR-Cas system research, focusing on their applications in viral detection and their evolution over recent years. A bibliometric analysis and systematic review were [...] Read more.

Viral infections impose a significant burden on global public health and the economy. This study examines the current state of CRISPR-Cas system research, focusing on their applications in viral detection and their evolution over recent years. A bibliometric analysis and systematic review were conducted using articles published between 2019 and 2024, retrieved from Web of Science, Scopus, and PubMed databases. Out of 2713 identified articles, 194 were included in the analysis. The findings reveal substantial growth in scientific output related to CRISPR-Cas systems, with the United States leading in research and development in this field. The rapid increase in CRISPR-Cas research during this period underscores its immense potential to transform viral diagnostics. With advantages such as speed, precision, and suitability for deployment in resource-limited settings, CRISPR-Cas systems outperform many traditional diagnostic methods. The concerted efforts of scientists worldwide further highlight the promising future of this technology. CRISPR-Cas systems are emerging as a powerful alternative, offering the possibility of expedited and accessible point-of-care testing and paving the way for more equitable and effective diagnostics on a global scale. Full article

(This article belongs to the Section Biosensor Materials)

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25 pages, 3696 KiB

Open AccessReview

Research Progress on Multiplexed Pathogen Detection Using Optical Biosensors

by Yue Wu, Xing Xu, Yinchu Zhu, Jiaxin Wan, Xingbo Wang, Xin Zhou, Xiangjun Li and Weidong Zhou

Biosensors 2025, 15(6), 378; https://doi.org/10.3390/bios15060378 - 12 Jun 2025

Viewed by 271

Abstract

The rapid and precise identification of multiple pathogens is critical for ensuring food safety, controlling epidemics, diagnosing diseases, and monitoring the environment. However, traditional detection methods are hindered by complex workflows, the need for skilled operators, and reliance on sophisticated equipment, making them [...] Read more.

The rapid and precise identification of multiple pathogens is critical for ensuring food safety, controlling epidemics, diagnosing diseases, and monitoring the environment. However, traditional detection methods are hindered by complex workflows, the need for skilled operators, and reliance on sophisticated equipment, making them unsuitable for rapid, on-site testing. Optical biosensors, known for their rapid analysis, portability, high sensitivity, and multiplexing capabilities, offer a promising solution for simultaneous multi-pathogenic identification. This paper explores recent advancements in the utilization of optical biosensors for multiple pathogenic detection. First, it provides an overview of key sensing principles, focusing on colorimetric, fluorescence-based, surface-enhanced Raman scattering (SERS), and surface plasmon resonance (SPR) techniques, as well as their applications in pathogenic detection. Then, the research progress and practical applications of optical biosensors for multiplex pathogenic detection are discussed in detail from three perspectives: microfluidic devices, nucleic acid amplification technology (NAAT), and nanomaterials. Finally, the challenges presented by optical biosensing technologies in multi-pathogen detection are discussed, along with future prospects and potential innovations in the field. Full article

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

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13 pages, 2540 KiB

Open AccessArticle

Simple Nanochannel-Modified Electrode for Sensitive Detection of Alkaline Phosphatase Through Electrochemiluminescence Signal Quenching by Enzymatic Reaction

by Tianjun Ma, Xuan Luo, Fengna Xi and Nuo Yang

Biosensors 2025, 15(6), 377; https://doi.org/10.3390/bios15060377 - 11 Jun 2025

Viewed by 227

Abstract

Development of sensitive and convenient alkaline phosphatase (ALP) detection methods is of great significance for food analysis, biomedical applications, and clinical tests. In this work, a sensitive detection method for ALP was established based on nanochannel-modified electrodes, where the electrochemical luminescence (ECL) signal [...] Read more.

Development of sensitive and convenient alkaline phosphatase (ALP) detection methods is of great significance for food analysis, biomedical applications, and clinical tests. In this work, a sensitive detection method for ALP was established based on nanochannel-modified electrodes, where the electrochemical luminescence (ECL) signal was quenched by the enzymatic reaction product. Vertically ordered mesoporous silica film (VMSF) was rapidly grown on low-cost ITO via the electrochemically assisted self-assembly (EASA) method. The resulting modified electrode (VMSF/ITO) exhibited a uniform and ordered nanochannel structure with nanochannel diameter of 2–3 nm and charge-selective permeability, enabling the enrichment of cationic ECL emitter tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)₃²⁺). Compared to the ITO electrode, VMSF/ITO increased the ECL signal by 60 times. In the presence of ALP, it catalyzes the hydrolysis of its substrate, disodium phenyl phosphate hydrate (DPP), generating phenol (Phe), which quenched the ECL signal of Ru(bpy)₃²⁺ and the co-reactant N,N-Dipropyl-1-propanamine (TPA). Based on this principle, ECL detection of ALP can be achieved. The linear detection range for ALP was 0.01 U/L to 30 U/L, with a limit of detection (LOD) of 0.008 U/L. The sensor exhibited high selectivity. Combined with the anti-contamination and anti-interference capabilities of VMSF, the constructed sensor enabled the detection of ALP levels in milk samples. Full article

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

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15 pages, 6302 KiB

Open AccessArticle

Fluorescent–Electrochemical–Colorimetric Triple-Model Immunoassays with Multifunctional Metal–Organic Frameworks for Signal Amplification

by Ning Xia, Chuye Zheng and Gang Liu

Biosensors 2025, 15(6), 376; https://doi.org/10.3390/bios15060376 - 11 Jun 2025

Viewed by 204

Abstract

Multimode immunoassays based on multiple response mechanisms have received great attention due to their capacity to effectively improve the accuracy and reliability of biosensing platforms. However, few strategies have been reported for triple-mode immunoassays due to the shortage of multifunctional sensing materials and [...] Read more.

Multimode immunoassays based on multiple response mechanisms have received great attention due to their capacity to effectively improve the accuracy and reliability of biosensing platforms. However, few strategies have been reported for triple-mode immunoassays due to the shortage of multifunctional sensing materials and the incompatibility of signal transduction methods in different detection modes. In this work, a fluorescent–electrochemical–colorimetric triple-mode immunoassay platform was proposed with Cu-based metal–organic frameworks (MOFs) as the signal labels. The captured Cu-MOFs were successfully decomposed under an acidic condition, leading to the release of numerous Cu²⁺ ions and 2-aminobenzene-1,4-dicarboxylic acid (NH₂-BDC) ligands. The released NH₂-BDC were determined by fluorescence titration. Meanwhile, the released Cu²⁺ were readily quantified by differential pulse voltammetry (DPV) and simply detected through the catalytic oxidation of chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB). Taking alpha-fetoprotein (AFP) as a model analyte, the designed triple-mode immunoassays showed good performances with the linear range of 10–200 pg/mL, 10–200 pg/mL, and 1–100 pg/mL for the fluorescent, electrochemical, and colorimetric modes, respectively. The proposed triple-mode biosensing platforms show great potential for the applications in disease diagnosis, since they can be easily extended to other bioassays by changing the targets and recognition elements. Full article

(This article belongs to the Special Issue Signal Amplification in Biosensing)

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27 pages, 2382 KiB

Open AccessReview

Advances of Nanozyme-Driven Multimodal Sensing Strategies in Point-of-Care Testing

by Ziyi Chang, Qingjie Fu, Mengke Wang and Demin Duan

Biosensors 2025, 15(6), 375; https://doi.org/10.3390/bios15060375 - 10 Jun 2025

Viewed by 302

Abstract

Point-of-care testing (POCT) has garnered widespread attention due to its rapid, convenient, and efficient detection capabilities, particularly playing an increasingly pivotal role in medical diagnostics and significantly improving the efficiency and quality of healthcare services. Nanozymes, as novel enzyme-mimicking materials, have emerged as [...] Read more.

Point-of-care testing (POCT) has garnered widespread attention due to its rapid, convenient, and efficient detection capabilities, particularly playing an increasingly pivotal role in medical diagnostics and significantly improving the efficiency and quality of healthcare services. Nanozymes, as novel enzyme-mimicking materials, have emerged as a research hotspot owing to their superior catalytic performance, low cost, and robust stability. This review provides a systematic overview of the fundamental characteristics and classifications of nanozymes, along with various sensing strategies employed in POCT applications, colorimetric, electrochemical, fluorescent, chemiluminescent, and surface-enhanced Raman scattering (SERS)-based approaches. Furthermore, this review highlights innovative designs that enhance the sensitivity and accuracy of POCT across multiple domains, such as biomarker detection, environmental monitoring, and food safety analysis, thereby offering novel perspectives for the practical implementation of nanozymes in point-of-care diagnostics. Finally, this review analyzes current challenges in nanozyme-based POCT systems, including limitations in optimizing catalytic activity, ensuring nanozyme homogeneity, and achieving large-scale production, while proposing future development trajectories. Full article

(This article belongs to the Special Issue Advances in Nanozyme-Based Biosensors)

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21 pages, 2609 KiB

Open AccessArticle

Assessing the Role of EEG Biosignal Preprocessing to Enhance Multiscale Fuzzy Entropy in Alzheimer’s Disease Detection

by Pasquale Arpaia, Maria Cacciapuoti, Andrea Cataldo, Sabatina Criscuolo, Egidio De Benedetto, Antonio Masciullo, Marisa Pesola and Raissa Schiavoni

Biosensors 2025, 15(6), 374; https://doi.org/10.3390/bios15060374 - 10 Jun 2025

Viewed by 296

Abstract

Quantitative electroencephalography (QEEG) has emerged as a promising tool for detecting Alzheimer’s disease (AD). Among QEEG measures, Multiscale Fuzzy Entropy (MFE) shows great potential in identifying AD-related changes in EEG complexity. However, MFE is intrinsically linked to signal amplitude, which can vary substantially [...] Read more.

Quantitative electroencephalography (QEEG) has emerged as a promising tool for detecting Alzheimer’s disease (AD). Among QEEG measures, Multiscale Fuzzy Entropy (MFE) shows great potential in identifying AD-related changes in EEG complexity. However, MFE is intrinsically linked to signal amplitude, which can vary substantially among EEG systems, and this hinders the adoption of this metric for AD detection. To overcome this issue, this study investigates different preprocessing strategies to make the calculation of MFE less dependent on the specific amplitude characteristics of the EEG signals at hand. This contributes to generalizing and making more robust the adoption of MFE for AD detection. To demonstrate the robustness of the proposed preprocessing methods, binary classification tasks with Support Vector Machines (SVMs), Random Forest (RF), and K-Nearest Neighbor (KNN) classifiers are used. Performance metrics, such as classification accuracy and Matthews Correlation Coefficient (MCC), are employed to assess the results. The methodology is validated on two public EEG datasets. Results show that amplitude transformation, particularly normalization, significantly enhances AD detection, achieving mean classification accuracy values exceeding 80% with an uncertainty of 10% across all classifiers. These results highlight the importance of preprocessing in improving the accuracy and the reliability of EEG-based AD diagnostic tools, offering potential advancements in patient management and treatment planning. Full article

(This article belongs to the Section Biosensors and Healthcare)

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17 pages, 2881 KiB

Open AccessArticle

Biological Sensing Using Vertical MoS₂-Graphene Heterostructure-Based Field-Effect Transistor Biosensors

by Ying Chen, Nataly Vicente, Tung Pham and Ashok Mulchandani

Biosensors 2025, 15(6), 373; https://doi.org/10.3390/bios15060373 - 10 Jun 2025

Viewed by 263

Abstract

Our study develops two configurations of MoS₂ and graphene heterostructures—MoS₂ on graphene (MG) and graphene on MoS₂ (GM)—to investigate biomolecule sensing in field-effect transistor (FET) biosensors. Leveraging MoS₂ and graphene’s distinctive properties, we employ specialized functionalization techniques for each [...] Read more.

Our study develops two configurations of MoS₂ and graphene heterostructures—MoS₂ on graphene (MG) and graphene on MoS₂ (GM)—to investigate biomolecule sensing in field-effect transistor (FET) biosensors. Leveraging MoS₂ and graphene’s distinctive properties, we employ specialized functionalization techniques for each configuration: graphene with MoS₂ on top uses a silane-based method with triethoxysilylbutyraldehyde (TESBA), and MoS₂ with graphene on top utilizes 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE). Our research explores the application of MoS₂–Graphene heterostructures in biosensors, emphasizing the roles of synthesis, fabrication, and material functionalization in optimizing sensor performance. Through our experimental investigations, we have observed that doping MoS₂ and graphene leads to noticeable changes in the Raman spectrum and shifts in transfer curves. Techniques such as XPS, Raman, and AFM have successfully confirmed the biofunctionalization. Transfer curves were instrumental in characterizing the biosensing performance, revealing that GM configurations exhibit higher sensitivity and a lower limit of detection (LOD) compared to MG configurations. We demonstrate that GM heterostructures offer superior sensitivity and specificity in biosensing, highlighting their significant potential to advance biosensor technologies. This research contributes to the field by detailing the creation process of vertical MoS₂–graphene heterostructures and evaluating their effectiveness in accurate biomolecule detection, advancing biosensing technology. Full article

(This article belongs to the Special Issue Application of Functional Nanomaterials in Photo/Electrical Biosensing)

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12 pages, 694 KiB

Open AccessArticle

Sudomotor Dysfunction as an Early Marker of Autonomic and Cardiovascular Risk in Diabetes: Insights from a Cross-Sectional Study Using SUDOSCAN

by Larisa Anghel, Claudiu Cobuz, Laura-Cătălina Benchea, Vasile Maciuc, Maricela Cobuz, Radu-Andy Sascău and Cristian Stătescu

Biosensors 2025, 15(6), 372; https://doi.org/10.3390/bios15060372 - 10 Jun 2025

Viewed by 183

Abstract

Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to [...] Read more.

Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to measure ESC in the hands and feet. Clinical and laboratory parameters, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, lipid profile, and cardiovascular risk, were analyzed for correlations with ESC. Neuropathy status was evaluated, and ROC analysis was performed to assess diagnostic accuracy. Results: Sudomotor dysfunction was prevalent, particularly in patients with a diabetes duration exceeding 20 years (p < 0.05). Men showed significantly higher right foot ESC than women (76.5 ± 13.1 vs. 74.0 ± 13.5 µS, p = 0.041). A strong inverse correlation was found between cardiovascular risk score and right foot ESC (r = −0.455, p < 0.001). Left foot ESC also correlated inversely with cardiovascular risk (r = −0.401, p < 0.001) and HbA1c (r = −0.150, p = 0.049), while a weak positive correlation was seen with BMI (r = 0.145, p = 0.043). ROC analysis showed the highest area under the curve (AUC) in right foot ESC for autonomic neuropathy (AUC = 0.750, 95% CI: 0.623–0.877, p < 0.001). Conclusions: This study is among the few to systematically correlate ESC with validated cardiovascular risk scores in a diabetic outpatient cohort, highlighting its potential as a novel early screening biomarker for autonomic and cardiovascular complications. Full article

(This article belongs to the Section Biosensors and Healthcare)

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47 pages, 1518 KiB

Open AccessReview

Advances in MoS₂-Based Biosensors: From Material Fabrication and Characterization to Biomedical, Environmental, and Industrial Applications

by Chun-Liang Lai, Arvind Mukundan, Riya Karmakar, Roopmeet Kaur, Kuo-Liang Huang and Hsiang-Chen Wang

Biosensors 2025, 15(6), 371; https://doi.org/10.3390/bios15060371 - 10 Jun 2025

Viewed by 425

Abstract

The growing demand for low-cost biosensors has stimulated the study of new technologies and materials like molybdenum disulfide (MoS₂). Due to its electroconductive nature and high surface-to-volume ratio, it allows for the ultra-sensitive detection of biomarkers. The crystal structure of MoS [...] Read more.

The growing demand for low-cost biosensors has stimulated the study of new technologies and materials like molybdenum disulfide (MoS₂). Due to its electroconductive nature and high surface-to-volume ratio, it allows for the ultra-sensitive detection of biomarkers. The crystal structure of MoS₂ provides it with a unique micrometer thickness, making it appropriate for biosensing in healthcare, environmental monitoring, and food safety. As compared to traditional materials, MoS₂ can work without labels (through field-effect transduction or plasmonic shifts) while maintaining biocompatibility and low-cost fabrication, which fill significant voids in the early diagnosis of diseases. This paper provides an overview of the recent advancements in MoS₂-based biosensors, which are primarily focused on the field-effect transistors and surface plasmon resonance techniques and fabrication methods for MoS₂-based biosensors like mechanical exfoliation, liquid-phase exfoliation, physical vapor deposition, chemical vapor deposition, and chemical exfoliation, applications in various industries, and their characterization techniques to evaluate the quality and functionality of MoS₂ nanosheets in biosensors. While certain challenges remain like improving conductivity and scalability, MoS₂-based biosensors serve as a powerful tool for the precise and reliable detection of biomarkers in environmental, food, and healthcare industries. Full article

(This article belongs to the Collection Novel Sensing System for Biomedical Applications)

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11 pages, 1351 KiB

Open AccessArticle

Improving the Enrichment of Submicron-Sized Particles by Size Decreasing of Cruciform Cross-Sectional Microchannel in Viscoelastic Microfluidics

by Jaekyeong Jang, Eunjin Kim, Sungdong Kim, Ok-Chan Jeong, Sangwook Lee and Younghak Cho

Biosensors 2025, 15(6), 370; https://doi.org/10.3390/bios15060370 - 9 Jun 2025

Viewed by 229

Abstract

The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating [...] Read more.

The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating the separation and focusing of various cell types, including blood cells, circulating tumor cells (CTCs), and microalgae. However, the viscoelastic nature of the particles imposes limitations in the handling of submicron-sized particles, due to a significant decrease in the viscoelastic force acting on the particle. In this study, we propose a microfluidic device featuring a cruciform cross-sectional microchannel with 45 µm and 45 µm of its vertical and horizontal size, respectively. The cruciform microchannel, which has a 270° reflex angle on four corners, can increase the viscoelastic force on the particles, allowing the device to focus submicron-sized particles down to 180 nm in a single-stream manner. It is important to note that the single-stream formation was maintained, while the channel width at the outlet region was drastically increased, allowing for the enrichment of submicron-sized particles. For biological feasibility, the proposed device also demonstrates the single-stream focusing on biological particles such as bacteria. The presented microfluidic device would have great potential for the focusing and enrichment of nanoparticles including bacteria in a highly robust manner, expecting its use in the various fields such as diverse biological analysis and biomedical research. Full article

(This article belongs to the Section Nano- and Micro-Technologies in Biosensors)

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12 pages, 1925 KiB

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 - 9 Jun 2025

Viewed by 320

Abstract

Sub-wavelength metallic nanostructures allow the squeezing of light within nanoscale regions, called plasmonic hotspots. Squeezed near-field light has been demonstrated to detect, modulate, and generate light in more effective ways. The enhanced electric field in the plasmonic hotspots are also utilized for identifying [...] Read more.

Sub-wavelength metallic nanostructures allow the squeezing of light within nanoscale regions, called plasmonic hotspots. Squeezed near-field light has been demonstrated to detect, modulate, and generate light in more effective ways. The enhanced electric field in the plasmonic hotspots are also utilized for identifying molecular fingerprints in a more sensitive manner, i.e., surface-enhanced Raman spectroscopy (SERS). SERS is a versatile tool used to characterize chemicals and biomolecules with the advantages of label-free detection, specificity, and high sensitivity compared to fluorescence and colorimetric sensing methods. With its practical and diverse applications such as biomedical sensing, the evaluation of SERS on diverse nano-structure platforms and materials is highly in demand. Nanogap structures are promising SERS platforms which can be fabricated over a large area with uniform nanoscale gap size. Here, we demonstrate the fabrication of large-area metal–insulator–metal nanogap structures with different metals (i.e., Au and Ag) and analyze material dependence on SERS. While both nanometer-sized gap structures exhibit a large enhancement factor for Raman spectroscopy, Ag-based structures exhibit 58- and 15-times-larger enhancement factors for bottom and top plasmonic hotspots, respectively. The enhanced detection on a silver nanogap platform is attributed to enhanced electric field in the gap, as confirmed by simulation. Our findings provide not only a way to better understand SERS in different metallic nano platforms but also insights for designing highly sensitive nanoscale chemical and biomedical sensors. Full article

(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)

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10 pages, 1763 KiB

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 - 7 Jun 2025

Viewed by 339

Abstract

Terahertz (THz) biosensing faces critical challenges in balancing high sensitivity and broadband spectral coverage, particularly under miniaturized device constraints. Conventional quasi-bound states in the continuum (QBIC) metasurfaces achieve high quality factor (Q) but suffer from narrow bandwidth, while angle-scanning strategies for broadband detection [...] Read more.

Terahertz (THz) biosensing faces critical challenges in balancing high sensitivity and broadband spectral coverage, particularly under miniaturized device constraints. Conventional quasi-bound states in the continuum (QBIC) metasurfaces achieve high quality factor (Q) but suffer from narrow bandwidth, while angle-scanning strategies for broadband detection require complex large-angle illumination. Here, we propose a symmetry-engineered, all-dielectric metasurface that leverages multipolar interference coupling to overcome this limitation. By introducing angular perturbation, the metasurface transforms the original magnetic dipole (MD)-dominated QBIC resonance into hybridized, multipolar modes. It arises from the interference coupling between MD, toroidal dipole (TD), and magnetic quadrupole (MQ). This mechanism induces dual counter-directional, frequency-shifted, resonance branches within angular variations below 16°, achieving simultaneous 0.42 THz broadband coverage and high Q of 499. Furthermore, a derived analytical model based on Maxwell equations and mode coupling theory rigorously validates the linear relationship between frequency splitting interval and incident angle with the Relative Root Mean Square Error (RRMSE) of 1.4% and the coefficient of determination (

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

Viewed by 304

Abstract

Background: The influence of gait speed on lower-extremity coordination while walking in people with Parkinson’s disease (pwPD) is poorly understood. This study sought to investigate the relationship between gait speed and hip–knee coordination and coordination variability in older adults and pwPD. Methods: A [...] Read more.

Background: The influence of gait speed on lower-extremity coordination while walking in people with Parkinson’s disease (pwPD) is poorly understood. This study sought to investigate the relationship between gait speed and hip–knee coordination and coordination variability in older adults and pwPD. Methods: A total of 27 pwPD and 21 healthy older adults were recruited. Participants walked in a straight line at slow, preferred, and fast walking speeds. Gait data were collected using inertial measurement units, and the kinematics of the hip and knee were calculated. Coordination and coordination variability at the hip–knee joint pair were determined using continuous relative phase. A repeated measures two-way ANCOVA tested the impact of gait speed on coordination and coordination variability, while group differences were evaluated using statistical parametric mapping (SPM). Results: Neither the healthy older adults nor the pwPD adjusted their hip–knee coordination in response to changes in gait speed. pwPD also displayed a trend towards restricted hip and knee joint excursion compared to older adults, which may further limit their ability to adapt gait strategies. Conclusions: These findings suggest that interventions addressing both joint excursion and motor adaptability may be important for improving gait function in individuals with Parkinson’s disease. Real-world applicability can be found in the potential of wearable sensors to become a valuable tool in routine clinical practice for both diagnosis and ongoing management. Trial registration: The study is registered in the German Clinical Trials Register (DRKS00022998). Full article

(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

Viewed by 295

Abstract

Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of [...] Read more.

Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of the present work was to investigate whether the electroconductive polymer polypyrrole (PPy) could be used for fabricating such electrodes, as PPy is several orders softer than metals. For this purpose, we here investigated if electrodes made using coatings and films of PPy doped with naphthalin-2-sulfonic acid (PPy/N) are capable to record and elicit by stimulation cardiac monophasic action potentials (MAPs) and if PPy/N is also biocompatible. The results of this study showed that the tested PPy/N electrodes are capable of recording MAPs almost identical to the MAPs recorded with platinum electrodes and eliciting stimulation-evoked MAPs almost identical to the spontaneous MAPs. In addition, we show here that the cell cultures that we used for biocompatibility tests grew in a similar manner on PPy/N and platinum substrates. We, therefore, conclude that PPy/N coatings and films have recording and electrical stimulation capabilities that are similar to those of platinum electrodes and that PPy/N substrates are as biocompatible as the platinum substrates. Full article

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

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24 pages, 1476 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

Viewed by 232

Abstract

This study investigated the effect of wearable ultrasound-imaging-based visual feedback (UVF) on assisting paretic ankle dorsiflexion training of chronic stroke survivors. Thirty-three participants with unilateral hemiplegia performed maximal isometric contractions on an isokinetic dynamometer in randomized conditions with and without UVF that provided [...] Read more.

This study investigated the effect of wearable ultrasound-imaging-based visual feedback (UVF) on assisting paretic ankle dorsiflexion training of chronic stroke survivors. Thirty-three participants with unilateral hemiplegia performed maximal isometric contractions on an isokinetic dynamometer in randomized conditions with and without UVF that provided by a wearable ultrasound imaging system. Torque parameters (mean, peak, percentage of maximal voluntary contraction) and tibialis anterior muscle thickness were analyzed across different contraction phases. Statistical comparisons were conducted using paired t-tests or Wilcoxon tests. Correlation analyses were performed using Pearson’s or Spearman’s tests. Results demonstrated that UVF significantly improved torque output, as evidence by the increased percentage of maximal voluntary contraction (%MVC) during entire contractions (p = 0.007), increased mean (p ≤ 0.022) and peak (p ≤ 0.044) torque and the %MVC (p ≤ 0.004) during mid and end phases, and larger muscle thickness during mid contraction (p = 0.045). Moderate correlations were found between torque and muscle thickness (r ≥ 0.30, p ≤ 0.049). These findings preliminarily supported the positive outcomes of real-time wearable UVFs in enhancing paretic ankle dorsiflexion strength and force control during isometric contractions in chronic stroke survivors. While the developed and validated new training protocol may potentially serve as a practical adjunct to existing rehabilitation approaches, further investigations emphasizing the functional outcomes and clinical translations are still needed to verify the clinical utility. Full article

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

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13 pages, 1960 KiB

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

Viewed by 347

Abstract

Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. The early detection of aggressive forms is critical. Current diagnostic methods, including PSA testing and biopsies, are invasive and often yield false results. MicroRNA-141 (miRNA-141) has emerged [...] Read more.

Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. The early detection of aggressive forms is critical. Current diagnostic methods, including PSA testing and biopsies, are invasive and often yield false results. MicroRNA-141 (miRNA-141) has emerged as a promising non-invasive biomarker due to its elevated levels in the urine of patients with metastatic prostate cancer. Here, a low-cost, paper-based electrochemical biosensor for the sensitive detection of miRNA-141 in synthetic urine is reported. The device employs inkjet-printed gold electrodes on photopaper, functionalized with thiolated single-stranded DNA-141 capture probes for specific target recognition. The biosensor achieves a sensitivity of 78.66 fM µA⁻¹ cm⁻² and a linear detection range of 1 fM to 100 nM, encompassing clinically relevant concentrations of miRNA-141 found in patients with metastatic prostate cancer. A low limit of detection of 2.15 fM, strong selectivity against non-target sequences, and a rapid response time of 15 min further highlight the diagnostic potential of the device. This platform represents a significant advancement in the development of point-of-care diagnostic tools for prostate cancer and is readily adaptable for detecting other disease-specific miRNAs through simple probe modification. As such, it holds broad promise for accessible, early-stage cancer detection and longitudinal disease monitoring in diverse clinical settings. Full article

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

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43 pages, 9912 KiB

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

Viewed by 379

Abstract

Background: Food safety remains a global concern due to biological and chemical contaminants, including adulterants, pathogens, antibiotic residues, and pesticides. Traditional detection methods are accurate but limited by time requirements, complex sample preparation, high costs, and poor field applicability. Surface-Enhanced Raman Spectroscopy [...] Read more.

Background: Food safety remains a global concern due to biological and chemical contaminants, including adulterants, pathogens, antibiotic residues, and pesticides. Traditional detection methods are accurate but limited by time requirements, complex sample preparation, high costs, and poor field applicability. Surface-Enhanced Raman Spectroscopy (SERS) offers non-destructive analysis with low detection limits and high specificity, yet conventional SERS substrates face challenges with reproducibility, nanoparticle aggregation, and sensitivity in food matrices. Hydrogels have emerged as supporting materials for SERS due to their water content, tunable porosity, flexibility, and ability to entrap plasmonic nanostructures. Scope and Approach: This review examines recent advances in hydrogel-integrated SERS platforms for food safety applications. The three-dimensional structure of hydrogels enables homogeneous distribution of metal nanoparticles, prevents aggregation, and offers analyte enrichment. We analyze material design, functionalization strategies, and how hydrogel properties—crosslinking density, porosity, surface charge, and nanoparticle distribution—influence SERS performance in food matrices. Key Findings and Conclusions: Hydrogel-integrated SERS platforms demonstrate superior performance in detecting various food contaminants—including pesticides, adulterants, and additives—in real food matrices, often achieving detection limits in the nanomolar to picomolar range, depending on the analyte and substrate design. Current limitations include storage stability concerns, batch-to-batch variability, and regulatory acceptance hurdles. Future research directions should focus on multiplex detection capabilities, integration with smart sensing technologies, and industrial scalability to facilitate practical deployment in global food safety monitoring across diverse supply chains. Full article

(This article belongs to the Special Issue Advanced SERS Biosensors for Detection and Analysis)

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