Biosensors

19 pages, 1061 KiB

Open AccessArticle

Development and Characterisation of a Microneedle Sensor for Intrapartum Fetal Monitoring

by Jill M Mitchell, Chinmay V Thatte, Ryan Sebastian, Conor O’Mahony, R A Greene, J R Higgins, Paul Galvin, F P McCarthy and Sofia R Teixeira

Biosensors 2025, 15(8), 517; https://doi.org/10.3390/bios15080517 - 8 Aug 2025

Abstract

This study presents the in vitro and preliminary ex vivo development of a novel microneedle-based pH sensor for continuous intrapartum fetal monitoring. The objective was to evaluate the feasibility of using microneedle sensors to monitor fetal pH during labour and to develop a [...] Read more.

This study presents the in vitro and preliminary ex vivo development of a novel microneedle-based pH sensor for continuous intrapartum fetal monitoring. The objective was to evaluate the feasibility of using microneedle sensors to monitor fetal pH during labour and to develop a proof-of-principle microneedle pH sensor that meets clinical requirements such as high sensitivity to small pH changes (0.05 units) within a relevant range (6.50–7.45), minimal tissue disruption, and a compact design suitable for transcervical placement on the fetal scalp (<40 mm diameter). Platinum microneedles were passivated with ArCare medical adhesive and coated with iridium oxide via electrodeposition. Sensitivity was tested in phosphate buffered saline (PBS) and artificial interstitial fluid (ISF), using both external Ag/AgCl and internal platinum pseudo-reference electrodes. In PBS, the sensor exhibited linear responses in increments of 0.05 pH units over the clinically relevant range (6.5–7.45), with slopes of −60.49 mV/pH (R² = 0.946, accuracy = 97.65%) and −63.2 mV/pH (R² = 0.910, accuracy = 93.70%) in the external and internal configurations, respectively. In ISF, a slope of −25.5 mV/pH (R² = 0.979) was obtained. Ex vivo testing on human skin confirmed successful microneedle penetration without visible iridium oxide transfer or tissue damage, as indicated by methylene blue staining. These findings support the potential for continuous minimally invasive fetal pH monitoring during labour, representing a significant step toward more objective and specific intrapartum assessment. Full article

(This article belongs to the Special Issue Nano/Micro Biosensors for Biomedical Applications (2nd Edition))

17 pages, 18925 KiB

Open AccessArticle

Theory Design of a Virtual Polarizer with Multiscale and Multi-Biomass Sensing

by Chuanqi Wu and Haifeng Zhang

Biosensors 2025, 15(8), 516; https://doi.org/10.3390/bios15080516 - 8 Aug 2025

Abstract

Recently, more and more attention has been paid to human health with the rapid development of society. A designed virtual polarizer (VP) can realize multiscale and multi-biomass sensing, including temperature, cancerous cells, and COVID-19. Based on coherent perfect polarization conversion, a certain polarization [...] Read more.

Recently, more and more attention has been paid to human health with the rapid development of society. A designed virtual polarizer (VP) can realize multiscale and multi-biomass sensing, including temperature, cancerous cells, and COVID-19. Based on coherent perfect polarization conversion, a certain polarization conversion can be fulfilled within 1.72~2.14 THz. Then, through observing the displacement of a perfect matching point (PMP), variations in temperature can be accurately determined, covering from 299 K to 315 K, with a sensitivity (S) of 0.0198 THz/K. Moreover, a sharp coherent perfect absorption (CPA) peak generated from the VP can be employed for the detection of cancerous cells and COVID-19. The refractive index (RI) detection range of cancerous cells is from 1.36 RIU to 1.41 RIU with the sensitivity being −4.45881 THz/RIU. The average quality factor (Q), figure of merit (FOM), and detection limit (DL) are 825.36, 241.11 RIU⁻¹, and −36.83 dB. For the COVID-19 solution concentration (SC) from 0 mM to 525 mM, by mapping SC to RI, the RI sensing range is 1.344 RIU–1.355 RIU with the S being −5.03467 THz/RIU. The relevant Q, FOM, and DL are 760.85, 244.94 RIU⁻¹, and −36.89 dB. Based on two strategies of PMP and CPA, the proposed VP is capable of multiscale and multi-biomass sensing with excellent detection performance, providing a new detection method for biosensing. Full article

(This article belongs to the Special Issue Advanced Optics and Photonics in Biosensing Applications)

15 pages, 2906 KiB

Open AccessArticle

Cell Observation and Analysis with a Three-Dimensional Optical Wave Field Microscope

by Shimon Matsumoto, Shoko Itakura, Junta Minato, Masahiro Hashimoto, Shu Obana, Mai Kanai, Masaki Kobayashi, Makiya Nishikawa and Kosuke Kusamori

Biosensors 2025, 15(8), 515; https://doi.org/10.3390/bios15080515 - 8 Aug 2025

Abstract

Cell observation is crucial in life science research, and advancements in microscopy are essential for deciphering biological phenomena. These technological developments have significantly enhanced our understanding of cellular mechanisms and processes. Light, characterized by its wave-like properties, is fundamental to scientific observation. Recently, [...] Read more.

Cell observation is crucial in life science research, and advancements in microscopy are essential for deciphering biological phenomena. These technological developments have significantly enhanced our understanding of cellular mechanisms and processes. Light, characterized by its wave-like properties, is fundamental to scientific observation. Recently, new technologies have been developed to detect changes in light wavelengths upon illumination, using them as signals for visualization. Three-dimensional optical wave field microscopy (3D-OWFM), a recent innovation in optimal imaging, leverages the wave properties of light to capture objects without labels, invasive procedures, or direct contact, thus facilitating non-invasive observation. In this study, we observed and analyzed mammalian cell structure and behaviors using 3D-OWFM. The 3D-OWFM revealed the intrinsic structure of the cells, including the cytoplasm and nucleus, with high clarity. The optical path difference (OPD) intensity effectively highlighted nuclear complexity. Furthermore, time-lapse imaging captured cell division process through variations in OPD signal intensity. These findings indicate that 3D-OWFM has significant potential for cell observation, offering insights not attainable with conventional microscopes. Full article

(This article belongs to the Special Issue Biosensing Applications for Cell Monitoring)

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19 pages, 8504 KiB

Open AccessArticle

Fiber-Based Ultra-High-Speed Diffuse Speckle Contrast Analysis System for Deep Blood Flow Sensing Using a Large SPAD Camera

by Quan Wang, Renzhe Bi, Songhua Zheng, Ahmet T. Erdogan, Yi Qi, Chenxu Li, Yuanyuan Hua, Mingliang Pan, Yining Wang, Neil Finlayson, Malini Olivo, Robert K. Henderson and David Uei-Day Li

Biosensors 2025, 15(8), 514; https://doi.org/10.3390/bios15080514 - 7 Aug 2025

Abstract

Diffuse speckle contrast analysis (DSCA), also called speckle contrast optical spectroscopy (SCOS), has emerged as a groundbreaking optical imaging technique for tracking dynamic biological processes, including blood flow and tissue perfusion. Recent advancements in single-photon avalanche diode (SPAD) cameras have unlocked exceptional sensitivity, [...] Read more.

Diffuse speckle contrast analysis (DSCA), also called speckle contrast optical spectroscopy (SCOS), has emerged as a groundbreaking optical imaging technique for tracking dynamic biological processes, including blood flow and tissue perfusion. Recent advancements in single-photon avalanche diode (SPAD) cameras have unlocked exceptional sensitivity, time resolution, and high frame-rate imaging capabilities. Despite this, the application of large-format SPAD arrays in speckle contrast analysis is still relatively uncommon. This study introduces a pioneering use of a large-format SPAD camera for DSCA. By harnessing the camera’s high temporal resolution and photon-detection efficiency, we significantly enhance the accuracy and robustness of speckle contrast measurements. Our experimental results demonstrate the system’s remarkable ability to capture rapid temporal variations over a broad field of view, enabling detailed spatiotemporal analysis. Through simulations, phantom experiments, and in vivo studies, we validated the proposed approach’s potential for cerebral blood flow and functional tissue monitoring. This work highlights the transformative impact of large SPAD cameras on DSCA, setting the stage for breakthroughs in optical imaging. Full article

(This article belongs to the Special Issue Optical Biosensors for Healthcare: An Artificial Intelligence Approach)

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25 pages, 1054 KiB

Open AccessReview

Gut Feeling: Biomarkers and Biosensors’ Potential in Revolutionizing Inflammatory Bowel Disease (IBD) Diagnosis and Prognosis—A Comprehensive Review

by Beatriz Teixeira, Helena M. R. Gonçalves and Paula Martins-Lopes

Biosensors 2025, 15(8), 513; https://doi.org/10.3390/bios15080513 - 7 Aug 2025

Abstract

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on [...] Read more.

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article

(This article belongs to the Special Issue Feature Papers of Biosensors)

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28 pages, 6652 KiB

Open AccessArticle

White Light Spectroscopy for Sampling-Free Bacterial Contamination Detection During CAR T-Cells Production: Towards an On-Line and Real-Time System

by Bruno Wacogne, Naïs Vaccari, Claudia Koubevi, Charles-Louis Azzopardi, Bilal Karib, Alain Rouleau and Annie Frelet-Barrand

Biosensors 2025, 15(8), 512; https://doi.org/10.3390/bios15080512 - 6 Aug 2025

Abstract

Advanced therapy medicinal products (ATMPs), especially effective against cancer, remain costly due to their reliance on genetically modified T cells. Contamination during production is a major concern, as traditional quality control methods involve samplings, which can themselves introduce contaminants. It is therefore necessary [...] Read more.

Advanced therapy medicinal products (ATMPs), especially effective against cancer, remain costly due to their reliance on genetically modified T cells. Contamination during production is a major concern, as traditional quality control methods involve samplings, which can themselves introduce contaminants. It is therefore necessary to develop methods for detecting contamination without sampling and, if possible, in real time. In this article, we present a white light spectroscopy method that makes this possible. It is based on shape analysis of the absorption spectrum, which evolves from an approximately Gaussian shape to a shape modified by the 1/λ component of bacterial absorption spectra when contamination develops. A warning value based on this shape descriptor is proposed. It is demonstrated that a few hours are sufficient to detect contamination and trigger an alarm to quickly stop the production. This time-saving should reduce the cost of these new drugs, making them accessible to as many people as possible. This method can be used regardless of the type of contaminants, provided that the shape of their absorption spectrum is sufficiently different from that of pure T cells so that the shape descriptor is efficient. Full article

(This article belongs to the Special Issue Biosensing Applications for Cell Monitoring)

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43 pages, 8518 KiB

Open AccessReview

Cutting-Edge Sensor Technologies for Exosome Detection: Reviewing Role of Antibodies and Aptamers

by Sumedha Nitin Prabhu and Guozhen Liu

Biosensors 2025, 15(8), 511; https://doi.org/10.3390/bios15080511 - 6 Aug 2025

Abstract

Exosomes are membranous vesicles that play a crucial role as intercellular messengers. Cells secrete exosomes, which can be found in a variety of bodily fluids such as amniotic fluid, semen, breast milk, tears, saliva, urine, blood, bile, ascites, and cerebrospinal fluid. Exosomes have [...] Read more.

Exosomes are membranous vesicles that play a crucial role as intercellular messengers. Cells secrete exosomes, which can be found in a variety of bodily fluids such as amniotic fluid, semen, breast milk, tears, saliva, urine, blood, bile, ascites, and cerebrospinal fluid. Exosomes have a distinct bilipid protein structure and can be as small as 30–150 nm in diameter. They may transport and exchange multiple cellular messenger cargoes across cells and are used as a non-invasive biomarker for various illnesses. Due to their unique features, exosomes are recognized as the most effective biomarkers for cancer and other disease detection. We give a review of the most current applications of exosomes derived from various sources in the prognosis and diagnosis of multiple diseases. This review also briefly examines the significance of exosomes and their applications in biomedical research, including the use of aptamers and antibody–antigen functionalized biosensors. Full article

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

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15 pages, 2022 KiB

Open AccessArticle

Dual-Emission Au-Ag Nanoclusters with Enhanced Photoluminescence and Thermal Sensitivity for Intracellular Ratiometric Nanothermometry

by Helin Liu, Zhongliang Zhou, Zhiwei Wang, Jianhai Wang, Yu Wang, Lu Huang, Tianhuan Guo, Rongcheng Han and Yuqiang Jiang

Biosensors 2025, 15(8), 510; https://doi.org/10.3390/bios15080510 - 6 Aug 2025

Abstract

We report the development of highly luminescent, bovine serum albumin (BSA)-stabilized gold–silver bimetallic nanoclusters (Au-AgNCs@BSA) as a novel platform for high-sensitivity, ratiometric intracellular temperature sensing. Precise and non-invasive temperature sensing at the nanoscale is crucial for applications ranging from intracellular thermogenesis monitoring to [...] Read more.

We report the development of highly luminescent, bovine serum albumin (BSA)-stabilized gold–silver bimetallic nanoclusters (Au-AgNCs@BSA) as a novel platform for high-sensitivity, ratiometric intracellular temperature sensing. Precise and non-invasive temperature sensing at the nanoscale is crucial for applications ranging from intracellular thermogenesis monitoring to localized hyperthermia therapies. Traditional luminescent thermometric platforms often suffer from limitations such as high cytotoxicity and low photostability. Here, we synthesized Au-AgNCs@BSA via a one-pot aqueous reaction, achieving significantly enhanced photoluminescence quantum yields (PL QYs, up to 18%) and superior thermal responsiveness compared to monometallic counterparts. The dual-emissive Au-AgNCs@BSA exhibit a linear ratiometric fluorescence response to temperature fluctuations within the physiological range (20–50 °C), enabling accurate and concentration-independent thermometry in live cells. Time-resolved PL and Arrhenius analyses reveal two distinct emissive states and a high thermal activation energy (E_a = 199 meV), indicating strong temperature dependence. Silver doping increases radiative decay rates while maintaining low non-radiative losses, thus amplifying fluorescence intensity and thermal sensitivity. Owing to their small size, excellent photostability, and low cytotoxicity, these nanoclusters were applied to non-invasive intracellular temperature mapping, presenting a promising luminescent nanothermometer for real-time cellular thermogenesis monitoring and advanced bioimaging applications. Full article

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

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40 pages, 8156 KiB

Open AccessReview

Advances in the Direct Nanoscale Integration of Molecularly Imprinted Polymers (MIPs) with Transducers for the Development of High-Performance Nanosensors

by Ibrar Muhammad Asif, Tiziano Di Giulio, Francesco Gagliani, Cosimino Malitesta and Elisabetta Mazzotta

Biosensors 2025, 15(8), 509; https://doi.org/10.3390/bios15080509 - 6 Aug 2025

Abstract

Molecularly imprinted polymers (MIPs) have emerged as robust, cost-effective analogues of bioreceptors, offering high selectivity and stability. When applied in sensors, one key step is the integration of MIPs with the transducer, which critically affects sensor performance. Demanding challenges come when such integration [...] Read more.

Molecularly imprinted polymers (MIPs) have emerged as robust, cost-effective analogues of bioreceptors, offering high selectivity and stability. When applied in sensors, one key step is the integration of MIPs with the transducer, which critically affects sensor performance. Demanding challenges come when such integration involves nanoscaling processes, meaning that the transducer is nanostructured or the MIP itself is nanosized on a bulk transducer. In both cases, the integration results in the development of nanosensors, with advantages arising from the nanoscale, such as a high MIP surface-to-volume ratio, with surface-located, easily accessible binding sites, fast binding kinetics, and, thus, a rapid sensor response. Major advantages come also from nanostructured transducers, with nanoscale geometry enabling highly sensitive signal generation processes, not allowed on their bulk counterparts. In this review, we discuss advances in imprinting technologies, focusing on techniques that, enabling the nanoscale control of MIP synthesis, are conveniently applied to directly integrate MIPs with nanosensors in a one-step process. Two main approaches are reviewed, consisting in MIP nanostructuring on bulk transducers and in the direct growth of MIPs on nanotransducers, highlighting how different strategies achieve good conformity at the nanoscale and address spatial complexity to ensure stable and accurate signal acquisition. Finally, we consider future directions in MIP-based nanosensor development. Full article

(This article belongs to the Special Issue Recent Advances in Molecularly Imprinted-Polymer-Based Biosensors)

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2 pages, 134 KiB

Open AccessCorrection

Correction: Vitazkova et al. Transforming Sleep Monitoring: Review of Wearable and Remote Devices Advancing Home Polysomnography and Their Role in Predicting Neurological Disorders. Biosensors 2025, 15, 117

by Diana Vitazkova, Helena Kosnacova, Daniela Turonova, Erik Foltan, Martin Jagelka, Martin Berki, Michal Micjan, Ondrej Kokavec, Filip Gerhat and Erik Vavrinsky

Biosensors 2025, 15(8), 508; https://doi.org/10.3390/bios15080508 - 6 Aug 2025

Abstract

Text Correction [...] Full article

18 pages, 2879 KiB

Open AccessArticle

Smartphone-Compatible Colorimetric Detection of CA19-9 Using Melanin Nanoparticles and Deep Learning

by Turgut Karademir, Gizem Kaleli-Can and Başak Esin Köktürk-Güzel

Biosensors 2025, 15(8), 507; https://doi.org/10.3390/bios15080507 - 5 Aug 2025

Abstract

Paper-based colorimetric biosensors represent a promising class of low-cost diagnostic tools that do not require external instrumentation. However, their broader applicability is limited by the environmental concerns associated with conventional metal-based nanomaterials and the subjectivity of visual interpretation. To address these challenges, this [...] Read more.

Paper-based colorimetric biosensors represent a promising class of low-cost diagnostic tools that do not require external instrumentation. However, their broader applicability is limited by the environmental concerns associated with conventional metal-based nanomaterials and the subjectivity of visual interpretation. To address these challenges, this study introduces a proof-of-concept platform—using CA19-9 as a model biomarker—that integrates naturally derived melanin nanoparticles (MNPs) with machine learning-based image analysis to enable environmentally sustainable and analytically robust colorimetric quantification. Upon target binding, MNPs induce a concentration-dependent color transition from yellow to brown. This visual signal was quantified using a machine learning pipeline incorporating automated region segmentation and regression modeling. Sensor areas were segmented using three different algorithms, with the U-Net model achieving the highest accuracy (average IoU: 0.9025 ± 0.0392). Features extracted from segmented regions were used to train seven regression models, among which XGBoost performed best, yielding a Mean Absolute Percentage Error (MAPE) of 17%. Although reduced sensitivity was observed at higher analyte concentrations due to sensor saturation, the model showed strong predictive accuracy at lower concentrations, which are especially challenging for visual interpretation. This approach enables accurate, reproducible, and objective quantification of colorimetric signals, thereby offering a sustainable and scalable alternative for point-of-care diagnostic applications. Full article

(This article belongs to the Special Issue AI-Enabled Biosensor Technologies for Boosting Medical Applications)

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14 pages, 2981 KiB

Open AccessArticle

LAMP-Based 4-Channel Microfluidic Chip for POCT Detection of Influenza A H1N1, H3N2, and Influenza B Victoria Viruses

by Xue Zhao, Jiale Gao, Yijing Gu, Zheng Teng, Xi Zhang, Huanyu Wu, Xin Chen, Min Chen and Jilie Kong

Biosensors 2025, 15(8), 506; https://doi.org/10.3390/bios15080506 - 4 Aug 2025

Abstract

Background: Influenza viruses are major pathogens responsible for respiratory infections and pose significant risks to densely populated urban areas. RT-qPCR has made substantial contributions in controlling virus transmission during previous COVID-19 epidemics, but it faces challenges in terms of detection time for [...] Read more.

Background: Influenza viruses are major pathogens responsible for respiratory infections and pose significant risks to densely populated urban areas. RT-qPCR has made substantial contributions in controlling virus transmission during previous COVID-19 epidemics, but it faces challenges in terms of detection time for large sample sizes and susceptibility to nucleic acid contamination. Methods: Our study designed loop-mediated isothermal amplification primers for three common influenza viruses: A/H3N2, A/H1N1, and B/Victoria, and utilized a 4-channel microfluidic chip to achieve simultaneous detection. The chip initiates amplification by centrifugation and allows testing of up to eight samples at a time. Results: By creating a closed amplification system in the microfluidic chip, aerosol-induced nucleic acid contamination can be prevented through physically isolating the reaction from the operating environment. The chip can specifically detect A/H1N1, A/H3N2, and B/Victoria and has no signal for other common respiratory viruses. The testing process can be completed within 1 h and can be sensitive to viral RNA at concentrations as low as 10⁻³ ng/μL for A/H1N1 and A/H3N2 and 10⁻¹ ng/μL for B/Victori. A total of 296 virus swab samples were further analyzed using the microfluidic chip method and compared with the classical qPCR method, which resulted in high consistency. Conclusions: Our chip enables faster detection of influenza virus and avoids nucleic acid contamination, which is beneficial for POCT establishment and has lower requirements for the operating environment. Full article

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

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58 pages, 8116 KiB

Open AccessReview

Electrochemical Detection of Heavy Metals Using Graphene-Based Sensors: Advances, Meta-Analysis, Toxicity, and Sustainable Development Challenges

by Muhammad Saqib, Anna N. Solomonenko, Nirmal K. Hazra, Shojaa A. Aljasar, Elena I. Korotkova, Elena V. Dorozhko, Mrinal Vashisth and Pradip K. Kar

Biosensors 2025, 15(8), 505; https://doi.org/10.3390/bios15080505 - 4 Aug 2025

Abstract

Contamination of food with heavy metals is an important factor leading to serious health concerns. Rapid identification of these heavy metals is of utmost priority. There are several methods to identify traces of heavy metals in food. Conventional methods for the detection of [...] Read more.

Contamination of food with heavy metals is an important factor leading to serious health concerns. Rapid identification of these heavy metals is of utmost priority. There are several methods to identify traces of heavy metals in food. Conventional methods for the detection of heavy metal residues have their limitations in terms of cost, analysis time, and complexity. In the last decade, voltammetric analysis has emerged as the most prominent electrochemical determination method for heavy metals. Voltammetry is a reliable, cost-effective, and rapid determination method. This review provides a detailed primer on recent advances in the development and application of graphene-based electrochemical sensors for heavy metal monitoring over the last decade. We critically examine aspects of graphene modification (fabrication process, stability, cost, reproducibility) and analytical properties (sensitivity, selectivity, rapid detection, lower detection, and matrix effects) of these sensors. Furthermore, to our knowledge, meta-analyses were performed for the first time for all investigated parameters, categorized based on graphene materials and heavy metal types. We also examined the pass–fail criteria according to the WHO drinking water guidelines. In addition, the effects of heavy metal toxicity on human health and the environment are discussed. Finally, the contribution of heavy metal contamination to the seventeen Sustainable Development Goals (SDGs) stated by the United Nations in 2015 is discussed in detail. The results confirm the significant impact of heavy metal contamination across twelve SDGs. This review critically examines the existing knowledge in this field and highlights significant research gaps and future opportunities. It is intended as a resource for researchers working on graphene-based electrochemical sensors for the detection of heavy metals in food safety, with the ultimate goal of improving consumer health protection. Full article

(This article belongs to the Special Issue New Trends in Electrochemical Biosensors for Healthcare and Environmental Monitoring)

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36 pages, 7197 KiB

Open AccessReview

Microfluidic Platforms for Ex Vivo and In Vivo Gene Therapy

by Sungjun Kwak, Hyojeong Lee, Dongjun Yu, Tae-Joon Jeon, Sun Min Kim and Hyunil Ryu

Biosensors 2025, 15(8), 504; https://doi.org/10.3390/bios15080504 - 4 Aug 2025

Abstract

Recent studies have demonstrated the clinical potential of nucleic acid therapeutics (NATs). However, their efficient and scalable delivery remains a major challenge for both ex vivo and in vivo gene therapy. Microfluidic platforms have emerged as a powerful tool for overcoming these limitations [...] Read more.

Recent studies have demonstrated the clinical potential of nucleic acid therapeutics (NATs). However, their efficient and scalable delivery remains a major challenge for both ex vivo and in vivo gene therapy. Microfluidic platforms have emerged as a powerful tool for overcoming these limitations by enabling precise intracellular delivery and consistent therapeutic carrier fabrication. This review examines microfluidic strategies for gene delivery at the cellular level. These strategies include mechanoporation, electroporation, and sonoporation. We also discuss the synthesis of lipid nanoparticles, polymeric particles, and extracellular vesicles for systemic administration. Unlike conventional approaches, which treat ex vivo and in vivo delivery as separate processes, this review focuses on integrated microfluidic systems that unify these functions. For example, genetic materials can be delivered to cells that secrete therapeutic extracellular vesicles (EVs), or engineered cells can be encapsulated within hydrogels for implantation. These strategies exemplify the convergence of gene delivery and carrier engineering. They create a single workflow that bridges cell-level manipulation and tissue-level targeting. By synthesizing recent technological advances, this review establishes integrated microfluidic platforms as being fundamental to the development of next-generation NAT systems that are scalable, programmable, and clinically translatable. Full article

(This article belongs to the Special Issue Microfluidics for Biomedical Applications (3rd Edition))

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13 pages, 1388 KiB

Open AccessArticle

A Proof-of-Concept Study on Bioelectric-Based Biosensing for Prostate-Specific Antigen Detection in Serum Samples

by Georgios Giannakos, Sofia Marka, Konstantina Georgoulia, Spyridon Kintzios and Georgia Moschopoulou

Biosensors 2025, 15(8), 503; https://doi.org/10.3390/bios15080503 - 3 Aug 2025

Abstract

Prostate cancer is among the most prevalent malignancies in men worldwide, underscoring the need for early and accurate diagnostic tools. This study presents a proof-of-concept and pilot clinical validation of a novel bioelectric impedance-based biosensor for the detection of prostate-specific antigen (PSA) in [...] Read more.

Prostate cancer is among the most prevalent malignancies in men worldwide, underscoring the need for early and accurate diagnostic tools. This study presents a proof-of-concept and pilot clinical validation of a novel bioelectric impedance-based biosensor for the detection of prostate-specific antigen (PSA) in human serum. The system integrates Molecular Identification through Membrane Engineering (MIME) with the xCELLigence real-time cell analysis platform, employing Vero cells electroinserted with anti-PSA antibodies. Optimization experiments identified 15,000 cells/well as the optimal configuration for impedance response. The biosensor exhibited specific, concentration-dependent changes in impedance upon exposure to PSA standard solutions and demonstrated significant differentiation between PSA-positive and PSA-negative human serum samples relative to the clinical threshold of 4 ng/mL. The biosensor offered rapid results within one minute, unlike standard immunoradiometric assay (IRMA), while showing strong diagnostic agreement. The system’s specificity, sensitivity, and reproducibility support its potential for integration into point-of-care screening workflows. This bioelectric assay represents one of the fastest PSA detection approaches reported to date and offers a promising solution for reducing overdiagnosis while improving clinical decision-making and patient outcomes. Full article

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

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23 pages, 5029 KiB

Open AccessReview

Synthesis and Biomedical Applications of PLA-HPG-Based Biodegradable Nanocarriers: A Review

by Yijun Shen, Xuehan He and Lei Chen

Biosensors 2025, 15(8), 502; https://doi.org/10.3390/bios15080502 - 3 Aug 2025

Abstract

The development of biodegradable nanocarriers has long been a priority for researchers and medical professionals in the realm of drug delivery. Because of their inherent benefits, which include superior biocompatibility, customizable degradability, easy surface functionalization, and stealth-like behavior, polylactic acid-hyperbranched polyglycerol (PLA-HPG) copolymers [...] Read more.

The development of biodegradable nanocarriers has long been a priority for researchers and medical professionals in the realm of drug delivery. Because of their inherent benefits, which include superior biocompatibility, customizable degradability, easy surface functionalization, and stealth-like behavior, polylactic acid-hyperbranched polyglycerol (PLA-HPG) copolymers have demonstrated a promising future in the field of biomedical research. The synthesis of PLA-HPG copolymers and the creation of their nanoparticles for biomedical uses have been the focus of current efforts. In this review, we summarize the synthetic strategies of PLA-HPG copolymers and corresponding nanoparticles, and highlight their physicochemical properties, biocompatibility, and degradation properties. Furthermore, we introduce a number of PLA-HPG nanoparticles that are utilized for surface skin delivery, wound dressing, and in vivo drug delivery biological applications. Finally, we conclude by offering our thoughts on how this nanoplatform might advance in the future. Full article

(This article belongs to the Special Issue State-of-the-Art Biosensors in China (2nd Edition))

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16 pages, 1702 KiB

Open AccessArticle

Mobile and Wireless Autofluorescence Detection Systems and Their Application for Skin Tissues

by Yizhen Wang, Yuyang Zhang, Yunfei Li and Fuhong Cai

Biosensors 2025, 15(8), 501; https://doi.org/10.3390/bios15080501 - 3 Aug 2025

Abstract

Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the [...] Read more.

Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the autofluorescence signals of biological tissues are relatively weak, making them challenging to be captured by photoelectric sensors. Moreover, the absorption and scattering properties of biological tissues lead to a substantial attenuation of the autofluorescence of biological tissues, thereby worsening the signal-to-noise ratio. This has also imposed limitations on the development and application of compact-sized autofluorescence detection systems. In this study, a compact LED light source and a CMOS sensor were utilized as the excitation and detection devices for skin tissue autofluorescence, respectively, to construct a mobile and wireless skin tissue autofluorescence detection system. This system can achieve the detection of skin tissue autofluorescence with a high signal-to-noise ratio under the drive of a simple power supply and a single-chip microcontroller. The detection time is less than 0.1 s. To enhance the stability of the system, a pressure sensor was incorporated. This pressure sensor can monitor the pressure exerted by the skin on the detection system during the testing process, thereby improving the accuracy of the detection signal. The developed system features a compact structure, user-friendliness, and a favorable signal-to-noise ratio of the detection signal, holding significant application potential in future assessments of skin aging and the risk of diabetic complications. Full article

(This article belongs to the Special Issue Advances in Portable and Wearable Sensing Systems for Biochemical Monitoring)

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17 pages, 1763 KiB

Open AccessArticle

Target-Guided Droplet Routing on MEDA Biochips Considering Shape-Dependent Velocity Models and Droplet Splitting

by Yuta Hamachiyo, Chiharu Shiro, Hiroki Nishikawa, Hiroyuki Tomiyama and Shigeru Yamashita

Biosensors 2025, 15(8), 500; https://doi.org/10.3390/bios15080500 - 3 Aug 2025

Abstract

In recent years, digital microfluidic biochips (DMFBs), based on microfluidic technology, have attracted attention as compact and flexible experimental devices. DMFBs are widely applied in biochemistry and medical fields, including point-of-care clinical diagnostics and PCR testing. Among them, micro electrode dot array (MEDA) [...] Read more.

In recent years, digital microfluidic biochips (DMFBs), based on microfluidic technology, have attracted attention as compact and flexible experimental devices. DMFBs are widely applied in biochemistry and medical fields, including point-of-care clinical diagnostics and PCR testing. Among them, micro electrode dot array (MEDA) biochips, composed of numerous microelectrodes, have overcome the limitations of conventional chips by enabling finer droplet manipulation and real-time sensing, thus significantly improving experimental efficiency. While various studies have been conducted to enhance the utilization of MEDA biochips, few have considered the shape-dependent velocity characteristics of droplets in routing. Moreover, methods that do take such characteristics into account often face significant challenges in solving time. This study proposes a fast droplet routing method for MEDA biochips that incorporates shape-dependent velocity characteristics by utilizing the distance information to the target cell. The experimental results demonstrate that the proposed method achieves approximately a 67.5% reduction in solving time compared to existing methods, without compromising solution quality. Full article

(This article belongs to the Special Issue Feature Papers of Biosensors)

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21 pages, 1147 KiB

Open AccessReview

Recent Advances in Developing Cell-Free Protein Synthesis Biosensors for Medical Diagnostics and Environmental Monitoring

by Tyler P. Green, Joseph P. Talley and Bradley C. Bundy

Biosensors 2025, 15(8), 499; https://doi.org/10.3390/bios15080499 - 3 Aug 2025

Abstract

Cell-free biosensors harness the selectivity of cellular machinery without living cells’ constraints, offering advantages in environmental monitoring, medical diagnostics, and biotechnological applications. This review examines recent advances in cell-free biosensor development, highlighting their ability to detect diverse analytes including heavy metals, organic pollutants, [...] Read more.

Cell-free biosensors harness the selectivity of cellular machinery without living cells’ constraints, offering advantages in environmental monitoring, medical diagnostics, and biotechnological applications. This review examines recent advances in cell-free biosensor development, highlighting their ability to detect diverse analytes including heavy metals, organic pollutants, pathogens, and clinical biomarkers with high sensitivity and specificity. We analyze technological innovations in cell-free protein synthesis optimization, preservation strategies, and field deployment methods that have enhanced sensitivity, and practical applicability. The integration of synthetic biology approaches has enabled complex signal processing, multiplexed detection, and novel sensor designs including riboswitches, split reporter systems, and metabolic sensing modules. Emerging materials such as supported lipid bilayers, hydrogels, and artificial cells are expanding biosensor capabilities through microcompartmentalization and electronic integration. Despite significant progress, challenges remain in standardization, sample interference mitigation, and cost reduction. Future opportunities include smartphone integration, enhanced preservation methods, and hybrid sensing platforms. Cell-free biosensors hold particular promise for point-of-care diagnostics in resource-limited settings, environmental monitoring applications, and food safety testing, representing essential tools for addressing global challenges in healthcare, environmental protection, and biosecurity. Full article

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

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