Nano-Biosensors and Their Applications for In Vivo/Vitro Diagnosis—3rd Edition

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensor Materials".

Deadline for manuscript submissions: 15 June 2026 | Viewed by 3705

Special Issue Editor


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Guest Editor
Marshall Laboratory of Biomedical Engineering, Research Center for Biosensor and Nanotheranostic, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Interests: chemical and biological sensors; optical sensors; metal nanomaterials; catalysis; plasmonics; microfluidics; disease diagnosis; environmental monitoring
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Special Issue Information

Dear Colleagues,

Following the successful publication of the first and second editions of the Special Issue entitled “Nano-Biosensors and Their Applications for In Vivo/Vitro Diagnosis”, we are pleased to launch the third volume of this ongoing series. The previous editions have received broad attention and have significantly advanced the field of nano-biosensing. Building on this foundation, the third edition aims to further explore nanotechnology-enabled diagnostics, with renewed focus on innovation, translational potential, and interdisciplinary integration.

Nano-biosensors represent a distinctive class of analytical tools that integrate the molecular recognition capabilities of biomolecules (such as antibodies, aptamers, nucleic acids, and enzymes) with the unique properties of nanostructures (such as optical, catalytic, magnetic, and plasmonic features). This powerful synergy offers superior sensitivity, specificity, and versatility for the detection of biological targets in both in vitro and in vivo settings.

In recent years, we have witnessed exciting developments in the field, including the emergence of digital and wearable biosensors, artificial intelligence-assisted signal processing, and multiplexed detection platforms tailored for clinical applications. These advances have expanded the scope of nano-biosensing beyond fundamental research toward practical implementation in disease diagnosis, health monitoring, and personalized medicine.

This Special Issue welcomes original research and review articles focused on the design of novel nanostructures, the development of high-performance biosensors, innovative signal amplification mechanisms, and the detection of emerging biomarkers. Of particular interest are studies involving point-of-care diagnostics, implantable and wearable devices, and intelligent biosensing systems powered by artificial intelligence.

We look forward to your contributions that will further shape this rapidly evolving and multidisciplinary research area.

Dr. Zhuangqiang Gao
Guest Editor

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Keywords

  • nanostructures
  • nanomaterials
  • nanodevices
  • biosensors
  • biomarkers
  • artificial intelligence
  • in vivo/vitro diagnosis

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Published Papers (3 papers)

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Research

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11 pages, 1138 KB  
Article
Ultra-Sensitive Detection of Mercury by Using Field-Effect Transistor Biosensors Based on Single-Walled Carbon Nanotubes
by Chao Lu, Qiuxiang Lv, Yuanwei Lin and Li Gao
Biosensors 2025, 15(12), 779; https://doi.org/10.3390/bios15120779 - 26 Nov 2025
Viewed by 229
Abstract
In recent years, the amount of mercury discharged by human activities has continued to increase. Most of the mercury in surface water settles into the sediment, where it can be directly or indirectly transformed into mercury ion (Hg2+) compounds (such as [...] Read more.
In recent years, the amount of mercury discharged by human activities has continued to increase. Most of the mercury in surface water settles into the sediment, where it can be directly or indirectly transformed into mercury ion (Hg2+) compounds (such as dimethylmercury) under the action of microorganisms. Hg2+ display high toxicity and bioaccumulation in food, such as fish and rice, and thus the contamination of mercury ion is a serious concern for human health. Practical Hg2+ detection methods are usually limited by the sensitivity and selectivity of the used methods, such as colorimetric determination and fluorescence biosensor based on the solution phase. Therefore, it is urgent to develop Hg2+ detection methods in the practical environment with high sensitivity and selectivity. DNA is low-cost, relatively stable, and has been used for different fields. In this study, DNA for Hg2+detection was absorbed on the surface of single-walled carbon nanotubes (SWNTs) by using 1,5-diaminonaphthalene (DAN) based on field-effect transistor (FET) biosensors. The interaction between DNA and Hg2+ can be directly converted into electrical signals based on the SWNTs biosensors. The experimental results showed that the limit of detection (LOD) of Hg2+ without the phase-locked amplifier was about 42.6 pM. The function of the phase-locked amplifier is to achieve fast detection of the biosensor with strong anti-noise ability. Intriguingly, the sensitivity of the biosensor combined with a phase-locked amplifier to detect Hg2+ was further improved to be 5.14 pM compared with some current methods of biosensors. Furthermore, this biosensor has an excellent selectivity and practical detection in tap water, which demonstrates its high performance and low cost in practical application in Hg2+ detection. These results show this method for Hg2+ detection using SWNTs biosensors with a phase-locked amplifier is promising. Full article
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16 pages, 3041 KB  
Article
Rigor & Reproducibility: pH Adjustments of Papain with L-Cysteine Dissociation Solutions and Cell Media Using Phenol Red Spectrophotometry
by Joshua M. Hilner, Allison Turner, Calissa Vollmar-Zygarlenski and Larry J. Millet
Biosensors 2025, 15(11), 727; https://doi.org/10.3390/bios15110727 - 1 Nov 2025
Viewed by 806
Abstract
Phenol red is a widely used, low-cost, label-free colorimetric pH indicator that bridges traditional colorimetric assays with modern quantitative imaging and cell-based screening platforms. Its protonation-dependent absorbance shift (430–560 nm) allows for the real-time monitoring of extracellular acidification, which indirectly reflects cellular metabolism, [...] Read more.
Phenol red is a widely used, low-cost, label-free colorimetric pH indicator that bridges traditional colorimetric assays with modern quantitative imaging and cell-based screening platforms. Its protonation-dependent absorbance shift (430–560 nm) allows for the real-time monitoring of extracellular acidification, which indirectly reflects cellular metabolism, growth, and respiration. Although phenol red lacks the molecular specificity of genetically encoded or fluorogenic biosensors, it remains useful in systems where pH changes are effective proxies for physiological processes. Existing tissue digestion protocols often overlook key parameters, especially pH control and enzyme cofactor use. This study presents a straightforward, spectrophotometric method to monitor and adjust the pH of low-volume (1 mL) buffered enzymatic dissociation media using phenol red and a plate reader. We titrated dissociation solutions to physiological pH (~7.4) using spectrophotometric pH measurements validated against conventional glass pH probe readings, confirming method reliability. Accurate pH assessment is critical for isolating viable primary cells for downstream applications such as tissue engineering, single-cell omics, and neurophysiological assays. We highlight that papain-based dissociation media supplemented with L-cysteine can be acidic (pH 6.6) if unadjusted, compromising cell viability. This accessible approach enhances reproducibility by promoting pH documentation concerning dissociation conditions that contribute to advancing consistency in biomedical, cellular, neuronal, and tissue engineering research. Full article
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Review

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19 pages, 1908 KB  
Review
Enhancing ELISA Sensitivity: From Surface Engineering to Synthetic Biology
by Hye-Bin Jeon, Dong-Yeon Song, Yu Jin Park and Dong-Myung Kim
Biosensors 2025, 15(7), 434; https://doi.org/10.3390/bios15070434 - 6 Jul 2025
Cited by 1 | Viewed by 2431
Abstract
Accurate and sensitive detection of protein biomarkers is critical for advancing in vitro diagnostics (IVD), yet conventional enzyme-linked immunosorbent assays (ELISA) often fall short in terms of sensitivity compared to nucleic acid-based tests. Bridging this sensitivity gap is essential for improving diagnostic accuracy, [...] Read more.
Accurate and sensitive detection of protein biomarkers is critical for advancing in vitro diagnostics (IVD), yet conventional enzyme-linked immunosorbent assays (ELISA) often fall short in terms of sensitivity compared to nucleic acid-based tests. Bridging this sensitivity gap is essential for improving diagnostic accuracy, particularly in diseases where protein levels better reflect disease progression than nucleic acid biomarkers. In this review, we present strategies developed to enhance the sensitivity of ELISA, structured according to the sequential steps of the assay workflow. Beginning with surface modifications, we then discuss the methodologies to improve mixing and washing efficiency, followed by a summary of recent advances in signal generation and amplification techniques. In particular, we highlight the emerging role of cell-free synthetic biology in augmenting ELISA sensitivity. Recent developments such as expression immunoassays, CRISPR-linked immunoassays (CLISA), and T7 RNA polymerase–linked immunosensing assays (TLISA) demonstrate how programmable nucleic acid and protein synthesis systems can be integrated into ELISA workflows to surpass the present sensitivity, affordability, and accessibility. By combining synthetic biology-driven amplification and signal generation mechanisms with traditional immunoassay formats, ELISA is poised to evolve into a highly modular and adaptable diagnostic platform, representing a significant step toward the next generation of highly sensitive and programmable immunoassays. Full article
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