Lighting Up Single-Molecule Biosensors and Bioimaging: Now and the Decade to Come

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

Deadline for manuscript submissions: 31 July 2025 | Viewed by 4118

Special Issue Editors


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Guest Editor
Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing, China
Interests: label-free biosensing and imaging; single-molecule imaging; cell analysis
Special Issues, Collections and Topics in MDPI journals
Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
Interests: capillary electrophoresis (CE); surface plasmon resonance imaging (SPRi); biological mass spectrometry (bMS)

Special Issue Information

Dear Colleagues,

Single-molecule biosensing and bioimaging approaches have pushed beyond the ensemble average and revealed the statistical qualities of molecular properties and activites, thus allowing for an understanding of the biological processes at a high level of detail. Single-molecular biosensing methods, such as nanopore sensors, have developed the capability to recognize the sequences of DNA, RNA, and protein molecules, providing new tools to understand their molecular microstructures. Single-molecule bioimaging approaches, such as the widely used fluorescence microscopy, have provided high throughput when simultaneously determining the properties of multiple molecules for statistical analysis, and have demonstrated the capability to track the movements of single molecules in order to understand the effects of molecular motions on biological activities. In recent years, label-free single-molecule imaging approaches have further expanded the applications of single-molecule detection methods. These approaches can determine intrinsic molecular properties such as mass and molecular binding kinetics without the interference of labels, thus providing us with a thorough understanding of molecular properties and enabling single-molecule analysis under conditions which are otherwise challenging for the labeling of target molecules. Nonetheless, the demand for building new single-molecule biosensing and bioimaging schemes that are cost effective, user friendly, highly repeatable, and more sensitive than current approaches is ever increasing. In addition, the existing gaps between single-molecule detection approaches and practical applications urgently need to be bridged, because it remains unclear whether the heterogeneity of the microscopic molecular properties has substantial impact on the biological behaviors of living organisms. In this Special Issue, we focus on newfound developments and the outlook of highly sensitive biosensing and imaging approaches that already or may soon acquire single-molecule detection capabilities, along with their applications in multilevel analyses of molecular interactions for understanding the relationship between microscopic molecular properties and biological behaviors, such as cell activities or disease symptoms. We invite research submissions capable of helping in advancing the field of single-molecule biosensing and bioimaging, and their applications for the efficient analysis of biological activities.

Dr. Pengfei Zhang
Dr. Yi Chen
Guest Editors

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Keywords

  • single molecules
  • biosensing
  • bioimaging
  • molecular interaction and recognition
  • biological behaviors

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Published Papers (4 papers)

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Research

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14 pages, 4489 KiB  
Article
Back Propagation Artificial Neural Network Enhanced Accuracy of Multi-Mode Sensors
by Xue Zou, Xiaohong Wang, Jinchun Tu, Delun Chen and Yang Cao
Biosensors 2025, 15(3), 148; https://doi.org/10.3390/bios15030148 - 26 Feb 2025
Viewed by 422
Abstract
The detection of small molecules is critical in many fields, but traditional electrochemical detection methods often exhibit limited accuracy. The construction of multi-mode sensors is a common strategy to improve detection accuracy. However, most existing multi-mode sensors rely on the separate analysis of [...] Read more.
The detection of small molecules is critical in many fields, but traditional electrochemical detection methods often exhibit limited accuracy. The construction of multi-mode sensors is a common strategy to improve detection accuracy. However, most existing multi-mode sensors rely on the separate analysis of each mode signal, which can easily lead to sensor failure when the deviation between different mode results is too large. In this study, we propose a multi-mode sensor based on Prussian Blue (PB) for ascorbic acid (AA) detection. We innovatively integrate back-propagation artificial neural networks (BP ANNs) to comprehensively process the three collected signal data sets, which successfully solves the problem of sensor failure caused by the large deviation of signal detection results, and greatly improves the prediction accuracy, detection range, and anti-interference of the sensor. Our findings provide an effective solution for optimizing the data analysis of multi-modal sensors, and show broad application prospects in bioanalysis, clinical diagnosis, and related fields. Full article
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9 pages, 1393 KiB  
Article
Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
by Stefanus Renaldi Wijaya, Augusto Martins, Katie Morris, Steven D. Quinn and Thomas F. Krauss
Biosensors 2025, 15(1), 50; https://doi.org/10.3390/bios15010050 - 15 Jan 2025
Viewed by 858
Abstract
The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer’s disease. A biomarker’s low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the [...] Read more.
The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer’s disease. A biomarker’s low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor’s surface. To address this challenge, we used a resonant Young’s slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio. As a result, we achieved a limit of detection of 2.9 × 10−6 refractive index units (RIU). We validated our sensor’s low molecular weight capability by demonstrating the detection of Aβ-42, a 4.5 kDa peptide indicative of Alzheimer’s disease, and reached the clinically relevant pg/mL regime. This system builds on the guided mode resonance modality we previously showed to be compatible with handheld operation using low-cost components. We expect this development will have far-reaching applications beyond Aβ-42 and become a workhorse tool for the label-free detection of low-molecular-weight biomarkers across a range of disease types. Full article
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13 pages, 4419 KiB  
Article
High-Performance Photocatalytic Multifunctional Material Based on Bi4Ti3O12-Supported Ag and Ti3C2Tx for Organic Degradation and Antibacterial Applications
by Kexi Zhang, Bingdong Yan, Xiaohong Wang, Yang Cao, Wanjun Hao and Jinchun Tu
Biosensors 2025, 15(1), 11; https://doi.org/10.3390/bios15010011 - 31 Dec 2024
Viewed by 862
Abstract
With the rapid development of modern science and technology and the diversification of social needs, traditional single-performance materials struggle to meet the complex and changeable application scenarios. To address the multifaceted requirements of biomedical applications, such as disease diagnosis and treatment, scientists are [...] Read more.
With the rapid development of modern science and technology and the diversification of social needs, traditional single-performance materials struggle to meet the complex and changeable application scenarios. To address the multifaceted requirements of biomedical applications, such as disease diagnosis and treatment, scientists are dedicated to developing new multifunctional biomaterials with multiple activities. Bi4Ti3O12 (BTO), despite its versatility and application potential, has insufficient photocatalytic performance. Silver nanoparticles (Ag) and Ti3C2Tx are particularly effective as antibacterial materials but they have relatively single functions. In this study, BTO/Ag/Ti3C2Tx biomultifunctional materials were constructed by combining BTO with Ag and Ti3C2Tx. We discovered that the addition of Ag and Ti3C2Tx effectively optimized the visible light absorption characteristics of BTO, reduced the electron transfer resistance, and increased the carrier concentration, thus significantly improving the photocatalytic performance of composite material, thereby markedly improving the composite’s photocatalytic performance and its efficacy in photochemical sensing and photodegradation. At the same time, BTO, as a carrier, effectively avoids Ag and Ti3C2Tx agglomeration and gives full play to its antibacterial properties. In the specific performance studies, ascorbic acid and MB were used as the subjects of photochemical sensing and photodegradation properties, while Escherichia coli and Staphylococcus aureus were tested for antibacterial properties. The BTO/Ag/Ti3C2Tx composite showed remarkable results in all assessments, demonstrating its potential as a versatile antibacterial and photocatalytic material. Full article
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Review

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20 pages, 20317 KiB  
Review
Dielectric Surface-Based Biosensors for Enhanced Detection of Biomolecular Interactions: Advances and Applications
by Liangju Li, Jingbo Zhang, Yacong Li, Caixin Huang, Jiying Xu, Ying Zhao and Pengfei Zhang
Biosensors 2024, 14(11), 524; https://doi.org/10.3390/bios14110524 - 30 Oct 2024
Viewed by 1263
Abstract
Surface plasmon resonance (SPR) biosensors are extensively utilized for analyzing molecular interactions due to their high sensitivity and label-free detection capabilities. Recent innovations in surface-sensitive biosensors with dielectric surfaces address the inherent limitations associated with traditional gold surfaces, such as thermal effects and [...] Read more.
Surface plasmon resonance (SPR) biosensors are extensively utilized for analyzing molecular interactions due to their high sensitivity and label-free detection capabilities. Recent innovations in surface-sensitive biosensors with dielectric surfaces address the inherent limitations associated with traditional gold surfaces, such as thermal effects and biocompatibility issues, which can impede broader applications. This review examines state-of-the-art biosensor configurations, including total internal reflection, optical waveguide, photonic crystal resonators, Bloch surface wave biosensors, and surface electrochemical biosensors, which can enhance analyte signals and augment the molecular detection efficiency at the sensor interface. These technological advancements not only improve the resolution of binding kinetics analysis and single-molecule detection but also extend the analytical capabilities of these systems. Additionally, this review explores prospective advancements in augmenting field enhancement and incorporating multimodal sensing functionalities, emphasizing the significant potential of these sophisticated biosensing technologies to profoundly enhance our understanding of molecular interactions. Full article
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