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Biosensors
Special Issues
Single-Molecule Biosensing: Recent Advances and Future Challenges
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Single-Molecule Biosensing: Recent Advances and Future Challenges

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Nano- and Micro-Technologies in Biosensors".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 5111

Special Issue Editor

Prof. Dr. Chunyang Zhang

E-Mail Website
Guest Editor
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China
Interests: single-molecule detection; single-molecule imaging; biosensors; nanosensors; nucleic acids; enzymes; quantum dots
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sensitive and accurate detection of interested biomolecules greatly contributes to both fundamental biomedical research and practical clinical applications. Single-molecule detection is a state-of-the-art bioanalysis technology, and it provides the ultimate sensitivity for the detection of low-abundance targets. Superior to the conventional bioanalysis method that measures the ensemble average, single-molecule detection can probe individual molecule information; it possesses the distinct advantages of ultrahigh sensitivity, low sample consumption, and visualization capability; and it can efficiently avoid interferences from stochastic signal fluctuation and varied reaction conditions. The development of single-molecule biosensing technologies has emerged as a hot topic in recent years, and it provides a powerful tool for the efficient detection of rare analytes in complex biological and clinical samples.

For this Special Issue, we welcome original research papers and reviews on current advances in the design of single-molecule biosensing systems based on single-molecule fluorescent, plasmonic, electrochemical, and surface-enhanced Raman spectroscopic detection and their applications in the detection of DNAs, RNAs, proteins, enzymes, and other biomolecules. Single-molecule detection-related theoretical research and device developments are also encouraged. The applications of single-molecule detection-based platforms for in vivo imaging and point-of-care detection of clinical disease biomarkers is of special interest. Reviews should provide an in-depth examination of the most recent research in a specific context or discuss the future challenges related to single-molecule detection.

Prof. Dr. Chunyang Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • single-molecule detection
  • biosensor
  • diagnosis
  • biomarker

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Published Papers (3 papers)

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Research

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12 pages, 4167 KiB  
Article
Single Nucleotide Recognition and Mutation Site Sequencing Based on a Barcode Assay and Rolling Circle Amplification
by Linmin Zhong, Huiping Chen, Shuang Cao and Shanwen Hu
Biosensors 2024, 14(11), 521; https://doi.org/10.3390/bios14110521 - 25 Oct 2024
Viewed by 972
Abstract
Single nucleotide polymorphisms (SNPs) present significant challenges in microbial detection and treatment, further raising the demands on sequencing technologies. In response to these challenges, we have developed a novel barcode-based approach for highly sensitive single nucleotide recognition. This method leverages a dual-head folded [...] Read more.
Single nucleotide polymorphisms (SNPs) present significant challenges in microbial detection and treatment, further raising the demands on sequencing technologies. In response to these challenges, we have developed a novel barcode-based approach for highly sensitive single nucleotide recognition. This method leverages a dual-head folded complementary template probe in conjunction with DNA ligase to specifically identify the target base. Upon recognition, the system triggers rolling circle amplification (RCA) followed by the self-assembly of CdSe quantum dots onto polystyrene microspheres, enabling a single-particle fluorescence readout. This approach allows for precise base identification at individual loci, which are then analyzed using a bio-barcode array to screen for base changes across multiple sites. This method was applied to sequence a drug-resistant mutation site in Helicobacter pylori (H. pylori), demonstrating excellent accuracy and stability. Offering high precision, high sensitivity, and single nucleotide resolution, this approach shows great promise as a next-generation sequencing method. Full article
(This article belongs to the Special Issue Single-Molecule Biosensing: Recent Advances and Future Challenges)
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15 pages, 2447 KiB  
Article
APPROACH: Sensitive Detection of Exosomal Biomarkers by Aptamer-Mediated Proximity Ligation Assay and Time-Resolved Förster Resonance Energy Transfer
by Ying Li, Meiqi Qian, Yongpeng Liu and Xue Qiu
Biosensors 2024, 14(5), 233; https://doi.org/10.3390/bios14050233 - 8 May 2024
Cited by 3 | Viewed by 2088
Abstract
Exosomal biomarker detection holds great importance in the field of in vitro diagnostics, offering a non-invasive and highly sensitive approach for early disease detection and personalized treatment. Here, we proposed an “APPROACH” strategy, combining aptamer-mediated proximity ligation assay (PLA) with rolling circle amplification [...] Read more.
Exosomal biomarker detection holds great importance in the field of in vitro diagnostics, offering a non-invasive and highly sensitive approach for early disease detection and personalized treatment. Here, we proposed an “APPROACH” strategy, combining aptamer-mediated proximity ligation assay (PLA) with rolling circle amplification (RCA) and time-resolved Förster resonance energy transfer (TR-FRET) for the sensitive and semi-homogenous detection of exosomal biomarkers. PLA probes consisted of a cholesterol-conjugated oligonucleotide, which anchored to the membrane of an exosome, and a specific aptamer oligonucleotide that recognized a target protein of the exosome; the proximal binding of pairs of PLA probes to the same exosome positioned the oligonucleotides in the vicinity of each other, guiding the hybridization and ligation of two subsequently added backbone and connector oligonucleotides to form a circular DNA molecule. Circular DNA formed from PLA underwent rolling circle amplification (RCA) for signal amplification, and the resulting RCA products were subsequently quantified by TR-FRET. The limits of detection provided by APPROACH for the exosomal biomarkers CD63, PD-L1, and HER2 were 0.46 ng∙μL−1, 0.77 ng∙μL−1, and 1.1 ng∙μL−1, respectively, demonstrating excellent analytical performance with high sensitivity and quantification accuracy. Furthermore, the strategy afforded sensitive detection of exosomal CD63 with a LOD of 1.56 ng∙μL−1 in complex biological matrices, which underscored its anti-interference capability and potential for in vitro detection. The proposed strategy demonstrates wide-ranging applicability in quantifying diverse exosomal biomarkers while exhibiting robust analytical characteristics, including high sensitivity and accuracy. Full article
(This article belongs to the Special Issue Single-Molecule Biosensing: Recent Advances and Future Challenges)
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Review

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23 pages, 6163 KiB  
Review
Recent Advance in Single-Molecule Fluorescent Biosensors for Tumor Biomarker Detection
by Jie Zhang, Jiawen Liu, Lixue Qiao, Qian Zhang, Juan Hu and Chun-yang Zhang
Biosensors 2024, 14(11), 540; https://doi.org/10.3390/bios14110540 - 7 Nov 2024
Viewed by 1392
Abstract
The construction of biosensors for specific, sensitive, and rapid detection of tumor biomarkers significantly contributes to biomedical research and early cancer diagnosis. However, conventional assays often involve large sample consumption and poor sensitivity, limiting their further application in real samples. In recent years, [...] Read more.
The construction of biosensors for specific, sensitive, and rapid detection of tumor biomarkers significantly contributes to biomedical research and early cancer diagnosis. However, conventional assays often involve large sample consumption and poor sensitivity, limiting their further application in real samples. In recent years, single-molecule biosensing has emerged as a robust tool for detecting and characterizing biomarkers due to its unique advantages including simplicity, low sample consumption, ultra-high sensitivity, and rapid assay time. This review summarizes the recent advances in the construction of single-molecule biosensors for the measurement of various tumor biomarkers, including DNAs, DNA modifications, RNAs, and enzymes. We give a comprehensive review about the working principles and practical applications of these single-molecule biosensors. Additionally, we discuss the challenges and limitations of current single-molecule biosensors, and highlight the future directions. Full article
(This article belongs to the Special Issue Single-Molecule Biosensing: Recent Advances and Future Challenges)
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