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Biosensors
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Aptamer-Based Biosensors for Point-of-Care Diagnostics
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Aptamer-Based Biosensors for Point-of-Care Diagnostics

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

Deadline for manuscript submissions: 15 November 2025 | Viewed by 9345

Special Issue Editors

Dr. Ana Díaz-Fernández

E-Mail Website
Guest Editor
Departamento de Química Física y Analítica, Universidad de Oviedo, Av. Julián Clavería 8, 33006 Oviedo, Spain
Interests: biosensors; electrochemistry; cancer; aptamers; gly-cans
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Cecilia Cristea

E-Mail Website
Guest Editor
Department of Analytical Chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania
Interests: electrochemical and optical sensors; graphene; nanomaterials based electrodes; bioanalysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The dynamic field of molecular diagnostics and personalized medicine demands innovative approaches that deliver accurate and sensitive results in a fast, simple, and convenient manner at the point of need. The rapid advancement of point-of-care (POC) diagnostics has revolutionized healthcare by enabling timely and accurate disease detection outside traditional laboratory settings. Aptamer-based biosensors, leveraging the unique binding capabilities of aptamers—synthetic nucleic acid ligands—represent a promising approach to enhancing the sensitivity, specificity, and versatility of POC devices. These biosensors can detect a wide range of biomarkers (targets), including proteins, pathogens, and small molecules, making them invaluable tools in clinical diagnostics, infectious disease management, and personalized medicine.

This Special Issue aims to bring together innovative research and comprehensive reviews that highlight the development, optimization, and application of aptamer-based biosensors specifically for point-of-care diagnostics. We invite contributions from researchers across multidisciplinary fields to share their latest findings and insights. Topics include, but are not limited to, the following areas:

  1. Aptamer Selection and Engineering: Novel methods for the selection, design, and bioengineering of aptamers for enhanced binding specificity and stability.
  2. Biosensor Development: Innovative designs and fabrication techniques for aptamer-based biosensors tailored for POC applications, such as wearable formats, paper-based devices, and microfluidics.
  3. Detection Techniques: Exploration of signal transduction methods, including electrochemical, optical, and mass-sensitive detection approaches.
  4. Field Applications: Research demonstrating the use of aptamer-based biosensors in real-world POC settings, particularly in clinical diagnostics and infectious disease detection.

We look forward to your valuable contributions that will advance the field of aptamer-based biosensors and their impactful applications in point-of-care diagnostics.

Dr. Ana Díaz-Fernández
Prof. Dr. Cecilia Cristea
Guest Editors

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 2200 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

  • aptamer
  • biosensor
  • point of care
  • SELEX
  • diagnostics
  • precision medicine

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Published Papers (7 papers)

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Research

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14 pages, 1906 KB  
Article
FRET-Based TURN-ON Aptasensor for the Sensitive Detection of CK-MB
by Rabia Asghar, Madiha Rasheed, Xuefei Lv and Yulin Deng
Biosensors 2025, 15(7), 446; https://doi.org/10.3390/bios15070446 - 11 Jul 2025
Viewed by 1210
Abstract
A fluorescent sandwich assay was devised to quantify CK-MB. In a typical immunoassay, antibodies bind to the target, and the detected signal is quantified according to the target’s concentration. We innovated a unique fluorescence assay known as the “enzyme-linked aptamer assay” (ELAA) by [...] Read more.
A fluorescent sandwich assay was devised to quantify CK-MB. In a typical immunoassay, antibodies bind to the target, and the detected signal is quantified according to the target’s concentration. We innovated a unique fluorescence assay known as the “enzyme-linked aptamer assay” (ELAA) by substituting antibodies with a pair of high-affinity aptamers labelled with biotin, namely apt. A1 and apt. A2. Avidin-labelled ALP binds to biotin-labelled aptamers, hydrolyzing its substrate, 2-phosphoascorbic acid trisodium salt, resulting in the formation of ascorbic acid. The catalytic hydrolysate functions as a reducing agent, causing the deterioration of MoS2 nanosheets. This results in the transformation of MoS2 nanosheets into nanoribbons, leading to the release of quenched AGQDs. The reestablishment of fluorescence is triggered by Förster Resonance Energy Transfer (FRET) between the MoS2 nanoribbons and AGQDs, enhancing the sensitivity of disease biomarker detection. The working range for detection falls between 2.5 nM and 160 nM, and the limit of detection (LOD) for CK-MB is verified at 0.20 nM. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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13 pages, 1792 KB  
Article
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
Cited by 1 | Viewed by 2099
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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Review

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26 pages, 3265 KB  
Review
Kinetics and Activation Strategies in Toehold-Mediated and Toehold-Free DNA Strand Displacement
by Yuqin Wu, Mingguang Jin, Cuizheng Peng, Guan Alex Wang and Feng Li
Biosensors 2025, 15(10), 683; https://doi.org/10.3390/bios15100683 - 9 Oct 2025
Viewed by 335
Abstract
Nucleic acid strand displacement reactions (SDRs) are fundamental building blocks of dynamic DNA nanotechnology. A detailed understanding of their kinetics is crucial for designing efficient sequences and regulating reaction networks with applications in biosensing, synthetic biology, biocomputing, and medical diagnostics. Since the development [...] Read more.
Nucleic acid strand displacement reactions (SDRs) are fundamental building blocks of dynamic DNA nanotechnology. A detailed understanding of their kinetics is crucial for designing efficient sequences and regulating reaction networks with applications in biosensing, synthetic biology, biocomputing, and medical diagnostics. Since the development of toehold-mediated strand displacement, researchers have devised many strategies to adjust reaction kinetics. These efforts have expanded the available tools in DNA nanotechnology. This review summarizes the basic principles and recent advances in activation strategies, emphasizing the role of strand proximity as a central driving force. Proximity-based approaches include toehold docking, associative toeholds, remote toeholds, and allosteric designs, as well as strategies that operate without explicit toehold motifs. These methods enable flexible and scalable construction of DNA reaction networks. We further discuss how combining different activation and kinetic control approaches gives rise to dynamic networks with complex and dissipative behaviors, providing new directions for DNA-based nanotechnology. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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38 pages, 2377 KB  
Review
CRISPR-Cas-Based Diagnostics in Biomedicine: Principles, Applications, and Future Trajectories
by Zhongwu Zhou, Il-Hoon Cho and Ulhas S. Kadam
Biosensors 2025, 15(10), 660; https://doi.org/10.3390/bios15100660 - 2 Oct 2025
Viewed by 1010
Abstract
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems, originally identified as prokaryotic adaptive immune mechanisms, have rapidly evolved into powerful tools for molecular diagnostics. Leveraging their precise nucleic acid targeting capabilities, CRISPR diagnostics offer rapid, sensitive, and specific detection solutions for a [...] Read more.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems, originally identified as prokaryotic adaptive immune mechanisms, have rapidly evolved into powerful tools for molecular diagnostics. Leveraging their precise nucleic acid targeting capabilities, CRISPR diagnostics offer rapid, sensitive, and specific detection solutions for a wide array of targets. This review delves into the fundamental principles of various Cas proteins (e.g., Cas9, Cas12a, Cas13a) and their distinct mechanisms of action (cis- and trans-cleavage). It highlights the diverse applications spanning infectious disease surveillance, cancer biomarker detection, and genetic disorder screening, emphasizing key advantages such as speed, high sensitivity, specificity, portability, and cost-effectiveness, particularly for point-of-care (POC) testing in resource-limited settings. The report also addresses current challenges, including sensitivity limitations without pre-amplification, specificity issues, and complex sample preparation, while exploring promising future trajectories like the integration of artificial intelligence (AI) and the development of universal diagnostic platforms to enhance clinical translation. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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30 pages, 3363 KB  
Review
Surface Plasmon Resonance Aptasensors: Emerging Design and Deployment Landscape
by Fahd Khalid-Salako, Hasan Kurt and Meral Yüce
Biosensors 2025, 15(6), 359; https://doi.org/10.3390/bios15060359 - 4 Jun 2025
Viewed by 1364
Abstract
SPR biosensors operate on the principle of evanescent wave propagation at metal–dielectric interfaces in total internal reflection conditions, with consequent photonic energy attenuation. This plasmonic excitation occurs in specific conditions of incident light wavelength, angle, and the dielectric refractive index. This principle has [...] Read more.
SPR biosensors operate on the principle of evanescent wave propagation at metal–dielectric interfaces in total internal reflection conditions, with consequent photonic energy attenuation. This plasmonic excitation occurs in specific conditions of incident light wavelength, angle, and the dielectric refractive index. This principle has been the basis for SPR-based biosensor setups wherein mass/concentration-induced changes in the refractive indices of dielectric media reflect as plasmonic resonance condition changes quantitatively reported as arbitrary response units. SPR biosensors operating on this conceptual framework have been designed to study biomolecular interactions with real-time readout and in label-free setups, providing key kinetic characterization that has been valuable in various applications. SPR biosensors often feature antibodies as target affinity probes. Notably, the operational challenges encountered with antibodies have led to the development of aptamers—oligonucleotide biomolecules rationally designed to adopt tertiary structures, enabling high affinity and specific binding to a wide range of targets. Aptamers have been extensively adopted in SPR biosensor setups with promising clinical and industrial prospects. In this paper, we explore the growing literature on SPR setups featuring aptamers, specifically providing expert commentary on the current state and future implications of these SPR aptasensors for drug discovery as well as disease diagnosis and monitoring. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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19 pages, 9558 KB  
Review
Photoactivatable Aptamer-Based Biosensors for Point-of-Care Testing: Advances and Applications
by Siyuan Wang, Xinyun Cui, Zixuan Zhong and Jingjing Zhang
Biosensors 2025, 15(6), 336; https://doi.org/10.3390/bios15060336 - 24 May 2025
Cited by 1 | Viewed by 1489
Abstract
Photoactivatable aptamer sensing technology is widely used in various detection fields due to its precise spatiotemporal regulation ability, flexible material compatibility, and excellent detection performance. By introducing an optical response mechanism to regulate the efficient recognition of the target by the sensor, this [...] Read more.
Photoactivatable aptamer sensing technology is widely used in various detection fields due to its precise spatiotemporal regulation ability, flexible material compatibility, and excellent detection performance. By introducing an optical response mechanism to regulate the efficient recognition of the target by the sensor, this strategy further broadens the regulation means of the aptamer. The application of photoactivated aptamer biosensors in point-of-care testing (POCT) can significantly improve the selectivity, sensitivity, and dynamic response ability of the POCT system. This review systematically explores the design principle and regulation mechanism of photoactivatable aptamers, with a focus on reviewing the application progress of them in the POCT platform. In addition, the existing challenges and future development trends are also discussed. It is expected that this biosensor based on photoactivatable aptamers will continue to drive POCT towards higher sensitivity, intelligence, and scene adaptability, providing innovative tools for precision medicine and environmental health monitoring. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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Other

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20 pages, 2342 KB  
Systematic Review
Trends and Challenges of SPR Aptasensors in Viral Diagnostics: A Systematic Review and Meta-Analysis
by Elba Mauriz
Biosensors 2025, 15(4), 245; https://doi.org/10.3390/bios15040245 - 12 Apr 2025
Cited by 2 | Viewed by 1087
Abstract
Surface plasmon resonance (SPR) aptasensors benefit from the SPR phenomenon in measuring aptamer interactions with specific targets. Integrating aptamers into SPR detection enables extensive applications in clinical analysis. Specifically, virus aptasensing platforms are highly desirable to face the ongoing challenges of virus outbreaks. [...] Read more.
Surface plasmon resonance (SPR) aptasensors benefit from the SPR phenomenon in measuring aptamer interactions with specific targets. Integrating aptamers into SPR detection enables extensive applications in clinical analysis. Specifically, virus aptasensing platforms are highly desirable to face the ongoing challenges of virus outbreaks. This study systematically reviews the latest advances in SPR aptasensors for virus detection according to PRISMA guidelines. The literature search recovered 322 original articles from the Scopus (n = 152), Web of Science (n = 83), and PubMed (n = 87) databases. The selected articles (29) deal with the binding events between the aptamers immobilized on the sensor surface and their target molecule: virus proteins or intact viruses according to different SPR configurations. The methodological quality of each study was assessed using QUADAS-2, and a meta-analysis was conducted with the CochReview Manager (RevMan) Edition7.12.0 Data were analyzed, focusing on the types of viruses, the virus target, and the reference method. The pooled sensitivity was 1.89 (95%, CI 1.29, 2.78, I2 = 49%). The analysis of different types of plasmonic sensors showed the best diagnostic results with the least heterogeneity for SPR conventional configurations: 3.23 (95% CI [1.80, 5.79]; I2 = 0%, p = 0.65). These findings show that even though plasmonic biosensors effectively analyze viruses through aptamer approaches, there are still big challenges to using them regularly for diagnostics. Practical considerations for measuring label-free interactions revealed functional capabilities, technological boundaries, and future outlooks of SPR virus aptasensing. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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