Aug 2026· Biosensors· Vol 16, pp. 465· 0 citations· 45 references
Abstract
Accessible molecular diagnostics is fundamental to effective healthcare. While most current point-of-care devices detect only the presence of a molecular biomarker(s), biomarker quantification can be equally important for decision-making on disease treatment and containment. Here, we present a diagnostic platform that enables the equipment-free quantification of molecular biomarkers with the simplicity of a binary (yes/no) readout. This capability is achieved by integrating a stoichiometric quantitative approach with widely available and easy-to-use lateral flow dipsticks. To implement the approach, we engineer negative cooperativity into target–probe binding interactions for oligonucleotide targets as a model system. The resulting threshold-based semi-quantitative assay with lateral flow dipsticks quantifies targets in the low-nanomolar range and operates reliably in complex biological backgrounds. A key advantage of this platform is its potential adaptability to new and emerging targets: repurposing will require only reagent redesign, without the need for additional fabrication.
This review systematically evaluates the fundamental design principles and advanced applications of DNA circuits in precision diagnostics, and reviews recent advancements in applying DNA circuits to detect various biomarkers, such as nucleic acids and proteins.
Ziwei He, Yiqing Yi, Min Mi et al.· Analytical Methods· 0 citations
Single-molecule immunoassays (SMIs) overcome the sensitivity limitations of conventional bulk measurements by enabling a paradigm shift from analog to digital signal readouts, thereby facilitating highly sensitive quantification of ultra-low-abundance biomarkers for precision diagnostics. This review provides a systematic overview of recent advances in SMI technologies and the conceptual framework underlying their evolution. First, discretization strategies for single-molecule counting are classified into hard discretization, based on physical confinement, and soft discretization, based on spatiotemporal isolation, within heterogeneous and homogeneous assay systems, respectively. The fundamental mechanisms by which these strategies mitigate diffusion limitations and enhance signal-to-noise ratios are discussed. Second, the integration of SMIs with CRISPR-based diagnostic systems (CRISPR-dx) is examined, with particular emphasis on their complementary roles in target recognition and signal amplification. Finally, recent applications of SMIs in the diagnosis of oncological, neurological, infectious, and cardiovascular diseases are summarized, along with a critical discussion of current engineering challenges and future directions toward clinical translation.
Mingxin Lu, Jie Cheng, Jinhong Guo· ACS Sensors· 0 citations
Early detection of many diseases remains difficult because they often develop silently over the course of years. Circular RNAs are now at the forefront as biomarker candidates with a covalently closed structure, making them highly stable with exonuclease resistance and long half-lives. With their disease-specific expression pattern and their presence in biofluids, they offer easier and noninvasive monitoring of molecular signatures. Conventional detection techniques require centralized laboratories, sophisticated instrumentation, and specialized personnel, which restrict their widespread clinical adoption and limit their applicability in point-of-care diagnostic settings, but recent advances in biosensor technologies enable rapid, sensitive, and highly specific circRNA detection in biological matrices without complex equipment. Integration with nanomaterials, enzymatic amplification, and microfluidic or portable devices further enhances the specificity, signal strength, and clinical applicability. This Tutorial critically evaluates these emerging biosensing strategies, discusses current challenges, and provides practical guidelines for selecting circRNA biomarkers and corresponding detection methods. By bridging circRNA biology with advanced biosensor design, this work aims to accelerate translational research and guide the development of next-generation diagnostics for early disease detection, supporting a shift from reactive treatment to proactive health care.
A. Glovi, P. Kalligosfyri, A. Miglione et al.· Analytical Chemistry· 0 citations
Compact and ultrasensitive detection of viral RNA and cancer-associated biomarkers is essential for early diagnosis and disease management. Conventional lateral flow assays (LFA), however, often lack the sensitivity and quantitative reliability required for low-abundance nucleic acids in complex matrices without amplification. Here, we present a quantum-enabled, magnetically modulated fluorescent nanodiamond LFA (FND-LFA) for amplification-free RNA detection through nucleic acid hybridization. Fluorescent nanodiamonds provide photostable, spin-dependent fluorescence, while magnetic modulation separates target-associated signals from background. Pixel-wise contrast analysis with Gaussian modeling enables robust quantitative readout, and sequence-optimized probes selectively hybridize to low-secondary-structure RNA regions without denaturation. The platform achieves a 10 fM detection limit and a linear range of 10 fM to 10 pM for SARS-CoV-2 RNA, together with a 100 fM detection limit for cancer-associated miRNAs. This strategy offers a compact and generalizable route for sensitive, amplification-free RNA diagnostics.
Wei Wang, Shreyans Chatterjee, Qi Lu et al.· Nano letters (Print)· 0 citations
A single-pot electrochemical sensing platform that enables rapid and ultrasensitive quantitative detection of AD biomarkers directly from untreated blood or plasma within 20 min of collection, without sample preparation, washing, or using additional reagents is reported.
Xuewei Du, Taoping Zhang, Zhongzhong Wan et al.· ACS Sensors· 0 citations
Real-time, high-sensitivity biosensors are essential for personalized healthcare, enabling early disease diagnosis and continuous monitoring. Organic field-effect transistor (OFET) sensors offer label-free detection, rapid response, and low cost, but noise interference and inherent architectural limitations hinder their use in high-throughput, multi-signal analysis. To address these issues, this study presents a gate-array-based OFET biosensor that improves detection sensitivity, stability, and analytical throughput. The integrated gate-array architecture and signal modulation strategies enable rapid acquisition of multiple transfer curves for efficient concentration analysis of unknown samples. To validate the approach, the sensor detects the thrombotic biomarker D-Dimer with an ultra-low limit of 0.354 ng/mL in PBS, well below clinical thresholds, and performs reliably in human serum and patient samples. This work introduces a robust platform for high-throughput, multi-target detection in complex biological environments, advancing next-generation biomedical diagnostics and personalized healthcare.
Jing Zhang, Qi-Ting Wang, Tian-Tian Song et al.· Talanta: The International J...· 0 citations
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