Quantum-biological interface in biosensor design: detecting proteins with electrochemical aptasensor

MicroRNA-451 (miR-451), a colorectal cancer (CRC)-associated biomarker, is of interest for minimally invasive analysis. Herein, we report a biosensing platform for ultrasensitive miR-451 detection by coupling off-chip hybridization chain reaction (HCR)-initiated amplification with in situ single-nanoparticle LSPR monitoring of the biocatalytic etching process within a microfluidic chip. In the presence of miR-451, HCR between two hairpin probes was first carried out in solution to generate long DNA duplexes containing G-quadruplex sequences. After binding with hemin, the resulting hemin-G4 DNAzymes catalyzed H2O2 to produce reactive species capable of etching the silver shell of Au@Ag core-shell nanoparticles (Au@AgNPs) immobilized in the microfluidic chip, leading to a measurable LSPR redshift. By tracking the spectra of the same individual nanoparticles before and after etching, the platform minimized spatial sampling errors associated with conventional ensemble-based LSPR measurements. The proposed method achieved a limit of detection of 40.96 aM and a linear range from 100 aM to 100 pM, with high specificity toward nontarget and mismatched sequences. Its applicability was preliminarily evaluated in fetal bovine serum and further assessed in commercial human serum through spike-in recovery experiments, while RT-qPCR provided auxiliary verification of the concentration-dependent response trend. These results support the potential of this platform for ultrasensitive miRNA analysis in complex biological matrices.

Electrochemical sensors face critical challenges in achieving ultra-high sensitivity and specificity within complex biological matrices. To address these limitations, this study proposes an integrated electrochemical computational model (IECM), a novel end-to-end framework that couples kinetics, electrochemistry, and signal amplification sub-modules to predict and optimize sensor performance. Unlike previous descriptive reviews, this work validates the IECM through rigorous experimentation using reduced graphene oxide MXene/ anchors gold nanoparticles nanocomposite interfaces. The limit of detection was determined based on the standard definition (3sigma/slope, where sigma is the standard deviation of the blank signal), yielding exceptionally low values of 0.12 fg ml-1for prostate-specific antigen and 5.0 × 10-18M for microRNA-21, with corresponding calibration curve slopes confirming high signal-to-noise ratios. In complex matrices such as serum and saliva, the sensor demonstrated robust anti-interference capabilities, achieving recovery rates of 92.0% ± 3.5% and cross-reactivity rates below 3.5%. Long-term stability tests indicated a signal retention of 68.7% after 8 weeks under moderate storage conditions. Furthermore, double-blind clinical trials against gold-standard assays revealed a high concordance rate (κ = 0.93), confirming the model's predictive accuracy and the sensor's clinical potential. This research establishes a unified computational-experimental paradigm for the rational design of next-generation biosensors.

Human chorionic gonadotropin (β-hCG) is a key biomarker for the diagnosis and monitoring of gestational trophoblastic disease (GTD). Current gold standard methods, such as chemiluminescent immunoassays and ELISA, are limited by high operational costs, long analysis times, and the requirements for centralized laboratory facilities, which restrict their accessibility, especially in resource-limited settings. As a promising alternative, electrochemical biosensors offer rapid, sensitive, selective, and cost-effective β-hCG detection, suitable for point-of-care applications. This review summarizes recent advances in the development of electrochemical β-hCG biosensors, with an emphasis on innovations in electrode engineering, interface design, biological recognition elements, and signal amplification strategies that significantly improve analytical performance, including detection limits and linear dynamic range. Considerable focus is assigned to biosensors that are capable of accurately measuring β-hCG at high concentrations, as required for effective clinical management of GTD. The review also discusses major challenges, such as prolonged stability, selectivity in complex biological matrices, reproducibility, and consistent measurement performance at clinically relevant high β-hCG levels. Finally, emerging trends such as miniaturization, microfluidic integration, and multiple detection are highlighted as promising directions to support real-time GTD monitoring.

Novel boronate affinity molecularly imprinted nanomaterials for selective dispersive magnetic solid-phase extraction of catecholamines from equine urine

Electrochemical microRNA biosensors for gallbladder cancer: Translational perspectives for clinical chemistry and point-of-care diagnostics.

3-mercaptopropionic acid agent-based biosensor system using gold-screen printed electrode for aflatoxin B1 detection.

Ovarian cancer ranks as the seventh most prevalent malignancy among women globally. Human epididymis protein 4 (HE4) is an FDA-approved tumor biomarker for the early detection of malignant ovarian cancer. In this work, a portable, electrochemical HE4 immunosensor was fabricated for the rapid, sensitive, and practical analysis of HE4 levels in commercial human blood serum. In the preparation of immunosensors, nanomaterials such as Ti3C2, Ti3C2-COOH, and gold nanoparticles (AuNPs), as well as disposable screen-printed carbon electrodes, were used. The influence of nanomaterials on the electrochemical efficiency of electrodes and immunosensors was examined. The materials of Ti3C2, Ti3C2-COOH, and AuNP, and the modified electrodes with these materials, were characterized by FE-SEM-EDX, FTIR, and XRD. Optimization studies and evaluation of analytical performance of the HE4 immunosensor were conducted using a portable electrochemical reader with DPV. The linear range and the detection limit of HE4 immunosensors were determined to be 5–250 pM and 0.34 pM, respectively. Stability was observed for 60 days, and shelf life was assessed for 24 weeks. The selectivity of HE4 immunosensors was tested in the presence of other ovarian cancer biomarkers and found to be highly selective for HE4. In repeatability tests, HE4 immunosensors responded to seven repetitions (RSD: 3.38%, n = 7). Method validation of the immunosensor platform was confirmed by ELISA. The HE4 levels in commercial human blood serum were directly measured on-screen in picomolar (pM) (immunosensor setup time: 105 min; antibody-antigen-BSA incubations) and a portable electrochemical reader (device reading time: 20–30 s). The developed HE4 immunosensors are potential candidates in point-of-care testing.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s00216-026-06457-7.

Enzyme-based chemical biosensors are based on biological recognition. In order to operate, the enzymes must be available to catalyze a specific biochemical reaction and be stable under the normal operating conditions of the biosensor. Design of biosensors is based on knowledge about the target analyte, as well as the complexity of the matrix in which the analyte has to be quantified. This article reviews the problems resulting from the interaction of enzyme-based amperometric biosensors with complex biological matrices containing the target analyte(s). One of the most challenging disadvantages of amperometric enzyme-based biosensor detection is signal reduction from fouling agents and interference from chemicals present in the sample matrix. This article, therefore, investigates the principles of functioning of enzymatic biosensors, their analytical performance over time and the strategies used to optimize their performance. Moreover, the composition of biological fluids as a function of their interaction with biosensing will be presented.

Label-free biosensor for trace insulin-like growth factor-I assay based on rGO-SnS2 heterostructure nanocomposite

Selective and Sensitive MIP-Based Electrochemical Sensor for the Analytical Determination of Lanreotide

A green perspective for the first electrochemical detection and application of balsalazide via recycled waste core-shell carbon/CdO nanoparticles-based hybrid nanosensor

A comparative study of capacitive immunosensors based on self-assembled monolayers formed from thiourea, thioctic acid, and 3-mercaptopropionic acid

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide due to the limited sensitivity of current surveillance and diagnostic strategies for early-stage detection. Electrochemical biosensors have emerged as promising tools for HCC diagnostics owing to their high sensitivity, rapid response, low cost, and compatibility with point-of-care testing. This review provides a comprehensive overview of recent advances in electrochemical biosensors for HCC detection, focusing on key biomarkers such as alpha-fetoprotein (AFP), glypican-3 (GPC-3), AFP-L3, and circulating nucleic acids. We discuss developments in biorecognition strategies, nanomaterial-assisted signal amplification, and analytical performance of reported sensor platforms. In addition, the review critically examines the gap between laboratory-scale sensor performance particularly ultra-low detection limits and practical clinical requirements, including selectivity in complex biological matrices, reproducibility, long-term stability, and validation using clinical samples. The review also discusses how nanomaterial selection, fabrication complexity, and device variability influence the clinical translation of electrochemical biosensors. Finally, the review highlights future directions for developing clinically viable electrochemical biosensors, including multiplex biomarker detection, standardized validation with real clinical samples, scalable manufacturing approaches, and integration with artificial intelligence and digital health platforms to improve HCC monitoring.

Nucleic acid probes in living organisms play an essential role in therapeutics and diagnosis. Through the imaging and sensing of nucleic acid probes in complex biological matrices, a variety of diseases-related biological process, pathogenic process, or pharmacological responses to a therapeutic intervention have been discovered. However, a critical challenge of nucleic acid probes applied in complex matrices lies in enhancing the stability of nucleic acid probes, especially when it suffers from nuclease degradation and protein adsorption. In order to enhance the application of nucleic acid nanoprobes in complex matrices, great efforts have been devoted to improving the stability of probes operated in complex media, including construction of nucleic acid nanoprobes with nuclease resistance and protein adsorption resistance, sample pretreatment, anti-biofouling and signal correction. In this review, we aim to summarize recent advances in the stability of nucleic acid nanoprobes in complex matrices, including the methods of enhancing the stability of probes or signals, and the application of nucleic acid nanoprobes for disease diagnosis.

Vibrio vulnificus is a halophilic marine bacterium widely distributed in coastal environments and seafood products and is responsible for severe human infections and foodborne disease outbreaks. Rapid and sensitive detection of V. vulnificus is therefore critical for clinical diagnosis and seafood safety monitoring. The objective of this study was to develop and evaluate a rapid, sensitive, and specific nucleic acid detection method for V. vulnificus suitable for application in complex biological and food matrices. An ERA-CRISPR/Cas13a-based nucleic acid detection assay was established by coupling enzymatic recombinase amplification (ERA) with Cas13a-mediated collateral cleavage of fluorescent RNA reporters. The analytical performance of the assay was systematically evaluated using V. vulnificus standard plasmids, artificially contaminated human serum samples, and spiked oyster homogenates. The assay exhibited high specificity for V. vulnificus, with no cross-reactivity observed for other common Vibrio species. The limit of detection (LOD) was 1 × 10-1 copies/μL for standard plasmid templates. In complex matrices, including human serum and oyster samples, the assay achieved an LOD of 1 × 101 CFU/mL. The entire detection process was completed under isothermal conditions within 45 min. A sensitive and specific ERA-CRISPR/Cas13a-based assay for the detection of V. vulnificus was successfully developed and validated. The method demonstrates strong analytical performance in both biological and seafood matrices. A rapid isothermal ERA-CRISPR/Cas13a assay for V. vulnificus detection was developed. High specificity was achieved without cross-reactivity to other Vibrio species. The assay enables sensitive detection in serum and oyster samples. The method shows potential for routine seafood safety surveillance and marine pathogen monitoring.