Aug 2026· Biosensors & bioelectronics· Vol 313, pp.
119119
· 0 citations· 39 references
Medicine
TL;DR
A one-step, dual-antifouling electrochemical interface by co-assembling phase-transited bovine serum albumin and a cyclic multifunctional peptide that significantly suppresses non-specific protein adsorption while enabling oriented target recognition is developed.
Abstract
Soluble programmed death-ligand 1 (sPD-L1) is a promising non-invasive biomarker for early cancer diagnosis and immunotherapy monitoring. However, electrochemical detection of sPD-L1 in serum remains challenging due to severe biofouling that compromises sensitivity and specificity. We developed a one-step, dual-antifouling electrochemical interface by co-assembling phase-transited bovine serum albumin (PTB) and a cyclic multifunctional peptide (CP). PTB forms a dense, amyloid-like nanofilm that acts as a robust protein shield, while CP introduces a zwitterionic antifouling loop and a PD-L1-binding motif. This synergistic architecture significantly suppresses non-specific protein adsorption while enabling oriented target recognition. The sensor achieves a detection limit of 37.4 pg/mL and accurately distinguishes cancer patients from healthy individuals using neat serum without dilution or pretreatment. The PTB/CP dual-antifouling platform offers a simple, sensitive, and clinically translatable strategy for sPD-L1 detection, with broad potential for point-of-care cancer diagnostics and immune monitoring.
The precise detection of biomarkers in complex biofluids remains a significant challenge for electrochemical biosensors, largely due to the nonspecific adsorption of proteins and other molecules. While zwitterionic peptides offer excellent antifouling properties, their typical linear architectures are prone to protease hydrolysis, compromising performance and limiting practical use. To overcome this limitation, we engineered a linear peptide through structural modulation, stabilizing it into a hairpin-shaped conformation by introducing two disulfide-directed bridges, and designated it as the hairpin-shaped antifouling peptide (HAP). This structural modulation maintains its inherent antifouling properties while the conferred conformational constraints significantly enhance its resistance to enzymatic hydrolysis. Based on this HAP, an antifouling electrochemical biosensor was constructed, which effectively resists nonspecific adsorption while maintaining high enzymatic stability, enabling the direct detection of carbohydrate antigen 15-3 (CA15-3) in human serum with a detection limit of 2.64 mU·mL-1. Importantly, the HAP-based biosensor demonstrates reliability on par with commercial enzyme-linked immunosorbent assay methods and successfully discriminates between healthy individuals and cancer patients. With its high accuracy and capacity for direct detection, the platform offers a promising strategy for analyzing cancer biomarkers in serum, potentially enabling more timely and effective clinical diagnosis and treatment.
Shuyu Jiang, Shicheng Liu, Zhen Song et al.· Analytical Chemistry· 0 citations
Biofouling, arising from the nonspecific adsorption of proteins, cells, and other biomolecules, remains a major challenge that compromises the stability and reliability of diagnostic and therapeutic platforms. To address this issue, a super-antifouling electrochemical aptasensor was developed by integrating a biomimetic "gemini" zwitterionic monomer (BSMMP) with polydopamine (PDA). The covalent assembly of BSMMP and PDA forms a multi-site anchoring layer that enables the stable functionalization of the affinity aptamer GC20. Owing to its dense hydration shell, the PDA-BSMMP hybrid interface acts as a physical barrier against nonspecific adsorption, maintaining electron-transfer stability in undiluted human serum. Differential pulse voltammetry confirmed that this interface markedly reduced biofouling-induced signal loss, limiting attenuation to less than 15%, nearly fourfold lower than that of the unmodified surface. The platform achieved a low limit of detection of 0.97 ng/mL, a broad linear range from 1 ng/mL to 100 μg/mL, and high selectivity for trastuzumab in a label-free format without secondary antibodies or additional signal amplification. Finally, this platform successfully quantified trastuzumab in serum from breast cancer patients, with results consistent with commercial ELISA kits. Overall, this super-antifouling aptasensor offers great potential for therapeutic drug monitoring, advancing zwitterionic interface-based biosensing strategies for point-of-care diagnostics.
Zheng Zhao, Wan-Qing Yu, Haidong Li et al.· Bioelectrochemistry· 0 citations
It is challenging to develop a highly selective and antifouling mass spectrometry (MS) ionization interface for the rapid and sensitive detection of trace analytes in complex matrices, such as aflatoxins (AFs) in Traditional Chinese Medicines (TCMs) and milk. In this study, a bifunctional 8-arm PEG derivative (NH2HCl-8armPEG10K-(MTz)7) was engineered to construct a dense hydration layer on a gold-coated stainless steel (SSS) substrate via polydopamine (PDA) chemistry. This multiarm PEG scaffold not only provides superior steric hindrance against nonspecific adsorption but also serves as a robust linker to immobilize streptavidin (SA) via an efficient copper-free click reaction. Subsequently, biotinylated aptamers targeting six AFs were immobilized with high density and specific orientation. The resulting specific ionization element (AP@SSS) exhibits outstanding anticontamination capabilities and highly specific spatial recognition ability, which has been confirmed through molecular dynamics (MD) simulations and density functional theory (DFT) calculations. After simple sample preparation, the AP@SSS can be directly coupled with ambient electrospray ionization MS, achieving a detection time <1 min. The method demonstrated high sensitivity with limits of detection (LODs) of 0.05–0.380 μg/kg and limits of quantitation (LOQs) of 0.16–1.240 μg/kg. At the same time, good accuracy (recoveries 82.1–102.5%) and precision (RSD: 2.36–17.82%) for AFs in milk and TCM matrices were obtained. The functionalized AP@SSS provides a robust and high-throughput tool for the ultrasensitive monitoring of trace toxins in complex samples.
A cascade-driven dual-signal attenuation strategy that holds great promise for high‑performance electrochemical biosensing in complex biological samples.
Ge Song, Jiaqing Wang, Xianrui Jiang et al.· Analytical and Bioanalytical...· 0 citations
Breast cancer following metastatic dissemination is associated with high mortality rates, severely threatening women's health. As principal mediators of intercellular communication within the tumor microenvironment, secretory autophagosomes (SAPs) propel breast cancer progression and metastasis by modulating the establishment of the pre-metastatic niche, thereby positioning them as highly promising biomarkers for breast cancer. However, the paucity of accurate and simplified quantitative tools has impeded the direct detection of circulating SAPs. This study presents a sensing platform that couples nanozyme cascade catalysis with a covalent organic frameworks (COFs)-derived nanohydrogel (CGNH) for precisely assessing trace-level SAPs. The AuNBP@PtPd-MoS2 nanozyme, via its stereoconfiguration and trimetallic synergy, recapitulates the dual enzyme-mimicking activities of GOx/CAT. Hence, it enables self-sustained interfacial charge transfer. As a signal probe, it efficiently accelerates self-cascade catalysis and electrochemical mass transfer. Additionally, CGNH creates an ideal interface for SAPs enrichment and cascade catalysis, featuring a hierarchical pore structure, a hybrid conductive network, and suitable biocompatibility. With self-assembled antifouling peptide nanoparticles (APNP) as a shielding barrier, the platform reliably detects SAPs in intricate biological matrices verified using cellular, murine and clinical specimens. Compared with conventional biomarkers, SAPs produce more informative readouts on disease progression. This electrochemical platform differentiates between benign and malignant breast diseases and healthy controls with high diagnostic accuracy (AUC = 0.962), especially for gray-zone differentiation and metastasis forecasting. This study offers new avenues for SAPs-based liquid biopsy to identify signs of breast cancer metastasis and is expected to become a reliable non-invasive tool for personalized breast cancer management.
Yue Zhang, Shuyi Chen, Jie Ma et al.· Biosensors & bioelectronics· 0 citations
Designing robust, fully synthetic receptors capable of selective protein detection remains critical for advanced clinical diagnostics. Molecularly imprinted polymers (MIPs) are a promising alternative to antibodies, but their application is often limited by empirical epitope selection and incomplete integration into functional assays. Here, we present an end-to-end platform combining data-driven epitope selection with polynorepinephrine-based molecular imprinting to produce fully synthetic protein receptors. The Python script "Epitope Selection Rational Approach" (ESRA), integrating physicochemical descriptor analysis and supervised machine learning, was developed and applied to human myoglobin (MYG) to identify effective imprintable peptide epitopes in the pre-analytical stage. Five selected epitopes were used to fabricate molecularly imprinted PNE nanofilms (MIPNE-NFs) and nanoparticles (MIPNE-NPs), targeting distinct regions of MYG. Systematic kinetic and affinity characterization by surface plasmon resonance (SPR) revealed pronounced epitope- and format-dependent recognition, underscoring the need for parallel evaluation of nanofilm and nanoparticle architectures. The optimal NF/NP combination, exploited as a capturing probe and a signal enhancer, respectively, was implemented in a fully antibody-free SPR sandwich assay. This configuration achieved sensitive detection over 4-125 ng mL-1, with a limit of detection of 0.9 ± 0.5 ng mL-1 in buffer and 0.70 ± 0.02 ng mL-1 in 1/200 diluted serum, covering the clinically relevant range for acute myocardial infarction, rhabdomyolysis, and muscle injury. This work establishes a generalizable workflow, from rational epitope selection to imprinting, kinetic validation, and assay integration, demonstrating that MIPNE can provide robust, antibody-free alternatives for sensitive protein detection in complex biological matrices.
D. Sestaioni, S. Ventisette, G. Ciacci et al.· ACS Sensors· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
