Skip to content

Ultrafast Self-Assembly of Zeolitic Imidazolate Framework-8 Enables Antibody Orientation for Ultrasensitive Lateral Flow Immunoassays.

Jul 2026 · ACS Nano · Vol 20, pp. 19256-19271 · 1 citation · 49 references
Medicine

Abstract

Gold-nanoparticles-based lateral flow immunoassays (AuNPs-LFIAs) are widely used for point-of-care testing, yet their sensitivity remains fundamentally limited, likely because random antibody orientation on AuNP surfaces restricts Fab accessibility and antigen recognition efficiency. Precise control of antibody orientation is thus critical for maximizing probe activity, yet existing directional conjugation strategies are often multistep, technically complex, and poorly scalable. Here, we report an ultrafast biomimetic mineralization strategy that enables one-step, room-temperature self-assembly of zeolitic imidazolate framework-8 (ZIF-8) with antibodies and dual-ligand AuNPs, producing uniform hybrid nanoprobes within 5 min. ZIF-8 shell preserves the plasmonic properties of AuNPs while simultaneously enhancing colloidal stability and optical signal intensity. Molecular dynamics simulations suggest a two-step orientation model: (i) rapid electrostatic attraction between negatively charged Fc regions and Zn2+ ions initiates nucleation, followed by (ii) Fc-associated interfacial interactions that promote preferential Fc-oriented binding and anisotropic Fc/Fab distribution, thereby enhancing Fab exposure for efficient antigen recognition. This controlled assembly increases Fab accessibility more than 3-fold relative to conventional adsorption or co-precipitation strategies, minimizes nonspecific adsorption, and amplifies signal output. When applied to competitive LFIAs, the oriented nanoprobes enabled ultrasensitive detection of chloramphenicol down to 13 pg/mL, corresponding to approximately 1 order of magnitude higher sensitivity than AuNPs-based LFIA gold standard. By integrating mechanistic insight with operational simplicity, this work establishes a generalizable platform for ultrafast, scalable, and antibody-orientation-controlled nanoprobe fabrication for next-generation LFIAs in food safety, clinical diagnostics, and environmental monitoring.

View source

Similar papers

Jul 2026

Linker-optimized bivalent nanobodies combined with photothermal gold liposome nanocomposites for enhanced dual-mode lateral flow immunoassay.

Lateral flow immunoassay (LFIA) has been widely used for rapid on-site analysis because of its simplicity, portability, and low cost. However, its performance in competitive assays, particularly for small molecule toxins, remains limited, as the properties of antibodies and the reliance on single-mode signal often lead to insufficient sensitivity and reliability. To address this challenge, we developed an enhanced colorimetric-photothermal LFIA by integrating linker-optimized bivalent nanobodies (BvNbs) and gold-liposome nanocomposites (Au-LNCs). Using tetrodotoxin (TTX) as a representative analyte, a series of BvNbs with different linker lengths were constructed. Molecular docking and molecular dynamics simulations further demonstrated that linker length modulates BvNbs detection performance by regulating conformational stability, local flexibility, and persistent interactions with free target molecules. In parallel, photothermal Au-LNCs were prepared, which exhibited broadband near-infrared absorption and a photothermal conversion efficiency as high as 78.06%. The resulting LFIA achieved a photothermal LOD of 1.89 ng/mL, corresponding to an approximately 10.7-fold improvement in sensitivity compared with conventional colloidal gold-based LFIA, while maintaining good reliability in real samples. Overall, this study provides mechanistic insight into the rational design of BvNbs and a promising strategy for improving LFIA performance.

Jinzhi Han, Hongzhi Liang, Lin Luo et al. · 0 citations
Open access Jul 2026

Interface Self-Assembly of Au10 Nanoclusters for Enhanced Electrochemiluminescence and Alzheimer's Disease Biomarker Detection.

Atomically precise metal nanoclusters (NCs), as ultrasmall materials with well-defined composition and structure, exceptional biocompatibility, and unique optical properties, position them as strong candidates in the field of electrochemiluminescence (ECL). However, the ECL efficiency of NCs is relatively low, which dramatically constrained their applications due to the demands of detection sensitivity and brightness. In this study, we report the interface self-assembly of Au10 nanoclusters for the first time, and ultimately formed a fibrous structure with a high aspect ratio, Au10-Fiber, which is an innovative approach that significantly enhances the ECL activity of Au10 NCs. By employing time-dependent and in situ spectroscopic techniques, we visually monitored the dynamic assembly process, and elucidated the interface self-assembly mechanism mediated by aurophilic interaction and π-π stacking. The increase in local electronic density, enhanced conductivity of the ordered structure, and accelerated electron transfer within the π-conjugated system collectively contributed to the significant enhancement of the ECL performance, thereby revealing the key structural factors responsible for ECL enhancement. As a proof of concept, we successfully constructed an ECL immunosensor based on Au10-Fiber for the detection of Alzheimer's disease biomarker Aβ1-42, achieving a detection limit below 3.33 fg/mL.

Zhiying Jin, Yao Peng, Mengting Sheng et al. · 0 citations
Jul 2026

Avidin-Functionalized Gold Nanoparticles Enable Cationic Isotachophoresis for Enhanced Lateral Flow Assays.

The LIGMA assay is established as a viable electrokinetic strategy for improving paper-based biosensors, providing a foundation for expanded applications in clinical diagnostics, multiplexed detection, and portable field-deployable biosensing platforms.

D. McCornack, C. Ivory, Zhihong Zhang et al. · 0 citations
Open access Aug 2026

Pyrene-Tagged Polyimidazolium Nanoclays Enable Modular Excimer Emission for Multi-Analyte Fluorescence Sensing

We introduce a modular platform for engineering excimer-active fluorescent nanoclays by covalently installing pyrene onto imidazolium-functionalized polyionic nanoclays (PINCs) using thiol-maleimide Michael addition. Precise control of pyrene surface densities (0.1–15 mol %) affords a synthetically tunable monomer–excimer landscape, with systematic shifts in excimer-to-monomer intensity ratios (IE/IM) and solvent-dependent photophysics that confirm periodic probe spacing rather than clustering. The cationic PINC framework dramatically enhances analyte accessibility and local concentration, enabling solution-phase detection of nitroaromatic and nitrate-based explosives with Stern–Volmer constants of up to 1.56 × 104 M–1 for TNT, an order-of-magnitude enhancement over neutral pyrene (Py) controls. Py-PINCs also exhibit strong and selective quenching by halides, highlighting synergistic electrostatic and collisional pathways. In the solid state, PINC-immobilized pyrene functions as an environment-responsive oxygen sensor, displaying linear quenching (KSV = 5.29 bar–1) and a rapid reversible response (2.5 s). These results establish pyrene-tagged PINCs as an attractive class of charge-amplified, excimer-programmable 2D hybrid materials that unify tunable photophysics with multimodal chemical sensing, expanding the functional scope of designer PINCs for security, environmental, and analytical technologies.

Piyuni Ishtaweera, N. E. Larm, Gary A. Baker · 0 citations
Open access Aug 2026

Electron-Donating Benzenethiols Direct Rapid Formation of Plasmonic Gold Nanoflowers

Gold nanostructures with branched morphologies exhibit strong plasmonic properties, enabling advanced biosensing and biochemical applications. Here, we report a rapid and scalable synthesis of gold nanoflowers (AuNFs) using modified benzenethiols as both reducing and capping agents. Benzenethiols bearing electron-donating substituents promoted rapid Au3+ reduction and anisotropic branch growth, completing particle formation in less than 10 seconds without seed preparation or organic-aqueous transfer steps. The resulting AuNFs had abundant plasmonic hot spots and intrinsic Raman reporters, serving as dual-modality probes for colorimetry and surface-enhanced Raman scattering (SERS). When integrated into lateral flow assays, AuNFs markedly enhanced analytical sensitivity. In oxycodone detection, limits of detection reached 4.48 pg/mL (colorimetry) and 0.38 fg/mL (SERS), representing 700-fold and 1,200-fold improvements, respectively, over spherical gold nanoparticles. This performance enabled accurate quantification of oxycodone in plasma samples from murine addiction models. The developed method provides a practical route for preparing high-performance plasmonic nanomaterials for applications in biosensing, catalysis, and analytical chemistry.

Jin-Ho Park, Young Kwan Cho, Victoria L. Schaal et al. · 0 citations