Lou Yafei, Chen Junhao, Sun Linan, Chen Siyu, Yang Zhiyuan, Li Miaosi, Cao Rong, Tian Junfei
State Key Laboratory of Pulp and Paper Engineering, School of Light Industry and Engineering, South China University of Technology, Guangzhou 510640, China.
NHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, China.
Anal Chem. 2025 Aug 12;97(31):17204-17215. doi: 10.1021/acs.analchem.5c03476. Epub 2025 Aug 2.
Dual-mode lateral flow assays (LFAs) have gained significant attention, yet existing systems predominantly combine optical modalities, leaving hybrid colorimetric-electrochemical configurations underexplored despite their potential to achieve diagnostic synergy and minimize interference. Here, we present a universally compatible, low-cost lateral flow platform leveraging dual-signal nanohybrids for synchronized colorimetric-electrochemical detection. A hierarchically hollow Cu/Zn-metal-organic framework (MOF) bearing carboxyl functional groups was rationally designed to anchor gold nanoparticles (AuNPs) in situ for colorimetric signaling, followed by covalent immobilization of aminoferrocene to establish electrochemical signaling. This architecture strategically preserves AuNPs' antibody-binding capacity while confining ferrocene electroactivity within carboxyl-enriched domains. A nitrocellulose-free lateral flow device was developed using chitosan-modified filter paper as a membrane replacement with disposable screen-printed electrodes vertically integrated beneath the test zone, thereby enabling seamless integration with commercial AuNP-based LFA strips for simultaneous dual-signal readouts without cross-interference. This design not only allows parallel signal acquisition but also maintains the cost-effectiveness, single-step operation, and "sample-in-answer-out" workflow characteristics of traditional LFAs. When applied to okadaic acid detection, the device simultaneously performs visual screening at 2 ng/mL that meets regulatory requirements and laboratory-grade electrochemical quantification with a detection limit of 0.06 ng/mL. Furthermore, it achieves the broadest linear dynamic range and the lowest detection limit reported for okadaic acid detection on lateral flow platforms. Through coupling functionally compartmentalized nanoarchitectures with minimally modified lateral flow frameworks, we establish a universal paradigm for dual-mode colorimetric/electrochemical LFAs.
双模式侧向流动分析（LFA）已引起广泛关注，然而现有的系统主要是将光学模式结合起来，尽管具有实现诊断协同作用和最小化干扰的潜力，但混合比色-电化学配置仍未得到充分探索。在此，我们展示了一种通用兼容、低成本的侧向流动平台，该平台利用双信号纳米杂化物实现同步比色-电化学检测。合理设计了一种带有羧基官能团的分级中空铜/锌金属有机框架（MOF），用于原位锚定金纳米颗粒（AuNP）以进行比色信号传导，随后通过共价固定氨基二茂铁来建立电化学信号传导。这种结构策略性地保留了AuNP的抗体结合能力，同时将二茂铁的电活性限制在富含羧基的区域内。使用壳聚糖修饰的滤纸替代膜，开发了一种无硝酸纤维素的侧向流动装置，并在测试区域下方垂直集成了一次性丝网印刷电极，从而能够与基于商业AuNP的LFA试纸条无缝集成，实现同时双信号读出且无交叉干扰。这种设计不仅允许并行信号采集，还保持了传统LFA的成本效益、单步操作和“样品进-答案出”的工作流程特点。当应用于冈田酸检测时，该装置在2 ng/mL时可同时进行视觉筛选，满足监管要求，并进行实验室级别的电化学定量分析，检测限为0.06 ng/mL。此外，它实现了侧向流动平台上报道的冈田酸检测最宽的线性动态范围和最低的检测限。通过将功能区室化的纳米结构与经过最小化修饰的侧向流动框架相结合，我们建立了一种双模式比色/电化学LFA的通用范式。
