Hollow Cu/Zn-MOF@Au/Ferrocene Nanoarchitectures: A Universal Leap from Colorimetric to Dual-Mode Colorimetric/Electrochemical Lateral Flow Assays

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.