ABSTRACT The early detection of diseases often hinges on identifying minute quantities of biomolecular markers in complex bodily fluids. However, traditional immunosensors, while offering operational simplicity and rapid response, face significant limitations in sensitivity. This is particularly evident when detecting disease markers in complex biological environments, where the movement of labels is impeded by the high resistance arising from the viscous nature of these media. In this work, we present an inverse design strategy for engineering powerful nanomotors with optimal topological architecture for ultra‐efficient target capture and enhanced biosensing in complex biological environments. Through simulation calculations, four types of potential nanomotor architectures are screened and identified the optimal topology that maximizes capture efficiency. The optimal PS‐Z‐SiO 2 @Au (PZSA) nanomotor was then experimentally synthesized employing a selective interface self‐assembly strategy, exhibiting superior movement speed (3.97 times faster than static particles), 1.92 times better target capture efficiency, and 104.1‐fold higher sensitivity compared to traditional immunosensors. Clinical sample testing demonstrated strong consistency with chemiluminescent immunoassays, highlighting the potential of the PZSA nanomotor for ultra‐sensitive and rapid immunosensor platforms. This study demonstrates the feasibility of reverse design in micro‐nanodriven devices and provides a framework for the rational design and synthesis of nanomotors for next‐gen biosensing applications.
Jing et al. (2026) studied this question.