Multifunctional nanorobot system in precise evaluation and manipulation of virus capsid

Abstract

It is imperative to have high adaptive techniques for sensing and manipulating biological targets at the nanoscale. This necessity becomes particularly crucial when dealing with fragile living bio-organisms like viruses, where the expression of capsids is closely linked to viral functions and genome constitution. Therefore, the development of a comprehensive system for dissecting and measuring viruses holds significant implications for the pharmaceutical industry and drug manufacturing. Leveraging the sub-nanometer spatial resolution and controllable tip-cantilever architecture of atomic force microscopy (AFM), a probe-laser system has been integrated as a self-sensing robotic end effector. To address intrinsic challenges in AFM-based robotic systems such as the lack of real-time monitoring, low scanning rates, and nonlinear motion caused by piezoelectric actuators, an augmented reality robotic system has been implemented. This system incorporates stereoscopic vision, a haptic feedback controller, a position recovery scheme, and a real-time force control algorithm. The integration of these components enhances the system’s capability to accurately dissect virus capsids. Operators can now perform highly efficient nanoscale tasks with multidimensional perception, utilizing the combination of stereoscopic vision and haptic force control. The position correction during manipulation can achieve a frame rate of over 30 frames per second, imperceptible to the operator, enabling closed-loop operation control. By adopting the proposed nanorobotic system in virology studies, it becomes possible to achieve accurate manipulation and dissection of SARS-CoV-2 pseudovirus capsids, and derive multi-parametric properties such as structural integrity, protein fragment thickness, and adhesive forces. The established nanobot system and experimental results serve as a guiding platform for high-accuracy evaluation in drug manufacturing development.