Lyapunov-Based Nonlinear Control Strategies for Manipulation of Particles and Biomolecules Using Optical Tweezers

Abstract

Tweezers-based nanorobots, optical tweezers in particular, are renowned for their exceptional precision, and among their biomedical applications are cellular manipulation, unzipping DNAs, and elongating polypeptide chains. This thesis introduces a series of Lyapunov-based feedback control frameworks that address both stability and controlled instability for biological manipulation, applied within the context of optical tweezers. At the core of this work are novel controllers that stabilize or destabilize specific molecular configurations, enabling fine manipulation of particles like polystyrene beads and tethered polymers under focused laser beams. Chapter 1 covers the foundational principles and surveys existing literature on the modeling and control of optical tweezers, emphasizing gaps in the stability and instability control of molecular systems. Chapter 2 presents a robust Control Lyapunov Function (CLF) approach, designed to stabilize spherical particles under optical trapping. By formulating a smooth, norm-bounded feedback controller, we achieve lateral stabilization despite external disturbances, using a real-time, static nonlinear programming (NLP) solution. Simulations verify the effectiveness of this CLF framework, even with significant initial displacements from the laser focus and under thermal forces modeled as a white Gaussian noise. Chapter 3 addresses controlled instability through a Control Chetaev Function (CCF) framework, specifically targeting protein unfolding applications. Linearization with respect to the control input facilitates the application of destabilizing universal controls for affine- in-control system dynamics. The resulting CCF-based norm-bounded feedback controller induces system instability by laterally extending the trapped DNA handle, thereby increasing the molecular extension and providing insights into protein denaturation and unfolding pathways. This controller is robust to stochastic thermal forces and optimized for real-time computational efficiency. These Lyapunov and Chetaev-based control designs collectively expand the capabilities of optical tweezers, advancing single-molecule manipulation under both stable and unstable conditions. These findings advance precision nanomanipulation, opening new avenues for exploring the molecular mechanics of protein unfolding and DNA elasticity