Ultra-sensitive lock-in amplifier coupled oscillatory magnetic tweezers for piconewton force manipulation applications

Abstract

We have developed lock-in amplifier coupled oscillatory magnetic tweezers, aiming to synchronize the oscillatory magnetic force application and single-molecule response detection at the applied oscillatory frequency by incorporating an optical lock-in amplifier detection. The designed home-built lock-in amplifier detection instrument enables an exact reference signal input and hence reveals an accurate and sensitive magnetic response synchronization. We have further demonstrated the approach with the rhodamine 6G stained super-paramagnetic beads by monitoring the below-the-noise-background weak fluorescence signal changes due to the magnetic response of the super-paramagnetic beads under the oscillatory force manipulation. The integration of the lock-in amplifier and the oscillating magnetic tweezers can significantly expand the application of the magnetic tweezers for signal detection below the noise background, such as adapting to the important applications in the detailed exploration of mechanical properties of biomolecules and studies of the protein conformational fluctuation dynamics.