A Self-Reference Interference Sensor Based on Coherence Multiplexing

Abstract

Interferometry has been widely used in biosensing due to its ability to acquire molecular affinity and kinetics in real-time. However, interferometric-based sensors are susceptible to environmental disturbances, including temperature and non-specific binding of target molecules, which reduces their detection robustness. To address this shortcoming, this paper proposes a self-referencing interference sensor based on coherence multiplexing to resist environmental disturbances. The proposed sensor can address temperature and non-specific binding, but it is not limited only to these types of disturbances. In the proposed sensor design, each sensor signal is encoded using a specific optical path difference determined by the optical thickness of a sensor chip. In addition, two sensor signals for disturbances tracking and biomolecule detection are detected simultaneously without additional cost to the second spectrometer and then differenced to achieve real-time self-reference. The temperature fluctuations experiments and specific binding experiments of protein A to IgG are performed to verify the performance of the proposed sensor. The results demonstrate that the proposed sensor can eliminate non-specific binding and temperature disturbances in real-time during biomolecule detection, achieving higher detection robustness. The proposed sensor is suitable for applications that require large-scale testing of biomolecular interactions, such as drug screening.

Keywords: biomolecular interaction; biosensing; differential measurement; label-free detection; phase-sensitive interferometry.