Ultrasensitive Screening of Endocrine-Disrupting Chemicals Using a Surface Plasmon Resonance Biosensor with Polarization-Compensated Laser Heterodyne Feedback

Developing an ultrasensitive and reliable device for continuous monitoring of various endocrine-disrupting chemicals (EDCs) is in high demand, yet it remains a significant challenge. Traditional label-free surface plasmon resonance (SPR) sensing relies on the interaction of the surface plasmon wave and the sensing liquid via intensity modulation, endowed with simple structure and easy-to-miniaturization, however suffering from inferior sensitivity and stability. Here, we propose a novel optical structure in which the frequency-shifted light of different polarization returned to the laser cavity to stimulate laser heterodyne feedback interferometry (LHFI), hence amplifying the reflectivity change caused by the refractive index (RI) variations on the gold-coated SPR chip surface, and the s-polarized light could be further used as a reference to compensate for the noise of the LHFI-amplified SPR system, resulting in nearly three orders of magnitude enhancement of the RI sensing resolution (5.9 × 10–8 RIU) compared to the original SPR system (2.0 × 10–5 RIU). To further boost intense signal enhancement, custom-designed gold nanorods (AuNRs), which were optimized by the finite-difference time-domain (FDTD) simulation, were used to generate localized surface plasmon resonance (LSPR). By exploiting the estrogen receptor as the recognition material, estrogenic active chemicals were detected with a 17β-estradiol/L detection limit of 0.004 ng, which is nearly 180-fold lower than that of the system without introducing AuNRs. The developed SPR biosensor is expected to be capable of screening various EDCs with universality by using several nuclear receptors, such as the androgen receptor and thyroid receptor, and will substantially accelerate the assessment of global EDCs.