Ultrasensitive optofluidic enzyme-linked immunosorbent assay by on-chip integrated polymer whispering-gallery-mode microlaser sensors

Optical whispering-gallery-mode (WGM) microcavities offer great promise in ultrasensitive biosensors because of their unique ability to enable resonant recirculation of light to achieve strong light-matter interactions in microscale volumes. However, it remains a challenge to develop cost-effective, high-performance WGM microcavity-based biosensing devices for practical disease diagnosis applications. In this paper, we present an optofluidic chip that is integrated with directly-printed, high-quality-factor (Q) polymer WGM microlaser sensors for ultrasensitive enzyme-linked immunosorbent assay (ELISA). Optical 3D μ-printing technology based on maskless ultraviolet lithography is developed to rapidly fabricate high-Q suspended-disk WGM microcavities. After deposition with a thin layer of optical gain material, low-threshold WGM microlasers are fabricated and then integrated together with optical fibres upon a microfluidic chip to achieve an optofluidic device. With flexible microfluidic technology, on-chip, integrated, WGM microlasers are further modified in situ with biomolecules on surface for highly selective biomarker detection. It is demonstrated that such an optofluidic biochip can measure horseradish peroxidase (HRP)-streptavidin, which is a widely used catalytic molecule in ELISA, via chromogenic reaction at the concentration level of 0.3 ng mL-1. Moreover, it enables on-chip optofluidic ELISA of the disease biomarker vascular endothelial growth factor (VEGF) at the extremely low concentration level of 17.8 fg mL-1, which is over 2 orders of magnitude better than the ability of current commercial ELISA kits.