Microfluidics Integrated Lithography‐Free Nanophotonic Biosensor for the Detection of Small Molecules

Abstract Currently, labeling techniques are mostly used to study the binding kinetics of small molecules and their detection (molecular weights <500 Daltons) at low analyte concentrations. However, the fluorescent tags used in this method for conjugation may modify or prevent the functionality of the targeted molecules. Although label‐free techniques provide more accurate quantitative and kinetic measurements by monitoring the binding of analytes in their usual forms, the monitoring of small molecule binding at lower concentrations is still impossible using conventional refractometric sensing devices. Here, a label‐free and cost‐effective technique is demonstrated for the detection of ultralow molecular weight biomolecules such as biotin (244 Daltons) at very low concentrations. This extreme sensitivity is realized by utilizing the phase singularity feature of lithography‐free nanophotonic cavities. The proposed four‐layered metal‐dielectric‐dielectric‐metal asymmetric Fabry–Perot cavity exhibits point‐of‐darkness and phase singularity at the Brewster angle. Since the singular phase behavior depends on the topology of the cavity surface, it is very challenging to realize singular phase in reflection mode for a microfluidics integrated nanophotonic cavity. To overcome this issue, a specially designed polymethylmethacrylate microfluidic channel is integrated with the cavity.