Subpicogram Per Milliliter Detection of Interleukins Using Silicon Photonic Microring Resonators and an Enzymatic Signal Enhancement Strategy

Abstract

The detection of biomolecules at ultralow (low to subpicogram per milliliter) concentrations and within complex, clinically relevant matrices is a formidable challenge that is complicated by limitations imposed by the Langmuir binding isotherm and mass transport, for surface-based affinity biosensors. Here we report the integration of an enzymatic signal enhancement scheme onto a multiplexable silicon photonic microring resonator detection platform. To demonstrate the analytical value of this combination, we simultaneously quantitated levels of the interleukins IL-2, IL-6, and IL-8 in undiluted cerebrospinal fluid in an assay format that is multiplexable, relatively rapid (90 min), and features a 3 order of magnitude dynamic range and a limit of detection ≤1 pg/mL. The modular nature of this assay and technology should lend itself broadly amenable to different analyte classes, making it a versatile tool for biomarker analysis in clinically relevant settings.