Indicator Displacement Assay Inside Dye-Functionalized Covalent Organic Frameworks for Ultrasensitive Monitoring of Sialic Acid, an Ovarian Cancer Biomarker

Identifying biomolecules for disease diagnosis requires simple, accurate, and reliable analytical techniques. Multiple signal transduction pathways have promoted the development of various biological analysis systems. However, most systems are largely limited by a single mechanism or model analysis, which can easily lead to false-positive/negative results. Herein, we report a covalent organic framework (COF) (TpPa-1) functionalized with a dye (fluorescein sodium) and design this hybrid material (TpPa-1@Dye) to fabricate hydrogels for subsequent analysis with the indicator displacement assay (IDA) method. Selecting a suitable metal cation (Cr³⁺) for the preparation of hydrogels can reduce the background fluorescence, improve the detection sensitivity, and increase the corresponding sensing selectivity. The TpPa-1@Dye functions as an indicator in the IDA-in-COF system, and Cr³⁺ is a receptor of the analyte (sialic acid (SA), a biomarker for ovarian cancer diagnosis). Based on the above studies, the integrative logic operations (AND + IMP) are further established, it helps in elucidating the design rules of the IDA-in-COF approach. This work represents the first effort in designing IDA-in-COF luminescent sensors with an On–Off–On mechanism to determine biomarkers and provides a new approach for developing hybrid COF luminescent materials as analysis platforms for human health monitoring.