Ultrasensitive Detection of FKBP12 Using a Synthetic Receptor-Functionalized QCM Nanoplatform

Abstract FKBP12, a peptidyl-prolyl isomerase implicated in cancer, neurodegenerative diseases, and post-transplant anti-rejection mechanisms, represents a critical biomarker for early diagnosis and monitoring. Here, a novel diagnostic nanoplatform is presented for the detection of FKBP12 at nanomolar to picomolar concentrations in biological fluids. The platform integrates a gold-coated Quartz Crystal Microbalance (QCM) functionalized with a synthetic receptor (GPS-SH1) and spacers within a Self-Assembled Monolayer (SAM), enabling direct and label-free detection of FKBP12 in complex biological samples. A careful strategy for the in-silico design and custom synthesis of the receptor is adopted, ensuring optimal binding affinity and additional chemical functionalities for surface chemisorption. The designed nano-architecture demonstrates exceptional sensitivity, with a detection limit in the picomolar range, and high selectivity, as confirmed by minimal interference from abundant serum proteins such as Serum Albumin and Immune Gamma Globulin. Furthermore, the SAM-functionalized sensors exhibit remarkable stability, retaining functionality for up to six months under storage conditions. This work not only advances the field of nanoscale biosensing but also provides a robust, reusable tool for FKBP12 detection, with potential applications in point-of-care diagnostics and personalized medicine. The platform's ability to operate in biologically relevant environments underscores its promise for real-world healthcare applications, including early disease diagnostics.