Aptamer-Antibody Birecognized Sandwich SERRS Biosensor in Accurate and Rapid Identification of Intraoperative Parathyroid Hormone

With the increasing incidence of thyroid cancer worldwide and the increasing demand for surgery, the risk of parathyroid injury is also increasing, which will lead to postoperative hypoparathyroidism (HP) and hypocalcemia. In order to improve the quality of life of patients after surgery, there is an urgent need to develop a novel platform that can identify the parathyroid gland immediately during surgery. The parathyroid gland promotes the increase of blood calcium concentration by secreting parathyroid hormone (PTH). Therefore, in this study, we used the sensitive surface-enhanced Raman spectroscopy (SERS) technique for rapid detection of PTH, while the near-infrared dye IR808 was used for resonance with the incident excitation wavelength of 785 nm to achieve the surface enhanced resonance Raman spectroscopy (SERRS) effect and provide a higher signal. The signal is enhanced by up to 200-fold compared to nonresonant sulfhydryl molecules. In addition, we used an aptamer-antibody mode with low Gibbs free energy (ΔG) and low dissociation constant (K_d), using the sandwich method, to achieve specific recognition of PTH. By optimizing the incubation temperature, aptamer dosage, particle concentration, and other key factors, the optimal detection conditions of the system were obtained. The sensitivity of PTH detection was as high as 9.75 pg/mL at a 5 min incubation time. In this work, we achieved an extension from standard products to rats to clinically practical samples. Finally, the eluate samples obtained from the actual clinical operations were compared with the lateral flow biosensor (LFB), chemiluminescence microparticle immunoassay (CMIA), and SERRS, respectively. Finally, using the CMIA results as the reference standard, the SERRS assay achieved a sensitivity of 94% and a specificity of 100%. This study provides new ideas and methods for the refined development of thyroid cancer surgery, improving postoperative safety and quality of life of patients, and promoting the new mode of intraoperative diagnosis and treatment.