In glioblastoma (GBM) patients, maximal safe resection remains a challenge today due to its invasiveness and diffuse parenchymal infiltration. In this context, plasmonic biosensors could potentially help to discriminate tumor tissue from peritumoral parenchyma based on differences in their optical properties. A nanostructured gold biosensor was used ex vivo to identify tumor tissue in a prospective series of 35 GBM patients who underwent surgical treatment. For each patient, two paired samples, tumor and peritumoral tissue, were extracted. Then, the imprint left by each sample on the surface of the biosensor was individually analyzed, obtaining the difference between their refractive indices. The tumor and non-tumor origins of each tissue were assessed by histopathological analysis. The refractive index (RI) values obtained by analyzing the imprint of the tissue were significantly lower (p = 0.0047) in the peritumoral samples (1.341, Interquartile Range (IQR) 1.339–1.349) compared with the tumor samples (1.350, IQR 1.344–1.363). The ROC (receiver operating characteristic) curve showed the capacity of the biosensor to discriminate between both tissues (area under the curve, 0.8779, p < 0.0001). The Youden index provided an optimal RI cut-off point of 0.003. The sensitivity and specificity of the biosensor were 81% and 80%, respectively. Overall, the plasmonic-based nanostructured biosensor is a label-free system with the potential to be used for real-time intraoperative discrimination between tumor and peritumoral tissue in patients with GBM.

Background: Brain metastases have traditionally been considered well-demarcated lesions; however, increasing evidence demonstrates frequent microscopic infiltration of the surrounding brain parenchyma, with relevant prognostic implications, despite current intraoperative tools. The aim of this study was to evaluate the feasibility and diagnostic performance of a label-free nanoplasmonic biosensor for intraoperative discrimination between tumor tissue and peritumoral brain in brain metastases surgery. Methods: A prospective multicenter study was conducted in patients undergoing surgical resection of brain metastases. Paired tumor and adjacent peritumoral tissue samples were collected intraoperatively following a standardized protocol across participating centers. Samples were analyzed ex vivo using a plasmonic nanostructured biosensor, which detects tissue-specific refractive index differences. Histopathological examination served as the reference standard. Paired comparisons were performed using the Wilcoxon signed-rank test, and diagnostic performance was assessed using receiver operating characteristic analysis. Results: Twenty paired tumor and peritumoral samples from a consecutive series of 20 patients were analyzed. Refractive index values were significantly higher in tumor tissue compared with peritumoral brain ( p = 0.0008). In 85% of cases, tumor samples showed higher refractive index values than their paired peritumoral counterparts. Using the optimal cut-off value, sensitivity was 76% and specificity was 68%. Conclusion: Tumor and peritumoral brain tissue can be discriminated through the measurement of intrinsic biophysical properties with a label-free nanoplasmonic biosensor, supporting its potential role as an objective intraoperative tool for margin assessment without the need of exogenous agents.