Current method for monitoring patients for cancer recurrence after treatment requires patients to travel to a centralized laboratory, causing time in scheduling appointments/waiting for results, financial burden in travel costs to clinics, and invasive procedures (i.e., biopsies) leading to discomfort in patients. To improve convenience, outcomes, and enable more frequent monitoring of cancer recurrence, we propose using an implantable hydrogel sensor for remote cancer surveillance. Gold nanostars (GNS), efficient plasmonic nanomaterials, embedded in hydrogels, enhance Raman scattering signals of cancer biomarkers. A handheld Raman spectroscopy probe collects these signals, representing the unique vibrational molecular fingerprint. Toward this effort, this study demonstrates the performance of a GNS-embedded hydrogel for discriminating serum in two preclinical mouse prostate cancer models: NSG and C57BL/6J mice. GNS labeled with 4- mercaptobenzoic acid (4-MBA) were embedded in 70μL hydrogels. Six serum samples from NSG mice (3 with LNCaP subcutaneous tumors, 3 normal) and eight serum samples from C57BL/6J mice (3 wild type, 5 transgenic modified– TRAMP with prostate cancer) were obtained. Serum (70μL) was incubated overnight (4°C) with the hydrogel sample. Raman spectra were collected at five distinct locations using the Raman handheld probe. Spectral analysis involved intensity normalization, principal component analysis (PCA) for dimension reduction, and linear discriminate analysis (LDA) for classification with leave-one-spectra-out cross-validation. NSG mice exhibited band differences at 775-825 cm-1, 1202-1249 cm-1, and 1430-1478 cm-1 (LDA ROC AUC = 0.83), while C57BL/6J mice showed differences at 1152-1245 cm-1 and 1362-1407 cm-1 (LDA ROC AUC = 0.98). Successful discrimination of serum in mouse models demonstrates the presence of biomarkers that differentiate cancer-bearing mice and the potential for remote cancer monitoring.
Early cancer detection is critical for successful treatment. Current cancer detection methods require travel to a centralized laboratory for testing which can be time-consuming, costly, invasive, and infrequent. Patients could benefit from a less invasive method to monitor recurrence which could be performed more frequently from the comfort of their home. We propose an implanted hydrogel sensor for remote cancer monitoring. Gold nanostars (GNS) embedded within the hydrogel produce surface enhanced Raman scattering signals of cancer biomarkers collected remotely using a handheld probe, with the results being sent to their provider. Here, we present results demonstrating the ability to discriminate human prostate cancer plasma. GNS were labeled with 4-mercaptobenzoic acid (4-MBA) and embedded into 70μL hydrogels. Four prostate cancer samples and five non-prostate cancer samples were obtained from a biobank. 70μL of each sample were combined with one hydrogel per sample and incubated overnight at 4°C. A handheld probe was used to collect Raman spectra at 5 different locations across each hydrogel face. The classification algorithm included intensity normalization based on intensity of the 4MBA signal, principal component analysis (PCA) for dimension reduction, and linear discriminate analysis (LDA) or logistic regression for classification with leave-one-sample- out cross validation. Comparison of cancer and non-cancer spectra shows relative peak intensity differences between the two groups including at 726cm-1 and 1450cm-1. The area under the ROC curve was up to 0.94 for logistic regression. Results show the potential of remote cancer monitoring with a hydrogel SERS sensor.
Portable Raman and surface-enhanced Raman scattering spectroscopy (SERS) systems have gained great interest in biomedical science, especially when combined with microfluidics, since it allows the application of this sensitive technology in low-resource settings, providing fast results at a low-cost level. Moreover, these portable systems are also more versatile and user-friendly than microscope-based approaches. In this work, we propose the design of a complete portable SERS equipment for the analysis of biofluids. The system was optimized and tested using the Raman reporter 4- mercaptobenzoic acid (4-MBA) and, as a proof of concept, we performed a calibration curve using another Raman reporter: 1-naphtalenethiol (1NAT), being able to detect concentrations as lower as 2*10-4 M. The results presented here show the potential of the system to detect different and relevant biomarkers, and even be part of more complex systems like Point-of-care or Lab-on-a-chip devices.
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