The early-stage diagnosis and monitoring of disease evolution is still one of the most challenging tasks in the field of cancer research. Several research have been driven toward the discovery of new cancer biomarkers as well as to the development of biosensors able to detect these biomarkers with high specificity and sensitivity. Many types of cancer have been detected at an advanced stage and, in particular, epithelial ovarian cancer (EOC) has a high incidence of diagnosis in the metastatic stage. This cancer is considered as the most aggressive type of gynecological cancer with a 5-year survival and until now, no specific biomarkers have been identified. Nevertheless, some studies have indicated that mesothelin, a protein overexpressed by tumour cells in the ovary, interacts with the CA-125 biomarker present in the blood system accelerating the metastatic process. Therefore, the simultaneous presence of CA-125 and mesothelin in the blood during the evolution of EOC could be used to diagnose this disease before the metastasis. Therefore, with this motivation, this work aimed at the development of a biosensor capable of simultaneously detecting mesothelin and CA-125 at low concentrations. A biosensor based on the surface plasmon resonance imaging (SPRi) technique was developed and gold nanoparticles (AuNPs) were used in order to enhance the sensitivity. The study analysed successive injections of the biomarkers CA-125 and mesothelin, both in solution (analytical range of 9–120 nM). The limits of detection were obtained for CA-125 and mesothelin, being of 3.03 nM and 13.62 nM, respectively. The biosensor detected mesothelin at a concentration close to the cutoff point for EOC (3 nM) and was able to detect the biomarker CA-125 at 9 nM. Furthermore, the biosensor interacted preferentially and simultaneously with the biomarkers CA-125 and mesothelin incubated in fetal bovine serum. Finally, the use of AuNPs increased the sensor signal for CA-125 detection compared to its direct detection and showed greater selectivity for both biomarkers. Therefore, the biosensor has important characteristics that allow testing with real samples. In a future project, it could be applied in the research of diagnosis and prognosis of EOC.

疾病演变的早期诊断和监测仍然是癌症研究领域最具挑战性的任务之一。一些研究致力于发现新的癌症生物标志物以及开发能够以高特异性和灵敏度检测这些生物标志物的生物传感器。许多类型的癌症都是在晚期才被发现的，特别是上皮性卵巢癌（EOC）在转移期的诊断率很高。这种癌症被认为是最具侵袭性的妇科癌症，生存期为 5 年，但迄今为止，尚未发现特定的生物标志物。然而，一些研究表明间皮素（一种由卵巢肿瘤细胞过度表达的蛋白质）与血液系统中存在的 CA-125 生物标志物相互作用，加速转移过程。因此，在EOC进化过程中血液中同时存在CA-125和间皮素可用于在转移前诊断该疾病。因此，本着这一动机，本工作旨在开发能够同时检测低浓度间皮素和CA-125的生物传感器。开发了一种基于表面等离子共振成像（SPRi）技术的生物传感器，并使用金纳米颗粒（AuNP）来提高灵敏度。该研究分析了生物标志物 CA-125 和间皮素的连续注射，两者均在溶液中（分析范围为 9-120 nM）。 CA-125 和间皮素的检测限分别为 3.03 nM 和 13.62 nM。该生物传感器检测到的间皮素浓度接近 EOC 的截止点 (3 nM)，并且能够检测到 9 nM 的生物标志物 CA-125。此外，生物传感器优先并同时与在胎牛血清中孵育的生物标志物CA-125和间皮素相互作用。最后，与直接检测相比，AuNP 的使用增加了 CA-125 检测的传感器信号，并且对两种生物标志物显示出更高的选择性。因此，生物传感器具有允许使用真实样品进行测试的重要特性。在未来的项目中，它可以应用于EOC的诊断和预后研究。