Department of Materials, Imperial College London, London SW7 2AZ, U.K.
ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China.
ACS Nano. 2023 Aug 8;17(15):14619-14631. doi: 10.1021/acsnano.3c01812. Epub 2023 Jul 20.
Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.
基于石墨烯场效应晶体管(GFET)的生物传感器具有开发用于早期疾病检测的即时诊断工具的潜力。然而,石墨烯传感器的重现性和制造产量问题,以及德拜屏蔽和对非特异性物质的不希望的检测,阻碍了石墨烯技术的更广泛临床应用。在这里,我们证明了我们的晶圆级 GFET 阵列平台能够实现有意义的临床结果。作为一个具有高度临床相关性的案例研究,我们通过在 45 分钟内检测患者血浆中的特定外泌体(GPC-1 表达),展示了一种用于检测胰腺导管腺癌(PDAC)的准确且稳健的便携式 GFET 阵列生物传感器平台。为了促进在血浆中的可重现检测,我们通过应用内部控制通道和开发优化的测试协议来优化 GFET 生物传感器的分析性能。基于 18 名 PDAC 患者和 8 名健康对照者的样本,GFET 生物传感器阵列能够准确地区分两组,并且能够检测早期癌症阶段,包括 1 期和 2 期。此外,我们证实了 GPC-1 的更高表达,并发现 PDAC 血浆中的浓度平均比健康样本高 1 个数量级以上。我们发现,这些 GPC-1 癌性外泌体的特征导致石墨烯表面上的靶向外泌体数量增加,从而提高了 GFET 生物传感器的信号响应。这种 GFET 生物传感器平台有望开发出用于快速诊断胰腺癌的准确工具。