Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.
Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.
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DOI：
10.1021/acsnano.3c01812
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发表时间：
2023-08-08
期刊：
影响因子：
17.1
通讯作者：
Klein, Norbert
中科院分区：
文献类型：
--
作者：
Yin, Tianyi;Xu, Lizhou;Gil, Bruno;Merali, Nabeel;Sokolikova, Maria S. S.;Gaboriau, David C. A.;Liu, Daniel S. K.;Muhammad Mustafa, Ahmad Nizamuddin;Alodan, Sarah;Chen, Michael;Txoperena, Oihana;Arrastua, Maria;Gomez, Juan Manuel;Ontoso, Nerea;Elicegui, Marta;Torres, Elias;Li, Danyang;Mattevi, Cecilia;Frampton, Adam E. E.;Jiao, Long R. R.;Ramadan, Sami;Klein, Norbert
基于石墨烯场效应晶体管（GFET）的生物传感器有可能开发用于早期疾病检测的即时诊断工具。然而，石墨烯传感器的再现性和制造产率的问题，以及德拜筛选和非特异性物质的不必要检测的问题，阻碍了石墨烯技术的更广泛的临床应用。在这里，我们证明了我们的晶圆级可扩展GFET阵列平台能够实现有意义的临床结果。作为一个高度临床相关性的案例研究，我们展示了一种准确可靠的便携式GFET阵列生物传感器平台，用于通过特异性外泌体检测患者血浆中的胰腺导管腺癌（PDAC）为了促进血浆中的可再现检测，我们通过应用内部控制通道和开发优化的测试方案来优化GFET生物传感器的分析性能。基于来自18名PDAC患者和8名健康对照的样本，GFET生物传感器阵列可以准确区分这两组，同时能够检测早期癌症阶段，包括第1和第2阶段。此外，我们证实了GPC-1的较高表达，并发现PDAC血浆中的浓度平均比健康样品高1个数量级以上。我们发现GPC-1癌性外泌体的这些特征是石墨烯表面上靶外泌体数量增加的原因，从而改善了GFET生物传感器的信号响应。这种GFET生物传感器平台对于开发用于胰腺癌快速诊断的准确工具具有很大的希望。
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.
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影响因子：
8.4
作者：
Kim, Hyo Eun;Schuck, Ariadna;Kim, Yong-Sang
通讯作者：
Kim, Yong-Sang
影响因子：
--
作者：
Frampton AE;Prado MM;López-Jiménez E;Fajardo-Puerta AB;Jawad ZAR;Lawton P;Giovannetti E;Habib NA;Castellano L;Stebbing J;Krell J;Jiao LR
通讯作者：
Jiao LR
影响因子：
4.6
作者：
Kibria G;Ramos EK;Lee KE;Bedoyan S;Huang S;Samaeekia R;Athman JJ;Harding CV;Lötvall J;Harris L;Thompson CL;Liu H
通讯作者：
Liu H
影响因子：
17.1
作者：
Lewis, Jean M.;Vyas, Ankit D.;Heller, Michael J.
通讯作者：
Heller, Michael J.
影响因子：
14.6
作者：
Lee, Chulyeon;Kim, Hwajeong;Kim, Youngkyoo
通讯作者：
Kim, Youngkyoo