Article

Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients’ Blood Plasma Samples

Tianyi YinDepartment of Materials, Imperial College London, London SW7 2AZ, U.KLizhou XuDepartment of Materials, Imperial College London, London SW7 2AZ, U.KBruno M. G. RosaHamlyn Centre, Imperial College London, London SW7 2AZ, U.KNabeel MeraliHPB Surgical Unit, Royal Surrey NHS Foundation Trust, Guildford, Surrey GU2 7XX, U.KMaria S. SokolikovaDepartment of Materials, Imperial College London, London SW7 2AZ, U.KDavid C. A. GaboriauFacility for Imaging By Light Microscopy, Imperial College London, London SW7 2AZ, U.KDaniel LiuDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, U.KAhmad Nizamuddin Muhammad MustafaDepartment of Materials, Imperial College London, London SW7 2AZ, U.KSarah AlodanDepartment of Materials, Imperial College London, London SW7 2AZ, U.KMichael ChenDepartment of Materials, Imperial College London, London SW7 2AZ, U.KOihana TxoperenaGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainMaría ArrastuaGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainJuan Manuel GómezGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainNerea OntosoGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainMarta EliceguiGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainElias TorresGraphenea Semiconductor, Paseo Mikeletegi 83, San Sebastián ES 20009, SpainDanyang LiResearch Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, ChinaCecilia MatteviDepartment of Materials, Imperial College London, London SW7 2AZ, U.KAdam E. FramptonDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, U.KLong R. JiaoDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, U.KSami RamadanDepartment of Materials, Imperial College London, London SW7 2AZ, U.KNorbert KleinDepartment of Materials, Imperial College London, London SW7 2AZ, U.K

2023en

ABI

Abstract

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.

Identifiers

DOI: 10.1021/acsnano.3c01812

Citations and references

Cited by 20 references

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