Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.
Tianyi YinLizhou XuBruno Miguel Gil RosaNabeel MeraliMaria S SokolikovaDavid C A GaboriauDaniel S K LiuAhmad Nizamuddin Muhammad MustafaSarah AlodanMichael ChenOihana TxoperenaMaría ArrastuaJuan Manuel GomezNerea OntosoMarta EliceguiElias TorresDanyang LiCecilia MatteviAdam E FramptonLong R JiaoSami RamadanNorbert KleinPublished in: ACS nano (2023)
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.
Keyphrases
- label free
- end stage renal disease
- loop mediated isothermal amplification
- chronic kidney disease
- mesenchymal stem cells
- newly diagnosed
- stem cells
- ejection fraction
- early stage
- high resolution
- prognostic factors
- high throughput
- peritoneal dialysis
- sensitive detection
- quantum dots
- gold nanoparticles
- risk assessment
- carbon nanotubes
- long non coding rna
- single cell
- binding protein
- low cost
- deep learning
- big data
- liquid chromatography